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Autism spectrum disorders (ASD) are highly disabling developmental disorders with a population prevalence of 1-3%. Despite a strong genetic etiology, there are no current therapeutic options that target the core symptoms of ASD. Emerging evidence suggests that dysfunction of glutamatergic signaling, in particular through metabotropic glutamate receptor 5 (mGluR5) receptors, may contribute to phenotypic deficits and may be appropriate targets for pharmacologic intervention. This study assessed the therapeutic potential of 2-methyl-6-phenylethyl-pyrididine (MPEP), an mGluR5-receptor antagonist, on repetitive and anxiety-like behaviors in the valproic acid (VPA) mouse model of autism. Mice were exposed prenatally on day E13 to VPA and assessed for repetitive self-grooming and marble burying behaviors as adults. Anxiety-like behavior and locomotor activity were measured in an open-field. VPA-exposed mice displayed increased repetitive and anxiety-like behaviors, consistent with previously published results. Across both marble burying and self-grooming assays, MPEP significantly reduced repetitive behaviors in VPA-treated mice, but had no effect on locomotor activity. These results are consistent with emerging preclinical literature that mGluR5-antagonists may have therapeutic efficacy for core symptoms of autism.

This study assesses the possibilities of the Integrated Multi-satellite Retrievals for Global Precipitation Measurement (IMERG-GPM) to estimate extreme rainfall anomalies. A web application, the IMERG Precipitation Extractor (IPE), was developed which allows for the querying, visualization, and downloading of time-series satellite precipitation data for points, watersheds, country extents, and digitized areas. The tool supports different temporal resolutions ranging from 30 min to 1 week and facilitates advanced analyses such as anomaly detection and storm tracking, an important component for climate change study. To validate the IMERG precipitation data for anomaly estimation over a 22-year period (2001 to 2022), the Rainfall Anomaly Index (RAI) was calculated and compared with RAI data from 2360 NOAA stations across the conterminous United States (CONUS), considering both dry and wet climate regions. In the dry region, the results showed an average correlation coefficient (CC) of 0.94, a percentage relative bias (PRB) of −22.32%, a root mean square error (RMSE) of 0.96, a mean bias ratio (MBR) of 0.74, a Nash–Sutcliffe Efficiency (NSE) of 0.80, and a Kling–Gupta Efficiency (KGE) of 0.52. In the wet region, the average CC of 0.93, PRB of 24.82%, RMSE of 0.96, MBR of 0.79, NSE of 0.80, and KGE of 0.18 were computed. Median RAI indices from both the IMERG and NOAA indicated an increase in rainfall intensity and frequency since 2010, highlighting growing concerns about climate change. The study suggests that IMERG data can serve as a valuable alternative for modeling extreme rainfall anomalies in data-scarce areas, noting its possibilities, limitations, and uncertainties. The IPE web application also offers a platform for extending research beyond CONUS and advocating for further global climate change studies.

The study of indoor pollutants and radioactive nuclides imposes importance on human health as we spend most of our time indoors. Out of all the natural radioactive elements, Radon-222 and Radon220 are present in large abundance indoors. Both are radioactive and decay to various short-lived progenies by emitting high-energy alpha particles, so inhalation of such gases can harm the human body in various ways. In the present report, the concentration of Rn-222 and Rn-220 and its progenies are estimated from some dwellings of Samana city of Patiala district, Punjab. Pin-hole dosimeters with DRPS and DTPS were employed in 15 houses in the study area to measure indoor Rn-222 and Rn-220 concentrations. The concentration of Rn-222 ranges between 401.96 Bq/m 3 and 27.36 Bq/m 3 with mean value of 138.82 Bq/m3, and the concentration of Rn-220 varies from 222.2 Bq/ m 3 to 50 Bq/m 3 with the mean weight of 131.12 Bq/m 3 . The average inhalation dose was also calculated from the results and was found to have an average value of 2.19 mSv per year. The average weight of radon concentration was below the ICRP recommendation of 200-300 Bq/m 3 but the value is above these limits at some locations. Radon and thoron emission rates from soil samples near to the dwellings was also calculated.

Proton Pump Inhibitors (PPI) are one of the most prescribed medications in the United States. However, PPIs have been shown to increase the risk of enteric infections. Our study aims to evaluate the correlation between PPI and COVID-19 severity. We performed a retrospective cohort study on patients who tested positive for SARS-CoV-2 from March to August 2020. Patients were categorized based on PPI user status. Primary outcomes included need for hospital or ICU admission and 30-day mortality. Secondary outcomes looked to determine the severity of COVID-19 infection and effect of comorbid conditions. 2,594 patients were reviewed. The primary outcomes of our study found that neither active nor past PPI use was associated with increased hospital admission or 30-day mortality following completion of multivariate analysis. Additionally, there was no association between COVID-19 infection and the strength of PPI dosing (low, standard, high). However, the following covariates were independently and significantly associated with increased admission: age, male gender, diabetes, COPD, composite cardiovascular disease, kidney disease, and obesity. The following covariates were associated with increased mortality: age, male gender, COPD, and kidney disease. In conclusion, the high risk features and comorbidities of PPI users were found to have a stronger correlation to severe COVID-19 infection and poor outcomes as opposed to the use of PPI therapy.

