Rational Approach toward COVID-19's Main Protease Inhibitors: A Hierarchical Biochemoinformatics Analysis.

This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from -6.2 to -9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein-ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.

Immediate effect of extracorporeal shockwave therapy in patients with chronic non-specific low back pain: A randomised placebo-controlled triple-blind trial.

OBJECTIVE: To compare the immediate effects of shockwave therapy using two different tips in patients with chronic non-specific low back pain. DESIGN: Randomised placebo-controlled study with three intervention groups. SETTING: The patients recruited for this study were sent for physiotherapy treatment at primary care between May and July 2022. PARTICIPANTS: Eighty-one patients with chronic non-specific low back pain aged 18-80 years with pain for ≥3 months and pain intensity ≥3 were randomly recruited for the study. INTERVENTION: The patients received a single intervention of radial shockwave therapy with 2000 discharges at 100 mJ energy and 5 Hz frequency using concave or convex tips or placebo treatment. MAIN MEASURES: The primary outcome was pain intensity immediately post-intervention. The secondary outcomes were pressure pain threshold, temporal summation of pain, and functional performance. Data were collected at baseline and post-intervention. RESULTS: The post-intervention pain intensity in the concave tip group is an average of two points lower (95% CI = -3.6, -0.4; p < 0.01) than that in the placebo group. The post-intervention pressure pain threshold for the concave tip group was an average of 62.8 kPa higher (95% CI = 0.4, 125.1; p < 0.05) than for the convex tip group and 76.4 kPa higher (95% CI = 14, 138.7; p < 0.01) than in the placebo group. CONCLUSION: The concave tip shockwave therapy is effective in reducing pain and local hyperalgesia in patients with chronic non-specific low back pain.

Cultivable Fungi from Amazon River Dolphins Engaged in Wildlife Ecotourism in the Anavilhanas National Park, Brazil.

Amazon River dolphins are an important flagship species in the Anavilhanas National Park, Brazil, where they interact with visitors. This study aimed to quantify and identify fungi isolated from dolphin skin and oral samples and their surrounding environment in this unique ecosystem. Samples were collected from three dolphins and water samples from Flutuante dos Botos and the Novo Airão city harbor. Fungi were isolated using culture media and identified through micromorphology assays and ITS region sequencing. Oral swab samples resulted in culture of Trichosporon montevideense and Exophiala dermatitidis. Skin samples from one dolphin revealed Toxicocladosporium irritans and Diaporthe lithocarpus. Water samples exhibited higher fungal counts and diversity, with Rhodotorula mucilaginosa, Exophiala dermatitidis, Penicillium citrinum, Fomitopsis meliae, and Nectria pseudotrichia identified at the collection site and Candida spencermartinsiae and Penicillium chermesinum at the city harbor. This study provides important insights into the fungal diversity associated with Amazon River dolphins and their environment, enhancing our understanding of the public health and ecological dynamics in the Anavilhanas National Park.

Adapted Sequential Extraction Protocol to Study Mercury Speciation in Gold Mining Tailings: Implications for Environmental Contamination in the Amazon.

Artisanal small-scale gold mining (ASGM), an increasingly prevalent activity in South America, generates mercury-contaminated tailings that are often disposed of in the environment, leading to the introduction of mercury into ecosystems and the food web, where it bioaccumulates. Therefore, studying the geochemical processes involved in the desorption and dissolution of mercury in these tailings is essential for critical risk evaluations in the short and long term. For this purpose, sequential extraction procedures (SEPs) can be useful because they help to identify the phases to which Hg is associated, although they also have limitations such as a lack of selectivity and specificity. In this work, we propose a modified four-step SEP: exchangeable mercury (F1), oxidizable mercury (F2), mercury bound to Fe oxides (F3), and strongly bound mercury (F4). To test this adapted sequential extraction method, we evaluated the Hg contamination in mercury-contaminated tailings of the Amazon basin. The results revealed a total mercury concentration of 103 ± 16 mg·kg-1 in the tailings, with a significant portion in F1 (28% of the total), where Hg was bioavailable. The large Hg concentration in F3 (36%) suggested that Fe oxides likely contribute to mercury retention. Together, the SEP results emphasize the urgent need for improved surveillance of gold mining activities and responsible tailings management practices to mitigate environmental contamination and safeguard the health of the Amazon ecosystem.

