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Sodium valproate is used for the management of seizures, status epilepticus, chronic pain syndrome, bipolar, and other affective disorders. Even with an acceptable safety profile, severe idiosyncratic reactions can occur with valproate use. A rare, serious, and life-threatening side effect of valproate is valproate-induced hyperammonemic encephalopathy (VHE). We intend to analyze the clinical presentation, diagnosis, treatment options, and outcome of VHE in neurosurgical patients and review the pertinent literature on this rare sequelae. We retrospectively reviewed patients who developed VHE following valproate use, either for the treatment of epilepsy or for seizure prophylaxis in our centre. We analyzed the demographic details, clinical presentation, diagnosis, management, and outcomes. A total of four patients with a mean age of 26.3 ± 5.1 (range 19 - 32 years). Valproate was prescribed for primary seizure prophylaxis in 2 patients (50%). The commonest etiology for valproate prescription was for brain tumors (3, 75%) followed by drug-refractory epilepsy (DRE) (1, 25%). None of the patients were documented to have urea cycle disorder. The mean daily prescribed dosage of valproate was 1250 ± 559 mg and the mean duration of administration was 13 ± 13.3 months (range 4 months - 36 months). The mean serum NH3 level was 136,5 ± 44.2 µmol/L (range 107 - 212.8) and all patients (4, 100%) had hyperammonemia with a mortality rate of 50% (2 patients). The hyperammonemia was treated by stopping the valproate use (4, 100%) and dialysis (2, 50%). Normalization of ammonia levels led to clinical improvement in 50% (2 patients). Neurological deterioration in the postoperative period is a diagnostic challenge. VHE is a rare and life-threatening sequelae of Valproate-associated Hyperammonemia (VAH) in neurosurgical patients. A high index of suspicion is required due to its ambiguous presentation. Early diagnosis and prompt treatment can change the course of this life-threatening sequelae., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Astroblastoma, a unique entity of glial tumor, predominantly occur in young women with distinctive MN1 rearrangement, Given its limited documentation in existing literature, we report eight cases of astroblastoma, detailing their clinical, radiological, and histopathological characteristics along with molecular analysis. We conducted a retrospective analysis of our neuropathology archive database spanning the past 8 years. We included all cases that underwent Magnetic Resonance Imaging (MRI), surgical resection, histopathological examination, molecular testing, and follow-up. Histopathological examination involving immunohistochemistry and Fluorescence In Situ Hybridization (FISH) was carried out for all cases. All tumors were found to be located in the supratentorial region (cerebral hemisphere). The median age of the group was 35.1 years, with a female-to-male ratio of 1.6:1. The most common clinical presentation was headache. Morphologically, all tumors exhibited astroblastic features with pseudorosettes and perivascular hyalinization. Immunohistochemistry consistently revealed positivity for EMA and variable immunoreactivity for GFAP, OLIG2, and D2-40. Fluorescence In Situ Hybridization (FISH) analysis conducted for all cases showed MN1 rearrangement in 7 cases. The mean follow-up period was 45 months (ranging from 12 to 105 months). Radiotherapy was administered for high-grade and recurrent astroblastomas. All patients are currently alive and in good health. Astroblastomas are uncommon central nervous system (CNS) tumors with characteristics morphology and molecular signatures. They typically carry a favorable prognosis. High level suspicion is required for their diagnosis and molecular analysis is must to distinguish them from other morphological mimics., Competing Interests: Declaration of Competing Interest There are no declaration of interest from the authors, (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: A glaring gender inequality persists in global neurosurgery, influenced by various factors, including the notion that female neurosurgeons have lower academic output. This study aims to compare the research output of female and male neurosurgeons at the leading academic institutions in India., Methods: The pertinent details regarding female neurosurgeons were collected from the Neurological Society of India (NSI) and Women In Neurosurgery (India) database. The institutes with at least five neurosurgery faculty recognised by the Medical Council of India (MCI) were included in the study. Various bibliometric parameters of male and female faculty at these academic centres were collected and compared using PubMed and Web of Science databases., Results: Among the 2643 neurosurgeons in NSI, 113 were females (4.27%). Out of 156 faculty members across eighteen academic institutions, only seven (4.7%) were female, with eleven institutions lacking female faculty. Female academic neurosurgeons had slightly higher h-index (9.57 vs. 9.56), citation per publication (8.82 vs. 8.54), and original article percentage (47.5 vs. 46.5) compared to males. They also had more citations per year (34.01 vs. 33.17), while males had more total publications (51.19 vs. 46.71) and citations (565.22 vs. 533.57), but these differences weren't statistically significant. Only 4.1% (327/7955) of neurosurgery research was contributed by females. Female neurosurgeons authored articles received 3735 citations (4.2%) out of 87,953 total citations., Conclusion: Female academic neurosurgeons in India exhibit comparable or superior academic output compared to their male counterparts, suggesting gender equality or even superiority in certain aspects of academic performance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In this pre-specified sub-study of the POISE-3 trial, we examined the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of postoperative acute kidney injury (AKI). Altogether,7307 patients were included from 110 hospitals in 22 countries. Patients were 45 years and older, had or were at risk of atherosclerotic disease, took at least one antihypertensive medication, and were scheduled for noncardiac surgery. Hypotension-avoidance strategy: (i) target intraoperative mean arterial pressure (MAP) 80 mm Hg or over, (ii) on day of surgery and for two days after, hold renin-angiotensin-aldosterone system inhibitors and use other antihypertensives in stepwise fashion if systolic blood pressure (SBP) 130 mm Hg or more. Hypertension-avoidance strategy: (i) target intraoperative MAP 60 mm Hg or more, (ii) continue all antihypertensives before and after surgery. Primary outcome: postoperative AKI, an increase in serum creatinine concentration of either 26.5 μmol/L or more (0.3 mg/dL or more) within 48 hours of randomization or 50% or more within seven days of randomization. The hypotension-avoidance group (3654 patients) used fewer antihypertensive medications than the hypertension-avoidance group (3653 patients); specifically, 6% vs. 38% used an ACEI or ARB on the day of surgery, and 6% vs. 47% and 7% vs. 50% one and two days after surgery, respectively. Patients also spent about half as much intraoperative time with a MAP under 80 mm Hg (27 vs 60 minutes, respectively), but had little difference in average BP before or after surgery. There was no significant difference in AKI risk (15.1% vs. 14.4%). Results were consistent with other definitions of AKI and in patients with preexisting chronic kidney disease. Thus, a hypotension-avoidance strategy targeting a MAP greater than 80 mm Hg in the operating room and discontinued blood pressure medication during the perioperative period did not confer a lower risk of AKI compared to a hypertension avoidance strategy., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: This study compares the effectiveness of virtual reality simulators (VRS) and a saw bone model for learning lumbar pedicle screw insertion (LPSI) in neurosurgery., Methods: A single-center, cross-sectional, randomized controlled laboratory investigation was conducted involving residents and fellows from a tertiary care referral hospital. Participants were divided into two groups (A and B). Group A performed 3 LPSI tasks: the first on a saw bone model, the second on VRS, and the third on another saw bone model. Group B completed 2 LPSI tasks: the first on a saw bone model and the second on another saw bone model. The accuracy of LPSI was evaluated through noncontrast computed tomography scans for the saw bone models, while the in-built application of VRS was utilized to check for accuracy of screw placement using the simulator., Results: The study included 38 participants (19 in each group). Group A participants showed reduced mean entry point error (0.11 mm, P 0.024), increased mean purchase length (4.66 cm, P 0.007), and no cortical breaches (P 0.031) when placing the second saw bone model screw. Similar improvements were observed among group A participants in PGY 1-3 while placing the second saw bone model screws., Conclusions: Virtual reality simulators (VRS) prove to be an invaluable tool for teaching complex neurosurgical skills, such as LPSI, to trainees. This technology investment can enhance the learning curve while maintaining patient safety., (Copyright © 2024. Published by Elsevier Inc.)

