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Background: Apolipoprotein E (ApoE) is a ubiquitous protein involved in maintaining cholesterol homeostasis and lipoprotein clearance from circulation. It is coded by three alleles (ε2, ε3, ε4) with six genotypes (ε3/ε3, ε3/ε4, ε2/ε3, ε4/ε4, ε2/ε4, and ε2/ε2). Several studies have shown a relationship between ApoE-specific isoforms and different diseases. There are few data about the prevalence of ApoE polymorphism in the Romanian population. We aimed to assess the prevalence of Apolipoprotein E alleles in a healthy population from Romania and compare it with the data found in other countries of Europe.

Colorectal cancer (CRC) remains a major public health burden worldwide, despite increased knowledge on its pathogenesis and advances in therapy. We aimed to evaluate a new histological grading system based on poorly differentiated clusters (PDCs) counting – the PDCs grade (PDCs-G), and its clinicopathological and prognostic significance, compared to the World Health Organisation (WHO) grading system (WHO grade). We reviewed 71 surgical resection specimens for CRC from the Emergency County Hospital “Pius Brînzeu” Timisoara. The cases were graded using the WHO grade and the PDCs-G, with further analysis of their association with the other recognised prognostic parameters. Using the WHO grade, 9% of the analysed cases were G1, 80% G2, 11% G3, and none of the tumours was graded G4, while in the PDCs-G 16% were G1, 45% G2, and 39% G3. In multivariate analysis PDCs-G was significantly associated with the American Joint Committee on Cancer stage of the disease (AJCC stage) (p = 0.0003), depth of invasion (pT) (p = 0.0084), nodal status (LNM) (p < 0.0001), lymphovascular invasion (LVI) (p < 0.0001), perineural invasion (PNI) (p < 0.0052), and tumour border configuration (p < 0.0001). The novel grading system based on PDCs counting is an additional histological tool in the evaluation of CRC and a promising new prognostic factor for these patients.

Recent evidence demonstrates that a region of the posterior superior temporal sulcus (pSTS) is selective to visually observed social interactions in adults. In contrast, little is known about neural responses to social interactions in children. Here, we used fMRI to ask whether the pSTS is ‘tuned’ to social interactions in children at all, and if so, how selectivity might differ from adults. This was investigated in the pSTS, along with several other socially-tuned regions in neighbouring temporal cortex: extrastriate body area, face selective STS, fusiform face area, and mentalizing selective temporo-parietal junction.Both children and adults showed selectivity to social interaction within right pSTS, while only adults showed selectivity on the left. Adults also showed both more focal and greater selectivity than children (6–12 years) bilaterally. Exploratory sub-group analyses showed that younger children (6–8), but not older children (9–12), are less selective than adults on the right, while there was a continuous developmental trend (adults > older > younger) in left pSTS. These results suggest that, over development, the neural response to social interactions is characterized by increasingly more selective, focal, and bilateral pSTS responses, a process that likely continues into adolescence.

Introduction. Chronic pancreatitis is morphologically characterized by ductal dysplasia, breeding grounds for the proliferation of the ductal cells, the degenerative changes in pancreatic acinar cells and fibrosis, and it is defined on the basis of the clinical, morphological and functional criteria.

Autophagy, a homeostatic process involved in nutrient regeneration and immune responses, may be involved in intracellular killing of M. tuberculosis. Several studies linked variation in autophagy genes with susceptibility to pulmonary tuberculosis, but others did not confirm these findings.

