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In a Europe that is undergoing digital transformation, the COGNITWIN project is contributing to accelerate the transformation and introduce Industry 4.0 to the European process industries. The opportunities here can be illustrated by the SPIRE 2050 Vision document (https://www.spire2030.eu/sites/default/files/users/user85/Vision_Document_V6_Pages_Online_0.pdf), which states that “Digitalisation of process industries has a tremendous potential to dramatically accelerate change in resource management, process control and in the design and the deployment of disruptive new business models.” The process industries are characterized with harsh environments where sensors are either costly, not available, or may be subject to costly maintenance. The development of digital twins that can exploit the combinations of data-based and physics-based models is often found to be a preferred path to robust digital twins that can help cutting costs and reduce energy consumption. In this article, we present 5 out of 6 industrial pilots that are developed in the COGNITWIN project. We discuss the commonalities and differences between the selected approaches and give some ideas about how cognition can be incorporated into the digital twins. The aim of this article is to inspire similar projects in related industries.

Introduction: Single-cell RNA sequencing (scRNAseq) and flow cytometry studies in skin are methodologically complex and costly, limiting their accessibility to researchers worldwide. Ideally, RNA and protein-based analyses should be performed on the same lesion to obtain more comprehensive data. However, current protocols generally focus on either scRNAseq or flow cytometry of healthy skin., Methods: We present a novel label-free sample multiplexing strategy, building on the souporcell algorithm, which enables scRNAseq analysis of paired blood and skin samples. Additionally, we provide detailed instructions for simultaneous flow cytometry analysis from the same sample, with necessary adaptations for both healthy and inflamed skin specimens., Results: This tissue multiplexing strategy mitigates technical batch effects and reduces costs by 2-4 times compared to existing protocols. We also demonstrate the effects of varying enzymatic incubation durations (1, 3, and 16 hours, with and without enzyme P) on flow cytometry outcomes. Comprehensive explanations of bioinformatic demultiplexing steps and a detailed step-by-step protocol of the entire experimental procedure are included., Discussion: The protocol outlined in this article will make scRNAseq and flow cytometry analysis of skin samples more accessible to researchers, especially those new to these techniques., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Khoshbakht, Albayrak, Tiryaki, Ağcaoğlu, Öktem, Pınar Sun, Er Gülbezer, Seda Ertekin, Boyvat, Vural and Vural.)

Objective: It has been shown that clonal mutations occur in hematopoietic stem cells with advancing age and increase the risk of death due to atherosclerotic vascular diseases, similarly to myeloproliferative neoplasms. Endothelial cells (ECs) and hematopoietic stem cells develop from common stem cells called hemangioblasts in the early embryonic period. However, the presence of hemangioblasts in the postnatal period is controversial. In this study, JAK2 gene variants were examined in patients with atherosclerotic carotid disease and without any hematological malignancies., Materials and Methods: Ten consecutive patients (8 men and 2 women) with symptomatic atherosclerotic carotid stenosis were included in this study. ECs (CD31 + CD45 - ) were separated from tissue samples taken by carotid endarterectomy. JAK2 variants were examined in ECs, peripheral blood mononuclear cells, and oral epithelial cells of the patients with next-generation sequencing., Results: The median age of the patients was 74 (range: 58-80) years and the median body mass index value was 24.44 (range: 18.42-30.85) kg/m 2 . Smoking history was present in 50%, hypertension in 80%, diabetes in 70%, and ischemic heart disease in 70% of the cases. The JAK2 V617F mutation was detected in the peripheral blood mononuclear cells of 3 of the 10 patients, and 2 patients also had the JAK2 V617F mutation in their ECs. The JAK2 V617F mutation was not found in the oral epithelial cells of any of the patients., Conclusion: In this study, for the first time in the literature, we showed that the JAK2 V617F mutation was found somatically in both peripheral blood cells and ECs in patients with atherosclerosis. This finding may support that ECs and hematopoietic cells originate from a common clone or that somatic mutations can be transmitted to ECs by other mechanisms. Examining the molecular and functional changes caused by the JAK2 V617F mutation in ECs may help open a new avenue for treating atherosclerosis., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2024 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Purpose: Accounting for about 15% of invasive lobular carcinomas and 1% of breast carcinomas, pleomorphic lobular carcinoma is known to be a rare histological subtype of invasive lobular carcinoma. Yet, it is more aggressive and produces a worse prognosis than other breast cancers. Ultimately, the present study compares the clinicopathological features of pleomorphic and invasive lobular breast carcinomas., Methods: In the study, we retrospectively evaluated the data of 262 patients with histological subtypes of classical and pleomorphic lobular cancers having been recruited for surgical operations. After resorting to Kolmogorov-Smirnov and Shapiro-Wilk tests to check the normality of distribution, the categorical and continuous variables were compared between the groups using the chi-square test and independent samples t test, respectively. In all analyses, we considered a P -value of <.05 to be statistically significant., Results: Our findings revealed that the groups with lobular and pleomorphic groups significantly differed by Ki-67 value, estrogen receptor negativity, grade, multicentricity, multifocality, surgical margin positivity, completion mastectomy, and metachronous contralateral tumor ( P < .05)., Conclusion: We discovered that pleomorphic type was associated with higher grades, estrogen receptor negativity, and Ki-67 expression. The incidence of metachronous breast cancer was high in the pleomorphic group, which may be a noteworthy finding to be considered in follow-ups. In addition, the high rates of multicentricity and multifocality of tumors in the pleomorphic group may be associated with increased surgical margin positivity and a higher likelihood of mastectomy. In a nutshell, our findings may guide patients and surgeons regarding the type of intervention and reconstruction options to be adopted in prospective surgeries., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In this study, we aimed to investigate the changes in the B cell subpopulations after homologous or heterologous COVID-19 boosters. Blood samples were collected after baseline (3-5 months after two doses of CoronaVac), 1 and 3 months after BNT162b2 (n=28 and n=6), and CoronaVac (n=7 and n=4) boosters. Peripheral blood mononuclear cells (PBMCs) were isolated and stained with B cell markers, the ratios of naïve (CD19+CD20+CD27-), memory (CD19+CD20+CD27+), memory B cells expressing IgG (CD19+CD20+CD27+IgG+), and effector memory B cells (CD19+CD20+CD27+CD38+) were identified with flow cytometry. Significantly higher expression of memory B cells was observed in one month with BNT162b2 (12.16% one month, 5.98% three months) and CoronaVac (14.18% one month, 9.00% three months) boosters. IgG expressing memory B cell expression was significantly higher with BNT162b2 than with CoronaVac booster in one month (22.70% and 13.95%, respectively). The ratio of effector B cells in the first month after CoronaVac booster (25.44%) was significantly higher than the BNT162b2 booster (9.90%, p =0.0263)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Infectious Diseases and Clinical Microbiology.)