Freshwater crabs ( Potamiscus manipuriensis ), commonly consumed as local delicacies by the native people in the state of Manipur, were found to harbour metacercariae of Microphallus sp. (Family Microphyllidae), which were morphologically different from metacercariae of Microphallus spp reported earlier from different regions. So, PCR-based molecular characterization of this metacercaria was done utilizing rDNA marker regions: larger subunit (LSU) or 28S (D1-D3 region) and inter-transcribed spacer 2 (ITS2). Sequence and phylogenetic analyses confirmed that the taxon under study belonged to family Microphyllidae of genus Microphallus ., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© Indian Society for Parasitology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

In this study, we describe a one-pot three-component synthesis of bioactive tetrahydopyrimidinecarboxamide derivatives employing lanthanum triflate as a catalyst. Out of the synthesized compounds, 4f had the most potent anti-cancer activity and impeded cell cycle progression effectively. Anti-cancer bioactivity was observed in 4f against liver, breast, and lung cancers as well as primary patient-derived glioblastoma cell lines. Compound 4f effectively inhibited the 3D neurosphere formation in primary patient-derived glioma stem cells. Specifically, 4f exhibited synergistic cytotoxicity with the EGFR inhibitor that is the clinical epidermal growth factor receptor inhibitor osimertinib. 4f does not exhibit anti-kinase activity and is cytostatic in nature, and further work is needed to understand the true molecular target of 4f and its derivatives. Through our current work, we establish a promising tetrahydopyrimidinecarboxamide-based lead compound with anti-cancer activity, which may exhibit potent anti-cancer activity in combination with specific clinically relevant small molecule kinase inhibitors., Competing Interests: DBU, JN, RMV, SB, and HMP are named inventors on the patent no. 528662 awarded by the government of India on 18th March 2024 pertaining to these reported compounds. No other conflicts of interest reported., (This journal is © The Royal Society of Chemistry.)

Remdesivir, a C-nucleotide prodrug binds to the viral RNA-dependent-RNA polymerase ( RdRp ) and inhibits the viral replication by terminating RNA transcription prematurely. It is reported in literature that interaction between the C-1'β-CN moiety of Remdesivir ( RDV ) and the Ser861 residue in RdRp enzyme, causes a delayed chain termination during the RNA replication process and is one of the important aspect of its mechanism of action. In the pursuance of increasing the biological activity of RDV and enhancing the SAR studies, against RNA viruses, we have designed its fourteen C1'β substituted analogs, 10 - 23 bearing 4/5-membered heterocyclic rings. The docking and 100 ns molecular dynamics (MD) simulations of 10 - 23 to the RdRp protein (PDB ID: 7L1F) revealed important interactions between 2',3'-diol, oxo group of phosphoramidate, nitrogen residues of heterocyclic rings of synthetic molecules with Arg555, Arg553, Ser759, Cys622, Asn691, Asp623 amino acid residues of protein. The docking score of 2-ethylbutyl ((S)-(((2R,3S,4R,5R)-5-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-3,4-dihydroxy-5-(1H-1,2,3-triazol-4-yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate, 11 was found to be the higher than RDV among 14 new compounds i.e. -5.20 kcal/mol. Out of 3 compounds, 10 , 12 and 13 submitted for MD simulations and Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis, trifluoro-oxadiazole derivative, 13 showed higher binding energy as compared to Remdesivir. The predicted ADMET properties of 14 compounds showed their potential for being drug candidates. The present study suggests that substitution at the C1'β position by 4/5-membered rings plays an important role in the interactions between nucleoside/tide and target protein., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Vibha Tandon reports financial support was provided by 10.13039/501100001843Science and Engineering Research Board. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Bael is a fruit crop that is extensively distributed throughout South-East Asia and is underutilized in medicine. The potential applications of bael's therapeutic and nutritional qualities in diverse ethnic communities are enormous. This study focuses on evaluating the morpho-pomological and molecular characteristics, utilizing SSR markers, of 80 wild bael genotypes alongside the NB-5 and NB-9 cultivars, derived from the North Western plains of India. Based on the evaluated morpho-pomological features, substantial variations were found between all genotypes. The fruit's inner diameter and pulp weight varied from 4.41 to 11.54 cm and 34.63 to 786.41 g, respectively. Numerous variations in the genotypes were observed in the shell weight/fruit, fruit skull thickness and fruit yield/plant. The bael fruit mucilage's total soluble solids (TSS) and total sugar content varied from 40.10 to 49.60 o brix and 8.11 to 21.17%, respectively. Using ward cluster analysis, the genotypes were divided into two primary clusters. Among the bael genotypes, the population structure analysis identified three subpopulations. SSR markers are used to measure genetic variety; of the 27 polymorphic markers, 17 show allelic diversity between genotypes. Molecular genetic diversity analysis, on the other hand, highlighted the genotypes genetic distinctiveness by classifying them into three major clusters. These findings offer valuable insights into the rich diversity and intricate interactions among the bael genotypes under investigation, paving the way for more strategic future breeding and selection efforts to elevate the quality of this remarkable fruit., (© 2024. The Author(s).)

Background: During the COVID-19 pandemic, a multitude of surveys have analyzed the impact virus spreading on the everyday medical practice, including neurosurgery. However, none have examined the perceptions of neurosurgeons towards the pandemic, their life changes, and the strategies they implemented to be able to deal with their patients in such a difficult time., Methods: From April 2021 to May 2021 a modified Delphi method was used to construct, pilot, and refine the questionnaire focused on the evolution of global neurosurgical practice during the pandemic. This survey was distributed among 1000 neurosurgeons; the responses were then collected and critically analyzed., Results: Outpatient department practices changed with a rapid rise in teleservices. 63.9% of respondents reported that they have changed their OT practices to emergency cases with occasional elective cases. 40.0% of respondents and 47.9% of their family members reported to have suffered from COVID-19. 56.2% of the respondents reported having felt depressed in the last 1 year. 40.9% of respondents reported having faced financial difficulties. 80.6% of the respondents found online webinars to be a good source of learning. 47.8% of respondents tried to improve their neurosurgical knowledge while 31.6% spent the extra time in research activities., Conclusions: Progressive increase in operative waiting lists, preferential use of telemedicine, reduction in tendency to complete stoppage of physical clinic services and drop in the use of PPE kits were evident. Respondents' age had an impact on how the clinical services and operative practices have evolved. Financial concerns overshadow mental health.

