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Cristina Dragomir,1 Roxana Popescu,2,3 Monica Alisa Jurca,4 Ruxandra Laza,5 Roxana Ivan Florian,6 Ion Dragomir,7 Romeo Negrea,8 Marius Craina,9 Cristina Adriana Dehelean10,11 1Doctoral School, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 2Department II – Microscopic Morphology, Discipline of Cellular and Molecular Biology, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 3ANAPATMOL Research Center, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 4County Emergency Clinical Hospital “Pius Brinzeu”, Timisoara, Romania; 5Department XIII, Discipline of Infectious Disease, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 6Dynata Company, Timisoara, Romania; 7Individual Family Medical Office, Ostroveni, Dolj, Romania; 8Department of Mathematics, Polytechnica University of Timisoara, Timisoara, Romania; 9Department XII - Obstetrics-Gynecology, Discipline of Obstetrics-Gynecology III, University of Medicine and Pharmacy “Victor Babes”, Timisoara, Romania; 10Department of Toxicology and Drug Industry, Faculty of Pharmacy, University of Medicine and Pharmacy, Timisoara “Victor Babes”, Timișoara, Romania; 11FARMATOX Research Centre for Pharmaco-Toxicological Evaluation, University of Medicine and Pharmacy “Victor Babes”, Timisoara, RomaniaCorrespondence: Roxana Popescu; Cristina Dragomir, University of Medicine and Pharmacy “Victor Babes”, Eftimie Murgu Square, No. 2, Timisoara, 300041, Romania, Tel +40723649886 ; +40753036306, Email popescu.roxana@umft.ro; dr.cristinadragomir@yahoo.comPurpose: The purpose of this study is to identify the relationships between postpartum emotional manifestations and various neonatal variables, as well as variables within this category, in the context of hospitalization together after birth.Patients and Methods: Between 1 March 2020 and 1 September 2020, a cross-sectional research design was used including mother–child couples (112 mothers, 121 newborns - 13 twins/triplets).Results: Using a t-test for independent samples, we observed: a) the symptoms of depression were more severe in mothers of newborns hospitalized in neonatal intensive care units (NICUs) [t(110) = 4.334)], provided oxygen therapy [t(109.99) = 3.162], born prematurely [t(110) = 3.157], or with adjustment disorders [t(109) = − 2.947] (p < 0.01); b) a similar, for anxiety as a state [t(82.38) = 5.251], t(107.29) = 4.523, t(110) = 3.416, t(109) = − 3.268, p < 0.01], and as a trait was more common [t(80.79) = 4.501, t(108.790) = 4.669, t(109) = − 3.268, p < 0.001] compared to other mothers. Using Pearson’s test (p < 0.001), several very strong correlations were observed between neonatal variables, including number (no.) of days of hospitalization with birth weight (BW) (r = − 0.802), head circumference (HC) (r = − 0.822), and gestational age (GA) (r = − 0.800) and the mother’s postpartum anxiety as a state/trait (r = 0.770). Using Poisson regression, it was observed that anxiety as a state (Λ = 0.020, z = 4.029, p < 0.001) and as a trait (Λ = 0.800, z = 6.160, p < 0.001) stimulated the intensity of symptoms of postpartum depression (optimal models).Conclusion: Postpartum maternal psychological manifestations were associated with NICU hospitalization, pathology, and some neonatal therapies. We also noticed, that the duration of hospitalization, BW, HC, and GA, were correlated with maternal emotional disorders. Results will facilitate future optimization of birth management and postnatal care.Keywords: anxiety as a state, anxiety as a trait, attachment, postpartum depression symptoms, newborn at risk, prematurity

The COVID-19 virus frequently causes neurological complications. These have been described in various forms in adults and children. Headache, seizures, coma, and encephalitis are some of the manifestations of SARS-CoV-2-induced neurological impairment. Recent publications have revealed important aspects of viral pathophysiology and its involvement in nervous-system impairment in humans. We evaluated the latest literature describing the relationship between COVID-19 infection and the central nervous system. We searched three databases for observational and interventional studies in adults published between December 2019 and September 2022. We discussed in narrative form the neurological impairment associated with COVID-19, including clinical signs and symptoms, imaging abnormalities, and the pathophysiology of SARS-CoV2-induced neurological damage.

Parkinson's disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa - LEV+CARB), and a mixture of six

Significant global consumption of mineral water is fueled by perceived therapeutic and medicinal qualities, cultural habits and taste. In Valcea County are several resorts with such mineral springs, which can have multiple benefits for human health. For this reason, it is important to investigate the level of their pollution with heavy metals. The aim of this study was to detect the level of heavy metals present in the studied mineral waters, to evaluate the analytical results using environmental statistical indices, and to compare the results with the legislation in force. Thus, mineral water samples were collected from three resorts of Valcea County (Baile Olanesti, Calimanesti-Caciulata and Baile Govora). The analyzed metals (Cd, Cr, Fe, Mn, Ni, Pb and Zn) were determined with the ICP-EOS technique and the obtained results were compared to enforce legislation. Statistical analyses were applied and two environmental statistical indices, namely the metal distribution coefficient (kd) and the total environmental risk index (IER) were evaluated. The calculated values for the total environmental risk index were below 0 (IER ≤ 0), which indicates that none of the studied water samples pose a risk for the environment. The low values of the distribution coefficient indicate a low ability to bind the metal in particles and therefore, insignificant toxicity. The distribution coefficient calculated for zinc (1.12 L/kg) and lead (0.68 L/kg) in Baile Olanesti indicates a high capacity of the metals to bind in particles, compared to other metals.