Background: The Live Donor Assessment Tool (LDAT) is a semi-structured psychosocial assessment tool for evaluating potential organ donors. It enables standardization of the psychosocial evaluation across institutions and allows the quantification of the evaluation result., Objective: To evaluate the validity and reliability of the German version of the LDAT in living kidney donors., Methods: We assessed the internal consistency and convergent validity (using known groups) of the German version of the LDAT in donor candidates who were evaluated at Hannover Medical School from May 2017 to December 2021., Results: One hundred fifty-two donor candidates were evaluated. The mean age was 50.9 (standard deviation, 12.0), 99 were female (65.1%) and 53 (34.9%) were male candidates. LDAT scores ranged from 39 to 78 (possible maximum score = 82). The mean and median LDAT scores in the entire sample were 69 (standard deviation, 6.4) and 71 (95% confidence interval, 68; 70), respectively. The LDAT items demonstrated good internal consistency (α = 0.737). LDAT scores were significantly lower in high and moderate risk donors compared to a low/no risk group as determined by clinical evaluation. We found a significant positive association of the LDAT total score with age and a negative correlation with levels of depression and anxiety. The best cutoff score in our sample was 66.5 with an area under the curve of 93%., Conclusions: The German version of the LDAT was found to be a reliable and valid tool, which seems suitable to support psychosocial donor evaluation., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Gallbladder diseases are an important health concern affecting approximately 20% of the population in developed countries. Acute cholecystitis is the most common complication of gallstones. The aim of our study is to determine the use of Nesfatin-1, which is an easily applicable and fast resulting and is thought to have an association with inflammatory events, in the diagnosis and grading of acute cholecystitis., Methods: Patients who admitted and were hospitalized and treated with the acute cholecystitis diagnosis in İstanbul Training and Research Hospital between July 1, 2020, and December 1, 2020, were included in the study. The patients were divided in threemain groups as mild, moderate, and severe according to Tokyo Guidelines 2018 based on their routine blood tests and imaging results. All patients who are included in the study were tested for their blood leukocyte, neutrophil, lymphocyte, Nesfatin-1 levels, and neutrophil/lymphocyte ratios within the first 24 h of their hospitalization., Results: With at least 15 patients in each group, 61 volunteers in total were included in the study as healthy volunteers, mild, moderate, and severe cholecystitis. The average age of the participants were 58.11±19.76 years. About 47.54% of the participants were female and 52.46% weremale. In the study, Nesfatin-1 levels in the patient groups were found to be lower than the control group. In the subgroup analyzes, Nesfatin-1 values in the middle patient group were found to be significantly lower than the control group; however, there was no statistically significant relationship between the severity of the disease and Nesfatin-1., Conclusion: Nesfatin-1 may guide the clinician for the diagnosis of the disease; however, no significant relationship was found between Nesfatin-1 and the severity or stage of the disease.

