Perceived Stress and Emotional Exhaustion among Undergraduate Medical Students of Gujranwala Medical College, Pakistan

Objective: To determine a student's performance. A survey of undergraduate medical students was done to determine the factors linked to increased stress and emotional tiredness among medical students at Gujranwala Medical College (GMC) Pakistan. Material and Methods:  Data was collected using a structured questionnaire collected from undergraduate medical students. Information related to stress, nervousness, being upset, daily life restlessness, being irritated, being focused, satisfaction with the lecturing, financial strains, family-related stress, living problems, and career, was collected from the respondents via proforma with permission. Results:  40.4% of students felt they had often faced stress during their last month with 37.1% facing unexpected events. Often students (34.4%) found restlessness during their last month with 39.1% of subjects feeling irritated by things happening around them. Some 35.8% of subjects had given thoughts to the future, 26.5% felt worthless and 33.1% forgot simple things or tasks. 39.1% felt they had difficulty focusing on the tasks given to them. Financial strain was always there in 3.3% and was rarely felt in 33.8% of subjects.  Family-related problems were always there in 7.3% of subjects. 33.1% always felt dissatisfied with the quality of food in the mess. 29.8% of subjects felt they were unable to fulfill their parents’ expectations while 22.5% felt they face stress about their career. Conclusion:  40% of students are experiencing various forms of stress and emotional exhaustion. 33 percent of students always felt tension due to messed-up food, and 26.5 percent felt they always felt alone to deal with their problems.

PHENOTYPIC AND GENOTYPIC CHARACTERISTICS OF PROGRESSIVE FAMILIAL INTRAHEPATIC CHOLESTASIS TYPE 3 IN PEDIATRIC POPULATION IN PAKISTAN

OBJECTIVE: To determine the phenotypic and genotypic characteristics of progressive familial intrahepatic cholestasis (PFIC) type 3 in Pakistani children in a hospital setting. METHODS: This cross-sectional observational study was conducted at department of Pediatrics Gastroenterology & Hepatology, The Children’s Hospital Lahore, Pakistan from October 2020 to March 2021. Patients of either sex under 16 years of age presenting with jaundice, pruritus, neonatal cholestasis or with chronic liver and gamma glutamyl transferase >100 IU/ml were included in the study after taking informed consent by parents. For Molecular genetics 2ml blood in EDTA was sent to an international laboratory free of cost on research basis. Reports were assessed and levels were noted and genetic coding was also recorded. Data was entered and analyzed in SPSS version 22. Molecular data was interpreted with the help of clinical geneticist. RESULTS: Out of 34 children, 14 (41.2%) were males and 20 (58.8%) were females. Mean age of children was 6.71±3.10 years. Consanguinity was noted in 32 (94.1%) parents having positive family history in 24 (70.6%) cases. The most common mutation was c. 1783C>T p.(Arg595*),  noted in 12 (35.3%) cases, followed by c. 2861G>T p.(Gly954 ASP) [8 (23.5%) cases], c. 153G>A p.(Trp51) [3 (8.8%) cases], c. 1714 C>T p.(Gln572*) c. 1906C>T p. (Gln636), c. 3220G>A p.(Gly1074Arg, c. 3433del p. (val1145Leufsx7)  in 2 (5.9%) cases each, c. 3859 C>T p.(1287Argext*) c. 88-91del p.(Lys30gly fsx7) and c. 1429c>T p. (Gln477) in one (2.9%) case each. CONCLUSION: Children with PFIC type 3 have variable phenotypic and genotypic presentation

Etiological and Clinical Spectrum of Acute Liver Failure of Infancy in Pakistan

  Objective: To describe the aetiology and clinical spectrum of acute liver failure of infancy at a tertiary care hospital Study Design: Cross-sectional study. Place and Duration of Study: Department of Paediatric Gastroenterology, Hepatology & Nutrition, Children Hospital and Institute of Child Health, Lahore, from Nov 2020 to May 2021. Methodology: Infants under 12 months of age were enrolled having liver-based coagulopathy (not corrected after two doses of parenteral vitamin K, 10 mg) with INR > 2, whether encephalopathy was present or not. Encephalo-pathy is difficult to identify in infants, so it was not essential for the diagnosis of ALFI in our study. Infants diagnosed with chronic liver disease at presentation or those without final etiological diagnosis were excluded. Results: A total of 31 infants were enrolled fulfilling the criteria of acute liver failure of infancy and were studied about aetiology and clinical presentation. The mean age of presentation was 4.64±3.16 months, and males predominated in the study group (64.5%). Common clinical features were in descending order ascites in 29 (93.5%), jaundice in 28 (90.3%), pallor in 24 (77.4%) and peripheral oedema in 21 (67.7%). Metabolic liver diseases were the common cause of ALFI, constituting around(18, 58%) followed by sepsis (9, 29%).Galactosemia (11, 35.5%) stands out among the metabolic causes. Conclusion: Metabolic disorders followed by sepsis are the most common cause of ALFI

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

GALACTOSAEMIA -PRESENTATION, DIAGNOSIS AND MANAGEMENT

Galactosaemia is a rare autosomal recessive metabolic disorder. It presents in early life of glycosuria as determined by negative Clinistix test and (c) rapid clinical improvement on elimination of galactose from the diet of infants. Diagnosis of galactosaemia was made in 18 infants over the study period. Their age at presentation ranged from 35 days -9 months (median 10 weeks). There were 12 males and 6 females (M: F ratio 2:1). Most common mode of presentation was fulminant hepatic failure (FHF). Cataract was present in the majorit

