Successful use of intra venous tenecteplase for acute ischemic stroke in pregnancy.

Intravenous thrombolysis (IVT) with tenecteplase or alteplase is the standard of care in, patients with Acute Ischemic Stroke (AIS) presenting within 3-4.5 h. However here, are no established guidelines for such treatment during pregnancy. We report a case, of AIS in third trimester of pregnancy successfully treated with Tenecteplase. To the, best of our knowledge, this is the first and only case of acute ischemic stroke in, pregnancy treated with Tenecteplase.

Effect of serial night shifts on the cognitive, psychomotor, and moral performance of residents in the department of Emergency Medicine.

OBJECTIVES: The objective was to study the effect of serial night shifts on the cognitive, psychomotor, and moral performance of emergency medicine residents of an academic Emergency Medicine Department. METHODS: This prospective case-crossover study compared emergency medicine residents' sleep time, subjective sleepiness, cognitive function, moral judgment, and psychomotor skills after 5 consecutive days versus night shifts using sleep diaries, activity monitors, and multiple performance tests. Paired t-tests and Wilcoxon signed-rank tests were used to analyze data based on normality. Correlation analysis was done using Spearman's correlation test. Subgroup analysis was also performed to find any difference based on gender and year of residency. RESULTS: Twenty-seven emergency medicine residents participated (13 males, 48.1%). The distribution across residency years was as follows: 44.4% in their first year, 25.9% in their second year, and 29.6% in their third year. Following five consecutive night shifts, total sleep duration decreased significantly from 338.1 ± 67.8 to 307.4 ± 71.0 min (p < 0.001), while subjective sleepiness scores increased from 9.6 ± 3.3 to 13.6 ± 4.6. Psychomotor performance and reaction times did not significantly differ between night and day shifts. However, working memory declined, assessed by self-paced three-back test scores (median [IQR] 517.1 [471.9-546.7] vs. 457.6 [334.4-508.8]; p = 0.034) and interference test scores (445.5 ± 59.9 vs. 407.2 ± 56.8; p < 0.001), along with moral judgment (median [IQR] 19 [18-28] vs. 15 [11-21]; p = 0.010) after serial night shifts. No correlations existed between performance measures nor differences based on gender or residency year. CONCLUSIONS: Residents sleep less following night versus day shifts, reporting the highest sleepiness levels after 5 consecutive nights. Despite this, psychomotor performance and reaction times did not significantly differ. However, considerable reductions occurred in moral judgment, working memory, and interference test performance after serial night shifts.

Mapping serogroup distribution and seroprevalence of leptospirosis in livestock of Assam, Northeastern State of India: Unveiling uncommon Leptospira serogroups.

Leptospirosis is a significant zoonotic disease affecting livestock, leading to reproductive issues and economic losses. Despite its endemic status in India, research has predominantly focused on coastal regions, leaving the North Eastern Region (NER) underexplored. This study aims to investigate the seroprevalence and serogroup distribution of leptospirosis in livestock across Assam, a major state in the North Eastern Region (NER) of India. Serum samples (n=811) from cattle, buffalo, sheep, goats, and pigs were collected between 2016 and 2019 and screened using the Microscopic Agglutination Test (MAT) for 24 serogroups. The overall seroprevalence was 22.9 % (186/811), with highest prevalence in cattle (26.2 %) and buffalo (25 %), followed by small ruminants (19.8 %) and pigs (18.6 %) . Notably, uncommon serovars such as Mini (28.8 %), Manhao (12.4 %), and Cynopteri (7.5 %) were identified, indicating a unique epidemiological pattern in Assam. High seroprevalence was observed in districts like Bongaigaon (66.7 %), Kamrup Metropolitan (50.0 %), and Nalbari (40.0 %), emphasizing the need for targeted intervention strategies. The presence of these uncommon serogroups, typically found in neighbouring countries and other regions, suggests potential transboundary transmission from these countries. This study provides valuable insights into the seroprevalence and serogroup distribution of leptospirosis in Assam's livestock, highlighting the need for region-specific surveillance and control measures. These findings underscore the importance of understanding the local epidemiological landscape to develop effective disease management and prevention strategies, ultimately reducing the impact of leptospirosis in the NER of India.

Flattening the learning curve - Early experience of robotic-assisted pedicle screw placement in spine surgery.

