Bromelain-Based Enzymatic Debridement Versus Standard of Care in Deep Burn Injuries: A Systematic Review and Meta-Analysis.

Deep burn injuries necessitate effective debridement to promote healing and reduce complications. Traditional surgical debridement is the standard of care; however, it can lead to significant tissue loss, excessive bleeding and delayed healing. Bromelain-based enzymatic debridement offers a potential less invasive alternative that aims to selectively remove necrotic tissue while preserving viable ones. Therefore, this systematic review and meta-analysis comprehensively compares bromelain debridement versus standard care in the management of partial and full-thickness burns. Cochrane Library, Embase, and Medline were searched until May 30th, 2024 for studies comparing bromelain debridement versus standard care. R version 4.4.0 was used to pooled risk ratio and mean difference in a random-effects model. We included seven studies, comprising 484 participants, of whom 238 (49%) were treated with enzymatic debridement. Bromelain significantly reduced time to eschar removal (MD - 7.60 days 95% CI [-9.76, -5.44]; I² = 70%) in comparison with standard care. Additionally, bromelain group presented a significant reduction in the risk of surgical excision (RR 0.17; 95% CI [0.06, 0.47]; I² = 79%) and need for autografts (RR 0.40; 95% CI [0.18, 0.93]; I² = 76%) in comparison with standard group. No differences were found in behalf of time to wound closure (MD -7.64; 95% CI [-18.46]-[3.18]; I2 = 86%), nor in Modified Vancouver Scar Scale (MD -0.36; 95% CI [-0.96]-[0.23]; I2 = 0%). Bromelain-based enzymatic debridement may accelerate eschar removal and reduce the need for surgical excision and autografts, without adversely affecting wound closure time or long-term scar quality.

Magnesium sulfate infusion for emergence agitation in adult patients after general anesthesia: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Emergence agitation following general anesthesia poses significant risks to both patients and medical staff. While extensive research has explored the efficacy of magnesium sulfate (MgSO4) in managing pediatric emergence agitation, its effectiveness in adults remains uncertain. Therefore, this meta-analysis seeks to evaluate the efficacy of MgSO4 in mitigating emergence agitation following general anesthesia in adult populations. EVIDENCE ACQUISITION: A systematic search was conducted across PubMed, Embase, Cochrane Library, and Web of Science databases to identify randomized controlled trials (RCTs) comparing MgSO4 or placebo infusion during surgical procedures involving adult patients under general anesthesia. Key outcomes assessed included the incidence of emergence agitation, agitation severity scores, extubation duration, and postoperative nausea and vomiting (PONV). Statistical analyses were conducted using Review Manager 5.4.1 (Cochrane, London, UK), with heterogeneity evaluated using I2 statistics. Significance was defined at P<0.05 for Odds Ratios (OR), mean differences (MD), and standard mean differences (SMD). EVIDENCE SYNTHESIS: Five RCTs encompassing 605 participants were included. MgSO4 resulted in a lower emergence agitation incidence (OR=0.29 [95% CI: 0.12;0.72]; P=0.007). There were no significant differences between groups for patient's agitation severity scores (SMD=-0.69 [95% CI: -1.82; 0.44]; P=0.23), extubation time (MD=1.16 [95% CI: -1.06; 3.37]; P=0.30), or PONV incidence (OR=0.52 [95% CI: 0.15-1.76]; P=0.29). CONCLUSIONS: Magnesium sulfate infusion during general anesthesia was associated with lower incidence of emergence agitation in adults. However, no significant differences were observed regarding emergence agitation severity scores, PONV, or extubation time.

Green Nanotechnology Through Papain Nanoparticles: Preclinical in vitro and in vivo Evaluation of Imaging Triple-Negative Breast Tumors.