Background: It is essential to know about immune response levels after booster doses of the two different types of vaccines, mRNA, and the inactivated, currently used against COVID-19. For this purpose, we aimed to determine the effects of BNT162b2 (BNT) and CoronaVac (CV) boosters on the humoral and cellular immunity of individuals who had two doses of CV vaccination., Methods: The study was conducted in three centers (Koc University Hospital, Istanbul University Cerrahpasa Hospital, and Istanbul University, Istanbul Medical School Hospital) in Istanbul, Turkey. Individuals who had been previously immunized with two doses of CV and no history of COVID-19 were included. The baseline blood samples were collected 3-5 months after the second dose of CV. Follow-up blood samples were taken 1 and 3 months after administration of third doses of CV, or one dose of BNT boosters. Neutralizing antibody titers were measured by plaque reduction assay. The CD4+ T cell, CD8+ T cell, effector CD4+CD38+CD69+ T cell, and effector CD8+CD38+CD69+ T cell ratios were determined by flow cytometry. The intracellular IFN-γ and IL-2 responses were measured by ELISpot assay., Results: We found a 3.38-fold increase in neutralizing antibody geometric mean titers (NA GMT, 78.69) 1 month after BNT booster and maintained at the third month (NA GMT, 80). Nevertheless, in the CV booster group, significantly lower NA GMT than BNT after 1 month and 3 months were observed (21.44 and 28.44, respectively) (p < .001). In the ELISpot assay, IL-2 levels after BNT were higher than baseline and CV booster (p < .001) while IFN-γ levels were significantly higher than baseline (p < .001). The CD8+CD38+CD69+ and CD4+CD38+CD69+ T cells were stimulated predominantly in the third month of the BNT boosters., Conclusion: The neutralizing antibody levels after 3 months of the BNT booster were higher than the antibody levels after CV in fully vaccinated individuals. On the contrary, ratio of the effector T cells increased along with greater IFN-γ activation after BNT booster. By considering the waning immunity, we suggest a new booster dose with BNT for the countries that already had two doses of primary CV regimens., (© 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Purpose: This study evaluated the efficacy of treating periodontitis using subgingival nano-hydroxyapatite powder with an air abrasion device (NHAPA) combined with scaling and root planing (SRP)., Methods: A total of 28 patients with stage III periodontitis (grade B) were included in this study, although 1 was lost during follow-up and 3 used antibiotics. The patients were divided into a test group and a control group. All patients first received whole-mouth SRP using hand instruments, and a split-mouth approach was used for the second treatment. In the test group, the teeth were treated with NHAPA for 15 seconds at 70% power per pocket. Subgingival plaque samples were obtained from the 2 deepest pockets at the test and control sites before treatment (baseline) and 3 months after treatment. The full-mouth plaque index (PI), gingival index (GI), papillary bleeding index (PBI), bleeding on probing (BOP), probing depth (PD) and clinical attachment level (CAL) were recorded at baseline and at 1- and 3-month post-treatment. Real-time polymerase chain reaction was used to determine the colonisation of Treponema denticola ( Td ), Porphyromonas gingivalis ( Pg ), and Aggregatibacter actinomycetemcomitans in the subgingival plaque., Results: From baseline to the first month, the test group showed significantly larger changes in BOP and CAL (43.705%±27.495% and 1.160±0.747 mm, respectively) than the control group (36.311%±27.599% and 0.947±0.635 mm, respectively). Periodontal parameters had improved in both groups at 3 months. The reductions of PI, GI, BOP, PD, and CAL in the test group at 3 months were greater and statistically significant. The total bacterial count and Td and Pg species had decreased significantly by the third month in both groups ( P <0.05)., Conclusions: Applying NHAPA in addition to SRP improves clinical periodontal parameters more than SRP alone. Subgingival NHAPA may encourage clot adhesion to tooth surfaces by increasing surface wettability., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2022. Korean Academy of Periodontology.)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive deterioration of cognitive functions (dementia) and represents a growing public health concern since the population in the age groups at risk is increasing. The latter raises an urgent need to translate research findings in the basic brain and behavioral sciences into anti-AD drugs and disease-modifying therapies. Origanum onites (L.), also called Turkish oregano, is a perennial and herbaceous plant species grown for centuries for medicinal, cosmetic and culinary purposes. This is the first study to investigate the putative neuroprotective and pro-cognitive activities of O. onites essential oil (OOEO) against scopolamine-induced amnesia of AD-type in Wistar albino rats. The results of behavioral tests revealed that OOEO administration was able to significantly alleviate learning and memory impairments induced by scopolamine in vivo. The observed effects could be attributed to inhibition of acetylcholinesterase activity, attenuation of oxidative stress and prevention of neuronal apoptosis in the hippocampus and frontal cortex of AD rats. Modulation of pro-inflammatory enzymes, including cyclooxygenase-2, inducible nitric oxide synthase and myeloperoxidase, might further contribute to the neuroprotective properties of OEOO, as predicted by our in silico models. These findings offer novel insights into the therapeutic potential of OEOO in patients with AD., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: Whether acute phase and immune responses are minimally affected following minimally invasive lung surgery needs further investigation. We performed a pilot study to evaluate the immune profile of patients who underwent video-assisted thoracoscopic surgery or robot-assisted thoracic surgery lobectomies for the treatment of suspicious or known stage I non-small-cell lung cancer., Methods: Blood samples were taken preoperatively and 3 and 24 h postoperatively were analysed for C-reactive protein, glucose, cortisol, tumour necrosis factor alpha (TNF-α), interleukin 8 (IL-8) and interleukin 10 (IL-10) levels. TNF-α, IL-8 and IL-10 were also measured in lung tissues. T (CD4, CD8), B (CD19) and natural killer (CD56, CD16) cell counts and natural killer cell functions were analysed using a flow cytometry-based assay before and after surgery., Results: Minimally invasive surgery (robot-assisted thoracic surgery + video-assisted thoracoscopic surgery) significantly decreased IL-10 (P = 0.016) levels after surgery. No significant differences were detected in TNF-α (P = 0.48) and IL-8 (P = 0.15) levels before and after surgery. C-reactive protein (P < 0.001), cortisol (P < 0.001) and glucose levels (P < 0.001) increased significantly after surgery. Lymphocyte, total T cell, CD3+CD4+ and CD3+CD8+ CD16+CD56+ cell counts were significantly lower on postoperative day 1., Conclusion: There seems to be a dynamic balance between pro- and anti-inflammatory cytokines and immune cells following minimally invasive lobectomy., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

