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Tetramethrin (Tm) is a commonly used pesticide that has been reported to exert estrogen-antagonistic effects selectively on female rats. The present study was undertaken to assess the protective role of lobaric acid (La) on estrous cycle in Tm-treated female Wistar rats. Female rats were exposed to Tm (50 mg/kg b.w/day) only or in combination with La at low (50 mg/kg b.w/day) or high (100 mg/kg b.w/day) dose for 30 days. The results showed that Tm altered the estrous cycle of female rats by decreasing the levels of luteinizing hormone, follicular-stimulating hormone, progesterone, estrone, and estradiol while increasing testosterone level. The morphology of vaginal smears of Tm-treated female rats showed the presence of abnormal cells and/or structures at different phases of estrus cycle. Strikingly, in (Tm + La)-treated rats, all the observed adverse effects of Tm on the hormonal parameters, cell morphology, and the length of each phase of estrous cycle were significantly diminished in a dose-dependent manner. The docking results showed that La competes with Tm for Gonadotropin-Releasing Hormone (GnRH) receptor, thereby reducing the toxicity of Tm but did not cancel the response of GnRH receptor completely. In conclusion, our results designated that La could be used as a potential candidate in the management of insecticide-induced alterations of the reproductive cycle of rodents.

Background Patients with out‐of‐hospital cardiac arrest (OHCA) in rural areas experience longer emergency response times and have lower survival rates compared with patients in urban areas. Volunteer responders might improve care and outcomes for patients with OHCA specifically in rural areas. Therefore, we investigated volunteer responder interventions based on the degree of urbanization. Methods and Results We included 1310 OHCAs from 3 different regions in Denmark where volunteer responders had arrived at the OHCA location. The location was classified as urban, suburban, or rural according to the Eurostat Degree of Urbanization Tool. A logistic regression model was used to examine associations between the degree of urbanization and volunteer responder arrival before emergency medical services, cardiopulmonary resuscitation, or defibrillation. We found the odds for volunteer responder arrival before emergency medical services more than doubled in rural areas (odds ratio [OR], 2.60 [95% CI, 1.91–3.53]) and suburban areas (OR, 2.05 [95% CI, 1.56–2.69]) compared with urban areas. In OHCA cases where volunteer responders arrived first, odds for bystander cardiopulmonary resuscitation was tripled in rural areas (OR, 3.83 [95% CI, 1.64–8.93]) and doubled in suburban areas (OR, 2.27 [95% CI, 1.17–4.41]) compared with urban areas. Bystander defibrillation was more common in suburban areas (OR, 1.53 [95% CI, 1.02–2.31]), where almost 1 out of 4 patients received bystander defibrillation, compared with urban areas. Conclusions Volunteer responders are significantly more likely to arrive before emergency medical services in rural and suburban areas than in urban areas. Patients with OHCA received more cardiopulmonary resuscitation in rural and suburban areas and more defibrillation in suburban areas than in urban areas.

Background: While several drugs are in the pipeline for treatment of various grades of COVID-19 disease, none of them have shown promise until now. Medicinal plants are crucial in developing and developed countries for their primary and basic health needs owing to better tolerability, superior compatibility with human body and having lesser side effects. Objective: To test adjuvant effect of AEV01, a patented herbal extract of kutki (Picrorhiza kurroa), in mild COVID19 in elderly patients at risk of complications and aging immunity. Methods: A prospective, phase 3, randomized, multicentric, placebo controlled double blinded parallel group interventional trial was conducted in elderly patients aged above 50 years diagnosed as COVID-19 with mild symptoms. 70 patients were randomized into two groups to receive AEV01 capsule (100 mg) and placebo respectively thrice daily for 30 days along with standard care of treatment as per national (WHO/ICMR) guidelines in both the groups. Clinical improvement timelines and corresponding scores using 8-point ordinal scale and NEWS were assessed for efficacy and safety of AEV01 in COVID-19 patients. Results: AEV01 group showed a significant improvement (p = 0.0001) in the normalization of the SpO2 rate and relief from cough. There was also significant difference in time to recovery, with patients in the AEV01 drug treated group recovering in 4.5 days as compared to Placebo in 9.1 days. ESR, LDH, serum ferritin, Neutrophil-Lymphocyte ratio (NLR), TNF- alpha, IL-6 and CD4 cell counts, which are considered as prognostic markers in COVID-19 infected patients, showed a significant improvement in patients treated with AEV01. The AEV01 drug treated group showed significant clinical improvement in the 8-point ordinal scale severity rating and National Early Warning Score (NEW) Score from day 3 onwards which continued up to end of study. Conclusion: AEV01 has shown a significant improvement in clinical and laboratory parameters. There was also reduction in the progression of the COVID-19 disease in unvaccinated elderly patients from mild to moderate when treated at an earlier stage.

