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1. The impact of theory of mind, stress and professional experience on empathy in Romanian community nurses—a cross-sectional study

Author: Lidia Onofrei, Costela Lacrimioara Serban, Adela Chirita-Emandi, Roxana Maria Jeleriu, and Maria Puiu
Subjects: Community nurses, Empathy, Theory of mind, Stress, Nursing, RT1-120
Abstract: Abstract Background High empathy levels in health professionals represent an important factor in patient satisfaction and compliance, reducing patient anxiety and pain, enhancing diagnostic and clinical results and strengthening patient empowerment. Our purpose was to determine empathy level and to identify which of the socioeconomic status (SES) and psychological factors were able to predict highest empathy levels in a Romanian sample of community nurses. Methods Community nurses were invited in January-February 2023 to provide an answer to an online survey, using an advertisement in a professional network. 1580 participants voluntarily agreed to take part in this study, with a response rate of 85.8%. The survey included the Toronto Empathy Questionnaire, the Reading the Mind in the Eyes Test and socio-economic status items. A multivariate model for the prediction of belonging to the highest quartile of empathy as opposed to lowest quartile was constructed using SES and psychological variables as factors. Results The mean (SD) empathy level was 49.1 (6.7), with 74.7% of participants over the threshold of high empathy level. In the multivariate analysis, predictors of belonging to the highest quartile of TEQ, as opposed to the lowest quartile were: low self-perceived stress level (OR = 2.098, 95%CI 1.362–3.231), higher experience as a community nurse (OR = 1.561, 95%CI 1.120–2.175) and higher levels of the theory of mind (OR = 1.158, 95%CI 1.118–1.199), when controlling for gender, age, relationship status, presence of children in families, education, and income. Conclusions Training programs targeting to increase emotional competences, reduce levels of stress and encourage personnel retention have the potential to increase the quality of community nursing in Romania.
Published: 2023
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2. A comprehensive analysis concerning eating behavior associated with chronic diseases among Romanian community nurses

Author: Lidia-Manuela Onofrei, Maria Puiu, Adela Chirita-Emandi, and Costela Lacrimioara Serban
Subjects: chronic diseases, non-communicable diseases, community nurses, eating behavior, high carbohydrate diet, low carbohydrate diet score, Public aspects of medicine, RA1-1270
Abstract: IntroductionLifestyle factors, including inadequate eating patterns, emerge as a critical determinant of chronic disease. Apart from caring for patients, nurses should also take an active role in monitoring and managing their own health. Understanding the intricate relationship between nurses’ eating behavior and managing their own health is crucial for fostering a holistic approach to healthcare, therefore our study aimed to evaluate eating behavior and demographic factors influencing chronic disease prevalence in a sample of community nurses from Romania.MethodsBetween October–November 2023, 1920 community nurses were invited to answer an online survey, using an advertisement in their professional network. Of them, 788 responded. In the survey, which included a semi-quantitative food frequency questionnaire with 53 food items, the Intuitive Eating Survey 2 (IES-2), and demographic items were used.ResultsA multivariate model was built for the prediction of the association between eating behavior and other factors associated with chronic diseases. The majority of participants were females (95.1%), with the largest age group falling between 40 and 49.9 years (48.2%). Regarding the EFSA criteria for adequate carbohydrate and fat intake, 20.2% of the group have a high intake of carbohydrates, respectively, 43.4% of the group have a high intake of fat. Analysis of chronic diseases indicated that 24.9% of individuals reported at least one diagnosis by a physician. The presence of chronic disease was associated with a low level of perceived health status, with an OR = 3.388, 95%CI (1.684–6.814), compared to those reporting excellent or very good perceived health status. High stress had an OR = 1.483, 95%CI (1.033–2.129). BMI had an OR = 1.069, 95%CI (1.032–1.108), while low carbohydrate diet score had an OR = 0.956, 95%CI (0.920–0.992). Gender and IES-2 did not significantly contribute to the model, but their effect was controlled.DiscussionBy unraveling the intricate interplay between nutrition, lifestyle, and health outcomes in this healthcare cohort, our findings contribute valuable insights for the development of targeted interventions and support programs tailored to enhance the well-being of community nurses and, by extension, the patients they support.
Published: 2024
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3. Genotype-Phenotype Insights of Inherited Cardiomyopathies—A Review

Author: Oana Raluca Voinescu, Adina Ionac, Raluca Sosdean, Ioana Ionac, Luca Silvia Ana, Nilima Rajpal Kundnani, Stelian Morariu, Maria Puiu, and Adela Chirita-Emandi
Subjects: heritable cardiomyopathies, genetic testing, family screening, genetic counseling, Medicine (General), R5-920
Abstract: Background: Cardiomyopathies (CMs) represent a heterogeneous group of primary myocardial diseases characterized by structural and functional abnormalities. They represent one of the leading causes of cardiac transplantations and cardiac death in young individuals. Clinically they vary from asymptomatic to symptomatic heart failure, with a high risk of sudden cardiac death due to malignant arrhythmias. With the increasing availability of genetic testing, a significant number of affected people are found to have an underlying genetic etiology. However, the awareness of the benefits of incorporating genetic test results into the care of these patients is relatively low. Aim: The focus of this review is to summarize the current basis of genetic CMs, including the most encountered genes associated with the main types of cardiomyopathies: hypertrophic, dilated, restrictive arrhythmogenic, and non-compaction. Materials and Methods: For this narrative review, we performed a search of multiple electronic databases, to select and evaluate relevant manuscripts. Results: Advances in genetic diagnosis led to better diagnosis precision and prognosis prediction, especially with regard to the risk of developing arrhythmias in certain subtypes of cardiomyopathies. Conclusions: Implementing the genomic information to benefit future patient care, better risk stratification and management, promises a better future for genotype-based treatment.
Published: 2024
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4. Genetic Characterization of Dilated Cardiomyopathy in Romanian Adult Patients

Author: Oana Raluca Voinescu, Bogdana Ioana Ionescu, Sebastian Militaru, Andreea Sorina Afana, Radu Sascau, Laura Vasiliu, Sebastian Onciul, Mihaela Amelia Dobrescu, Ramona Alina Cozlac, Dragos Cozma, Raluca Rancea, Bogdan Dragulescu, Nicoleta Ioana Andreescu, Maria Puiu, Ruxandra Oana Jurcut, and Adela Chirita-Emandi
Subjects: dilated cardiomyopathy, heart failure, genetic testing, next-generation sequencing, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Dilated cardiomyopathy (DCM) represents a group of disorders affecting the structure and function of the heart muscle, leading to a high risk of heart failure and sudden cardiac death (SCD). DCM frequently involves an underlying genetic etiology. Genetic testing is valuable for risk stratification, treatment decisions, and family screening. Romanian population data on the genetic etiology of DCM are lacking. We aimed to investigate the genetic causes for DCM among Romanian adult patients at tertiary referral centers across the country. Clinical and genetic investigations were performed on adult patients presenting to tertiary hospitals in Romania. The genetic investigations used next-generation sequencing panels of disease-associated DCM genes. A total of 122 patients with DCM underwent genetic testing. The mean age at DCM diagnosis was 41.6 ± 12.4 years. The genetic investigations identified pathogenic or likely pathogenic variants in 50.8% of participants, while 25.4% had variants of unknown significance. Disease-causing variants in 15 genes were identified in people with DCM, with 31 previously unreported variants. Variants in TTN, LMNA, and DSP explained 75% of genetic causes for DCM. In total, 52.4% of patients had a family history of DCM/SCD. Left ventricular ejection fraction of
Published: 2024
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5. Phospholamban p.Leu39* Cardiomyopathy Compared with Other Sarcomeric Cardiomyopathies: Age-Matched Patient Cohorts and Literature Review

Author: Andreea Sorina Afana, Laura Vasiliu, Radu Sascău, Robert Daniel Adam, Cristina Rădulescu, Sebastian Onciul, Eliza Cinteză, Adela Chirita-Emandi, and Ruxandra Jurcuț
Subjects: phospholamban, hypertrophic cardiomyopathy, genetic testing, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic disorder, most often caused by sarcomeric gene mutations, with a small proportion due to variants in non-sarcomeric loci. Phospholamban (PLN) is a phosphoprotein associated with the cardiac sarcoplasmic reticulum, a major determinant of cardiac contractility and relaxation. We conducted a retrospective study to determine the prevalence, phenotypical spectrum and clinical course of patients carrying the PLN p.Leu39* variant. A cohort including 11 PLN patients was identified among all patients with HCM (9/189, 4.8%) and DCM (2/62, 3.2%) who underwent genetic testing from two tertiary centers and five more were detected through cascade screening. Complete phenotyping was performed. PLN p.Leu39* variant-driven cardiomyopathy presented mostly as hypertrophic, with frequent progression to end-stage dilated HCM. We proceeded to compare these results to a similar analysis of a control cohort consisting of age-matched individuals that inherited pathogenic or likely pathogenic variants in common sarcomeric genes (MYBPC3/MYH7). Overall, the clinical characteristics and examination findings of patients carrying PLN p.Leu39* were not different from patients with cardiomyopathy related to sarcomeric mutations except for the presence of pathological Q waves and the incidence of non-sustained ventricular arrhythmias, which were higher in PLN patients than in those with MYBPC3/MYH7-related diseases.
Published: 2024
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6. Copy number variation analysis in 189 Romanian patients with global developmental delay/intellectual disability

Author: Diana Miclea, Sergiu Osan, Simona Bucerzan, Delia Stefan, Radu Popp, Monica Mager, Maria Puiu, Cristian Zimbru, Adela Chirita-Emandi, and Camelia Alkhzouz
Subjects: Global developmental delay, Intellectual disability, Chromosomal microarray analysis, Copy number variants, Etiology, Pediatrics, RJ1-570
Abstract: Abstract Background Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis. Methods We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis. Results Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%). Conclusions The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.
Published: 2022
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7. When Mast Cells Run Amok: A Comprehensive Review and Case Study on Severe Neonatal Diffuse Cutaneous Mastocytosis

Author: Emilian-Gheorghe Olteanu, Mihaela Bataneant, Maria Puiu, and Adela Chirita-Emandi
Subjects: neonatal diffuse cutaneous mastocytosis, KIT gene, case report, systemic mastocytosis, review, Genetics, QH426-470
Abstract: Neonatal diffuse cutaneous mastocytosis (NDCM) is defined as the infiltration of the epidermis by a clonal proliferation of mast cells, observed at birth, without initial signs of systemic involvement. The typical driver mutation is in the KIT gene. We report a rare case of a boy, born at term, already presenting at birth with generalized subcutaneous nodules on the face, scalp, trunk, back, hands, and feet. The spleen, liver, and inflammatory markers were normal at birth. Tryptase was significantly elevated. A bone marrow biopsy showed no mast cell involvement at age 2 months. A punch biopsy at age 2 months revealed CD117-positive cells diffusely infiltrating the skin, with subsequent DNA NGS sequencing for the formalin-fixed paraffin embedded tissue (FFPE) identifying the pathogenic NM_000222.3:c.1504_1509dup; p.(Ala502_Tyr503dup) variant in the KIT gene previously associated with cutaneous mastocytosis. At 2 years follow-up, he had splenomegaly and multiple cervical and inguinal adenopathy, while the skin nodules persisted, especially on the scalp with accompanying pruritus. He received oral and local sodium cromoglycate, oral antihistamines, antibiotic cream for skin infection, and iron supplementation; however, compliance to treatment was relatively low. The prognosis is difficult to predict, as he developed systemic involvement, failure to thrive, and mild psychomotor delay. A case aggregation of NDCM reported in the literature was performed to provide a comprehensive overview of this rare pathology, to better understand the prognosis. NDCM is a life-threatening disease with severe complications. Almost half had severe complications, such as mast hepatosplenomegaly, adenopathy, bacterial infections, mast cell leukaemia, and systemic involvement.
Published: 2023
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8. Case Report: Novel Biallelic Variants in DNAJC21 Causing an Inherited Bone Marrow Failure Spectrum Phenotype: An Odyssey to Diagnosis

Author: Adela Chirita-Emandi, Carmen-Angela-Maria Petrescu, Cristian G. Zimbru, Florina Stoica, Catalin Marian, Andreea Ciubotaru, Mihaela Bataneant, and Maria Puiu
Subjects: DNAJC21 gene, ribosomopathy, bone marrow failure syndrome, Shwachman–Diamond syndrome, telomeres, Genetics, QH426-470
Abstract: Bone marrow failure represents an umbrella diagnosis for several life-threatening disorders. In many people, the etiology remains unknown for a long time, leading to an odyssey to diagnosis, with numerous tests performed and sometimes inappropriate treatment. Biallelic pathogenic variants in the DNAJC21 gene were recently discovered to cause bone marrow failure syndrome type 3, having phenotypic overlap with Fanconi anemia, dyskeratosis congenita, Shwachman–Diamond syndrome, and Diamond–Blackfan anemia. Herein, we report an 8-year-old boy, with normal intellect, presenting bone marrow failure; growth retardation; failure to thrive; recurrent infections (including sepsis); cryptorchidia; skeletal, skin, teeth, and hair abnormalities; joint hypermobility; eczema; palpebral ptosis; high myopia; rod–cone retinal dystrophy; and short telomeres. He underwent several tests and evaluations, including genetic investigations (panel and exome sequencing), before the DNAJC21 gene was known to cause disease. Whole-genome sequencing performed at the age of 7 years, identified two novel, pathogenic, and compound heterozygous variants in the DNAJC21 gene: NM_001012339.3:c.148C>T (stopgain-maternal origin), p.Gln50∗ and c.643_644delinsTTT (frameshift paternal origin), and p.Lys215Phefs∗71. He received aggressive treatments for his multisystem disease: blood cell transfusions, high-dose corticosteroids, immunoglobulins, multiple antibiotics, vitamins, growth hormone, and others. However, allogeneic hematopoietic stem cell transplantation was avoided. The clinical evolution of bone marrow failure and recurrent infections stabilized with age, yet the myopia progressed. Exocrine pancreatic insufficiency was not detected. This report widens the molecular and clinical understanding of bone marrow failure syndrome type 3. Genome sequencing directed a precise diagnosis that improved patient management and enabled family genetic counseling.
Published: 2022
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9. Challenges in the Surgical Treatment of Atrioventricular Septal Defect in Children With and Without Down Syndrome in Romania-A Developing Country

Author: Ioana-Cristina Olariu, Anca Popoiu, Andrada-Mara Ardelean, Raluca Isac, Ruxandra Maria Steflea, Tudor Olariu, Adela Chirita-Emandi, Ramona Stroescu, Mihai Gafencu, and Gabriela Doros
Subjects: atrioventricular septal defect, Down syndrome, congenital heart disease, pulmonary hypertension, risk factors, Pediatrics, RJ1-570
Abstract: Background: Atrioventricular septal defect (AVSD) is a cardiac malformation that accounts for up to 5% of total congenital heart disease, occurring with high frequency in people with Down Syndrome (DS). We aimed to establish the surgical challenges and outcome of medical care in different types of AVSD in children with DS compared to those without DS (WDS).Methods: The study included 62 children (31 with DS) with AVSD, evaluated over a 5 year period.Results: Complete AVSD was observed in 49 (79%) children (27 with DS). Six children had partial AVSD (all WDS) and seven had intermediate types of AVSD (4 with DS). Eight children had unbalanced complete AVSD (1 DS). Median age at diagnosis and age at surgical intervention in complete AVSD was not significantly different in children with DS compared to those WDS (7.5 months vs. 8.6). Median age at surgical intervention for partial and transitional AVSDs was 10.5 months for DS and 17.8 months in those without DS. A large number of patients were not operated: 13/31 with DS and 8/31 WDS.Conclusion: The complete form of AVSD was more frequent in DS group, having worse prognosis, while unbalanced AVSD was observed predominantly in the group without DS. Children with DS required special attention due to increased risk of pulmonary hypertension. Late diagnosis was an important risk factor for poor prognosis, in the setting of suboptimal access to cardiac surgery for patients in Romania. Although post-surgery mortality was low, infant mortality before surgery remains high. Increased awareness is needed in order to provide early diagnosis of AVSD and enable optimal surgical treatment.
Published: 2021
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10. Making Childhood Obesity a Priority: A Qualitative Study of Healthcare Professionals' Perspectives on Facilitating Communication and Improving Treatment

Author: Costela Lacrimioara Serban, Salomeia Putnoky, Anna Ek, Karin Eli, Paulina Nowicka, and Adela Chirita-Emandi
Subjects: children, family, overweight, obesity, parents, stigma, Public aspects of medicine, RA1-1270
Abstract: In Romania, one in four children has excess weight. Because childhood obesity is a sensitive topic, many healthcare professionals find it difficult to discuss children's excess weight with parents. This study aims to identify barriers and facilitators in childhood obesity-related communication, as perceived by healthcare professionals in Romania. As part of the STOP project, healthcare professionals (family physicians, pediatricians, and dieticians) who treat children with excess weight were invited to a telephone interview. The semi-structured questions were translated from a questionnaire previously used at the Swedish study site of the STOP project. Interviews were transcribed and then used for thematic analysis. Fifteen doctors and three dieticians (16 females and 2 males), with average 18.2 ± 10.1 years of experience, were interviewed. Four main themes were identified. Professionals reported that when children began experiencing obesity-related stigma or comorbidities, this became the tipping point of weight excess, where parents felt motivated to begin treatment. Barriers in communication were part of several layers of distrust, recognized as tension between professionals and caregivers due to conflicting beliefs about excess weight, as well as lack of trust in medical studies. Most respondents felt confident using models of good practice, consisting of a gentle approach and patient-centered care. Nonetheless, professionals noted systemic barriers due to a referral system and allocation of clinical time that hinder obesity treatment. They suggested that lack of specialized centers and inadequate education of healthcare professional conveys the system does not prioritize obesity treatment and prevention. The interviewed Romanian doctors and dieticians identified patient-centered care as key to treating children with obesity and building trust with their caregivers. Howevertheir efforts are hindered by healthcare system barriers, including the lack of specialized centers, training, and a referral system. The findings therefore suggest that, to improve childhood obesity prevention and treatment, systemic barriers should be addressed.Trial Registration:ClinicalTrials.gov, NCT03800823; 11 Jan 2019.
Published: 2021
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11. A randomized controlled trial for overweight and obesity in preschoolers: the More and Less Europe study - an intervention within the STOP project

Author: Anna Ek, Christine Delisle Nyström, Adela Chirita-Emandi, Josep A. Tur, Karin Nordin, Cristina Bouzas, Emma Argelich, J. Alfredo Martínez, Gary Frost, Isabel Garcia-Perez, Marc Saez, Corina Paul, Marie Löf, and Paulina Nowicka
Subjects: Children, Family, mHealth, Obesity, Overweight, Treatment, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Childhood overweight and obesity is a serious public health issue with an increase being observed in preschool-aged children. Treating childhood obesity is difficult and few countries use standardized treatments. Therefore, there is a need to find effective approaches that are feasible for both health care providers and families. Thus, the overall aim of this study is to assess the acceptance and effectiveness of a parent support program (the More and Less, ML) for the management of overweight and obesity followed by a mobile health (mHealth) program (the MINISTOP application) in a socially diverse population of families. Methods/design A two-arm, parallel design randomized controlled trial in 300 2-to 6-year-old children with overweight and obesity from Romania, Spain and Sweden (n = 100 from each). Following baseline assessments children are randomized into the intervention or control group in a 1:1 ratio. The intervention, the ML program, consists of 10-weekly group sessions which focus on evidence-based parenting practices, followed by the previously validated MINISTOP application for 6-months to support healthy eating and physical activity behaviors. The primary outcome is change in body mass index (BMI) z-score after 9-months and secondary outcomes include: waist circumference, eating behavior (Child Eating Behavior Questionnaire), parenting behavior (Comprehensive Feeding Practices Questionnaire), physical activity (ActiGraph wGT3x-BT), dietary patterns (based on metabolic markers from urine and 24 h dietary recalls), epigenetic and gut hormones (fasting blood samples), and the overall acceptance of the overweight and obesity management in young children (semi-structured interviews). Outcomes are measured at baseline and after: 10-weeks (only BMI z-score, waist circumference), 9-months (all outcomes), 15- and 21-months (all outcomes except physical activity, dietary patterns, epigenetics and gut hormones) post-baseline. Discussion This study will evaluate a parent support program for weight management in young children in three European countries. To boost the effect of the ML program the families will be supported by an app for 6-months. If the program is found to be effective, it has the potential to be implemented into routine care to reduce overweight and obesity in young children and the app could prove to be a viable option for sustained effects of the care provided. Trial registration ClinicalTrials.gov NCT03800823; 11 Jan 2019.
Published: 2019
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12. Intake Differences between Subsequent 24-h Dietary Recalls Create Significant Reporting Bias in Adults with Obesity