To evaluate the impact of Birdshot-Retinochoroidopathy (BSRC) and Serpiginous Choroiditis (SC) on depression, anxiety, and vision-related quality of life. 72 individuals (BSRC: n = 28, SC: n = 8; healthy control group (HC): n = 36) completed the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and the Visual Function Questionnaire (VFQ-25). Multivariate linear regression models were used to analyze different subscales of the PHQ-9, the GAD-7 and the VFQ-25. The results showed that the mean of PHQ-9 was significantly higher while the mean of the VFQ-25 and its´ subscales were consistently lower in the disease group compared to HC. The mean of GAD-7 was not significantly lower in the disease group compared to HC. Stratification for different disease severity stages and duration of disease did not reveal any differences in sum scores of PHQ-9, GAD-7, and VFQ-25, whereas there were significant differences in some subscales of the VFQ-25. We conclude that BSRC and SC patients show higher levels of depression and a reduced visual quality of life due to imminent loss of vision. Because depression and quality of life are adversely affected by lack of social contacts and functioning, psychological treatment should enable patients to maintain their independence and ability to social interaction. Psychosomatic care should be taken in account for the treatment of BSRC and SC., Competing Interests: The authors have declared that no competing interests exist.

The aim of this study was to test the nano-hydroxyapatite powder decontamination method on intraorally contaminated titanium discs and to compare this method with current decontamination methods in the treatment of peri-implantitis. Contaminated discs were assigned to six treatment groups (n = 10 each): titanium hand curette; ultrasonic scaler with a plastic tip (appropriate for titanium); ultrasonic scaler with a plastic tip (appropriate for titanium) + H 2 O 2 ; short-term airflow system (nano-hydroxyapatite airborne-particle abrasion for 30 seconds); long-term airflow system (nano-hydroxyapatite airborne-particle abrasion for 120 seconds); Er:YAG laser (120 mJ/pulse at 10 Hz). There were also two control groups (n = 10 each): contaminated disc (negative control) and sterile disc (positive control). Scanning electron microscopy, energy-dispersive x-ray spectroscopy, and dynamic contact angle analysis were used to determine the most effective surface-treatment method. The highest percentage of carbon (C) atoms was observed in the negative control group, and the lowest percentage of C atoms was found in the long-term airflow group, followed by the short-term airflow, laser, ultrasonic + H 2 O 2 , ultrasonic, and mechanical groups. When the groups were examined for wettability, the lowest contact angle degree was observed in the long-term airflow, short-term airflow, and laser groups. Nano-hydroxyapatite and laser treatments for detoxifying and improving infected titanium surfaces may show the most suitable results for reosseointegration.