Background: Recent advancements in nanomedicine and nanotechnology have expanded the scope of multifunctional nanostructures, offering innovative solutions for targeted drug delivery and diagnostic agents in oncology and nuclear medicine. Nanoparticles, particularly those derived from natural sources, hold immense potential in overcoming biological barriers to enhance therapeutic efficacy and diagnostic accuracy. Papain, a natural plant protease derived from Carica papaya, emerges as a promising candidate for green nanotechnology-based applications due to its diverse medicinal properties, including anticancer properties. Purpose: This study presents a novel approach in nanomedicine and oncology, exploring the potential of green nanotechnology by developing and evaluating technetium-99m radiolabeled papain nanoparticles (99mTc-P-NPs) for imaging breast tumors. The study aimed to investigate the efficacy and specificity of these nanoparticles in breast cancer models through preclinical in vitro and in vivo assessments. Methods: Papain nanoparticles (P-NPs) were synthesized using a radiation-driven method and underwent thorough characterization, including size, surface morphology, surface charge, and cytotoxicity assessment. Subsequently, P-NPs were radiolabeled with technetium-99m (99mTc), and in vitro and in vivo studies were conducted to evaluate cellular uptake at tumor sites, along with biodistribution, SPECT/CT imaging, autoradiography, and immunohistochemistry assays, using breast cancer models. Results: The synthesized P-NPs exhibited a size mean diameter of 9.3 ± 1.9 nm and a spherical shape. The in vitro cytotoxic activity of native papain and P-NPs showed low cytotoxicity in HUVEC, MDA-MB231, and 4T1 cells. The achieved radiochemical yield was 94.2 ± 3.1% that were sufficiently stable (≥90%) for 6 h. The tumor uptake achieved in the 4T1 model was 2.49 ± 0.32% IA/g at 2 h and 1.51 ± 0.20% IA/g at 6 h. In the spontaneous breast cancer model, 1.19 ± 0.20% IA/g at 2 h and 0.86 ± 0.31% IA/g at 6 h. SPECT/CT imaging has shown substantial tumor uptake of the new nanoradiopharmaceutical and clear tumor visualization. 99mTc-P-NPs exhibited a high affinity to tumoral cells confirmed by ex vivo autoradiography and immunohistochemistry assays. Conclusion: The findings underscore the potential of green nanotechnology-driven papain nanoparticles as promising agents for molecular imaging of breast and other tumors through SPECT/CT imaging. The results represent a substantial step forward in the application of papain nanoparticles as carriers of diagnostic and therapeutic radionuclides to deliver diagnostic/therapeutic payloads site-specifically to tumor sites for the development of a new generation of nanoradiopharmaceuticals.

Incidence and Risk Factors of Delayed Intracranial Hemorrhage in Anticoagulated Head Trauma Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study aims to provide a current and comprehensive analysis of the incidence of delayed intracerebral hemorrhage (dICH) in head trauma patients on oral anticoagulants (ACs) and to evaluate various potential risk factors. METHODS: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-Analysis of Observational Studies in Epidemiology guidelines. PubMed and Cochrane Central Register of Controlled Trials were searched for studies on dICH in anticoagulated head trauma patients undergoing repeat computed tomography scans. Studies reporting dICH incidence on repeat computed tomography within 24 hours of an initial negative scan were included. Data on demographics, AC type, risk factors, and clinical outcomes were extracted and analyzed. RESULTS: From 634 identified articles, 26 studies with 7218 patients were included. The overall incidence of dICH was 2.0%, with 43.8% of these cases requiring hospital admission or changes in clinical management. Only 0.1% required neurosurgical intervention, and 0.1% resulted in death. Meta-analysis of 20 studies revealed pooled dICH incidence per 1000 persons at risk was 27.1 for vitamin K antagonists and 20.5 for direct oral ACs. Significant risk factors for dICH included Glasgow Coma Scale <15, loss of consciousness, post-traumatic amnesia, and Abbreviated Injury Scale head ≥3. CONCLUSIONS: A low incidence of dICH requires neurosurgical intervention; however, further studies are required to assess the need for other medical management in these patients. Furthermore, selective imaging for high-risk patients could improve care and resource allocation.

Human outbreaks of a novel reassortant Oropouche virus in the Brazilian Amazon region.

The Brazilian western Amazon is experiencing its largest laboratory-confirmed Oropouche virus (OROV) outbreak, with more than 6,300 reported cases between 2022 and 2024. In this study, we sequenced and analyzed 382 OROV genomes from human samples collected in Amazonas, Acre, Rondônia and Roraima states, between August 2022 and February 2024, to uncover the origin and genetic evolution of OROV in the current outbreak. Genomic analyses revealed that the upsurge of OROV cases in the Brazilian Amazon coincides with spread of a novel reassortant lineage containing the M segment of viruses detected in the eastern Amazon region (2009-2018) and the L and S segments of viruses detected in Peru, Colombia and Ecuador (2008-2021). The novel reassortant likely emerged in the Amazonas state between 2010 and 2014 and spread through long-range dispersion events during the second half of the 2010s. Phylodynamics reconstructions showed that the current OROV spread was driven mainly by short-range (< 2 km) movements consistent with the flight range of vectors. Nevertheless, a substantial proportion (22%) of long-range (>10 km) OROV migrations were also detected, consistent with viral dispersion by humans. Our data provide a view of the unprecedented spread and evolution of OROV in the Brazilian western Amazon region.

