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The planned missions to the Moon and Mars will present more significant health challenges to astronauts compared to low earth orbit missions. During deep space missions, astronauts will be constantly exposed to Space radiation (SR). Multiple rodent studies suggest that < 25 cGy of SR impairs performance in executive functions, which play a key role in advanced cognitive processes, but also regulate response inhibition and impulse control. There is the possibility that SR exposure may exacerbate aberrant behaviors evoked by psychological stress related to exposure to isolated and confined (ICE) hostile environment or independently induce additional aberrant behaviors. This study has determined that female Wistar rats exposed to 10 cGy of 250 MeV/n He had an increased risk taking propensity (RTP)\compared to shams. The increased RTP of the He-exposed rats was associated with significantly increased reaction times during the trials, suggesting a SR-induced loss of processing speed. The response times of the He-exposed rats were even further reduced in trials that immediately followed a loss, raising the possibility that conflict and interference avoidance may be impaired after SR exposure. Whether these findings occur following other types of SR exposure, and/or in male rats remains to be determined., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare in relation to the studies reported in this manuscript., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: The authors declare no conflict of interest. Both authors contributed equally.

Introduction: Terson syndrome is characterized by intraocular hemorrhage, which includes retinal, subretinal, subhyaloid, and vitreous hemorrhages, typically associated with sub-arachnoid, intracerebral, and traumatic brain injuries. The incidence of Terson syndrome varies significantly, ranging from 10 to 40% following sub-arachnoid hemorrhage., Case Presentation: A 48-year-old woman presented to the emergency department with a loss of consciousness for 1 h, 8 h prior to presentation, accompanied by teeth clenching, upward rolling of eyes, and frothing from the mouth. A non-contrast-enhanced computed tomography scan of the head revealed sub-arachnoid hemorrhage. Two days post-admission, the patient experienced decreased vision. Visual acuity tests showed significant impairment, and fundus examination revealed vitreous hemorrhage in both eyes. Digital subtraction angiography identified an aneurysm in the V4 segment of the left vertebral artery. Following flow diverter placement, the patient's visual acuity improved and normalized after 21 days., Discussion: Terson syndrome is often linked with sub-arachnoid hemorrhage due to elevated intracranial pressure. It frequently occurs with aneurysms of the anterior communicating or internal carotid arteries. Diagnosis is often delayed until after patient stabilization. Ophthalmic evaluations, such as fundoscopic examinations and ocular ultrasonography, are crucial for early detection. The presence of Terson Syndrome correlates with higher mortality rates in SAH patients. While spontaneous resolution of intraocular hemorrhage is common, some cases necessitate surgical intervention for quicker recovery., Conclusion: Comprehensive ophthalmic assessments in sub-arachnoid hemorrhage patients are essential for early detection and intervention, potentially preventing long-term visual impairment., Competing Interests: The authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Susceptibility-weighted imaging (SWI) can help in the diagnosis of thrombus within the vessel in acute ischemic stroke, known as susceptibility vessel sign (SVS), and detection of SVS within the vessel can predict treatment modality and outcome. In this study, the purpose is to correlate the SVS on SWI with different parameters of stroke., Methods: This prospective cross-sectional study enrolled consecutive stroke patients with vessel occlusion on magnetic resonance angiography (MRA) over 1 year. The relationship between SVS on SWI with risk factors, territory involved, and length of thrombus was correlated with the National Institutes of Health Stroke Scale (NIHSS)., Results: A total of 105 patients were enrolled in this study. Sixty-two percent (66 out of 105) of patients showed SVS on SWI with MRA-positive occlusion. A positive correlation was observed between SVS on SWI and the risk factor ( p  = 0.003, chi-square test), with 86% of patients with heart disease and 47% with hypertension exhibiting SVS. Additionally, a positive correlation was observed between SVS on SWI and territorial occlusion ( p  = 0.000, chi-square test). A moderate positive correlation was observed between the NIHSS and thrombus length ( p  = 0.002, Pearson's correlation coefficient), with a Pearson's coefficient of 0.367., Conclusions: SWI can be useful in identifying the location of the thrombus, and NIHSS can determine the thrombus length in acute stroke. A higher incidence of SVS can be associated with risk factors, and it also depends upon the site of occlusion of the vessel., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

Flocking behavior is observed in biological systems from the cellular to superorganismal length scales, and the mechanisms and purposes of this behavior are objects of intense interest. In this paper, we study the collective dynamics of bovine sperm cells in a viscoelastic fluid. These cells appear not to spontaneously flock, but transition into a long-lived flocking phase after being exposed to a transient ordering pulse of fluid flow. Surprisingly, this induced flocking phase has many qualitative similarities with the spontaneous polar flocking phases predicted by Toner-Tu theory, such as anisotropic giant number fluctuations and nontrivial transverse density correlations, despite the induced nature of the phase and the clearly important role of momentum conservation between the swimmers and the surrounding fluid in these experiments. We also find a self-organized global vortex state of the sperm cells, and map out an experimental phase diagram of states of collective motion as a function of cell density and motility statistics. We compare our experiments with a parameter-matched computational model of persistently turning active particles and find that the experimental order-disorder phase boundary as a function of cell density and persistence time can be approximately predicted from measures of single-cell properties. Our results may have implications for the evaluation of sample fertility by studying the collective phase behavior of dense groups of swimming sperm.

