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Antiviral drugs are a class of medications used for treating viral infections. Due to their widespread use, especially in cases of pandemics and limited human metabolism, antivirals have been detected in multiple environmental matrices. This study aims to evaluate the chronic effects of acyclovir, efavirenz, lamivudine and zidovudine using Ceriodaphnia dubia and Raphidocelis subcapitata. The results with R. subcapitata showed the following toxicities: zidovudine (IC50 = 5.442 mg L−1) < acyclovir (IC50 = 3.612 mg L−1) < lamivudine (IC50 = 3.013 mg L−1) < efavirenz (IC50 = 0.034 mg L−1). The results of the chronic bioassay with C. dubia demonstrated that zidovudine is the least toxic (EC50 = 5.671 mg L−1), followed by acyclovir (EC50 = 3.062 mg L−1), lamivudine (EC50 = 1.345 mg L−1) and efavirenz (EC50 = 0.026 mg L−1). Both species have been shown to be sensitive to efavirenz. A risk quotient (RQ) was calculated, and efavirenz had an RQ greater than 1 for both species, and lamivudine had an RQ greater than 1 for C. dubia, representing a high ecological risk for these organisms. Antivirals pose a significant environmental risk to aquatic organisms and should be taken into consideration in future monitoring of water sources.

Essential oils have shown promise as antiviral agents against several pathogenic viruses. In this work we hypothesized that essential oil components may interact with key protein targets of the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A molecular docking analysis was carried out using 171 essential oil components with SARS-CoV-2 main protease (SARS-CoV-2 Mpro), SARS-CoV-2 endoribonucleoase (SARS-CoV-2 Nsp15/NendoU), SARS-CoV-2 ADP-ribose-1″-phosphatase (SARS-CoV-2 ADRP), SARS-CoV-2 RNA-dependent RNA polymerase (SARS-CoV-2 RdRp), the binding domain of the SARS-CoV-2 spike protein (SARS-CoV-2 rS), and human angiotensin−converting enzyme (hACE2). The compound with the best normalized docking score to SARS-CoV-2 Mpro was the sesquiterpene hydrocarbon (E)-β-farnesene. The best docking ligands for SARS−CoV Nsp15/NendoU were (E,E)-α-farnesene, (E)-β-farnesene, and (E,E)−farnesol. (E,E)−Farnesol showed the most exothermic docking to SARS-CoV-2 ADRP. Unfortunately, the docking energies of (E,E)−α-farnesene, (E)-β-farnesene, and (E,E)−farnesol with SARS-CoV-2 targets were relatively weak compared to docking energies with other proteins and are, therefore, unlikely to interact with the virus targets. However, essential oil components may act synergistically, essential oils may potentiate other antiviral agents, or they may provide some relief of COVID-19 symptoms.

Frailty assessment has been identified as critical approach in chronic respiratory diseases with substantial impact in the health status and functionality in later life. Aging modifies the immune response leading to a chronic pro-inflammatory state and increased susceptibility to airway infections. Since epigenetic changes, airway epithelium dysfunction and inflammatory cytokine activity seem to be more pronounced in the immunosenescence, elderly asthmatics are at higher risk of poor clinical outcomes. Therefore, we hypothesize that frailty would be associated with the degree of asthma control in elderly patients with moderate to severe asthma. The aims of this study are to investigate association between frailty and asthma control in patients over 60 years old to estimate the prevalence of frailty in this study population. We plan to conduct a cross-sectional study with at least 120 patients above 60 years old with diagnostic of moderate to severe asthma according to Global Initiative for Asthma (GINA) guidelines, treated at a referral outpatient clinic. We defined asthma control by the six-domain Asthma Control Questionnaire (ACQ-6) and frailty phenotype in accordance with Fried scale and visual scale of frailty (VS-Frailty). We hope to analyze the multidimensional relationships between frailty and asthma and contribute to innovative therapeutic plans in geriatric asthma.

Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections. Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by (AgNP ) in combination with simvastatin against reference and multidrug-resistant bacterial strains. Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL against MRSA. AgNP with a size of 77.68± 33.95 nm and zeta potential -34.6 ± 12.7 mV showed an MIC of 0.212 mg mL against including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNP combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNP demonstrated antibacterial activity against producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNP and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA. Our results indicate that the combination of AgNP and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNP are required, with the same antibacterial activity.

The comparison between long acting insulin analogues (LAIA) and human insulin (NPH) has been investigated for decades, with many randomized controlled trials (RCTs) and systematic reviews giving mixed results. This overlapping and contradictory evidence has increased uncertainty on coverage decisions at health systems level. To conduct an overview of systematic reviews and update existing reviews, preparing new meta-analysis to determine whether LAIA are effective for T1D patients compared to NPH. We identified systematic reviews of RCTs that evaluated the efficacy of LAIA glargine or detemir, compared to NPH insulin for T1D, assessing glycated hemoglobin (A1C) and hypoglycemia. Data sources included Pubmed, Cochrane Library, EMBASE and hand-searching. The methodological quality of studies was independently assessed by two reviewers, using AMSTAR and Jadad scale. We found 11 eligible systematic reviews that contained a total of 25 relevant clinical trials. Two reviewers independently abstracted data. We found evidence that LAIA are efficacious compared to NPH, with estimates showing a reduction in nocturnal hypoglycemia episodes (RR 0.66; 95% CI 0.57; 0.76) and A1C (95% CI 0.23; 0.12). No significance was found related to severe hypoglycemia (RR 0.94; 95% CI 0.71; 1.24). This study design has allowed us to carry out the most comprehensive assessment of RCTs on this subject, filling a gap in diabetes research. Our paper addresses a question that is important not only for decision makers but also for clinicians.

ObjectiveThis study estimated the association between stress and periodontitis.Materials and methodsA cross-sectional study was conducted with a sample of 621 individuals. Information about individuals was obtained through a questionnaire. Stress was evaluated using the Perceived Stress Scale. The diagnosis of periodontitis was based on a complete periodontal examination including clinical attachment level, probing depth, and bleeding on probing. Prevalence ratios (PR), crude and adjusted, and their respective 95% confidence intervals (95%CI) were estimated by Poisson regression analysis.ResultsIn the final sample, 48.47% (301) of the individuals were classified as having stress, of which, 23.92% (72) had the diagnosis of periodontitis. Association measurements between stress and probing depth ≥ 4 mm (PRadjusted = 1.28, 95%CI [1.04 to 1.58]), stress and clinical attachment level ≥ 5 mm (PRadjusted = 1.15, 95%CI [1.01 to 1.31]), and stress and periodontitis (PRadjusted = 1.36, 95%CI [1.01 to 1.83]) showed that the frequency of these outcomes among those exposed to stress was 15–36% higher than those without the condition of stress, after adjustment for age, sex, schooling level, current smoking habit, pulmonary disease, and body mass index.ConclusionsThe findings showed positive association between exposure to stress and the presence of periodontitis, reaffirming the need to prevent and control stress.Clinical relevanceAlthough there are limitations in this study, the results showed that an association exists between stress and periodontitis, signaling the necessity of a multidisciplinary attention when considering the psychological status in the management of oral and general health conditions of the individual.

In a phase 3 trial, the addition of neoadjuvant and adjuvant pembrolizumab to standard care improved event-free survival among participants with locally advanced head and neck cancer without affecting surgical outcomes.