Immediate versus delayed postpartum insertion of long-acting reversible contraception methods: meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to conduct a meta-analysis of randomized trials comparing the immediate versus delayed provision of long-acting reversible contraceptives in postpartum subjects, focusing on short-interval pregnancies, utilization rates, and adverse events. DATA SOURCES: Cochrane Central, Embase, PubMed and ClinicalTrials.gov were systematically searched from inception up to December 19, 2023, without filters or language limitation. STUDY ELIGIBILITY CRITERIA: We selected randomized controlled trials assessing the immediate insertion of long-acting reversible contraceptives in women during postpartum period in comparison with the delayed provision. STUDY APPRAISAL AND SYNTHESIS METHODS: We calculated relative risks (RR) with 95% confidence intervals to analyze the primary outcome of utilization rates and secondary endpoints, including initiation rates, pregnancy, any breastfeeding, exclusive breastfeeding, and serious adverse events. A random effects model was employed in the R software. Moreover, we assessed the risk of bias of selected RCTs using version 2 of the Cochrane Risk of Bias Assessment Tool. RESULTS: We included 24 randomized trials comprising 2,507 participants, of whom 1,293 (51.6%) were randomized to the immediate insertion. Postpartum women in the immediate group had lower risk of pregnancy (RR 0.16; 95% CI 0.04-0.71; P = 0.02) compared with delayed group, and higher rates of long-acting reversible contraceptives at 6 months of follow-up (RR 1.23; 95% CI 1.09-1.37; P < 0.01). CONCLUSIONS: Inserting long-acting reversible contraceptives before hospital discharge was associated with a reduction in the risk of pregnancy, and increased rates of its utilization at 6 months of follow-up. This intervention may be an effective contraception strategy for postpartum women.

Levothyroxine for subclinical hypothyroidism during pregnancy: an updated systematic review and meta-analysis of randomized controlled trials.

PURPOSE: We aimed to perform a systematic review and meta-analysis addressing the efficacy of levothyroxine therapy in pregnant women with subclinical hypothyroidism considering most recent evidence and subgroups of interest for clinical practice. METHODS: PubMed, Embase, and Cochrane Central were searched from inception for randomized controlled trials (RCTs) comparing levothyroxine with placebo or no intervention in pregnant women with subclinical hypothyroidism. We used a random-effects model and conducted subgroup analyses based on thyroid peroxidase antibody status, thyroid stimulating hormone levels, fertility treatment, and recurrent miscarriage. RESULTS: We included 11 RCTs comprising 2,749 pregnant women with subclinical hypothyroidism. Patients treated with levothyroxine (1,439; 52.3%) had significantly lower risk of pregnancy loss (risk ratio 0.69; 95% confidence interval 0.52-0.91; p < 0.01; 6 studies). However, there was no significant association between levothyroxine and live birth (risk ratio 1.01; 95% confidence interval 0.99-1.03; p = 0.29; 8 studies). No statistically significant interaction was observed across subgroups (p > 0.05). CONCLUSION: Levothyroxine replacement therapy for subclinical hypothyroidism during pregnancy may decrease pregnancy loss when early prescribed. Nevertheless, further investigation is needed in patients with thyroid stimulating hormone above four milliunits per liter, especially when associated with recurrent miscarriage or infertility.

Shorter versus longer-course of antibiotic therapy for urinary tract infections in pediatric population: an updated meta-analysis.