Introduction: Carotid cavernous fistulas are uncommon vascular abnormalities marked by anomalous connections between the carotid artery and the cavernous sinus. The authors present a case of a direct carotid cavernous fistula and its successful treatment in a 42-year-old female., Case Presentation: A 42-year-old female presented with right eye painful swelling and visual disturbance. She had no known comorbidities or history of injury. Examination showed proptosis, chemosis, and orbital bruit. Carotid angiography confirmed a carotid cavernous fistula, which was managed endovascularly. The patient fully recovered after treatment., Discussion: Carotid cavernous fistula occurs spontaneously or as a result of trauma or other vascular abnormalities. Common clinical manifestations include proptosis, chemosis, and orbital bruit, with vision loss being a feared complication. Diagnosis is typically confirmed through angiography, with digital subtraction angiography being the gold standard. Endovascular treatment is usually effective, although surgical management may be necessary in certain cases., Conclusion: Carotid cavernous fistula is a rare but potentially sight-threatening neurological condition. Treatment with a transvenous approach is effective for the management of direct carotid cavernous fistula., Competing Interests: The authors report no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Meat- and seafood products close to their expiry date (MSPCED) are one of the significant contributors to the growing food waste. Therefore, this study aims to investigate consumers' attitudes and willingness to buy MSPCED., Methods: An online questionnaire was used to collect data from 400 Danish consumers., Results and Discussion: Three consumer segments were identified based on their willingness to buy MSPCED: 39.8% of the participants showed a high willingness to buy MSPCED close to their expiry date ("All High"), 34.5% were selective with a high willingness to buy meat close to their expiry date but not seafood ("High meat, low seafood"), while 25.7% showed a low willingness to buy MSPCED ("All Low"). Consumers' willingness to buy MSPCED is influenced by the perceived quality of the products, food safety, social acceptability, and price. Consumers were willing to pay a higher price for minced beef close to the expiry date when compared to cod fillets, pork cuts, and chicken breasts. However, consumers were willing to buy cod fillets with the lowest discount percentage when compared to pork cuts, minced beef, and chicken breast. The findings suggest that price reduction and discount percentage can have varying effects in influencing willingness to pay for MSPCED. This study provides valuable insights, for food waste practitioners in the retail sector, to develop effective strategies for reducing food waste by influencing consumer willingness to buy and pay for perishable products like meat and seafood., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pandey, Bohl, Favari, Mora, Phuyal, Sojková, Budhathoki and Thomsen.)

Competing Interests: We declare no competing interests.

Background Moyamoya disease (MMD) can be a major cause of hemorrhagic stroke. Though extensive angiographic studies have been undertaken, the understanding of the association between aneurysms and MMD remains unanswered. In this study, we explore the association of the aneurysm with MMD and its management. We have also reviewed such associations described in the literature and how the present cases differ from those previously described. Materials and methods The clinical and radiologic data of moyamoya disease cases were accessed from medical and radiological records between January 2010 and July 2017. Two neuroradiologists independently analyzed the data and imaging details. Results Out of 103 patients with MMD, eight patients (7.77%) had associated intracranial aneurysms with eleven aneurysms. Out of the 11 aneurysms, five were the tip of the basilar artery aneurysms and were the most common location for aneurysm (45.5%), followed by lenticulostriate artery, PCA perforator, and distal ACA (DACA) in the P1 PCA, P2 PCA, and P3 PCA artery aneurysms. Out of eight patients, five (62.5%) had a hemorrhage on a non-contrast computed tomography (NCCT) scan of the brain, whereas three (37.5%) had an ischemic presentation. Out of 11 aneurysms, seven aneurysms, including three basilar tip aneurysms (unruptured) and one PCA perforator (ruptured), and three saccular PCA (P1, P2, and P3) (ruptured) were treated by endovascular coiling. Follow-up angiography showed stable aneurysmal occlusion except in one basilar tip, where recurrence was observed. Conclusions MMD-intracranial aneurysm is commonly observed in patients with intracranial hemorrhage and carries a higher risk of rupture. Therefore, identification of the aneurysm is essential for management. Endovascular treatment, either with coil or glue embolization, can be a safe and effective treatment method for such aneurysms with long-term good results., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Phuyal et al.)

Mechanobiology studies the mechanisms by which cells sense and respond to physical forces, and the role of these forces in shaping cells and tissues themselves. Mechanosensing can occur at the plasma membrane, which is directly exposed to external forces, but also in the cell's interior, for example, through deformation of the nucleus. Less is known on how the function and morphology of organelles are influenced by alterations in their own mechanical properties, or by external forces. Here, we discuss recent advances on the mechanosensing and mechanotransduction of organelles, including the endoplasmic reticulum (ER), the Golgi apparatus, the endo-lysosmal system, and the mitochondria. We highlight open questions that need to be addressed to gain a broader understanding of the role of organelle mechanobiology., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A man in his early 80s presented with acute onset aphasia and right-sided weakness with an NIH Stroke Scale (NIHSS) of 17. He was last seen normal 9 hours before the presentation. MRI of the brain showed acute infarcts in the left caudate, lentiform nucleus and corona radiata. MRI angiogram (MRA) revealed an occluded left main middle cerebral artery (MCA) and an associated ipsilateral patent duplicated middle cerebral artery (DMCA). Mechanical thrombectomy (MT) was performed, and he was discharged with an NIHSS of 8. In this report, we review and discuss the challenges during the intervention of MCA occlusion in the presence of duplicated MCA, a rare anomaly., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: None

