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El objetivo de este estudio fue identificar el panorama científico con respecto a los estudios con entrenadores de balonmano. Para esto, se realizó una revisión sistemática con búsquedas en diferentes bases de datos desde el año 2000. El análisis de los artículos seleccionados permitió identificar tres temas: a) intervención de los entrenadores para el desempeño; b) intervención de entrenadores centrados en aspectos psicológicos; y c) perfil y formación de entrenadores. Los artículos analizados destacaron la formación de los entrenadores, teniendo como temas principales abordados por los investigadores las intervenciones de los entrenadores relacionadas con los contenidos técnico-tácticos, los comentarios, la preparación física, las formas de liderazgo y la relación con los jugadores. Se concluyó que los estudios con entrenadores deben ser estimulados para ayudarlos en el proceso de aprendizaje profesional, pero también se debe dar más énfasis a las categorías iniciales de entrenamiento deportivo, ya que se encontró preferencia por artículos que retratan la categoría de adultos.

In the last 60 years, the largest displacement of the magnetic equator (by about 1100 km northwards) occurred in the Brazilian longitudinal sector. The magnetic equator passed by Tatuoca magnetic observatory (TTB) in northern Brazil in 2012 and continues to move northward. Due to the horizontal geomagnetic field geometry at the magnetic equator, enhanced electric currents in the ionosphere are produced – the so-called equatorial electrojet (EEJ). The magnetic effect of the EEJ is observed in the range of ±3° from the magnetic equator, where magnetic observatories record an amplified daily variation of the H component. In order to track the spatial and temporal variation of this phenomena, a new magnetometer station was installed in Macapá (MAA), which is about 350 km northwest of TTB. In this paper, we present the setup and data analysis of MAA station from November 2019 until September 2021. Because of its special configuration, we develop a method for temperature correction of the vector magnetometer data.

Abstract Textile dyes are frequently disposable in aqueous effluents, making it difficult to remove them from industrial effluents before their release to natural waters. This paper deals with the fabrication of cellulose-based adsorbents by reacting nanocelulose crystalline (nanocel) with N-[3-(trimethoxysilyl)propyl]ethylenediamine (TMSPEDA), forming the hybrid (silylpropyl)ethylenediamine@nanocellulose (SPEDA@nanocel), which was employed as adsorbent for the uptake of reactive yellow 2 dye (RY-2) from aqueous effluents. Characterisation of SPEDA@nanocel was carried out using FTIR, SEM–EDS, XRD, TGA, surface area, pHpzc, and hydrophobicity/hydrophilicity ratio (HI). Also, adsorption studies were thoroughly investigated. The effect of initial pH indicated that the maximum uptake of RY-2 takes place at pH 2, which is an indication of the electrostatic mechanism. The kinetic data carried out with 250 and 500 mg L−1 RY-2 with SPEDA@nanocel followed better the nonlinear fractional-like pseudo-first-order model. The t0.5 and t0.95 for the dye uptake were about 30 and 141 min, respectively. The equilibrium data from 10 to 45 °C indicated that the Liu isotherm model was the best-fitted isothermal model. The maximum sorption capacity attained was 112.3 mg g−1 at 45 °C. The thermodynamic data have shown that the equilibrium was favorable and endothermic, and the ΔH° was compatible with an electrostatic attraction between RY-2 and SPEDA@nanocel. Experiments of desorption of loaded adsorbent showed promising results for real applications since at least 5 adsorption/desorption cycles could be employed without significant changes in the recovery and with high precision.