This study aimed to describe the effect of initial antifungal therapy on patient mortality and to detail the current distribution and resistance patterns of Candida spp. among patients with candidaemia. A prospective observational study was performed among consecutive patients with candidaemia from 10 Turkish medical centres between January 2015 and November 2018. The primary outcome was 10-day mortality. Species were identified using MALDI-TOF/MS. A total of 342 patients with candidaemia were included, of which 175 (51.2%) were male and 68 (19.9%) were aged <18 years. The most common species were Candida albicans (47.4%), Candida parapsilosis (26.6%), Candida tropicalis (9.6%) and Candida glabrata (7.6%). Among all Candida spp., the 10-day case fatality rate (CFR) was 32.2%. The CFR was highest in patients with C. albicans (57.3%) and lowest in patients with C. parapsilosis (21.8%). The resistance rate to fluconazole was 13% in C. parapsilosis, with no significant effect on mortality. No resistance to echinocandins was detected. In the multivariate analysis, being in the ICU [OR = 2.1 (95% CI 1.32-3.57); P = 0.002], renal failure [OR = 2.4 (1.41-3.97); P = 0.001], total parenteral nutrition [OR = 2 (1.22-3.47); P = 0.006], C. albicans infection [OR = 1.7 (1.06-2.82); P = 0.027] and echinocandin as primary agent [OR = 0.6 (0.36-0.99); P = 0.047] were significantly associated with mortality. Candidaemia is a deadly infection. Fluconazole resistance is emerging, although it was not significantly related to mortality. Using an echinocandin as the primary agent could be life-saving., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The aim of this study is to investigate the therapeutic potential of adipose-derived mesenchymal stem cell (AD-MSC) from brown adipose tissue on erectile dysfunction (ED) in experimentally induced spinal cord injury in rats. 24 male Wistar rats were divided into 3 groups; control, spinal cord injury (SCI) + vehicle, and SCI + AD-MSC. To induce SCI, a standard weight-drop method that induced a moderate to severe injury (100 g/cm force) at T7-T10, was used. AD-MSC (3 × 105 cells /5 μL) was applied by local transplantation into the region of injury. At the end of four-weeks, rats underwent neurological examinations and then intracavernosal and mean arterial pressures (ICP and MAP) measurements. After decapitation, spinal cord and cavernosal tissue samples were taken to analyze neuronal nitric oxide synthase (n-NOS), proto-oncogene protein c-FOS and nerve growth factor (NGF). Tissues were also examined histologically. Spinal cord injury caused decrease on NGF and n-NOS levels while c-FOS was increased. The ICP/MAP value in vehicle-treated SCI rats was found to be significantly higher than the control group. On the other hand, in SCI + AD-MSC group, all these parameters were reversed back to control levels. AD-MSC therapy may be beneficial against erectile dysfunction in experimentally induced SCI by ameliorating neuronal damage.

Objective: It is well known that the occurrence of mental disorders is more common in lung transplant candidates compared to the general population. After transplantation mental disorders may negatively affect quality of life, adherence to immunosuppressive medication, as well as overall survival. Therefore, the identification of patients at risk is of utmost importance and in Germany pre-transplant psychosocial evaluation of the patients is required. To ensure high quality and comparability of these assessments, the use of psychometrically sound instruments is recommended. We applied the Transplant Evaluation Rating Scale (TERS), a broadly used expert interview. Two research groups have detected a two-factor structure of the TERS in different transplant samples; however, with slightly different results. The present study investigated which of the models would fit best in our sample of lung transplant patients. Additionally, we assessed convergent and predictive validity of the best fitting model to evaluate its clinical usefulness., Methods: Between 2016 and 2019, 390 lung transplant candidates were evaluated and included in the study. The median age was 53 years and 54% were male. TERS interviews were conducted by trained medical doctors and psychologists. The participants completed questionnaires assessing quality of life and levels of depression and anxiety. Transplant- and disease-specific variables (lung disease, listing date, oxygen use) were taken from the patient charts. Confirmatory factor analysis was used to test the two proposed TERS-models in the present sample., Results: The two-factor structure of the TERS reported by Hoodin and Kalbfleisch fit our sample best, showing good psychometric properties. The factor "emotional sensitivity" was highly correlated with quality of life and measures of psychosocial health while the factor "defiance" correlated with obstructive lung disease and older age but not with quality of life. The two factors showed differential predictive validity with regard to time until listing and pulmonary-specific quality of life 1 year after transplantation., Conclusions: The two factors showed good psychometric properties, and differential convergent and predictive validity. However, further studies concentrating on the predictive value of the TERS and its factors regarding somatic outcomes (mortality, graft functioning) are required., (Copyright © 2020 Nöhre, Paslakis, Albayrak, Bauer-Hohmann, Brederecke, Eser-Valeri, Tudorache and de Zwaan.)