Antifungal susceptibility and multilocus sequence typing (MLST) of Cryptococcus neoformans complex from HIV-associated cryptococcal meningitis patients in Manaus, Amazonas, Brazil.

Cryptococcus neoformans is primarily responsible for cases of cryptococcal meningitis in individuals with HIV/AIDS. This study evaluated the susceptibility of C. neoformans obtained from individuals with cryptococcal meningitis associated with HIV/AIDS in Manaus, Amazonas, Brazil, against the action of the antifungals amphotericin B, flucytosine, fluconazole, itraconazole and posaconazole and analyzed it using Multilocus Sequence Typing (MLST) in order to identify the Sequence Types (STs). We analyzed 30 isolates of C. neoformans, from 24 HIV/AIDS patients diagnosed with cryptococcosis from 2017 to 2019 in a reference hospital, in addition to 3 environmental isolates: 1 isolate obtained in the home of a patient and 2 isolates obtained from neighboring homes of patients. 86.6% (n = 26/30) of the clinical isolates were identified as C. neoformans VNI ST93, 6.6% (n = 2/30) as C. neoformans VNI ST5, 3.3% (n = 1/30) as C. neoformans VNI ST32 and 3.3% (n = 1/30) as C. neoformans VNB ST232. The environmental isolates were identified as C. neoformans VNI ST93 (n = 3/3). 96.6% (n = 29/30) isolates were sensitive to amphotericin B, though there was variation in the MIC. 60% (n = 18/30) presented a MIC above the proposed epidemiological cutoff values for one or more antifungals. All environmental isolates were sensitive to the tested antifungals. The MLST showed that there is an important relationship between C. neoformans VNI ST93 and individuals with HIV/AIDS, including in the environmental isolates analyzed. C. neoformans VNB ST232 was observed for the first time in Amazonas. Amphotericin B was proven to be the best drug, but fluconazole and posaconazole also showed relevant action.

Impact of the COVID-19 pandemic on perinatal care and outcomes: A retrospective study in a tertiary hospital in Northern Ghana.

BACKGROUND: Perinatal mortality remains a global challenge. This challenge may be worsened by the negative effects of the COVID-19 pandemic on maternal and child health. OBJECTIVES: Examine the impact of the COVID-19 pandemic on perinatal care and outcomes in the Tamale Teaching Hospital in northern Ghana. METHODS: A hospital-based retrospective study was conducted in the Tamale Teaching Hospital. We compared antenatal care attendance, total deliveries, cesarean sections, and perinatal mortality before the COVID-19 pandemic (March 1, 2019 to February 28, 2020) and during the COVID-19 pandemic (March 1, 2020 to February 28, 2021). Interrupted time series analyses was performed to evaluate the impact of the COVID-19 pandemic on perinatal care and outcomes at TTH. RESULTS: A total number of 35,350 antenatal visits and 16,786 deliveries were registered at TTH from March 2019 to February 2021. Antenatal care, early neonatal death, and emergency cesarean section showed a rapid decline after the onset of the pandemic, with a progressive recovery over the following months. The total number of deliveries and fresh stillbirths showed a step change with a marked decrease during the pandemic, while the macerated stillbirths showed a pulse change, a temporary marked decrease with a quick recovery over time. CONCLUSION: The COVID-19 pandemic had a negative impact on perinatal care and outcomes in our facility. Pregnancy monitoring through antenatal care should be encouraged and continued even as countries tackle the pandemic.

Applicability of machine learning algorithm to predict the therapeutic intervention success in Brazilian smokers.

Smoking cessation is an important public health policy worldwide. However, as far as we know, there is a lack of screening of variables related to the success of therapeutic intervention (STI) in Brazilian smokers by machine learning (ML) algorithms. To address this gap in the literature, we evaluated the ability of eight ML algorithms to correctly predict the STI in Brazilian smokers who were treated at a smoking cessation program in Brazil between 2006 and 2017. The dataset was composed of 12 variables and the efficacies of the algorithms were measured by accuracy, sensitivity, specificity, positive predictive value (PPV) and area under the receiver operating characteristic curve. We plotted a decision tree flowchart and also measured the odds ratio (OR) between each independent variable and the outcome, and the importance of the variable for the best model based on PPV. The mean global values for the metrics described above were, respectively, 0.675±0.028, 0.803±0.078, 0.485±0.146, 0.705±0.035 and 0.680±0.033. Supporting vector machines performed the best algorithm with a PPV of 0.726±0.031. Smoking cessation drug use was the roof of decision tree with OR of 4.42 and importance of variable of 100.00. Increase in the number of relapses also promoted a positive outcome, while higher consumption of cigarettes resulted in the opposite. In summary, the best model predicted 72.6% of positive outcomes correctly. Smoking cessation drug use and higher number of relapses contributed to quit smoking, while higher consumption of cigarettes showed the opposite effect. There are important strategies to reduce the number of smokers and increase STI by increasing services and drug treatment for smokers.