Glioblastoma multiforme (GBM) are resistant to TNF α -induced apoptosis and blockade of TNF α -induced NF- κ B activation sensitizes glioma cells to apoptosis. As Casein kinase-2 (CK2) induces aberrant NF- κ B activation and as we observed elevated CK2 levels in GBM tumors, we investigated the potential of CK2 inhibitors (CK2-Is) - DRB and Apigenin in sensitizing glioma cells to TNF α -induced apoptosis. CK2-Is and CK2 small interfering RNA (siRNA) reduced glioma cell viability, inhibited TNF α -mediated NF- κ B activation, and sensitized cell to TNF α -induced apoptosis. Importantly, CK2-Is activated p53 function in wild-type but not in p53 mutant cells. Activation of p53 function involved its increased transcriptional activation, DNA-binding ability, increased expression of p53 target genes associated with cell cycle progression and apoptosis. Moreover, CK2-Is decreased telomerase activity and increased senescence in a p53-dependent manner. Apoptotic gene profiling indicated that CK2-Is differentially affect p53 and TNF α targets in p53 wild-type and mutant glioma cells. CK2-I decreased MDM2-p53 association and p53 ubiquitination to enhance p53 levels. Interestingly, CK2-Is downregulated SIRT1 activity and over-expression of SIRT1 decreased p53 transcriptional activity and rescued cells from CK2-I-induced apoptosis. This ability of CK2-Is to sensitize glioma to TNF α -induced death via multiple mechanisms involving abrogation of NF- κ B activation, reactivation of wild-type p53 function and SIRT1 inhibition warrants investigation.

India retains the world’s largest burden of anemia despite decades of economic growth and anemia prevention programming. Accurate screening and estimates of anemia prevalence are critical for successful anemia control. Evidence is mixed on the performance of HemoCue, a point-of-care testing device most widely used for large-scale surveys. The use of dried blood spots (DBS) to assess hemoglobin (Hb) concentration is a potential alternative, particularly in field settings. The objective of this study is to assess Hb measurement agreement between capillary HemoCue and DBS among two age groups, children 6–59 months and females age 12–40 years. We analyzed data from the baseline round of a cluster randomized rice fortification intervention in Cuddalore district of Tamil Nadu, India. Capillary blood was collected from a subset of participants for Hb assessment by HemoCue 301 and DBS methods. We calculated Lin’s concordance correlation coefficient, and tested bias by conducting paired t-tests of Hb concentration. Independence of the bias and Hb magnitude was examined visually using Bland–Altman plots and statistically tested by Pearson’s correlation. We assessed differences in anemia classification using McNemar’s test of marginal homogeneity. Concordance between HemoCue and DBS Hb measures was moderate for both children 6–59 months ( ρ c  = 0.67; 95% CI 0.65, 0.71) and females 12–40 years ( ρ c  = 0.67: 95% CI 0.64, 0.69). HemoCue measures were on average 0.06 g/dL higher than DBS for children (95% CI 0.002, 0.12; p = 0.043) and 0.29 g/dL lower than DBS for females (95% CI − 0.34, − 0.23; p < 0.0001). 50% and 56% of children were classified as anemic according to HemoCue and DBS, respectively (p < 0.0001). 55% and 47% of females were classified as anemic according to HemoCue and DBS, respectively (p < 0.0001). There is moderate statistical agreement of Hb concentration between HemoCue and DBS for both age groups. The choice of Hb assessment method has important implications for individual anemia diagnosis and population prevalence estimates. Further research is required to understand factors that influence the accuracy and reliability of DBS as a methodology for Hb assessment.

Context: Pro-inflammatory markers play a key role in the pathogenesis of various Flavivirus infection. Aim: In this study, we evaluated the role of these markers in neurological manifestations of dengue. Settings and Designs: Consecutive dengue cases with different neurological manifestations who presented between August 2012 and July 2014 were studied in hospital-based case-control study. Materials and Methods: Interleukin (IL-6) and IL-8 level were measured in serum and cerebrospinal fluid (CSF) of dengue cases with different neurological manifestations and also in age- and sex-matched controls. Level was analyzed with various parameters and outcomes. Statistical Analysis: Statistical analysis was done using SPSS version 16.0 by applying appropriate statistical methods. P < 0.05 considered statistically significant. Results: Out of the 40 enrolled cases of dengue with neurological manifestations, 29 had central nervous system and 11 had peripheral nervous system (CNS/PNS) manifestations. In CNS group, both IL-6 and IL-8 (CSF and serum) were significantly elevated (P < 0.001), whereas CSF IL-6 (P = 0.008), serum IL-6 (P = 0.001), and serum IL-8 (P = 0.005) were significantly elevated in PNS group. CSF IL-6, serum IL-6, and IL-8 were significantly elevated in poor outcome patients in CNS group (P < 0.05). CSF IL-6 and IL-8 were significantly elevated in CSF dengue positive cases as compared to CSF negative patients (P < 0.05). Cytokine level was not significantly correlated with neuroimaging abnormality in CNS group. Nine patients died and the remainder recovered. Conclusion: Elevated level of IL-6 and IL-8 is associated with different neurological manifestations and poor outcome, but whether they are contributing to neuropathogenesis or simply a correlate of severe disease remains to be determined.