Introduction: In humans, the normal metabolic activity produces free radicals that constantly, along with other risk factors, including hypercholesterolemia may be responsible for the onset of degenerative diseases. Some bioactive compounds present in blackberry (Rubus spp.) have the ability to act as natural antioxidants can make the food to minimize effects on the body caused by reactive oxygen species. Objective: This study verified the benefits of blackberry nectar through the quantification of triglycerides, total and fraction cholesterol HDL (high density lipoprotein) and LDL-cholesterol (low density lipoprotein), blood glucose and lipid peroxidation in hypercholesterolemic hamsters. Methods: Two groups were treated with hypercholesterolemic diets (0.1% cholesterol), one of them receiving an additional 5 mL of nectar daily, and a third (control group) treated only with a standard diet. In the blood the quantification of lipids, blood glucose and lipid peroxidation was performed. In the brain, liver and small intestine the lipid peroxidation was determined and in other organs, histopathological evaluations were carried out. Results: The blackberry nectar reduced the triglycerides serum levels, total cholesterol and LDL-cholesterol in hypercholesterolemic hamsters, without influencing the HDL and blood glucose concentrations. A decrease in the initiation of lipid peroxidation reactions in the blood, brain and small intestine was also observed. Only the liver showed histopathological changes (steatosis), due to excess cholesterol, with no positive influence from the nectar.Introducción: En los seres humanos, la actividad metabólica normal produce radicales libres que constantemente, junto con otros factores de riesgo, incluyendo la hipercolesterolemia puede ser responsable de la aparición de enfermedades degenerativas. Algunos de los compuestos bioactivos presentes en mora (Rubus spp.) tienen la capacidad de actuar como antioxidantes naturales pueden hacer que los alimentos para minimizar los efectos sobre el cuerpo causados por las especies reactivas de oxígeno. Objetivo: Verificar los beneficios del néctar de mora a través de la cuantificación de triglicéridos, colesterol total y fracciones HDL (lipoproteína de alta densidad) y colesterol-LDL (liproteína de baja densidad), glucosa en la sangre y la peroxidación lipídica en hamsters hipercolesterolémicos. Métodos: Dos grupos fueron tratados con dieta hipercolesterolémica (0,1% de colesterol), que consumían diariamente, otros 5 mL de néctar, y un tercero (grupo control) tratados sólo con dieta estándar. En el sangre se realizo la cuantificación del lípidos, glucosa y la peroxidación lipídica. En el cerebro, el hígado y el intestino delgado se determinó la peroxidación lipídica y en otros órganos, evaluaciones histopatológicas. Resultados: El néctar de mora reduce los triglicéridos séricos, colesterol total y LDL-colesterol en hamsters hipercolesterolémicos, no influyen en los niveles de colesterol HDL y glucosa en la sangre. También se observo la disminución de las reacciones de iniciación de la peroxidación de lípidos en la sangre, el cerebro y el intestino delgado. El hígado, mostraron cambios patológicos (esteatosis), debido al exceso de colesterol, sin la influencia positiva de néctar.

Abstract The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.

MOSFiT (Magnetic Observatories and Stations Filtering Tool) is a Python package to visualize and filter data from magnetic observatories and magnetometer stations. The purpose of MOSFiT is to automatically isolate and analyze the secular variation (SV) information measured by geomagnetic observatory data. External field contributions may be reduced by selecting data according to local time and geomagnetic indices and by subtracting the magnetospheric field predictions of the CHAOS-7 model. MOSFiT calculates the SV by annual differences of monthly means, and geomagnetic jerk occurrence time and amplitude are automatically calculated by fitting two straight-line segments in a user-defined time interval of the SV time series. Here, we present the new Python package, validate it against independent results from previous publications and show its application. In particular, we quantify the RMS misfit between SV derived from processing schemes and the SV predicted by CHAOS-7. Analyzing the International Real-time Magnetic Observatory Network (INTERMAGNET) quasi-definitive data with MOSFiT allows for a timely investigation of SV, such as the detection of recent geomagnetic jerks. It can also be used for data selection for, e.g., external field studies or quality control of geomagnetic observatory data.

Peroxiporins are a specialized subset of aquaporins, which are integral membrane proteins primarily known for facilitating water transport across cell membranes. In addition to the classical water transport function, peroxiporins have the unique capability to transport hydrogen peroxide (H2O2), a reactive oxygen species involved in various cellular signaling pathways and regulation of oxidative stress responses. The regulation of H2O2 levels is crucial for maintaining cellular homeostasis, and peroxiporins play a significant role in this process by modulating its intracellular and extracellular concentrations. This ability to facilitate the passage of H2O2 positions peroxiporins as key players in redox biology and cellular signaling, with implications for understanding and treating various diseases linked to oxidative stress and inflammation. This review provides updated information on the physiological roles of peroxiporins and their implications in disease, emphasizing their potential as novel biomarkers and drug targets in conditions where they are dysregulated, such as inflammation and cancer.