Author: Costela Lacrimioara Serban, Adela Chirita-Emandi, Iulia Teodora Perva, Alexandra Sima, Nicoleta Andreescu, Salomeia Putnoky, Mihai Dinu Niculescu, and Maria Puiu
Subjects: training bias, order of 24-h recalls, exacerbating underreporting, weekend–weekday differences, low quality diet, nutrient intakes, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: In depth understanding of the dietary patterns of individuals with obesity is needed in practice and research, in order to support dietitians and physicians in the design and implementation of nutritional management. We aimed to analyze the consistency of energy, macro-, and micronutrient reported intakes in four non-consecutive 24-h dietary recalls from 388 adults with obesity using information collected in the NutriGen Study (ClinicalTrials.gov, NCT02837367). Significant decreases were identified for reported energy and several, macro- and micronutrient intakes, between the first and subsequent 24-h recalls. Significant differences of reported intakes were identified in sensitivity analyses, suggesting that the first recall (also the only one performed on site, face-to-face) might be a point of bias. A comparison of the differences in intakes between weekend and weekday, after adjustment for false discovery rate were non-statistically significant either in male, females, or in total. To overcome this potential bias, studies should be carefully conducted, starting from the design phase, through to the analysis and interpretation phases of the study. Prior to averaging specific intakes across all sessions of reporting, a preliminary analysis must be conducted to identify if a certain time point had significant differences from all other time points and overview potential sources of bias: reporting bias, training bias, or behavioral changes could be responsible for such differences.
Published: 2022
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13. Antibiotic Resistance Patterns of Uropathogens Causing Urinary Tract Infections in Children with Congenital Anomalies of Kidney and Urinary Tract

Author: Raluca Isac, Diana-Georgiana Basaca, Ioana-Cristina Olariu, Ramona F. Stroescu, Andrada-Mara Ardelean, Ruxandra M. Steflea, Mihai Gafencu, Adela Chirita-Emandi, Iulia Cristina Bagiu, Florin George Horhat, Dan-Dumitru Vulcanescu, Dan Ionescu, and Gabriela Doros
Subjects: antibiotic resistance, urine culture, drug-resistant bacteria, children, abnormal urinary tract, Pediatrics, RJ1-570
Abstract: Background: Urinary tract infections (UTI) are common in children worldwide. Congenital anomalies of kidney and urinary tract (CAKUT) increase the risk of UTI and consequently antibiotic resistance. Antibiotic resistance represents an important public health issue worldwide. We aimed to evaluate the local trend in terms of bacterial uropathogen resistance in the western part of Romania in children with CAKUT and UTI. Methods: 252 children with CAKUT were admitted to our hospital over a five-year period. Of them, 91 developed at least one UTI episode, with a total number of 260 positive urine cultures. We collected data about age at diagnosis of CAKUT, sex, origin environment, type and side of CAKUT, number of UTIs, type of uropathogen, and uropathogens antibiotic resistance. Results: Distribution of uropathogens was Escherichia coli (38.84%), Klebsiella spp. (21.15%), Enterococcus spp. (15.76%), Proteus spp. (8.07%), Pseudomonas spp. (8.07%), Enterobacter spp. (2.3%), other Gram-negative bacteria (2.3%), and other Gram-positive bacteria (3.45%). High antibiotic resistance was detected for ampicillin, amoxicillin, and second-generation cephalosporins. Escherichia coli presented high resistance for cefepime and ceftriaxone. Pseudomonas spp. remained susceptible to amikacin, quinolones, and colistin. Vancomycin, teicoplanin, linezolid, and piperacillin/tazobactam remained effective in treating Gram-positive UTI. Conclusions: High antibiotic resistance was identified for frequently used antibiotics. Lower antibiotic resistance was observed for some broad-spectrum antibiotics. Understanding uropathogens’ antibiotic resistance is important in creating treatment recommendations, based on international guidelines, local resistance patterns, and patient particularities.
Published: 2021
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14. Overweight and Underweight Prevalence Trends in Children from Romania - Pooled Analysis of Cross-Sectional Studies between 2006 and 2015

Author: Adela Chirita-Emandi, Carmen Gabriela Barbu, Elena Eliza Cinteza, Bianca Ioana Chesaru, Mihai Gafencu, Veronica Mocanu, Ionela M. Pascanu, Simona Alexandra Tatar, Mihaela Balgradean, Michaela Dobre, Simona Vasilica Fica, Gabriela Edita Ichim, Raluca Pop, and Maria Puiu
Subjects: Obesity, Romania, Children, Overweight, Nutrition. Foods and food supply, TX341-641, Nutritional diseases. Deficiency diseases, RC620-627
Abstract: Aim: High-quality national representative data on obesity in Romanian children are needed to shape public health policies. To provide a unified data landscape on national prevalence, trends and other factors associated with underweight, overweight, and obesity in Romanian children aged 6-19 years, across the last decade (2006-2015). Methods: Using a common protocol, we selected published and unpublished studies that measured Romanian children in schools between 2006 and 2015. Children's BMI was classified using the current WHO, IOTF, and CDC references. Results: 25,060 children from 8 Romanian counties were included in the analysis. The prevalence of underweight children was 5%/4.5%/8.5% (WHO/IOTF/CDC), while the prevalence of overweight (including obese) children was 28.3%/23%/23.2% (WHO/IOTF/CDC). The prevalence of overweight children did not change significantly over the last decade (chi-square test p = 0.6). Male gender (odds ratio (OR) 1.37; 95% CI 1.29-1.45, compared to female); prepubertal age (OR = 3.86; 95% CI 3.41-4.36,compared to postpubertal age), and urban environment (OR 1.12; 95% CI 1.01-1.26, compared to rural environment) had higher risk for overweight. Conclusion: While the prevalence of underweight children was low, almost one in four children in Romania was overweight or obese (according to WHO criteria) between 2006 and 2015. This prevalence remained relatively stable over the last decade. Male gender, prepubertal age, and urban environment, were the most relevant risk factors associated with overweight status in Romanian children.
Published: 2016
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15. Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity

Author: Vlad Serafim, Adela Chirita-Emandi, Nicoleta Andreescu, Diana-Andreea Tiugan, Paul Tutac, Corina Paul, Iulian Velea, Alexandra Mihailescu, Costela Lăcrimioara Șerban, Cristian G. Zimbru, Maria Puiu, and Mihai Dinu Niculescu
Subjects: polyunsaturated fatty acids, pemt, mthfr, children, obesity, red blood cells, Nutrition. Foods and food supply, TX341-641
Abstract: Polyunsaturated fatty acids (PUFAs) play important roles in health and disease. PUFA levels are influenced by nutrition and genetic factors. The relationship between PUFA composition in red blood cells (RBCs) and genetic variations involved in PUFA metabolism has not been investigated in children with obesity. This study evaluated the association between several genetic variations and PUFA levels in RBCs in children with obesity. One hundred ninety-six children with obesity (101 females, 95 males) were evaluated using anthropometric measurements, dietary intakes, plasma and RBC PUFA quantification, blood biochemistry, and 55 single nucleotide polymorphisms within 14 genes. phosphatidylethanolamine N-methyltransferase (PEMT) rs1109859 and methylenetetrahydrofolate reductase gene (MTHFR) rs4846052 genotypes were associated with PUFA levels in RBCs. PUFA intake did not influence the RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. Higher RBC DHA and EPA levels were observed for PEMT rs1109859 GG and GA genotypes versus the AA genotype. Higher levels of RBC DHA, EPA, arachidonic acid (ARA), and linoleic acid (LA) and were observed for MTHFR rs4846052 TT genotype versus TC and CC genotypes. Genetic variations in PEMT rs1109859 and MTHFR rs4846052 were associated with different PUFA levels in RBC membranes and are estimators for PUFA species in RBCs. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children.
Published: 2019
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16. Vitamin D Status: A Different Story in the Very Young versus the Very Old Romanian Patients.

Author: Adela Chirita-Emandi, Demetra Socolov, Carmen Haivas, Anca Calapiș, Cristina Gheorghiu, and Maria Puiu
Subjects: Medicine, Science
Abstract: In Romania (latitude 48°15'N to 43°40'N), vitamin D supplementation is common practice mostly in infants 0-1 year old. No published information is available regarding epidemiological data on vitamin D status in the Romanian population for a wide age range and geographical territory. In this context, we aimed to evaluate the seasonal and age variation of vitamin D status in a large Romanian population.6631 individuals from across Romania had performed 7544 vitamin D assessments (2012-2014) in a chain of private laboratories. Vitamin D (25-hydroxyvitamin D2 and 25-hydroxyvitamin D3) was measured using High Performance Liquid Chromatography. Vitamin D levels were classified as severe deficiency100 ng/ml.Male to female ratio was 1:2.9. Age ranged from 0 to 85 years. Mean vitamin D levels increased from April (26.3n g/ml) to September (35.6 ng/ml) and decreased from October (33.5 ng/ml) to March (24.4 ng/ml). Overall 40% had sufficient vitamin D, while the rest were insufficient 33%, deficient 22%, severely deficient 4% and 1% potentially harmful (of them 81% under 1 year old). Males compared to females showed higher percentages of sufficiency (47% vs. 38%). Children 0- 2 years presented the highest percentage of vitamin D sufficiency (77%). Lowest percentages (21%) of sufficiency were in people 80-84 years.In Romania, suboptimal vitamin D levels are common (59%), especially in older age, wintertime and in women. Vitamin D supplementation would be most warranted from January to April in the Romanian population. 25-hydroxyvitamin D levels > 100 ng/ml were relatively prevalent in children 0-1 year old (17.3%). This was attributed to supplementation errors and the fact that high-risk individuals were more likely to visit for medical check-up. Nonetheless, it stresses the need to increase awareness of the importance of preventing Vitamin D supplementation administration errors in the young.
Published: 2015
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17. Use of a Micronutrient Cocktail to Improve Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) in Adults with Obesity: A Randomized, Double-Blinded Pilot Clinical Trial

Author: Iulia Teodora Perva, Iulia Elena Simina, Renata Bende, Alexandru Cătălin Motofelea, Adela Chirita Emandi, Nicoleta Andreescu, Alexandra Sima, Adrian Vlad, Ioan Sporea, Cristian Zimbru, Paul Calin Tutac, Maria Puiu, and Mihai Dinu Niculescu
Subjects: 5-MTHF, betaine, choline, omega-3 fatty acids, vitamin B12, metabolic syndrome, Medicine (General), R5-920
Abstract: Background and Objectives: The goal of this study was to assess the impact of supplementation with a combination of nutrients on metabolic-dysfunction-associated steatotic liver disease (MASLD)-related liver parameters, and other parameters related to metabolic syndrome in adults with obesity. These measurements included anthropometric and lipid profiling, and FibroScan technology (controlled attenuation parameter (CAP) and transient elastography (TE) values). Materials and Methods: A double-blind, placebo-controlled pilot clinical trial was conducted over a three-month treatment period. Adults with metabolic syndrome and obesity were allocated to receive either a cocktail of nutrients with defined daily dosages (5-MTHF, betaine, alpha-linolenic acid, eicosapentaenoic acid, choline bitartrate, docosahexaenoic acid, and vitamin B12) or a placebo. The participants were evaluated at the start and the end of the three-month treatment period. Results: A total of 155 participants entered the study, comprising 84 in the treatment group and 71 in the placebo group. The administration of the nutritional supplement resulted in a notable reduction in both CAP and TE scores when compared to the placebo group. The treatment group exhibited a mean reduction in CAP of 4% (p < 0.05) and a mean reduction in TE of 7.8% (p < 0.05), indicative of a decline in liver fat content and fibrosis. Conclusions: The supplementation over a period of three months led to a significant amelioration of liver fibrosis and steatosis parameters in adults with metabolic syndrome and obesity. These findings suggest that this supplementation regimen could be a beneficial adjunct therapy for improving liver health in adults with obesity-induced MASLD.
Published: 2024
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18. A comprehensive analysis concerning eating behavior associated with chronic diseases among Romanian community nurses.

Author: Onofrei, Lidia-Manuela, Puiu, Maria, and Serban, Adela Chirita-Emandi Costela Lacrimioara
Published: 2024

19. Copy number variation analysis in 189 Romanian patients with global developmental delay/intellectual disability

Author: Radu A. Popp, Adela Chirita-Emandi, Diana Miclea, Delia Stefan, Camelia Alkhzouz, Cristian G. Zimbru, Simona Bucerzan, Sergiu Osan, Monica Mager, and Maria Puiu
Subjects: Chromosome Aberrations, DNA Copy Number Variations, Romania, Developmental Disabilities, Romanian, General Medicine, Uniparental Disomy, medicine.disease, language.human_language, Developmental psychology, Intellectual Disability, Intellectual disability, language, medicine, Humans, Global developmental delay, Copy-number variation, Child, Psychology
Abstract: Background Developmental delay and intellectual disability represent a common pathology in general population, involving about 3% of the pediatric age population, the genetic etiology being often involved. The aim of this study was to determine the clinically relevant copy number variants in patients diagnosed with global developmental delay/intellectual disability in our population, using the chromosomal microarray analysis. Methods We analyzed 189 patients diagnosed with global developmental delay/intellectual disability, presented in Clinical Emergency Hospital for Children, Cluj-Napoca. The patients were completely clinically investigated, including dysmorphic and internal malformations evaluation, psychiatric, neuropsychological and metabolic evaluation, standard karyotyping. Genomic analysis was done using chromosomal microarray analysis. Results Pathogenic findings (including uniparental disomy) and variants of unknown significance were detected in 53 of 189 patients (28.04%). Pathogenic copy number variants and uniparental disomy were observed in 35 of 189 patients (18.51%). Two patients presented uniparental disomy for chromosome 15, one with clinical phenotype of Prader-Willi syndrome and the other with clinical phenotype with Angelman syndrome. Within the category of pathogenic findings, the recurrent copy number variants were seen in 21 of 35 patients (60%). Conclusions The increased percentage of pathogenic structural variants observed in patients with global developmental delay/intellectual disability analyzed by chromosomal microarray technique supports its use in patients with a non-specific phenotype such as these neurodevelopmental disorders. The high percentage of recurrent pathogenic variants between these findings is a finding that support their initial evaluation when a genetic testing algorithm could be a useful option.
Published: 2022

20. CHDH-PNPLA3 Gene–Gene Interactions Predict Insulin Resistance in Children with Obesity

Author: Corina Paul, Nicoleta Andreescu, Costela Lacrimioara Serban, Iulian Velea, Paul Tutac, Alexandra Mihailescu, Diana-Andreea Tiugan, Adela Chirita-Emandi, Cristian G. Zimbru, Maria Puiu, Mihai D. Niculescu, and Vlad Serafim
Subjects: Pharmacology, medicine.medical_specialty, business.industry, Fatty liver, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, 030204 cardiovascular system & hematology, medicine.disease, Obesity, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin resistance, Endocrinology, Gene interaction, chemistry, Internal medicine, Internal Medicine, medicine, Homeostatic model assessment, Choline, Metabolic syndrome, business
Abstract: Introduction Insulin resistance plays a major role in metabolic syndrome and is recognized as the most common risk factor for non-alcoholic fatty liver disease (NAFLD). Identifying predictors for insulin resistance could optimize screening and prevention. Purpose To evaluate the contribution of multiple single nucleotide polymorphisms across genes related to NAFLD and choline metabolism, in predicting insulin resistance in children with obesity. Methods One hundred fifty-three children with obesity (73 girls), aged 7-18 years, were evaluated within the NutriGen Study (ClinicalTrials.gov-NCT02837367). Insulin resistance was defined by Homeostatic Model Assessment for insulin-resistance cut-offs that accommodated pubertal and gender differences. Anthropometric, metabolic, intake-related variables, and 55 single nucleotide polymorphisms related to NAFLD and choline metabolism were evaluated. Gene-gene interaction effects were assessed using Multiple Data Reduction Software. Results Sixty percent (93/153) of participants showed insulin resistance (58.7% of boys, 63% of girls). Children with insulin resistance presented significantly higher values for standardized body mass index, triglycerides, transaminases and plasma choline when compared to those without insulin resistance. Out of 52 single nucleotide polymorphisms analysed, the interaction between genotypes CHDH(rs12676) and PNPLA3(rs738409) predicted insulin resistance. The model presented a 6/10 cross-validation consistency and 0.58 testing accuracy. Plasma choline levels and alanine aminotransferase modulated the gene interaction effect, significantly improving the model. Conclusion The interaction between genotypes in CHDH and PNPLA3 genes, modulated by choline and alanine aminotransferase levels, predicted insulin-resistance status in children with obesity. If replicated in larger cohorts, these findings could help identify metabolic risk in children with obesity.
Published: 2020

21. Biallelic variants in BRCA1 gene cause a recognisable phenotype within chromosomal instability syndromes reframed as BRCA1 deficiency

Author: Smaranda Arghirescu, Mihai Ioana, Nicoleta Andreescu, Razvan Mihail Plesea, Anca-Lelia Riza, Cristina Popa, Adela Chirita-Emandi, Alexandra Mihailescu, and Maria Puiu
Subjects: 0301 basic medicine, Microcephaly, business.industry, Bone marrow failure, Diepoxybutane, Disease, medicine.disease, Phenotype, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, chemistry, 030220 oncology & carcinogenesis, Chromosome instability, Immunology, Genetics, Medicine, business, Genetics (clinical), Immunodeficiency, Brca1 gene
Abstract: Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients’ health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.
Published: 2020

22. Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Luxia Zhang, Young-Ho Khang, Ellina Rakhimova, Kairit Mikkel, Tiina Vlasoff, Eruke E. Egbagbe, Sidsel Graff-Iversen, Ilona Nenko, Magdalena Klimek, Mathilde Savy, Sanjib Kumar Sharma, Alfonso Siani, Luís Lopes, Vanina Bongard, Gregor Jurak, Jacqueline F. Price, Christina-Paulina Lambrinou, Maria Lc Iurilli, Rainford J. Wilks, Bontha V. Babu, Fereidoun Azizi, Harunobu Nakamura, Marialaura Bonaccio, Angela Döring, Zhenyu Zhang, Naser Ahmadi, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Clive Osmond, Thirunavukkarasu Sathish, Robert J. Adams, Themistoklis Tzotzas, Reina Engle-Stone, Atul Trivedi, Shoichiro Tsugane, Niels Møller, Jorge Bezerra, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Badreya Al-Lahou, J. Jaime Miranda, Bahram Mohajer, Sigmund A. Anderssen, Lital Keinan Boker, Eero Kajantie, Martin Gulliford, Maties Torrent, Sumit Bharadwaj, Toshiharu Ninomiya, Zbigniew Gaciong, Nayu Ikeda, Li Juan Wu, Adrian Richter, Licia Iacoviello, Marc J. Gunter, Wenbin Wei, Norsyamlina Che Abdul Rahim, Eman Aly, Ambady Ramachandran, Nils Lehmann, Soile E. Puhakka, Giovanni Veronesi, Hongsheng Bi, Eiji Oda, Jia Li Duan, Per Tynelius, José María Huerta, Janne Schurmann Tolstrup, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Hanno Ulmer, Shukri F. Mohamed, Anthony Kafatos, Suyeon Park, Mohsen Ibrahim, Hamed Pouraram, Bin Zhou, May Soe Aung, Lars Bo Andersen, Erfan Ghasemi, René Charles Sylva, Himanshu K. Chaturvedi, Luc Dauchet, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Valérie Deschamps, Ko Ko Zaw, Peter Vollenweider, Tomas Vega, Yves Martin-Prével, Mahfuzar Rahman, Dorja Vočanec, Roman Topor-Madry, Vinay Nangia, Herculina S. Kruger, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Cecilia Björkelund, Tatjana Hejgaard, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Carlos P. Boissonnet, Santosh K. Bhargava, Patrick Kolsteren, Dermot O'Reilly, Bahareh Kheiri, Wolfgang Kratzer, Susanne R. de Rooij, H. Bas Bueno-de-Mesquita, Günther Fink, José R. Banegas, Michele Monroy-Valle, Drude Molbo, Mahmudur Rahman, Hynek Pikhart, Rafael N. Pichardo, Massimo Salvetti, Hui Cai, Sarah Filippi, Georg Posch, Hung-Kwan So, Yonghua Hu, Katsuyasu Kouda, Joana Carvalho, Gailute Bernotiene, Hannu Uusitalo, Thein Thein Htay, Felix Kaducu, Maigeng Zhou, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Michel Joffres, Sabina Zambon, Ronald D. Gregor, Vayia Rarra, Seyed Mohammad Hashemi-Shahri, Loreto Santa Marina, Galina Obreja, Rudolf Kaaks, Aya Mostafa, Maria do Carmo Franco, Beata Gurzkowska, Chien-Jen Chen, Marie Moitry, Nizal Sarrafzadegan, Xiangjun Wang, Diego Giulliano Destro Christofaro, Imperia Brajkovich, Fangfang Chen, Francesco Panza, Ling Yang, Holly E. Syddall, Cecily Kelleher, Michael Tornaritis, Ningli Wang, Lutgarde Thijs, Marjolein Visser, Angelika Schaffrath Rosario, María José Tormo, Jostein Steene-Johannessen, Norbert Amougou, Emmanuella Magriplis, Mar Alvarez-Pedrerol, Jingli Gao, Stig E. Bojesen, Giuseppe Grosso, Seongjun Ha, Lauren Lissner, Mikhail Benet, Anastasia Markaki, Sanjay Rampal, Antônio Augusto Moura da Silva, Maria Lorenza Muiesan, Angelique Chan, Yvonne T. van der Schouw, Annamari Lundqvist, Philippe Amouyel, Kristyna Zejglicova, Charalambos Hadjigeorgiou, João Breda, Jørgen Meisfjord, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Vilma Irazola, Leng Huat Foo, Óscar Lopes, Dickman Gareta, Flavio Nervi, Imre Janszky, Ruzena Kubinova, Terho Lehtimäki, Mario V. Capanzana, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Shuohua Chen, Arvind Pandey, Luigi Palmieri, Roya Kelishadi, Srinivasan Kannan, Jie Mi, Robert Beaglehole, Liliana Dacica, Jyrki K. Virtanen, Mohan Deepa, Peter Ueda, Isti Ilmiati Fujiati, Hermann Pohlabeln, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, Mohsen Azimi-Nezhad, Henry Völzke, Karolina Milkowska, Zahra Mohammadi, Belgin Ünal, Magda Gasull, George S. Stergiou, Marshall K. Tulloch-Reid, Seppo Koskinen, James E. Bennett, Marcela González-Gross, Virginija Dulskiene, Idris Guessous, Assembekov Batyrbek, Kamarul Imran Musa, Jeannette Lee, Josep Redon, Bihungum Bista, Luisa M Macieira, Johan Sundström, Andres Metspalu, Lariane M Ono, Flora A. Ukoli, Salar Rahimikazerooni, Andrea Gualtieri, Trevor S. Ferguson, Félicité Tchibindat, Eliza Cinteza, Ha Tp Do, Tajana Zeljkovic Vrkic, Tuyen D Le, Alison J. Hayes, Abdul Basit, Chandini Nekkantti, Teresa Norat, Eunice Ugel, Gulmira Aitmurzaeva, Mariachiara Di Cesare, Abdul Hamid Zargar, Vincenzo Solfrizzi, Garry L. Jennings, Aline Meirhaeghe, Kaare Christensen, Päivi Mäki, Xu Lin, Ali Esmaeili, Joanna Baran, Aneta Grajda, Renata Cifkova, Alexandre C. Pereira, Martin Bobak, Iuliia A Rusakova, Keiu Nelis, Damian K Francis, Guansheng Ma, Axel C. Carlsson, Alejandro Diaz, Alireza Ansari-Moghaddam, N Capkova, Zumin Shi, Maria Turley, Imelda A. Agdeppa, Helena I. S. Nogueira, Marcia Scazufca, Katharina Maruszczak, Natascia Rinaldo, Paulo A. Lotufo, Nuno Lunet, Thor Aspelund, Caroline H.D. Fall, Antonio Cabrera de León, Ahmad Faudzi Yusoff, Holger Theobald, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Mihai Gafencu, Tandi E. Matsha, Ana B. Crujeiras, Ahmad Reza Dorosty, Alain Morejon, Weili Yan, Dominique Hange, Bekbolat Zholdin, Frédéric Gottrand, Jorge Mota, Jana Námešná, Stevo Popovic, Louise Eriksen, Line Lund Kårhus, Cihangir Erem, Juergen Breckenkamp, Mathilde Kersting, Yi Song, Martin McKee, Aleksandra Gomula, Rafaela Rosário, Enzo Manzato, S. Goya Wannamethee, Sounnia Mediene Benchekor, Azim Nejatizadeh, Krishna Kumar Aryal, Juan P. González-Rivas, Vedrana Sember, Stephen T. McGarvey, Jukka T. Salonen, Patrick Pasquet, Patricia Varona-Pérez, Amelia C. Crampin, Ramin Heshmat, Violeta Iotova, Juvenal Soares Dias-da-Costa, Oye Gureje, Aletta E. Schutte, João Luiz Bastos, Anelise Reis Gaya, Konrad Jamrozik, Dalia Luksiene, Amina Barkat, Maria Paula Santos, José Camolas, Azli Baharudin, Diego Vanuzzo, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, Albertino Damasceno, Davood Khalili, Simona Bo, Martina Müller-Nurasyid, Dominique Cottel, Markku Peltonen, Fikru Tullu, Ana Isabel Rito, Angélica Ochoa-Avilés, Annette J. Dobson, Christopher T. Cowell, Charumathi Sabanayagam, Rildo de Souza Wanderley Júnior, Oanh T. H. Trinh, Farahnaz Joukar, Mostafa K. Mohamed, Mostafa Qorbani, Jeongseon Kim, Helmut Schröder, Machi Suka, Natasja M. van Schoor, Jussi Kauhanen, Teresa Haugsgjerd, Goodarz Danaei, M. Fernanda Lima-Costa, Yong Tao, Elisabetta L. Romeo, Grazyna Jasienska, Victor Guillermo Sequera, Kazem Mohammad, Yanina Zócalo, Fernanda Cunha Soares, Jianfeng Wu, Mohammad Esmaeel Motlagh, María Elena Díaz-Sánchez, Monika Zuziak, Eldridge Ferrer, Anette Varbo, Leila Beltrami Moreira, Jeremy M. Jacobs, Kenneth James, Elena Sacchini, Pascal Bovet, Mahboubeh Parsaeian, Tania Lopez, Ya Xing Wang, Wojciech Drygas, Jody C Miller, Svetlana A. Shalnova, Maria Elisa Zapata, Chung T Nguyen, Nimmathota Arlappa, Edwige Landais, Thorkild I. A. Sørensen, Jeannette Klimont, Amirabbas Momenan, Erik J. Timmermans, Mari-Liis Tammesoo, Jost B. Jonas, Stefania Toselli, Maria Teresa Anselmo Olinto, Bahman Cheraghian, Kouamelan Doua, Esteban Carmuega, Marjeta Mišigoj-Duraković, Bo Werner, M. Arfan Ikram, Breige A. McNulty, Christa Meisinger, Clara Homs, Namuna Shrestha, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Alicia Matijasevich, Alison J Price, Ala'a Alkerwi, Kristine H. Allin, Lorenza Pilotto, Mohannad Al Nsour, Ingunn Holden Bergh, Marianna Noale, Heba Fouad, Vilnis Dzerve, Novie O. Younger-Coleman, Peter Willeit, Andrea R. V. R. Horimoto, Freda Pitakaka, Habiba Ben Romdhane, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Cristina Padez, Sarah P. Garnett, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tien Yin Wong, Rosa Haghshenas, Jonathan Giovannelli, Christina Howitt, Marleen E. Hendriks, Fadia AlBuhairan, Huashuai Chen, Gretchen A Stevens, Luís B. Sardinha, David Goltzman, Jenny M. Kindblom, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Rajendra Pradeepa, Yi-Ting Lin, Martin Neovius, Juan Francisco Miquel, Ellis Owusu-Dabo, Anil Poudyal, Marzieh Katibeh, Tanja Stocks, Veronica Mocanu, Ulla Roggenbuck, Robespierre Ribeiro, Gabriele Eiben, Mary Simon, Christine Cameron, Hamid Hakimi, Kamel Ajlouni, Jakub Stokwiszewski, Iulia Jurca Simina, Pietro Amedeo Modesti, Frederick C. W. Wu, Peter Kristensen, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Martijn Huisman, Betina H. Thuesen, Queenie Chan, Antonisamy Belavendra, Artur Mazur, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Marcos André Moura-dos-Santos, Jean Ferrières, Farhad Zamani, Shina Avi, Yves Kameli, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Thomas Meinertz Dantoft, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Azaliia M Tuliakova, Vera Lanska, Tint Swe Latt, Matthias Bopp, Abbas Rezaianzadeh, Rod Jackson, Johan Van der Heyden, Reecha Sofat, Koen Van Herck, Allan G. Hill, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Stela McLachlan, Ulrike Gehring, Ranko Stevanovic, Nagalla Balakrishna, Lekhraj Rampal, Marjolijn C. E. Bragt, Saeid Eslami, Napoleón Pérez-Farinós, G. K. Mini, Viktoria Anna Kovacs, Rosemarie Martin, Nahla Hwalla, Wei Zheng, Hoang Van Minh, Edward D Janus, Laetitia Huiart, Farhad Pourfarzi, Sudha Ramachandra Rao, Fred Paccaud, Marcia Makdisse, Aye Aye Sein, Enrique Gutiérrez-González, Yang Yang, Anneke Blokstra, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Wan Nazaimoon Wan Mohamud, Jesús Ibarluzea, Julio Zuñiga Cisneros, Laura Lauria, Argyro Karakosta, Dragana P Jovic, Jun Hata, Elio Riboli, Piotr Bandosz, Xun Tang, Parvina Mukhtorova, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Aleksandra Piwońska, Dusan Grafnetter, Mette Rasmussen, Daniel Weghuber, Sherali Rakhmatulloev, Martine Vrijheid, Johann Willeit, Motahareh Kheradmand, Małgorzata Mossakowska, Lechaba Tshepo, Dongfeng Gu, Hyeon Chang Kim, Vilmundur Gudnason, Maria Forsner, Peter Bjerregaard, Leon A. Simons, Rachael McLean, Japhet Killewo, Ramón Suárez-Medina, Y Nikitin, Eng Joo Tan, Jean Claude Mbanya, Aroor Bhagyalaxmi, Renata Kuciene, Kairat Davletov, Jose Eugenio Lozano, Afshin Ostovar, Niloofar Peykari, Guy De Backer, Soheir H Ahmed, Nicholas J. Wareham, Sai Yin Ho, Constanta Huidumac Petrescu, Maria Hassapidou, Iris Pigeot, Myriam Galfo, Susana Cararo Confortin, Blanca Sandra Ruiz-Betancourt, W. M. Monique Verschuren, Catterina Ferreccio, Fabio Galvano, Leila Houti, Daniel Bia, Annika Rosengren, Marcin Rutkowski, Biruta Velika, Joana Araújo, Fernando Rigo, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Marie Kunešová, Boban Mugoša, Sania Nishtar, Mangesh S. Pednekar, Shahla AlDhukair, Helle-Mai Loit, Antonis Zampelas, Altan Onat, Maciej Banach, Shohreh Naderimagham, Hajer Aounallah-Skhiri, Maja Bæksgaard Jørgensen, Yin Guo, Ewelina Czenczek-Lewandowska, Parasmani Dasgupta, Elvis Oa Wambiya, Inge Huybrechts, Raimund Erbel, Jari Jokelainen, Ana P. Ortiz, Stefan Kiechl, Emmanuel Cohen, Caleb Ochimana, Shynar Abdrakhmanova, Laura Censi, Iqbal Bata, Geetha R Menon, Snehalatha Chamukuttan, Pedro Plans-Rubio, Domenico Palli, Ana Azevedo, Slawomir Koziel, Benoît Salanave, Parinaz Mehdipour, Shu Ti Chiou, Lela Sturua, Lubica Ticha, Felipe Vogt Cureau, Jin Soo Moon, Ming-Hui Zhao, Urho M. Kujala, Nathalie Michels, Ertugrul Celikcan, Jaakko Tuomilehto, Judith Benedics, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, Andrea Rodriguez-Martinez, Tai Hing Lam, Yn-Tz Sung, Jürgen König, Kodavanti Mallikharjuna Rao, Hazzaa M. Al-Hazzaa, Karen Morgan, Bogdan Wojtyniak, Cynthia M. Pérez, Ilse Khouw, Manoli Garcia-de-la-Hera, Dong Wook Shin, Genc Burazeri, Ausra Petrauskiene, Charles Sossa Jérome, Kenisha Russell Jonsson, José Boggia, Daniela Galeone, Alice Bonilla-Vargas, Han Cg Kemper, Rahman Shiri, Stefaan Demarest, Else Karin Grøholt, San-Lin You, Adelheid Weber, Juha Auvinen, Aida Pilav, Sibel Gogen, Suzanne N Morin, Wan Mohamad Wan Bebakar, Viviane Cunha Cardoso, Kavumpurathu Raman Thankappan, Hana Zamrazilová, Frank Claessens, Karien Stronks, Helen Gonçalves, Tahir Aris, Luis Revilla, Sérgio Viana Peixoto, Zhamilya Battakova, Jing Liu, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Priscilla Duboz, Sandjaja, Tiina Laatikainen, Rafel Ramos, Sareh Eghtesad, Judith Simons, Orn Olafsson, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Aung Soe Htet, Bente Sparboe-Nilsen, Paul Elliott, Soon-Woo Park, Angel R. Gonzalez, Ying-Wei Wang, Rob M. van Dam, Ryutaro Ohtsuka, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Lynell V Maniego, Fariborz Mansour-Ghanaei, Maria Dorobantu, Giovanni Viegi, Xiaoguang Yang, Honor Bixby, Prakash C. Gupta, Ofra Kalter-Leibovici, Eugene Sobngwi, Ričardas Radišauskas, Jurate Medzioniene, Roy A Wong-McClure, Kim F. Michaelsen, Antonia Trichopoulou, Tania Tello, Francesco Branca, Johanna Gunnlaugsdottir, Els Clays, Wei-Yen Lim, Suzanne C. Ho, Toomas Veidebaum, Rebecca Goldsmith, Margot González-León, Matthias Nauck, Alibek Mereke, Marta Buoncristiano, Jakob Tarp, Rosalba Rojas-Martínez, Maya Tanrygulyyeva, Reza Malekzadeh, Abdonas Tamosiunas, Dimitrios Poulimeneas, Pedro Ordunez, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Anne Juolevi, Vassilis Zafiropulos, Emanuela Gualdi-Russo, Jordi Sunyer, Manu Raj, Chaoqiang Jiang, Sofia Malyutina, Efthymios Kapantais, Maria Lazo-Porras, Maung Maung Than Htike, Michael Hobbs, Ranjit Mohan Anjana, Merike Liivak, Johan G. Eriksson, Margarita Samoutian, Andreia N. Pizarro, Mohammed Rasoul Tarawneh, Jean Woo, Kaspar Staub, Maria Teresa Menzano, Mojtaba Farjam, Adroaldo Cesar Araujo Gaya, Mohammad El-khateeb, Zulfiqar A Bhutta, Mukharram M. Bikbov, Hsien-Ho Lin, Oscar Noboa, Thomas Waldhör, Garry Brian, Simona Costanzo, Frank Tanser, Nor Azwany Yaacob, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ioannis Pagkalos, Ivan Pećin, Carlo M. Barbagallo, Abla M. Sibai, Yuna He, Matsuda Fumihiko, Bharathi Viswanathan, Ali Reza Safarpour, Wei Cheng Lo, Abdullatif Husseini, Jiang He, Liv Elin Torheim, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, William R. Tebar, Yingfeng Zheng, Eha Nurk, Bhawesh Koirala, Ana Jelakovic, Suhad Bahijri, Freja B Kampmann, Qi Sheng You, Marika Ferrari, María-Elena González-Villalpando, Aline Wagner, Olfa Saidi, Anwar Batieha, Eduardo Capuano, Coimbatore Subramaniam Shanthirani, Dong Wook Kim, Albina A Fakhretdinova, Tom Wilsgaard, Maria Avdicova, Moesijanti Soekatri, Chiara Donfrancesco, Salim Mohanna, Paola Russo, Uruwan Yamborisut, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Khairil Si-Ramlee, Kirsten Mehlig, Christina Mavrogianni, Raluca Pop, Lèlita Santos, Graziella Bruno, Valentina Peterkova, Iná S. Santos, Georg Lappas, Alberto Palloni, Malay K. Mridha, Andrzej Pajak, Marta García-Solano, Stefaan De Henauw, Daniel Ferrante, Rute Santos, Anders Grøntved, Lucjan Szponar, Mihaela Vladulescu, Chien-An Sun, Jan A. Staessen, Paula Duarte de Oliveira, Norazizah Ibrahim Wong, Maria Nordendahl, Elaine M. Dennison, Jeonghee Lee, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Noushin Mohammadifard, Igor Spiroski, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Valéria Regecová, Cláudia S. Minderico, Johanna A. Otero, Jamila Abubakar Garba, Vesselka Duleva, Rui Ornelas, Ilpo Huhtaniemi, Cesar G. Victora, Lijuan Liu, Rody G. Sy, Mahmood Moosazadeh, Ali Ahmadi, Antonio Pedro Graça, Natalia Nowak-Szczepanska, Miao Li Chee, Michael Sjöström, Charles Agyemang, Shiqi Zhen, Xiu-Hua Guo, Pawel Kurjata, Jardena J. Puder, Mehrdad Azmin, Neil Murphy, Kaosar Afsana, Alireza Sadjadi, Johanna M. Geleijnse, Prashant Mathur, Elysée Claude Bika Lele, Raphael Mendes Ritti-Dias, Yannis Manios, Majid Shirani, Rosemary B. Duda, Liis Nelis, Jurate Klumbiene, Zhengming Chen, Wichai Aekplakorn, Alun Evans, Andrzej Wiecek, Lars Lind, Denise Eldemire-Shearer, Bernardo L. Horta, Macia Enguerran, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Kumiko Ohara, Ursula Kiechl-Kohlendorfer, Hermann Brenner, Przemyslaw Slusarczyk, Espen Bjertness, Jutta Stieber, Augusto Di Castelnuovo, Joel G. R. Roy, Aryeh D. Stein, Ruth Frikke-Schmidt, Vera Musil, Amaneh Shayanrad, Marcel Goldberg, Ramon O. Jimenez, Mohammad Reza Fattahi, Jolanda Hyska, Amir Houshang Mehrparvar, Elin Kolle, Mohamed Bamoshmoosh, Michelle Holdsworth, Felipe F. Casanueva, Børge G. Nordestgaard, Niels Wedderkopp, Eva Corpeleijn, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Larissa Pruner Marques, Slavica Sović, Olli T. Raitakari, Marco Aurélio Peres, Alexandra Cucu, Gregorio Varela-Moreiras, Janine Clarke, Andrea Gazzinelli, Mieczysław Litwin, Sara Schramm, Xenophon Theodoridis, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Dimitrios Papandreou, Peter T. Katzmarzyk, Benjamin Acosta-Cazares, Ben Schöttker, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Sadaf G. Sepanlou, Adolfo Rubinstein, Francis Delpeuch, Julianne Williams, Abbas Dehghan, Leanne M. Riley, Heloisa Bettiol, Gabriele Nagel, Ellisiv B. Mathiesen, Ekaterina Stoyanova, Alisha N. Wade, Zhamyila Usupova, Arnaud Chiolero, Oonagh Markey, Jacqueline Ramke, Elena Bogova, Niveen M E Abu-Rmeileh, Nguyen D Nguyen, Tomasz Zdrojewski, Marjo-Riitta Järvelin, Jose Sanchez-Abanto, Rômulo Araújo Fernandes, Lourdes Ribas-Barba, Nalan Uysal, Mohamad Hasnan Ahmad, Krista Fischer, Maria Wany Louzada Strufaldi, Ramiro Guerrero, Farnam Mohebi, Tran Quoc Bao, Flávio Danni Fuchs, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Farzad Hadaegh, Robert Lundqvist, Saeid Safiri, Iraj Mohebbi, George Luiz Lins Machado-Coelho, Annette Peters, Gonzalo Valdivia, Magdalena Korzycka, Rajiv T Erasmus, Masanori Iwasaki, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Quang Ngoc La, Ricky Eddie, Petra Rust, Daniela Rodrigues, Dirk De Bacquer, Karen Sparrenberger, Agneta Sjöberg, Thet Thet Mu, Katarzyna Dereń, Cora L. Craig, Jorge Motta, Janina Petkeviciene, Boyd Swinburn, Paibul Suriyawongpaisal, Visnja Djordjic, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Daan Kromhout, Marius B. Bjertness, Stefano Marventano, Juel Jarani, Alireza Khosravi, Eva Martos, David De Ridder, Lizzy M. Brewster, Nico Dragano, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Hashem Jaddou, Grzegorz Sobek, Dimitrios Trichopoulos, Marvin Cervantes-Loaiza, Abu Am Hanif, Elaine M. Murtagh, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Kyungwon Oh, Heiner Boeing, Regina Heidinger-Felso, André Luiz Sena Guimarães, Balkish M. Naidu, Avula Laxmaiah, Ana M. B. Menezes, Marie Eliasen, Francesco Pistelli, Yuan He, Dusko Bjelica, José A. Casajús, Guang Ning, Lutgart Braeckman, Dirk Vanderschueren, Jochanan Stessman, Ivana Radic, Yi Zeng, Hans Concin, Damaskini Valvi, Sari Hantunen, Catherine Kyobutungi, Diego Augusto Santos Silva, Wenhua Zhao, Sok King Ong, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Mattias Johansson, Samuel C. Dumith, Magdalena Muc, Sabine Schipf, Idowu O Senbanjo, Jim Mann, Rajaa Al-Raddadi, Yih Chung Tham, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Sahar Saeedi Moghaddam, Reza Mohammadpourhodki, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Camilla T. Damsgaard, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Constance Schultsz, Santiago F. Gomez, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Pierre Traissac, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Eleonora d'Orsi, Irene G. M. van Valkengoed, Anna Fijałkowska, Wen-Harn Pan, Gregor Starc, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Abdullah Alkandari, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Saeed Dastgiri, Lien Braeckevelt, Nasheeta Peer, Radka Taxová Braunerová, Mohamed M. Ali, Steiner Krokstad, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Silvana Donoso, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paola Nardone, Alberto Barceló, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Miquel Porta, Vesna Jureša, Alexander D. Deev, David Faeh, Antonio Bernabe-Ortiz, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Anjani Kumar Jha, Thamara Hubler Figueiró, Jana Kratenova, Claudia M. Hormiga, Maria Tsigga, Zivka Dika, Indrapal I. Meshram, Ei Ei K. Nang, Ian Rouse, Rusidah Selamat, Paul Korrovits, Grethe S. Tell, Julie Taylor, Anabela Mota-Pinto, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Frank J Rühli, Shelly R. McFarlane, Sara Santos Sanz, Edyta Łuszczki, Maria G. Stathopoulou, Tara Coppinger, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Muhammad Islam, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Maria Ruiz-Castell, Daniela Pierannunzio, Cristina Taddei, Gowri Mahasampath, Gustavo Velasquez-Melendez, Hanna Tolonen, Sudhir Kowlessur, Bagher Larijani, Laura Torres-Collado, Susi Kriemler, Ali Akbar Shayesteh, Cynthia Robitaille, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Line Tang Møllehave, Vincent Jr DeGennaro, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Kodanda R Kanala, Gert B. M. Mensink, Abhijit Sen, Sergej M. Ostojic, Hanan F. Abdul Rahim, Hélène Delisle, Francisco J. Félix-Redondo, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Bethlehem D. Solomon, Erik Lykke Mortensen, Nikhil D. Patel, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Son Thai Pham, Simona Giampaoli, Dong Zhao, Indah Suci Widyahening, Merete Osler, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, Giota Touloumi, Janice Luisa Lukrafka, Adela Chirita-Emandi, Maryam Kavousi, Sanja Musić Milanović, Jean-Michel Gaspoz, Jalila El Ati, Sauli Herrala, Liang Xu, Pilar Guallar-Castillón, Bee Koon Poh, Luis Serra-Majem, Jonathan E. Shaw, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Yuki Fujita, Tiffany K. Gill, Nish Chaturvedi, Erkin M. Mirrakhimov, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Deepak Amarapurkar, Deepa Weerasekera, Diana A. 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Chan School of Public Health, Middlesex University [London], Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Montpellier Interdisciplinary center on Sustainable Agri-food systems (Social and nutritional sciences) (UMR MoISA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Centre International de Hautes Etudes Agronomiques Méditerranéennes - Institut Agronomique Méditerranéen de Montpellier (CIHEAM-IAMM), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Wellcome TrustEuropean Commission, Clinical Developmental Psychology, APH - Mental Health, Sociology, The Social Context of Aging (SoCA), Nutrition and Health, Iurilli, Maria LC [0000-0003-0409-1635], Zhou, Bin [0000-0002-1741-8628], Ezzati, Majid [0000-0002-2109-8081], Apollo - University of Cambridge Repository, Epidemiology and Data Science, APH - Aging & Later Life, APH - Societal Participation & Health, Public and occupational health, APH - Health Behaviors & Chronic Diseases, VU University medical center, APH 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Ltd, Orebro University, University of London, Universitas Indonesia, Institute of Food and Nutrition Development of Ministry of Agriculture and Rural Affairs, Children’s Hospital of Fudan University, University of Cyprus, Niigata University, International Medical University, Iran University of Medical Sciences, Center for Diabetes and Endocrine Care, Peking University First Hospital, Jiangsu Provincial Center for Disease Control and Prevention, Sun Yat-sen University, West Kazakhstan Medical University, Inner Mongolia Medical University, University of Ghana, Maria Lc Iurilli , Bin Zhou , James E Bennett , Rodrigo M Carrillo-Larco , Marisa K Sophiea , Andrea Rodriguez-Martinez , Honor Bixby , Bethlehem D Solomon , Cristina Taddei , Goodarz Danaei , Mariachiara Di Cesare , Gretchen A Stevens , Leanne M Riley , Stefan Savin , Melanie J Cowan , Pascal Bovet , Albertino Damasceno , Adela Chirita-Emandi , Alison J Hayes , Nayu Ikeda , Rod T Jackson , Young-Ho Khang , Avula Laxmaiah , Jing 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, Yves Martin-Prevel , Rosemarie Martin , Reynaldo Martorell , Eva Martos , Katharina Maruszczak , Stefano Marventano , Luis P Mascarenhas , Shariq R Masoodi , Ellisiv B Mathiesen , Prashant Mathur , Alicia Matijasevich , Tandi E Matsha , Christina Mavrogianni , Artur Mazur , Jean Claude N Mbanya , Shelly R McFarlane , Stephen T McGarvey , Martin McKee , Stela McLachlan , Rachael M McLean , Scott B McLean , Breige A McNulty , Sounnia Mediene Benchekor , Jurate Medzioniene , Parinaz Mehdipour , Kirsten Mehlig , Amir Houshang Mehrparvar , Aline Meirhaeghe , Jørgen Meisfjord , Christa Meisinger , Ana Maria B Menezes , Geetha R Menon , Gert Bm Mensink , Maria Teresa Menzano , Alibek Mereke , Indrapal I Meshram , Andres Metspalu , Haakon E Meyer , Jie Mi , Kim F Michaelsen , Nathalie Michels , Kairit Mikkel , Karolina Milkowska , Jody C Miller , Cláudia S Minderico , G K Mini , Juan Francisco Miquel , Mohammad Reza Mirjalili , Daphne Mirkopoulou , Erkin Mirrakhimov , Marjeta 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, Jaakko Mursu , Elaine M Murtagh , Kamarul Imran Musa , Sanja Music Milanovic , Vera Musil , Norlaila Mustafa , Iraj Nabipour , Shohreh Naderimagham , Gabriele Nagel , Balkish M Naidu , Farid Najafi , Harunobu Nakamura , Jana Námešná , Ei Ei K Nang , Vinay B Nangia , Martin Nankap , Sameer Narake , Paola Nardone , Matthias Nauck , William A Neal , Azim Nejatizadeh , Chandini Nekkantti , Keiu Nelis , Liis Nelis , Ilona Nenko , Martin Neovius , Flavio Nervi , Chung T Nguyen , Nguyen D Nguyen , Quang Ngoc Nguyen , Ramfis E Nieto-Martínez , Yury P Nikitin , Guang Ning , Toshiharu Ninomiya , Sania Nishtar , Marianna Noale , Oscar A Noboa , Helena Nogueira , Teresa Norat , Maria Nordendahl , Børge G Nordestgaard , Davide Noto , Natalia Nowak-Szczepanska , Mohannad Al Nsour , Irfan Nuhoglu , Eha Nurk , Terence W O'Neill , Dermot O'Reilly , Galina Obreja , Caleb Ochimana , Angélica M Ochoa-Avilés , Eiji Oda , Kyungwon Oh , Kumiko Ohara , Claes Ohlsson , Ryutaro Ohtsuka , Örn Olafsson , Maria 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Paola, Nauck, Matthia, Neal, William A, Nejatizadeh, Azim, Nekkantti, Chandini, Nelis, Keiu, Nelis, Lii, Nenko, Ilona, Neovius, Martin, Nervi, Flavio, Nguyen, Chung T, Nguyen, Nguyen D, Nguyen, Quang Ngoc, Nieto-Martínez, Ramfis E, Nikitin, Yury P, Ning, Guang, Ninomiya, Toshiharu, Nishtar, Sania, Noale, Marianna, Noboa, Oscar A, Nogueira, Helena, Norat, Teresa, Nordendahl, Maria, Nordestgaard, Børge G, Noto, Davide, Nowak-Szczepanska, Natalia, Al Nsour, Mohannad, Nuhoglu, Irfan, Nurk, Eha, O'Neill, Terence W, O'Reilly, Dermot, Obreja, Galina, Ochimana, Caleb, Ochoa-Avilés, Angélica M, Oda, Eiji, Oh, Kyungwon, Ohara, Kumiko, Ohlsson, Clae, Ohtsuka, Ryutaro, Olafsson, Örn, Olinto, Maria Teresa A, Oliveira, Isabel O, Omar, Mohd Azahadi, Onat, Altan, Ong, Sok King, Ono, Lariane M, Ordunez, Pedro, Ornelas, Rui, Ortiz, Ana P, Ortiz, Pedro J, Osler, Merete, Osmond, Clive, Ostojic, Sergej M, Ostovar, Afshin, Otero, Johanna A, Overvad, Kim, Owusu-Dabo, Elli, Paccaud, Fred Michel, Padez, 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Salvador, Vineis, Paolo, Vioque, Jesu, Virtanen, Jyrki K, Visser, Marjolein, Visvikis-Siest, Sophie, Viswanathan, Bharathi, Vladulescu, Mihaela, Vlasoff, Tiina, Vocanec, Dorja, Vollenweider, Peter, Völzke, Henry, Voutilainen, Ari, Voutilainen, Sari, Vrijheid, Martine, Vrijkotte, Tanja GM, Wade, Alisha N, Wagner, Aline, Waldhör, Thoma, Walton, Janette, Wambiya, Elvis OA, Bebakar, Wan Mohamad Wan, Mohamud, Wan Nazaimoon Wan, de Souza Wanderley Júnior, Rildo, Wang, Ming-Dong, Wang, Ningli, Wang, Qian, Wang, Xiangjun, Wang, Ya Xing, Wang, Ying-Wei, Wannamethee, S Goya, Wareham, Nichola, Weber, Adelheid, Wedderkopp, Niel, Weerasekera, Deepa, Weghuber, Daniel, Wei, Wenbin, Weres, Aneta, Werner, Bo, Whincup, Peter H, Widhalm, Kurt, Widyahening, Indah S, Wiecek, Andrzej, Wilks, Rainford J, Willeit, Johann, Willeit, Peter, Williams, Julianne, Wilsgaard, Tom, Wojtyniak, Bogdan, Wong-McClure, Roy A, Wong, Andrew, Wong, Jyh Eiin, Wong, Tien Yin, Woo, Jean, Woodward, Mark, Wu, Frederick C, Wu, Jianfeng, Wu, Li Juan, Wu, Shouling, Xu, Haiquan, Xu, Liang, Yaacob, Nor Azwany, Yamborisut, Uruwan, Yan, Weili, Yang, Ling, Yang, Xiaoguang, Yang, Yang, Yardim, Nazan, Yaseri, Mehdi, Yasuharu, Tabara, Ye, Xingwang, Yiallouros, Panayiotis K, Yoosefi, Moein, Yoshihara, Akihiro, You, Qi Sheng, You, San-Lin, Younger-Coleman, Novie O, Md Yusof, Safiah, Yusoff, Ahmad Faudzi, Zaccagni, Luciana, Zafiropulos, Vassili, Zainuddin, Ahmad A, Zakavi, Seyed Rasoul, Zamani, Farhad, Zambon, Sabina, Zampelas, Antoni, Zamrazilová, Hana, Zapata, Maria Elisa, Zargar, Abdul Hamid, Ko Zaw, Ko, Zdrojewski, Tomasz, Zejglicova, Kristyna, Vrkic, Tajana Zeljkovic, Zeng, Yi, Zhang, Luxia, Zhang, Zhen-Yu, Zhao, Dong, Zhao, Ming-Hui, Zhao, Wenhua, Zhen, Shiqi, Zheng, Wei, Zheng, Yingfeng, Zholdin, Bekbolat, Zhou, Maigeng, Zhu, Dan, Zins, Marie, Zitt, Emanuel, Zocalo, Yanina, Cisneros, Julio Zuñiga, Zuziak, Monika, Ezzati, Majid, Filippi, Sarah, Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Centre International de Hautes Études Agronomiques Méditerranéennes (CIHEAM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, and Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)
Subjects: Population -- Health aspects, Leanness, Baixo peso/Underweight, none, Double burden, alipainoisuus, tulotaso, global health, systematic analysis, Sedentary behaviors, RC1200, Prospective associations, 0302 clinical medicine, underweight, nälänhätä, Biology (General), skin and connective tissue diseases, Children, ComputingMilieux_MISCELLANEOUS, Body mass index, Human Nutrition & Health, education.field_of_study, Humane Voeding & Gezondheid, ylipaino, General Medicine, kansainvälinen vertailu, 3. Good health, World health, Medicine, A100 Pre-clinical Medicine, Population distribution, medicine.medical_specialty, QH301-705.5, Science, Socio-culturale, Nursing, Social sciences, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Thinness, SDG 3 - Good Health and Well-being, BMI, epidemiology, obesity, None, Humans, Obesidade/Obesity, SDG 2 - Zero Hunger, education, VLAG, US adults, Omvårdnad, body mass index, malnutrition, obesity, underweight, nutritional and metabolic diseases, medicine.disease, terveellisyys, Obesity, Faculdade de Ciências Sociais, Body Mass Index, Prevalence, Risk Factors, General Biochemistry, WIAS, lihavuus, RA, Demography, N.A, double burden, Settore MED/09 - Medicina Interna, alueelliset erot, Nutrition and Disease, Animal Nutrition, [SDV]Life Sciences [q-bio], Medizin, 030204 cardiovascular system & hematology, 0601 Biochemistry and Cell Biology, Change distribution of body mass index, RA0421, Voeding en Ziekte, Epidemiology, Medicine and Health Sciences, Global health, Índice de massa corporal/Body Mass Index, 030212 general & internal medicine, Underweight, painoindeksi, 2. Zero hunger, General Neuroscience, aliravitsemus, elintarvikkeet, health, Public Health, Global Health, Social Medicine and Epidemiology, Diervoeding, 3142 Public health care science, environmental and occupational health, purl.org/pe-repo/ocde/ford#3.01.03 [https], Chinese adults, pooled analysis, medicine.symptom, Diet quality, B120 Physiology, Research Article, trends, purl.org/pe-repo/ocde/ford#1.06.03 [https], prevalence, Population, Mothers, Genetics and Molecular Biology, 3121 Internal medicine, medicine, Life Science, ddc:610, 3125 Otorhinolaryngology, ophthalmology, kehonkoostumus, Nutrition, Australian adults, General Immunology and Microbiology, purl.org/pe-repo/ocde/ford#3.01.04 [https], Ciências sociais, Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi, Malnutrition, Epidemiology and Global Health, sense organs, Estilos de Vida e Impacto na Saúde
Abstract: From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions., Wellcome Trust, Medical Research Council, peer-reviewed
Published: 2021