Abstract Type 2 Diabetes (T2D) is often managed with metformin as the drug of choice. While it is effective overall, many patients progress to exhibit complications. Strategic drug combinations to tackle this problem would be useful. We constructed a genome-wide protein-protein interaction network capturing a global perspective of perturbations in diabetes by integrating T2D subjects’ transcriptomic data. We computed a ‘frequently perturbed subnetwork’ in T2D that captures common perturbations across tissue types and mapped the possible effects of Metformin onto it. We then identified a set of remaining T2D perturbations and potential drug targets among them, related to oxidative stress and hypercholesterolemia. We then identified Probucol as the potential co-drug for adjunct therapy with Metformin and evaluated the efficacy of the combination in a rat model of diabetes. We find Metformin-Probucol at 5:0.5 mg/kg effective in restoring near-normal serum glucose, lipid, and cholesterol levels.

Periodontal disease (PerioD) is a chronic inflammatory disease of dysbiotic etiology. Animal models and few human data showed a relationship between oral bacteria and gut dysbiosis. However, the effect of periodontal inflammation and subgingival dysbiosis on the gut is unknown. We hypothesized that periodontal inflammation and its associated subgingival dysbiosis contribute to gut dysbiosis even in subjects free of known gut disorders. We evaluated and compared elderly subjects with Low and High periodontal inflammation (assessed by Periodontal Inflamed Surface Area (PISA)) for stool and subgingival derived bacteria (assayed by 16S rRNA sequencing). The associations between PISA/subgingival dysbiosis and gut dysbiosis and bacteria known to produce short-chain fatty acid (SCFA) were assessed. LEfSe analysis showed that, in Low PISA, species belonging to Lactobacillus, Roseburia, and Ruminococcus taxa and Lactobacillus zeae were enriched, while species belonging to Coprococcus, Clostridiales, and Atopobium were enriched in High PISA. Regression analyses showed that PISA associated with indicators of dysbiosis in the gut mainly reduced abundance of SCFA producing bacteria (Radj = −0.38, p = 0.03). Subgingival bacterial dysbiosis also associated with reduced levels of gut SCFA producing bacteria (Radj = −0.58, p = 0.002). These results suggest that periodontal inflammation and subgingival microbiota contribute to gut bacterial changes.

SnO2-based gas sensors have been widely synthesized and used for the detection of various hazardous gases. However, the use of doped SnO2 in sensing applications has recently attracted increased interest due to the formation of a synergistic effect between the dopant and the host. Moreover, in the case of a surface acoustic wave (SAW) sensor, the piezoelectric material used in the fabrication of the sensor plays a crucial role in defining the response of the SAW sensor. As a ferroelectric material, barium strontium titanate (Ba0.6Sr0.4TiO3) has recently been studied due to its intriguing dielectric and electromechanical properties. Its high acoustic velocity and coupling coefficient make it a promising candidate for the development of acoustic devices; however, its use as a piezoelectric material in SAW sensors is still in its infancy. In this paper, we present the design, fabrication and validation of an indium doped SnO2-based SAW gas sensor on Ba0.6Sr0.4TiO3 thin film for room temperature (RT) applications. Pulsed laser deposition was used to deposit thin films of Ba0.6Sr0.4TiO3 and indium-doped SnO2. Different characterization techniques were employed to analyze the morphology and crystallization of the films. The performance of the fabricated sensor was validated by exposing it to different concentrations of ethanol and then analyzing the recorded frequency shift. The sensor exhibited fast response (39 s) and recovery (50 s) times with a sensitivity of 9.9 MHz/Δ. Moreover, the sensor had good linear response and reproducibility. The fabricated indium-doped SnO2-based SAW gas sensor could be suitable for practical room temperature applications.