Pulmonary Alveolar Proteinosis (PAP) is a rare, usually autoimmune, disease, where surfactant accumulates within alveoli due to decreased clearance, causing dyspnea and hypoxemia. The disease is even more rare in pregnancy; nevertheless, it has been reported in pregnant women and can even appear for the first time during pregnancy as an asthma-like illness. Therefore, awareness is important. Similarly to many autoimmune diseases, it can worsen during pregnancy and postpartum, causing maternal and fetal/neonatal complications. This paper offers a narrative literature review of PAP and pregnancy, while illustrating a case of a pregnant patient with known PAP who developed preeclampsia in the third trimester but had an overall fortunate maternal and neonatal outcome.

Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p

Endometriosis is a disease very common nowadays affecting 1-2% of the female population, by estrogen-dependent mechanism. The identification of mutations in the gene encoding for the FSH receptor (FSHR) has been reported since 1995. Physiology teaches us that follicle-stimulating hormone (FSH) is a hormone that is vital in the steroidogenesis regulation mechanisms, while FSH receptor (FSHR) activation helps to promote folliculogenesis and estrogensynthesis. Therefore, studies to show if there are any correlations between endometriosis and FSHR are acquired. Genotyping of FSHR gene polymorphisms were performed using PCR - Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. We analysed a total of 78 patients, 44 infertile patients with endometriosis and 34 controls (non-infertile, pregnant patients). The endometriosis group included women with diagnosis of endo-metriosis confirmed by laparoscopy and /or laparotomy and histological evidence of disease with the endometriosis staging according to American Society for Reproductive Medicine (ASRM). Corroborated with the severity of endometriosis, A919G and A2039G tests found that 71.4% of the M (GG) results were associated with primary infertility, not statistically significant (p=0.994) and 42.9% of the total M results had moderate or severe forms of endometriosis (p = 0.185). The genetic involvement in different pathologies such as endometriosis, has yet to be understood, but knowing more about its mechanism, will help physician target the disease at a more profound level.

To describe the incidence and the characteristics of pregnancies complicated by hypertensive disorders of pregnancy (HDP) in one of the largest maternity hospitals in Romania.A retrospective cohort study including all deliveries at ≥24 weeks' gestation was performed.The incidence of preeclampsia was 1.2%, of gestational hypertension 2.2% and of chronic hypertension 0.4%. Pregnancies with HDP had higher rates of stillbirth, birthweight10Incidence of HDP in our population was relatively low, and was associated with early gestational age and adverse perinatal outcomes.

Cancer poses an ongoing global challenge, despite the substantial progress made in the prevention, diagnosis, and treatment of the disease. The existing therapeutic methods remain limited by undesirable outcomes such as systemic toxicity and lack of specificity or long-term efficacy, although innovative alternatives are being continuously investigated. By offering a means for the targeted delivery of therapeutics, nanotechnology (NT) has emerged as a state-of-the-art solution for augmenting the efficiency of currently available cancer therapies while combating their drawbacks. Melanin, a polymeric pigment of natural origin that is widely spread among many living organisms, became a promising candidate for NT-based cancer treatment owing to its unique physicochemical properties (e.g., high biocompatibility, redox behavior, light absorption, chelating ability) and innate antioxidant, photoprotective, anti-inflammatory, and antitumor effects. The latest research on melanin and melanin-like nanoparticles has extended considerably on many fronts, allowing not only efficient cancer treatments via both traditional and modern methods, but also early disease detection and diagnosis. The current paper provides an updated insight into the applicability of melanin in cancer therapy as antitumor agent, molecular target, and delivery nanoplatform.

Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They are the site of important biochemical pathways, including the tricarboxylic acid cycle, parts of the ureagenesis cycle, or haem synthesis. Mitochondria are responsible for the majority of cellular ATP production through OXPHOS. Mitochondrial dysfunction has been associated with metabolic pathologies such as diabetes, obesity, hypertension, neurodegenerative diseases, cellular aging, and cancer. In this article, we describe the pathophysiological changes in, and mitochondrial role of, metabolic disorders (diabetes, obesity, and cardiovascular disease) and their correlation with oxidative stress. We highlight the genetic changes identified at the mtDNA level. Additionally, we selected several representative biomarkers involved in oxidative stress and summarize the progress of therapeutic strategies.

Combined observations from UV to IR wavelengths are necessary to fully account for the star-formation in galaxy clusters. Low mass (log M/Msun, 13 pages, 5 figures, accepted to ApJ

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75–80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recognition of the importance of chromosomal abnormalities, the amplification of the oncogenes, the aberration of tumor suppressor genes, as well as the dysregulation of cellular signaling and cell cycle control. Lately, novel therapies that have already proven efficient on relapsed/refractory ALL in adults are being evaluated in clinical trials for young patients. Tirosine kinase inhibitors are, by now, part of the standardized treatment of Ph+ALL pediatric patients, and Blinatumomab, with promising results in clinical trials, received both FDA and EMA approval for use in children. Moreover, other targeted therapies such as aurora-kinase inhibitors, MEK-inhibitors, and proteasome-inhibitors are involved in clinical trials that include pediatric patients. This is an overview of the novel leukemia therapies that have been developed starting from the molecular discoveries and those that have been applied in pediatric populations.