The Pulmonary-Specific Quality-of-Life Scale (PQLS) is a validated self-report questionnaire assessing health-related quality of life (HRQoL) in patients with end-stage lung disease awaiting lung transplantation. The aim of our study was to evaluate the psychometric properties of the German version of the PQLS. One hundred and forty patients awaiting lung transplantation (55% men) with a median age of 53 years [Interquartile range (IQR) 13] answered the PQLS. A group of the participants ( n = 43) was evaluated again 1 year later after transplantation. A confirmatory factor analysis (CFA) of the PQLS was conducted to test the three-factor structure of the PQLS. We examined the internal consistency of the scales using Cronbach's α . Convergent validity was explored through correlations with generic measures of HRQoL [Short-Form 8 Health Survey (SF-8), 10-item quality of life (QoL) scale], measures of depression (nine-item Patient Health Questionnaire-Depression Scale), anxiety (Generalized Anxiety Scale), and measures of lung disease severity (supplemental oxygen use, stairway steps). In the group of 43 patients assessed before and after transplantation, sensitivity to change was explored. The CFA confirmed the three-factor model with an acceptable fit. The PQLS total and the three subscale scores "task interference," "psychological," and "physical" showed acceptable internal consistency. The PQLS and its subscales showed a significant negative correlation with the 10-item QoL measure and the physical component score of the SF-8, whereas the mental component score of the SF-8 showed a significant negative correlation only with the PQLS subscale "psychological." Negative correlation was found due to the opposed alignment of the PQLS compared to the 10-item QoL and the SF-8. Symptoms of depression and anxiety were significantly and positively correlated with the subscale "psychological." Measures of lung disease severity also exhibited a significant positive correlation with the subscales "task interference" and "physical" but not "psychological." In patients 1 year after a successful transplantation, the PQLS scores were significantly reduced by 50%. The three-factor structure of the PQLS could be replicated using CFA. The results indicate good reliability, validity, and sensitivity to change of the German version of the PQLS.

Objective: Current lifestyle interventions for children and adolescents with obesity often exclude patients with an eating pathology, leaving the impact of eating pathologies on treatment outcomes largely unconsidered. We investigated the predictive value of disordered eating symptoms on BMI z-score reduction in a sample of 111 German children and adolescents with overweight (90th percentile ≤ BMI < 97th percentile) and obesity (BMI > 97th percentile) aged 7-15 years in an outpatient lifestyle intervention program., Methods: We defined a BMI z-score reduction of more than 5% after 12 months as a successful outcome. Disordered eating symptoms (i.e., dietary restraint, emotional eating, external eating, and binge eating) were assessed at baseline with the Eating Pattern Inventory (EPI-C) and the "bulimia" scale of the Eating Disorder Inventory (EDI-2). Covariates were: baseline z-BMI, age, gender, and maternal education level., Results: Multiple regression analysis revealed that dietary restraint significantly predicted change in BMI z-scores between baseline and T1. Higher levels of dietary restraint were associated with a lower BMI z-score reduction between T0 and T1. To compare non-completers with completers on the 4 eating behavior scales, we used MANCOVA. At baseline, children who subsequently dropped out of the program prematurely showed significantly higher dietary restraint scores than children who completed the intervention, irrespectively of their gender, age, and BMI z-score at baseline and their mother's education level., Discussion: Our results provide further evidence that the analysis of treatment processes in lifestyle intervention programs for children and adolescents with overweight and obesity should take into account a broader multidimensional approach including eating and dietary habits., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Leptin is essential for the control of energy homeostasis and eating behaviour. We investigated potential associations between serum leptin levels and food addiction in adolescent psychiatric inpatients (n = 228). The most frequent psychiatric diagnoses were mood disorders, anxiety disorders, and substance use disorders. More than three quarters of the study group suffered from more than one psychiatric disorder. Food addiction was assessed with the Yale Food Addiction Scale. Leptin was determined in serum. Analyses were conducted for the whole body weight range and for distinct weight categories to evaluate a potential impact of known nonlinearity between leptin levels and satiety due to leptin resistance in obese. A weak negative association between food addiction and leptin in normal weight patients (ß = -0.11, p = .022) was detected. In contrast, food addiction was associated with a significantly higher serum leptin (ß = 0.16. p = .038) in overweight patients. Food addiction in normal weight patients might be associated with restrained eating, previously shown to involve reduced leptin levels. The small positive association of food addiction with higher serum leptin in overweight patients might reflect leptin resistance and overeating., (© 2018 John Wiley & Sons, Ltd and Eating Disorders Association.)

