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The PLEKHG5 gene encodes a protein that induces the nuclear factor kappa B (NFjB) signaling pathway. Biallelic pathogenic variants in PLEKHG5 have been linked to distal spinal muscular atrophy IV and intermediate axonal neuropathy. We present a six-year-old girl complaining of difficulties climbing stairs and getting up from crouching. Neurological examination revealed a symmetrical proximal limb weakness with milder distal weakness. While the patellar reflexes were absent, the biceps reflexes were hyporeflexic. Electromyography showed a mild denervation pattern in the proximal muscle groups with normal nerve conduction studies. MLPA in SMN1 showed no abnormalities. Exome sequencing revealed a homozygous missense variant in PLEKHG5 (c.1399G>A: NM_020631.4 [p.Glu467Lys]). Their unaffected mother and father were both carriers. [ABSTRACT FROM AUTHOR]

The rewarding taste of food is critical for motivating animals to eat, but whether taste has a parallel function in promoting meal termination is not well understood. Here, we show that hunger-promoting agouti-related peptide (AgRP) neurons are rapidly inhibited during each bout of ingestion by a signal linked to the taste of food. Blocking these transient dips in activity via closed-loop optogenetic stimulation increases food intake by selectively delaying the onset of satiety. We show that upstream leptin-receptor-expressing neurons in the dorsomedial hypothalamus (DMH LepR ) are tuned to respond to sweet or fatty tastes and exhibit time-locked activation during feeding that is the mirror image of downstream AgRP cells. These findings reveal an unexpected role for taste in the negative feedback control of ingestion. They also reveal a mechanism by which AgRP neurons, which are the primary cells that drive hunger, are able to influence the moment-by-moment dynamics of food consumption., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: critically ill cirrhotic patients may present a serious clinical condition defined as acute-on-chronic liver failure with high mortality. While established scoring systems like Child-Pugh and Model for End-stage Liver Disease (MELD) offer prognostic insights, their limitations warrant exploration of alternative markers. The lactate/albumin ratio (LAR) serves as a potential prognostic indicator in critical care settings, yet its utility in cirrhotic patients remains underexplored., Methods: one hundred and seventy-five critically ill cirrhotic patients were assessed in this retrospective cohort study. Clinical severity scores, including Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Chronic Liver Failure-Organ Failure Score (CLIF-OF) were compared with LAR along with traditional liver failure scoring systems. Logistic regression and receiver operating characteristic (ROC) curve analysis were used to evaluate prognostic performance., Results: Intensive Care Unit (ICU) nonsurvivors had significantly higher scores in all liver failure and clinical severity scores compared to survivors (p < 0.001). Median LAR was significantly higher in nonsurvivors (p < 0.001). ROC analysis revealed comparable prognostic accuracy between LAR, APACHE II, SOFA, and CLIF-OF scores in predicting ICU mortality. Logistic regression identified SOFA score at 48th hour, LAR, and requirement of mechanical ventilation as independent predictors of ICU mortality., Conclusion: LAR demonstrates promising prognostic utility in predicting ICU mortality among critically ill cirrhotic patients, complementing established scoring systems. Early reassessment using SOFA score at 48th hour may guide therapeutic interventions and improve patient outcomes. Further prospective studies are warranted to validate these findings and optimize clinical management strategies.