2q37 microdeletion/deletion syndrome (2q37DS) is one of the most common subtelomeric deletion disorders, caused by a 2q37 deletion of variable size. The syndrome is characterized by a broad and diverse spectrum of clinical findings: characteristic facial dysmorphism, developmental delay/intellectual disability (ID), brachydactyly type E, short stature, obesity, hypotonia in infancy, and abnormal behavior with autism spectrum disorder. Although numerous cases have been described so far, the exact mapping of the genotype and phenotype have not yet been achieved. Materials and Methods: In this study we analyzed nine newly diagnosed cases with 2q37 deletion (3 male/6 female, aged between 2 and 30 years old), and followed up at the Iasi Regional Medical Genetics Centre. All patients were tested first with MLPA using combined kits P036/P070 subtelomeric screening mix and follow-up mix P264; after, the deletion size and location were confirmed via CGH-array. We compared our findings with the data of other cases reported in the literature. Results: From nine cases, four had pure 2q37 deletions of variable sizes, and five presented deletion/duplication rearrangements (with chromosomes 2q, 9q, and 11p). In most cases, characteristic phenotypic aspects were observed: 9/9 facial dysmorphism, 8/9 global developmental delay and ID, 6/9 hypotonia, 5/9 behavior disorders, and 8/9 skeletal anomalies—especially brachydactyly type E. Two cases had obesity, one case had craniosynostosis, and four had heart defects. Other features found in our cases included translucent skin and telangiectasias (6/9), and a hump of fat on the upper thorax (5/9). Conclusions: Our study enriches the literature data by describing new clinical features associated with 2q37 deletion, and possible genotype–phenotype correlations.

Background and Objectives: In this study, we investigated the changes of platelet count and other platelet indices, such as mean platelet volume (MPV), in cases with severe early intrauterine fetal growth restriction (IUGR). Materials and Methods: We retrospectively analyzed all pregnancies diagnosed with severe early onset IUGR, that were followed up in our hospital between 2010 and 2015 (before implementation of screening and prophylaxis with aspirin). Pregnancies which resulted in birth of a newborn with a birthweight less than 5th percentile for gestational age, that required delivery for fetal or maternal indication before 32 weeks, were selected for the IUGR group. The IUGR cases were divided into two groups according to preeclampsia (PE) association. All cases with a complete blood count (CBC) performed within 7 days prior to delivery were included in the study, as the IUGR group. The control group included normal singleton pregnancies, delivered at term, with birthweight above 10th centile and a CBC taken at 30–32 weeks. Results: There was a significant difference in platelet count and MPV values between the IUGR group and control. Cases with IUGR presented lower platelet count and higher MPV values; there was no significant difference of these parameters when PE was associated with IUGR. Conclusions: Our results suggest that in cases of severe early IUGR, even in the absence of clinically diagnosed PE, there may be maternal endothelial damage and platelet consumption in the systemic and uteroplacental circulation. Platelet count and MPV values are simple and widely available laboratory tests that might be used as indicator of placental insufficiency; however, prospective data are required to establish the mechanistic link and to which extent these parameters are good predictors of severity or adverse perinatal outcomes.

This paper presents the case of a 58-year-old heavy smoker female who came to our clinic with acute pain, as well as mastication and feeding difficulties. The macroscopic examination revealed oral erosive lesions and ulcerations. The polymorphic aspect of the lesions required the differential diagnosis of oral erythroplakia or carcinoma, which were excluded by biopsy. At the same time, we assessed the expression of S100 protein, Ki67 and the cluster of differentiation (CD) 4, CD8 (T-cell) and CD20 (B-cell) immune cell markers by immunohistochemical analysis. As a result, after the clinical and pathological assessment, the diagnosis of oral lichen planus was established, and a therapy plan was conducted. We observed a favorable clinical evolution after the administration of corticosteroids and immunomodulatory agents.

Objectives The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.-280G>T) polymorphisms and endometriosis in Romanian women. Material and methods We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). Results There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.-280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). Conclusions FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

Aim: The involvement of proinflammatory interleukins (IL) in diabetic kidney disease of Type 2 diabetes mellitus (DM) patients was studied in relation to a particular miRNA profile. Materials & methods: A total of 117 patients with Type 2 DM and 11 controls were enrolled in a case series study. Serum and urinary ILs and miRNAs were assessed. Results: IL-1α correlated with miRNA21, 124, estimated glomerular filtration rate (eGFR) and negatively with miRNA125a and 192; IL-8 with miRNA21, 124, eGFR and negatively with miRNA125a, 126 and 146a; IL-18 with miRNA21, 124 and negatively with miRNA146a, 192, eGFR. Conclusion: There is an association between specific serum and urinary ILs and serum and urinary miRNAs profiles in the inflammatory response in Type 2 DM patients with diabetic kidney disease.

Objective. Our research aims to assess a possible connection between tumour localization and histological subtypes of grade II meningiomas. Material and methods. 143 patients with grade II WHO meningiomas underwent surgical resection in "Prof. Dr. N. Oblu" Emergency Clinical Hospital Ia?i between 1990 and 2015. The collected data included: patient age, gender, tumour localization and histopathological diagnosis (atypical, clear cells and chordoid meningioma). Results. 135 (94.4%) of all 143 patients with grade II meningiomas were atypical meningiomas, 6 (4.2%) were cell clear meningiomas and only 2 (1.4%) were chordoid meningiomas. As concerns their distribution by gender, 79 (55.2%) were female and 64 (44.8%) were male. Grade II meningiomas were most commonly located at convexity 49.7% (n=71), followed by skull base in 30.8% (n=44) of the cases and parasagittal/falcine in 14.7% (n=21) of the patients. Conclusions. The most common localization of grade II meningiomas was convexity, followed by skull base, parasagittal/falcine and intraventricular areas. We have also noticed that convexity meningiomas are more frequent in women, unlike the other anatomical localizations in which the male-female ratio is almost equal. Therefore, further research is necessary to determine the role of embryological, anatomopathological and genetic factors in underlying the connection between meningioma grade and anatomical localization.