23. Antibiotic Resistance Patterns of Uropathogens Causing Urinary Tract Infections in Children with Congenital Anomalies of Kidney and Urinary Tract

Author: Ramona Stroescu, Gabriela Doros, Raluca Isac, Mihai Gafencu, Iulia Cristina Bagiu, Adela Chirita-Emandi, Florin George Horhat, Diana-Georgiana Basaca, Dan Ionescu, Ioana-Cristina Olariu, Ruxandra Maria Steflea, Dan-Dumitru Vulcanescu, and Andrada-Mara Ardelean
Subjects: medicine.medical_specialty, antibiotic resistance, medicine.drug_class, Cefepime, Antibiotics, Pediatrics, Article, RJ1-570, 03 medical and health sciences, 0302 clinical medicine, Antibiotic resistance, children, 030225 pediatrics, Internal medicine, Ampicillin, medicine, 030212 general & internal medicine, urine culture, business.industry, Teicoplanin, Amoxicillin, bacterial infections and mycoses, abnormal urinary tract, Amikacin, Pediatrics, Perinatology and Child Health, drug-resistant bacteria, business, medicine.drug, Piperacillin
Abstract: Background: Urinary tract infections (UTI) are common in children worldwide. Congenital anomalies of kidney and urinary tract (CAKUT) increase the risk of UTI and consequently antibiotic resistance. Antibiotic resistance represents an important public health issue worldwide. We aimed to evaluate the local trend in terms of bacterial uropathogen resistance in the western part of Romania in children with CAKUT and UTI. Methods: 252 children with CAKUT were admitted to our hospital over a five-year period. Of them, 91 developed at least one UTI episode, with a total number of 260 positive urine cultures. We collected data about age at diagnosis of CAKUT, sex, origin environment, type and side of CAKUT, number of UTIs, type of uropathogen, and uropathogens antibiotic resistance. Results: Distribution of uropathogens was Escherichia coli (38.84%), Klebsiella spp. (21.15%), Enterococcus spp. (15.76%), Proteus spp. (8.07%), Pseudomonas spp. (8.07%), Enterobacter spp. (2.3%), other Gram-negative bacteria (2.3%), and other Gram-positive bacteria (3.45%). High antibiotic resistance was detected for ampicillin, amoxicillin, and second-generation cephalosporins. Escherichia coli presented high resistance for cefepime and ceftriaxone. Pseudomonas spp. remained susceptible to amikacin, quinolones, and colistin. Vancomycin, teicoplanin, linezolid, and piperacillin/tazobactam remained effective in treating Gram-positive UTI. Conclusions: High antibiotic resistance was identified for frequently used antibiotics. Lower antibiotic resistance was observed for some broad-spectrum antibiotics. Understanding uropathogens’ antibiotic resistance is important in creating treatment recommendations, based on international guidelines, local resistance patterns, and patient particularities.
Published: 2021

24. Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability

Author: Adela Chirita-Emandi, Maria Puiu, Diana Micleaa, Cristina Ghervan, Cristian G. Zimbru, Simona Bucerzan, Sergiu Osan, Camelia Al-Khzouza, Radu A. Popp, and Victoria Cret
Subjects: Male, 0301 basic medicine, Pediatric Obesity, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Developmental Disabilities, Endocrinology, Diabetes and Metabolism, Single-nucleotide polymorphism, Disease, 030105 genetics & heredity, Polymorphism, Single Nucleotide, 03 medical and health sciences, Endocrinology, Intellectual Disability, Internal medicine, Intellectual disability, medicine, Humans, SNP, Genetic Testing, Copy-number variation, Child, Chromosome Aberrations, Romania, business.industry, Infant, Genomics, Microarray Analysis, Prognosis, medicine.disease, Uniparental disomy, 030104 developmental biology, Child, Preschool, Pediatrics, Perinatology and Child Health, Etiology, Female, business, Biomarkers, Follow-Up Studies, SNP array
Abstract: Background Obesity with developmental disability/intellectual disability (DD/ID) is the most common association in syndromic obesity. Genomic analysis studies have allowed the decipherment of disease aetiology, both in cases of syndromic obesity as well as in cases of isolated or syndromic DD/ID. However, more data are needed to further elucidate the link between the two. The aim of this pangenomic study was to use single nucleotide polymorphism (SNP) array technology to determine the copy number variant (CNV) type and frequency associated with both obesity and DD/ID. Methods Thirty-six patients were recruited from the Clinical Emergency Hospital for Children, in Cluj-Napoca, Romania during the period 2015–2017. The main inclusion criterion was a diagnosis that included both obesity and DD/ID. Genomic analysis via SNP array technology was performed. Results Out of the 36 patients, 12 (33%) presented CNVs with a higher degree of pathogenicity (A group) and 24 (66%) presented benign CNVs (B group). The SNP array results for the A group were as follows: pathogenic CNVs in 8/12 patients (67%); variants of unknown significance (VOUS) in 2/12 patients (16%); and uniparental disomy (UPD) in 2/12 patients (16%). Conclusions Some of these CNVs have already been observed in patients with both obesity and DD/ID, but the others were noticed only in DD/ID patients and have not been described until now in association with obesity.
Published: 2019

25. Synthesis and preliminary characterization of polyurethane nanoparticles with ginger extract as a possible cardiovascular protector

Author: Livia-Cristina Borcan, Ramona C. Albulescu, Adela Chirita-Emandi, Florin Borcan, Maria Puiu, Mirela Cleopatra Tomescu, and Nicoleta Andreescu
Subjects: Ginger Extract, Biophysics, Pharmaceutical Science, Nanoparticle, Bioengineering, 02 engineering and technology, 010402 general chemistry, medicine.disease_cause, 01 natural sciences, Biomaterials, chemistry.chemical_compound, Blowing agent, Drug Discovery, medicine, Polyurethane, Aqueous solution, Chemistry, Organic Chemistry, General Medicine, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Zingiber officinale, Irritation, 0210 nano-technology, Drug carrier, Nuclear chemistry
Abstract: Background and aim: The extract of ginger, obtained from the rhizome of Zingiber officinale, contains 6-gingerol, 6-shogaol, 8-gingerol, and 10-gingerol. It has many therapeutic effects such as being chemopreventive against stroke and heart diseases, malabsorption, bacterial infections, indigestion, and nausea, which have been observed since ancient times. The main aim of this study is to evaluate the polyurethane (PU) as a proper material for the hollow nanoparticles' preparation. Methods: The PU nanoparticles were obtained by a spontaneous emulsification, in the presence of a nonionic surfactant, combined with an interfacial polyaddition process between an aliphatic diisocyanate and different mixtures of etheric and esteric polyols. The synthesis was done without any PU additives, such as catalysts, blowing agents, chains promoters, cross-linking agents, and stabilizers. Results: The particles present almost neutral pH values and low water solubility. They are heat resistant up to 280°C. Decreased irritation level was found in the assay of PU nanoparticles loaded with pure ginger extract (GE) on the murine skin tests than the irritation level recorded for pure GE. Conclusion: This research shows the reduced noxiousness of these PU nanoparticles and consequently the possibility of their use as a possible cardiovascular protector.
Published: 2019