Introduction A 56-year-old patient diagnosed with bipolar affective disorder type II, who remains stable, with no manifest episodes, thanks to aripiprazole 60mg daily. Objectives The aim is to carry out a brief review of the use of the drug as the only stabiliser in bipolar affective disorder. Methods A 56-year-old patient, who has been suffering from episodes of hypomania since the age of 40, with episodes of depression. After poor tolerance to the use of the usual stabilisers, and the impossibility of using antidepressants due to hypomanic swings, it was decided to start treatment with aripiprazole orally, up to a maximum of 60mg daily. Despite the fact that the patient, with this treatment, had no side effects and remained more stable psychopathologically, the patient did not comply adequately with the correct dosage, due to his rotating work shifts. This fact explained that although he acknowledged an improvement, he continued with episodes of depressive symptoms lasting several days followed by episodes of hypomanic characteristics. Results For this reason, it was decided to change treatment to aripiprazole long-acting injectable, in order to ensure linear blood levels of the drug. Initially, it was decided to prescribe 400mg every 28 days. However, after the first administration, 20 days later, the patient began to show dysphoric mood, with marked emotional lability, living in an egodystonic manner. For this reason, the dose was increased to 600mg on a monthly basis. Since then, after a year and a half with the same treatment, the patient has been stable and in line. There has been no further decompensation of the underlying psychopathology and no side effects. Conclusions Aripiprazole in TAB is superior to placebo in type I patients, mainly affecting manic and mixed episodes, but not so much in depressive episodes. It has also been observed that it not only acts in the acute phases, but also has a stabilising function, preventing manic episodes. One study showed that up to 65% of patients on oral aripiprazole in whom it was replaced by AOM remained clinically stable. In the same study, approximately 50% of those who completed 52 weeks of follow-up were able to maintain clinical stability. Disclosure of Interest None Declared

This study aimed to investigate the impact of dietary inclusion of babassu oil (BO) associated with sunflower oil (SO) on feeding behavior, water intake, and physiological parameters of feedlot lambs. Thirty-five castrated male lambs (16.6 kg ± 3.9 kg) were distributed in a randomized block design with 5 treatments (diets) and 7 replications. The tested diets were oil-free diet (OF), 45 g/kg BO (BO), 30 g/kg BO with an additional 15 g/kg SO (1.5 SO), 22.5 g/kg BO with an additional 22.5 g/kg SO (2.25 SO), and 30 g/kg SO with an additional 15 g/kg BO (3.0 SO) on dry matter (DM) basis. The experimental period lasted 60 days. Animals that received BO diet and the combination of BO with SO had lower intakes of DM and neutral detergent fiber (NDF) compared to the control diet (P

Abstract Background Infusion Pumps (IP) are medical devices that were developed in the 1960s and generate fluid flow at pressures higher than that of normal blood pressure. Various hospital sectors make use of them, and they have become indispensable in therapies requiring continuity and precision in the administration of medication and/or food. As they are classified Class III (high risk) equipment, their maintenance is crucial for proper performance of the device, as well as patient and operator safety. The principal consideration of the pump is the volume infused, and the device demands great attention to detail when being calibrated. A lack of necessary care with this equipment can lead to uncertainty in volume and precision during the administration of substances. Because of this, it is essential to evaluate its reliability, to prevent possible failures at time of execution. This control aims at the quality of the intended infusion result, becoming an indication of quality. Methods This systematic review summarizes studies done over the last 10 years (2011 to December 2021) that address the reliability and accuracy of hospital infusion pumps, in order to identify planning of maintenance and/or other techniques used in management of the equipment. The Prisma method was applied and the databases utilized were Embase, MEDLINE/Pubmed, Web of Science, Scopus, IEEE Xplore, and Science Direct. In addition, similar reviews were studied in Prospero and the Cochrane Library. For data analysis, softwares such as Mendeley, Excel, RStudio, and VOSviewer were used, and Robvis helped in plotting risk of bias results for studies performed with Cochrane tools. Results The six databases selected produced 824 studies. After applying eligibility criteria (inclusion and exclusion), removing duplicates, and applying filters 1 and 2, 15 studies were included in the present review. It was found that the most relevant sources came from the Institute of Electrical and Electronics Engineers (IEEE) and that the most relevant keywords revolved around the terms (“device failure”, “infusion pumps”, “adverse effects”, “complications”, etc.). These results made clear that there remains substantial room for improvement as it relates to the study of accuracy and reliability of infusion. Conclusions We verified that the reliability and precision analysis of hospital infusion pumps need to be performed in a more detailed and consistent way. New developments, considering the model and IP specification, are intended, clearly explaining the adopted methodology.