Non-Hodgkin's lymphoma are neoplasms derived from T cells and B cells and their precursors in the lymphoid system with higher susceptibility in involvement of extra-nodal sites. Predominant ureteric involvement is an unusual presentation. We present a case of diffuse large B-cell lymphoma with secondary involvement of ureter who had symptoms of urinary tract infection in absence of positive urine culture, non-responsive to broad spectrum antibiotics and masquerading pyogenic infection leading to pyelonephritis with ureteritis. Radiological examination revealed mass like soft tissue thickening of ureter extending from renal pelvis throughout the length of ureter. FNAC as well as biopsy from the periureteric thickening revealed lymphomatous involvement of ureter. The following case report provides insight on differentials and varied symptoms of lymphomatous involvement of ureter., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Background: Myocardial injury after a hip fracture is common and has a poor prognosis. Patients with a hip fracture and myocardial injury may benefit from accelerated surgery to remove the physiological stress associated with the hip fracture. This study aimed to determine if accelerated surgery is superior to standard care in terms of the 90-day risk of death in patients with a hip fracture who presented with an elevated cardiac biomarker/enzyme measurement at hospital arrival., Methods: The HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) trial was a randomized controlled trial designed to determine whether accelerated surgery for hip fracture was superior to standard care in reducing death or major complications. This substudy is a post-hoc analysis of 1392 patients (from the original study of 2970 patients) who had a cardiac biomarker/enzyme measurement (>99.9% had a troponin measurement and thus "troponin" is the term used throughout the paper) at hospital arrival. The primary outcome was all-cause mortality. The secondary composite outcome included all-cause mortality and non-fatal myocardial infarction, stroke, and congestive heart failure 90 days after randomization., Results: Three hundred and twenty-two (23%) of the 1392 patients had troponin elevation at hospital arrival. Among the patients with troponin elevation, the median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] = 5 to 13) in the accelerated surgery group and 29 hours (IQR = 19 to 52) in the standard care group. Patients with troponin elevation had a lower risk of mortality with accelerated surgery compared with standard care (17 [10%] of 163 versus 36 [23%] of 159; hazard ratio [HR] = 0.43 [95% confidence interval (CI) = 0.24 to 0.77]) and a lower risk of the secondary composite outcome (23 [14%] of 163 versus 47 [30%] of 159; HR = 0.43 [95% CI = 0.26 to 0.72])., Conclusions: One in 5 patients with a hip fracture presented with myocardial injury. Accelerated surgery resulted in a lower mortality risk than standard care for these patients; however, these findings need to be confirmed., Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The HIP ATTACK-1 trial was supported by the Canadian Institutes of Health Research, the Ontario Strategy for Patient Oriented Research Support Unit, the Ontario Ministry of Health and Long-Term Care, the Hamilton Health Sciences Foundation, the Physicians’ Services Incorporated Foundation, the Michael G. DeGroote Institute for Pain Research and Care, Smith & Nephew (to recruit patients in Spain), and Indiegogo Crowdfunding. This substudy received funding from a McMaster General Internal Medicine Research Grant. Funders had no role in the study design, conduct, analyses, or manuscript preparation. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJS/I117)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Surgical patients are often transfused to manage bleeding and anemia. Best practices for red blood cell (RBC) transfusion administration in patient having noncardiac surgery remains controversial and a robust evaluation and description of perioperative transfusion practices is lacking. We characterized perioperative hemoglobin concentrations and transfusion practices from the prospective VISION cohort which included 39,222 patients aged ≥45 years who had inpatient noncardiac surgery. Variations in transfusion practices were analyzed using hierarchical mixed models, and associations with mortality and complications were evaluated using a nested frailty survival model. Within the cohort, 16.1% (n = 6296) were given perioperative RBC transfusions, with the fraction declining from 20% to 13% over the 6-year study period. The proportion of patients transfused varied by surgery type from 6.4% for low-risk operations (i.e., minor surgery) to 31.5% for orthopedic surgeries. Variations were largely associated with patient hemoglobin concentrations, but also with center (range: 3.7%-27.3%) and country (0.4%-25.3%). Even after adjusting for baseline hemoglobin, comorbidities and type of surgery, both center and country were significant sources of variation in transfusion practices. Among transfused participants, 60.4% (n = 3728/6170) had at least 1 hemoglobin concentration ≤80g/L and 86.0% (n = 5305/6170) had at least 1 hemoglobin concentration ≤90g/L, suggesting that relatively restrictive transfusion strategies were used in most. The proportion of patients receiving at least 1 RBC transfusion declined from 20% to 13% over 6 years. However, there was considerable unexplained variation in transfusion practices., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Recently, World Health Organization declared antimicrobial resistance as the third greatest threat to human health. Absence of known cross-resistance, new class, new target, and a new mode of action are few major strategies being undertaken by researches to combat multidrug resistant pathogen. PPEF.3HCl, a bisbenzimidazole was developed as highly potent antibacterial agent against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens, targeting topoisomerase IA. The present work encompasses a radical on-site generation of In-situ nanosuspension of PPEF.3HCl with enhanced efficacy against methicillin resistant S. aureus in septicemia model. We have generated instantaneously a PPEF.3HCl nanosuspension (IsPPEF.3HCl-NS) by mixing optimized monophasic PPEF.3HCl preconcentrate in propylene glycol into an aqueous medium comprising tween 80 as stabilizer. The IsPPEF.3HCl-NS showed precipitation efficiency of > 90 %, average particle size < 500 nm, retained upto 5 h, a negative zeta potential and bi/trimodal particle size distribution. Differential scanning calorimetry, X-ray diffraction confirmed partial amorphization and transmission electron microscopy revealed spherical particles. IsPPEF.3HCl-NS was non-hemolytic and exhibited good stability in serum. More significantly, it exhibited a ∼ 1.6-fold increase in macrophage uptake compared to free PPEF.3HCl in the RAW 264.7 macrophage cell line. Confocal microscopy revealed accumulation of IsPPEF.3HCl-NS within the lysosomal compartment and cell cytosol, proposing high efficacy. In terms of antimicrobial efficacy, IsPPEF.3HCl-NS outperforms free PPEF.3HCl against clinical methicillin sensitive and resistant S. aureus strains. In a pivotal experiment, IsPPEF.3HCl-NS exhibited over 83 % survival at 8 mg/kg.bw and an impressive reduction of ∼ 4-5 log-fold in bacterial load, primarily in the kidney, liver and spleen of septicemia mice. IsPPEF.3HCl-NS prepared by the In-situ approach, coupled with enhanced intramacrophage delivery and superior efficacy, positions IsPPEF.3HCl-NS as a pioneering and highly promising formulation in the battle against antimicrobial resistance., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Vibha Tandon reports financial support was provided by India Ministry of Science & Technology Department of Biotechnology. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper]., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To determine timing and risk factors associated with readmission within 30 days of discharge following noncardiac surgery., Background: Hospital readmission after noncardiac surgery is costly. Data on the drivers of readmission have largely been derived from single-center studies focused on a single surgical procedure with uncertainty regarding generalizability., Methods: We undertook an international (28 centers, 14 countries) prospective cohort study of a representative sample of adults ≥45 years of age who underwent noncardiac surgery. Risk factors for readmission were assessed using Cox regression (ClinicalTrials.gov, NCT00512109)., Results: Of 36,657 eligible participants, 2744 (7.5%; 95% confidence interval [CI], 7.2-7.8) were readmitted within 30 days of discharge. Rates of readmission were highest in the first 7 days after discharge and declined over the follow-up period. Multivariable analyses demonstrated that 9 baseline characteristics (eg, cancer treatment in past 6 months; adjusted hazard ratio [HR], 1.44; 95% CI, 1.30-1.59), 5 baseline laboratory and physical measures (eg, estimated glomerular filtration rate or on dialysis; HR, 1.47; 95% CI, 1.24-1.75), 7 surgery types (eg, general surgery; HR, 1.86; 95% CI, 1.61-2.16), 5 index hospitalization events (eg, stroke; HR, 2.21; 95% CI, 1.24-3.94), and 3 other factors (eg, discharge to nursing home; HR, 1.61; 95% CI, 1.33-1.95) were associated with readmission., Conclusions: Readmission following noncardiac surgery is common (1 in 13 patients). We identified perioperative risk factors associated with 30-day readmission that can help frontline clinicians identify which patients are at the highest risk of readmission and target them for preventive measures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: This survey was conducted to explore the perceptions of undergraduate (UG) medical students regarding enrolling in a neurosurgical training program. The purpose was to understand' expectations, reasons, apprehensions, and variables influencing students' decisions to pursue a career in neurosurgery. The results shed light on students' perceptions and can help educational institutions and training programs draw in and encourage aspiring neurosurgeons., Methods: A 35-point online questionnaire was created using Google Forms (Google LLC) after content and face validation and circulated using social media platforms among various public medical colleges across India. Responses were collected over a period of 3 months, from February 2023 to April 2023. A 5-point Likert scale was used to collect the responses wherever applicable., Results: A total of 1042 respondents from 47 medical colleges completed the survey. The majority of the students were not exposed to neurosurgery during their UG program, but despite this, 60.1% (n = 627) were willing to consider it as their career option. Around 91.4% of the respondents perceived neurosurgery to be a challenging but prestigious specialty that has a long learning curve and the worst work-life balance when compared with other specialties. The majority of the respondents (strongly disagree = 24.3%, n = 253; disagree = 31.7%, n = 330) did not view neurosurgery as a male-dominated specialty. Most students preferred a 6-year training program over a 3-year program (P = 0.001) if their medical college had such a course., Conclusions: Our study reveals that although a majority of the UG students would like to join neurosurgery residency, there are significant barriers in the form of less exposure, negative perceptions, and apprehensions toward the branch. Enhancing medical students' awareness about neurosurgery necessitates the integration of hands-on workshops, simulation-based training, didactic lectures, and neurosurgery rotations into the UG curriculum., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: The objective of this study is to study the secondary structure analysis of Fasciola flukes from a rare mithun host from Manipur. Fascioliasis, a neglected tropical trematodiasis, is poorly studied in India and is widely believed to be predominantly caused by F. gigantica. Through this study, we want to assess the flukes from the rare semi-wild ruminants of Northeast India. This study is important as the mithun population is semi-wild and its population is declining in Manipur., Methods: Sample collected from the difficult and challenging terrain of Northeast India. The sample was collected from mithun and observed under the microscope. DNA was isolated, sequenced, and analyzed using various bioinformatics tools. The secondary structure analysis of the Internal Transcribed Spacer 2 (ITS2) region was also performed., Results: The secondary structure species tree corroborated the Bayesian inference and, hence, strengthened the phylogeny reconstructed. The annotated ITS2 sequence and RNA secondary of the Manipur isolate displayed the typical four-helix or four-domain model. Helix III reveals the presence of the UGGU motif with other deviations like UGG and GGU., Conclusion: This is an in-depth analysis of the secondary structure of Fasciola species. The present study has demonstrated the usefulness of ITS2 and its secondary structures for characterizing parasites. The information on fascioliasis in the mithun's population presents itself useful with regards to their conservation strategy as their populations in both Manipur and Nagaland are dwindling., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: In neurosurgical practice, continuous care after discharge and the ability to detect subtle indicators of clinical deterioration are mandatory to prevent the progression of a disease. The care of 'unknown' patients discharged to rehabilitation homes may not have this privilege, especially in resource-poor countries such as India., Objective: We have attempted to study the causes and outcomes of re-admissions of 'unknown' patients with previous traumatic brain injury (TBI) to estimate the quality of nursing care in our rehabilitation centers., Material and Methods: The electronic hospital records of all consecutive 'unknown' TBI patients with unplanned re-admissions at our institute from January 2014 to December 2018 were retrospectively reviewed and analyzed for the factors determining the risk and outcomes of re-admission., Results: Out of 245 patients sent to rehabilitation homes at discharge, 47 patients (19.18%) were re-admitted. A total of 33 patients (70%) were re-admitted between 1 month and 1 year. Out of these, 38 patients (80.9%) were re-admitted because of preventable causes. Fifteen patients (31.9%) died during the hospital stay. The rest of the 32 (68%) patients were discharged after the management of the concerned condition with an average hospital stay of 9 ± 11.1 days. The average Glasgow coma scale (GCS) at re-admission of the patients who died was 6 (range 3-11). Two patients were brought in the brain dead status, whereas 20 patients (42.6%) had a GCS of 5 or below at the time of re-admission. The risk of mortality among patients with non-preventable causes was 88.9% (8/9) compared to preventable causes 18.4% (7/38). However, preventable causes for re-admission are much more common, resulting in nearly a similar overall contribution to mortality., Conclusions: There is a high rate of mortality and morbidity in 'unknown' patients with TBI because of poor post-discharge care in developing countries. Because preventable causes are the major contributor to re-admissions, the re-admission rate is a good indicator of a lack of adequate rehabilitative services. The need for improving the post-discharge management of 'unknown' patients with TBI in resource-poor countries cannot be over-emphasized., (Copyright © 2024 Copyright: © 2024 Neurology India, Neurological Society of India.)