The mutational landscape of genetic cholestatic diseases in Pakistani children

Objective: To report the mutational landscape of a clinically diagnosed cohort of paediatric patients with cholestasis liver diseases. Method: The retrospective study was conducted at the University of Child Health Sciences, The Children Hospital, Lahore, Pakistan, from December 10, 2021, to March 31, 2022, and comprised data collected from the Paediatric Gastroenterology and Hepatology unit on demographics, clinical and laboratory findings related to children of either gender aged <12 years and diagnosed with cholestatic liver disease from July 2018 to June 2021. The diagnosis was based on clinical and biochemical findings, with no evidence of biliary atresia and metabolic liver disease. Molecular characterisation was done through whole exome sequencing. Results: Of the 171 children evaluated, 92(53.8%) were diagnosed with genetic cholestatic disorders. There were 52(56%) boys and 41(44%) girls. The median age at presentation was 19.5 months (interquartile range: 51 months). Consanguinity was found in 82(88.1%) cases, and positive family history with one or more affected siblings was noted in 60(64.5%). Exome sequencing identified pathogenic mutations in 13 genes underlying the hereditary cholestasis; ATP8B1, ABCB11, ABCB4, TJP2, NR1H4, DCDC2, ACOX2, AKR1D1, HSD3B7, ABCC2, USP53, SLC10A1, and SLC51A. Of the 70 variants identified, 50(71.4%) were novel variants. The ABCB11-related hereditary cholestasis was the most frequent 27(29%), followed by ABCB4 (26(27.9%).  Homozygosity was frequently seen in all except 8(8.6%) children, who had compound heterozygous pathogenic variants. There was no evidence of phenotypic expression in the carrier parents despite the severe nature of the respective mutations identified in the patients. Conclusions: Genetic heterogeneity of paediatric intrahepatic cholestasis showed recurrent and novel mutations. Key Words: Cholestasis, Progressive familial intrahepatic cholestasis, Neonatal sclerosing cholangitis, Genetic mutation, USP53, Bile acid synthetic defects, CLD

Sensitivity and specificity of wearables for atrial fibrillation in elderly populations: A systematic review

Purpose of review: This study aims to evaluate the sensitivity and specificity of wearable devices for AF detection in older adults, as well as examine the incidence of AF across various studies, contextual factors impacting AF detection, and safety and adverse events associated with wearable use. Recent findings: A systematic search of three databases identified 30 studies on wearables for AF detection in older adults, encompassing 111,798 participants. Both PPG-based and single-lead electrocardiography-based wearables show scalable potential for screening and managing AF. The results of this systematic review demonstrate that wearable devices, such as smartwatches, can effectively identify arrhythmias like AF in older adults, with scalable potential in PPG-based and single-lead electrocardiography-based wearables. As wearable technologies continue to gain prominence in healthcare, it is crucial to understand their challenges and incorporate them as preventative and monitoring tools for AF detection in elderly populations to improve patient care and prevention technique

An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from Pakistan). Overall, 701 pathogenic/likely pathogenic unique SNVs and 40 CNVs were identified. In 620 patients, the result of the biochemical tests guided variant classification and reporting. Top five diagnosed diseases were: Gaucher disease, Niemann-Pick disease type A/B, phenylketonuria, mucopolysaccharidosis type I, and Wilson disease. We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. More importantly, up to 43% of these patients ( n  = 610) could benefit from medical treatments (e.g., enzyme replacement therapy). This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs

Bi-allelic loss-of-function variants in TMEM147 cause moderate to profound intellectual disability with facial dysmorphism and pseudo-Pelger-Huët anomaly

International audienceThe transmembrane protein TMEM147 has a dual function: first at the nuclear envelope, where it anchors lamin B receptor (LBR) to the inner membrane, and second at the endoplasmic reticulum (ER), where it facilitates the translation of nascent polypeptides within the ribosome-bound TMCO1 translocon complex. Through international data sharing, we identified 23 individuals from 15 unrelated families with bi-allelic TMEM147 loss-of-function variants, including splice-site, nonsense, frameshift, and missense variants. These affected children displayed congruent clinical features including coarse facies, developmental delay, intellectual disability, and behavioral problems. In silico structural analyses predicted disruptive consequences of the identified amino acid substitutions on translocon complex assembly and/or function, and in vitro analyses documented accelerated protein degradation via the autophagy-lysosomal-mediated pathway. Furthermore, TMEM147-deficient cells showed CKAP4 (CLIMP-63) and RTN4 (NOGO) upregulation with a concomitant reorientation of the ER, which was also witnessed in primary fibroblast cell culture. LBR mislocalization and nuclear segmentation was observed in primary fibroblast cells. Abnormal nuclear segmentation and chromatin compaction were also observed in approximately 20% of neutrophils, indicating the presence of a pseudo-Pelger-Huët anomaly. Finally, co-expression analysis revealed significant correlation with neurodevelopmental genes in the brain, further supporting a role of TMEM147 in neurodevelopment. Our findings provide clinical, genetic, and functional evidence that bi-allelic loss-of-function variants in TMEM147 cause syndromic intellectual disability due to ER-translocon and nuclear organization dysfunction