Objective To evaluate the performance of diagnostic tools for diabetes mellitus, Including laboratory methods and clinical risk scores, In newly-diagnosed pulmonary tuberculosis patients from four middle-income countries.Methods In a multicentre, prospective study, we recruited 2185 patients with pulmonary tuberculosis from sites in Indonesia, Peru, Romania ' and South Africa from January 2014 to September 2016. Using laboratory-measured glycated haemoglobin (HbA1c) as the gold standard, we measured the diagnostic accuracy of random plasma glucose, point-of-care HbA1c, fasting blood glucose, urine dipstick, published and newly derived diabetes mellitus risk scores and anthropometric measurements. We also analysed combinations of tests, including a two-step test using point-of-care HbA1cwhen Initial random plasma glucose was [greater than or equal to] 6.1 mmol/L.Findings The overall crude prevalence of diabetes mellitus among newly diagnosed tuberculosis patients was 283/2185 (13.0%; 95% confidence interval, CI: 11.6-14.4). The marker with the best diagnostic accuracy was point-of-care HbA1c (area under receiver operating characteristic curve: 0.81; 95% CI: 0.75-0.86). A risk score derived using age, point-of-care HbA1c and random plasma glucose had the best overall diagnostic accuracy (area under curve: 0.85; 95% CI: 0.81-0.90). There was substantial heterogeneity between sites for all markers, but the two-step combination test performed well in Indonesia and Peru.Conclusion Random plasma glucose followed by point-of-care HbA1c testing can accurately diagnose diabetes in tuberculosis patients, particularly those with substantial hyperglycaemla, while reducing the need for more expensive point-of-care HbA1c testing. Risk scores with or without biochemical data may be useful but require validation.Objectif Evaluer la performance des outils de diagnostic du diabete sucre, et notamment les methodes de laboratoire et les cotes de risque clinique, chez les patients souffrant d'une tuberculose pulmonaire recemment diagnostiquee dans quatre pays a revenu intermediaire.Methodes Dans le cadre d'une etude multicentrique et prospective, nous avons recrute 2185 patients atteints de tuberculose pulmonaire dans differents endroits en Afrique du Sud, en Indonesie, au Perou et en Roumanie entre janvier 2014 et septembre 2016. En utilisant comme referencel'hemoglobineglyquee (HbA1c) mesuree en laboratoire, nous avons evalue la precision diagnostique de la glycemie aleatoire, de l'HbAI c sur le lieu d'intervention, de la glycemie a jeun, de la bandelette urinaire, des cotes de risque deja publiees et recemment obtenues pour le diabete sucre et des mesures anthropometriques. Nous avons egalement analyse des combinaisons de tests, et notamment un test en deux etapes qui utilise l'HbA1c sur le lieu d'intervention lorsque la glycemie aleatoire initiale est [greater than or equal to] 6,1 mmol/LResultats La prevalence brute generale du diabete sucre chez les patients souffrant d'une tuberculose recemment diagnostiquee etait de 283/2185 (13,0%; intervalle de confiance, IC, a 95%: 11,6-14,4). Le marqueur fournissant la meilleure precision diagnostique etait l'HbA1c sur le lieu d'intervention (aire sous la courbe ROC: 0,81; IC a 95%: 0,75-0,86). La meilleure precision diagnostique generale a ete obtenue a l'aide d'une cote de risque calculee au moyen de l'age, de l'HbA1c sur le lieu d'intervention et de la glycemie aleatoire (aire sous la courbe ROC: 0,85; IC a 95%: 0,81-0,90). Une forte heterogeneite entre les differents endrolts a ete constatee pourtous les marqueurs, mais le test en deux etapes a donne de bons resultats en Indonesie et au Perou.Conclusion L'utilisation de la glycemie aleatoire suivie de l'HbA1c sur le lieu d'intervention permet de diagnostiquer avec precision le diabete chez les patients atteints de tuberculose, en particulier lorsqu'ils souffrent d'une importante hyperglycemie, tout en diminuant le besoin de tests HbA1c sur le lieu d'intervention, plus couteux. Les cotes de risque associees ou non a des donnees biochimiques peuvent etre utiles, mais doivent etre validees.Objetivo Evaluar el rendimiento de las herramientas de diagnostico para la diabetes mellitus, incluidos los metodos de laboratorio y los indices de riesgo clinico, en pacientes recien diagnosticados con tuberculosis pulmonar de cuatro paises de ingresos medios.Metodos En un estudio prospectivo multicentrico, se seleccionaron 2185 pacientes con tuberculosis pulmonar de algunas regiones de Indonesia, Peru, Rumania y Sudafrica entre enero de 2014 y septiembre de 2016. Usando hemoglobina glicosilada medida en laboratorio (HbA1 c) como el patron de excelencia, se midio la precision diagnostica de glucosa plasmatica al azar, estando HbA1 c en el punto de atencion, glucemia en sangre en ayunas, tira reactiva de orina, indices de riesgo de diabetes mellitus publicados recientemente y medidas antropometricas. Tambien se analizaron combinaciones de pruebas, incluida una prueba de dos pasos con HbA1c en el punto de atencion cuando la glucosa plasmatica aleatoria inicial fue [greater than or equal to] 6,1 mmol/L.Resultados La prevalencia general cruda de diabetes mellitus entre los pacientes con tuberculosis recien diagnosticados fue de 283/2185 (13,0 %, intervalo de confianza del 95 %, IC: 11,6-14,4). El marcador con la mejor precision diagnostica fue la HbA1c en el punto de atencion (area bajo la curva caracteristica operativa del receptor: 0,81; IC del 95 %: 0,75-0,86). Un indice de riesgo derivado de la edad, la HbA1c en el punto de atencion y la glucosa plasmatica al azar obtuvieron la mejor precision diagnostica general (area bajo la curva: 0,85; IC del 95 %: 0,81 -0,90). Hubo una heterogeneidad sustancial entre las regiones para todos los marcadores, pero la prueba combinada de dos pasos funciono de manera correcta en Indonesia y Peru.Conclusion La glucosa plasmatica al azar seguida de la prueba de HbA1c en el punto de atencion puede diagnosticar con precision la diabetes en pacientes con tuberculosis, particularmente en aquellos con hiperglucemia sustancial, mientras se reduce la necesidad de pruebas mas costosas de HbA1 c en el punto de atencion. Los indices de riesgo con o sin datos bioquimicos pueden ser utiles, pero requieren validacion., [phrase omitted]IntroductionTuberculosis is a major global public health concern. In 2016, the World Health Organization (WHO) estimated that there were 10.4 million new tuberculosis patients worldwide and 1.8 million tuberculosis-related [...]