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV., (© 2024. The Author(s).)

Purpose of Program: A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires, and specialist consultations. Donor candidates make several trips to hospitals and clinics, and often spend months waiting for appointments and test results. The median evaluation time for a donor candidate in Ontario, Canada, is nearly 1 year. Longer wait times are associated with poorer outcomes for the kidney transplant recipient and higher health care costs. A shorter, more efficient donor evaluation process may help more patients with kidney failure receive a transplant, including a pre-emptive kidney transplant (ie, avoiding the need for dialysis). In this report, we describe the development of a quality improvement intervention to improve the efficiency, effectiveness, and patient-centeredness of the donor candidate evaluation process. We developed a One-Day Living Kidney Donor Assessment Clinic, a condensed clinic where interested donor candidates complete all testing and consultations within 1 day., Sources of Information: The One-Day Living Kidney Donor Assessment Clinic was developed after performing a comprehensive review of the literature, receiving feedback from patients who have successfully donated, and meetings with transplant program leadership from St. Joseph's Healthcare Hamilton. A multistakeholder team was formed that included health care staff from nephrology, transplant surgery, radiology, cardiology, social work, nuclear medicine, and patients with the prior lived experience of kidney donation. In the planning stages, the team met regularly to determine the objectives of the clinic, criteria for participation, clinic schedule, patient flow, and clinic metrics., Methods: Donor candidates entered the One-Day Clinic if they completed initial laboratory testing and agreed to an expedited process. If additional testing was required, it was completed on a different day. Donor candidates were reviewed by the nephrologist, transplant surgeon, and donor coordinator approximately 2 weeks after the clinic for final approval. The team continues to meet regularly to review donor feedback, discuss challenges, and brainstorm solutions., Key Findings: The One-Day Clinic was implemented in March 2019, and has now been running for 4 years, making iterative improvements through continuous patient and provider feedback. To date, we have evaluated more than 150 donor candidates in this clinic. Feedback from donors has been uniformly positive (98% of donors stated they were very satisfied with the clinic), with most noting that the clinic was efficient and minimally impacted work and family obligations. Hospital leadership, including the health care professionals from each participating department, continue to show support and collaborate to create a seamless experience for donor candidates attending the One-Day Clinic., Limitations: Clinic spots are limited, meaning some interested donor candidates may not be able to enter a One-Day Clinic the same month they come forward., Implications: This patient-centered quality improvement intervention is designed to improve the efficiency and experience of the living kidney donor evaluation, result in better outcomes for kidney transplant recipients, and potentially increase living donation. Our next step is to conduct a formal evaluation of the clinic, measuring qualitative feedback from health care professionals working in the clinic and donor candidates attending the clinic, and measuring key process and outcome measures in donor candidates who completed the one-day assessment compared with those who underwent the usual care assessment. This program evaluation will provide reliable, regionally relevant evidence that will inform transplant centers across the country as they consider incorporating a similar one-day assessment model., Competing 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) 2024.)

Objectives: This study aims to compare low-grade lytic spondylolisthesis (LS) and degenerative spondylolisthesis (DS) radiologically. In addition, it seeks to identify underlying similarities between LS and DS., Methods: This study included patients with low-grade single-level spondylolisthesis at L4-L5 or L5-S1. They were categorized into LS and DS. Radiological features, including pedicle height, width, transverse, and sagittal angle, as well as anterior vertebral heights (AVH) and posterior vertebral heights (PVH), were measured using T1-weighted magnetic resonance imaging., Results: The study involved 88 patients: 46 in the DS group and 42 in the LS group. In the LS group, the AVH was significantly higher than the posterior height at L4 and L5 (L4 PVH/AVH ratio 0.93 in LS vs. 0.96 in DS; L5 PVH/AVH ratio 0.84 in LS vs. 0.92 in DS), and pedicles were more medially oriented (L4: 19.62° in LS vs. 17.7° in DS; L5: 28.92° in LS vs. 26.47° in DS). In addition, at L5, the pedicle height (10.67 mm in LS vs. 11.48 mm in DS) and width (13.56 mm in LS vs. 14.37 mm in DS) were smaller compared to the DS group., Conclusions: Low-grade LS shows distinct radiological vertebral and pedicle anatomy compared to DS. Short and thin pedicles and wedge-shaped vertebrae in LS resemble DS, indicating its dysplastic origin., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Craniovertebral Junction and Spine.)