Background: With an increasing burden of stroke, it is essential to minimize the incidence of stroke and improve stroke care by emphasizing areas that bring out the maximum impact. The care situation remains unclear in the absence of a national stroke care registry and a lack of structured hospital-based data monitoring. We conducted this systematic review and meta-analysis to assess the status of stroke care in Nepal and identify areas that need dedicated improvement in stroke care., Methods: A systematic literature review was conducted to identify all studies on stroke epidemiology or stroke care published between 2000 and 2020 in Nepal. Data analysis was done with Statistical Package for Social Sciences (SPSS) and Comprehensive Meta-analysis (CMA-3)., Results: We identified 2533 studies after database searching, and 55 were included in quantitative and narrative synthesis. All analyses were done in tertiary care settings in densely populated central parts of Nepal. Ischemic stroke was more frequent (70.87%) than hemorrhagic (26.79%), and the mean age of stroke patients was 62,9 years. Mortality occurred in 16.9% (13-21.7%), thrombolysis was performed in 2.39% of patients, and no studies described thrombectomy or stroke unit care., Conclusion: The provision of stroke care in Nepal needs to catch up to international standards, and our systematic review demonstrated the need to improve access to quality stroke care. Dedicated studies on establishing stroke care units, prevention, rehabilitation, and studies on lower levels of care or remote regions are required., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like syndrome (MELAS) is a rare neurodegenerative inherited disorder that is characterized by stroke-like episodes, seizures, endocrine, and multiple system involvement. It is important to consider it as a differential diagnosis in a young patient with stroke-like episodes as it is progressive and has multiple complications., Case Presentation: A 28-year-old male presented with slurring of speech and drowsiness for 7 h. He was a diagnosed case of type 2 diabetes mellitus, Wolf-Parkinson-White syndrome, and bilateral hearing loss., Clinical Findings and Investigations: The patient had expressive aphasia with impaired fluency, repetition, and naming. After being discharged, he represented with loss of consciousness and involuntary movements of the whole body. MRI and MRS showed extension of hyperintense lesions to parieto-occipital regions from temporal regions not limited by vascular territories. MELAS was considered, which was confirmed by molecular genetic analysis. Coenzyme Q10 was used for MELAS. Insulin, Linagliptin, and levetiracetam were used for diabetes and seizures. Regular follow-up was advised to the patient.MELAS is an important syndrome to consider in any young patient presenting with unexplained stroke disorders. A high index of suspicion is needed in an appropriate clinical setting to avoid misdiagnosis., Competing Interests: No conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Our understanding of how speed and persistence of cell migration affects the growth rate and size of tumors remains incomplete. To address this, we developed a mathematical model wherein cells migrate in two-dimensional space, divide, die or intravasate into the vasculature. Exploring a wide range of speed and persistence combinations, we find that tumor growth positively correlates with increasing speed and higher persistence. As a biologically relevant example, we focused on Golgi fragmentation, a phenomenon often linked to alterations of cell migration. Golgi fragmentation was induced by depletion of Giantin, a Golgi matrix protein, the downregulation of which correlates with poor patient survival. Applying the experimentally obtained migration and invasion traits of Giantin depleted breast cancer cells to our mathematical model, we predict that loss of Giantin increases the number of intravasating cells. This prediction was validated, by showing that circulating tumor cells express significantly less Giantin than primary tumor cells. Altogether, our computational model identifies cell migration traits that regulate tumor progression and uncovers a role of Giantin in breast cancer progression., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: D.F. is an employee of Xilio Therapeutics and a former employee and a shareholder of Eli Lilly and Company. The other authors declare that they have no competing interests., (Copyright: © 2023 Ghannoum et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective  Endovascular therapy has become the mainstay of treatment of acute ischemic stroke (AIS) due to large vessel occlusion. A direct aspiration first-pass technique (ADAPT) using large bore aspiration catheters has been introduced as a rapid, simple method for achieving good revascularization and good clinical outcomes. The aim of this study was to assess the safety and efficacy of ADAPT in the treatment of AIS due to large-vessel occlusion in the Nepali patient population. Materials and Methods  Retrospective data were collected for all consecutive patients treated for AIS with ADAPT from March 2019 through January 2021 at two hospitals. Outcomes were successful revascularization (modified thrombolysis in cerebral infarction score of 2b-3), time to revascularization, procedural complications, and good clinical outcome (modified Rankin Scale score of 0 to 2) and mortality at 90 days. Statistical Analysis  Retrospective data were collected and descriptive statistics were calculated. Results  Sixty-eight patients treated for AIS with ADAPT were included. The median National Institutes of Health Stroke Scale score at presentation was 13 (IQR 10-13.25). The median time from arterial puncture to revascularization was 40 minutes (IQR 30-45). Successful revascularization was achieved in 54 patients (79.4%). No cases of symptomatic intracranial hemorrhage occurred. At 90-day follow-up, good clinical outcome was achieved in 57 patients (83.8%), and 4 patients died (5.9%). Conclusion  A direct aspiration first pass technique appears to be a fast, simple, safe, and effective method for the management of AIS in the Nepali patient population., Competing Interests: Conflict of Interest None declared., (Asian Congress of Neurological Surgeons. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Lysosome integrity is essential for cell viability, and lesions in lysosome membranes are repaired by the ESCRT machinery. Here, we describe an additional mechanism for lysosome repair that is activated independently of ESCRT recruitment. Lipidomic analyses showed increases in lysosomal phosphatidylserine and cholesterol after damage. Electron microscopy demonstrated that lysosomal membrane damage is rapidly followed by the formation of contacts with the endoplasmic reticulum (ER), which depends on the ER proteins VAPA/B. The cholesterol-binding protein ORP1L was recruited to damaged lysosomes, accompanied by cholesterol accumulation by a mechanism that required VAP-ORP1L interactions. The PtdIns 4-kinase PI4K2A rapidly produced PtdIns4P on lysosomes upon damage, and knockout of PI4K2A inhibited damage-induced accumulation of ORP1L and cholesterol and led to the failure of lysosomal membrane repair. The cholesterol-PtdIns4P transporter OSBP was also recruited upon damage, and its depletion caused lysosomal accumulation of PtdIns4P and resulted in cell death. We conclude that ER contacts are activated on damaged lysosomes in parallel to ESCRTs to provide lipids for membrane repair, and that PtdIns4P generation and removal are central in this response., (© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Twin-twin transfusion syndrome occurs in multiple gestations and involves a chronic flow of blood from one twin to another twin and is a rare entity. We present a case of 32-years-old primigravida with a twin pregnancy who presented with increasing abdominal girth inappropriate with her gestational age at 21 weeks of her pregnancy. Ultrasound findings were suggestive of twin-twin transfusion syndrome. The patient was provided with treatment options but due to polyhydramnios and short cervix, the patient went into spontaneous labour the same day with a poor pregnancy outcome. Twin-twin transfusion syndrome leads to a high rate of perinatal morbidity due to its poorly understood aetiology and difficulty in diagnosing and treatment. Early diagnosis during antenatal ultrasound is important in reducing morbidity and mortality rates., Keywords: case reports; fetoscopy; oligohydramnios; polyhydramnios; twins.