Leishmaniasis is a group of parasitic diseases with the potential to infect more than 1 billion people; however, its treatment is still old and inadequate. In order to contribute to changing this view, this work consisted of the development of complexes derived from MI metal ions with thioureas, aiming to obtain potential leishmanicidal agents. The thiourea ligands (HLR) were obtained by reactions of p-toluenesulfohydrazide with R-isothiocyanates and were used in complexation reactions with AgI and AuI, leading to the formation of complexes of composition [M(HLR)2]X (M = Ag or Au; X = NO3− or Cl−). All compounds were characterized by FTIR, 1H NMR, UV-vis, emission spectroscopy and elemental analysis. Some representatives were additionally studied by ESI-MS and single-crystal XRD. Their properties were further analyzed by DFT calculations. Their cytotoxicity on Vero cells and the extracellular leishmanicidal activity on Leishmania infantum and Leishmania braziliensis cells were evaluated. Additionally, the interaction of the complexes with the Old Yellow enzyme of the L. braziliensis (LbOYE) was examined. The biological tests showed that some compounds present remarkable leishmanicidal activity, even higher than that of the standard drug Glucantime, with different selectivity for the two species of Leishmania. Finally, the interaction studies with LbOYE revealed that this enzyme could be one of their biological targets.

Abstract Zinc (Zn) is an essential micronutrient involved in the physiology of nervous system and pain modulation. There is little evidence for the role of nutritional Zn alternations to the onset and progression of neuropathic (NP) and inflammatory pain. The study investigated the effects of a zinc restricted diet on the development of pain. Weaned mice were submitted to a regular (38 mg/kg of Zn) or Zn deficient (11 mg/kg of Zn) diets for four weeks, pain responses evaluated (mechanical, cold and heat allodynia; formalin- and carrageenan-induced inflammatory hypernociception), plasma and tissues collected for biochemical and metabolomic analysis. Zn deficient diet inhibited animal growth (37%) and changed mice sensitivity pattern, inducing an intense allodynia evoked by mechanical, cold and heat stimulus for four weeks. The inflammatory pain behavior of formalin test was drastically reduced or absent when challenged by an inflammatory stimulus. Zn restriction also reduce plasma TNF, increase neuronal activation, oxidative stress, indicating a disruption of the immune response. Liver metabolomic analyses suggest a downregulation of lipid metabolism of arachidonic acid. Zn restriction since weaned disrupts pain signaling considerably and reduce inflammatory pain. Zn could be considered a predisposing factor for the onset of chronic pain such as painful neuropathies.

Multiple factors, including vaccine platform and prior vaccinations, influence vaccine responses. We compared antibody responses to CoronaVac (Sinovac) and ChAdOx1-S (AstraZeneca-Oxford) vaccination in 874 healthcare workers in Brazil. As participants were randomised to BCG vaccination or placebo in the preceding 0-6 months as part of the BCG vaccination to reduce the impact of COVID-19 in healthcare workers (BRACE) trial, we also investigated the influence of recent BCG vaccination on antibody responses to these COVID-19 vaccines. Twenty-eight days after the second dose of each vaccine, ChAdOx1-S induced a stronger anti-spike IgG response than CoronaVac vaccination. Recent BCG vaccination did not impact IgG antibody responses to ChAdOx1-S or CoronaVac.

Abstract The extracts of medicinal plants are used for the treatment of seeds in order to reduce the action of phytopathogens and increase the vigor of the seeds. Currently, computerized image analysis has been used to assess the physiological quality of seed lots. The objective was to evaluate the efficiency of the Vigor-S® software in the evaluation of the physiological quality of cowpea seeds treated with essential oils, comparing with a traditional test and the principal component analysis. Two cowpea cultivars were analyzed, BRS Tumucumaque and BRS Guariba, treated with doses of natural extracts of Alfavaca, garlic, horsetail, citronella and pyroligneous acid. The traditional method consisted of evaluations for germination, first germination count, seedling emergence, emergence speed index, accelerated aging, fresh matter and dry matter of seedling and the image analysis for: seedling length, growth index, uniformity index, vigor index, and germination. A Principal component analysis was applied to reduce the number of variables. Horsetail, Alfavaca and citronella extracts were efficient in increasing the physiological quality of the seeds of at least one cultivar. The Vigor-S® software proved to be efficient compared to traditional tests to assess the physiological quality of seeds. Principal Component Analysis is an ally to identify the best extracts and doses to be used. The image analysis method proved to be effective when compared to the traditional method and can therefore be used.