Background: In previous analyses, myocardial injury after noncardiac surgery, major bleeding, and sepsis were independently associated with most deaths in the 30 days after noncardiac surgery, but most of these deaths occurred during the index hospitalization for surgery. The authors set out to describe outcomes after discharge from hospital up to 1 yr after inpatient noncardiac surgery and associations between predischarge complications and postdischarge death up to 1 yr after surgery., Methods: This study was an analysis of patients discharged after inpatient noncardiac surgery in a large international prospective cohort study across 28 centers from 2007 to 2013 of patients aged 45 yr or older followed to 1 yr after surgery. The study estimated (1) the cumulative postdischarge incidence of death and other outcomes up to a year after surgery and (2) the adjusted time-varying associations between postdischarge death and predischarge complications including myocardial injury after noncardiac surgery, major bleeding, sepsis, infection without sepsis, stroke, congestive heart failure, clinically important atrial fibrillation or flutter, amputation, venous thromboembolism, and acute kidney injury managed with dialysis., Results: Among 38,898 patients discharged after surgery, the cumulative 1-yr incidence was 5.8% (95% CI, 5.5 to 6.0%) for all-cause death and 24.7% (95% CI, 24.2 to 25.1%) for all-cause hospital readmission. Predischarge complications were associated with 33.7% (95% CI, 27.2 to 40.2%) of deaths up to 30 days after discharge and 15.0% (95% CI, 12.0 to 17.9%) up to 1 yr. Most of the association with death was due to myocardial injury after noncardiac surgery (15.6% [95% CI, 9.3 to 21.9%] of deaths within 30 days, 6.4% [95% CI, 4.1 to 8.7%] within 1 yr), major bleeding (15.0% [95% CI, 8.3 to 21.7%] within 30 days, 4.7% [95% CI, 2.2 to 7.2%] within 1 yr), and sepsis (5.4% [95% CI, 2.2 to 8.6%] within 30 days, 2.1% [95% CI, 1.0 to 3.1%] within 1 yr)., Conclusions: One in 18 patients 45 yr old or older discharged after inpatient noncardiac surgery died within 1 yr, and one quarter were readmitted to the hospital. The risk of death associated with predischarge perioperative complications persists for weeks to months after discharge., (Copyright © 2023 American Society of Anesthesiologists. All Rights Reserved.)

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated., (© Journal of the Association of Physicians of India 2024.)

Objective: The objective of this study was to analyze the potential and convenience of using mixed reality as a teaching tool for craniovertebral junction (CVJ) anomaly pathoanatomy., Methods: CT and CT angiography images of 2 patients with CVJ anomalies were used to construct mixed reality models in the HoloMedicine application on the HoloLens 2 headset, resulting in four viewing stations. Twenty-two participants were randomly allocated into two groups, with each participant rotating through all stations for 90 seconds, each in a different order based on their group. At every station, objective questions evaluating the understanding of CVJ pathoanatomy were answered. At the end, subjective opinion on the user experience of mixed reality was provided using a 5-point Likert scale. The objective performance of the two viewing modes was compared, and a correlation between performance and participant experience was sought. Subjective feedback was compiled and correlated with experience., Results: In both groups, there was a significant improvement in median (interquartile range [IQR]) objective performance with mixed reality compared with DICOM: 1) group A: case 1, median 6 (IQR 6-7) versus 5 (IQR 3-6), p = 0.009; case 2, median 6 (IQR 6-7) versus 5 (IQR 3-6), p = 0.02; 2) group B: case 1, median 6 (IQR 5-7) versus 4 (IQR 2-5), p = 0.04; case 2, median 6 (IQR 6-7) versus 5 (IQR 3-7), p = 0.03. There was significantly higher improvement in less experienced participants in both groups for both cases: 1) group A: case 1, r = -0.8665, p = 0.0005; case 2, r = -0.8002, p = 0.03; 2) group B: case 1, r = -0.6977, p = 0.01; case 2, r = -0.7417, p = 0.009. Subjectively, mixed reality was easy to use, with less disorientation due to the visible background, and it was believed to be a useful teaching tool., Conclusions: Mixed reality is an effective teaching tool for CVJ pathoanatomy, particularly for young neurosurgeons and trainees. The versatility of mixed reality and the intuitiveness of the user experience offer many potential applications, including training, intraoperative guidance, patient counseling, and individualized medicine; consequently, mixed reality has the potential to transform neurosurgery.

Background: Higher levels of inflammatory biomarkers are associated with an increased risk of perioperative atrial fibrillation and myocardial injury after non-cardiac surgery (MINS). Colchicine is an anti-inflammatory drug that might reduce the incidence of these complications., Methods: COP-AF was a randomised trial conducted at 45 sites in 11 countries. Patients aged 55 years or older and undergoing major non-cardiac thoracic surgery were randomly assigned (1:1) to receive oral colchicine 0·5 mg twice daily or matching placebo, starting within 4 h before surgery and continuing for 10 days. Randomisation was done with use of a computerised, web-based system, and was stratified by centre. Health-care providers, patients, data collectors, and adjudicators were masked to treatment assignment. The coprimary outcomes were clinically important perioperative atrial fibrillation and MINS during 14 days of follow-up. The main safety outcomes were a composite of sepsis or infection, and non-infectious diarrhoea. The intention-to-treat principle was used for all analyses. This trial is registered with ClinicalTrials.gov, NCT03310125., Findings: Between Feb 14, 2018, and June 27, 2023, we enrolled 3209 patients (mean age 68 years [SD 7], 1656 [51·6%] male). Clinically important atrial fibrillation occurred in 103 (6·4%) of 1608 patients assigned to colchicine, and 120 (7·5%) of 1601 patients assigned to placebo (hazard ratio [HR] 0·85, 95% CI 0·65 to 1·10; absolute risk reduction [ARR] 1·1%, 95% CI -0·7 to 2·8; p=0·22). MINS occurred in 295 (18·3%) patients assigned to colchicine and 325 (20·3%) patients assigned to placebo (HR 0·89, 0·76 to 1·05; ARR 2·0%, -0·8 to 4·7; p=0·16). The composite outcome of sepsis or infection occurred in 103 (6·4%) patients in the colchicine group and 83 (5·2%) patients in the placebo group (HR 1·24, 0·93-1·66). Non-infectious diarrhoea was more common in the colchicine group (134 [8·3%] events) than the placebo group (38 [2·4%]; HR 3·64, 2·54-5·22)., Interpretation: In patients undergoing major non-cardiac thoracic surgery, administration of colchicine did not significantly reduce the incidence of clinically important atrial fibrillation or MINS but increased the risk of mostly benign non-infectious diarrhoea., Funding: Canadian Institutes of Health Research, Accelerating Clinical Trials Consortium, Innovation Fund of the Alternative Funding Plan for the Academic Health Sciences Centres of Ontario, Population Health Research Institute, Hamilton Health Sciences, Division of Cardiology at McMaster University, Canada; Hanela Foundation, Switzerland; and General Research Fund, Research Grants Council, Hong Kong., Competing Interests: Declaration of interests DC received research grants from the Canadian Institutes of Health Research (CIHR), speaker fees from Servier outside of the current study, and advisory board fees from Roche Diagnostics and Trimedics outside of the current study. EP is funded by a research contract (SLT017/20/000089) supported by the Department of Health of the Generalitat de Catalunya, Spain. DIS serves on advisory boards and has equity interests in Calorint, TransQtronics, the Health Data Analytics Institute, Medasense, and Perceptive Medical. DIS is the chair of the Department of Outcomes Research at the Cleveland Clinic. WFM received speaker fees from Bayer, Servier, and Eli Lilly, and consulting fees from AtriCure and Trimedics, all outside the current study. SSJ received grant support from Boston Scientific, and speaker fees from Pendopharm and Penumbra. JSH received research grants and speaker fees from Boston Scientific, BMS/Pfizer, and Medtronic. PJD is a member of a research group with a policy of not accepting honorariums or other payments from industry for own personal financial gain. They do accept honorariums or payments from industry to support research endeavours and costs to participate in meetings. Based on study questions that PJD originated and grants he has written, he has received grants from Abbott Diagnostics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cloud DX, Coviden, Octapharma, Philips Healthcare, Roche Diagnostics, Siemens, and Stryker. He has also participated in an advisory board meeting for GlaxoSmithKline and an expert panel meeting with AstraZeneca, Boehringer Ingelheim, and Roche. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Human telomeric DNA can fold into G-quadruplex structures involving the interaction of four guanine bases in a square planar arrangement. The highly distinctive nature of quadruplex topologies suggests that they can act as novel therapeutic targets. In this study, we provide the evidence of human telomeric G4 destabilization in dilute and cell-mimicking molecular crowing conditions upon peptide binding. We have used three human telomeric sequences of different lengths. CD data showed that these sequences folded into anti-parallel G-quadruplex and CD intensity decreased significantly on increasing the peptide concentration. UV-thermal melting results showed significant decrease in hypochromicity due to formation of G4-peptide complex at 295 nm. Fluorescence data showed the quenching on titrating the peptide with human telomere G4. Electrophoretic mobility shift assay confirmed the unfolding of G4 structure. Cell viability was significantly reduced in the presence of QW5 peptide with IC 50 values as 8.78  μ M and 7.72  μ M after 72 and 96 hours of incubation respectively. These results confirmed that QW5 peptide has an ability to bind and unfold to human telomeric G-quadruplex and hence might be the key modulator for targeting diseases having over-representation of G4 motifs and their destabilization will be helpful in increasing the efficiency of DNA replication, transcription or duplex reannealing.Communicated by Ramaswamy H. Sarma.