Urinary tract infections (UTI) affect between 3% to 7.5% of the febrile pediatric population each year, being one of the most common bacterial infections in pediatrics. Nevertheless, there is no consensus in the medical literature regarding the duration of per oral (p.o.) antibiotic therapy for UTI among these patients. Therefore, our meta-analysis aims to assess the most effective therapy length in this scenario. PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing short (≤ 5 days) with long-course (≥ 7 days) per os (p.o.) antibiotic therapy for children with UTI. Statistical analysis was performed using R Studio version 4.2.1, heterogeneity was assessed with I2 statistics, and the risk of bias was evaluated using the RoB-2 tool. Risk Ratios (RR) with p < 0.05 were considered statistically significant. Seventeen studies involving 1666 pediatric patients were included. Of these, 890 patients (53.4%) were randomized to receive short-course therapy. Patients undergoing short-course therapy showed higher treatment failure rates (RR 1.61; 95% CI 1.15-2.27; p = 0.006). Furthermore, there were no statistically significant differences between groups regarding reinfection (RR 0.73; 95% CI 0.47-1.13; p = 0156) and relapse rates (RR 1.47; 95% CI 0.8-2.71; p = 0.270).  Conclusion: In summary, our results suggest that long-course p.o. antibiotic therapy is associated with a lower rate of treatment failure when compared to short-course p.o. antibiotic therapy. There was no statistical difference between both courses regarding reinfection and relapse rates within 15 months.    PROSPERO identifier: CRD42023456745. What is Known: • Urinary tract infections (UTIs) are common in children, affecting around 7.5% of those under 18. • The optimal duration of antibiotic treatment for pediatric UTIs has been a subject of debate. What is New: • Short-course therapy (5 or fewer days) was associated with a significantly higher failure rate when compared to long-course therapy. • There was no significant difference in reinfection and relapse rates within 15 months between short and long-course therapy.

Evaluating the persistence of malachite green residues in tilapia and pacu fish.

Although banned in food-producing animals, residues of malachite green (MG) and its primary metabolite, leucomalachite green (LMG), have been found in fish due to illegal use in aquaculture and the release of industrial wastewater, which represent a serious risk to food and environmental securities. This study aimed to investigate the residue depletion profile of MG and LMG in edible tissues of Nile tilapia (Oreochromis niloticus) and pacu (Piaractus mesopotamicus) cultured simultaneously under the same environmental conditions to support control measures in case of abuse. An analytical method involving QuEChERS sample preparation and liquid chromatography coupled to tandem mass spectrometry was developed, validated, and applied to quantify MG and LMG residues in fish fillets from two depletion experiments after treatment by immersion bath (MG at 0.10 mg L-1 for 60 min). During the experiment, the average water temperature was 30 ºC, while the pH was 6.9. The method is selective, precise (CV = 0.4 - 22%) and accurate (recovery 92 - 114%). The limits of detection and quantification are 0.15 and 0.5 ng g-1, respectively. In both species, the sum of MG and LMG residues were quantified up to the 32nd day post-exposure, and the concentrations were significantly higher in the pacu fillets (up to 3284 ng g-1) than in Nile tilapia (up to 432 ng g-1). The sums of MG and LMG residues were below 2 ng g-1 at 44 days and 342 days for Nile tilapia and pacu, respectively - the Minimum Required Performance Limit (MRPL) for analytical methods intended to monitor forbidden substances in food according to old European Commission guidelines. The persistence of MG residues in pacu may be attributed to its higher lipid content, which favors the accumulation of the non-polar metabolite LMG. These results provide insights into the concern about human, animal, and environmental health risks resulting from unauthorized use or aquatic contamination by industrial wastewater containing MG residues.

Óbitos neonatais por enterocolite necrosante: estudo de coorte retrospectiva / Neonatal deaths from necrotizing enterocolitis: a retrospective cohort study / Muertes neonatales por enterocolitis necrozante: estudio de cohorte retrospectivo