Objective: Our aims were to investigate the relationship between food addiction and mental disorders including eating disorders (ED), eating-related psychopathology and body mass index-standard deviation score in a sample of adolescent psychiatric inpatients., Methods: Food addiction was assessed with the Yale Food Addiction Scale (YFAS). Eating-related psychopathology was measured with the Three-Factor Eating Questionnaire (TFEQ). Psychiatric diagnoses were assessed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The sample consisted of n = 242 adolescent psychiatric inpatients, of which n = 37 (15.3%) met criteria for an ED. Multiple regression analysis was used to examine the association between YFAS symptom count, TFEQ scales and ED controlling for age and gender., Results: Food addiction frequency was 16.5%, and the mean YFAS symptom count was 2.39 (SD: 1.60). In patients with food addiction, TFEQ scale scores were significantly higher than patients without food addiction. Frequency of ED was 42.9% in patients with and 9.9% in patients without food addiction. The TFEQ subscales disinhibition and hunger as well as diagnosis of ED were associated with YFAS symptom count., Discussion: Food addiction in adolescent psychiatric inpatients occurs with rates higher than those seen in community samples of children, adolescents and adults. Food addiction might be associated with eating styles related to susceptibility to hunger and feelings of loss of control. The implications of high-YFAS scores in restricting-type anorexia nervosa warrant further investigations to explore which and how the respective items are interpreted in this ED subgroup. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association., (Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.)

Today, food addiction has become an increasing area of research. Multiple studies aim to characterize individuals in terms of food addiction based on the assumption, that hyperpalatable foods rich of salt, sugar and fat may induce a cluster of behavioral changes that may resemble a substance use disorder, despite the fact that to date there is no evidence, that nutritional factors lead to an addictive eating-like behavior in humans. In this review article, we aim to introduce the basic experiments, that build the framework upon which food addiction is being investigated and to critically discuss the concept of food addiction., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: In anorexia nervosa (AN) hypercortisolism has been described using urine, plasma and saliva samples as short-term markers for the hypothalamic-pituitary-adrenal (HPA)-axis. Here, for the first time, we analyse hair cortisol concentration (HCC) as a marker for long-term integrated cortisol secretion in female patients with AN compared to female healthy controls (HC) and female psychiatric controls (PC)., Methods: HCC was assessed in 22 female adolescent psychiatric inpatients with AN compared to 20 female HC and to 117 female PC of the same age range. For further analyses we examined the associations of age and body mass index (BMI) with HCC., Results: Log HCC was lower in AN-patients compared to HC (p = 0.030). BMI-standard deviation scores (SDS) but not age correlated with log HCC (BMI-SDS: r = 0.19, bias corrected accelerated 95% confidence interval: [.04, .34], p = 0.015; age: r = 0.10, bias corrected accelerated 95% confidence interval: [-.07, .25], p = 0.213) when combining AN, HC and PC samples., Discussion: We find lower HCC in AN, compared to HC and PC, respectively. Based on the relationship between HCC and BMI-SDS across AN, HC and PC, we argue that HCC might not capture endocrine alterations because of AN pathology-related processes but rather shows consistent relationships with BMI, which extent even to the very low range of BMI values, as present in AN patients. Alternatively, incorporation of cortisol into the hair follicle might have been compromised because of trophic hair follicle disturbances that had been reported in AN patients, previously. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association., (Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.)

This article looks at food addiction as a subject situated between psychiatry, neurobiology, nutritional science, internal medicine, food industry, and public health. Essentially, the question is whether or not individual nutritional components can induce physical dependence, similar to the well-known effects of drugs such as alcohol and cocaine, or whether food addiction is rather a behavioral addiction. The literature describes many overlaps as well as differences of substance-based and non-substance-based addiction in both clinical and neurobiological terms. Until recently it was argued that food addiction appears only in the realms of obesity and eating disorders (e.g., binge-eating disorder, BED). Some studies, however, described the prevalence of food addiction symptoms and diagnoses independent of overweight or that they were in subjects who do not fulfill the criteria for BED. This article sums up the controversial discussion about the phenomenological and neurobiological classification of food addiction. Implications of food addiction for children and adolescents as well as public-health-related issues are also discussed.

With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH.