Background: People with diabetes are more likely to develop tuberculosis (TB) and to have poor TB‐treatment outcomes than those without. We previously showed that blood transcriptomes in people with TB‐diabetes (TB‐DM) co‐morbidity have excessive inflammatory and reduced interferon responses at diagnosis. It is unknown whether this persists through treatment and contributes to the adverse outcomes. Methods: Pulmonary TB patients recruited in South Africa, Indonesia and Romania were classified as having TB‐DM, TB with prediabetes, TB‐related hyperglycaemia or TB‐only, based on glycated haemoglobin concentration at TB diagnosis and after 6 months of TB treatment. Gene expression in blood at diagnosis and intervals throughout treatment was measured by unbiased RNA‐Seq and targeted Multiplex Ligation‐dependent Probe Amplification. Transcriptomic data were analysed by longitudinal mixed‐model regression to identify whether genes were differentially expressed between clinical groups through time. Predictive models of TB‐treatment response across groups were developed and cross‐tested. Results: Gene expression differed between TB and TB‐DM patients at diagnosis and was modulated by TB treatment in all clinical groups but to different extents, such that differences remained in TB‐DM relative to TB‐only throughout. Expression of some genes increased through TB treatment, whereas others decreased: some were persistently more highly expressed in TB‐DM and others in TB‐only patients. Genes involved in innate immune responses, anti‐microbial immunity and inflammation were significantly upregulated in people with TB‐DM throughout treatment. The overall pattern of change was similar across clinical groups irrespective of diabetes status, permitting models predictive of TB treatment to be developed. Conclusions: Exacerbated transcriptome changes in TB‐DM take longer to resolve during TB treatment, meaning they remain different from those in uncomplicated TB after treatment completion. This may indicate a prolonged inflammatory response in TB‐DM, requiring prolonged treatment or host‐directed therapy for complete cure. Development of transcriptome‐based biomarker signatures of TB‐treatment response should include people with diabetes for use across populations. [ABSTRACT FROM AUTHOR]