Introdução:A enterocolite necrosante é uma doença que pode afetar o trato gastrointestinal de recém-nascidos,cujas manifestações clínicas podem ser caracterizadas por vômitos biliosos, sangue nas fezes, distensão abdominal, além de alterações nos parâmetros hemodinâmicos e instabilidade térmica. As populações mais vulneráveis a essa enfermidade são recém-nascidos de baixo peso,expostos ao ambiente de terapia intensiva neonatal. Objetivos: Identificar o perfil de recém-nascidos e os fatores maternos e neonatais associados à ocorrência de óbitos por enterocolite necrosante, em maternidade de referência do Ceará-Brasil. Metodologia: Trata-se de coorte retrospectiva, estudo que objetiva a descrição da incidência de determinado evento ao longo do tempo, além do estabelecimento de relações causais entre os fatores associados ao acontecimento. Incluíram-serecém-nascidos que tiveram óbitos por enterocolite necrosante entre 2019 e 2021, comficha de investigação de óbitos neonatais preenchida corretamente, não sendo excluído nenhum recém-nascido, totalizando amostra de 29 óbitos.Resultados: Identificou-se que o perfil dos recém-nascidos foi,em maioria, deprematuros e com baixo peso e fatores de risco para outras doenças associadas,como a sepse, o que acarretourealização de procedimentos invasivos e internação em ambiente de terapia intensiva neonatal.Conclusões: A prematuridade e o baixo peso ao nascer foram as variáveis relevantes no estudo e podem estar associadas à piora das condições clínicas do recém-nascido e ao desenvolvimento de enterocolite necrosante (AU).

Introduction: Necrotizing Enterocolitis is a disease that can affect the gastrointestinal tract of newborns, whose clinical manifestations can be characterized by bilious vomiting, blood in stool, abdominal distension, in addition to changes in hemodynamic parameters and thermal instability. The populations most vulnerable to this disease are low birth weight newborns exposed to the neonatal intensive care environment. Objectives: This study aimed to identify the profile of newborns and maternal and neonatal factors associated with the occurrence of deaths from necrotizing enterocolitis in a reference maternity hospital in Ceará, Brazil. Methodology: This is a retrospective cohort study seeking to describe the incidence ofa particular event over time, as well as establish causal relationships between the factors associated with the event. The study population comprised newborns who died from necrotizing enterocolitis between 2019 and 2021, who had neonatal death investigation forms filled out correctly, with no newborns being excluded, totaling a sample of 29 deaths. Results: It was identified that the profile of newborns was mostly premature, of low birth weight and with risk factors for other associated diseases such as sepsis, leading to invasive procedures and hospitalization in a neonatal intensive care environment. Conclusions: Prematurity and low birth weight were relevant variables in the study and may be associated with worsening of the newborn's clinical conditionsand development of necrotizing enterocolitis (AU).

ntroducción:La Enterocolitis Necrotizante es enfermedad que puede afectar el tracto gastrointestinal del recién nacido, cuyas manifestaciones clínicas pueden caracterizarse por vómitos biliosos, sangre en las heces, distensión abdominal, además de cambios en los parámetros hemodinámicos e inestabilidad térmica.Las poblaciones más vulnerables a esta enfermedad son recién nacidos con bajo peso expuestos al entorno de cuidados intensivos neonatales.Objetivos: Identificar el perfil de recién nacidos y los factores maternos y neonatales asociados a la ocurrencia de muertes por enterocolitis necrotizante, en maternidad de referencia en el Ceará-Brasil.Metodología: Estudio de cohorte retrospectivo, para describir la incidencia de determinado evento a lo largo del tiempo, además de establecer relaciones causales entre los factores asociados al evento.Se incluyeron recién nacidos fallecidos por enterocolitis necrotizante entre 2019 y 2021, quienes tuvieron formulario de investigación de muerte neonatal correctamente diligenciado, no excluyéndose ningún recién nacido, totalizando muestra de 29 defunciones.Resultados:El perfil de los recién nacidos fue mayoritariamente prematuro y de bajo peso al nacer y con factores de riesgo para otras enfermedades asociadas, como sepsis, con procedimientos invasivos y hospitalización en ambiente de cuidados intensivosneonatales.Conclusiones:La prematuridad y el bajo peso al nacer fueron variables relevantes en el estudio y pueden estar asociados con empeoramiento de las condiciones clínicas de recién nacidos y desarrollo de enterocolitis necrotizante (AU).

Molecular Footprints on Osmoregulation-Related Genes Associated with Freshwater Colonization by Cetaceans and Sirenians.