Purpose: To study the relationship of size of corpus callosum with white matter changes in the elderly population., Materials and Methods: This was a retrospective analytical cross-sectional study. The relationship between the corpus callosum and white matter changes was studied using the magnetic resonance imaging technique, where white matter changes were graded based on Fazekas grading. The Spearman rank order correlation was used to assess the relationship between the size of corpus callosum and white matter changes., Results: The whole corpus callosum (ρ = 0.165, p = 0.044) and rostrum (ρ = -0.232, p = 0.004) was significantly correlated with white matter changes based on Fazekas severity grading. Similarly, in bivariate regression analysis, white matter changes were strongly correlated with rostrum (standardized β-coefficient = -0.186, p = 0.023). While taking gender in sub-group analysis, white matter changes were significantly correlated with rostrum (ρ = -0.252, p = 0.021) and splenium (ρ = -0.229, p = 0.036) in male and with rostrum (ρ = -0.245, p = 0.048) only in female groups., Conclusions: Corpus callosum size is associated with white matter changes in the elderly population. This association can give insight into the neuropathology of diseases involving the central nervous system., Competing Interests: The authors report no conflicts of interest., (© 2022 The Authors.)

Power electronics is seeing an increase in the use of sophisticated self-learning controllers as single board computers and microcontrollers progress faster. Traditional controllers, such as PI controllers, suffer from transient instability difficulties. The duty cycle and output voltage of a DC/DC converter are not linear. Due to this non-linearity, the PI controller generates variable levels of voltage fluctuations depending on the operating region of the converter. In some cases, non-linear controllers outperform PI controllers. The non-linear model of a non-linear controller is determined by data availability. So, a self-calibrating controller that collects data and optimizes itself as the operation goes on is necessary. Iteration and oscillation can be minimized with a well-trained reinforcement learning model utilizing a non-linear policy. A boost converter's output power supply capacity changes with a change in load, due to which the maximum duty cycle limit of a converter also changes. A support vector calibrated by reinforcement learning can dynamically change the duty cycle limit of a converter under variable load. This research highlights how reinforcement learning-based non-linear controllers can improve control and efficiency over standard controllers. The proposed concept is based on a microgrid system. Simulation and experimental analysis have been conducted on how reinforcement learning-based controller works for DC-DC boost converter., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s).)