Parkinson s disease is the second pathological neurological condition that affects millions of people annually. Up to now there is no curative treatment for this condition. Our study was conducted on a group of 99 patients who were followed periodically, clinically and radiologically for a period of three years after diagnosis with Parkinson�s disease. The results of our study show that MRI examination can be an important tool for differential diagnosis, etiopathogenicity and the prognosis of these patients. Patient follow up is required in personalizing and improving current treatment schedules of Levodopa.

The most frequent microdeletion, 22q11.2 deletion syndrome (22q11.2DS), has a wide and variable phenotype that causes difficulties in diagnosis. 22q11.2DS is a contiguous gene syndrome, but due to the existence of several low-copy-number repeat sequences (LCR) it displays a high variety of deletion types: typical deletions LCR A–D—the most common (~90%), proximal deletions LCR A–B, central deletions (LCR B, C–D) and distal deletions (LCR D–E, F). Methods: We conducted a retrospective study of 59 22q11.2SD cases, with the aim of highlighting phenotype–genotype correlations. All cases were tested using MLPA combined kits: SALSA MLPA KIT P245 and P250 (MRC Holland). Results: most cases (76%) presented classic deletion LCR A–D with various severity and phenotypic findings. A total of 14 atypical new deletions were identified: 2 proximal deletions LCR A–B, 1 CES (Cat Eye Syndrome region) to LCR B deletion, 4 nested deletions LCR B–D and 1 LCR C–D, 3 LCR A–E deletions, 1 LCR D–E, and 2 small single gene deletions: delDGCR8 and delTOP3B. Conclusions: This study emphasizes the wide phenotypic variety and incomplete penetrance of 22q11.2DS. Our findings contribute to the genotype–phenotype data regarding different types of 22q11.2 deletions and illustrate the usefulness of MLPA combined kits in 22q11.2DS diagnosis.

Background and objectives: The postpartum maternal physical and psychological state played a fundamental role in the mother–child relationship at the beginning of the COVID-19 pandemic. The aim of the study is to analyze the influence of maternal psychological manifestations on the mother–child couple through three objectives (briefly expressed): (I) Determination of the main acute and chronic conditions of newborns/infants. (II) Verification of the hypothesis of the existence of a link between the following neonatal variables: gestational age, birth weight, number of days of hospitalization, and specific neonatal therapies (oxygen, surfactant, and blood products’ transfusion). (III) Verification of the influence of postpartum maternal psychological status on the mother–child couple through three hypotheses. Materials and methods: This cross-sectional study was conducted in two hospitals in Timișoara, Romania, between 1 March and 1 September 2020, and included 165 mothers and their 175 newborns. Mothers answered the Edinburgh Postnatal Depression Scale, Spielberger’s Inventory of State-Trait Anxiety, and the Collins and Read Revised Adult Attachment Scale. Results: (I) The acute and chronic pathology of the infants in the study group was polymorphic. (II) Large correlations were identified between the following infant variables: gestational age with birth weight, and number of hospitalization days with birth weight, gestational age, and use of blood product transfusion (all p < 0.001). (III) (1) State anxiety was the only significant predictor of number of hospitalization days (p = 0.037), number of acute disorders (p = 0.028), and number of infant chronic diseases (p = 0.037). (2) Maternal depressive symptoms were the only predictor of postpartum maternal attachment (p = 0.018). (3) Depressive symptoms, state, and trait anxiety were non-significant in all models studied (all p > 0.05). Conclusions: Postpartum maternal physical and psychological state plays a fundamental role on the mother–child relationship in the new social and complex family conditions.

Background and Aims Glomerular injury and proximal tubule (PT) dysfunction have intricate mechanisms in diabetic kidney disease (DKD). Pro-inflammatory cytokines are involved in the initiation and progression of DKD through mediating the inflammatory response, both at glomerular and proximal tubular level. miRNAs are able to modulate cellular and biochemical functions, thus intervening in the pathogenesis of DKD. The aim of the study, performed on patients with type 2 diabetes mellitus (DM), was to evaluate selective pro-inflammatory cytokines in relation to biomarkers of podocyte lesion and of PT dysfunction. Particular molecular pathways, such as specific miRNA profiles operating in this relation, have also been studied. Method A number of 126 patients with type 2 DM, staged by albuminuria [39 normoalbuminuric – urinary albumin/creatinine ratio UACR)300mg/g], and 23 healthy control subjects were included in a cross-sectional study. All patients were evaluated concerning biomarkers of podocyte injury (nephrin, podocalyxin, synaptopodin) and of PT dysfunction [Kidney injury molecule-1(KIM-1), N-acetyl-beta-D-glucuronidase (NAG), alpha 1- microglobulin]. Also, serum and urinary levels of specific interleukins (IL-6, IL-17), serum cystatin C, and eGFR were determined. Serum and urinary miRNAs (miRNA-21, miRNA-124, miRNA-146a, miRNA-192) were assessed by RT-PCR. Results The biomarkers of podocyte lesion and of PT dysfunction were increased, even in normoalbuminuric type 2 DM patients. Serum and urinary IL-6 and IL-17 showed increased levels in type 2 DM patients, across all groups studied. The model provided by univariable regression analysis showed that IL-6 and IL-17 correlated directly with biomarkers of podocyte injury (nephrin, podocalyxin, synaptopodin), of PT dysfunction (KIM-1, NAG, alpha 1-microglobulin), as well as with UACR. Negative correlations have been identified regarding eGFR. In multivariable regression analysis, serum IL-6 correlated directly with synaptopodin, NAG, and negatively with eGFR (p Also, important associations were found between specific interleukins and miRNAs. In univariable regression analysis, IL-6 and IL-17 correlated directly with miRNA-21 and miRNA-124, and negatively with miRNA-146a and miRNA-192. The models provided by multivariable regression analysis showed that urinary IL-6 correlated directly with urinary miRNA-21, and negatively with urinary miRNA-192 (p Conclusion In the early stages of DKD, there is an association of pro-inflammatory cytokines with specific miRNAs, and with biomarkers of podocyte injury and of PT dysfunction. IL-6 and IL-17, as well as dysregulated miRNA-21, miRNA-124, miRNA-146a, and miRNA-192 display a particular molecular pattern, in relation to complex mechanisms that can initiate and maintain the chronic inflammatory response in DKD. Routine detection of these interleukins may provide biomarkers to refine the diagnosis of early renal involvement in the course of type 2 DM, independently of albuminuria and level of renal function.