Aims and objectives: To determine accuracy of pedicle screws placed by freehand, fluoroscopy-assistance and robotic-assistance with intraoperative image acquisition, and determine the presence of learning curve in robotic spine surgery in a prospective single centre study. Materials and methods: In a prospective study, a total of 1120 pedicle screws were placed in Freehand group (n = 175), 1250 screws were placed in fluoroscopy-assisted group (n = 172), and 1225 screws were inserted in Robotic-assisted group(n = 180). Surgical parameters and screw accuracy were analyzed between the three groups. The preoperative plan was overlapped with post operative O-arm scan to determine if the screws were executed as planned. Results: The frequency of clinically acceptable screw placement (Gertzbein and Robbins grade A, B) in the Freehand, Fluoroscopy-assisted, and Robotic-assisted groups were 97.7 %, 98.6 %, and 99.34 % respectively. Higher pedicle screw accuracy, and lower blood loss were seen with robotic assistance. There was no significant difference in these parameters between surgeries commencing before and after 2 p.m. We found no statistically significant differences between the planned and executed screw trajectories in robotic assisted group irrespective of surgical experience. Conclusion: The third-generation robotic-assisted pedicle screw placement system, used in conjunction with intraoperative 3D O-arm imaging, consistently lowered blood loss and increased accuracy of pedicle screw placement in the thoracolumbar spine. It also has easy adaptability into spine practice with minimal learning curve.

A systematic review and meta-analysis informing the role of adjuvant radiotherapy (RT) in Grade 2 and 3 oligodendroglioma.

BACKGROUND AND PURPOSE: Evidence and clinical guidelines support the use of adjuvant RT in high-risk low-grade gliomas. However, patients with oligodendroglioma have a more indolent disease course and delaying or avoiding RT is often considered to reduce treatment-related toxicities. As the optimal adjuvant management for oligodendroglioma is unclear, we aimed to assess the effect of adjuvant RT on overall survival (OS) and progression-free survival (PFS). METHODS: MEDLINE, EMBASE, CENTRAL and CINAHL were searched from January 1990 to February 2023 for studies comparing adjuvant RT versus no adjuvant RT for patients with oligodendroglioma. RESULTS: This review found 17 eligible studies including 14 comparative retrospective studies and 3 randomized controlled trials. Using random-effects model, the results suggested that adjuvant RT improved OS by 28 % (HR 0.72, 95 % CI (0.56-0.93), I2 = 86 %), and PFS by 48 % (HR 0.52, (95 % CI 0.40-0.66), I2 = 48 %) compared to patients without adjuvant RT. Subgroup analysis showed that upfront adjuvant RT improved OS and PFS compared to salvage RT. There were no significant differences in OS and PFS between adjuvant RT versus adjuvant chemotherapy. There was improvement in PFS but not OS for adjuvant chemoradiotherapy versus adjuvant chemotherapy alone. Adjuvant RT improved OS in WHO Grade 3 but not WHO Grade 2 oligodendroglioma. CONCLUSION: Overall, adjuvant RT improved OS and PFS in patients with oligodendroglioma. In patients with low-risk features (e.g. Grade 2, gross total resection), alternative approaches and individualization of management such as adjuvant chemotherapy alone may be reasonable considering the lack of survival benefit. Future efforts should prospectively investigate these treatment regimens on molecularly-classified oligodendroglioma patients (defined by presence of IDH mutation and 1p/19q co-deletion), balancing between maximizing survival outcomes and reducing RT-related toxicities.

Assessment of nomophobia and its determinants among adults and adolescents in Semi-urban Chennai.

Introduction: The mobile phone has evolved into an indispensable accessory carried by everyone. With its increasing usage, there is a parallel rise in mobile phone addictions. Nomophobia, short for no mobile phone phobia, is characterized as a fear specific to the absence of mobile phones. Objectives: (1) To assess the prevalence of nomophobia among adolescents and adults residing in semi-urban Chennai. (2) To understand the patterns of mobile phone usage and explore the health-related consequences of nomophobia. Methods: This cross-sectional study was conducted among adolescents and adults (15-50 years) in semi-urban Chennai from July to September 2022. The sample size was 220, and the study utilized the Test of Mobile Phone Dependence Brief as an assessment tool. Participants scoring >30 were identified as nomophobic, indicating mobile phone dependence. Results: Among the 220 study participants, there was an almost equal distribution between males and females, with a majority falling within the 21-25 age group. Approximately 26.1% belonged to the upper middle class and 89.1% were married. The prevalence of nomophobia was notably high at 68.6% (151 out of 220). A significant association was found between social class and mobile phone addiction, with the middle class exhibiting higher levels of addiction. Conclusion: The study highlights that a substantial majority of adults exhibit mobile phone addiction, almost two-thirds of the participants. There is a pressing need for health awareness programmes targeting adults to educate them about the adverse effects of mobile phone addiction. Additionally, reinforcing strategies for effective and time-restricted mobile phone usage is essential.