Mycotoxins are carcinogenic secondary metabolites of fungi that have been linked to infant growth faltering. In this study, we quantified co‐occurring mycotoxins in breast milk and food samples from Haryana, India, and characterized determinants of exposure. Deterministic risk assessment was conducted for mothers and infants. We examined levels of eight mycotoxins (Aflatoxin B1, B2, G1, G2, M1, M2; Ochratoxin A, B) in 100 breast milk samples (infants 2–4 months) using ultra‐high‐performance liquid chromatography tandem mass spectrometry. Aflatoxin B1 (AFB1), fumonisin B1 (FB1) and deoxynivalenol (DON) were detected in several food items (n = 298) using enzyme‐linked immunosorbent assays. We report novel data on the presence of mycotoxins in breast milk samples from India. Whereas breast milk concentrations (AFM1 median: 13.7; range: 3.9–1200 ng/L) remain low, AFM1 was detected above regulatory limits in 27% of animal milk samples. Additionally, 41% of infants were above provisional maximum tolerable daily intake (PMTDI) limits for AFM1 due to consumption of breast milk (mean: 3.04, range: 0.26–80.7 ng kg−1 bw day−1). Maternal consumption of breads (p < 0.05) was associated with breast milk AFM1 exposure. AFB1 (μg/kg) was detected in dried red chilies (15.7; 0–302.3), flour (3.13; 0–214.9), groundnuts (0; 0–249.1), maize (56.0; 0–836.7), pearl millet (1.85; 0–160.2), rice (0; 0–195.6), wheat (1.9; 0–196.0) and sorghum (0; 0–63.5). FB1 (mg/kg) was detected in maize (0; 0–61.4), pearl millet (0; 0–35.4) and sorghum (0.95; 0–33.2). DON was not detected in food samples. Mothers in our study exceeded PMTDI recommendations for AFB1 due to consumption of rice and flour (mean: 75.81; range: 35.2–318.2 ng kg−1 bw day−1). Our findings show the presence of Aflatoxin B1 and M1 at various levels of the food chain and in breast milk, with estimated intakes exceeding PMTDI recommendations. Aflatoxins are known carcinogens and have also been linked to stunting in children. Their presence across the food system and in breast milk is concerning, thus warranting further research to replicate and expand on our findings and to understand implications for maternal and child health.

Anticancer chemotherapy (ACT) remains a cornerstone in cancer treatment, despite significant advances in pharmacology over recent decades. However, its associated side effect toxicity continues to pose a major concern for both oncology clinicians and patients, significantly impacting treatment protocols and patient quality of life. Current clinical strategies to mitigate ACT-induced toxicity have proven largely unsatisfactory, leaving a critical unmet need to block toxicity mechanisms without diminishing ACT's therapeutic efficacy. This review aims to document the molecular mechanisms underlying ACT toxicity and highlight research efforts exploring the protective effects of trace elements (TEs) and their nanoparticles (NPs) against these mechanisms. Our literature review reveals that the primary driver of ACT toxicity is redox imbalance, which triggers oxidative inflammation, apoptosis, endoplasmic reticulum stress, mitochondrial dysfunction, autophagy, and dysregulation of signaling pathways such as PI3K/mTOR/Akt. Studies suggest that TEs, including zinc, selenium, boron, manganese, and molybdenum, and their NPs, can potentially counteract ACT-induced toxicity by inhibiting oxidative stress-mediated pathways, including NF-κB/TLR4/MAPK/NLRP3, STAT-3/NLRP3, Bcl-2/Bid/p53/caspases, and LC3/Beclin-1/CHOP/ATG6, while also upregulating protective signaling pathways like Sirt1/PPAR-γ/PGC-1α/FOXO-3 and Nrf2/HO-1/ARE. However, evidence regarding the roles of lncRNA and the Wnt/β-catenin pathway in ACT toxicity remains inconsistent, and the impact of TEs and NPs on ACT efficacy is not fully understood. Further research is needed to confirm the protective effects of TEs and their NPs against ACT toxicity in cancer patients. In summary, TEs and their NPs present a promising avenue as adjuvant agents for preventing non-target organ toxicity induced by ACT.