In the search for new chemotherapeutic alternatives for cutaneous leishmaniasis (CL), essential oils are promising due to their diverse biological potential. In this study, we aimed to investigate the chemical composition and leishmanicidal and anti-inflammatory potential of the essential oil isolated from the leaves of Plinia cauliflora (PCEO). The chemical composition of PCEO showed β-cis-Caryophyllene (24.4%), epi-γ-Eudesmol (8%), 2-Naphthalenemethanol[decahydro-alpha] (8%), and trans-Calamenene (6.6%) as its major constituents. Our results showed that the PCEO has moderate cytotoxicity (CC50) of 137.4 and 143.7 μg/mL on mice peritoneal exudate cells (mPEC) and Vero cells, respectively. The PCEO was able to significantly decrease mPEC infection by Leishmania amazonensis and Leishmania braziliensis. The value of the inhibitory concentration (IC50) on amastigote forms was about 7.3 µg/mL (L. amazonensis) and 7.2 µg/mL (L. braziliensis). We showed that PCEO induced drastic ultrastructural changes in both species of Leishmania and had a high selectivity index (SI) > 18. The in silico ADMET analysis pointed out that PCEO can be used for the development of oral and/or topical formulation in the treatment of CL. In addition, we also demonstrated the in vivo anti-inflammatory effect, with a 95% reduction in paw edema and a decrease by at least 21.4% in migration immune cells in animals treated with 50 mg/kg of PCEO. Taken together, our results demonstrate that PCEO is a promising topical therapeutic agent against CL.

We examined the asymptomatic rates of SARS-CoV-2 infection during the Delta and Omicron waves in the city of São Paulo. Nasopharyngeal swabs were collected at strategic points of the city (open-air markets, bus terminals, airports) for SARS-CoV-2 RNA testing. Applying the questionnaire, the symptomatic individuals were excluded, and only asymptomatic cases were analyzed. During the Delta wave, a total of 4315 samples were collected, whereas 2372 samples were collected during the first Omicron wave. The incidence of the asymptomatic SARS-CoV-2 infection was 0.6% during the Delta wave and 0.8% during the Omicron wave. No statistical differences were found in the threshold amplification cycle. However, there was a statistical difference observed in the sublineage distribution between asymptomatic and symptomatic individuals. Our study determined the incidence of asymptomatic infection by monitoring individuals who remained symptom-free, thereby providing a reliable evaluation of asymptomatic SARS-CoV-2 carriage. Our findings reveal a relatively low proportion of asymptomatic cases, which could be attributed to our rigorous monitoring protocol for the presence of clinical symptoms. Investigating asymptomatic infection rates is crucial to develop and implement effective disease control strategies.

Introduction: The association between the intensity of obstructive sleep apnea and skeletal alterations in the face and hyoid bone is still scarcely addressed in the literature. Objective: To evaluate whether the intensity of obstructive sleep apnea is associated with craniofacial alterations and the position of the hyoid bone in children with mixed dentition. Methods: 76 children aged 7 to 10 years old were examined by otorhinolaryngological evaluation, polysomnography, and orthodontic assessment, including cephalometry. The participants were divided in 3 groups: primary snoring, mild obstructive sleep apnea and moderate to severe obstructive sleep apnea. Cephalometric measures of the face and hyoid bone were assessed. These measures were compared among the different groups by unpaired Student's t test. Moreover, these measures were correlated with the patient's obstructive apnea and hypopnea index variable using Pearson's correlation test. Results: Of the 76 children, 14 belonged to group 1, with primary snoring; 46 to group 2, with mild obstructive sleep apnea; and 16 to group 3, with moderate-severe obstructive sleep apnea. There was no difference between the groups regarding the craniofacial variables. Children with obstructive sleep apnea showed a longer distance from the hyoid bone to the mandibular plane when compared to the primary snoring group (p

