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Plumbagin, a hydroxy-1,4-naphthoquinone, confers neuroprotection via antioxidant and anti-inflammatory properties. The present study aimed to assess the effect of plumbagin on behavioral and memory deficits induced by intrahippocampal administration of Quinolinic acid (QA) in male Wistar rats and reveal the associated mechanisms. QA (300 nM/4 μL in Normal saline) was administered i.c.v. in the hippocampus. QA administration caused depression-like behavior (forced swim test and tail suspension tests), anxiety-like behavior (open field test and elevated plus maze), and elevated anhedonia behavior (sucrose preference test). Furthermore, oxidative–nitrosative stress (increased nitrite content and lipid peroxidation with reduction of GSH), inflammation (increased IL-1β), cholinergic dysfunction, and mitochondrial complex (I, II, and IV) dysfunction were observed in the hippocampus region of QA-treated rats as compared to normal controls. Plumbagin (10 and 20 mg/kg; p.o.) treatment for 21 days significantly ameliorated behavioral and memory deficits in QA-administered rats. Moreover, plumbagin treatment restored the GSH level and reduced the MDA and nitrite level in the hippocampus. Furthermore, QA-induced cholinergic dysfunction and mitochondrial impairment were found to be ameliorated by plumbagin treatment. In conclusion, our results suggested that plumbagin offers a neuroprotective potential that could serve as a promising pharmacological approach to mitigate neurobehavioral changes associated with neurodegeneration.

Background and Aims: Goal-directed fluid therapy (GDFT) has conflicting evidence regarding outcomes in neurosurgical patients. This meta-analysis aimed to compare the effect of GDFT and conventional fluid therapy on various perioperative outcomes in patients undergoing neurosurgical procedures. Methods: A comprehensive literature search was conducted using PubMed, EMBASE, Scopus, ProQuest, Web of Science, EBSCOhost, Cochrane and preprint servers. The search was conducted up until 16 October 2023, following PROSPERO registration. The search strategy included terms related to GDFT, neurosurgery and perioperative outcomes. Only randomised controlled trials involving adult humans and comparing GDFT with standard/liberal/traditional/restricted fluid therapy were included. The studies were evaluated for risk of bias (RoB), and pooled estimates of the outcomes were measured in terms of risk ratio (RR) and mean difference (MD). Results: No statistically significant difference was observed in neurological outcomes between GDFT and conventional fluid therapy [RR with 95% confidence interval (CI) was 1.10 (0.69, 1.75), two studies, 90 patients, low certainty of evidence using GRADEpro]. GDFT reduced postoperative complications [RR = 0.67 (0.54, 0.82), six studies, 392 participants] and intensive care unit (ICU) and hospital stay [MD (95% CI) were -1.65 (-3.02, -0.28) and -0.94 (-1.47, -0.42), respectively] with high certainty of evidence. The pulmonary complications were significantly lower in the GDFT group [RR (95% CI) = 0.55 (0.38, 0.79), seven studies, 442 patients, high certainty of evidence]. Other outcomes, including total intraoperative fluids administered and blood loss, were comparable in GDFT and conventional therapy groups [MD (95% CI) were -303.87 (-912.56, 304.82) and -14.79 (-49.05, 19.46), respectively]. Conclusion: The perioperative GDFT did not influence the neurological outcome. The postoperative complications and hospital and ICU stay were significantly reduced in the GDFT group. Keywords: Craniotomy, fluid therapy, goal-directed, meta-analysis, neurosurgery, neurological outcomes, Author(s): Kiran Jangra [1]; Aravind P. Gandhi [2]; Nitasha Mishra (corresponding author) [3]; Muhammad Aaqib Shamim [4]; Bijaya K Padhi [5] INTRODUCTION Fluid therapy during intraoperative period is vital since [...]