Fat grafting can restore facial volume for reconstructive and cosmetic indications. Common practice often involves extracting lipoaspirate from the most abundant anatomic location. However, grafted fat retains the phenotypic characteristics of its original location and can undergo exaggerated hypertrophy with patient weight fluctuations. The aim of this study was to systematically assess the literature to summarize the reported effects of postoperative weight gain on facial hypertrophy in patients after facial fat grafting and to determine potentially avoidable factors. A search through PubMed/MEDLINE was conducted on October 4, 2022, to identify relevant articles with appropriate search terms. No lower date limit was applied and all eligible nonanimal clinical articles in English were included for review. Reports were summarized and presented as descriptive statistics. The search generated 714 articles. After abstract and full-text review of the initial set of articles, 6 were included in our analysis. All articles described poor cosmetic outcomes resulting from nonanatomic hypertrophy of the grafted fat. None of the articles reported a thorough methodology for selecting the donor site to minimize fat hypertrophy with potential future weight fluctuations. Grafted facial fat is susceptible to exaggerated hypertrophy as a result of changes in patient weight. Specifically, harvesting lipoaspirate from maximally abundant areas of the body may increase this risk. Individualizing the area of fat donation may attenuate unwanted fat growth and further contribute to increased patient quality of life., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We have designed and synthesized three pyrazole analogs (4, 5a, 5b), pyrazole-based chalcones (6a-6d) and (8a-8h), and N -formyl/acetyl 1,3,5-trisubstituted pyrazoline analogs (7a-7d), (9a-9d). FT-IR, 1 H, 13 C NMR, and mass spectrometry techniques were used to describe the structures of all the synthesized analogs. The single crystal X-ray method was used to identify the molecular structure of derivatives 4 and 5a. All synthesized analogs were screened by MTT assay on two cancer cell lines, the human lung cancer cell line (A549) and cervical cancer cell line (HeLa). Among all compounds, analog 9d demonstrates significant anticancer activity against HeLa (IC 50 = 23.6 μM) and A549 (IC 50 = 37.59 μM). The non-interactive interaction of active compound (9d) with Calf thymus DNA (Ct-DNA) has been investigated through various methods, such as UV-vis absorption, emission, cyclic voltammetry and circular dichroism. The DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical has been used to measure the antioxidant capacity of the pyrazoline derivative (9d). The outcomes showed that active analog has significant antioxidant activity. In addition, MD simulation of the EGFR tyrosine kinase protein-ligand complex was performed at a time scale of 100 ns. The MMGBSA data of ligand-protein complex are showed stable interactions up to 100 ns., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A regioselective direct carboxamidation reaction of 2-indolylmethanols with readily available isocyanoesters/isocyanides has been reported in this work. The reaction was catalyzed by Bronsted acid such as p -TsOH to deliver the benzylic regioselective amides in 67-86% yield under mild conditions. The developed methodology provides alternative access to traditional metal-free carboxamidation via C-C and C-O bond formation with high atom economy. Furthermore, the developed approach was diversified to synthesize chiral indole-2-carboxamide derivatives with a moderate enantiomeric excess (61-73% ee ) using an ( R )-chiral phosphoric acid.

Background: Spinal atypical teratoid rhabdoid tumor (AT/RT) is an extremely rare tumor and represents less than 2% of all AT/RTs., Methods: Available medical literature on spinal AT/RT in English was retrieved from PubMed and comprehensively reviewed. Clinical presentation, diagnosis, management, prognosis, and outcome in patients with spinal AT/RT have been elucidated by citing a case of extradural AT/RT of the cervicodorsal spine., Results: The age at presentation is usually less than 3 years. The most common site is the cervicodorsal spine. The most frequent tumor location is intradural extramedullary. A contrast-enhanced magnetic resonance imaging (MRI) of the entire neuraxis is the imaging modality of choice. The incidence of leptomeningeal dissemination is high (15-30%). Histopathological examination shows an admixture of primitive neuroectodermal, mesenchymal, and epithelial elements along with rhabdoid cells. Loss of SMARCB1/INI1 is considered pathognomonic of AT/RT. Maximal safe resection of tumor is the initial management of choice. Thereafter focal radiotherapy for localized tumor or craniospinal irradiation for leptomeningeal dissemination should be considered. Post-operative intensive polychemotherapy including intrathecal and high-dose chemotherapy (with autologous stem cell rescue) is usually considered to optimize survival. Typically, the time to recurrence and overall survival are less than 6 and 12 months, respectively. However, with judicious multimodality management long-term survivors are increasingly being recognized. The illustrative patient was a 18-month-old girl diagnosed with extradural AT/RT of the cervicodorsal spine (C3-D1), who was managed with maximal safe resection of tumor, multiagent chemotherapy (ICE-ifosfamide, carboplatin, etoposide) and focal RT to the tumor bed-50.4 Gy/28 fractions/5.5 weeks. At the last follow-up visit, 30 months after surgery, she had complete clinicoradiological response., Conclusion: Multimodal treatment comprising maximal safe resection of tumor, multiagent chemotherapy (ICE), and focal RT can lead to successful outcome in patients with localized spinal AT/RT, under the age of 3 years., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Studies suggest that the 1'β-CN moiety in remdesivir sterically clashes with the Ser861 residue of the RNA-dependent-RNA polymerase (RdRp), causing a delayed chain termination in the RNA replication process. Replacing C1'β-CN with 5-membered heterocycles such as tetrazoles, oxadiazoles, and triazoles can augment the inhibitory activity and pharmacokinetic profile of C-nucleotides. Synthesis of tetrazole-, triazole-, and oxadiazole-integrated C1' analogues of remdesivir was attempted using general synthetic routes. The final compounds 26 , 28 , and 29 did not inhibit viral replication; however, the synthetic intermediates, i.e., 27 and 50 , exhibited an IC 90 = 14.1 μM each. The trifluoromethyl-substituted 1,2,4-oxadiazole 59 showed an IC 90 of 33.5 μM. This work adds to the growing evidence of the beneficial medicinal impact of C1,1'-disubstituted C-nucleotides.