Antimicrobial activity of carvacrol and its derivatives on Mycobacterium spp.: systematic review of preclinical studies.

Background: The scope of the study was to analyze original preclinical studies on the antimicrobial effects of carvacrol and derivatives on the Mycobacterium genus. Materials & methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, four databases (PubMed, Web of Science, SCOPUS and EMBASE) were searched. Results: The search retrieved 392 records, of which 11 papers were selected. Heterogeneity in the techniques and mycobacterial targets was observed. Carvacrol demonstrated synergistic antimycobacterial activity with rifampicin against multidrug-resistant Mycobacterium tuberculosis on membranes and biofilms. In silico approaches showed specific targets in mycobacteria, by inhibition and molecular docking assays, on the enzyme chorismate mutase and the heat shock protein 16.3. Conclusion: Carvacrol has been shown to be a scaffold candidate for future molecules with activity against mycobacteria.

Histoplasmosis in HIV/AIDS patients in Amazonas, Northern Brazil.

Histoplasmosis is commonly observed in AIDS patients as a neglected opportunistic disease that has an important relationship with environmental factors. The present study described the clinical characteristics of HIV/AIDS patients diagnosed with disseminated histoplasmosis in a tertiary healthcare facility in Manaus, Amazonas, Brazil, and evaluated the patients' homes and urban environmental samples as a source of exposure to Histoplasma capsulatum. A review of medical records from 2017 to 2019 of patients with HIV/AIDS associated with histoplasmosis was carried out, as well as the collection of environmental samples in the homes of these patients. These samples were subjected to DNA extraction and then subjected to qPCR. A total of 62 patients diagnosed with HIV/AIDS and histoplasmosis were identified, which corresponds to 4.5% (n = 62/1372) of the HIV/AIDS cases detected in the period. Of these, 68% (n = 42/62) were male, with a mean age of 36 years and low education. In 47% (n = 29/62) of the cases, the diagnosis of HIV/AIDS and histoplasmosis occurred simultaneously. Mortality was 45% (n = 28/62), and 68% (n = 42/62) of these patients did not regularly use highly active antiretroviral therapy. The main symptoms found were respiratory, gastrointestinal, and weight loss, and in 81% (n = 50/62), the place of residence was in an urban area. A total of 57 environmental samples were analyzed, and the presence of Histoplasma capsulatum was not detected in any of the analyzed samples. There was a high mortality rate in the studied group of patients with AIDS and histoplasmosis. Most patients reported residing in urban areas of Manaus, with no history of travel to other areas previously known as being high risk for histoplasmosis.

State-Dependent Blockade of Dorsal Root Ganglion Voltage-Gated Na+ Channels by Anethole.

Anethole is a phenolic compound synthesized by many aromatic plants. Anethole is a substance that humans can safely consume and has been studied for years as a biologically active molecule to treat a variety of conditions, including nerve damage, gastritis, inflammation, and nociception. Anethole is thought to carry out its biological activities through direct interaction with ion channels. Anethole is beneficial for neurodegenerative Alzheimer's and Parkinson's diseases. Nevertheless, nothing has been investigated regarding the effects of anethole on voltage-gated Na+ channels (VGSCs), which are major players in neuronal function. We used cultured dorsal root ganglion neurons from neonatal rats as a source of natively expressed VGSCs for electrophysiological studies using the whole-cell patch-clamp technique. Our data show that anethole interacts directly with VGSCs. Anethole quickly blocks and unblocks (when removed) voltage-activated Na+ currents in this preparation in a fully reversible manner. Anethole's binding affinity to these channels increases when the inactive states of these channels are populated, similar to lidocaine's effect on the same channels. Our data show that anethole inhibits neuronal activity by blocking VGSCs in a state-dependent manner. These findings relate to the putative anesthetic activity attributable to anethole, in addition to its potential benefit in neurodegenerative diseases.

