MicroRNA-502-3p regulates GABAergic synapse function in hippocampal neurons

Gamma-aminobutyric acid(GABA)ergic neurons,the most abundant inhibitory neurons in the human brain,have been found to be reduced in many neurological disorders,including Alzheimer's disease and Alzheimer's disease-related dementia.Our previous study identified the upregulation of microRNA-502-3p(miR-502-3p)and downregulation of GABA type A receptor subunitα-1 in Alzheimer's disease synapses.This study investigated a new molecular relationship between miR-502-3p and GABAergic synapse function.In vitro studies were perfo rmed using the mouse hippocampal neuronal cell line HT22 and miR-502-3p agomiRs and antagomiRs.In silico analysis identified multiple binding sites of miR-502-3p at GABA type A receptor subunitα-1 mRNA.Luciferase assay confirmed that miR-502-3p targets the GABA type A receptor subunitα-1 gene and suppresses the luciferase activity.Furthermore,quantitative reve rse transcription-polymerase chain reaction,miRNA in situ hybridization,immunoblotting,and immunostaining analysis confirmed that overexpression of miR-502-3p reduced the GABA type A receptor subunitα-1 level,while suppression of miR-502-3p increased the level of GABA type A receptor subunitα-1 protein.Notably,as a result of the overexpression of miR-502-3p,cell viability was found to be reduced,and the population of necrotic cells was found to be increased.The whole cell patch-clamp analysis of human-GABA receptor A-α1/β3/γ2L human embryonic kidney(HEK)recombinant cell line also showed that overexpression of miR-502-3p reduced the GABA current and overall GABA function,suggesting a negative correlation between miR-502-3p levels and GABAergic synapse function.Additionally,the levels of proteins associated with Alzheimer s disease were high with miR-502-3p overexpression and reduced with miR-502-3p suppression.The present study provides insight into the molecular mechanism of regulation of GABAergic synapses by miR-502-3p.We propose that micro-RNA,in particular miR-502-3p,could be a potential therapeutic to rget to modulate GABAergic synapse function in neurological disorders,including Alzheimer's disease and Alzheimer's diseaserelated dementia.

Synaptosome microRNAs:emerging synapse players in aging and Alzheimer’s disease

Synaptosome:Synapses are the most critical portion of neuron connections,necessary for cellular organization of the brain.Synapse integrity is uttermost important for healthy brain functioning.Any perturbation in the synapse structure and/or function initiates neurological disorders.Synapses are the prime targets that are smashed in almost all neurodegenerative diseases.The vital components of synapse are essential for neurotransmission,synaptic plasticity and overall synapse function.Synapse dysfunctions are well studied in Alzheimer’s disease(AD)and other neurodegenerative diseases(Gowda et al.,2021).The best way to study the synapse dysfunctions in neurological diseases is the biochemical analysis of“synaptosome”.

Management and outcome of pancreatic trauma:a 6-year experience at a level I trauma center

Background: Pancreatic trauma (PT) accounts for less than 1% of all trauma admissions. Occasionally, PT is undetected during theprimary survey and becomes apparent only when complications arise. It occurs in up to 5% of blunt abdominal trauma cases and 12%of individuals with penetrating abdominal injuries. Management is determined by the status of the main pancreatic duct and associatedinjuries.Methods: This was an ambispective study conducted at the Jai Prakash Narayan Apex Trauma Center, All India Institute ofMedical Sciences,New Delhi, from January 2015 to December 2017 (retrospective), and January 2019 to December 2020 (prospective). In total, 113patients with PT were included in this study.Results:We analyzed the data of 113 patients with PT included in this study, of whichmales predominated (93.7%). Blunt PT was presentin 101 patients (89.4%) and penetrating PT in 12 patients (10.6%). Half of the patients (51.3%) had the American Association for theSurgery of Trauma grade III PT, followed by grade II (18.6%), and grade I (15%). Of the total 113 patients, 68 (60.2%) were treated withoperative management, and 45 (39.8%) with nonoperative management. Distal pancreatectomy, with or without splenectomy, was themost common procedure performed in our study, followed by drainage. There were 27 mortalities (23.8%) during the study period, ofwhich 7 were directly related to PT and 20 were due to other organ-related sepsis and hemorrhagic shock.Conclusion: Pancreatic trauma is rare but challenging for trauma surgeons, with persistent management controversies. Early diagnosisis important for favorable results;however, a delay in diagnosis has been associated with higher morbidity and mortality. Low-grade pancreaticinjuries can be successfully managed nonoperatively, whereas high-grade pancreatic injuries require surgical intervention.