26. No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova

Author: Chiril Boiciuc, Paul Tutac, Maria Puiu, Adela Chirita-Emandi, Nicoleta Andreescu, Victoria Sacara, Corina Paul, Iulian Velea, Natalia Usurelu, Agneta Maria Pusztai, Lorina Vudu, Diana Munteanu, and Victoria Hlistun
Subjects: Male, Pediatric Obesity, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Protein Serine-Threonine Kinases, 030204 cardiovascular system & hematology, Overweight, Polymorphism, Single Nucleotide, Body Mass Index, Germinal Center Kinases, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Humans, Obesity, Insulin-Like Growth Factor I, Child, Adaptor Proteins, Signal Transducing, Romania, business.industry, Insulin, Moldova, Prognosis, medicine.disease, PPAR gamma, Repressor Proteins, Case-Control Studies, Child, Preschool, Pediatrics, Perinatology and Child Health, Insulin Receptor Substrate Proteins, Homeostatic model assessment, Female, Insulin Resistance, medicine.symptom, Metabolic syndrome, business, Co-Repressor Proteins, Biomarkers, Follow-Up Studies
Abstract: Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D). We investigated the associations of these previously reported common variants in these genes with insulin resistance in overweight children from Romania and Moldova. Methods Six single nucleotide polymorphisms (SNPs), IGF1 (rs35767), IRS1 (rs2943634), GCKR (rs780094), PPARG (rs1801282), GCK1 (rs1799884) and KCTD15 (rs29941), were genotyped in 100 overweight children along with clinical and metabolic parameters. Homeostatic model assessment of insulin resistance (HOMA-IR) above 3.4 (defining insulin resistance) was used as the outcome. Results Children differed in insulin resistance status despite having similar body mass index (BMI) standard deviation scores (SDS) (World Health Organization, [WHO] reference). The identified predictors for altered insulin metabolism were higher cholesterol levels, higher diastolic blood pressure and higher waist-to-hip-ratio (as a marker for increased abdominal fat). None of the SNPs showed significant association with increase in the risk for insulin resistance in children (p range=0.478–0.724; odds ratio [OR] range=1.924–4.842); however, the risk allele in GCKR (rs780094, p=0.06, OR=6.871) demonstrated near statistical significance. Conclusions The interrogated risk alleles did not show any significant association with insulin resistance in children in our cohort; however, the GCKR (rs780094) might be a viable candidate in larger cohorts. The lack of replication of the proposed association may point to differences in linkage disequilibrium or effect modifiers across studies.
Published: 2019

27. Author response: Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight

Author: Zahra Mohammadi, Abdul Basit, Helena I. S. Nogueira, Soile E. Puhakka, Hongsheng Bi, Ari Voutilainen, Davood Khalili, Bin Zhou, Dermot O'Reilly, Natascia Rinaldo, Paulo A. Lotufo, Bahareh Kheiri, Thein Thein Htay, Simona Giampaoli, Goodarz Danaei, M. Fernanda Lima-Costa, Simona Bo, Peter Schnohr, Jerzy Chudek, Francesco Panza, Ling Yang, Katia Vergetti Bloch, Vincenzo Capuano, Holly E. Syddall, Dong Zhao, Indah Suci Widyahening, Maria Lorenza Muiesan, Leng Huat Foo, Mohsen Azimi-Nezhad, Merete Osler, Laura Torres-Collado, Manu Raj, Adroaldo Cesar Araujo Gaya, Susi Kriemler, Ali Akbar Shayesteh, Aneta Grajda, Anette Varbo, Kazem Mohammad, Leila Beltrami Moreira, Shu Ti Chiou, Iuliia A Rusakova, Jyh Eiin Wong, Torben Jørgensen, Lela Sturua, Lubica Ticha, Hamid Hakimi, Hazzaa M. Al-Hazzaa, Yanina Zócalo, Freda Pitakaka, Savvas C. Savva, Rajeev Gupta, Jennifer Servais, Marie Kunešová, Johanna M. Geleijnse, Elysée Claude Bika Lele, Yannis Manios, Jorge Escobedo-de la Peña, Yufang Bi, Chinh Nguyen Huu, Sibel Gogen, Viviane Cunha Cardoso, Kristine H. Allin, Ana Azevedo, Line Tang Møllehave, Vincent Jr DeGennaro, Novie O. Younger-Coleman, Gretchen A Stevens, Dickman Gareta, Holger Theobald, Anja Schienkiewitz, Bekbolat Zholdin, Janice Luisa Lukrafka, Adela Chirita-Emandi, Ulla Roggenbuck, Kenisha Russell Jonsson, Robespierre Ribeiro, Gabriele Eiben, Eero Kajantie, Sounnia Mediene Benchekor, Fariborz Mansour-Ghanaei, Mary Simon, Prakash C. Gupta, Mohammad Esmaeel Motlagh, Emanuela Gualdi-Russo, María Elena Díaz-Sánchez, Pilar Guallar-Castillón, Bee Koon Poh, Cristina Padez, Azaliia M Tuliakova, Sarah P. Garnett, William R. Tebar, Yingfeng Zheng, Suhad Bahijri, Christina Mavrogianni, Mihaela Vladulescu, Jan A. Staessen, Paula Duarte de Oliveira, Rui Ornelas, Michael Sjöström, Charles Agyemang, Slawomir Koziel, Shohreh Naderimagham, Jari Jokelainen, Stephen T. McGarvey, Patrick Pasquet, Farnam Mohebi, Nader Saki, Aida Pilav, Azim Nejatizadeh, Marianna Noale, Habiba Ben Romdhane, Luís B. Sardinha, Laura Lauria, Jun Hata, Kodanda R Kanala, Gert B. M. Mensink, Nils Lehmann, Elio Riboli, Carolina Tarqui-Mamani, Rodrigo M. Carrillo-Larco, Rosangela Fernandes Lucena Batista, Victoria E Soto-Rojas, Luis Serra-Majem, Martina Müller-Nurasyid, Felipe Vogt Cureau, Lekhraj Rampal, Zhamilya Battakova, Ludmila Sevcikova, Suhaila Abdul Ghaffar, Fikru Tullu, Aung Soe Htet, Angel R. Gonzalez, Annette J. Dobson, Kavumpurathu Raman Thankappan, Hélène Delisle, Francisco J. Félix-Redondo, Ramón Suárez-Medina, Annika Rosengren, Sania Nishtar, Tanja G. M. Vrijkotte, Wolfgang Ahrens, Osvaldo Santos, Maria Cecília Formoso Assunção, Kazi M. Jamil, Stefano Marventano, Wenbin Wei, Norsyamlina Che Abdul Rahim, Shukri F. Mohamed, Bente Sparboe-Nilsen, Soon-Woo Park, Ana Isabel Rito, David Goltzman, W. M. Monique Verschuren, Catterina Ferreccio, Marta Buoncristiano, Ramón Alberto Rascón-Pacheco, Pradeep Joshi, Edward D Janus, Laetitia Huiart, Ala'a Alkerwi, Lorenza Pilotto, Mohannad Al Nsour, Daan Kromhout, Marius B. Bjertness, Oanh T. H. Trinh, Nico Dragano, Angélica Ochoa-Avilés, Ingunn Holden Bergh, Yuki Fujita, Juraci Almeida Cesar, Hajer Aounallah-Skhiri, Maria Dorobantu, Jordi Sunyer, Wolfgang Kratzer, Susanne R. de Rooij, Drude Molbo, Rebecca Goldsmith, Jean Woo, Mohammad El-khateeb, Tiffany K. Gill, Nish Chaturvedi, Benjamin Acosta-Cazares, Erik Lykke Mortensen, Nikhil D. Patel, Francesco Pistelli, Yuan He, Ivana Radic, Yi Zeng, Ilse Khouw, Reynaldo Martorell, Ching-Yu Cheng, Stine Schramm, Hana Shimizu-Furusawa, Jacek Jóźwiak, Radwan Qasrawi, Isti Ilmiati Fujiati, Charles Sossa Jérome, Ben Schöttker, Mikhail Benet, Anastasia Markaki, Christopher T. Cowell, Bharathi Viswanathan, Renata Kuciene, Jose Eugenio Lozano, Pedro J Ortiz, Delphine De Smedt, Elaine M. Murtagh, Kamel Ajlouni, Carlos A. Aguilar-Salinas, Graziella D'Arrigo, Xiangjun Wang, Lars Lind, Macia Enguerran, Marjeta Mišigoj-Duraković, Bo Werner, Jean-Michel Gaspoz, Kyungwon Oh, Seyed Rasoul Zakavi, Daniel Fernández-Bergés, Felix Kaducu, Ramon O. Jimenez, Jonathan E. Shaw, Nipa Rojroongwasinkul, Aicha Soumare, Astrid Petersmann, Tomasz Grodzicki, Parvina Mukhtorova, Eha Nurk, Bhawesh Koirala, Óscar Lopes, Ana Jelakovic, Karolina Milkowska, Magda Gasull, Regina Heidinger-Felso, Marcela González-Gross, Belong Cho, Daphne Mirkopoulou, Salvador Villalpando, Tran Quoc Bao, José Boggia, Daniela Galeone, Josep Redon, Matthias Bopp, Abbas Rezaianzadeh, Dusko Bjelica, Amir Houshang Mehrparvar, Felipe F. Casanueva, Khairil Si-Ramlee, Soheir H Ahmed, Maria Nordendahl, Luciana Zaccagni, Mahboubeh Parsaeian, Rod Jackson, Jorge Motta, Keiu Nelis, Fernando Rigo, Andrzej Pajak, Christa Meisinger, Clara Homs, Namuna Shrestha, Mar Alvarez-Pedrerol, Xun Tang, Johann Willeit, Motahareh Kheradmand, Jean Dallongeville, Jean-Bernard Ruidavets, Anne Tjønneland, Diana A. Santos, Lynne M. Boddy, Jie Hao, David Alejandro González-Chica, Elin Kolle, Jingli Gao, Małgorzata Mossakowska, Isabel O. Oliveira, Giuseppe Grosso, Seongjun Ha, Olfa Saidi, Albina A Fakhretdinova, Oye Gureje, Raluca Pop, Iulia Jurca Simina, Nuno Lunet, Maria Forsner, Peter Bjerregaard, Rachael McLean, Antonio Cabrera de León, Guy De Backer, José A. Casajús, Guang Ning, Emmanuella Magriplis, Laura Censi, Graziella Bruno, Valentina Peterkova, Angelique Chan, Yvonne T. van der Schouw, Charalambos Hadjigeorgiou, Anjani Kumar Jha, Toomas Veidebaum, Thamara Hubler Figueiró, Jana Kratenova, Michelle Cilia, Ivo Rakovac, Bill Stavreski, Ya Xing Wang, Oscar Noboa, Romana Roccaldo, Sara Magnacca, Johan Sundström, Peter Stehle, Tania Lopez, Francis Delpeuch, Julianne Williams, Ellisiv B. Mathiesen, Leanne M. Riley, Claudia M. Hormiga, Joanne Katz, Ekaterina Stoyanova, Heloisa Bettiol, Gabriele Nagel, Alireza Khosravi, Lars Bo Andersen, João Breda, Jørgen Meisfjord, Ahmad Faudzi Yusoff, Marjeta Majer, Robert Beaglehole, Caleb Ochimana, Shynar Abdrakhmanova, George S. Stergiou, Blanca Sandra Ruiz-Betancourt, Leon A. Simons, Eng Joo Tan, Victoria Farrugia Sant'Angelo, Gry Skodje, Maryam Keramati, Liv Elin Torheim, Seppo Koskinen, Assembekov Batyrbek, Jaakko Tuomilehto, Marjo-Riitta Järvelin, Ming-Hui Zhao, Krista Fischer, Tobias F. Rinke de Wit, Agnès Le Port, Reza Homayounfar, James E. Bennett, Yuna He, Matsuda Fumihiko, Qi Sheng You, Angela Spinelli, Scott B. McLean, Shirin Djalalinia, Thet Thet Mu, Yves Martin-Prével, Rafael N. Pichardo, Gailute Bernotiene, Pietro Amedeo Modesti, Frederick C. W. Wu, Chandini Nekkantti, Daniela Rodrigues, Tandi E. Matsha, Mihai Gafencu, Xingwang Ye, Salar Rahimikazerooni, Trevor S. Ferguson, Christophe Tzourio, Marie Zins, Fernando Rodríguez-Artalejo, Xu Ma, Elin Pettersen Sørgjerd, Lourdes Ribas-Barba, Nalan Uysal, Salim Berkinbayev, Enisa Kujundzic, Sari Voutilainen, Iraj Mohebbi, Heiner Boeing, Jorge Mota, Jana Námešná, Maria Tsigga, Zivka Dika, Gulmira Aitmurzaeva, Xu Lin, Valéria Regecová, Herman Schargrodsky, Stevo Popovic, Amelia C. Crampin, Hannu Uusitalo, André Luiz Sena Guimarães, Ali Esmaeili, Catherine Kyobutungi, Virginija Dulskiene, Diego Augusto Santos Silva, David De Ridder, Lizzy M. Brewster, Hashem Jaddou, Eunice Ugel, José Camolas, Azli Baharudin, Idris Guessous, Sok King Ong, Tabara Yasuharu, Ali Ghanbari, Anne W. Taylor, Iraj Nabipour, Justyna Godos, Cyrus Cooper, Bruna Gonçalves Cordeiro da Silva, Gonzalo Valdivia, Gyulli M. Kazakbaeva, Takuro Furusawa, Pawel Kurjata, Diego Vanuzzo, Marvin Cervantes-Loaiza, Karen Morgan, Mostafa Qorbani, Rute Santos, Marika Ferrari, Diego Salmerón, Ida Maria Schmidt, Gao Pei, Abu Am Hanif, Balkish M. Naidu, Maria Wany Louzada Strufaldi, Moesijanti Soekatri, Marcia Scazufca, Katharina Maruszczak, Jacqueline Ramke, Elvis Oa Wambiya, Kairit Mikkel, Napoleón Pérez-Farinós, Natalia Nowak-Szczepanska, Miao Li Chee, Jose Sanchez-Abanto, Rajaa Al-Raddadi, Michel Joffres, Vayia Rarra, Ningli Wang, Charmaine A. Duante, Sheikh Mohammed Shariful Islam, Manoli Garcia-de-la-Hera, Weili Yan, Dong Wook Shin, Rômulo Araújo Fernandes, Ilona Nenko, Sanjib Kumar Sharma, Alfonso Siani, Indrapal I. Meshram, Imelda A. Agdeppa, Ei Ei K. Nang, Ian Rouse, Avula Laxmaiah, Ana M. B. Menezes, Yih Chung Tham, Ebrahim Eftekhar, María José Tormo, Felicia Cañete, Marie Eliasen, Lutgart Braeckman, Dirk Vanderschueren, Genc Burazeri, Kari Kuulasmaa, Jesús Vioque, Marisa K. Sophiea, Agneta Sjöberg, Katarzyna Dereń, Albertino Damasceno, Jochanan Stessman, Stig E. Bojesen, Aline Meirhaeghe, Else Karin Grøholt, Flávio Danni Fuchs, Robert Lundqvist, Frédéric Gottrand, Jeongseon Kim, Helmut Schröder, Joanna Baran, Karina Mary de Paiva, Yousef Khader, Eric Monterrubio-Flores, Aneta Weres, Hans Concin, Damaskini Valvi, Sari Hantunen, Machi Suka, Elena Sacchini, Norbert Amougou, Ursula Kiechl-Kohlendorfer, Edwige Landais, Viktoria Anna Kovacs, Rosemarie Martin, Kenneth James, Amaneh Shayanrad, Grethe S. Tell, Norazizah Ibrahim Wong, Vedrana Sember, Anelise Reis Gaya, Konrad Jamrozik, Thorkild I. A. Sørensen, Martin Neovius, Urho M. Kujala, Nathalie Michels, Marcel Goldberg, Alexandra Cucu, Liliana Dacica, Adelheid Weber, Hermann Pohlabeln, Sandjaja, Jukka T. Salonen, Patricia Varona-Pérez, Tiina Laatikainen, Jolanta Słowikowska-Hilczer, Ana Paula Carlos Cândido, Julie Taylor, Anabela Mota-Pinto, Cora L. Craig, Teresa Shamah-Levy, María Dolores Chirlaque, Mohd Azahadi Omar, Dominique Cottel, Charumathi Sabanayagam, Andrea Gazzinelli, Mieczysław Litwin, Sadaf G. Sepanlou, Adolfo Rubinstein, Abbas Dehghan, Rildo de Souza Wanderley Júnior, Wenhua Zhao, Aleksandra Piwońska, Yong Tao, Bontha V. Babu, Marc J. Gunter, Harunobu Nakamura, Wojciech Drygas, Eiji Oda, Jia Li Duan, Stefan Söderberg, Anthony Kafatos, Lynell V Maniego, Els Clays, Wei-Yen Lim, Marshall K. Tulloch-Reid, Mariachiara Di Cesare, Mattias Johansson, Simona Costanzo, Margot González-León, Matthias Nauck, Henry Völzke, George Luiz Lins Machado-Coelho, Annette Peters, Rajiv T Erasmus, Juan Francisco Miquel, Andrea Gualtieri, Abdul Hamid Zargar, Kaare Christensen, Peter Willeit, Tanja Stocks, Christine Cameron, Samuel C. Dumith, Janina Petkeviciene, Boyd Swinburn, Magdalena Muc, Sabine Schipf, Tajana Zeljkovic Vrkic, Martin Bobak, Damian K Francis, Veronica Mocanu, Karien Stronks, Antonisamy Belavendra, Artur Mazur, Nagalla Balakrishna, Jardena J. Puder, Mehrdad Azmin, Shelly R. McFarlane, Sara Santos Sanz, Yang Yang, Anneke Blokstra, Rafel Ramos, Ertugrul Celikcan, Jody C Miller, Jesús Ibarluzea, Svetlana A. Shalnova, Maria Elisa Zapata, Guansheng Ma, Fereidoun Azizi, Beatriz D'Agord Schaan, Pedro Marques-Vidal, William A. Neal, Ana B. Crujeiras, Zhenyu Zhang, Naser Ahmadi, Abdullatif Husseini, Alun Evans, Jiang He, Edyta Łuszczki, Maria G. Stathopoulou, Alibek Mereke, Mari-Liis Tammesoo, Axel C. Carlsson, Helen Gonçalves, Idowu O Senbanjo, Jim Mann, Rajendra Pradeepa, Juel Jarani, Eva Martos, Eugene Sobngwi, Themistoklis Tzotzas, Vassilis Zafiropulos, Reina Engle-Stone, Atul Trivedi, Hui Cai, Sarah Filippi, Georg Posch, Galina Obreja, Cecily Kelleher, Sareh Eghtesad, Chung T Nguyen, Kay-Tee Khaw, Joseph Cacciottolo, Ana Henriques, Yi-Ting Lin, Anil Poudyal, Liam Smeeth, Kenji Shibuya, Emma Ruiz Moreno, Annamari Lundqvist, Thor Aspelund, Caroline H.D. Fall, Philippe Amouyel, Kristyna Zejglicova, Argyro Karakosta, Piotr Bandosz, Juvenal Soares Dias-da-Costa, Maria Lazo-Porras, Maung Maung Than Htike, Dalia Luksiene, Jutta Stieber, Augusto Di Castelnuovo, Aryeh D. Stein, Lechaba Tshepo, Judith Benedics, Aletta E. Schutte, Jürgen König, Magdalena Korzycka, Grzegorz Sobek, Dimitrios Trichopoulos, Tai Hing Lam, Yn-Tz Sung, Masanori Iwasaki, Elias F. Gudmundsson, Antonio Mistretta, Daniel Lemogoum, Nimmathota Arlappa, Isabelle Herter-Aeberli, Khanh Le Nguyen Bao, Shoichiro Tsugane, Kaosar Afsana, Alireza Sadjadi, Myriam Galfo, Jean Claude Mbanya, Bernardo L. Horta, Marleen E. Hendriks, M. Arfan Ikram, Fadia AlBuhairan, Huashuai Chen, Marzieh Katibeh, Sidsel Graff-Iversen, Sahar Saeedi Moghaddam, Larissa Pruner Marques, Louise Eriksen, Aleksandra Gomula, Ricky Eddie, Maciej Banach, Jost B. Jonas, Andrea R. V. R. Horimoto, Slavica Sović, Charles Mondo, Felix Gutzwiller, Mariana Sbaraini, Aye Aye Sein, Henrike Galenkamp, Jaume Marrugat, Nazan Yardim, Cecilia Björkelund, Luigi Palmieri, Roya Kelishadi, Jie Mi, Nahla Hwalla, Jing Liu, Davide Noto, Panayiotis K. Yiallouros, Kelias P. Msyamboza, Judith Simons, Sofia Malyutina, Michele Monroy-Valle, Andres Metspalu, Lariane M Ono, Rafaela Rosário, Flora A. Ukoli, Efthymios Kapantais, Enzo Manzato, S. Goya Wannamethee, Alison J Price, Gregorio Varela-Moreiras, Ali Reza Safarpour, Erfan Ghasemi, Janine Clarke, René Charles Sylva, Wan Nazaimoon Wan Mohamud, Zhamyila Usupova, Chaoqiang Jiang, Julio Zuñiga Cisneros, Freja B Kampmann, Wei Cheng Lo, Reza Mohammadpourhodki, Kaspar Staub, Mojtaba Farjam, Vincenzo Solfrizzi, Garry L. Jennings, Fabio Galvano, Monika Zuziak, Karin De Ridder, Lucie Viet, Anna Bugge, Mehdi Yaseri, Safiah Md Yusof, Sandra C. Fuchs, Emmanuel Cohen, Snehalatha Chamukuttan, Maria Ruiz-Castell, Karen Sparrenberger, Pedro Plans-Rubio, Wei Zheng, Eldridge Ferrer, Martijn Huisman, Maria Hassapidou, Iris Pigeot, Jakub Stokwiszewski, Domenico Palli, Ewelina Czenczek-Lewandowska, Ramiro Guerrero, Farzad Hadaegh, Han Cg Kemper, Saeid Safiri, Ivan Pećin, Arnaud Chiolero, Niels Møller, Jorge Bezerra, Ulrike Gehring, Iná S. Santos, Dénes Molnár, Muhammad Fadhli Mohd Yusoff, Marie Moitry, Nizal Sarrafzadegan, Jacqueline F. Price, Ranko Stevanovic, Sai Yin Ho, Georg Lappas, Alberto Palloni, Malay K. Mridha, Elaine M. Dennison, Jeonghee Lee, Saeid Eslami, Rahman Shiri, Japhet Killewo, Juergen Breckenkamp, Mathilde Kersting, Y Nikitin, Iqbal Bata, Geetha R Menon, Maria Avdicova, Sanjay Rampal, Antônio Augusto Moura da Silva, Kirsten Mehlig, Chien-An Sun, Ramin Heshmat, Violeta Iotova, Stefaan Demarest, Mette Rasmussen, Dirk De Bacquer, San-Lin You, Suzanne N Morin, Martin Gulliford, Maties Torrent, Luc Dauchet, Fred Paccaud, Paibul Suriyawongpaisal, Sherali Rakhmatulloev, Hyeon Chang Kim, Markku Peltonen, Ruth Frikke-Schmidt, Vera Musil, Ahmad Ali Zainuddin, Angela Chetrit, Dan Zhu, Gowri Mahasampath, Ulrich Keil, Sérgio Viana Peixoto, Haiquan Xu, Helle-Mai Loit, Valérie Deschamps, Ilpo Huhtaniemi, Lijuan Liu, Marialaura Bonaccio, Altan Onat, Rody G. Sy, José María Huerta, Ko Ko Zaw, Akihiro Yoshihara, Peter Ueda, Belgin Ünal, Rachel Dankner, Andrzej Wiecek, Eman Aly, Ruzena Kubinova, Justina Vaitkeviciute, Hanna Tolonen, Priscilla Duboz, Orn Olafsson, Yin Guo, Chiara Donfrancesco, Salim Mohanna, Dusan Grafnetter, Daniel Weghuber, Ali Ahmadi, Rosemary B. Duda, E. Shyong Tai, Louise A. Baur, Nihal Thomas, Prabhdeep Kaur, Norlaila Mustafa, Shariq Rashid Masoodi, Liis Nelis, Badreya Al-Lahou, J. Jaime Miranda, Lèlita Santos, Aroor Bhagyalaxmi, Mohamed Bamoshmoosh, Børge G. Nordestgaard, Jeannette Lee, Ahmad Reza Dorosty, Alain Morejon, Ying-Wei Wang, Jakob Tarp, Rosalba Rojas-Martínez, Luxia Zhang, Bahram Mohajer, Maja Bæksgaard Jørgensen, Jurate Klumbiene, Zhengming Chen, Ambady Ramachandran, Andrea Rodriguez-Martinez, Alisha N. Wade, Suyeon Park, Janne Schurmann Tolstrup, Lucjan Szponar, Krishna Kumar Aryal, Tahir Aris, Mahfuzar Rahman, Dorja Vočanec, Juan P. González-Rivas, Rob M. van Dam, Daniel Bia, Oonagh Markey, Ryutaro Ohtsuka, Kumiko Ohara, Ričardas Radišauskas, Jurate Medzioniene, Tiina Vlasoff, Tania Tello, Suzanne C. Ho, Kodavanti Mallikharjuna Rao, May Soe Aung, Vesselka Duleva, Michael Hobbs, Lutgarde Thijs, Marjolein Visser, Parasmani Dasgupta, Inge Huybrechts, Raimund Erbel, Alice Bonilla-Vargas, Hermann Brenner, Mohammad Reza Fattahi, Jolanda Hyska, Roman Topor-Madry, Ranjit Mohan Anjana, Merike Liivak, Eruke E. Egbagbe, Mathilde Savy, Herculina S. Kruger, Neil Murphy, Vinay Nangia, Cesar G. Victora, Mostafa K. Mohamed, H. Bas Bueno-de-Mesquita, Gabriella Gruden, Marcos André Moura-dos-Santos, Mohammed Rasoul Tarawneh, Maria Teresa Menzano, Francesco Branca, Abdonas Tamosiunas, Elena Bogova, Niveen M E Abu-Rmeileh, Maroje Sorić, Aleksander Giwercman, Elżbieta Dziankowska-Zaborszczyk, Tatjana Hejgaard, Yves Kameli, Margarita Samoutian, Andreia N. Pizarro, Jin Soo Moon, Frank Claessens, Zulfiqar A Bhutta, Frank Tanser, Nor Azwany Yaacob, Vanina Bongard, Gregor Jurak, Johan G. Eriksson, Christina-Paulina Lambrinou, Hanspeter Stamm, Kim Overvad, Yanping Li, Carsten Oliver Schmidt, Thomas Meinertz Dantoft, Wichai Aekplakorn, Anwar Batieha, Eduardo Capuano, Teresa Haugsgjerd, Jeremy M. Jacobs, Paola Russo, Nguyen D Nguyen, Luis Revilla, Hossein Poustchi, Farid Najafi, Giovanni de Gaetano, Wan Mohamad Wan Bebakar, Paul Elliott, Denise Eldemire-Shearer, Angela Döring, Giovanni Viegi, Xiaoguang Yang, María-Elena González-Villalpando, Maria Puiu, Maria Benedetta Donati, Andrew Wong, Tomasz Zdrojewski, Carlos P. Boissonnet, Mohamad Hasnan Ahmad, Mahmudur Rahman, Günther Fink, Marcia Makdisse, Dragana P Jovic, Aline Wagner, Coimbatore Subramaniam Shanthirani, Pascal Bovet, Dong Wook Kim, Tom Wilsgaard, Anders Grøntved, Thirunavukkarasu Sathish, Antonia Trichopoulou, Noushin Mohammadifard, Igor Spiroski, Natasja M. van Schoor, Cláudia S. Minderico, Betina H. Thuesen, Queenie Chan, Ulf Ekelund, Laura A. Rodríguez-Villamizar, Line Lund Kårhus, Cihangir Erem, Amina Barkat, Maria Paula Santos, Fernanda Cunha Soares, Constanta Huidumac Petrescu, Allan G. Hill, Honor Bixby, Benoît Salanave, Joana Carvalho, Maigeng Zhou, Ofra Kalter-Leibovici, Roy A Wong-McClure, Kim F. Michaelsen, Doris Stöckl, Rosalynn Siantar, Jouko Saramies, José R. Banegas, Quang Ngoc La, Uruwan Yamborisut, Parinaz Mehdipour, Farhad Pourfarzi, Sudha Ramachandra Rao, Katsuyasu Kouda, Chien-Jen Chen, Rafael dos Santos Henrique, Martin Nankap, Allan Linneberg, Ronald D. Gregor, Rudolf Kaaks, Maria do Carmo Franco, Marta García-Solano, Beata Gurzkowska, Bahman Cheraghian, Stefaan De Henauw, Daniel Ferrante, Johanna A. Otero, Jamila Abubakar Garba, Antonio Pedro Graça, Sumit Bharadwaj, Shiqi Zhen, Xiu-Hua Guo, Prashant Mathur, Raphael Mendes Ritti-Dias, Kouamelan Doua, Esteban Carmuega, Majid Shirani, Przemyslaw Slusarczyk, Petra Rust, Visnja Djordjic, Farahnaz Joukar, Johanna Gunnlaugsdottir, Leila Houti, Nayu Ikeda, Imperia Brajkovich, Amirabbas Momenan, Erik J. Timmermans, Marcin Rutkowski, Biruta Velika, Joana Araújo, Jostein Steene-Johannessen, Christa L. Lilly, Per Tynelius, Michael Tornaritis, Anne Juolevi, Fatima Zahra Laamiri, Carl Lachat, Kai-Uwe Saum, Espen Bjertness, Ana P. Ortiz, Joel G. R. Roy, Himanshu K. Chaturvedi, Michelle Holdsworth, Niels Wedderkopp, Johan Van der Heyden, Mukharram M. Bikbov, Hsien-Ho Lin, Eva Corpeleijn, Harshpal Singh Sachdev, Mohammad Reza Mirjalili, Maria del Cristo Rodriguez-Perez, Michala Lustigová, Tuyen D Le, Teresa Norat, Hana Zamrazilová, Garry Brian, Tien Yin Wong, Rosa Haghshenas, Clive Osmond, Diego Giulliano Destro Christofaro, Mahmood Moosazadeh, Vilma Irazola, Olli T. Raitakari, Marco Aurélio Peres, Terho Lehtimäki, Shuohua Chen, Dimitrios Papandreou, Robert J. Adams, Sigmund A. Anderssen, Peter T. Katzmarzyk, Luisa M Macieira, Félicité Tchibindat, Lital Keinan Boker, Toshiharu Ninomiya, Morten Sodemann, Jytte Halkjær, Zbigniew Kułaga, Sophie Visvikis-Siest, Farshad Farzadfar, N Capkova, Zumin Shi, Maria Turley, Zbigniew Gaciong, Giovanni Veronesi, Martin McKee, Veikko Salomaa, Gilad Twig, Elisabetta L. Romeo, Peter Kristensen, Grazyna Jasienska, Victor Guillermo Sequera, Mario V. Capanzana, Con Burns, Emanuela Pettenuzzo, Ming-Dong Wang, Jonathan Giovannelli, Stela McLachlan, Ellis Owusu-Dabo, Stefania Toselli, Maria Teresa Anselmo Olinto, Senthil K Vasan, Sara Schramm, Xenophon Theodoridis, Moyses Szklo, Ramfis Nieto-Martínez, Viswanathan Mohan, Guillermo Frontera, Rahul Malhotra, Thomas Ferrao, Dongfeng Gu, Tomas Vega, Hynek Pikhart, Päivi Mäki, Heba Fouad, Vilnis Dzerve, Christina Howitt, Seyed Mohammad Hashemi-Shahri, Jenny M. Kindblom, Marjolijn C. E. Bragt, G. K. Mini, Qian Wang, Liufu Cui, Andrzej Galbarczyk, Sylvain Sebert, Vilmundur Gudnason, Loreto Santa Marina, Kairat Davletov, Afshin Ostovar, Niloofar Peykari, Nicholas J. Wareham, Wilma M. Hopman, Karl-Heinz Jöckel, Jussi Kauhanen, Breige A. McNulty, Alina Kerimkulova, Youcef Laid, Claes Ohlsson, Stefan Kiechl, Alicia Matijasevich, Boban Mugoša, Srinivasan Kannan, Jyrki K. Virtanen, Mohan Deepa, Mangesh S. Pednekar, Shahla AlDhukair, Cynthia M. Pérez, Vera Lanska, Tint Swe Latt, Dominique Hange, João Luiz Bastos, Eliza Markidou Ioannidou, Leticia Hernandez Cadena, Maya Tanrygulyyeva, Reza Malekzadeh, Dimitrios Poulimeneas, Pedro Ordunez, Thomas Waldhör, Ioannis Pagkalos, Carlo M. Barbagallo, Abla M. Sibai, Peter Vollenweider, Asher Fawwad, Emily Sonestedt, Elena Pahomova, Santosh K. Bhargava, Patrick Kolsteren, Aya Mostafa, Fangfang Chen, Flavio Nervi, Imre Janszky, Arvind Pandey, Renata Cifkova, Alexandre C. Pereira, Alejandro Diaz, Alireza Ansari-Moghaddam, Rachakulla Hari Kumar, Jaakko Mursu, Luis A. Moreno, Glen Gironella, Jelena Kos, Tilema Cama, Haakon E. Meyer, Jun Ma, Raphael E. Arku, Ziad Abdeen, Rusidah Selamat, Dianna J. Magliano, Jitendra Jonnagaddala, Konstantinos Gkiouras, Paul Korrovits, Paola Nardone, Paolo Vineis, Kotsedi D Monyeki, Khuong Quynh Long, Alberto Barceló, Camilla T. Damsgaard, Constance Schultsz, Frank J Rühli, Santiago F. Gomez, Tara Coppinger, Muhammad Islam, Pierre Traissac, Eleonora d'Orsi, Irfan Nuhoglu, Rui Providência, Bernard Maire, Leandra Abarca-Gómez, Sinead Brophy, Daniela Pierannunzio, Cristina Taddei, Wen-Harn Pan, Gregor Starc, Abdullah Alkandari, Saeed Dastgiri, Lien Braeckevelt, Gustavo Velasquez-Melendez, Sudhir Kowlessur, Bagher Larijani, Cynthia Robitaille, Mohamed M. Ali, Steiner Krokstad, Noor Ani Ahmad, Anar Dushpanova, Agustinus Soemantri, Susana Sans, Ionela Pascanu, Gwenaëlle Le Coroller, Inger Ariansen, Abhijit Sen, Sergej M. Ostojic, Silvana Donoso, Felix K. Assah, Juan A Rivera, Peter H. Whincup, Oana-Florentina Gheorghe-Fronea, Hanan F. Abdul Rahim, Yadlapalli S. Kusuma, Michael Knoflach, Moein Yoosefi, Cassiano Ricardo Rech, Paul Ferdinand M. Reganit, Tomi-Pekka Tuomainen, Francesco Gianfagna, Stefania Maggi, Mohammad Hossein Somi, Behrooz Hamzeh, Bethlehem D. Solomon, Herman Borghs, Zhanna Kalmatayeva, Heidi Klakk, Akram Pourshams, Naomi S. Levitt, Miquel Porta, Vesna Jureša, Alexander D. Deev, Son Thai Pham, Paula Margozzini, Silvia Bel-Serrat, Dora Romaguera, Monira Alarouj, Winsome R. Parnell, Marloes Cardol, David Faeh, Antonio Bernabe-Ortiz, Giota Touloumi, Maryam Kavousi, Sanja Musić Milanović, Jalila El Ati, Sauli Herrala, Liang Xu, Sirkka Keinänen-Kiukaanniemi, Ian Hambleton, Stefan Savin, Andre Pascal Kengne, R. Krishna Kumar, Kurt Widhalm, Marco M Ferrario, Parisa Amiri, Yi Song, Jianfeng Wu, Jeannette Klimont, Jean Ferrières, Farhad Zamani, Shina Avi, Luis Paulo Gomes Mascarenhas, Aluísio J D Barros, Reecha Sofat, Koen Van Herck, Hoang Van Minh, Enrique Gutiérrez-González, Martine Vrijheid, Susana Cararo Confortin, Antonis Zampelas, Bogdan Wojtyniak, Ausra Petrauskiene, Juha Auvinen, Maryam Sharafkhah, Emanuel Zitt, Majid Ezzati, Young-Ho Khang, Ellina Rakhimova, Magdalena Klimek, Luís Lopes, Erkin M. Mirrakhimov, Maria Lc Iurilli, Günay Can, Mark Woodward, Esther Lopez-Garcia, Mauro Virgílio Gomes de Barros, Ahmed A. Madar, Rainford J. Wilks, Shoaib Afzal, Melanie J. Cowan, Gareth Stratton, Eduardo Salazar Martinez, Sameer Narake, Norie Sawada, Li Juan Wu, Adrian Richter, Licia Iacoviello, Hanno Ulmer, Deepak Amarapurkar, Mohsen Ibrahim, Hamed Pouraram, Massimo Salvetti, Hung-Kwan So, Yonghua Hu, Lars Ängquist, Thi Tuyet-Hanh Tran, Charles Lunogelo, Sabina Zambon, Angelika Schaffrath Rosario, Lauren Lissner, Kamarul Imran Musa, Deepa Weerasekera, Bihungum Bista, Takafumi Ishida, Ekaterina Chikova-Iscener, Mirjam M. Heinen, Tazeen H. Jafar, Semánová Csilla, Raija Korpelainen, Edward W. Gregg, Laura Gutierrez, Victor M. Herrera, Aristides M. Machado-Rodrigues, Fatemeh Malekzadeh, Shouling Wu, Jennifer L. Baker, Clicerio González-Villalpando, Irene G. M. van Valkengoed, Anna Fijałkowska, Meghnath Dhimal, Murat Topbaş, George Moschonis, Robert Eggertsen, Quang Ngoc Nguyen, Janette Walton, Elnaz Faramarzi, Nasheeta Peer, Radka Taxová Braunerová, Harald Geiger, Morteza Shamshirgaran, Lela Shengelia, María Ángeles Dal Re Saavedra, Khem Bahadur Karki, Timothy J. Key, Maria G. Grammatikopoulou, Susana Vale, Bernhard O. Boehm, Songhomitra Panda-Jonas, Iveta Pudule, Elisabete Ramos, Lacramioara Aurelia Brinduse, Paul H. Lee, Terence W O'Neill, Javad Aghazadeh-Attari, Margus Punab, Bojan Jelaković, Eliza Cinteza, Ha Tp Do, and Alison J. Hayes
Subjects: education.field_of_study, business.industry, Population, Distribution (economics), medicine.disease, Obesity, Geography, medicine, Underweight, medicine.symptom, education, business, Body mass index, Demography
Published: 2020