Familial hypercholesterolemia (FH) is a genetic disease marked by high levels of LDL-cholesterol. This condition has long-term clinical implications, such as cardiovascular events, that are evident during adult life. Here, we report on a single-center cross-sectional showcase study of genetic testing for FH in a Romanian pediatric group. Genetic testing for FH was performed on 20 Romanian pediatric patients, 10 boys and 10 girls, admitted with LDL-cholesterol levels over 130 mg/mL to the National Institute for Mother and Child Health "Alesssandrescu-Rusescu" in 2020. Genetic testing was performed using the Illumina TruSight Cardio panel. We identified pathogenic/likely pathogenic variants that could explain the phenotype in 5/20 cases. The involved genes were LDLR and APOB. Clinical signs that suggest the diagnosis of FH are scarce for the pediatric patient, although it can be diagnosed early during childhood by lipid panel screening. Prevention could prove lifesaving for some of these patients. [ABSTRACT FROM AUTHOR]

The genetic causes of autosomal recessive nonsyndromic hearing loss (ARNSHL) are heterogeneous and highly ethnic-specific. We describe GJB2 (connexin 26) variants and carrier frequencies as part of our study and summarize previously reported ones for the Romanian population. In total, 284 unrelated children with bilateral congenital NSHL were enrolled between 2009 and 2018 in northwestern Romania. A tiered diagnostic approach was used: all subjects were tested for c.35delG, c.71G>A and deletions in GJB6 (connexin 30) using PCR-based methods. Furthermore, 124 cases undiagnosed at this stage were analyzed by multiplex-ligation-dependent probe amplifications (MLPA), probe mix P163, and sequencing of GJB2 exon 2. Targeted allele-specific PCR/restriction fragment length polymorphism (RFLP) established definite ethio-pathogenical diagnosis for 72/284 (25.35%) of the cohort. Out of the 124 further analyzed, in 12 cases (9.67%), we found compound heterozygous point mutations in GJB2. We identified one case of deletion of exon 1 of the WFS1 (wolframin) gene. Carrier status evaluation used Illumina Infinium Global Screening Array (GSA) genotyping: the HINT cohort-416 individuals in northwest Romania, and the FUSE cohort-472 individuals in southwest Romania. GSA variants yielded a cumulated risk allele presence of 0.0284. A tiered diagnostic approach may be efficient in diagnosing ARNSHL. The summarized contributions to Romanian descriptive epidemiology of ARNSHL shows that pathogenic variants in the GJB2 gene are frequent among NSHL cases and have high carrier rates, especially for c.35delG and c.71G>A. These findings may serve in health strategy development. [ABSTRACT FROM AUTHOR]

The investigation of unexplained global developmental delay (GDD)/intellectual disability (ID) is challenging. In low resource settings, patients may not follow a standardized diagnostic process that makes use of the benefits of advanced technologies. Our study aims to explore the contribution of chromosome microarray analysis (CMA) in identifying the genetic etiology of GDD/ID. A total of 371 Romanian patients with syndromic or non-syndromic GDD/ID, without epilepsy, were routinely evaluated in tertiary clinics. A total of 234 males (63.07%) and 137 (36.93%) females, with ages ranging from 6 months to 40 years (median age of 5.5 years), were referred for genetic diagnosis between 2015 and 2022; testing options included CMA and/or karyotyping. Agilent Technologies and Oxford Gene Technology CMA workflows were used. Pathogenic/likely pathogenic copy number variations (pCNVs) were identified in 79 patients (21.29%). Diagnosis yield was comparable between mild ID (17.05%, 22/129) and moderate/severe ID 23.55% (57/242). Higher rates were found in cases where facial dysmorphism (22.97%, 71/309), autism spectrum disorder (ASD) (19.11%, 26/136) and finger anomalies (20%, 27/96) were associated with GDD/ID. GDD/ID plus multiple congenital anomalies (MCA) account for the highest detection rates at 27.42% (17/62). pCNVs represent a significant proportion of the genetic causes of GDD/ID. Our study confirms the utility of CMA in assessing GDD/ID with an uncertain etiology, especially in patients with associated comorbidities. [ABSTRACT FROM AUTHOR]