Many developments were made in the area of endovascular treatment of intracranial aneurysms, but this procedure also requires a good assessment of vascular anatomy prior to intervention. Seventy-six cases with brain aneurysms were selected and 1:1 scale 3D printed models were created. We asked three interventional neurosurgeons with different degrees of experience (ten years, four years, and a fourth-year resident) to review the cases using CTA (computed tomography angiogram) with MPR (multiplanar reconstructions) and VRT (volume rendering technique) and make a decision: coil embolization or stent-assisted coil embolization. After we provided them with the 3D printed models, they were asked to review their treatment plan. Statistical analysis was performed and the endovascular approach changed in 11.84% of cases for ten-year experienced neurosurgeons, 13.15% for four years experienced neurosurgeon, and 21.05% for residents. The interobserver agreement was very good between the ten years experienced interventionist and four years experienced interventionist when they analyzed the data set that included the 3D printed model. The agreement was higher between all physicians after they examined the printed model. 3D patient-specific printed models may be useful in choosing between two different endovascular techniques and also help the residents to better understand the vascular anatomy and the overall procedure.

Background Familial hypercholesterolemia(FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and non-traditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease(ASCVD) in this population. The aims of the study were: (a) to identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b) to evaluate the risk of new cardiovascular events at follow-up in FH patients stratified by lipid-lowering agents. Methods This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network(DLCN) and Simon Broome(SM) scores, 61 patients with DLCN score above 3 and possible/probable FH(SM score) were included. Results Nine hundred-eighty patients were examined and 61 (6.2%) were received the clinical diagnosis of FH. The mean age was 48.5±12.5 years, with more female patients than male patients (63.9% versus 36%). Hypertension was the main cardiovascular risk factor for both genders, followed by physical inactivity and obesity for the female group and active smoking for the male group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. The effective lipid-lowering drugs used were statin alone and statin in association with fenofibrate, which improved both the lipid profile values and the subclinical atherosclerosis markers (ankle-brachial index, carotid intima-media thickness and high-sensitivity C-reactive protein). New ASCVDs that emerged during the study were most commonly represented by coronary heart disease and stroke. At the same time, the new cardiovascular events were delayed in patients receiving the lipid-lowering drugs, without significant differences between them. Conclusions In patients with suspected FH, the lipid-lowering agents during the follow-up period delayed the new cardiovascular events, yet failed to reach the goals proposed by the guidelines.

Excessive use of antimicrobials and inadequate infection control practices has turned antimicrobial resistance (AMR) into a global, public health peril. We studied the expression of qnrA, qnrB, and qnrS plasmid in ciprofloxacin (CIP)-resistant strains of Escherichia coli in swine and humans from Romania, using the Polymerase Chain Reaction (PCR) technique. Antibiotic Susceptibility Testing (AST) for human subjects (H) on 147 samples and 53 swine (S) was ascertained as well as the isolation of bacterial DNA (E. coli) as follows: bacteriolysis, DNA-binding, rinsing, elution, amplification, and nucleic acids’ migration and U.V. visualization stages. From 24 samples of E. coli resistant to CIP collected from H subjects and 15 from S, for PCR analysis, 15 H and 12 S were used, with DNA purity of 1.8. The statistically analyzed results using the Crosstabs function (IBM SPSS Statistics-Ver. 2.1.), revealed the qnrS (417 bp) gene in 13 human subjects (52.0%), as well as in all swine samples studied. The qnrB (526 bp) gene was exposed in 9 of the human patients (36.0%) and in all swine isolates, and the qnrA (516 bp) gene was observed only in 3 of the isolates obtained from human subjects (12.0%) and was not discovered in pigs (p > 0.05). The presence of plasmids qnrA, qnrB, and qnrS in the human samples and of qnrB and qnrS in swine, facilitates the survival of pathogens despite the CIP action. The long-term use of CIP could cause a boost in the prevalence of qnr resistance genes, and resistance in the pigs destined for slaughter, a perturbing fact for public health and the human consumer.

Association of atopic dermatitis (AD) and several mutations of various genes of the immune system, in particular filament-aggregating protein gene (FLG) has been investigated in many studies. The association between defective FLG and AD in the Romanian population has not been assessed or published. The present study focused on the genetic background of AD, aiming to assess the prevalence of FLG mutations in Romanian patients with AD. Genetic background of AD was tested for common FLG-mutations: R501X, 2282del4, S3247X and R2447X. The study involved 48 Romanian Caucasian children aged between two months and six years diagnosed with AD, and 48 healthy volunteers; DNA extraction involved 50% of the patients to give samples by using buccal swabs and 50% by collection of whole blood samples. Genetic predisposition was evaluated based on family history, atopy history and profilaggrin genotyping. DNA extracted from blood samples was adequate to study FLG mutations, although no mutation was identified. Genetic factors do not have a unique critical role in AD; therefore, environmental factors unquestionably play an important role in this disease, but the clear-cut part that these factors trigger toward increasing the risk of AD in childhood is still obscure.