Comparison of ISS, NISS, and RTS score as predictor of mortality in pediatric fall

Background:Studies to identify an ideal trauma score tool representing prediction of outcomes of the pediatric fall patient remains elusive. Our study was undertaken to identify better predictor of mortality in the pediatric fall patients. Methods:Data was retrieved from prospectively maintained trauma registry project at level 1 trauma center developed as part of Multicentric Project—Towards Improving Trauma Care Outcomes (TITCO) in India. Single center data retrieved from a prospectively maintained trauma registry at a level 1 trauma center, New Delhi, for a period ranging from 1 October 2013 to 17 February 2015 was evaluated. Standard anatomic scores Injury Severity Score (ISS) and New Injury Severity Score (NISS) were compared with physiologic score Revised Trauma Score (RTS) using receiver operating curve (ROC). Results:Heart rate and RTS had a statistical difference among the survivors to nonsurvivors. ISS, NISS, and RTS were having 50, 50, and 86% of area under the curve on ROCs, and RTS was statistically significant among them. Conclusions: Physiologically based trauma score systems (RTS) are much better predictors of inhospital mortality in comparison to anatomical based scoring systems (ISS and NISS) for unintentional pediatric falls.

Innocuous cardiac gunshot that proved fatal： A bitter lesson learned

有保留的 intra 心囊的外国身体的血液动力学地正常的病人的管理仍然是一件事推测。可得到的文学支持如此的无害的外国身体的非起作用的管理。我们从火器损害与一个保留的 intra 心囊的小团报导我们一个血液动力学地正常的病人的经验。他开始收到了成功的非起作用的管理，但是开发了致命的 hemopericardium 在损害以后的 21 天。在这份报纸，我们考虑到可得到的文学在如此的损害的管理讨论了陷井并且总结了临床的经验。

Varied presentations, magnitude, and outcome of traumatic neck injuries at a level I trauma center

Introduction:Traumatic neck injuries(TNIs)constitute 5%–10%of all trauma cases.These injuries can be caused by either penetrating or blunt trauma.Patients can have a varied presentation like cut injury over the neck,bleeding,neck swelling,breathing difficulty,dysphagia,etc.Methods:This was a retrospective observational study conducted at a level I trauma center in India from January 2016 to March 2020.One hundred thirty patients who required admission and intervention due to TNIs were included in this study.Results:One hundred thirty patients with neck injuries were included in this study.Males were predominant(91.5%)with the age ranging from 10 to 70years.The most common mechanism of injury was physical assault(40.7%),followed by road traffic injury(23.8%)and self-inflicted injuries(18.4%).Penetrating trauma was predominant.Open neck wound with bleeding was the most common presenting symptom.Zone II injuries were more common(83.8%)followed by zone I(12.3%)and zone III(3.8%).Soft tissue injury including skin,platysma breach,and strap muscle injury was present in 46.9% of patients.Laryngopharyngeal injury was present in 13.8%,tracheal injury in 28.5%,vascular injury in 13.8%,and esophageal injury in 4.6% of patients.Conclusion:Penetrating neck trauma is more common than blunt in developing countries like India.Advanced Trauma Life Support(ATLS)protocol guides the initial management.The definitive management depends on the type and mechanism of injury,anatomical level,severity,and the organ injured.

An overview of pancreatic trauma

Pancreatic trauma remains a challenge to a trauma surgeon even with extensive advancement in medicine.The mortality and morbidity associated with this injury remain high.A high index of suspicion,mechanism of injury,and early identification hold key in the final outcome.The management of pancreatic injury should involve a multidisciplinary team comprising of trauma surgeons,radiologists,and gastroenterologists.This review highlights the burden of the pancreatic injury and its management.