BackgroundTesticular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center.Materials and methodsA cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan–Meier method and log-rank test.ResultsKRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable.ConclusionAlthough larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

Toxoplasma gondii is commonly transmitted among animals and humans by ingestion of infected animal tissues or by consumption of food and water contaminated with environmentally-resistant oocysts excreted by cats. Tissue cysts and oocysts have different walls, whose structures and compositions are poorly known. Herein, we describe an immunomagnetic separation (IMS) method that was successfully used for purification of T. gondii tissue cysts generated in cell culture. We used an IgG monoclonal antibody (mAb) that reacts against antigens in tissue cyst walls. Many in vitro produced cysts were obtained by this IMS; >2,000 T. gondii cysts were isolated from a single culture flask of 25 cm2. Tissue cysts from two Hammondia spp., H. hammondi, and H. heydorni, produced in cell culture were also separated using this method. As a reference, purification of tissue cysts by Percoll gradients was used. Percoll was able to separate T. gondii tissue cysts produced in mice but was not suitable for purifying T. gondii tissue cysts produced in vitro. The IMS described here should favor proteomic studies involving tissue cysts of T. gondii.

Abstract This study aimed to evaluate the air and water contamination level and to identify the microbes isolated from a rodent facility located at the Federal University of Uberlândia, Minas Gerais, Brazil. Colony forming units (CFU) per milliliter was used for monitoring water quantitatively; CFU per cubic meter was used for air monitoring. The isolated colonies were identified for qualitative monitoring. Due to absence of specific parameters for these facilities, the results were analyzed according to Brazilian and international standards, depending on which best suited each sample. The mean total number of microorganisms in water ranged from 0.015 ± 0.02 to 0.999 ± 0.91 CFU/mL. The number of microorganisms in air ranged from 9.1 ± 4.6 to 351.56 ± 158.2 CFU/m³. Forty-one microorganisms identified in the samples obtained from the rodent facility were potentially pathogenic or opportunistic for animals and humans (e.g., Corynebacterium spp.). We concluded that the water and air samples were contaminated with potentially pathogenic or opportunistic microorganisms that can harm rodents and humans. On the basis of our observations, specific sanitary standards suitable for these facilities should be developed for controlling microbial contamination, which will prevent zoonosis and ensure the reliability of scientific results obtained from animal experiments.

Background: The COVID-19 situation in Brazil is complex due to large differences in the shape and size of regional epidemics. Understanding these patterns is crucial to understand future outbreaks of SARS-CoV-2 or other respiratory pathogens in the country. Methods: We tested 97,950 blood donation samples for IgG antibodies from March 2020 to March 2021 in 8 of Brazil’s most populous cities. Residential postal codes were used to obtain representative samples. Weekly age- and sex-specific seroprevalence were estimated by correcting the crude seroprevalence by test sensitivity, specificity, and antibody waning. Results: The inferred attack rate of SARS-CoV-2 in December 2020, before the Gamma variant of concern (VOC) was dominant, ranged from 19.3% (95% credible interval [CrI] 17.5–21.2%) in Curitiba to 75.0% (95% CrI 70.8–80.3%) in Manaus. Seroprevalence was consistently smaller in women and donors older than 55 years. The age-specific infection fatality rate (IFR) differed between cities and consistently increased with age. The infection hospitalisation rate increased significantly during the Gamma-dominated second wave in Manaus, suggesting increased morbidity of the Gamma VOC compared to previous variants circulating in Manaus. The higher disease penetrance associated with the health system’s collapse increased the overall IFR by a minimum factor of 2.91 (95% CrI 2.43–3.53). Conclusions: These results highlight the utility of blood donor serosurveillance to track epidemic maturity and demonstrate demographic and spatial heterogeneity in SARS-CoV-2 spread. Funding: This work was supported by Itaú Unibanco ‘Todos pela Saude’ program; FAPESP (grants 18/14389-0, 2019/21585-0); Wellcome Trust and Royal Society Sir Henry Dale Fellowship 204311/Z/16/Z; the Gates Foundation (INV- 034540 and INV-034652); REDS-IV-P (grant HHSN268201100007I); the UK Medical Research Council (MR/S0195/1, MR/V038109/1); CAPES; CNPq (304714/2018-6); Fundação Faculdade de Medicina; Programa Inova Fiocruz-CE/Funcap - Edital 01/2020 Number: FIO-0167-00065.01.00/20 SPU N°06531047/2020; JBS – Fazer o bem faz bem.