28. Predicting Human Acceptor Splice Site Regions using Text Distance Methods

Author: Cristian G. Zimbru, Nicoleta Andreescu, Maria Puiu, and Adela Chirita-Emandi
Subjects: Computer science, Homo sapiens, RNA splicing, Genomics, splice, Computational biology, Predicting performance, Hamming code, Acceptor, DNA sequencing
Abstract: As genomic non-coding regions have gained significant research interest recently, the necessity to understand intronic sequences has become more stringent. This paper presents a study in which three computational text distance methods (Levenshtein, Hamming, Needleman-Wunsch) were used for predicting human acceptor splice site sequences. The Homo Sapiens Splice Site Dataset was used for evaluating the predicting performance of the methods. A python library was used for the implementation of the methods. Sensitivity, specificity, and the mean between the sensitivity and specificity were considered as performance metrics. For each method, several configurations were scanned. The first parameter in the configuration was the number of neighboring sequences. For this parameter, the odd values between one and eleven were considered. The second parameter represented the length of the DNA sequences (between nine and thirty-five). The overall predicting performance of Hamming and Levenshtein was lower than that of Needleman-Wunsch. The optimal configuration for Needleman-Wunsch was within nine neighboring sequences and twenty nucleotides, in which the method obtained an accuracy of 85.6%. The results can be further used for identifying cryptic acceptor splice sites in the deep intronic area of genes that occur due to genetic variants.
Published: 2020

29. Biallelic variants in

Author: Adela, Chirita-Emandi, Nicoleta, Andreescu, Cristina, Popa, Alexandra, Mihailescu, Anca-Lelia, Riza, Razvan, Plesea, Mihai, Ioana, Smaranda, Arghirescu, and Maria, Puiu
Subjects: Male, BRCA1 Protein, diagnosis, DNA Repair-Deficiency Disorders, Pedigree, Phenotypes, Phenotype, Mutation, child health, Humans, Genetic Predisposition to Disease, genetics, Symptom Assessment, Alleles, Biomarkers, Genetic Association Studies
Abstract: Pathogenic variants in BRCA1 gene in heterozygous state are known to be associated with breast-ovarian cancer susceptibility; however, biallelic variants cause a phenotype recognised as Fanconi anaemia complementation group S. Due to its rarity, medical management and preventive screening measures are insufficiently understood. Here, we present nine individuals (one new and eight previously presented) with biallelic variants in BRCA1 gene, to delineate clinical features in comparison with other chromosome instability syndromes and understand the patients’ health risk. Features seen in these 9 individuals (7 females/2 males) include prenatal and postnatal growth failure (9/9), microcephaly (9/9), hypo/hyperpigmented lesions (9/9), facial dysmorphism (9/9), mild developmental delay (8/9) and early-onset solid tumours (5/9). None presented bone marrow failure or immunodeficiency. Individuals with biallelic variants in BRCA1 also showed chromosomal instability by mitomycin and diepoxybutane test. The phenotype caused by biallelic BRCA1 variants is best framed between Fanconi anaemia and Nijmegen syndrome, yet distinct due to lack of bone marrow failure and immunodeficiency. We hypothesise that disease class should be reframed and medical management in people with biallelic variants in BRCA1 should emphasise on detection of solid tumour development and avoiding exposure to ionising radiation.
Published: 2020

30. Ordered 24-Hrs Recalls Associate with Systematic and Order-Specific Differences in Reported Energy and Carbohydrate Intakes by Individuals with Obesity: A methodological Approach in A Cross-Sectional Study

Author: Alexandra Sima, Mihai D. Niculescu, Iulia Teodora Perva, Salomeia Putnoky, Nicoleta Andreescu, Maria Puiu, Adela Chirita-Emandi, and Costela Lacrimioara Serban
Subjects: Order (business), Cross-sectional study, Environmental health, medicine, medicine.disease, Obesity, Mathematics
Abstract: Background. In depth understanding of dietary patterns of individuals with obesity is needed in practice and research, in order to support dietitians and physicians in the design and implementation of nutritional management. We aimed to analyze the consistency of energy, macro- and micronutrients reported intakes in four non-consecutive 24-hrs dietary recalls using information collected in the NutriGen Study (ClinicalTrials.gov, NCT02837367).Methods. Data included reported food intakes from 388 adults who completed four 24-hrs recalls. Results. Analyses indicated a significant decrease between the first and subsequent evaluations in regard to energy and several nutrients, with a systematic decrease in reporting energy and carbohydrates for the second evaluation. When excluding the second 24-hrs recall from the average, this new evaluation induced significant increases in the averages for reported energy, carbohydrates, and almost all micronutrients, indicating that the second recall is a point of controversy for whether to be included or not in further analyses.Conclusion. This study identified systematic differences in energy and carbohydrate reporting in the second recall, when four ordered 24-hour recalls were administered to adults with obesity. More studies are needed to identify the source of these differences, in order to ascertain whether reporting, training bias, or behavioral changes are responsible for such differences, and whether a time point with systematic differences should be included or not in further analyses.
Published: 2020

