Lixisenatide in early parkinson's disease: efficacy, safety, and future directions: a correspondence.

Parkinson's disease (PD) presents as a complex neurodegenerative disorder characterized by motor and non-motor symptoms, resulting from dopaminergic neuron degeneration. Current treatment strategies primarily aim to alleviate symptoms through pharmacotherapy and supportive therapies. However, emerging research explores novel therapeutic avenues, including the repurposing of drugs like lixisenatide, a GLP-1 receptor agonist initially developed for type 2 diabetes. This correspondence summarizes a phase 2 clinical trial investigating lixisenatide's efficacy in early PD, demonstrating a potential for mitigating motor disability progression. Findings reveal a marginal improvement or stabilization in motor function among lixisenatide-treated individuals compared to placebo, emphasizing its therapeutic promise. Nonetheless, the emergence of gastrointestinal adverse events underscores the need for careful monitoring and management. Further extensive trials are warranted to delineate lixisenatide's efficacy and safety profile, fostering collaborative efforts towards precision treatments in PD.

Diagnostic potential of various laboratory tests for Irritable Bowel Syndrome (IBS): A systematic review.

Objective: To identify possible tests along with their accuracies that may be used to diagnose irritable bowel syndrome. METHODS: The systematic review comprised literature search on Cochrane Library, PubMed, Science Direct and Elsevier databases for randomised controlled trials and cohort studies conducted from January 1, 2015, to December 31, 2022, using appropriate key words and Boolean operators. Focus was kept on studies that reported irritable bowel syndrome diagnosis as the primary outcome. The risk of bias was assessed using quality assessment, data abstraction, and synthesis version 2. RESULTS: Of the 2,798 studies initially identified, 10(0.35%) were analysed in detail. Of them, 4(40%) used enzyme-linked immunosorbent assay kits to test for anti-cytolethal distending toxin B and anti-vinculin levels, 2(20%) used the kits for serum cytokine profiling and serum calprotectin levels, and 4(40%) used either magnetic resonance imaging scans, faecal metabolic profiling, intestinal biopsy analysis with immunostaining or polymerase chain reaction for differential transferribonucleic acid-derived small ribonucleic acid. Out of the 4(40%) studies on anti-cytolethal distending toxin B and anti-vinculin levels, optical densities >1.56 and >1.60 recorded 100% specificity for irritable bowel syndrome with diarrhoea, but sensitivity was 22%. In contrast, rectal biopsies for cell densities of somatostatin and peptide YY showed high sensitivity and specificity for irritable bowel syndrome ranging 80-90%. Conclusion: Enzyme-linked immunosorbent assay testing for anti-cytolethal distending toxin B and anti-vinculin as well as rectal biopsies for cell densities could be potential diagnostic tests for irritable bowel syndrome.

Eating Disorders and Disordered Eating Behaviors Among Undergraduate Students in Pakistan as Measured by Eating Disorder Examination Questionnaire (EDE-Q).

Objectives Eating disorders (ED) are an emerging public health issue globally, especially in young adults studying at the undergraduate level. This study aims to assess the frequency of eating disorders, their types, and disordered eating behaviors among such students. Moreover, it aims to identify factors like weight concern, shape concern, eating concern, and restraint, along with assessing the shifting trend of BMI impact on eating disorders using a standardized Eating Disorder Examination Questionnaire (EDE-Q). Methods In this cross-sectional study, 400 undergraduate students (aged 18-25) from four public universities participated from July 2022 to November 2023. Data was collected using the Eating Disorder Examination Questionnaire (EDE-Q). The frequency of eating disorders was computed using SPSS version 27. Results Among the participants, 21.75% (n=84) were identified as having a score surpassing the clinical cut-off. This group comprised 5.5% males (n=22) and 16% females (n=64). The highest prevalence among the four subscales was observed in the Shape Concern subscale (10.5%). Objective binge episodes (19.3%) emerged as the most notable disordered eating attitude. Atypical anorexia nervosa accounted for 13.8% of different eating disorders, while disordered eating was noted in 19.5% (n=78) of individuals. Discussion This study offers critical insights into eating disorders among Pakistan undergraduate students, utilizing the EDE-Q 6.0. Disordered eating behaviors, particularly shape concern and objective binge eating, exhibit significant correlations with these disorders. Weight dissatisfaction emerges as a prominent predictor, suggesting societal influence. The study also reveals a moderate correlation between BMI and eating disorders, challenging conventional assumptions. Furthermore, a changing trend in the prevalence of eating disorders is observed among the male population.

PSMF1 variants cause a phenotypic spectrum from early-onset Parkinson's disease to perinatal lethality by disrupting mitochondrial pathways.

Dissecting biological pathways highlighted by Mendelian gene discovery has provided critical insights into the pathogenesis of Parkinson's disease (PD) and neurodegeneration. This approach ultimately catalyzes the identification of potential biomarkers and therapeutic targets. Here, we identify PSMF1 as a new gene implicated in PD and childhood neurodegeneration. We find that biallelic PSMF1 missense and loss-of-function variants co-segregate with phenotypes from early-onset PD and parkinsonism to perinatal lethality with neurological manifestations across 15 unrelated pedigrees with 22 affected subjects, showing clear genotype-phenotype correlation. PSMF1 encodes the proteasome regulator PSMF1/PI31, a highly conserved, ubiquitously expressed partner of the 20S proteasome and neurodegeneration-associated F-box-O 7 and valosin-containing proteins. We demonstrate that PSMF1 variants impair mitochondrial membrane potential, dynamics and mitophagy in patient-derived fibroblasts. Additionally, we develop models of psmf1 knockdown Drosophila and Psmf1 conditional knockout mouse exhibiting age-dependent motor impairment, with diffuse gliosis in mice. These findings unequivocally link defective PSMF1 to early-onset PD and neurodegeneration and suggest mitochondrial dysfunction as a mechanistic contributor.