Welcoming the new, revisiting the old: a brief glance at cytopathology reporting systems for lung, pancreas, and thyroid.

This review addresses new reporting systems for lung and pancreatobiliary cytopathology as well as the most recent edition of The Bethesda Reporting System for Thyroid Cytopathology. The review spans past, present, and future aspects within the context of the intricate interplay between traditional morphological assessments and cutting-edge molecular diagnostics. For lung and pancreas, the authors discuss the evolution of reporting systems, emphasizing the bridge between past directives and more recent collaborative efforts of the International Academy of Cytology and the World Health Organization in shaping universal reporting systems. The review offers a brief overview of the structure of these novel systems, highlighting their strengths and pinpointing areas that require further refinement. For thyroid, the authors primarily focus on the third edition of The Bethesda System for Reporting Thyroid Cytopathology, also considering the two preceding editions. This review serves as an invaluable resource for cytopathologists, offering a panoramic view of the evolving landscape of cytopathology reporting and pointing out the integrative role of the cytopathologist in an era of rapid diagnostic and therapeutic advancements.

Whole-body hypothermia in mild neonatal encephalopathy: protocol for a multicentre phase III randomised controlled trial.

BACKGROUND: Mild hypoxic ischemic encephalopathy is associated with sub optimal cognition and learning difficulties at school age. Although whole-body hypothermia reduces death and disability after moderate or severe encephalopathy in high-income countries, the safety and efficacy of hypothermia in mild encephalopathy is not known. The cooling in mild encephalopathy (COMET) trial will examine if whole-body hypothermia improves cognitive development of neonates with mild encephalopathy. METHODS: The COMET trial is a phase III multicentre open label two-arm randomised controlled trial with masked outcome assessments. A total of 426 neonates with mild encephalopathy will be recruited from 50 to 60 NHS hospitals over 2 ½ years following parental consent. The neonates will be randomised to 72 h of whole-body hypothermia (33.5 ± 0.5 C) or normothermia (37.0 ± 0.5 C) within six hours or age. Prior to the recruitment front line clinical staff will be trained and certified on expanded modified Sarnat staging for encephalopathy. The neurological assessment of all screened and recruited cases will be video recorded and centrally assessed for quality assurance. If recruitment occurs at a non-cooling centre, neonates in both arms will be transferred to a cooling centre for continued care, after randomisation. All neonates will have continuous amplitude integrated electroencephalography (aEEG) at least for the first 48 h to monitor for seizures. Predefined safety outcomes will be documented, and data collected to assess resource utilization of health care. A central team masked to trial group allocation will assess neurodevelopmental outcomes at 2 years of age. The primary outcome is mean difference in composite cognitive scores on Bayley scales of Infant and Toddler development 4th Edition. DISCUSSION: The COMET trial will establish the safety and efficacy of whole-body hypothermia for mild hypoxic ischaemic encephalopathy and inform national and international guidelines in high income countries. It will also provide an economic assessment of whole-body hypothermia therapy for mild encephalopathy in the NHS on cost-effectiveness grounds. TRIAL REGISTRATION NUMBER: NCT05889507 June 5, 2023.

Solasodine targets NF-κB signaling to overcome P-glycoprotein mediated multidrug resistance in cancer.

