Family-based association of HLA-DRB1 and DQB1 alleles and haplotypes in a group of Iranian Type 1 diabetes children.

This family-based study was conducted in a group of Iranians with Type 1 diabetes (T1D) to investigate the transmission from parents of risk and non-risk HLA alleles and haplotypes, and to estimate the genetic risk score for this disease within this population. A total of 240 T1D subjects including 111 parent-child trios (111 children with T1D, 133 siblings, and 222 parents) and 330 ethnically matched healthy individuals were recruited. High-resolution HLA typing for DRB1/DQB1 loci was performed for all study subjects (n = 925) using polymerase chain reaction-sequence-specific oligonucleotide probe method. The highest predisposing effect on developing T1D was conferred by the following haplotypes both in all subjects and in probands compared to controls: DRB1*04:05-DQB1*03:02 (Pc = 2.97e-06 and Pc = 6.04e-10, respectively), DRB1*04:02-DQB1*03:02 (Pc = 5.94e-17 and Pc = 3.86e-09, respectively), and DRB1*03:01-DQB1*02:01 (Pc = 8.26e-29 and Pc = 6.56e-16, respectively). Conversely, the major protective haplotypes included DRB1*13:01-DQB1*06:03 (Pc = 6.99e-08), DRB1*15:01-DQB1*06:02 (Pc = 2.97e-06) in the cases versus controls. Also, DRB1*03:01-DQB1*02:01/DRB1*04:02|05-DQB1*03:02 and DRB1*03:01-DQB1*02:01/DRB1*03:01-DQB1*02:01 diplotypes conferred the highest predisposing effect in the cases (Pc = 8.65e-17 and Pc = 6.26e-08, respectively) and in probands (Pc = 5.4e-15 and Pc = 0.001, respectively) compared to controls. Transmission disequilibrium test showed that the highest risk was conferred by DRB1*04:02-DQB1*03:02 (Pc = 3.26e-05) and DRB1*03:01-DQB1*02:01 (Pc = 1.78e-12) haplotypes and the highest protection by DRB1*14:01-DQB1*05:03 (Pc = 8.66e-05), DRB1*15:01-DQB1*06:02 (Pc = 0.002), and DRB1*11:01-DQB1*03:01 (Pc = 0.0003) haplotypes. Based on logistic regression analysis, carriage of risk haplotypes increased the risk of T1D development 24.5 times in the Iranian population (p = 5.61e-13). Also, receiver operating characteristic curve analysis revealed a high predictive power of those risk haplotypes in discrimination of susceptible from healthy individuals (area under curve: 0.88, p = 5.5e-32). Our study highlights the potential utility of genetic risk assessment based on HLA diplotypes for predicting T1D risk in individuals, particularly among family members of affected children in our population.

Infantile-onset pompe disease: a case report emphasizing the role of genetic counseling and prenatal testing.

BACKGROUND: Pompe disease, classified as glycogen storage disease type II, arises from a deficiency in the acid alpha-glucosidase (GAA) enzyme, leading to glycogen accumulation in multiple tissues. The unique correlation between genotype and enzyme activity is a key feature. This case highlights an infantile-onset form, emphasizing genetic counseling and prenatal testing importance. CASE PRESENTATION: An 18-week-old infant with respiratory distress, cyanosis, and fever was admitted. Born healthy, her sibling died from Pompe disease. She presented with cardiomegaly, hypotonia, and absent reflexes. Diagnosis was confirmed by significantly reduced GAA activity. Despite treatment initiation, the patient succumbed to cardiac arrest. CONCLUSIONS: The case underscores genetic counseling's role, offering insights into prenatal testing advancements, antenatal diagnosis through echocardiography, and the significance of early intervention, particularly in infantile-onset Pompe disease. SYNOPSIS: Genetic risk assessment and prenatal testing are crucial for families with a history of Pompe disease to improve early diagnosis and management outcomes.

Effects of bariatric surgery on cognitive function in older adults: a prospective longitudinal study.