The present study explored the correlation between different types of stress (acute and chronic) and the influence of their negative emotional manifestations on delinquent tendencies in adolescent students. Within the framework of the general strain theory, the study aims to analyse the intermediary role of depression in the relationship between anxiety and stress. This study investigated the relationship between stress, anxiety, depression, and delinquency proneness in adolescent school students in Sonepat, India. The present study utilised the descriptive survey method. Data were collected using standardised questionnaires based on self-reporting. Anxiety depression and stress scale and delinquency proneness scale were used to collect data from a sample of 200 students aged between 14 and 18 years from various schools in the district. The comparison (using independent t-test) revealed that levels of anxiety (t = -1.683, p = 0.094), depression (t = -0.196, p = 0.845), and delinquency proneness (t = -1.348, p = 0.179) were not significantly different between males and females, with the exception of stress (t = -2.929, p = 0.004). Furthermore, results of the Pearson product-moment correlation indicated a significant positive association between stress, anxiety, depression, and delinquency proneness. Regression analysis results showed that stress, anxiety, and depression have a significant effect on delinquency proneness (F(3, 196) = 28.2, p < 0.001). It further indicated that stress, anxiety, and depression cause 29.1% variation in delinquency proneness. In addition, results of mediation analysis showed that depression mediates the relationship between anxiety and delinquency proneness (accounts for 82.1% mediation). Furthermore, depression also mediates the relationship between stress and delinquency proneness (accounts for 74.5% mediation). The results support the general strain theory, which posits that strain (anxiety and stress) can lead to delinquency proneness, which is mediated by depression. Research shows that delinquency proneness, depression, and stress are prevalent among adolescents. To prevent juvenile delinquency, effective intervention programs should focus on equipping young people with interpersonal skills and coping strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes several proteins that inhibit host interferon responses. Among these, ORF6 antagonizes interferon signaling by disrupting nucleocytoplasmic trafficking through interactions with the nuclear pore complex components Nup98-Rae1. However, the roles and contributions of ORF6 during physiological infection remain unexplored. We assessed the role of ORF6 during infection using recombinant viruses carrying a deletion or loss-of-function (LoF) mutation in ORF6. ORF6 plays key roles in interferon antagonism and viral pathogenesis by interfering with nuclear import and specifically the translocation of IRF and STAT transcription factors. Additionally, ORF6 inhibits cellular mRNA export, resulting in the remodeling of the host cell proteome, and regulates viral protein expression. Interestingly, the ORF6:D61L mutation that emerged in the Omicron BA.2 and BA.4 variants exhibits reduced interactions with Nup98-Rae1 and consequently impairs immune evasion. Our findings highlight the role of ORF6 in antagonizing innate immunity and emphasize the importance of studying the immune evasion strategies of SARS-CoV-2.

Abstract Influenza viruses pose a threat to public health as evidenced by severe morbidity and mortality in humans on a yearly basis. Given the constant changes in the viral glycoproteins owing to antigenic drift, seasonal influenza vaccines need to be updated periodically and effectiveness often drops due to mismatches between vaccine and circulating strains. In addition, seasonal influenza vaccines are not protective against antigenically shifted influenza viruses with pandemic potential. Here, we have developed a highly immunogenic vaccination regimen based on live-attenuated influenza vaccines (LAIVs) comprised of an attenuated virus backbone lacking non-structural protein 1 (ΔNS1), the primary host interferon antagonist of influenza viruses, with chimeric hemagglutinins (cHA) composed of exotic avian head domains with a highly conserved stalk domain, to redirect the humoral response towards the HA stalk. In this study, we showed that cHA-LAIV vaccines induce robust serum and mucosal responses against group 1 stalk and confer antibody-dependent cell cytotoxicity activity. Mice that intranasally received cH8/1-ΔNS1 followed by a cH11/1-ΔNS1 heterologous booster had robust humoral responses for influenza A virus group 1 HAs and were protected from seasonal H1N1 influenza virus and heterologous highly pathogenic avian H5N1 lethal challenges. When compared with mice immunized with the standard of care or cold-adapted cHA-LAIV, cHA-ΔNS1 immunized mice had robust antigen-specific CD8+ T-cell responses which also correlated with markedly reduced lung pathology post-challenge. These observations support the development of a trivalent universal influenza vaccine for the protection against group 1 and group 2 influenza A viruses and influenza B viruses.