P-glycoprotein (P-gp) mediated multidrug resistance (MDR) is the leading cause of chemotherapy failure since it causes the efflux of chemotherapeutic drugs from the cancer cells. Solasodine, a steroidal alkaloid and oxaspiro compound, present in the Solanaceae family showed significant cytotoxic effects on various cancer cells. However, the effect of solasodine on reversing P-gp mediated drug resistance is still unknown. Primarily in this study, the integrative network pharmacology analysis found 71 common targets between solasodine and cancer MDR, among them NF-κB was found as a potential target. The results of immunofluorescence analysis showed that solasodine significantly inhibits NF-κB-p65 nuclear translocation which caused downregulated P-gp expression in KBChR-8-5 cells. Further, solasodine binds to the active sites of the TMD region of P-gp and inhibits P-gp transport activity. Moreover, solasodine significantly promotes doxorubicin intracellular accumulation in the drug resistant cells. Solasodine reduced the fold resistance and synergistically sensitized doxorubicin's therapeutic effects in KBChR-8-5 cells. Additionally, the solasodine and doxorubicin combination treatment increased the apoptotic cell populations and G2/M phase cell cycle arrest in KBChR-8-5 cells. The MDR tumor bearing xenograft mice showed tumor-suppressing characteristics and P-gp downregulation during the combination treatment of solasodine and doxorubicin. These results indicate that solasodine targets NF-κB signaling to downregulate P-gp overexpression, inhibit P-gp transport activity, and enhance chemosensitization in MDR cancer cells. Considering its multifaceted impact, solasodine represents a potent natural fourth-generation P-gp modulator for reversing MDR in cancer.

Application of liquid biopsy in lung cancer management.

ABSTRACT: Current advances in the understanding of the lung cancer landscape have drastically changed the approach to treating a patient with lung carcinoma. The field has progressed from analyzing single gene to using advanced techniques like next-generation sequencing and microarray technology. While a tumor tissue sample is considered the gold standard, it has several limitations. The limitations of invasive procedures, long processing periods, inaccessibility, and sample inadequacy are being addressed by sampling biofluids, termed 'liquid biopsy,' which offers a less invasive and more accessible way to obtain tumor-related information. Liquid biopsy has transformed the care of lung cancer patients by directly targeting somatic alterations from tumors. This article provides insights into the biology, technical aspects, limitations, and practical applications of 'liquid biopsy,' focusing on cell-free DNA and circulating tumor DNA in the context of lung cancer.

Is Gamma Knife surgery, omitting adjunct whole brain radiation treatment, feasible for patients with 20 or more brain metastases?

Background: The importance of the number of brain metastases (BM) when deciding between whole brain radiation treatment (WBRT) and radiosurgery is controversial. We hypothesized that the number of BM is of limited importance when deciding radiation strategy, and offered Gamma Knife surgery (GKS) also for selected patients with 20 or more BM. Methods: The outcome following single session GKS for 75 consecutive patients harboring 20 or more (20+) BM was analyzed. Data was collected both retro- and prospectively. Results: The median survival time was 9 months. Two grade 3 complications occurred, 1 resolved and 1 did not. Sex and clinical condition at the time of GKS (ECOG value) were the only parameters significantly related to survival time. Eighteen patients developed leptomeningeal dissemination with or without distant recurrences (DR), and another 32 patients developed DR a total of 73 times. DR was managed with GKS 24 times, with WBRT 3 times and with systemic treatment or best supportive care 46 times. The median time to developing DR was unrelated to the number of BM, but significantly longer for patients older than 65 years, as well as for patients with NSCLC. Conclusions: GKS is a reasonable treatment option for selected patients with 20 or more BM. It is better to decide the optimal management of post-GKS intracranial disease progression once it occurs rather than trying to prevent it by using adjunct WBRT.

Fixed-Dose Combination of Canagliflozin and Metformin as an Adjunct to Diet and Exercise in Indian Adults with Type 2 Diabetes Mellitus: Results from a Multicentric, Open-Label, Single-Arm, Phase IV Study.

BACKGROUND: Canagliflozin and metformin fixed-dose combination (CANA/MET FDC), an approved treatment for type 2 diabetes mellitus (T2DM) in India, effectively lowers glycated hemoglobin (HbA1c), promotes weight loss, and improves patient adherence. As a regulatory requirement, we aimed to evaluate the safety and efficacy of CANA/MET FDC in Indian patients with T2DM. RESEARCH DESIGN AND METHODS: This prospective, multicenter, open-label, single-arm, phase IV study included Indian patients with T2DM (aged 18-65 years) inadequately controlled on diet and exercise. Patients received CANA/MET (50/500 and 50/1000 mg) immediate-release (IR) FDC twice daily for 24 weeks. The primary endpoint was safety assessment, including adverse events (AEs) and serious AEs (SAEs). The secondary endpoint included a change in HbA1c from baseline to weeks 12 and 24. Descriptive statistics were used for all continuous safety variables and efficacy parameters. RESULTS: Of the 310 patients screened, 276 were enrolled. 114/274 (41.6%) patients had ≥1 treatment-emergent AE [treatment-emergent AEs (TEAEs), among which 29 (10.6%) were related to study intervention]. The most common TEAEs were dyslipidemia (4.7%), pyrexia (4.7%), genital infections (3.3%), hypoglycemia (3.3%), and urinary tract infections (2.6%). Three (1.1%) patients had serious TEAEs, and all cases were resolved. No deaths were reported. The mean change in HbA1c from baseline was -0.92 and -0.93% at weeks 12 and 24, respectively. CONCLUSION: The study demonstrates the safety and efficacy of CANA/MET FDC in Indian patients with T2DM, presenting a safe therapeutic option for diabetes management in India.

