Neurotransmitter is released synchronously and asynchronously following an action potential. Our recent study indicates that the release sites of these two phases are segregated within an active ...zone, with asynchronous release sites enriched near the center in mouse hippocampal synapses. Here we demonstrate that synchronous and asynchronous release sites are aligned with AMPA receptor and NMDA receptor clusters, respectively. Computational simulations indicate that this spatial and temporal arrangement of release can lead to maximal membrane depolarization through AMPA receptors, alleviating the pore-blocking magnesium leading to greater activation of NMDA receptors. Together, these results suggest that release sites are likely organized to activate NMDA receptors efficiently.
Astrocytes, a subtype of glial cells with a complex morphological structure, are active players in many aspects of the physiology of the central nervous system (CNS). However, due to their highly ...involved interaction with other cells in the CNS, made possible by their morphological complexity, the precise mechanisms regulating astrocyte function within the CNS are still poorly understood. This knowledge gap is also due to the current limitations of existing quantitative image analysis tools that are unable to detect and analyze images of astrocyte with sufficient accuracy and efficiency. To address this need, we introduce a new deep learning framework for the automated detection of GFAP-immunolabeled astrocytes in brightfield or fluorescent micrographs. A major novelty of our approach is the applications of YOLOv5, a sophisticated deep learning platform designed for object detection, that we customized to derive optimized classification models for the task of astrocyte detection. Extensive numerical experiments using multiple image datasets show that our method performs very competitively against both conventional and state-of-the-art methods, including the case of images where astrocytes are very dense. In the spirit of reproducible research, our numerical code and annotated data are released open source and freely available to the scientific community.
Amplification of the MYCN oncogene predicts treatment resistance in childhood neuroblastoma. We used a MYC target gene signature that predicts poor neuroblastoma prognosis to identify the histone ...chaperone FACT (facilitates chromatin transcription) as a crucial mediator of the MYC signal and a therapeutic target in the disease. FACT and MYCN expression created a forward feedback loop in neuroblastoma cells that was essential for maintaining mutual high expression. FACT inhibition by the small-molecule curaxin compound CBL0137 markedly reduced tumor initiation and progression in vivo. CBL0137 exhibited strong synergy with standard chemotherapy by blocking repair of DNA damage caused by genotoxic drugs, thus creating a synthetic lethal environment in MYCN-amplified neuroblastoma cells and suggesting a treatment strategy for MYCN-driven neuroblastoma.
Background Electrolytes (sodium, potassium, calcium, magnesium, chloride, phosphate) are required in specific amounts for proper functioning of the human body. Although the body has different organ ...systems, such as the kidneys, that regulate electrolyte levels in the blood, electrolyte abnormalities occur frequently in people with eating disorders. The objective of this review will be to examine the association between electrolyte imbalances and adverse outcomes in people with eating disorders. Methods A systematic review of studies on eating and electrolyte disorders shall be conducted. Electronic searches shall be done in the Ovid MEDLINE, EMBASE, and PsycINFO databases. Selected studies shall include randomized control trials (RCTs), non-randomized controlled trials, and cross-sectional studies published in English or French. Quality appraisal of studies and a narrative synthesis of extracted data shall be conducted. Discussion This review will synthesize existing evidence on electrolyte abnormalities in people with eating disorders. It will identify the type of electrolyte imbalances, their impact, and outcomes in people with eating disorders. We anticipate that information that will be useful to policy makers and clinicians in designing better policies to prevent eating disorders and or manage people with eating disorders shall be elucidated in this study. Dissemination The final manuscript will be submitted for publication in a journal. Review registration This protocol has been registered with the International Prospective Register of Systematic Reviews (PROSPERO); registration number CRD42023477497.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The article seeks to compare and contrast the critical canon based on transvestism with deliberations upon androgyny. The postmodern approach explores the liminal spaces in Shakespearian dramaturgy ...where rigid, hide-bound compartmentalization of dichotomies in gender fuse with a fluid, liminal space of hybrid interface. The earlier readings of misogyny and chauvinism into Shakespearian heroines’ assumption of the male identity open vistas in the liminal space where these characters are conferred a privilege to navigate spaces beyond conventional fixities. By subjecting gender binaries to artistic rendition and critical canon, Shakespearian dramas offer insight into the socio-political debate around gender roles and responsibilities. By breaking free with the status quo, Shakespeare's female protagonists emerge more empowered and emancipated in their deft handling of crisis where cross-dressing only serves as an expedient measure to earn them the requisite mobility to the echelons of power. On the other hand, it is on account of their intellectual acumen that poised on a critical juncture they are able to trigger a denouement of the dramatic complication.