Background/aim Human mesenchymal stem cells (hMSC) represent a versatile cell population, able to modulate the tumor microenvironment. Our aim was to recreate an open scene for the in vivo interaction between hMSC and the MCF-7 breast cancer cells (MCF-7), in order to enlighten the intimate involvement of hMSC in tumor vasculogenesis and angiogenesis. Materials and methods hMSC and MCF-7 were seeded onto the chick embryo chorioallantoic membrane (CAM) and incubated for 7 days. Consecutively, the morphology and the immunohistochemical profile of CAM were assessed. Results Following this complex interaction, MCF-7 acquired a more aggressive phenotype, hMSC switched to a vascular precursor phenotype, while CAM underwent a major reset to an earlier stage, with hotspots of angiogenesis, vasculogenesis and hematopoiesis. Conclusion The hallmark of this study was the establishment of a veritable in vivo experimental model of MSC involvement in tumor vasculogenesis and angiogenesis, allowing further analysis in the field.

BACKGROUND Late HIV diagnosis remains frequent among the gay, bisexual, and other men who have sex with men (GBMSM) population across Europe. HIV self-sampling could help remove barriers and facilitate access to testing for this high-risk population. OBJECTIVE We assessed the capacity of HIV self-sampling to increase the testing frequency among GBMSM living in Denmark, Germany, Greece, Portugal, Romania, and Spain, and evaluated the role of new technologies in the result communication phase. METHODS We analyzed a convenience sample of 5019 GBMSM with prior HIV testing experience who were recruited during 2016 through gay dating websites. We estimated the proportion of GBMSM who reported that the availability of self-sampling would result in an increase of their current testing frequency. We constructed a Poisson regression model for each country to calculate prevalence ratios and 95% CIs of factors associated with an increase of testing frequency as a result of self-sampling availability. RESULTS Overall, 59% (between country range 54.2%-77.2%) of the participants considered that they would test more frequently for HIV if self-sampling was available in their country. In the multivariate analysis, the increase of testing frequency as a result of self-sampling availability was independently associated with reporting a higher number of unprotected anal intercourse events in all countries except for Greece. Independent associations were also observed among GBMSM who were not open about their sex life in Germany, Greece, Portugal, and Spain; those with a lower number of previous HIV tests in Denmark, Greece, Portugal, and Spain; and for those that took their last test more than 3 months previously in Germany, Portugal, Romania, and Spain. In addition, 58.4% (range 40.5%-73.6%) of the participants indicated a preference for learning their result through one-way interaction methods, mainly via email (25.6%, range 16.8%-35.2%) and through a secure website (20.3%, range 7.3%-23.7%). Almost two thirds (65%) of GBMSM indicated preferring one of these methods even if the result was reactive. CONCLUSIONS Availability of HIV self-sampling kits as an additional testing methodology would lead to a much-needed increase of testing frequency, especially for the hidden, high-risk, and undertested GBMSM population. Online-based technologies without any personal interaction were preferred for the communication of the results, even for reactive results.

The highlighting of the bioaccumulation capacity of metals in the internal organs, the mode of distribution at the level of internal organs, the interactions between them, respectively, and the histological changes occurred at the level of the liver and kidneys are the main aspects addressed in the present study. The experiment was performed on 4 groups of Wistar rats: 3 groups which were administered water from rivers located in the vicinity of the Bor mining operation and 1 control group. The determination of the metal content in the administered water samples and in the internal organs was performed using the flame atomic absorption spectrophotometer. Tissue alterations were assessed by histological technique and hematoxylin-eosin staining. The metal retention capacity in the internal organs differs depending on the metal concentration in the administered water sample but also on the organ in which the determination was made. Also, correlations were established between the concentrations of metals at the level of the organs, showing (a) positive and significant correlations—at the level of the heart between Zn and Cu, Fe, and Mn and at the level of the lungs between Mn and Cd—but the most numerous were reported in the testicle; (b) moderate correlations at liver level between Fe and Zn, at spleen level between Cu and Mn and Cd and at the level of the kidneys between Pb and Zn, Cu, and Fe; (c) negative correlations at renal level between Pb and Mn; and (d) insignificant correlations between Pb and Fe. The histological changes identified at the level of the liver and kidney become more obvious, and their aggravation is registered with the increase of the metal content.

Background and Aims Interactions among multiple molecules and signalling pathways contribute to the pathogenesis and progression of diabetic kidney disease (DKD). Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aim of the study was to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients. The molecular mechanisms of lncRNAs intervention were evaluated in relation to a particular miRNA profile. Method A total of 136 patients with type 2 DM and 25 healthy subjects were enrolled in a cross-sectional case series study and assessed concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), and urinary miRNA21, 124, 93, 29a (quantified by a real-time PCR System). Results Multivariable regression analysis yielded models in which urinary lncRNA MALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93 and 29a (p Conclusion In patients with type 2 DM lncRNAs exert distinct functions in different cell types, either deleterious or protective, at both glomerular and tubular level. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.

The presence of maternal Anti-Ro/Anti-La antibodies causes a passively acquired autoimmunity that may be associated with serious fetal complications. The classic example is the autoimmune-mediated congenital heart block (CHB) which is due in most cases to the transplacental passage of Anti-Ro/Anti-La antibodies. The exact mechanisms through which these pathologic events arise are linked to disturbances in calcium channels function, impairment of calcium homeostasis and ultimately apoptosis, inflammation and fibrosis. CHB still represents a challenging diagnosis and a source of debate regarding the best management. As the third-degree block is usually irreversible, the best strategy is risk awareness and prevention. Although CHB is a rare occurrence, it affects one in 20,000 live births, with a high overall mortality rate (up to 20%, with 70% of in utero deaths). There is also concern over the lifelong consequences, as most babies need a pacemaker. This review aims to offer, apart from the data needed for a better understanding of the issue at hand, a broader perspective of the specialists directly involved in managing this pathology: the rheumatologist, the maternal–fetal specialist and the cardiologist. To better illustrate the theoretical facts presented, we also include a representative clinical case.