Silver-Catalyzed Olefination of Aryl Aldehydes Using Propiolates.

Olefination of aldehydes is one of the fundamental reactions in organic synthesis. The commonly used Wittig olefination reaction however uses stoichiometric quantities reagents under basic conditions resulting in stoichiometric amounts of byproducts. Known catalytic alternate to the Wittig reaction requires stoichiometric amounts of silane reducing agents and high temperature. Herein, we report a base-free olefination of aryl aldehydes using propiolates as a surrogate for the Witting reagent under silver catalysis. Trimethyl orthoformate, in the presence of a silver catalyst adds to the alkynoate to form the nucleophilic silver allenolate which reacts with the reactive oxocarbenium ion formed from aldehyde under the reaction conditions. Subsequently decarbonylation occurs to form the olefin. Trans olefin is formed exclusively from simple aryl aldehydes and cinnamaldehydes. Such a silver allenolate is conceptually novel and has not been explored so far.

Glutaminase - A potential target for cancer treatment.

The overexpression of glutaminase is reported to influence cancer growth and metastasis through glutaminolysis. Upregulation of glutamine catabolism is recently recognized as a critical feature of cancer, and cancer cells are observed to reprogram glutamine metabolism to maintain its survival and proliferation. Special focus is given on the glutaminase isoform, GLS1 (kidney type glutaminase), as the other isoform GLS2 (Liver type glutaminase) acts as a tumour suppressor in some conditions. Glutaminolysis linked with autophagy, which is mediated via mTORC1, also serves as a promising target for cancer therapy. Glutamine also plays a vital role in maintaining redox homeostasis. Inhibition of glutaminase aggravates oxidative stress by reducing glutathione level, thus leading to apoptotic-mediated cell death in cancer cells Therefore, inhibiting the glutaminase activity using glutaminase inhibitors such as BPTES, DON, JHU-083, CB-839, compound 968, etc. may answer many intriguing questions behind the uncontrolled proliferation of cancer cells and serve as a prophylactic treatment for cancer. Earlier reports neither discuss nor provide perspectives on exact signaling gene or pathway. Hence, the present review highlights the plausible role of glutaminase in cancer and the current therapeutic approaches and clinical trials to target and inhibit glutaminase enzymes for better cancer treatment.

Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

Robust brain tumor classification by fusion of deep learning and channel-wise attention mode approach.

Diagnosing brain tumors is a complex and time-consuming process that relies heavily on radiologists' expertise and interpretive skills. However, the advent of deep learning methodologies has revolutionized the field, offering more accurate and efficient assessments. Attention-based models have emerged as promising tools, focusing on salient features within complex medical imaging data. However, the precise impact of different attention mechanisms, such as channel-wise, spatial, or combined attention within the Channel-wise Attention Mode (CWAM), for brain tumor classification remains relatively unexplored. This study aims to address this gap by leveraging the power of ResNet101 coupled with CWAM (ResNet101-CWAM) for brain tumor classification. The results show that ResNet101-CWAM surpassed conventional deep learning classification methods like ConvNet, achieving exceptional performance metrics of 99.83% accuracy, 99.21% recall, 99.01% precision, 99.27% F1-score and 99.16% AUC on the same dataset. This enhanced capability holds significant implications for clinical decision-making, as accurate and efficient brain tumor classification is crucial for guiding treatment strategies and improving patient outcomes. Integrating ResNet101-CWAM into existing brain classification software platforms is a crucial step towards enhancing diagnostic accuracy and streamlining clinical workflows for physicians.

Outcomes in Patients with Vogt-Koyanagi-Harada Disease from the First-line Antimetabolites for Steroid-sparing Treatment Uveitis Trial.