Background: Cerebral venous thrombosis (CVT) is a rare thrombotic condition which is traditionally treated with anti-coagulation therapy. Subsets of patients with severe CVT have been treated with endovascular thrombectomy (EVT). Despite the high estimated mortality associated with severe CVT, there has been only one randomized control trial done regarding safety and efficacy of EVT in severe CVT compared to standard medical management. Evidence in this area is lacking., Objective: The aim of this systematic review is to analyze all existing literature and generate robust information regarding the role of EVT in the management of patients with severe CVT., Methods: This systematic review and meta-analysis followed PRISMA guideline. PubMed, Embase, Google Scholar, and CNKI were searched for eligible studies from 2007 to 2021. Safety and efficacy of EVT were evaluated by meta-analyzing recanalization status, the good functional outcome at follow-up, recurrent CVT, new hematoma. A pooled proportion with a 95% confidence interval was derived from a meta-analysis of various outcomes (CI)., Results: A total of 33 studies comprising 610 patients treated with EVT were included for analysis which comprised one randomized control trial, one prospective study and 31 retrospective studies. Based on pooled data, 85% of patients had good functional outcome, 62% had complete recanalization, 5% had all-cause mortality, and 3% had catheter related complications. The efficacy outcomes in this analysis had a significant heterogeneity and a subgroup analysis was also done to explain these findings. The minimum time of follow up was 3 months and varied EVT techniques were used across the studies., Conclusion: This meta-analysis suggests EVT may be safe and efficacious in treating patients with severe CVT., Registration: Our protocol was registered with PROSPERO: International prospective register of systematic reviews with the registration number CRD42021254760., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Collective swimming is evident in the sperm of several mammalian species. In bull ( Bos taurus ) sperm, high viscoelasticity of the surrounding fluid induces the sperm to form dynamic clusters. Sperm within the clusters swim closely together and align in the same direction, yet the clusters are dynamic because individual sperm swim into and out of them over time. As the fluid in part of the mammalian female reproductive tract contains mucus and, consequently, is highly viscoelastic, this mechanistic clustering likely happens in vivo . Nevertheless, it has been unclear whether clustering could provide any biological benefit. Here, using a microfluidic in vitro model with viscoelastic fluid, we found that the collective swimming of bull sperm in dynamic clusters provides specific biological benefits. In static viscoelastic fluid, clustering allowed sperm to swim in a more progressive manner. When the fluid was made to flow in the range of 2.43-4.05 1/sec shear rate, clustering enhanced the ability of sperm to swim upstream. We also found that the swimming characteristics of sperm in our viscoelastic fluid could not be fully explained by the hydrodynamic model that has been developed for sperm swimming in a low-viscosity, Newtonian fluid. Overall, we found that clustered sperm swam more oriented with each other in the absence of flow, were able to swim upstream under intermediate flows, and better withstood a strong flow than individual sperm. Our results indicate that the clustering of sperm can be beneficial to sperm migrating against an opposing flow of viscoelastic fluid within the female reproductive tract., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Phuyal, Suarez and Tung.)

Cells are constantly exposed to various chemical and physical stimuli. While much has been learned about the biochemical factors that regulate secretory trafficking from the endoplasmic reticulum (ER), much less is known about whether and how this trafficking is subject to regulation by mechanical signals. Here, we show that subjecting cells to mechanical strain both induces the formation of ER exit sites (ERES) and accelerates ER-to-Golgi trafficking. We found that cells with impaired ERES function were less capable of expanding their surface area when placed under mechanical stress and were more prone to develop plasma membrane defects when subjected to stretching. Thus, coupling of ERES function to mechanotransduction appears to confer resistance of cells to mechanical stress. Furthermore, we show that the coupling of mechanotransduction to ERES formation was mediated via a previously unappreciated ER-localized pool of the small GTPase Rac1. Mechanistically, we show that Rac1 interacts with the small GTPase Sar1 to drive budding of COPII carriers and stimulates ER-to-Golgi transport. This interaction therefore represents an unprecedented link between mechanical strain and export from the ER., (© 2022 The Authors. Published under the terms of the CC BY 4.0 license.)

Objective: We aim to correlate the prevalence of symptoms of the lateral medullary syndrome (LMS) based on radiological classification., Methods: A five-year record of 41 patients diagnosed with LMS and admitted to a tertiary care center in Nepal was reviewed. We used chi-square tests to compare symptoms between rostral and caudal groups and different horizontal subtypes., Results: The subtype prevalence in the horizontal classification of LMS was large (31.7%), lateral (22%), dorsal (19.5%), typical (14.6%), and ventral (12.2%). The most common symptoms in the typical subtype of the horizontal classification were: pain/temperature loss in the contralateral body (7.3%) and dysphagia (7.3%); in the ventral subtype, swaying on the Romberg test (12.2%), dysarthria (9.8%) and dizziness (9.8%); in the dorsal subtype, headache (12.2%) and vomiting (12.2%). Whereas headache (22.2%) and lateropulsion on standing (14.6%), swaying on the Romberg test (14.6%), nausea/vomiting (14.6%) were common in the large subtype, and nausea/vomiting (19.5%) and headache (17.1%) in the lateral subtypes. Whereas, in rostrocaudal classification, the rostral subtype (61%) was more common than the caudal subtype (31%). There was no significant variation in symptoms based on the rostrocaudal classification of LMS., Conclusion: The common clinical manifestations are different for different radiological subtypes of LMS. Further comprehensive studies are essential to understand the prevalence of symptoms in different radiological subtypes and the clinical-radiologic correlation in LMS., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Shrestha et al.)