Epileptogenesis and drug-resistant in focal cortical dysplasias: Update on clinical, cellular, and molecular markers.

Focal cortical dysplasia (FCD) is a cortical malformation in brain development and is considered as one of the major causes of drug-resistant epilepsiesin children and adults. The pathogenesis of FCD is yet to be fully understood. Imaging markers such as MRI are currently the surgeons major obstacle due to the difficulty in delimiting the precise dysplasic area and a mosaic brain where there is epileptogenic tissue invisible to MRI. Also increased gene expression and activity may be responsible for the alterations in cell proliferation, migration, growth, and survival. Altered expressions were found, particularly in the PI3K/AKT/mTOR pathway. Surgery is still considered the most effective treatment option, due to drug-resistance, and up to 60 % of patients experience complete seizure control, varying according to the type and location of FCD. Both genetic and epigenetic factors may be involved in the pathogenesis of FCD, and there is no conclusive evidence whether these alterations are inherited or have an environmental origin.

Correction: Applicability of machine learning technique in the screening of patients with mild traumatic brain injury.

[This corrects the article DOI: 10.1371/journal.pone.0290721.].

Histological investigation in aging male and female gerbil prostates after prenatal exposure to pequi (Caryocar brasiliense Cambess) oil and 17α-ethinylestradiol.

The female prostate, also known as Skene's gland, is present in both humans and rodents. Prenatal exposure to ethinylestradiol (EE2), a synthetic estrogen found in oral contraceptives, induces pormotes neoplasic prostate lesions in gerbils (Meriones unguiculatus). Conversely, pequi oil (Pe), extracted from the Brazilian Cerrado fruit, has antioxidant, anti-inflammatory, and anticancer properties, mitigates risks associated with chronic diseases related to lifestyle and aging. This study evaluates the impact of prenatal exposure to Pe (300 mg/kg) on senile gerbil offspring's male and female prostates under normal conditions and EE2 exposure (15 µg/kg/day). Histological and morphometric analyses revealed that Pe reduced male body weight and prostate epithelial height, along with a thinner muscle layer. In females, EE2 exposure reduced prostatic weight, while Pe exposure lowered epithelial height and the relative stromal compartment volume, increasing the muscle layer. Pequi oil holds potential in mitigating alterations induced by exposure to the endocrine disruptor EE2.

Mercury Contamination as an Indicator of Fish Species' Trophic Position in the Middle Araguaia River, Brazil.

This study evaluates the use of mercury (Hg) concentrations in fish muscle tissue to determine a species' trophic position (TP) in its environment. A campaign conducted in 2019 along 375 km in the middle Araguaia River basin, Brazil, resulted in 239 organisms from 20 species collected. The highest total mercury (THg) concentrations were found in Pellonacastelnaeana (6.93 µg·g-1, wet weight) and in Triportheus elongatus (3.18 µg·g-1, wet weight), whose TPs were different according to the FishBase database. However, they occupied the same trophic level in this study. The intra-specific comparison showed a difference in Hg concentrations between individuals captured in distinct sites. The study of the biota-sediment accumulation factor (BSAF) showed that spatiality interferes with a species' TP. Statistical analyses revealed that when we used a predicted species' TP based on each individual's size, it explained 72% of the variability in THg concentration across all fish species. Multiple regression analysis confirmed that standard length and FishBase values are positively associated with THg (R2 = 0.943). These results point to Hg as a viable indicator of a fish species' TP since it reflects regional, biological, and environmental factors, as demonstrated here for the middle Araguaia River.

Antibacterial and immunological properties of piperine evidenced by preclinical studies: a systematic review.

Aim: To review in vitro, in vivo, and in silico studies examining the antibacterial and immunomodulatory properties of piperine (PPN). Methods: This systematic review followed PRISMA guidelines, and five databases were searched. Results: A total of 40 articles were included in this study. Six aspects of PPN activity were identified, including antibacterial spectrum, association with antibiotics, efflux pump inhibition, biofilm effects, protein target binding, and modulation of immune functions/virulence factors. Most studies focused on Mycobacterium spp. and Staphylococcus aureus. Cell lineages and in vivo models were employed to study PPN antibacterial effects. Conclusion: We highlight PPN as a potential adjuvant in the treatment of bacterial infections. PPN possesses several antibacterial properties that need further exploration to determine the mechanisms behind its pharmacological activity.