Background: Lumbar discectomy is performed for symptomatic lumbar disc herniation and is one of the most widely performed spinal surgical procedures worldwide in a variety of ways. This survey aimed at providing an overview/perspective of different practice patterns and the impact of lumbar discectomy on axial back pain with or without sciatica., Methods: An online survey was performed using the application "Google Forms." The link to the questionnaire was distributed to neurosurgeons through personal E-mail and social media platforms., Results: We received 333 responses. The largest percentage of responses across five continents was from Asia (66.97%, n = 223). The mean age of the respondents was 40.08 ± 10.5 years. A total of 66 respondents (20%) had a spine practice of 7%-90%, and 28 respondents had a spine practice of 90%-100% (8.4%). The number of respondents who practiced microscopic discectomy using a tubular retractor ( n = 143 respondents, 42.9%) was nearly equal to the number of respondents who practiced open discectomy ( n = 142 respondents, 42.6%). An almost equal proportion of respondents believed discectomy does not help in relieving axial back pain. Only 20.4% ( n = 68) of respondents recommend bed rest for a longer duration postoperatively., Conclusions: Our survey revealed that only 22.2% of spine surgeons recommended discectomy in patients with radiological disc herniation with axial back pain alone and preferred a minimally invasive method of discectomy. Almost half of them believed discectomy to be ineffective for axial low back pain and only a few recommended prolonged bed rest postoperatively., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Craniovertebral Junction and Spine.)

Background: Transpedicular screws have proven the test of time, yet they are not devoid of complications. Many newer techniques such as 2 D and 3D fluoroscopy,O arm Navigation assisted surgery, robotic assisted surgery have come into existence to the increase precision in pedicle screw insertion. But, complications do occur in their presence. We propose an Extra pedicular screw and hook system (EPSH) system with similar biomechanical property, better safety profile and short learning curve compared to traditional pedicle screw., Purpose: To Compare the pull out strength of Traditional Pedicle screw Vs Extra pedicular screw and hook system(EPSH)., Methods: Biomechanical testing was conducted according ASTM F543 guidelines to compare the pull-out strength of EPSH based construct and traditional pedicle screw construct. Six saw bone samples in each group considered. Screw of 5.5 mm diameter and length of 35 mm was used in both the groups. Pull out strength assessed by giving 5 mm/min axial load. The axial load Vs displacement of the screw were recorded and plotted. The maximum load required for screw failure is noted in both the group. Statistical analysis was done., Results: The mean peak load of pedicle screw group was found to be 1670.9 ± 393.2 N with mean displacement at peak load was found to be 13.44 ± 1.7 mm and in EPSH group it was 1416.4 ± 341.4 N and 15.78 ± 3.9 mm respectively. A paired t -test showed no statistical difference(p < 0.05) between 2 groups., Conclusion: EPSH has shown to have almost similar biomechanical property as that pedicle screw construct. With Addition of the hook, it provides an extra rotational stability as well. Being an extra-pedicular screw it has high safety profile and needs less expertise for insertion., (© 2023 Delhi Orthopedic Association. All rights reserved.)

The current definition of high-sensitivity cardiac troponin (hs-cTn) assays is laboratory-based and their analytical attributes and characteristics have drawn significant attention in the literature at least partly due to the lower concentration cut-offs and changes in concentrations (i.e., deltas) employed in different algorithms and pathways to manage patient care. We propose that pre-analytical conditions such as sample type, storage conditions, and other interferences may also have a significant impact on hs-cTn concentrations and clinical management. The purpose of this literature review is to provide a summary of important pre-analytical and interference studies affecting hs-cTn concentrations. A breakdown of the literature for the major diagnostic companies providing core laboratory instrumentation (i.e., Abbott, Beckman, Ortho, Roche, and Siemens) is also provided. Finally, three cases are highlighted where knowledge of pre-analytical factors aids the hs-cTn clinically discordant investigations. This review highlights the importance of pre-analytical variables, especially storage condition, sample handling, and blood tubes used (i.e., sample type) when interpreting hs-cTn assays. Additional studies are needed to further elaborate on pre-analytical variables (i.e., centrifugation, sample type, stability) and interferences for all hs-cTn assays in clinical use, as knowledge of these variables may aid in hs-cTn clinically discordant investigations., Competing Interests: Declaration of Competing Interest Dr. Kavsak has received grants/reagents/consultant/advisor/honoraria from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche Diagnostics, Quidel, Siemens Healthcare Diagnostics and Thermo Fisher Scientific. McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular biomarker field. No other disclosures were reported., (Copyright © 2022 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Background: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively., Objective: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery., Design: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723)., Setting: 110 hospitals in 22 countries., Patients: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications., Intervention: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery., Measurements: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment., Results: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P  = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term., Limitation: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels., Conclusion: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications., Primary Funding Source: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-3157.

Objective: To compare the SimSpine (indigenously developed, low-cost model) and EasyGO! (Karl Storz, Tuttlingen, Germany) systems for simulation of endoscopic discectomy., Methods: Twelve neurosurgery residents, 6 in postgraduate years 1-4 or equivalent (junior) and 6 in postgraduate years 5-6 or equivalent (senior), were randomly allocated (1:1) to either EasyGO! or SimSpine endoscopic visualization systems for endoscopic lumbar discectomy simulation on the same physical simulator. After the first exercise, the participants switched over to the other system, and the exercise was repeated. Time taken to dock the system, time to reach annulus, time required for task completion, dural violation, and volume of disc material removed were used for calculating objective efficiency score. Subjective scoring (Neurosurgery Education and Training School [NETS] criteria) was performed by 4 blinded mentors based on recorded video on 2 separate occasions 2 weeks apart. Cumulative score was calculated based on efficiency and Neurosurgery Education and Training School scores., Results: Performance metrics were similar across the 2 platforms, regardless of participant seniority (P > 0.05). Time to reach disc space and discectomy time improved for both EasyGO! (P = 0.07 and P = 0.03, respectively) and SimSpine (P = 0.01 and P = 0.04, respectively) between first and second exercises. Efficiency and cumulative scores were better (P = 0.04 and P = 0.03 respectively) when EasyGO! was used as the first device compared with SimSpine., Conclusions: SimSpine is a cost-effective viable alternative to EasyGO for endoscopic lumbar discectomy simulation-based training., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Perioperative atrial fibrillation (AF) and myocardial injury after noncardiac surgery (MINS) are common complications after noncardiac surgery. Inflammation has been implicated in the pathogenesis of both disorders. The COP-AF trial tests the hypothesis that colchicine reduces the incidence of perioperative AF and MINS in patients undergoing major noncardiac thoracic surgery., Methods and Results: The 'COlchicine for the Prevention of Perioperative Atrial Fibrillation' (COP-AF) trial is an international, blinded, randomized trial that compares colchicine to placebo in patients aged at least 55 years and undergoing major noncardiac thoracic surgery with general anesthesia. Exclusion criteria include a history of AF and a contraindication to colchicine (eg, severe renal dysfunction). Oral colchicine at a dose of 0.5 mg or matching placebo is given within 4 hours before surgery. Thereafter, patients receive colchicine 0.5 mg or placebo twice daily for a total of 10 days. The 2 independent co-primary outcomes are clinically important perioperative AF (including atrial flutter) and MINS during 14 days of follow-up. The main safety outcomes are sepsis or infection and non-infectious diarrhea. We aim to enroll 3,200 patients from approximately 40 sites across 11 countries to have at least 80% power for the independent evaluation of the 2 co-primary outcomes. The COP-AF main results are expected in 2023., Conclusions: COP-AF is a large randomized and blinded trial designed to determine whether colchicine reduces the risk of perioperative AF or MINS in patients who have major noncardiac thoracic surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Myocardial injury after non-cardiac surgery (MINS), based on measurement of troponin T, is associated with perioperative major adverse cardiovascular events (MACE). We therefore determined the high-sensitivity troponin I (hsTnI) thresholds associated with 30 day MACE after non-cardiac surgery., Methods: We performed a nested biobank cohort study of 4553 patients from the Vascular Events in Non-Cardiac Surgery Patients Cohort Evaluation (VISION) Study. We measured hsTnI (ADVIA Centaur® hsTnI assay) on postoperative days 1 to 3 in patients ≥45 years undergoing non-cardiac surgery. An iterative Cox proportional hazard model determined peak postoperative hsTnI thresholds independently associated with MACE (i.e., death, myocardial infarction occurring on postoperative day 4 or after, non-fatal cardiac arrest, or congestive heart failure) within 30 days after surgery., Results: MACE occurred in 89/4545 (2.0%) patients. Peak hsTnI values of <75 ng/L, 75 ng/L to <1000 ng/L, and ≥1000 ng/L were associated with 1.2% (95% CI, 0.9-1.6), 7.1% (95% CI, 4.8-10.5), and 25.9% (95% CI, 16.3-38.4) MACE, respectively. Compared to peak hsTnI <75 ng/L, values 75 ng/L to <1000 ng/L and ≥1000 ng/L were associated with adjusted hazard ratios (aHR) of 4.53 (95% CI, 2.75-7.48) and 16.17 (95% CI, 8.70-30.07), respectively. MACE was observed in 9% of patients with peak hsTnI ≥75 ng/L vs 1% in patients with peak hsTnI <75 ng/L (aHR 5.76; 95% CI, 3.64-9.11). A peak hsTnI ≥75 ng/L was associated with MACE in the presence (aHR 9.35; 95% CI, 5.28-16.55) or absence (aHR 3.99; 95% CI, 2.19-7.25) of ischemic features of myocardial injury., Conclusion: A peak postoperative hsTnI ≥75 ng/L was associated with >5-fold increase in the risk of 30 days MACE compared to levels <75 ng/L. This threshold could be used for MINS diagnosis when the ADVIA Centaur hsTnI assay is used.Clinicaltrials.gov Registration Number: NCT00512109., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The use of biodegradable polymer drug-eluting stents (BP-DES) has been proven to minimize restenosis and stent thrombosis. The current post-marketing monitoring was observed at the 5-year clinical outcomes of individuals who had been treated with FlexyRap ® DES in the real world., Aim: To assess the safety and effectiveness of FlexyRap ® DES at the 5-year follow-up in real-world settings., Methods: Findings from a retrospective, multi-center, observational, post-market clinical follow-up study of patients treated with FlexyRap ® DES for de novo coronary artery disease (CAD) were reported. During the 12-mo follow-up, the primary endpoint was target lesion failure, which was defined as the composite of cardiovascular death, target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization., Results: The data of 500 patients received with FlexyRap ® DES was obtained at the completion of the surveillance timeline of 5-year. After the implantation of FlexyRap ® DES, the device success rate was 100%. Adverse events that led to major bleeding, permanent disability, or death were not experienced in the patients. The major adverse cardiac event rate at 12-mo, 3-year, and 5-year follow-up was 1 (0.2%), 0 (0%), and 1 (0.2%) respectively with 0 (0%) cardiovascular death, 2 (0.4%) TV-MI, and 0 (0%) TLR compositely. Furthermore, late stent thrombosis was found in 2 (0.4%) patients at the follow-up of 12-mo, very late stent thrombosis was observed in 2 patients (0.4%) at 3-year follow-up., Conclusion: FlexyRap ® DES was proved to be safe and efficacious in real-world patients with de novo CAD, indicating a lowered rate of cardiac events and stent thrombosis at 5-year follow-up., Competing Interests: Conflict-of-interest statement: Ms. Preeti and Dr. Malte are employees of Sahajanand Laser Technology Ltd. (SLTL), India. All other authors have nothing to disclose., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