Background: There is dearth of literature on impact of age - pediatric versus adult, Suzuki staging - early versus late, and revascularization type - indirect versus direct on clinical and angiographic outcome in moyamoya disease (MMD). Hence, we intend to comprehensively evaluate factors influencing outcome in MMD following surgical revascularization., Methods: MMD patients operated at our institute from January 2011 to August 2018 were followed for an average 24 months. Primary outcomes were modified Rankin score (mRS) and stroke risk reduction. Secondary outcome was angiographic outcome score (AOS)., Results: A total of 133 patients including 37.6% adults (>18 years; n = 50) underwent 175 revascularizations - 89 direct (DR) and 86 indirect (IR) subgroups. Mean mRS scores improved in pediatric DR (P < 0.001), IR (P < 0.001), adult IR (P = 0.10), and DR (P = 0.25) subgroups. Recurrent stroke rate was similar in pediatric-DR (2.7%) and IR (7.6%, P = 0.61), and adult-DR (0%) and IR (4.1%) subgroups (P = 1.00). AOS scores improved in pediatric DR (P = 0.002) and IR (P = 0.01), and adult-DR (P = 0.02) and IR (P = 0.06) subgroups. Late-stage MMD (Suzuki IV-VI) showed better improvement in mRS scores than early-stage-Suzuki (I-III; P < 0.001). Recurrent stroke rates were similar (P = 0.26) and AOS scores improved significantly in early- and late-stage MMD (P < 0.001)., Conclusions: In pediatrics, clinical and angiographic outcome significantly improved after revascularization procedure, and in adults, angiographic improvement was more evident than clinical recovery. Late-stage Suzuki MMD patients demonstrated significantly better clinical improvement than early stage. The angiographic improvement was equivalent to early stage, irrespective of age and type of revascularization., Competing Interests: None

Objective: There is an ongoing debate regarding the benefits of using transradial access (TRA) over transfemoral access (TFA) in endovascular therapies including endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) patients. This study sought to investigate the association of TRA and TFA with procedural success, access-site complications, first-pass reperfusion (FPR), puncture-to-recanalisation (PTR) time and hemorrhagic transformation (HT) by performing a meta-analysis., Materials and Methods: PubMed, EMBASE and Scopus were searched. Studies with patients aged ≥ 18 years and head-to-head TRA vs TFA comparisons were included. Random-effects modeling was performed to obtain summary effects and forest plots were plotted to study the association of TFA with access site complications, FPR, HT, PTR time and procedural success., Results: Six studies encompassing 945 patients (347 TRA and 598 TFA) were included in the meta-analysis. Meta-analysis revealed that in AIS patients receiving EVT, TRA was significantly associated with a decreased risk of access-site complications (RR 0.17, 95% CI 0.05 0.54; p = 0.003, z = -2.957) and HT (RR 0.07, 95% CI 0.02 0.27; p < 0.0001, z = -3.8841). However, TRA was not significantly associated with procedural success (RR 0.96, 95% CI 0.90 1.01; p = 0.141, z = -1.473), FPR (RR 0.91, 95% CI 0.79 1.05; p = 0.194, z = -1.299) and PTR time (SMD -0.14, 95% CI -0.42 -0.14; p = 0.323, z = -0.989)., Conclusion: Our meta-analysis demonstrated that TRA is a safe alternative to TFA, in AIS patients receiving EVT, with significantly decreased access-site complications and HT with TRA, albeit with comparable procedural success, FPR and PTR time to TFA., Data Availability Statement: The original contributions presented in the study are included in the article/Supplementary information, further inquiries can be directed to the corresponding author., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Intracranial aneurysms (IAs) are a significant public health concern. In populations without comorbidity and a mean age of 50 years, their prevalence is up to 3.2%. An efficient method for identifying subjects at high risk of an IA is warranted to provide adequate radiological screening guidelines and effectively allocate medical resources. Artificial intelligence (AI) has received worldwide attention for its impressive performance in image-based tasks. It can serve as an adjunct to physicians in clinical settings, improving diagnostic accuracy while reducing physicians' workload. AI can perform tasks such as pattern recognition, object identification, and problem resolution with human-like intelligence. Based on the data collected for training, AI can assist in decisions in a semi-autonomous manner. Similarly, AI can identify a likely diagnosis and also, select a suitable treatment based on health records or imaging data without any explicit programming (instruction set). Aneurysm rupture prediction is the holy grail of prediction modeling. AI can significantly improve rupture prediction, saving lives and limbs in the process. Nowadays, deep learning (DL) has shown significant potential in accurately detecting lesions on medical imaging and has reached, or perhaps surpassed, an expert-level of diagnosis. This is the first step to accurately diagnose UIAs with increased computational radiomicis. This will not only allow diagnosis but also suggest a treatment course. In the future, we will see an increasing role of AI in both the diagnosis and management of IAs., Competing Interests: JK is employed by VeeOne Health. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marasini, Shrestha, Phuyal, Zaidat and Kalia.)

Epistaxis is a common otorhinolaryngology emergency. There are several treatment modalities for epistaxis, but bleeding from the internal carotid artery necessitates a particular treatment technique. We report a case of a 22-years old man who presented to us recurrent episodes of epistaxis and blurry vision in the right eye for one month. The patient had undergone maxillo-facial surgery following a road traffic accident one year back. Bleeding episodes were occasionally severe with blood loss of up to 800 to 1000ml. These episodes were managed conservatively with posterior nasal packing and frequent blood transfusions. A computed tomography-angiography revealed a pseudoaneurysm arising from the cavernous segment of the right internal carotid artery which was managed successfully by embolization of the aneurysm sac with coils. Despite the rarity of internal carotid artery pseudoaneurysm in individuals with a history of trauma, doctors must be aware of the possibility. Timely identification and treatment of a pseudoaneurysm can save a person's life.