This method article describes the fabrication of graphene-epoxy nanocomposites using two different solvents, dimethylformamide (DMF) and acetone, and validates the resulting thermal conductivity improvements. The study compared the two solvents at a filler composition of 7 wt% and found that DMF resulted in more uniform dispersion of graphene nanoparticles in the epoxy matrix, leading to a 44% improvement in thermal conductivity compared to acetone. Laser scanning confocal microscopy (LSCM) imaging showed that DMF-based composites had more evenly dispersed graphene nanoplatelets than acetone-based composites, which exhibited larger graphene agglomerations. Effective medium theory calculations showed that DMF led to almost 35% lower interface thermal resistance between graphene and epoxy compared to acetone. The validated fabrication method and findings provide new possibilities for developing high thermal conductivity graphene-epoxy nanocomposites for various thermal management applications. • This article describes methods for fabricating graphene-epoxy composites using acetone and DMF as solvents, and validates that DMF is better for achieving higher thermal conductivity in the composite.

Introduction In Denmark, multiple national initiatives have been associated with improved bystander defibrillation and survival following out-of-hospital cardiac arrest (OHCA) in public places. However, OHCAs in residential neighbourhoods continue to have poor outcomes. The Cardiac Arrest in Residential Areas with MoBile volunteer responder Activation trial aims to improve bystander defibrillation and survival following OHCA in residential neighbourhoods with a high risk of OHCA. The intervention consists of: (1) strategically deployed automated external defibrillators accessible at all hours, (2) cardiopulmonary resuscitation (CPR) training of residents and (3) recruitment of residents for a volunteer responder programme.Methods and analysis This is a prospective, pair-matched, cluster-randomised, superiority trial with clusters of 26 residential neighbourhoods, testing the effectiveness of the intervention in a real-world setting. The areas are randomised for intervention or control. Intervention and control areas will receive the standard OHCA emergency response, including volunteer responder activation. However, targeted automated external defibrillator deployment, CPR training and volunteer responder recruitment will only be provided in the intervention areas. The primary outcome is bystander defibrillation, and the secondary outcome is 30-day survival. Data on patients who had an OHCA will be collected through the Danish Cardiac Arrest Registry.Ethics and dissemination Approval to store OHCA data has been granted from the Legal Office, Capital Region of Denmark (j.nr: 2012-58-0004, VD-2018-28, I-Suite no: 6222, and P-2021-670). In Denmark, formal approval from the ethics committee is only obtainable when the study regards testing medicine or medical equipment on humans or using genome or diagnostic imagine as data source. The Ethics Committee of the Capital Region of Denmark has evaluated the trial and waived formal approval unnecessary (H-19037170). Results will be published in peer-reviewed papers and shared with funders, stakeholders, and housing organisations through summaries and presentations.Trial registration number ClinicalTrials.gov Registry (NCT04446585).

Summary: Older individuals and people with HIV (PWH) were prioritized for COVID-19 vaccination, yet comprehensive studies of the immunogenicity of these vaccines and their effects on HIV reservoirs are not available. Our study on 68 PWH and 23 HIV-negative participants aged 55 and older post-three vaccine doses showed equally strong anti-spike IgG responses in serum and saliva through week 48 from baseline, while PWH salivary IgA responses were low. PWH had diminished live-virus neutralization responses after two vaccine doses, which were ‘rescued’ post-booster. Spike-specific T cell immunity was enhanced in PWH with normal CD4+ T cell count, suggesting Th1 imprinting. The frequency of detectable HIV viremia increased post-vaccination, but vaccines did not affect the size of the HIV reservoir in most PWH, except those with low-level viremia. Thus, older PWH require three doses of COVID-19 vaccine for maximum protection, while individuals with unsuppressed viremia should be monitored for adverse reactions from HIV reservoirs.