Abstract Providencia stuartii is one of the Enterobacteriaceae species of medical importance commonly associated with urinary infections, which can also cause other ones, including uncommon ones, such as liver abscess and septic vasculitis. This bacterium stands out in the expression of intrinsic and acquired resistance to antimicrobials. Besides, it uses mechanisms such as biofilm for its persistence in biotic and abiotic environments. This study investigated the cellular hydrophobicity profile of clinical isolates of P. stuartii. It also analyzed genes related to the fimbrial adhesin in this species comparing with other reports described for other bacteria from Enterobacteriaceae family. The investigated isolates to form biofilm and had a practically hydrophilic cell surface profile. However, fimH and mrkD genes were not found in P. stuartii, unlike observed in other species of Enterobacteriaceae. These results show that P. stuartii has specificities regarding its potential for biofilm formation, which makes it difficult to destabilize the infectious process and increases the permanence of this pathogen in hospital units.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a “lipid storm”, influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Background: Lipopolysaccharide (LPS), an effective stimulator of the immune system, has been widely applied in an experimental pig model for human sepsis. Aquaporins (AQPs), a family of small integral membrane proteins responsible for facilitating water fluxes through the cell membrane, offer potential promising drug targets for sepsis treatment due to their role in water balance and inflammation. Methods: In order to investigate the potential effect of a dietary amino acid mixture supplementation on LPS-challenged weaned piglets, a total of 30, 28-day-old, males were randomly allocated to 1 of 3 dietary treatments for a 5-week period, with 10 animals in each: diet 1 was a control (CTL) treatment; diet 2 was LPS treatment, where the piglets were intraperitoneally administered LPS (at 25 µg/kg body weight); diet 3 was LPS + cocktail treatment, where the piglets were intraperitoneally administered LPS and fed a diet supplemented with a mixture of arginine, branched-chain amino acids (BCAA, leucine, valine, and isoleucine), and cystine. Key organs that control sepsis were collected and processed by real time quantitative PCR (RT-qPCR) for the AQPs and cytokines transcriptional profiles. Results: Minor variations were detected for AQPs and inflammatory markers mRNA levels, upon the dependence of LPS or the amino acid cocktail suggesting the piglets’ immune recovery. Using a discriminant analysis tool, we report for the first time, a tissue-specific variation in AQPs and cytokines transcriptional profiles that clearly distinguish the small intestine and the kidney from the liver and the spleen. Conclusions: This study provides a novel insight into the gene expression signature of AQPs and cytokines in the functional physiology of each organ in piglets.

The quantity of seafood imported and produced by domestic aquaculture farming has increased. Recently, it has been reported that multidrug-resistant (MDR) Salmonella Typhimurium may be associated with seafood. However, information is limited to the antimicrobial resistance, virulence properties, and genetic diversity of S. Typhimurium recovered from imported and domestic seafood. This study investigated the antimicrobial resistance, virulence properties, and genetic diversity of S. Typhimurium isolated from domestic and imported catfish, shrimp, and tilapia. A total of 127 isolates were tested for the presence of multidrug-resistance (MDR), virulence genes (invA, pagC, spvC, spvR), and genetic diversity using the Sensititre micro-broth dilution method, PCR, and pulsed-field gel electrophoresis (PFGE), respectively. All isolates were uniformly susceptible to six (amoxicillin/clavulanic acid, ceftiofur, ceftriaxone, imipenem, nitrofurantoin, and trimethoprim/sulfamethoxazole) of the 17 tested antimicrobials and genetically diverse. Fifty-three percent of the Salmonella isolates were resistant to at least one antimicrobial and 49% were multidrug resistant. Ninety-five percent of the isolates possessed the invA gene, 67% pagC, and 43% for both spvC, and spvR. The results suggest that S. Typhimurium recovered from seafood is frequently MDR, virulent, and have the ability to cause salmonellosis.