The HIV-protease inhibitor nelfinavir has shown broad anticancer activity in various preclinical and clinical contexts. In patients with advanced, proteasome inhibitor (PI)-refractory multiple myeloma, nelfinavir-based therapy resulted in 65% partial response or better, suggesting that this may be a highly active chemotherapeutic option in this setting. The broad anticancer mechanism of action of nelfinavir implies that it interferes with fundamental aspects of cancer cell biology. We combined proteome-wide affinity-purification of nelfinavir-interacting proteins with genome-wide CRISPR/Cas9-based screening to identify protein partners that interact with nelfinavir in an activity-dependent manner alongside candidate genetic contributors affecting nelfinavir cytotoxicity. Nelfinavir had multiple activity-specific binding partners embedded in lipid bilayers of mitochondria and the endoplasmic reticulum. Nelfinavir affected the fluidity and composition of lipid-rich membranes, disrupted mitochondrial respiration, blocked vesicular transport, and affected the function of membrane-embedded drug efflux transporter ABCB1, triggering the integrated stress response. Sensitivity to nelfinavir was dependent on ADIPOR2, which maintains membrane fluidity by promoting fatty acid desaturation and incorporation into phospholipids. Supplementation with fatty acids prevented the nelfinavir-induced effect on mitochondrial metabolism, drug-efflux transporters, and stress-response activation. Conversely, depletion of fatty acids/cholesterol pools by the FDA-approved drug ezetimibe showed a synergistic anticancer activity with nelfinavir in vitro . These results identify the modification of lipid-rich membranes by nelfinavir as a novel mechanism of action to achieve broad anticancer activity, which may be suitable for the treatment of PI-refractory multiple myeloma. SIGNIFICANCE: Nelfinavir induces lipid bilayer stress in cellular organelles that disrupts mitochondrial respiration and transmembrane protein transport, resulting in broad anticancer activity via metabolic rewiring and activation of the unfolded protein response., (©2021 The Authors; Published by the American Association for Cancer Research.)

Export from the ER is COPII-dependent. However, there is disagreement on the nature of the cargo-containing carriers that exit the ER. Two new studies from Shomron et al. (2021. J. Cell Biol.https://doi.org/10.1083/jcb.201907224) and Weigel et al. (2021. Cell. https://doi.org/10.1016/j.cell.2021.03.035) present a new model, where COPII helps to select secretory cargo but does not coat the carriers leaving the ER., (© 2021 Phuyal and Farhan.)

There is little in vitro data available on long-term effects of TiO 2 exposure. Such data are important for improving the understanding of underlying mechanisms of adverse health effects of TiO 2 . Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm 2 ) of TiO 2 for 13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO 2 exposure increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several lipid classes involved in cellular stress and apoptosis. These findings were further supported by quantitative proteome profiling data showing an increase in proteins involved in cell stress and genomic maintenance pathways following TiO 2 exposure. Altogether, we suggest that cell stress response and cell death pathways may be important molecular events in long-term health effects of TiO 2 .

Background: Stroke related studies in Nepal are primarily hospital-based and mainly from the capital city., Objectives: We aimed to estimate the prevalence of stroke and stroke risk factors in the South-Western community of Nepal., Methods: A cross-sectional study was conducted from May to August 2018 among 549 randomly selected Nepalese participants from diverse ethnicity, aged ≥15 years, in a region with the availability of neurological support facilities. Data were collected using a stroke questionnaire designed for the purpose. Stroke was identified by enumerators using the Balance-Eyes-Face-Arms-Speech-Time (BEFAST) scale, and a senior neurologist confirmed it. We assessed the presence of major risk factors associated with stroke., Results: The crude and age-standardised prevalence of stroke were 2368 and 2967 per 100,000 respectively. Of all the surveyed participants, 61% (n=335) reported consumption of full-fat dairy products >3 days per week, 87.6% (n=481) reported a high intake of salt (>5 g/day), 83.6% (n=459) with a low intake of fruits and vegetables (<400 g/day), 45.2% (n=248) with perceived stress related to work or home, 51.6% (n=283) with financial stress (283, 51.6%), 86.7% (n=457) with low high-density lipoprotein, 96.2% (n=507) with high blood urea nitrogen, 47.1% (n=356) were either overweight or obese 20.4% (n=112) with hypertension and 6.2% (n=34) with diabetes., Conclusions: The prevalence of stroke in the community of the South-Western part of Nepal is relatively higher than that estimated in South-Asia and global context. Our findings suggest an urgent community intervention, particularly with healthy lifestyles changes for future stroke prevention in the high-risk group., Competing Interests: Declaration of Competing Interest The authors declared no conflict of interest concerning the research, authorship, and/or publication of this article, (Copyright © 2021 Elsevier Inc. All rights reserved.)

The COVID-19 pandemic has significantly affected health care delivery globally. COVID-19 is associated with varied neurological manifestations including acute ischemic stroke. In densely populated South Asian nations like Nepal that have suboptimal baseline health care systems, we foresee unique challenges during this pandemic to ensure effective stroke management as well as the safety of health care workers involved in the management of stroke patients. Keywords: COVID-19; health care workers; safety; stroke management.