Ecological risk of mercury in bottom sediments and spatial correlation with land use in Neotropical savanna floodplain lakes, Araguaia River, Central Brazil.

The Araguaia River floodplain is an important biogeographic boundary between the two largest South American biomes: the Cerrado (Brazilian Savanna) and the Amazon rainforest. The large-scale degradation due to land use conversion experienced in the Araguaia River watershed represents a potential source of mercury (Hg) transport to aquatic ecosystems. However, more information is needed about the dynamics of Hg distribution in savanna floodplains, including the Araguaia River floodplain. We analyzed total mercury (THg) concentrations in the bottom sediments of 30 lakes connected to the Araguaia River and four tributaries, aiming to evaluate the environment's integrity based on the geoaccumulation index (Igeo) and the ecological risk index (ERI). The principal component analysis was applied to examine associations between Hg concentrations, environmental conditions, and land use intensity among lakes associated with different river systems. We used indicator cokriging to identify areas with a greater probability of Hg pollution and ecological risk associated with land use intensity. The land use data showed the predominance of areas used for pasture in the Araguaia River basin. THg concentrations in the sediments varied between 22.6 and 81.9 ng g-1 (mean: 46.5 ± 17.7 ng g-1). Sediments showed no significant pollution (Igeo: 1.35 - 0.50; Classes 1 and 2) and low to considerable ecological risks (ERI: 23.5-85.1; Classes 1 to 3). THg in bottom sediments was associated with land use, water turbidity and electrical conductivity, and sediment organic matter. The indicator cokriging indicates a moderate to strong spatial dependence between land use intensity and Hg, confirming the contribution of anthropic sources to the increment of ecological risk but also the influence of extrinsic factors (such as environmental conditions, geology, and hydrology). Integrating sediment assessment and land use indices with geostatistical methods proved a valuable tool for identifying priority areas for Hg accumulation at a regional scale.

A classification model for municipalities in the paraense Amazon regarding the risk of violence against women: A multicriteria approach.

Violence against women (VAW) is a serious violation of the rights to life, health, and physical integrity. Recent studies point out that social, economic, and demographic factors directly impact the advance of this type of violence. In view of these facts, the state has its responsibility increased when it cannot provide the public equipment necessary for management strategies that collaborate with the confrontation of violence. This project aims to develop a multicriteria decision analysis model (MCDA) to classify Pará municipalities with regard to the propensity for VAW crime, based on the mapping of assistance and protection equipment, as well as socioeconomic indicators of each municipality. The model developed and the research findings represent an important step in elaboration. In turn, this model demonstrates its ability to be a possible instrument that decision makers and implementers of public policies aimed at protecting and supporting women victims of violence in order to anticipate new occurrences.

Postoperative local interventions for the palate as a gingival graft donor area: a scoping review.

OBJECTIVE: This scoping review aimed to systematically identify evidence-based interventions to stimulate healing or protect the harvested palate of patients undergoing gingival grafting. MATERIAL AND METHODS: The study followed guidelines from the Joanna Briggs Institute and PRISMA-ScR (protocol available at osf.io/zhafn). PubMed, Embase, and seven other databases were searched on November 2022, with additional monitoring until April 2023. The inclusion criteria focused on studies evaluating outcomes related to the donor area (palate) and interventions for healing or protecting it, regardless of publication year and language. Data from the included publications was extracted and presented through narrative text, tables, and figures. RESULTS: Eighty-one studies (including 64 clinical trials, four case series, five theses, and eight systematic reviews) and 37 clinical trial records were included. The number of studies on this topic has significantly increased, reflecting a growing interest in the field. Thirty-six interventions with published results and 12 interventions with unpublished results from clinical trial registers were identified. Some promising interventions that showed potential for improving patient-reported outcomes include cyanoacrylate adhesive, platelet-rich fibrin (PRF), and the combination of palatal stents and healing agents. CONCLUSIONS: Thirty-six interventions with published results were identified for postoperative use on the harvested palate, showing varying levels of evidence and conflicting effectiveness for specific outcomes. CLINICAL RELEVANCE: Postoperative discomfort and pain in the palate are commonly experienced by patients undergoing grafting procedures using this region as the donor area. Awareness of the available options and their levels of evidence is crucial for informed decision-making.