31. Challenges in reporting pathogenic/potentially pathogenic variants in 94 cancer predisposing genes - in pediatric patients screened with NGS panels

Author: Adela Chirita-Emandi, Smaranda Arghirescu, Margit Serban, Nicoleta Andreescu, Paul Tutac, Maria Puiu, and Cristian G. Zimbru
Subjects: Male, 0301 basic medicine, Cancer-Predisposing Gene, PALB2, In silico, lcsh:Medicine, medicine.disease_cause, Bioinformatics, Article, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Cancer genomics, Humans, Medicine, lcsh:Science, Child, Gene, Retrospective Studies, Multidisciplinary, business.industry, lcsh:R, High-Throughput Nucleotide Sequencing, Cancer, Prognosis, medicine.disease, FANCA, Neoplasm Proteins, FANCB, 030104 developmental biology, Risk factors, 030220 oncology & carcinogenesis, Mutation, lcsh:Q, Female, business, Carcinogenesis
Abstract: The benefit of reporting unsolicited findings in Next Generation Sequencing (NGS) related to cancer genes in children may have implications for family members, nevertheless, could also cause distress. We aimed to retrospectively investigate germline variants in 94 genes implicated in oncogenesis, in patients referred to NGS testing for various rare genetic diseases and reevaluate the utility of reporting different classes of pathogenicity. We used in silico prediction software to classify variants and conducted manual review to examine unsolicited findings frequencies in 145 children with rare diseases, that underwent sequencing - using a 4813 gene panel. The anonymized reanalysis revealed 18250 variants, of which 126 were considered after filtering. Six pathogenic variants (in BRCA1,BMPR1A,FANCA,FANCC,NBN genes) with cancer related phenotype and three unsolicited variants (in BRCA2,PALB2,RAD50 genes) were reported to patients. Additionally, three unsolicited variants in ATR, BLM (in two individuals), and FANCB genes presented potential cancer susceptibility, were not reported to patients. In retrospect, 4.8% (7/145) of individuals in our cohort had unsolicited NGS findings related to cancer. More efforts are needed to create an updatable consensus in reporting variants in cancer predisposing genes, especially for children. Consent process is crucial to inform of both value and risk of additional genetic information.
Published: 2020

32. Genetic and phenotypic characterization of NKX6‐2‐related spastic ataxia and hypomyelination

Author: Nicholas W. Wood, Saif Alshahrani, Dilek Colak, Michael C. Kruer, Kshitij Mankad, Zuhair Rahbeeni, Rozeena Huma, Khushnooda Ramzan, Rawan Almass, Stanislav Groppa, Moeenaldeen Al-Sayed, Indran Davagnanam, Fuad Almutairi, Maha S Al-Shammari, Maria Puiu, E Ghayoor Karimiani, N. Kaya, Stephanie Efthymiou, Nourelhoda A Haridy, M Beiraghi Toosi, Alya Qari, Muddathir H. Hamad, Mustafa A. Salih, Maysoon Alsagob, Somayeh Bakhtiari, Jessika Johannsen, Tatjana Bierhals, Reza Maroofian, Katja Kloth, Adela Chirita-Emandi, Henry Houlden, N T Malintan, Faiqa Imtiaz, Ibrahim A. Alorainy, Jana Vandrovcova, Laila AlQuait, Hamad Al-Zaidan, and Viorica Chelban
Subjects: Pediatrics, medicine.medical_specialty, leukodystrophy, animal structures, hypomyelination, Neonatal onset, Compound heterozygosity, 03 medical and health sciences, Epilepsy, 0302 clinical medicine, Intellectual Disability, Medicine, Humans, Spinocerebellar Ataxias, 030212 general & internal medicine, Child, Exome sequencing, SPAX8, Homeodomain Proteins, Cerebellar ataxia, business.industry, Leukodystrophy, Original Articles, medicine.disease, Disease gene identification, Hypotonia, 3. Good health, Optic Atrophy, Phenotype, Neurology, Muscle Spasticity, Mutation, embryonic structures, NKX6‐2, Original Article, Neurology (clinical), medicine.symptom, business, spastic ataxia 8, 030217 neurology & neurosurgery
Abstract: Background and purpose\ud Hypomyelinating leukodystrophies are a heterogeneous group of genetic disorders with a wide spectrum of phenotypes and a high rate of genetically unsolved cases. Bi‐allelic mutations in NKX6‐2 were recently linked to spastic ataxia 8 with hypomyelinating leukodystrophy.\ud \ud Methods\ud Using a combination of homozygosity mapping, exome sequencing, and detailed clinical and neuroimaging assessment a series of new NKX6‐2 mutations in a multicentre setting is described. Then, all reported NKX6‐2 mutations and those identified in this study were combined and an in‐depth analysis of NKX6‐2‐related disease spectrum was provided.\ud \ud Results\ud Eleven new cases from eight families of different ethnic backgrounds carrying compound heterozygous and homozygous pathogenic variants in NKX6‐2 were identified, evidencing a high NKX6‐2 mutation burden in the hypomyelinating leukodystrophy disease spectrum. Our data reveal a phenotype spectrum with neonatal onset, global psychomotor delay and worse prognosis at the severe end and a childhood onset with mainly motor phenotype at the milder end. The phenotypic and neuroimaging expression in NKX6‐2 is described and it is shown that phenotypes with epilepsy in the absence of overt hypomyelination and diffuse hypomyelination without seizures can occur.\ud \ud Conclusions\ud NKX6‐2 mutations should be considered in patients with autosomal recessive, very early onset of nystagmus, cerebellar ataxia with hypotonia that rapidly progresses to spasticity, particularly when associated with neuroimaging signs of hypomyelination. Therefore, it is recommended that NXK6‐2 should be included in hypomyelinating leukodystrophy and spastic ataxia diagnostic panels.
Published: 2020

33. Telemedicine strategy of the European Reference Network ITHACA for the diagnosis and management of patients with rare developmental disorders

Author: Francesca Clementina Radio, Bruno Dallapiccola, Mélanie Fradin, Alessandra Renieri, Alain Verloes, Jill Clayton-Smith, Michael Smith, Bronwyn Kerr, Rasika Sowmyalakshmi, Dorica Dan, Matteo Cassina, Massimiliano Rossi, Marketa Havlovicova, Laurence Faivre, Con Hennessy, Sofia Douzgou, Hany Mina, Siddharth Banka, Rasa Traberg, Aurélien Trimouille, Myfanwy Rawson, Ruta Marcinkute, Elizabeth Alexander, Ann Nordgren, Adela Chirita Emandi, Florence Riccardi, Jason Gavin, and Lianne Gompertz
Subjects: medicine.medical_specialty, Telemedicine, Service (systems architecture), Developmental disorders, European reference network, Rare disease, Process (engineering), Developmental Disabilities, lcsh:Medicine, Telehealth, behavioral disciplines and activities, Rare Diseases, Intellectual disability, medicine, Humans, Data Protection Act 1998, Pharmacology (medical), Child, Genetics (clinical), Research, lcsh:R, General Medicine, medicine.disease, Patient management, Europe, Medical genetics, Medical emergency, Psychology, Delivery of Health Care
Abstract: Background The European Reference Networks, ERNs, are virtual networks for healthcare providers across Europe to collaborate and share expertise on complex or rare diseases and conditions. As part of the ERNs, the Clinical Patient Management System, CPMS, a secure digital platform, was developed to allow and facilitate web-based, clinical consultations between submitting clinicians and relevant international experts. The European Reference Network on Intellectual Disability, TeleHealth and Congenital Anomalies, ERN ITHACA, was formed to harness the clinical and diagnostic expertise in the sector of rare, multiple anomaly and/or intellectual disability syndromes, chromosome disorders and undiagnosed syndromic disorders. We present the first year results of CPMS use by ERN ITHACA as an example of a telemedicine strategy for the diagnosis and management of patients with rare developmental disorders. Results ERN ITHACA ranked third in telemedicine activity amongst 24 European networks after 12 months of using the CPMS. Information about 28 very rare cases from 13 different centres across 7 countries was shared on the platform, with diagnostic or other management queries. Early interaction with patient support groups identified data protection as of primary importance in adopting digital platforms for patient diagnosis and care. The first launch of the CPMS was built to accommodate the needs of all ERNs. The ERN ITHACA telemedicine process highlighted a need to customise the CPMS with network-specific requirements. The results of this effort should enhance the CPMS utility for telemedicine services and ERN-specific care outcomes. Conclusions We present the results of a long and fruitful process of interaction between the ERN ITHACA network lead team and EU officials, software developers and members of 38 EU clinical genetics centres to organise and coordinate direct e-healthcare through a secure, digital platform. The variability of the queries in just the first 28 cases submitted to the ERN ITHACA CPMS is a fair representation of the complexity and rarity of the patients referred, but also proof of the sophisticated and variable service that could be provided through a structured telemedicine approach for patients and families with rare developmental disorders. Web-based approaches are likely to result in increased accessibility to clinical genomic services.
Published: 2020

34. Contributors

Author: Itziar Abete, Xabier Agirre, Jennie Ahlgren, Gorka Alkorta-Aranburu, Rocío Aller, Cristina Andres-Lacueva, Daniel Antonio de Luis, Darwin Babino, Shimrit Bar-El Dadon, Maria Luisa Bonet, Laura Bordoni, Patrick Borel, Annet M. Bosch, Steven Brown, Dolores Busso, Nadia Calabriso, Antonio Capurso, Cristiano Capurso, Marica Cariello, Maria Annunziata Carluccio, Patricia Casas-Agustench, Carol L. Cheatham, Adela Chirita-Emandi, Geetha Chittoor, Myung-Sook Choi, Sang-Woon Choi, Paul Cordero, Fernando J. Corrales, Víctor Cortés, Nicholas C.P. Cross, Ana B. Crujeiras, Rui Curi, Raffaele De Caterina, David de Lorenzo, Charles Desmarchelier, Olivia Dong, Ramón Estruch, Teresa Ezponda, Michael Fenech, Lynnette R. Ferguson, Karina Fischer, Luigi Fontana, Simonetta Friso, Rosita Gabbianelli, Marat Garaulet, Oihane Garcia-Irigoyen, Angel Gil, Purificación Gómez-Abellán, Ulf Görman, William S. Harris, Alain de J. Hernandez-Vazquez, Paul Hugenholtz, Lara K. Hyde, Clara Ibáñez, Olatz Izaola, Peter J.H. Jones, Richard Kirwan, Martin Kohlmeier, Natalia I. Krupenko, Eun-Young Kwon, Dudley W. Lamming, Rosa M. Lamuela-Raventos, Dominique Langin, Simon Langley-Evans, Cátia Lira do Amaral, Jesus Lopez-Minguez, Rosalinda Madonna, Maria L. Mansego, Clarisse Marotz, J. Alfredo Martinez, Marika Massaro, Susan McRitchie, Bayan Mesmar, Fermín I. Milagro, María J. Moreno-Aliaga, Isabel Moreno-Indias, Antonio Moschetta, Santiago Navas-Carretero, Mihai Niculescu, Karin Nordström, Francisco J. Novo, Jude A. Oben, Leticia Odriozola, Jose M. Ordovas, Andreu Palou, Virginia R. Parslow, Wimal Pathmasiri, José Luis Pérez-Castrillón, Louis Pérusse, Elena Piccinin, Julio Plaza-Diaz, Felipe Prósper, Lu Qi, Jessica C. Ralston, Ana Ramírez de Molina, George Rasti, Ram Reifen, Giulia Renda, José A. Riancho, José Antonio Riancho del Moral, Fernando Rivadeneira, Helen M. Roche, Marta Ruiz-Mambrilla, Francisco Javier Ruiz-Ojeda, Francisca Salas-Pérez, Rodrigo San-Cristobal, Nicolás Santander, José L. Santos, Jörg Saupe, Egeria Scoditti, Charles N. Serhan, Nicolas G. Simonet, Artemis P. Simopoulos, Nanette Steinle, Susan C.J. Sumner, Francisco J. Tinahones, Alejandro Vaquero, Itzel Vazquez-Vidal, Antonio Velazquez-Arellano, Nathalie Viguerie, Manlio Vinciguerra, Francesco Visioli, José L. Vizmanos, Johannes von Lintig, Venkata Saroja Voruganti, Ronald J.A. Wanders, Tiange Wang, Tim Wiltshire, Deyang Yu, Amir Zarrinpar, Steven H. Zeisel, and Maria Angeles Zulet
Published: 2020

35. Screening for Inborn Errors of Metabolism

Author: Adela Chirita-Emandi
Subjects: Newborn screening, medicine.medical_specialty, Nutritional Interventions, business.industry, Intervention (counseling), Screening programs, Medicine, business, Adverse effect, Intensive care medicine, Health outcomes, Specific enzyme, Primary therapy
Abstract: Inborn errors of metabolism (IEM) are genetic disorders in which specific enzyme defects disturb the metabolism of exogenous or endogenous proteins, carbohydrates, or fat. IEM disorders may manifest at any stage of life. Whereas onset in the newborn period or infancy is well-recognized, onset in adulthood is much less known. Furthermore, owing to early diagnosis and proper management, many adults received a diagnosis of IEM in childhood. Almost all countries around the globe include IEM in state newborn screening programs, but the number of diseases varies greatly between countries and among different states within the United States. In principle, the result of reduced or absent enzyme activity with all IEM leads to toxic metabolites that build up in the blood, brain, and other organs, whereas other compounds may become deficient, leading to adverse health outcomes. Therefore, nutritional interventions that can avoid or overcome metabolic consequences are warranted for some IEM. Early diagnosis and treatment, preferably at birth, can often diminish or surmount the adverse effects of some IEM, resulting in almost normal health. For many IEM, nutritional intervention is the primary therapy and is required lifelong. Therefore, screening programs represent an excellent opportunity to establish the diagnosis quickly.
Published: 2020

36. Methods for Global Nutrigenomics and Precision Nutrition

Author: Adela Chirita-Emandi and Mihai D. Niculescu
Subjects: Nutrigenomics, Metagenomics, Computer science, Personalized nutrition, InformationSystems_MISCELLANEOUS, Data science
Abstract: The concepts of personalized nutrition and precision nutrition allow researchers and nutrition practitioners to tailor individual nutrition requirements better. To address the complexity and diversity of nutrigenomic methods and output data successfully, researchers and nutrition practitioners need to choose appropriate methods for a given experiment design or inquiry, but also to make sure that the interpretation of data is adequate. Nutrigenomics applies many integrative methods concerning high-throughput “omics” technologies such as genomics, transcriptomics, proteomics, metabolomics, metagenomics, and epigenomics. Each analytic platform provides complementary information that needs to be integrated appropriately to achieve a better understanding of the mechanisms underlying nutrition and health. This chapter introduces the methods employed for nutrigenomic studies and nutrigenomic assessments from laboratory techniques in the omics fields to statistical/bioinformatics aspects to be considered when interpreting data generated by such technologies and platforms.
Published: 2020

37. Ethnicity-related DMD Genotype Landscapes in European and Non-European Countries

Author: Cristina Rusu, Selma Dounia Bensemmane, Mingyan Fang, Magdalena Sandu, Lyudmilla Angelova, Marcella Neri, Veneta Bojinova, Jadranka Sekelj Fureš, Fernanda Fortunato, Ivan Litvinenko, Maria Judith Molnar, Anna Potulska-Chromik, Oussama Dendane, C. Burloiu, Samira Makri-Mokrane, Daniela Vasile, Monica Panzaru, Zhiyuan Lu, Yamina Sifi, Niculina Butoianu, Oana Alexandra Iuhas, Birute Burnyte, Butnariu Lacramioara, Rachele Rossi, Djawed Bouchenak Khelladi, Ivan Lehman, Cecilia Trabanelli, Velina Guergueltcheva, Mariela Militaru, Léna Szabó, Anna Lusakowska, Mihaela Vintan, Sanja Delin, Monica Mager, Anna Kostera-Pruszczyk, Gabriela Visa, Agnes Herczegfalvi, Yurtsever Vildan, Andriy V. Shatillo, Dmitry Vlodavets, Balint Fekete, Adela Chirita Emandi, Rita Selvatici, Ivan S. Ivanov, Francesca Gualandi, Alessandra Ferlini, Alice Margutti, Diana Epure, and Theodore Kyriakides
Subjects: 0301 basic medicine, musculoskeletal diseases, congenital, hereditary, and neonatal diseases and abnormalities, Duchenne muscular dystrophy, Socio-culturale, Gene modifiers haplotypes, DMD, next-generation sequencing, Gene mutation, Biology, Article, 03 medical and health sciences, Ethnicity, Genotype, Europe, 0302 clinical medicine, Becker muscular dystrophies (BMD), medicine, Multiplex ligation-dependent probe amplification, Allele, Genetics (clinical), Duchenne muscular dystrophies (DMD), Genetics, DMD gene mutations, Whole-exome sequencing (WES), Haplotype, medicine.disease, 3. Good health, Eastern european, 030104 developmental biology, Mutation (genetic algorithm), Neurology (clinical), 030217 neurology & neurosurgery
Abstract: ObjectiveGenetic diagnosis and mutation identification are now compulsory for Duchenne (DMD) and Becker muscular dystrophies (BMD), which are due to dystrophin (DMD) gene mutations, either for disease prevention or personalized therapies. To evaluate the ethnic-related genetic assortments of DMD mutations, which may impact on DMD genetic diagnosis pipelines, we studied 328 patients with DMD and BMD from non-European countries.MethodsWe performed a full DMD mutation detection in 328 patients from 10 Eastern European countries (Poland, Hungary, Lithuania, Romania, Serbia, Croatia, Bosnia, Bulgaria, Ukraine, and Russia) and 2 non-European countries (Cyprus and Algeria). We used both conventional methods (multiplex ligation-dependent probe amplification [MLPA] followed by gene-specific sequencing) and whole-exome sequencing (WES) as a pivotal study ran in 28 patients where DMD mutations were already identified by standard techniques. WES output was also interrogated for DMD gene modifiers.ResultsWe identified DMD gene mutations in 222 male patients. We identified a remarkable allele heterogeneity among different populations with a mutation landscape often country specific. We also showed that WES is effective for picking up all DMD deletions and small mutations and its adoption could allow a detection rate close to 90% of all occurring mutations. Gene modifiers haplotypes were identified with some ethnic-specific configurations.ConclusionsOur data provide unreported mutation landscapes in different countries, suggesting that ethnicity may orient genetic diagnosis flowchart, which can be adjusted depending on the mutation type frequency, with impact in drug eligibility.
Published: 2020

38. Determining Splicing Signal Variation in Humans by Analyzing the Regulatory Splicing Motifs

Author: Adela Chirita-Emandi, Cristian G. Zimbru, Nicoleta Andreescu, Adriana Albu, and Maria Puiu
Subjects: 0303 health sciences, Signal variation, Computational biology, Biology, Silencer, Phenotype, 03 medical and health sciences, 0302 clinical medicine, Order (biology), 030220 oncology & carcinogenesis, RNA splicing, Genetic variation, Enhancer, 030304 developmental biology, Sequence (medicine)
Abstract: The project’s aim was to generate a method for determining the changes that unfold in the regulatory splicing signals when a genetic variation occurs in a human DNA sequence. Different motifs and scores, available in the literature, were used in order to compute two values that represent the variation in splicing enhancer and splicing silencer signals. The computed values offered only directional information about signals. With a few exceptions, the computed results matched the splicing phenotype associated with the genetic variants found in the test dataset. The signal variations have been successfully determined and the general direction corresponds with the direction indicated by methods and tools found in the literature. The method provides an overview of the changes in splicing regulatory signals that can benefit researchers and medical personnel in prioritization of genetic variants.
Published: 2019

39. Performance Evaluation of in Silico Predictors for the Classification of ClinVar Variants

Author: Antonius Stanciu, Adriana Albu, Cristian G. Zimbru, Maria Puiu, Nicoleta Andreescu, and Adela Chirita-Emandi
Subjects: 0303 health sciences, 03 medical and health sciences, In silico, Harmonic mean, 030305 genetics & heredity, Statistics, Genetic variants, Overall performance, Biology, Pathogenicity, 030304 developmental biology
Abstract: The purpose of this paper is to evaluate the performance obtained by the software tools (in silico) used by researchers and clinicians to determine the pathogenicity for the genetic variants. In order to evaluate their performance, variants that were reported pathogenic or benign were extracted from the ClinVar dataset. The variants were filtered by certain criteria and then they were annotated using specific tools (ANNOVAR and dbNSFP). In order to determine the performance, a series of statistical measures were extracted. The list of performance measures consisted of: specificity, sensitivity, precision, the harmonic mean (F 1 score) and the regular mean between sensitivity and specificity. We found that the three predictors who had the highest sensitivity scores (CADD 96.2%, DANN 98.1%, M-CAP 96.8%) for determining the pathogenic variants, had mediocre specificity scores. The best overall performance was attributed to another three predictors (REVEL 91.5%, MetaSVM 85.5%, PolyPhen-2 HVAR 85%), which had the highest regular mean score. As future use, a combination of these tools is suggested.
Published: 2019