The present study explored the correlation between different types of stress (acute and chronic) and the influence of their negative emotional manifestations on delinquent tendencies in adolescent students. Within the framework of the general strain theory, the study aims to analyse the intermediary role of depression in the relationship between anxiety and stress. This study investigated the relationship between stress, anxiety, depression, and delinquency proneness in adolescent school students in Sonepat, India.

Abstract The local interaction within poly(vinylidene fluoride)/poly(3,4‐ethyelenedioxythiophene):poly(styrelenesulfonate) (PVDF/PEDOT:PSS) composite films has been explored in this study. Vibrational and impedance spectroscopy were used extensively to investigate the potential interactions within the moieties of PVDF and PEDOT:PSS in the composite. The increased concentration of PEDOT:PSS used as additives enhanced the dielectric constant of the composite films significantly. Both the AC conductivity and the estimated mobility also increased in the composite films with increasing additives. X‐ray absorption spectroscopy gave an insight into the local chain interactions within the polymer composite films. A shift in the C K‐edge toward higher energy confirmed the local interaction of the polymer moieties, suggesting a change in the polymer chain structure due to the possible association of moieties.

Following India’s economic liberalization, rapid economic growth is driving urban sprawl in mid-sized cities, altering land use patterns from the core to the periphery of the city. This study offers a comprehensive analysis of the evolving urban landscape in the Sonipat-Kundli urban agglomeration within the Delhi-NCR region, focusing on land use changes. Leveraging remote sensing data and analytical techniques, the study spans 1991 to 2021, using Landsat imagery and ERDAS Imagine software. Employing a Maximum Likelihood Classifier, it creates Land Use Land Cover maps, evaluating accuracy with the Kappa coefficient. Utilizing built-up density and the Shannon Entropy model, it assesses urban sprawl dynamics. Zoning, based on road networks and CBD buffer zones, enhances the analysis. Land transformation indicates that large tracts of agricultural land are directly converted to built-up patches which are used majorly for residential and industrial purposes. Notably, a leapfrog pattern of sprawl, driven by industrial development, is observed encroaching on agricultural land in Kundli away from the core city of Sonipat. These findings provide vital insights for future urban planning, policy formulation, and sustainable development initiatives in the region.

Understanding the zoonotic risks posed by bat coronaviruses (CoVs) is critical for pandemic preparedness. Herein, we generated recombinant vesicular stomatitis viruses (rVSVs) bearing spikes from divergent bat CoVs to investigate their cell entry mechanisms. Unexpectedly, the successful recovery of rVSVs bearing the spike from SHC014-CoV, a SARS-like bat CoV, was associated with the acquisition of a novel substitution in the S2 fusion peptide-proximal region (FPPR). This substitution enhanced viral entry in both VSV and coronavirus contexts by increasing the availability of the spike receptor-binding domain to recognize its cellular receptor, ACE2. A second substitution in the S1 N-terminal domain, uncovered through the rescue and serial passage of a virus bearing the FPPR substitution, further enhanced spike:ACE2 interaction and viral entry. Our findings identify genetic pathways for adaptation by bat CoVs during spillover and host-to-host transmission, fitness trade-offs inherent to these pathways, and potential Achilles' heels that could be targeted with countermeasures.

Background: PCOS has been known to predispose to morbidity by its relationship with the metabolic syndrome and CVD. Dyslipidemia and alterations in anthropometric parameters are suggestive of the underlying metabolic risk in PCOS. Methods: Fifty patients of PCOS (aged 18-50 years) and equal number of healthy females of same age group were selected. Anthropometric measurements and lipid profile were estimated while non-HDL-C was calculated. The comparison amongst the groups was made on the basis of independent ‘t’ test, Pearson’s correlation and AUROC analysis. Results: Statistical analysis revealed that anthropometric measurements of the cases were significantly higher. Serum triglyceride and non-HDL-C levels were found to be significantly high whereas other lipid parameters could not correlate well. AUROC analysis revealed that the area under the curve for TG and non-HDL-C was found to be 0.653 (95% Confidence interval: 0.542, 0.763) and 0.627 (95% Confidence interval: 0.516, 0.739) respectively. Conclusion: The anthropometric parameters should be an integral part in the routine assessment of PCOS. Also, the weight management, lifestyle counselling and early screening should start from adolescence to attenuate the severity of PCOS.