The genetic basis underlying adaptive physiological mechanisms has been extensively explored in mammals after colonizing the seas. However, independent lineages of aquatic mammals exhibit complex patterns of secondary colonization in freshwater environments. This change in habitat represents new osmotic challenges, and additional changes in key systems, such as the osmoregulatory system, are expected. Here, we studied the selective regime on coding and regulatory regions of 20 genes related to the osmoregulation system in strict aquatic mammals from independent evolutionary lineages, cetaceans, and sirenians, with representatives in marine and freshwater aquatic environments. We identified positive selection signals in genes encoding the protein vasopressin (AVP) in mammalian lineages with secondary colonization in the fluvial environment and in aquaporins for lineages inhabiting the marine and fluvial environments. A greater number of sites with positive selection signals were found for the dolphin species compared to the Amazonian manatee. Only the AQP5 and AVP genes showed selection signals in more than one independent lineage of these mammals. Furthermore, the vasopressin gene tree indicates greater similarity in river dolphin sequences despite the independence of their lineages based on the species tree. Patterns of distribution and enrichment of Transcription Factors in the promoter regions of target genes were analyzed and appear to be phylogenetically conserved among sister species. We found accelerated evolution signs in genes ACE, AQP1, AQP5, AQP7, AVP, NPP4, and NPR1 for the fluvial mammals. Together, these results allow a greater understanding of the molecular bases of the evolution of genes responsible for osmotic control in aquatic mammals.

Levamisole incorporation in fish feed - Ensuring the medication dose and avoidance of leaching into the water.

Levamisole, an anthelmintic and immunostimulant drug, has been studied as a promising alternative for aquaculture use. While oral administration through feeding is the main route of administration in fish farming, no studies evaluating methods of levamisole incorporation into the feed have been reported so far. Therefore, this study aimed to evaluate potential procedures for levamisole incorporation in extruded fish feed using ethyl cellulose, gelatin, or vegetable oil, to avoid drug leaching to the water during the animal's medication. A suitable LC-MS/MS method was optimized (full factorial design), validated, and applied to evaluate the efficiency of the process, the homogeneity of the drug concentration, and the leaching rate. The method has been demonstrated to be selective, precise (RSD < 4.9%), accurate (recovery > 98.4%), and linear (r > 0.99, 125-750 mg kg-1). The incorporation procedures using the three coating agents showed high incorporation efficiency (70%) and a homogeneous drug concentration among the extruded feed pellets. A low levamisole leaching rate was verified in the feed prepared using the ethyl cellulose coating procedure (4.3% after 15 min of immersion in the water). On the other hand, fish feed coated with gelatin and oil resulted in a high leaching rate (30-35% after 15 min). Thus, this study shows that coating ethyl cellulose may be a promising procedure for levamisole incorporation in fish feed and with the potential to enhance its use in animal production while reducing environmental contamination.

Residue Depletion Profile and Estimation of Withdrawal Period for Sulfadimethoxine and Ormetoprim in Edible Tissues of Nile Tilapia (Oreochromis sp.) on Medicated Feed.

Sulfadimethoxine (SDM) and ormetoprim (OMP) are antimicrobials used in combination to treat bacterial infections in fish farming. The use of this drug combination is not yet regulated in some countries, such as Brazil. Due to the lack of regulated drugs for aquaculture in Brazil, this study investigated the residue depletion profile of SDM and OMP in Nile tilapia (Oreochromis sp.) after oral administration. Fish were treated with medicated feed containing a 5:1 ratio of SDM:OMP at the dose of 50 mg kg BW-1 for five consecutive days with an average water temperature of 28 °C. The drugs were incorporated into the feed by using a gelatin coating process which promoted homogeneity in drug concentration and prevented the drug leaching into the water during medication. The SDM and OMP determination in fish fillets (muscle plus skin in natural proportions) was performed using the QuEChERS approach followed by LC-MS/MS quantification. The analytical method was validated according to Brazilian and selected international guidelines. A withdrawal period of 9 days (or 252 °C days) was estimated for the sum of SDM and OMP residues at concentration levels below the maximum residue level of 100 µg kg-1.

Giants of the Amazon: How does environmental variation drive the diversity patterns of large trees?