There is a continuing demand of new inhibitors of HIV-1 Integrase (HIV-1 IN) due to mutations of HIV-1. This study aims to develop the synthesis of 3,6-diaryl 7-azaindoles and introspect the role of aryl groups on the strand transfer (ST) inhibition of HIV-1 IN. An efficient and chemo-selective one-pot method is established for the synthesis of the unexplored diverse C3 → C6 diaryl 7-azaindoles starting from 6-chloro-3-iodo- N -protected 7-azaindoles. Here we report Pd 2 dba 3 /SPhos catalyzed synthesis of eight selective C3 monoaryl 7-azaindoles ( 10a - h ) and eight C3,C6-diaryl 7-azaindoles ( 11a - f , 12a,b ) with yields in the ranges of 67-93% and 43-88% respectively. The synthesized derivatives inhibit the strand transfer (ST) activity of HIV-1 IN enzyme at 10 μM dose with 11d and 11f exhibiting %ST inhibitions of 72% and 71%, respectively. SAR studies indicate the para-substitution on the C3 aryl ring and C6 aryl is essential for enhanced %ST inhibition. 11b , c , 11e - f , and 12b showed lower cytotoxicity (IC 50 > 200 μM) against TZM-bl cells. Molecular docking of the diaryl 7-azaindoles and Raltegravir ( RAL ), to the PFV-integrase revealed favorable binding interactions., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Type IA topoisomerases maintain DNA topology by cleaving ssDNA and relaxing negative supercoils. The inhibition of its activity in bacteria prevents the relaxation of negative supercoils, which in turn impedes DNA metabolic processes leading to cell death. Using this hypothesis, two bisbenzimidazoles, PPEF and BPVF are synthesized, selectively inhibiting bacterial TopoIA and TopoIII. PPEF stabilizes the topoisomerase and topoisomerase-ssDNA complex, acts as an interfacial inhibitor. PPEF display high efficacy against ~455 multi-drug resistant gram positive and negative bacteria. To understand molecular mechanism of inhibition of TopoIA and PPEF, accelerated MD simulation is carried out, and results suggested that PPEF binds, stabilizes the closed conformation of TopoIA with -6Kcal/mol binding energy and destabilizes the binding of ssDNA. The TopoIA gate dynamics model can be used as a tool to screen TopoIA inhibitors as therapeutic candidates. PPEF and BPVF cause cellular filamentation and DNA fragmentation leading to bacterial cell death. PPEF and BPVF show potent efficacy against systemic and neutropenic mouse models harboring E. coli, VRSA, and MRSA infection without cellular toxicity., (© 2023. The Author(s).)

Moonlighting proteins (MLPs) are ubiquitous and provide a unique advantage to bacteria performing multiple functions using the same genomic content. Targeting MLPs can be considered as a futuristic approach in fighting drug resistance problem. This review follows the MLP trail from its inception to the present-day state, describing a few bacterial MLPs, viz., glyceraldehyde 3'-phosphate dehydrogenase, phosphoglucose isomerase glutamate racemase (GR), and DNA gyrase. Here, we carve out that targeting MLPs are the beacon of hope in an era of increasing drug resistance in bacteria. Evolutionary stability, structure-functional relationships, protein diversity, possible drug targets, and identification of new drugs against bacterial MLP are given due consideration. Before the final curtain calls, we provide a comprehensive list of small molecules that inhibit the biochemical activity of MLPs, which can aid the development of novel molecules to target MLPs for therapeutic applications.

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk., (© Journal of the Association of Physicians of India 2011.)

Preserving proteostasis is a major survival mechanism for cancer. Dual specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) is a key oncogenic kinase that directly activates the transcription factor heat-shock factor 1 (HSF1) and the 26S proteasome. Targeting DYRK2 has proven to be a tractable strategy to target cancers sensitive to proteotoxic stress; however, the development of HSF1 inhibitors remains in its infancy. Importantly, multiple other kinases have been shown to redundantly activate HSF1 that promoted ideas to directly target HSF1. The eventual development of direct HSF1 inhibitor KRIBB11 suggests that the transcription factor is indeed a druggable target. The current study establishes that concurrent targeting of HSF1 and DYRK2 can indeed impede cancer by inducing apoptosis faster than individual targetting. Furthermore, targeting the DYRK2-HSF1 axis induces death in proteasome inhibitor-resistant cells and reduces triple-negative breast cancer (TNBC) burden in ectopic and orthotopic xenograft models. Together the data indicate that cotargeting of kinase DYRK2 and its substrate HSF1 could prove to be a beneficial strategy in perturbing neoplastic malignancies., (© 2023 The Author(s).)