PURPOSE: To compare the effectiveness of methotrexate (MTX) and mycophenolate mofetil (MMF) in achieving corticosteroid-sparing control of uveitis in patients with Vogt-Koyanagi-Harada (VKH) disease. METHODS: A subanalysis of patients with VKH from the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial, a randomized, observer-masked, comparative effectiveness trial, with comparisons by treatment (MTX versus MMF) and disease stage (acute versus chronic). Individuals with noninfectious uveitis were placed on a standardized corticosteroid taper and block randomized 1:1 to either 25mg weekly oral MTX or 1.5g twice daily oral MMF. The primary outcome was treatment success defined by corticosteroid-sparing control of uveitis at 6 months. Additional outcomes included change in best spectacle-corrected visual acuity (BSCVA), retinal central subfield thickness (CST), and resolution of serous retinal detachment (SRD). RESULTS: Ninety-three out of 216 enrolled patients had VKH; 49 patients were randomized to MTX and 44 to MMF, of which 85 patients (46 on MTX, 39 on MMF) contributed to the primary outcome. There was no significant difference in treatment success by antimetabolite (80.4% for MTX compared to 64.1% for MMF; P=.12) or in BSCVA improvement (P=.78). Methotrexate was superior to MMF in reducing CST (P=.003) and resolving SRD (P=.02). There was no significant difference in treatment success by disease stage (P=.25), but patients with acute VKH had greater improvement in BSCVA (P<.001) and reduction of CST (P=.02) than chronic VKH patients. CONCLUSIONS: MTX and MMF have comparable outcomes as corticosteroid-sparing immunosuppressive therapies for VKH. Visual acuity improvement was greater in acute vs chronic VKH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00182929.

NLRC5 senses NAD+ depletion, forming a PANoptosome and driving PANoptosis and inflammation.

NLRs constitute a large, highly conserved family of cytosolic pattern recognition receptors that are central to health and disease, making them key therapeutic targets. NLRC5 is an enigmatic NLR with mutations associated with inflammatory and infectious diseases, but little is known about its function as an innate immune sensor and cell death regulator. Therefore, we screened for NLRC5's role in response to infections, PAMPs, DAMPs, and cytokines. We identified that NLRC5 acts as an innate immune sensor to drive inflammatory cell death, PANoptosis, in response to specific ligands, including PAMP/heme and heme/cytokine combinations. NLRC5 interacted with NLRP12 and PANoptosome components to form a cell death complex, suggesting an NLR network forms similar to those in plants. Mechanistically, TLR signaling and NAD+ levels regulated NLRC5 expression and ROS production to control cell death. Furthermore, NLRC5-deficient mice were protected in hemolytic and inflammatory models, suggesting that NLRC5 could be a potential therapeutic target.

Mental Health Issues Among School Children and Adolescents in India: A Systematic Review.

Childhood and adolescence are critical developmental stages for mental health, and the environment in which they grow has an impact on their well-being and growth. This study aims to assess mental health issues among school children and adolescents in India. A systematic search was conducted on the literature published between January 2013 and August 2023 in PubMed, Scopus, Cochrane Library, and Eric database. Thirty-one studies with a sample size of 30,970 were included in the final quantitative synthesis, of which 14,381 were male. The overall mean age of the school children and adolescents was 14.58 years, with a standard deviation of 1.35. A diverse range of mental health concerns have been documented in school children and adolescents, exhibiting differing degrees of severity and frequency. The analysis showed that depression was the most prevalent mental health issue among children, followed by social, behavioral, and emotional problems, anxiety, psychological distress, internet technology addiction, stress, social phobia, sexual and emotional abuse, violence, and attention deficit hyperactive disorder. The study concludes that school mental health research in India is critical for personalizing interventions to the specific requirements of the diverse student population, decreasing stigma, and enhancing overall student well-being within the cultural and educational context of the country.

A Detailed Protocol for the Induction of Anemia and RBC Transfusion-associated Necrotizing Enterocolitis in Neonatal Mice.

Anemia is a common and serious health problem, nearly universally diagnosed in preterm infants, and is associated with increased morbidity and mortality worldwide. Red blood cell (RBC) transfusion is a lifesaving and mainstay therapy; however, it has critical adverse effects. One consequence is necrotizing enterocolitis (NEC), an inflammatory bowel necrosis disease in preterm infants. The murine model of phlebotomy-induced anemia and RBC transfusion-associated NEC enables a detailed study of the molecular mechanisms underlying these morbidities and the evaluation of potential new therapeutic strategies. This protocol describes a detailed procedure for obtaining murine pups with phlebotomy-induced anemia and delivering an RBC transfusion that develops NEC.