(1) Background: Familial hypercholesterolemia (FH) is one of the most prevalent inherited metabolic disorders. The purpose of the study was to investigate the role in cardiovascular disease (CVD) of PAI-1, ACE, ApoB-100, MTHFR A1298C, and C677T. (2) Methods: From a group of 1499 patients, we included 52 patients diagnosed with FH phenotype and 17 patients in a control group. (3) Results: Most of the FH patients had multiple comorbidities compared to the control group, such as atherosclerosis (48.1% vs. 17.6%), atherosclerotic cardiovascular disease (ASCVD 32.7% vs. 11.8%), and metabolic syndrome (MetS, 40.4% vs. 11.8%). In total, 66.7% of the FH patients had PAI-1 4G/5G genotype and MetS. Between 4G/5G and 4G/4G, a statistically significant difference was observed (p = 0.013). FH patients with ApoB R3500Q polymorphism were correlated with ASCVD (p = 0.031). Both MTHFR C677T and A1298C polymorphisms had a significant correlation with gender, alcohol consumption, and smoking status. ACE polymorphism was associated with ATS in FH patients, statistically significant differences being observed between heterozygous and homozygous D genotype (p = 0.036) as well as between heterozygous and homozygous I genotype (p = 0.021). (4) Conclusions: A link between these polymorphisms was demonstrated in the FH group for ATS, ASCVD, and MetS.

The purpose of this study was to identify the optimal conditions for the operation of biological treatment plant by carrying out biodegradability tests for geothermal wastewaters with high salt content. The biodegradation tests for geothermal wastewaters were carried out in a discontinuous flow bioreactor. The phases of the biodegradation process were: adaptation of the biological sludge, control of the biological treatment process, experiments in the laboratory bioreactors (BATCH). The results of the biodegradability tests revealed that geothermal waters with high salt content influence the treatment process. The dilution of these waters with domestic water up to chlorine concentrations below 800 mg L-1, makes the purification process to have a good biodegradation yields for CCO-Cr (about 75%) and CBO-5 (about 72%). If these geothermal wastewaters are not diluted to concentrations lower than 800 mg L-1, the biological sludge after 6 days is mineralized, which makes the use of biological treatment plant to be impossible.

The most important natural resource which cannot be optimally used and sustained unless its quality is properly assessed, is groundwater. In the present study, the physicochemical variations of groundwater from the area of an chemical platform were determinate. The physicochemical parameters determined for the groundwater were evaluated by comparing the results obtained with the the limits allowed under current legislation. For this study were examining 16 drillings for a period of five years. Water samples were collected quarterly from each sampling point in the study. The physico-chemical quality indicators analyzed for each source were: pH, chlorides, sulfates, bicarbonates, carbonates, sodium, calcium, magnesium, ammonium, filterable residue, suspended matter, mercury and CCO-Mn.Interpretation of physicochemical data revealed that groundwaters studied was neutral to slightly alkaline. The cations such as sodium (Na+) for all groundwaters studied it was in general found above the limit imposed under the laws in vigor in almost all studied drillings except drillings generally located upstream of the industrial platform. The anions such as chlorides (Cl-) exceeded, in general, the limit allowed under current legislation. The filterable residue concentration was observed in all the studied drillings and the parameter such as sulfate (SO42-), were within the limit allowed under current legislation for the most all studied drillings, for the whole period investigated. In general, the sulfate quality indicator exceeds the required limit, for drilling located downstream and in vicinity of the chemical platform.

Graphite/diamond pastes modified with 1H-pyrrole-1-hexanoic acid were used for the design of stochastic sensors. The proposed stochastic sensors were used to determine four heavy metals, copper(II)...

The interest in the antimicrobial actions of chitosan is due to its multiple properties and effects. The aim of the study was to assess the potential antibacterial effects of chitosan applied on 7 bacterial strains: Escherichia coli, Streptococcus pyogenes, Pseudomonas aeruginosa, Enterococcus faecalis, Clostridium perfringens, Legionella pneumophila and Staphylococcus aureus. Six different concentrations of chitosan were dissolved in 1% acetic acid, following two working protocols (Kirby-Bauer method and testing for bacterial cell viability). The sensitivity of tested bacterial strains following the effect of exposure to chitosan decreased as follows: E. coli] L. pneumophila] S. aureus] S. pyogenes] C. perfringens] P. aeruginosa] E. faecalis. The inhibition rates for the bacterial strains E. faecalis, S. pyogenes and S. aureus highlighted again the strong antibacterial properties of this product. Conclude that the chitosan presents a different antibacterial effect against several bacterial strains of interest directly with the employed concentrations.

Blunt carotid artery injury is a relatively rare but potentially lethal injury that predominantly occurs in high-impact mechanisms such as motor-vehicle collision. Any simptoms or neurological deficits following a multiple trauma patient mandates a thorough evaluation and consideration of BCI. This is a case report on two young patients with neurologic simptoms developed after blunt trauma in the cervical region. Both patients had left internal carotid artery dissection diagnosed on a CT-angiography, followed by middle cerebral artery territory infarction. Although it can be a delayed onset with no signs of vascular demage, we believe that, by implementing a protocol with additional imaging for early detection, we can prevent a devastating outcome.