BACKGROUND: Obesity is now well-recognized as an independent risk factor for cognitive decline. Although extensive research has been conducted on cognitive outcomes following bariatric surgery in young adults, very little is known about the impact of advanced age on the cognitive benefits of weight-loss procedures. OBJECTIVES: This study aimed to assess cognitive function in older Iranian patients before and after bariatric surgery. SETTING: University Hospital METHODS: In this prospective longitudinal study, 24 older adults were examined before and 4 months after bariatric surgery using the Digit Span Test (DGS), the computerized version of the Wisconsin Card Sorting Test-64 (WCST-64), and the paper-and-pencil versions of the Trail Making Test (TMT), parts A and B, spanning the 4 cognitive domains of attention, working memory, processing speed, and executive functioning. The bariatric surgery group was simultaneously compared to a waiting list control group. RESULTS: At 4 months of follow-up, comparisons between the groups revealed that the surgical group performed significantly better than the control group on the forward DGS, WCST, and TMT parts A and B. In contrast, there was no significant difference between groups on the backward DGS. Further within-group comparisons demonstrated significant improvements from baseline in forward DGS, WCST, and TMT components A and B. Nevertheless, the same variables did not alter significantly over time in the control group. CONCLUSIONS: The study suggests measurable cognitive benefits following bariatric surgery in older adults.

Pulmonary embolism or COVID-19 pneumonia? A case report.

Pulmonary embolism (PE) is the most severe clinical presentation of venous thromboembolism (VTE), which can be challenging to diagnose due to its non-specific symptoms. The overlapping clinical symptoms of Coronavirus disease 2019 (COVID-19) and PE may make distinguishing between the two difficult. Thus, the diagnosis of PE may be delayed or missed, with grave consequences for the patient's outcome and safety. We herein present the case of a 63-year-old Iranian female admitted to our hospital showing symptoms of delirium superimposed on dementia. Soon after her admission, she developed a fever and respiratory symptoms. However, overestimating the likelihood of COVID-19 pneumonia and attributing the patient's symptoms to this disease led to a delayed diagnosis and treatment of pulmonary embolism, resulting in the patient's death. During the COVID-19 pandemic, a high index of suspicion is required for the timely diagnosis of PE, especially in patients with identifiable risk factors. This is specifically true for older patients who cannot express their symptoms due to neurocognitive disorders.

Sestrin2 and Beclin1 levels in Polycystic Ovary Syndrome.

BACKGROUND: Sestrin2 and beclin1 are two newly found proteins that have essential roles in autophagy. This study attempted to evaluate the plasma concentrations of sestrin2 and beclin1 in women with polycystic ovary syndrome (PCOS) and healthy controls and to explore the clinical value of these proteins as novel biomarkers for PCOS. METHODS: In this case-control study, plasma levels of sestrin2 and beclin1, fasting blood sugar (FBS), lipid profile, insulin, and androgens were evaluated in 63 women (31 patients and 32 controls). Sestrin2 and beclin1 levels were determined using enzyme-linked immunosorbent assay (ELISA). Descriptive statistics, correlation coefficients, logistic regression, and ROC curve analyses were used in this study. RESULTS: Plasma sestrin2 levels of the subjects with PCOS (40.74 [24.39-257.70]) were significantly lower than those of healthy subjects (255.78 [25.46-528.66]; p-value = 0.040). ROC curve analysis showed that a cutoff value of 420.5 ng/L had an appropriate sensitivity (83.87%) and specificity (46.88%) for discriminating individuals with and without PCOS, with the area under the curve (95% CI) of 0.648 (0.518 to 0.764), p = 0.036. There were no statistically significant differences between the two groups concerning plasma levels of beclin1, biochemical parameters, blood pressure, and anthropometric features. CONCLUSION: Our findings highlight the dysregulation of sestrin2 as a marker of autophagy in PCOS and its potential usefulness as a novel biomarker for PCOS. Further research is needed to better understand the role of this protein in the pathophysiology of PCOS and its value as a diagnostic tool for the evaluation of PCOS patients.