For more than three decades, major efforts in sampling and analyzing tree diversity in South America have focused almost exclusively on trees with stems of at least 10 and 2.5 cm diameter, showing highest species diversity in the wetter western and northern Amazon forests. By contrast, little attention has been paid to patterns and drivers of diversity in the largest canopy and emergent trees, which is surprising given these have dominant ecological functions. Here, we use a machine learning approach to quantify the importance of environmental factors and apply it to generate spatial predictions of the species diversity of all trees (dbh ≥ 10 cm) and for very large trees (dbh ≥ 70 cm) using data from 243 forest plots (108,450 trees and 2832 species) distributed across different forest types and biogeographic regions of the Brazilian Amazon. The diversity of large trees and of all trees was significantly associated with three environmental factors, but in contrasting ways across regions and forest types. Environmental variables associated with disturbances, for example, the lightning flash rate and wind speed, as well as the fraction of photosynthetically active radiation, tend to govern the diversity of large trees. Upland rainforests in the Guiana Shield and Roraima regions had a high diversity of large trees. By contrast, variables associated with resources tend to govern tree diversity in general. Places such as the province of Imeri and the northern portion of the province of Madeira stand out for their high diversity of species in general. Climatic and topographic stability and functional adaptation mechanisms promote ideal conditions for species diversity. Finally, we mapped general patterns of tree species diversity in the Brazilian Amazon, which differ substantially depending on size class.

Efeitos de um programa de intervenção, através da telerreabilitação, para pacientes com dor lombar crônica: um protocolo clínico / Effects of an intervention program, through telerehabilitation, for patients with chronic low back pain: a clinical protocol

Introdução: a dor lombar é um dos mais difundidos problemas de saúde pública enfrentados no mundo e, dessa forma, o acesso aos tratamentos baseados em evidências ­ como educação em neurociência da dor e exercícios terapêuticos ­ é frequentemente limitado devido a inúmeras barreiras. Objetivo: desenvolver um protocolo de intervenção que utilize um programa estruturado de educação em dor associado ao exercício terapêutico para o tratamento da dor lombar crônica, por meio de telerreabilitação. Método: este protocolo descreve um delineamento experimental do tipo ensaio clínico controlado, aleatorizado com avaliador e estatístico mascarados. Discussão: a hipótese aqui apresentada é a de que o programa de telerreabilitação beneficiará pacientes com dor lombar crônica, reduzindo a intensidade da dor, melhorando a função e fatores psicológicos.

Introduction: Low back pain is one of the most widespread public health problems faced in the world. The access to evidence-based treatment, such as pain neuroscience education and therapeutic exercises, is often limited due to numerous barriers. Objective: To develop an intervention protocol that uses a pain education program associated with therapeutic exercise for the treatment of chronic low back pain, through telerehabilitation. Method: This protocol describes an experimental design of the type controlled clinical trial, randomized with evaluator and blinded statistician. Discussion: Our hypothesis is that the telerehabilitation program will benefit patients with chronic low back pain, surprising pain intensity, improving function and psychological factors.

Mucoadhesive gellan gum-based and carboxymethyl cellulose -based hydrogels containing gemcitabine and papain for bladder cancer treatment.

Local treatment of bladder cancer faces several limitations such as short residence time or low permeation through urothelium tissue. The aim of this work was to develop patient-friendly mucoadhesive gel formulations combining gemcitabine and the enzyme papain for improved intravesical chemotherapy delivery. Hydrogels based on two different polysaccharides, gellan gum and sodium carboxymethylcellulose (CMC), were prepared with either native papain or papain nanoparticles (nanopapain) to explore for the first time their use as permeability enhancers through bladder tissue. Gel formulations were characterized regarding enzyme stability, rheological behavior, retention on bladder tissue and bioadhesion, drug release properties, permeation capacity, and biocompatibility. After 90 days of storage, the enzyme loaded in the CMC gels retained up to 83.5 ± 4.9 % of its activity in the absence of the drug, and up to 78.1 ± 5.3 with gemcitabine. The gels were mucoadhesive and the enzyme papain showed mucolytic action, which resulted in resistance against washing off from the urothelium and enhanced permeability of gemcitabine in the ex vivo tissue diffusion tests. Native papain shortened lag-time tissue penetration to 0.6 h and enhanced 2-fold drug permeability All formulations demonstrated pseudoplastic behavior and no irritability. Overall, the developed formulations have potential as an upgraded alternative to intravesical therapy for bladder cancer treatment.

Outbreak.info genomic reports: scalable and dynamic surveillance of SARS-CoV-2 variants and mutations.