Materials based on acrylic resins are commonly used in dental practice. These are obtained through various technologies, which determine the chemical, physical and biological properties of the final product, which can influence the inflammatory processes in the periodontal tissue. To evaluate the effects of these materials, we identified the concentrations of TGFb1 and IL8 in crevicular fluid in 23 patients with temporary dentures made of polymethyl methacrylate by two polymerization methods: (1) a product processed immediately prior to application, wherein the polymerization of the material occurs in the oral cavity; and (2) a product processed in the dental laboratory from a prepolymerized block (block-type PMMA), and applied directly into the patient�s mouth. The results of our study revealed a significant correlation between the IL-8 inflammation marker and the clinical parameters in the periodontal tissue exposed to the polymerization of the material in the oral cavity.

A simple, sensitive and selective fluorimetric method for the determination of trace amounts of nitrite in different water samples (e.g., underground water, geothermal waste water, domestic waste water and drinking water) was proposed. The fluorimetric determination is based on the diazotization reaction of nitrite with a fluorescent dye, tetraamino zinc (II) phthalocyanine in an acidic medium. Under the optimum experimental conditions, nitrite can be determined in the range 10− 6–10− 4 mol·L− 1 with the detection limit 2.04 × 10− 8 mol·L− 1. The proposed method has been successfully applied to the determination of nitrite in various water samples. The results compared favorably with the results from a standard isocertified method.

Pregnancy complications such as gestational diabetes (GDM) and hypertensive disorders of pregnancy (HDP) are frequent and influence not only fetal outcomes but also the maternal cardiac function. GDM and HDP may act as a proxy for increased metabolic and cardiovascular risk later in life. Speckle tracking echocardiography (STE) is a relatively new imaging technique that provides more sensitive assessment than conventional echocardiography of the maternal cardiac function. Recent research suggests that STE can be used during pregnancy and postpartum as a useful method of early detection of subclinical maternal cardiac changes related to pregnancy complications, such as GDM and HDP, and as an indicator for future maternal cardiovascular disorders. The aim of this review was to underline the current value of STE in the follow-up protocol of high-risk pregnant women, as a mean for pre- and postpartum monitoring. A review of the literature was conducted in the PubMed database to select relevant articles regarding the association of STE changes and HDP or GDM in the prenatal and postpartum maternal evaluations. Both GDM and HDP are associated with subtle myocardial changes in shape, size and function; these preclinical cardiac changes, often missed by conventional evaluation, can be detected using STE. Left ventricular global circumferential strain might be an important predictor of maternal cardiovascular disorders and might help to define a high-risk group that requires regular monitoring later in life and timely intervention.

Background: Anesthetic preconditioning (AP) is known to mimic ischemic preconditioning. The purpose of this study was to investigate the effects of an interrupted sevoflurane administration protocol on myocardial ischemia/reperfusion (I/R) injury. Methods: Male Wistar rats (n = 60) were ventilated for 30 min with room air (control group, CG) or with a mixture of air and sevoflurane (1 minimum alveolar concentration—MAC) in 5-min cycles, alternating with 5-min wash-out periods (preconditioned groups). Cytokines implicated in the AP response were measured. An (I/R) lesion was produced immediately after the sham intervention (CG) and preconditioning protocol (early AP group, EAPG) or 24 h after the intervention (late AP group, LAPG). The area of fibrosis, the degree of apoptosis and the number of c-kit+ cells was estimated for each group. Results: Cytokine levels were increased post AP. The area of fibrosis decreased in both EAPG and LAPG compared to the CG (p < 0.0001). When compared to the CG, the degree of apoptosis was reduced in both LAPG (p = 0.006) and EAPG (p = 0.007) and the number of c-kit+ cells was the greatest for the LAPG (p < 0.0001). Conclusions: Sevoflurane preconditioning, using an interrupted anesthesia protocol, is efficient in myocardial protection and could be beneficial to reduce perioperative or periprocedural ischemia in patients with increased cardiovascular risk.

The placenta is the site of connection between maternal and fetal circulation, and the liaison is established early in pregnancy. A large variety of pregnancy complications such as preterm birth, fetal growth restriction, or pregnancy loss have placental expression and can be accompanied in some cases of acute or chronic identifiable placental inflamatory lesions. Chronic placental inflammatory (CPI) lesions include chronic villitis of unknow etiology (CVUE), chronic intervillositis of unknown etiology, CIUE (also described as chronic histiocytic intervillositis, CHI), and chronic deciduits. Hydroxychloroquine (HCQ) has been prescribed with good results during pregnancy to prevent adverse perinatal outcomes in maternal autoimmune conditions. Its success has paved the way to its use in CPI as CIUE/CHI; however, to date, there are no prospective, informatively designed, controlled studies on its value in these setting. This review aims to explore the potential role of HCQ in CPI of unknown etiology. Ideally, properly designed, probably multicentric studies should be undertaken to fully understand HCQ’s role for prevention of adverse pregnancy outcomes after a chronic placental inflammation.

During gestation, the maternal body should increase its activity to fulfil the demands of the developing fetus as pregnancy progresses. Each maternal organ adapts in a unique manner and at a different time during pregnancy. In an organ or system that was already vulnerable before pregnancy, the burden of pregnancy can trigger overt clinical manifestations. After delivery, symptoms usually reside; however, in time, because of the age-related metabolic and pro-atherogenic changes, they reappear. Therefore, it is believed that pregnancy acts as a medical stress test for mothers. Pregnancy complications such as gestational hypertension, preeclampsia and gestational diabetes mellitus foreshadow cardiovascular disease and/or diabetes later in life. Affected women are encouraged to modify their lifestyle after birth by adjusting their diet and exercise habits. Blood pressure and plasmatic glucose level checking are recommended so that early therapeutic intervention can reduce long-term morbidity. Currently, the knowledge of the long-term consequences in women who have had pregnancy-related syndromes is still incomplete. A past obstetric history may, however, be useful in determining the risk of diseases later in life and allow timely intervention.