The monocyte chemoattractant protein 1 (MCP-1) belongs to the CC chemokine family and acts in the recruitment of C–C motif chemokine receptor 2 (CCR2)-positive immune cell types to inflammation sites. In testis, the MCP-1/CCR2 axis has been associated with the macrophage population’s functional regulation, which presents significant functions supporting germ cell development. In this context, herein, we aimed to investigate the role of the chemokine receptor CCR2 in mice testicular environment and its impact on male sperm production. Using adult transgenic mice strain that had the CCR2 gene replaced by a red fluorescent protein gene, we showed a stage-dependent expression of CCR2 in type B spermatogonia and early primary spermatocytes. Several parameters related to sperm production were reduced in the absence of CCR2 protein, such as Sertoli cell efficiency, meiotic index, and overall yield of spermatogenesis. Daily sperm production decreased by almost 40%, and several damages in the seminiferous tubules were observed. Significant reduction in the expression of important genes related to the Sertoli cell function (Cnx43, Vim, Ocln, Spna2) and meiosis initiation (Stra8, Pcna, Prdm9, Msh5) occurred in comparison to controls. Also, the number of macrophages significantly decreased in the absence of CCR2 protein, along with a disturbance in Leydig cell steroidogenic activity. In summary, our results show that the non-activation of the MCP-1/CCR2 axis disturbs the testicular homeostasis, interfering in macrophage population, meiosis initiation, blood–testis barrier function, and androgen synthesis, leading to the malfunction of seminiferous tubules, decreased testosterone levels, defective sperm production, and lower fertility index.

Cancer is as unique as the person fighting it. With the exception of a few biomarker-driven therapies, patients go through rounds of trial-and-error approaches to find the best treatment. Using patient-derived cell lines, we show that zebrafish larvae xenotransplants constitute a fast and highly sensitive in vivo model for differential therapy response, with resolution to reveal intratumor functional cancer heterogeneity. We screened international colorectal cancer therapeutic guidelines and determined distinct functional tumor behaviors (proliferation, metastasis, and angiogenesis) and differential sensitivities to standard therapy. We observed a general higher sensitivity to FOLFIRI [5-fluorouracil(FU)+irinotecan+folinic acid] than to FOLFOX (5-FU+oxaliplatin+folinic acid), not only between isogenic tumors but also within the same tumor. We directly compared zebrafish xenografts with mouse xenografts and show that relative sensitivities obtained in zebrafish are maintained in the rodent model. Our data also illustrate how KRAS mutations can provide proliferation advantages in relation to KRASWT and how chemotherapy can unbalance this advantage, selecting for a minor clone resistant to chemotherapy. Zebrafish xenografts provide remarkable resolution to measure Cetuximab sensitivity. Finally, we demonstrate the feasibility of using primary patient samples to generate zebrafish patient-derived xenografts (zPDX) and provide proof-of-concept experiments that compare response to chemotherapy and biological therapies between patients and zPDX. Altogether, our results suggest that zebrafish larvae xenografts constitute a promising fast assay for precision medicine, bridging the gap between genotype and phenotype in an in vivo setting.

Scrotal circumference data from 47,605 Nellore young bulls, measured at around 18 mo of age (SC18), were analyzed simultaneously with 27,924 heifer pregnancy (HP) and 80,831 stayability (STAY) records to estimate their additive genetic relationships. Additionally, the possibility that economically relevant traits measured directly in females could replace SC18 as a selection criterion was verified. Heifer pregnancy was defined as the observation that a heifer conceived and remained pregnant, which was assessed by rectal palpation at 60 d. Females were exposed to sires for the first time at about 14 mo of age (between 11 and 16 mo). Stayability was defined as whether or not a cow calved every year up to 5 yr of age, when the opportunity to breed was provided. A Bayesian linear-threshold-threshold analysis via Gibbs sampler was used to estimate the variance and covariance components of the multitrait model. Heritability estimates were 0.42 ± 0.01, 0.53 ± 0.03, and 0.10 ± 0.01, for SC18, HP, and STAY, respectively. The genetic correlation estimates were 0.29 ± 0.05, 0.19 ± 0.05, and 0.64 ± 0.07 between SC18 and HP, SC18 and STAY, and HP and STAY, respectively. The residual correlation estimate between HP and STAY was -0.08 ± 0.03. The heritability values indicate the existence of considerable genetic variance for SC18 and HP traits. However, genetic correlations between SC18 and the female reproductive traits analyzed in the present study can only be considered moderate. The small residual correlation between HP and STAY suggests that environmental effects common to both traits are not major. The large heritability estimate for HP and the high genetic correlation between HP and STAY obtained in the present study confirm that EPD for HP can be used to select bulls for the production of precocious, fertile, and long-lived daughters. Moreover, SC18 could be incorporated in multitrait analysis to improve the prediction accuracy for HP genetic merit of young bulls.