In response to the emergence of SARS-CoV-2 variants of concern, the global scientific community, through unprecedented effort, has sequenced and shared over 11 million genomes through GISAID, as of May 2022. This extraordinarily high sampling rate provides a unique opportunity to track the evolution of the virus in near real-time. Here, we present outbreak.info , a platform that currently tracks over 40 million combinations of Pango lineages and individual mutations, across over 7,000 locations, to provide insights for researchers, public health officials and the general public. We describe the interpretable visualizations available in our web application, the pipelines that enable the scalable ingestion of heterogeneous sources of SARS-CoV-2 variant data and the server infrastructure that enables widespread data dissemination via a high-performance API that can be accessed using an R package. We show how outbreak.info can be used for genomic surveillance and as a hypothesis-generation tool to understand the ongoing pandemic at varying geographic and temporal scales.

The molecular evolution of genes previously associated with large sizes reveals possible pathways to cetacean gigantism.

Cetaceans are a group of aquatic mammals with the largest body sizes among living animals, including giant representatives such as blue and fin whales. To understand the genetic bases of gigantism in cetaceans, we performed molecular evolutionary analyses on five genes (GHSR, IGF2, IGFBP2, IGFBP7, and EGF) from the growth hormone/insulin-like growth factor axis, and four genes (ZFAT, EGF, LCORL, and PLAG1) previously described as related to the size of species evolutionarily close to cetaceans, such as pigs, cows, and sheep. Our dataset comprised 19 species of cetaceans, seven of which are classified as giants because they exceed 10 m in length. Our results revealed signs of positive selection in genes from the growth hormone/insulin-like growth factor axis and also in those related to body increase in cetacean-related species. In addition, pseudogenization of the EGF gene was detected in the lineage of toothless cetaceans, Mysticeti. Our results suggest the action of positive selection on gigantism in genes that act both in body augmentation and in mitigating its consequences, such as cancer suppression when involved in processes such as division, migration, and cell development control.

The association of modified QuEChERS and DLLME to offer high analytical detectability to assess residual depletion profile of erythromycin in fish.

An analytical method for the determination of erythromycin A (ERY) residues in fish fillet was developed, optimized, and validated employing a modified QuEChERS procedure associated to DLLME technique as a preconcentration step. The obtained LOD and the LOQ were 0.1 µg kg-1 and 1 µg kg-1, respectively. The validated method provides linearity in the range of 1 to 20 µg kg-1, precision (CV < 6.3 %) and accuracy (recovery ranging from 103 to 110 %). The procedure was applied in an experimental study to evaluate the residual depletion profile of ERY in fish (Piaractus mesopotamicus) after oral administration. The treatment was carried out at a daily dose of 100 mg (kg BW)-1 of ERY, for 7 consecutive days and with an average water temperature of 30 °C. A withdrawal time of 240°-day was estimated for eliminating ERY residues at concentration levels below the maximum residue limit considered (MRL 100 µg kg-1).

Virome analysis in lakes of the South Shetland Islands, Antarctica - 2020.

Polar freshwater ecosystems are characterized by a distinct microbiota. However, little is known about viral diversity and abundance, especially regarding the ecology of RNA viruses. We used shotgun metagenomic analysis on samples from Antarctic ecosystems, and report here the characterization of the virome fraction, from different lakes located in the South Shetland Islands (Penguin, Ardley, Deception and King George Island) in the Peninsula Antarctica, in the summer season 2020. DNA viruses (99.4 %) prevailed over RNA viruses (0.6 %) in the lake samples. Six viral orders were identified in the metagenomic libraries: Caudovirales (dsDNA), which was prevalent in most lakes; Picornavirales (ssRNA+); Sobelivirales (ssRNA+); Tolivirales (ssRNA+); Petitvirales (ssDNA) and Baphyvirales (ssDNA), including eight viral families (Herelleviridae, Siphoviridae, Myoviridae, Microviridae, Marnaviridae, Bacilladnaviridae, Barnaviridae and Tombusviridae) and several other, mainly non-classified ssRNA(+) viruses in the lakes of Ardley Island. Bacteriophages (dsDNA) (Herelleviridae family) infecting the phylum Firmicutes and Siphoviridae were predominant in most lakes evaluated. Functional analysis demonstrated a prevalence of unknown proteins (68 %) in the virome. Our prospective study provides virome analysis data from different lakes in the South Shetland Islands, Antarctica, opening exploratory lines for future research related to the biodiversity and viral ecology in this extreme ecosystem.