Pneumonia remains a global health threat, in part due to expanding categories of susceptible individuals and increasing prevalence of antibiotic resistant pathogens. However, therapeutic stimulation ...of the lungs' mucosal defenses by inhaled exposure to a synergistic combination of Toll-like receptor (TLR) agonists known as Pam2-ODN promotes mouse survival of pneumonia caused by a wide array of pathogens. This inducible resistance to pneumonia relies on intact lung epithelial TLR signaling, and inducible protection against viral pathogens has recently been shown to require increased production of epithelial reactive oxygen species (ROS) from multiple epithelial ROS generators. To determine whether similar mechanisms contribute to inducible antibacterial responses, the current work investigates the role of ROS in therapeutically-stimulated protection against Pseudomonas aerugnosa challenges. Inhaled Pam2-ODN treatment one day before infection prevented hemorrhagic lung cytotoxicity and mouse death in a manner that correlated with reduction in bacterial burden. The bacterial killing effect of Pam2-ODN was recapitulated in isolated mouse and human lung epithelial cells, and the protection correlated with inducible epithelial generation of ROS. Scavenging or targeted blockade of ROS production from either dual oxidase or mitochondrial sources resulted in near complete loss of Pam2-ODN-induced bacterial killing, whereas deficiency of induced antimicrobial peptides had little effect. These findings support a central role for multisource epithelial ROS in inducible resistance against a bacterial pathogen and provide mechanistic insights into means to protect vulnerable patients against lethal infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BackgroundEquity, diversity and inclusion (EDI) in the healthcare field are crucial in meeting the healthcare needs of a progressively diverse society. In fact, a diverse healthcare workforce enables ...culturally sensitive care, promotes health equity and enhances the understanding of various needs and patients’ viewpoints, potentially resulting in more effective patient treatment and improved patient outcomes. Despite this, information on the effectiveness of policies or programmes promoting EDI in health institutions is scarce. The objective of this systematic review is to assess the effects and outcomes of EDI programmes in healthcare institutions.MethodsWe will conduct Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of studies on EDI programmes and describe their effects and outcomes in healthcare institutions. We will search PubMed, Scopus, Web of Science, CINAHL and PsycINFO databases. Selected studies will include randomised control trials (RCTs), non-RCTs and cross-sectional studies published either in English or French. Quality appraisal of studies and a narrative synthesis of extracted data will be conducted as well as a meta-analysis if possible. The quality of evidence in this review will be assessed by the Grades of Recommendation, Assessment, Development and Evaluation.Anticipated resultsWe anticipate that this systematic review will reveal information on the effect of EDI programmes and their outcomes in healthcare institutions. We expect this information will provide insights that will lead to improvements in designing EDI policies and programmes in healthcare institutions.Ethics and disseminationNo ethical clearance is required for this study as no primary data will be collected. The final manuscript will be submitted to a journal for publication. In addition to this, the results of the study will also be disseminated through conference presentations to inform the research and clinical practice.Review registrationThis protocol has been registered with the International Prospective Register of Systematic Reviews; registration number CRD42024502781.
The case report describes a patient with stage IV breast cancer which metastasized to the lungs. The patient's initial computed tomography (CT) scan revealed a malignant lesion in the upper outer ...quadrant of the left breast and multiple pulmonary nodules, suggesting pulmonary metastasis. After starting palliative chemotherapy with intravenous paclitaxel and subcutaneous injections of Herceptin, a follow-up CT scan 3 months after the initiation of treatment showed the disappearance of metastasis, and her cancer regressed to stage II breast cancer that could be surgically resected. This case report highlights the importance of timely and appropriate palliative treatment measures, which can lead to unexpected outcomes, such as the regression of metastatic lesions and the possibility of curative treatment in such advanced cancer.
Rumi's works have been characterized by a profound philosophical thrust. Widely translated, Rumi happens to be the most sought after poet in the English language. Coleman Barks, R. A. Nicholson, A.J. ...Arberry and Annemarie Schimmel have contributed to the enduring presence of Rumi in the English literary canon through their meticulous translations. Nevit O. Ergin and Will Johnson's translation, The Rubais of Rumi stands out by treating Rumi's evocative metrical composition, Rubai; a four-line stanza with literary dexterity. The prolific works of Rumi; whether the 23-volume magnum opus titled ‘Divan-i-Kabir, the 1700 Rubais, or the Mathnawi which has been referred to as a divine scripture in Persian language have opened new vistas of critical inquiry into the field of hermeneutics. The succinct, anaphoric and at times epigrammatic style belies the unfathomable depth that lies within the verses. Hence the vast diametrical stretches of his works embrace existential matters at one level; and the esoteric ones as spiritual dynamism and jurisprudence at another level.
Chikungunya is an infection caused by the Chikungunya virus and transmitted by the bite of infected mosquito. The most common symptoms of Chikungunya virus infection are fever, joint pain or rash. ...Chikungunya virus outbreaks had been identified in countries in Africa, Asia, Europe, and the Indian and Pacific Oceans. In late 2013, the first local transmission of Chikungunya virus in the Americas was identified in Caribbean countries and territories. Chikungunya virus disease became a nationally notifiable condition in 2015. There is a threat that Chikungunya will continue to spread to new areas in the Americas.
We describe 5 patients who presented to our hospital with Chikungunya infection, shortly after returning from endemic areas. Fever and travel history to endemic areas were documented in all of our cases. Skin rash, arthralgia and contact history were also reported by these patients. Persons with suspected Chikungunya infection should be counseled to avoid mosquito bites during illness to decrease the risk of local transmission. The transmitting mosquitos are present in the US, and limiting the viral spread is essential. In this report, we describe the clinical presentation, risk factors and laboratory tests of each patient, and attempt to ensure awareness on the risk of potential spread of the disease.
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