Aquaporin 3 (AQP3) is a peroxiporin, a membrane protein that channels hydrogen peroxide in addition to water and glycerol. AQP3 expression also correlates with tumor progression and malignancy and is, therefore, a potential target in breast cancer therapy. In addition, epithelial growth factor receptor (EGFR) plays an important role in breast cancer. Therefore, we investigated whether disruption of the lipid raft harboring EGFR could affect AQP3 expression, and conversely, whether AQP3 silencing would affect the EGFR/phosphoinositide-3-kinase (PI3K)/Protein kinase B (PKB or Akt) signaling pathway in breast cancer cell lines with different malignant capacities. We evaluated H2O2 uptake, cell migratory capacity, and expression of PI3K, pAkt/Akt in three breast cancer cell lines, MCF7, SkBr3, and SUM159PT, and in the nontumorigenic breast epithelial cell line MCF10A. Our results show different responses between the tested cell lines, especially when compared to the nontumorigenic cell line. Neither lipid raft disruption nor EGF stimuli had an effect on PI3K/Akt pathway in MCF10A cell line. AQP3-silencing in SkBr3 and SUM159PT showed that AQP3 can modulate PI3K/Akt activation in these cells. Interestingly, SUM159PT cells increase nuclear factor-E2–related factor 2 (NRF2) in response to lipid raft disruption and EGF stimuli, suggesting an oxidative-dependent response to these treatments. These results suggest that in breast cancer cell lines, AQP3 is not directly related to PI3K/Akt pathway but rather in a cell-line-dependent manner.

Glycerol is a key metabolite for lipid accumulation in insulin-sensitive tissues. We examined the role of aquaporin-7 (AQP7), the main glycerol channel in adipocytes, in the improvement of brown adipose tissue (BAT) whitening, a process whereby brown adipocytes differentiate into white-like unilocular cells, after cold exposure or bariatric surgery in male Wistar rats with diet-induced obesity (DIO) (n = 229). DIO promoted BAT whitening, evidenced by increased BAT hypertrophy, steatosis and upregulation of the lipogenic factors Pparg2, Mogat2 and Dgat1. AQP7 was detected in BAT capillary endothelial cells and brown adipocytes, and its expression was upregulated by DIO. Interestingly, AQP7 gene and protein expressions were downregulated after cold exposure (4 °C) for 1 week or one month after sleeve gastrectomy in parallel to the improvement of BAT whitening. Moreover, Aqp7 mRNA expression was positively associated with transcripts of the lipogenic factors Pparg2, Mogat2 and Dgat1 and regulated by lipogenic (ghrelin) and lipolytic (isoproterenol and leptin) signals. Together, the upregulation of AQP7 in DIO might contribute to glycerol influx used for triacylglycerol synthesis in brown adipocytes, and hence, BAT whitening. This process is reversible by cold exposure and bariatric surgery, thereby suggesting the potential of targeting BAT AQP7 as an anti-obesity therapy.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients (n = 200) and healthy controls (n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

This study has focused on describing the pH response of the CIP (clean in place) rinsing process in order to assess the volume of water consumed and rinsing time. A pilot plant with a heat exchanger, a temperature controller and a flow controller of the rinse water (4.0 to 16.0 L.min−1) was build up to study the process and experiments were conducted. The dynamic behavior presented non-linearities and an ANFIS model was applied for the prediction of the pH response for rinse water flowrate variations. When comparing the obtained model and the FOPDT model obtained from previous studies with the experimental data, the evaluation parameters showed that the ANFIS model exhibit a better precision. Added to that, differently from the FOPDT model, limited to the experimental values, the ANFIS model allows simulating the rinsing process for any flowrate value on the range studied. The simulation using the ANFIS model made it possible to perform the proposed study, saving time and specially water and chemicals, that would be used for the experiments. For the flowrate value of 10.0 L.min−1, the volume of water consumed is minimum and 4.91% smaller when compared to the condition that would provide a faster rinsing process. Since the volume of water consumed in industry is higher than the semi industrial facility considered in this study, this water consumption reduction can represent a higher impact in financial terms, and more importantly, an impact reduction for the environment. Additionally, it was implemented an algorithm of variable flowrate set point. The simulation presented practically the same volume of water consumed when compared to a fixed set point of 10.0 L.min−1, with the advantage that the rinsing time could be reduced 254.0 s (the production could be retaken earlier), bringing an improvement in financial terms. The study presents the proposal for a holistic perspective of the process leaving the results less influenced by assumptions. If extended to the other stages of the CIP cleaning process, it also makes it possible to add gains, both in terms of reducing the environmental impact and the financial aspect.