40. Single Nucleotide Polymorphisms in PEMT and MTHFR Genes are Associated with Omega 3 and 6 Fatty Acid Levels in the Red Blood Cells of Children with Obesity

Author: Maria Puiu, Costela Lăcrimioara Șerban, Corina Paul, Mihai D. Niculescu, Adela Chirita-Emandi, Alexandra Mihailescu, Diana-Andreea Tiugan, Paul Tutac, Iulian Velea, Vlad Serafim, Nicoleta Andreescu, and Cristian G. Zimbru
Subjects: medicine.medical_specialty, obesity, Linoleic acid, Single-nucleotide polymorphism, lcsh:TX341-641, Biology, chemistry.chemical_compound, children, Internal medicine, pemt, medicine, chemistry.chemical_classification, Nutrition and Dietetics, Fatty acid, food and beverages, Eicosapentaenoic acid, eye diseases, Endocrinology, chemistry, Docosahexaenoic acid, Methylenetetrahydrofolate reductase, biology.protein, Arachidonic acid, lipids (amino acids, peptides, and proteins), mthfr, lcsh:Nutrition. Foods and food supply, Food Science, Polyunsaturated fatty acid, polyunsaturated fatty acids, red blood cells
Abstract: Polyunsaturated fatty acids (PUFAs) play important roles in health and disease. PUFA levels are influenced by nutrition and genetic factors. The relationship between PUFA composition in red blood cells (RBCs) and genetic variations involved in PUFA metabolism has not been investigated in children with obesity. This study evaluated the association between several genetic variations and PUFA levels in RBCs in children with obesity. One hundred ninety-six children with obesity (101 females, 95 males) were evaluated using anthropometric measurements, dietary intakes, plasma and RBC PUFA quantification, blood biochemistry, and 55 single nucleotide polymorphisms within 14 genes. phosphatidylethanolamine N-methyltransferase (PEMT) rs1109859 and methylenetetrahydrofolate reductase gene (MTHFR) rs4846052 genotypes were associated with PUFA levels in RBCs. PUFA intake did not influence the RBC eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels. Higher RBC DHA and EPA levels were observed for PEMT rs1109859 GG and GA genotypes versus the AA genotype. Higher levels of RBC DHA, EPA, arachidonic acid (ARA), and linoleic acid (LA) and were observed for MTHFR rs4846052 TT genotype versus TC and CC genotypes. Genetic variations in PEMT rs1109859 and MTHFR rs4846052 were associated with different PUFA levels in RBC membranes and are estimators for PUFA species in RBCs. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children.
Published: 2019

41. Clinical relevance of retinal structure in children with laser-treated retinopathy of prematurity versus controls - using optical coherence tomography

Author: Adela Chirita-Emandi, Alina Stanciu, Maria Puiu, Nicoleta Andreescu, Florina Stoica, and Cristian G. Zimbru
Subjects: medicine.medical_specialty, Visual acuity, genetic structures, Term Birth, Eye disease, Visual Acuity, Gestational Age, Retina, 03 medical and health sciences, 0302 clinical medicine, Optical coherence tomography, 030225 pediatrics, Ophthalmology, medicine, Birth Weight, Humans, Retinopathy of Prematurity, Neonatology, Child, Laser Coagulation, medicine.diagnostic_test, Receiver operating characteristic, business.industry, Area under the curve, Gestational age, Retinopathy of prematurity, Organ Size, General Medicine, medicine.disease, eye diseases, Ophthalmoscopy, Case-Control Studies, Child, Preschool, 030221 ophthalmology & optometry, sense organs, medicine.symptom, business, Infant, Premature, Tomography, Optical Coherence
Abstract: PURPOSE We aimed to assess the macular anatomy using spectral domain optical coherence tomography (SD-OCT), in children born preterm who had laser-treated retinopathy of prematurity (ROP), and to investigate the relationship between structural changes in macula and visual function. METHODS Thirty-seven 3-8 years old children were included in the study in two groups: 20 children born preterm [(
Published: 2017

42. A Novel 3q29 Deletion in Association With Developmental Delay and Heart Malformation—Case Report With Literature Review

Author: Adela Chirita Emandi, Andreea Iulia Dobrescu, Gabriela Doros, Capucine Hyon, Diana Miclea, Calin Popoiu, Maria Puiu, Smaranda Arghirescu, West University of Timișoara [Roumanie] (WUT), Maladies génétiques d'expression pédiatrique [CHU Trousseau] (Inserm U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Babes-Bolyai University [Cluj-Napoca] (UBB), HAL-SU, Gestionnaire, Physiopathologie des maladies génétiques d'expression pédiatrique (UMRS_933), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Proband, Candidate gene, Microcephaly, Heart malformation, 3q29 microdeletion syndrome, 3q29, Case Report, 030204 cardiovascular system & hematology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Pediatrics, cytogenetics, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 030225 pediatrics, medicine, cardiac malformation, Genetics, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, behavior, lcsh:RJ1-570, lcsh:Pediatrics, medicine.disease, Phenotype, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism spectrum disorder, intellectual disability, Pediatrics, Perinatology and Child Health, business, SNP array
Abstract: International audience; 3q29 deletion syndrome is a rare disorder, causing a complex phenotype. Clinical features are variable and relatively non-specific. Our report aims to present an atypical, de novo deletion in chromosome band 3q29 in a preschool boy, first child of healthy non-consanguineous parents, presenting a particular phenotype (microcephaly, “full moon” face, flattened facial profile, large ears, auricular polyp, and dental dystrophies), motor and cognitive delay, characteristics of autism spectrum disorder and aggressive behavior. He also presented intrauterine growth restriction (birth weight 2,400 g) and a ventricular septal defect. SNP Array revealed a 962 kb copy number loss, on the chromosome 3q29 band (195519857–196482211), consistent with 3q29 microdeletion syndrome. FISH analysis using a RP11-252K11 probe confirmed the deletion in the proband, which was not present in the parents. Although the patient's deletion is relatively small, it partly overlaps the canonical 3q29 deletion (defined between TFRC and DLG1 gene) and extends upstream, associating a different facial phenotype compared to the classic 3q29 deletion, nonetheless showing a similar psychiatric disorder. This deletion is different from the canonical region, as it does not include the PAK2 and DLG1 genes, considered as candidates for causing intellectual disability. Thus, narrowing the genotype-phenotype correlation for the 3q29 band, FBX045 is suggested as a candidate gene for the neuropsychiatric phenotype.
Published: 2019

43. Overweight and Underweight Prevalence Trends in Children from Romania - Pooled Analysis of Cross-Sectional Studies between 2006 and 2015

Author: Carmen Barbu, Raluca Pop, Mihai Gafencu, Mihaela Balgradean, Veronica Mocanu, Simona Fica, Michaela Dobre, Elena Eliza Cinteza, Ionela Pascanu, Simona Tatar, Adela Chirita-Emandi, Gabriela Ichim, Bianca Ioana Chesaru, and Maria Puiu
Subjects: Male, Rural Population, Gerontology, medicine.medical_specialty, Health (social science), Adolescent, Urban Population, Cross-sectional study, Public Policy, lcsh:TX341-641, 030209 endocrinology & metabolism, Environment, Overweight, Social Environment, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Thinness, Risk Factors, Physiology (medical), Ethnicity, Odds Ratio, medicine, Humans, Obesity, 030212 general & internal medicine, Child, Children, lcsh:RC620-627, Male gender, Schools, Romania, business.industry, Public health, Odds ratio, medicine.disease, lcsh:Nutritional diseases. Deficiency diseases, Cross-Sectional Studies, Pooled analysis, Female, Original Article, medicine.symptom, Underweight, business, lcsh:Nutrition. Foods and food supply, Demography
Abstract: Aim: High-quality national representative data on obesity in Romanian children are needed to shape public health policies. To provide a unified data landscape on national prevalence, trends and other factors associated with underweight, overweight, and obesity in Romanian children aged 6-19 years, across the last decade (2006-2015). Methods: Using a common protocol, we selected published and unpublished studies that measured Romanian children in schools between 2006 and 2015. Children's BMI was classified using the current WHO, IOTF, and CDC references. Results: 25,060 children from 8 Romanian counties were included in the analysis. The prevalence of underweight children was 5%/4.5%/8.5% (WHO/IOTF/CDC), while the prevalence of overweight (including obese) children was 28.3%/23%/23.2% (WHO/IOTF/CDC). The prevalence of overweight children did not change significantly over the last decade (chi-square test p = 0.6). Male gender (odds ratio (OR) 1.37; 95% CI 1.29-1.45, compared to female); prepubertal age (OR = 3.86; 95% CI 3.41-4.36,compared to postpubertal age), and urban environment (OR 1.12; 95% CI 1.01-1.26, compared to rural environment) had higher risk for overweight. Conclusion: While the prevalence of underweight children was low, almost one in four children in Romania was overweight or obese (according to WHO criteria) between 2006 and 2015. This prevalence remained relatively stable over the last decade. Male gender, prepubertal age, and urban environment, were the most relevant risk factors associated with overweight status in Romanian children.
Published: 2016

44. Splice site pattern analysis and identification of similar sequences in the deep intron areas of human chromosome 21

Author: Mihai D. Niculescu, Antonius Stanciu, Nicoleta Andreescu, Ioan Silea, Maria Puiu, Cristian G. Zimbru, and Adela Chirita-Emandi
Subjects: 0301 basic medicine, Splice site mutation, In silico, Intron, Genomics, Computational biology, Biology, Molecular biology, DNA sequencing, 03 medical and health sciences, 030104 developmental biology, RNA splicing, splice, Chromosome 21
Abstract: We describe the results of an in silico experiment realized on the DNA sequence of human chromosome 21, with the aim of identifying splicing sites using a bioinformatics algorithm. The study was divided in two phases. In the first phase, we analyzed the branch site position and the characteristics of the pyrimidine tract. In the second phase, a search was conducted in the introns for sequences that are similar to splice sites using definition based on the result obtained in the previous phase. We found, in average, three similar sequences per intron. We also found that a number of splice sites have multiple branch point sequences.
Published: 2017

45. Analysis of decision tree performance in predicting the relationship between a scored outcome and multiple single nucleotide polymorphisms

Author: Adela Chirita-Emandi, Nicoleta Andreescu, Cristian G. Zimbru, Ioan Silea, Maria Puiu, and Mihai D. Niculescu
Subjects: 0301 basic medicine, 03 medical and health sciences, Tree (data structure), 030104 developmental biology, Cohen's kappa, Computer science, Statistics, Decision tree, Sampling (statistics), Single-nucleotide polymorphism, Pruning (decision trees), Minimum description length, Outcome (probability)
Abstract: We describe the results of an experiment for which we used decisional tree analysis to find a relationship between multiple single nucleotide polymorphisms (SNPs) and a scored health outcome based on a given dataset. We used Gini Index and Minimum Description Length (MDL) to optimize the accuracy of predicting the scored health outcome using SNPs as input variables. Decision tree models were generated using different configuration of pruning, sampling and split functions. We analyzed two parameters, the accuracy of the prediction and the Cohen's kappa coefficient, for each generated model. In regard to scoring stage, the experiment was divided in two phases. The first phase used a more detailed dataset and the second phase a less detailed dataset. The best models, with the highest accuracy, were obtained for a decision tree that used the split function Gini Index with the MDL pruning, and with the random sampling method. The model with the best prediction accuracy had a 91% identification rate. The results obtained for the Cohen's kappa coefficient were less accurate.
Published: 2017

46. A retrospective analysis of longitudinal changes in bone mineral content in cystic fibrosis

Author: Jane McNeilly, Andreas Kyriakou, Carol Dryden, Syed Faisal Ahmed, Donna Corrigan, Anne Devenny, Sheila Shepherd, and Adela Chirita-Emandi
Subjects: Male, medicine.medical_specialty, Longitudinal study, Adolescent, Cystic Fibrosis, Endocrinology, Diabetes and Metabolism, Cystic fibrosis, 03 medical and health sciences, Absorptiometry, Photon, 0302 clinical medicine, Endocrinology, Bone Density, 030225 pediatrics, Internal medicine, Vitamin D and neurology, medicine, Retrospective analysis, Humans, Longitudinal Studies, 030212 general & internal medicine, Child, Retrospective Studies, Lumbar Vertebrae, business.industry, Anthropometry, Bone area, medicine.disease, Pediatrics, Perinatology and Child Health, Disease Progression, Bone mineral content, Female, Lumbar spine, business, Whole-Body Irradiation
Abstract: Background:We aimed to describe the longitudinal changes in bone mineral content and influencing factors, in children with cystic fibrosis (CF).Methods:One hundred children (50 females) had dual X-ray absorptiometry (DXA) performed. Of these, 48 and 24 children had two to three scans, respectively over 10 years of follow-up. DXA data were expressed as lumbar spine bone mineral content standard deviation score (LSBMCSDS) adjusted for age, gender, ethnicity and bone area. Markers of disease, anthropometry and bone biochemistry were collected retrospectively.Results:Baseline LSBMCSDS was >0.5 SDS in 13% children, between −0.5; 0.5 SDS, in 50% and ≤−0.5 in the remainder. Seventy-eight percent of the children who had baseline LSBMCSDS >−0.5, and 35% of the children with poor baseline (LSBMCSDSConclusions:Bone mineral content as assessed by DXA is sub-optimal and decreases with time in most children with CF and this study has highlighted parameters that can be addressed to improve bone health.
Published: 2017

47. MEDICAL PRACTICE IN CHILDREN PRESENTING FEVER WITH PETECHIAL RASH TO AN EMERGENCY DEPARTMENT

Author: Ioana, Dumitrascu-Biris, Adela, Chirita-Emandi, Imelda, Lambert, Otilia, Marginean, and Farhana, Sharif
Subjects: Male, Fever, Romania, Infant, Exanthema, Risk Assessment, Severity of Illness Index, Diagnosis, Differential, Meningococcal Infections, Risk Factors, Child, Preschool, Nasopharynx, Prevalence, Humans, Female, Child, Emergency Service, Hospital, Respiratory Tract Infections, Purpura, Retrospective Studies
Abstract: The association of fever and petechiae in children is one of the most alarming findings for a paediatrician. To quickly distinguish between benign and life-threatening conditions is challenging in many cases. We aimed to evaluate the clinical practice of children presenting with fever and petechiae as initial symptoms.41 patients (age 3 months-11 years) presenting with fever and petechiae were identified in an Emergency Paediatric Assessment Unit over a period of 9 months. General data, symptoms and signs were assessed for each patient. The work-up consisted in: complete blood count, inflammatory tests, coagulation tests, Monospot test, nasopharyngeal rapid tests, blood culture, and cerebrospinal fluid culture where appropriate.Most children were5 years of age (70.7%). Female to male ratio was 1:2.4. The most common clinical diagnoses were: viral respiratory illness (48.8%, 20/41) and upper respiratory tract infection (17.1%, 7/41). Meningococcal disease was found in one case. CRP6 mg/l was poorly correlated with serious illness. The following variables were strongly associated with serious illness: ill appearance, shivering, lethargy, back rigidity, ESR50 mm/h and prolonged capillary refill time. 59% (24/41) of children were treated with antibiotics, however, at discharge 42%(10/24) of them, did not have a work-up suggestive for a bacterial illness.Screening for low prevalence but high morbidity conditions, as the meningococcal disease, with an extensive work-up is time and resource consuming and may lead to unmotivated antibiotic use. Larger studies are needed to change the emergency practice for management of fever and rash.
Published: 2016

48. HEAD CIRCUMFERENCE REFERENCES FOR SCHOOL AGE CHILDREN IN WESTERN ROMANIA

Author: Adela, Chirita-Emandi, Gabriela, Doros, Iulia Jurca, Simina, Mihai, Gafencu, and Maria, Puiu
Subjects: Adult, Male, Adolescent, Cephalometry, Romania, Age Factors, Body Height, Sex Factors, Belgium, Reference Values, Germany, Humans, Female, Growth Charts, Child, Retrospective Studies
Abstract: To provide head circumference references for school-aged children in western Romania, and compare them with references from other European countries.A total of 2742 children, aged 6-19 years, from Timis county, were examined by medical students, between February 2010-June 2011. Head circumference references were constructed by Cole's LMS method with LMSChartMaker software. The Romanian 3rd, 50th and 97th percentiles for head circumference were compared with recent references from Belgium and Germany.Generally, boys show significantly larger head circumference compared to girls at any age. The head circumference increments between 6 and 19 years are1 cm/year. Head circumference increments decrease in increasing age of the children. In girls, adult head circumference is reached at the age of 16 years, whereas head circumference growth continues, in boys, slowly until 18 years. The comparison of Romanian head percentiles with those from Belgium and Germany revealed a smaller head circumference in Romanian children (both girls and boys).Comparing head circumference references from Romania to those from Germany and Belgium, we found lower median head circumference in Romanian boys and girls, that could be explained by a taller stature of boys and girls in Germany and Belgium compared to Romania.
Published: 2016

49. Vitamin D Status: A Different Story in the Very Young versus the Very Old Romanian Patients

Author: Demetra Socolov, Anca Calapiș, Cristina Gheorghiu, Carmen Haivas, Maria Puiu, and Adela Chirita-Emandi
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Adolescent, Population, Parathyroid hormone, lcsh:Medicine, Context (language use), vitamin D deficiency, chemistry.chemical_compound, Young Adult, 25-Hydroxyvitamin D 2, Vitamin D and neurology, Medicine, Humans, Young adult, Vitamin D, education, Child, lcsh:Science, Aged, Calcifediol, Aged, 80 and over, education.field_of_study, Multidisciplinary, business.industry, Romania, lcsh:R, Infant, Newborn, Infant, Middle Aged, medicine.disease, Vitamin D Deficiency, Cross-Sectional Studies, chemistry, Parathyroid Hormone, Child, Preschool, Calcium, Female, lcsh:Q, Seasons, business, Research Article
Abstract: Background In Romania (latitude 48°15’N to 43°40’N), vitamin D supplementation is common practice mostly in infants 0-1 year old. No published information is available regarding epidemiological data on vitamin D status in the Romanian population for a wide age range and geographical territory. In this context, we aimed to evaluate the seasonal and age variation of vitamin D status in a large Romanian population. Methods 6631 individuals from across Romania had performed 7544 vitamin D assessments (2012-2014) in a chain of private laboratories. Vitamin D (25-hydroxyvitamin D2 and 25-hydroxyvitamin D3) was measured using High Performance Liquid Chromatography. Vitamin D levels were classified as severe deficiency100ng/ml. Results Male to female ratio was 1:2.9. Age ranged from 0 to 85 years. Mean vitamin D levels increased from April (26.3ng/ml) to September (35.6ng/ml) and decreased from October (33.5ng/ml) to March (24.4 ng/ml). Overall 40% had sufficient vitamin D, while the rest were insufficient 33%, deficient 22%, severely deficient 4% and 1% potentially harmful (of them 81% under 1 year old). Males compared to females showed higher percentages of sufficiency (47% vs. 38%). Children 0- 2 years presented the highest percentage of vitamin D sufficiency (77%). Lowest percentages (21%) of sufficiency were in people 80-84 years. Conclusion In Romania, suboptimal vitamin D levels are common (59%), especially in older age, wintertime and in women. Vitamin D supplementation would be most warranted from January to April in the Romanian population. 25-hydroxyvitamin D levels>100ng/ml were relatively prevalent in children 0-1 year old (17.3%). This was attributed to supplementation errors and the fact that high-risk individuals were more likely to visit for medical check-up. Nonetheless, it stresses the need to increase awareness of the importance of preventing Vitamin D supplementation administration errors in the young.
Published: 2015

50. Outcomes of neurofeedback training in childhood obesity management: a pilot study

Author: Adela Chirita-Emandi and Maria Puiu
Subjects: Male, Pediatrics, medicine.medical_specialty, Pediatric Obesity, Adolescent, Pilot Projects, Overweight, Childhood obesity, Body Mass Index, Quality of life, Weight loss, Intervention (counseling), Surveys and Questionnaires, Weight management, Weight Loss, medicine, Humans, Child, business.industry, Neurofeedback, medicine.disease, Treatment Outcome, Complementary and alternative medicine, Case-Control Studies, Physical therapy, Quality of Life, Female, medicine.symptom, business, Body mass index
Abstract: This pilot study sought to evaluate the neurofeedback training outcomes in childhood obesity management. The study involved 34 overweight and obese children, age 6-18 years (12 patients in the intervention group, 22 in the control group). Complete assessment of children was done before the intervention and 3 and 6 months after the intervention; eating behavior and quality-of-life questionnaires were assessed at study start and 6 months after. All children received classic lifestyle recommendations for weight management, while the intervention group also had 20 neurofeedback sessions (infra-low-frequency training). The neurofeedback intervention was associated with less weight loss compared with classic weight management. The mean change in body-mass index standard deviation score at 3 months was -0.29 for the intervention group and -0.36 for the control group (p=0.337); after 6 months, the changes were -0.30 and -0.56, respectively (p=0.035). Quality of life improved similarly for both groups. Subjective outcomes reported by patients in the intervention were less snacking, improved satiety, enhanced attention capacity, ameliorated hyperactivity, and better sleep patterns. Larger studies, with training methods involving both the left and right cortices, should further clarify the role of neurofeedback training in obesity management.
Published: 2014

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