Objectives: The main objective of this study is to identify the prevalence of hearing loss in school aged children of Nepal., Methods: This cross-sectional study was carried out on school aged children attending the government run schools of Nepal. A total of 79,340 children from grades 1 through 10 were included in the study. After taking brief history about ear diseases and hearing loss, children were screened for ear diseases in their respective classroom by otoscope. Hearing evaluation was carried out by pure tone audiometer and hearing threshold was obtained at 0.5-4 kHz. The results were then documented and analyzed., Results: The prevalence of hearing impairment in school aged children in Nepal is found to be 5.73% (4551 of 79,340). Conductive hearing loss was the most common type of hearing loss and was observed in 70.47% (n = 3207) of the children., Conclusions: This study shows that hearing loss is a common problem in children of Nepal. With the main cause of hearing loss due to preventable conditions such as chronic otitis media, it is believed that early standardized screening, detection and timely management of chronic otitis media in these children can prevent hearing loss and its impact on their educational, social and language development. School based ear health programs are a useful community-oriented solution for prevention of deafness. It shows how important it is to introduce hearing screening for primary school aged children to prevent hearing loss., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The presence of wax is a common finding during ear examination of children and it is one of the main causes of avoidable hearing impairment in children. The objective of this study was to find out the prevalence of wax in ear and evaluate the hearing loss in school-aged children. This is a cross sectional school-based study conducted over a four-year period. Children aged 5-16 were examined by otoscope and pure tone hearing thresholds were obtained at 0.5, 1, 2, and 4 kHz frequencies. A total of 53,970 children from 312 schools of Kathmandu valley were screened. The prevalence of ear wax was 34.64% (n=18697) and hearing impairment associated with wax was 0.88% (n=475). Ear wax and associated hearing loss is a common problem in Nepalese children. Lack of trained personnel and the costs involved in its treatment makes ear wax a big challenge for Nepal's rudimentary health care system., Competing Interests: None

Scientific research can act as the 'bedrock for development' which can provide a solid foundation for the overall socioeconomic transformation in a country through invention and innovation. The inclusion of seven groups of Nepalese monuments in the United Nations Educational, Scientific and Cultural Organization (UNESCO)'s world heritage sites provides evidence of the richness in architecture and civil engineering in the country, which also show how Nepal was influenced by arts and religious philosophy. The government of Nepal (GoN) has established different scientific departments, universities, and research institutions, and has tried to emphasize the application of science and research for the development of the nation. These institutions, however, have inadequate resources, exist in a poor academic and research environment and are subject to overt political influence. Despite these various problems, a variety of pioneer research and development activities have been conducted, which show positive rays of hope. This review presents history, current situation, progress and future perspective for scientific research and development in Nepal., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors.)

Posterior fossa arteriovenous malformations represent 7-15% of all intracranial AVMs. They carry a higher risk of rupture than supratentorial AVMs and are associated with considerable rates of morbidity and mortality. Available treatment options include conservative management, microsurgical resection, radiosurgery, endovascular embolization, or combinations of these modalities. Recent advances in endovascular techniques have revolutionized their management with better clinical outcomes. We illustrate two cases of posterior fossa AVMs treated by endovascular techniques with good clinical outcomes. The first patient also had associated flow-related aneurysms. One of these aneurysms had already ruptured, so it was coiled first followed by AVM nidus embolization using the same microcatheter. The second patient had a diffuse type of posterior fossa AVM for which staged-embolization was planned and the first-stage partial embolization was successfully performed.

Objectives: The main objective of the study was to ascertain the prevalence of chronic otitis media and determine the corresponding hearing loss in children from Nepal's Himalayan region now residing in Buddhist Monastic schools of Nepal., Methods: The study was conducted among children at Buddhist monastic school in different parts of Nepal. A total of 3174 children aged between 5 and 15 years, who were originally from the Himalayan region of Nepal and were currently residing in monastic schools, were screened for ear problems and hearing loss. They were examined by otoscope to diagnose chronic otitis media. Hearing was evaluated by pure tone audiometer, and 0.5-4 kHz air conduction hearing threshold was measured and documented., Results: Of the total of 3174 children who were screened for ear diseases and hearing loss, monks constituted 76.21% (n = 2419) and Nuns 23.78% (n = 755). Chronic otitis media was the most common otoscopic finding during the screening, and it affected a total of 344 (10.83%) children. Out of these 344, hearing loss of varying degrees was observed in 5.42% (n = 172) children., Conclusion: There is high prevalence of chronic otitis media in children belonging to the Himalayan region of Nepal, and it is the main cause of avoidable hearing loss. Timely diagnosis and treatment of chronic otitis media could prevent unnecessary hearing loss in these children., Competing Interests: None., (© 2020 PLA General Hospital Department of Otolaryngology Head and Neck Surgery. Production and hosting by Elsevier (Singapore) Pte Ltd.)

Giant intracranial aneurysms are defined as aneurysms that measure over 25 mm in the greatest dimension. They are rare vascular lesions that preferentially involve regions with high-velocity blood flow, such as the cavernous and supraclinoid segments of the internal carotid artery, the middle cerebral artery, the vertebrobasilar region, and the basilar apex. The treatment of giant aneurysms is challenging and associated with high rates of morbidity and mortality. Flow-diverter devices have revolutionized their treatment in recent times. We report the successful management of two patients with giant cavernous internal carotid artery aneurysms using flow-diverter devices for the first time in Nepal. Keywords: Endovascular; flow-diverter devices; giant aneurysm.