With the introduction of the category Substance-Related and Addictive Disorders in DSM-5 for the first time behavioral addictions have entered the medical classification system. Food Addiction can be diagnosed with a 25-item questionnaire based on DSM-IV criteria for substance dependence. Food Addiction centers between substance-based addiction and non-substance-based behavioral addiction. To date, there is no evidence for a food component displaying addictive properties similar to psychotropic substances, such as cocaine or heroin. There is a lack of valid and reliable psychiatric-diagnostic criteria that aim to characterize Eating-Addiction as a behavioral addiction., (© Georg Thieme Verlag KG Stuttgart · New York.)

"Food addiction" has become a focus of interest for researchers attempting to explain certain processes and/or behaviors that may contribute to the development of obesity. Although the scientific discussion on "food addiction" is in its nascent stage, it has potentially important implications for treatment and prevention strategies. As such, it is important to critically reflect on the appropriateness of the term "food addiction", which combines the concepts of "substance-based" and behavioral addiction. The currently available evidence for a substance-based food addiction is poor, partly because systematic clinical and translational studies are still at an early stage. We do however view both animal and existing human data as consistent with the existence of addictive eating behavior. Accordingly, we stress that similar to other behaviors eating can become an addiction in thus predisposed individuals under specific environmental circumstances. Here, we introduce current diagnostic and neurobiological concepts of substance-related and non-substance-related addictive disorders, and highlight the similarities and dissimilarities between addiction and overeating. We conclude that "food addiction" is a misnomer because of the ambiguous connotation of a substance-related phenomenon. We instead propose the term "eating addiction" to underscore the behavioral addiction to eating; future research should attempt to define the diagnostic criteria for an eating addiction, for which DSM-5 now offers an umbrella via the introduction on Non-Substance-Related Disorders within the category Substance-Related and Addictive Disorders., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Children with attention-deficit/hyperactivity disorder (ADHD) have a higher rate of obesity than children without ADHD. Obesity risk alleles may overlap with those relevant for ADHD. We examined whether risk alleles for an increased body mass index (BMI) are associated with ADHD and related quantitative traits (inattention and hyperactivity/impulsivity). We screened 32 obesity risk alleles of single nucleotide polymorphisms (SNPs) in a genome-wide association study (GWAS) for ADHD based on 495 patients and 1,300 population-based controls and performed in silico analyses of the SNPs in an ADHD meta-analysis comprising 2,064 trios, 896 independent cases, and 2,455 controls. In the German sample rs206936 in the NUDT3 gene (nudix; nucleoside diphosphate linked moiety X-type motif 3) was associated with ADHD risk (OR: 1.39; P = 3.4 × 10(-4) ; Pcorr  = 0.01). In the meta-analysis data we found rs6497416 in the intronic region of the GPRC5B gene (G protein-coupled receptor, family C, group 5, member B; P = 7.2 × 10(-4) ; Pcorr  = 0.02) as a risk allele for ADHD. GPRC5B belongs to the metabotropic glutamate receptor family, which has been implicated in the etiology of ADHD. In the German sample rs206936 (NUDT3) and rs10938397 in the glucosamine-6-phosphate deaminase 2 gene (GNPDA2) were associated with inattention, whereas markers in the mitogen-activated protein kinase 5 gene (MAP2K5) and in the cell adhesion molecule 2 gene (CADM2) were associated with hyperactivity. In the meta-analysis data, MAP2K5 was associated with inattention, GPRC5B with hyperactivity/impulsivity and inattention and CADM2 with hyperactivity/impulsivity. Our results justify further research on the elucidation of the common genetic background of ADHD and obesity., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: Among overweight and obese youths, rates of depression, anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder (ODD) are elevated. We analyze whether these emotional and behavioral problems are associated with specifically disordered eating pattern., Method: Participants in the study were 128 overweight and obese children/adolescents (BMI: m = 29.3, s = 4.5; BMI-SDS: m = 2.5, s = 0.4) between 8 and 15 years. Structured psychiatric assessments were conducted adopting a multimethod, multiinformant approach., Results: Children/adolescents with ODD symptoms showed increased eating in response to external cues and binge eating. ADHD symptoms were not associated with disordered eating behaviors. Children/adolescents with symptoms of depression and anxiety showed emotional and binge eating. In particular, overweight girls with symptoms of depression showed restrained eating., Discussion: Our results point to specific eating problems in overweight/obese children with ODD and depression/anxiety symptoms. The findings could help to tailor interventions to optimally meet the specific needs of overweight children with emotional and behavioral problems., (Copyright © 2012 Wiley Periodicals, Inc.)

Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4 × 10(-5) and 4 × 10(-6), respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3'UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity.