Side effects of COVID-19 vaccines in paediatric patients: a review systematic and meta-analysis protocol.

INTRODUCTION: The paediatric population represents a quarter of the world's population, and like adult patients, they have also suffered immeasurably from the SARS-CoV-2 pandemic. Immunisation is an effective strategy for reducing the number of COVID-19 cases. With the advancements in vaccination for younger age groups, parents or guardians have raised doubts and questions about adverse effects and the number of doses required. Therefore, systematic reviews focusing on this population are needed to consolidate evidence that can help in decision-making and clinical practice. This protocol aims to assess the safety of COVID-19 vaccines in paediatric patients and evaluate the correlation between the number of vaccine doses and side effects. METHODS AND ANALYSIS: We will search the PubMed, ClinicalTrials.gov, Web of Science, Embase, CINAHL, Latin American and Caribbean Health Sciences Literature, Scopus and Cochrane databases for randomised and quasi-randomised clinical trials that list the adverse effects of the COVID-19 vaccine and assess its correlation with the number of doses, without any language restrictions. Two reviewers will select the studies according to the inclusion and exclusion criteria, extract data and asses for risk of bias using the Cochrane risk-of-bias tool. The Review Software Manager (RevMan V.5.4.1) will be used to synthesise the data. We will use the Working Group's Grading of Recommendations Assessment, Development and Evaluations to grade the strength of the evidence of the results. ETHICS AND DISSEMINATION: Formal ethical approval is not required as no primary data are collected. This systematic review will be disseminated through a peer-reviewed publication. PROSPERO REGISTRATION NUMBER: CRD42023390077.

Anti-leishmanial activity of Eleutherine plicata Herb. and predictions of isoeleutherin and its analogues.

Introduction: Leishmaniasis is caused by protozoa of the genus Leishmania, classified as tegumentary and visceral. The disease treatment is still a serious problem, due to the toxic effects of available drugs, the costly treatment and reports of parasitic resistance, making the search for therapeutic alternatives urgent. This study assessed the in vitro anti-leishmanial potential of the extract, fractions, and isoeleutherin from Eleutherine plicata, as well as the in silico interactions of isoeleutherin and its analogs with Trypanothione Reductase (TR), in addition to predicting pharmacokinetic parameters. Methods: From the ethanolic extract of E. plicata (EEEp) the dichloromethane fraction (FDEp) was obtained, and isoeleutherin isolated. All samples were tested against promastigotes, and parasite viability was evaluated. Isoeleutherin analogues were selected based on similarity in databases (ZINK and eMolecules) to verify the impact on structural change. Results and Discussion: The extract and its fractions were not active against the promastigote form (IC50 > 200 µg/mL), while isoeleutherin was active (IC50 = 25 µg/mL). All analogues have high intestinal absorption (HIA), cell permeability was moderate in Caco2 and low to moderate in MDCK. Structural changes interfered with plasma protein binding and blood-brain barrier permeability. Regarding metabolism, all molecules appear to be CYP3A4 metabolized and inhibited 2-3 CYPs. Molecular docking and molecular dynamics assessed the interactions between the most stable configurations of isoeleutherin, analogue compound 17, and quinacrine (control drug). Molecular dynamics simulations demonstrated stability and favorable interactions with TR. In summary, fractionation contributed to antileishmanial activity and isoleutherin seems to be promising. Structural alterations did not contribute to improve pharmacokinetic aspects and analogue 17 proved to be more promising than isoeleutherin, presenting better stabilization in TR.

Physical energies for the management of genitourinary syndrome of menopause: An overview of a systematic review and network meta-analysis.

BACKGROUND: Energy-based devices (laser and radiofrequency) have been used to treat genitourinary syndrome of menopause (GSM). OBJECTIVES: To evaluate the efficacy and safety of physical energy use in managing GSM symptoms. SEARCH STRATEGY: Five databases were searched from inception to December 2022. Language restrictions were not imposed. SELECTION CRITERIA: We included all Cochrane and non-Cochrane systematic reviews with or without meta-analyses that described postmenopausal women with symptoms of GSM treated with physical energy. DATA COLLECTION AND ANALYSIS: We performed a network meta-analysis using frequentist methods to calculate standardized mean differences (SMDs) and their corresponding 95% confidence intervals (CIs). Methodological and reporting quality were assessed using the Assessment of Multiple Systematic Reviews (AMSTAR 2). MAIN RESULTS: Nine reviews were included in the overview, six of which were meta-analyses. Four randomized controlled trials, representing 218 participants and nine different study arms, met the criteria for inclusion in our component network meta-analysis. Confidence in review findings was low in six reviews and critically low in three. Our network meta-analysis results showed that premarin (SMD 2.60, 95% CI 7.76-3.43), conjugated estrogens (SMD 2.13, 95% CI 1.34-2.91), carbon dioxide laser (SMD 1.71, 95% CI 1.10-2.31), promestriene (SMD 1.41, 95% CI 0.59-2.24), and vaginal lubricant (SMD 1.37, 95% CI 0.54-2.20) were more effective than sham for reducing sexual dysfunction, with a consequent increase in Female Sexual Function Index (FSFI). Two studies showed a high risk of bias, owing to a lack of blinding. CONCLUSION: Several gaps in the use of physical energy for managing GSM still need to be addressed. The small number of blind clinical trials made the results fragile.

Efficacy, Safety, and Acceptability of Misoprostol in the Treatment of Incomplete Miscarriage: A Systematic Review and Meta-analysis.

OBJECTIVE: To assess the efficacy, safety, and acceptability of misoprostol in the treatment of incomplete miscarriage. DATA SOURCES: The PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Clinical Trials databases (clinicaltrials.gov) were searched for the relevant articles, and search strategies were developed using a combination of thematic Medical Subject Headings terms and text words. The last search was conducted on July 4, 2022. No language restrictions were applied. SELECTION OF STUDIES: Randomized clinical trials with patients of gestational age up to 6/7 weeks with a diagnosis of incomplete abortion and who were managed with at least 1 of the 3 types of treatment studied were included. A total of 8,087 studies were screened. DATA COLLECTION: Data were synthesized using the statistical package Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). For dichotomous outcomes, the odds ratio (OR) and 95% confidence interval (CI) were derived for each study. Heterogeneity between the trial results was evaluated using the standard test, I2 statistic. DATA SYNTHESIS: When comparing misoprostol with medical vacuum aspiration (MVA), the rate of complete abortion was higher in the MVA group (OR = 0.16; 95%CI = 0.07-0.36). Hemorrhage or heavy bleeding was more common in the misoprostol group (OR = 3.00; 95%CI = 1.96-4.59), but pain after treatment was more common in patients treated with MVA (OR = 0.65; 95%CI = 0.52-0.80). No statistically significant differences were observed in the general acceptability of the treatments. CONCLUSION: Misoprostol has been determined as a safe option with good acceptance by patients.

OBJETIVO: Avaliar a eficácia, segurança e aceitabilidade do misoprostol no tratamento do aborto incompleto. FONTES DE DADOS: Os bancos de dados PubMed, Scopus, Embase, Web of Science, Cochrane Library e bancos de dados de Ensaios Clínicos (clinicaltrials.gov) foram pesquisados para os artigos relevantes, e estratégias de busca foram desenvolvidas usando uma combinação de termos temáticos de Medical Subject Headings e palavras de texto. A última pesquisa foi realizada em 4 de julho de 2022. Nenhuma restrição de idioma foi aplicada. SELEçãO DOS ESTUDOS: Foram incluídos ensaios clínicos randomizados com pacientes com idade gestacional até 6/7 semanas com diagnóstico de aborto incompleto e que foram manejadas com pelo menos um dos três tipos de tratamento estudados. Um total de 8.087 estudos foram selecionados. COLETA DE DADOS: Os dados foram sintetizados usando o pacote estatístico Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). Para resultados dicotômicos, o odds ratio (OR, na sigla em inglês) e o intervalo de confiança (IC) de 95% foram derivados para cada estudo. A heterogeneidade entre os resultados do ensaio foi avaliada usando o teste padrão, estatística I2. SíNTESE DOS DADOS: Ao comparar misoprostol com aspiração a vácuo médico (MVA, na sigla em inglês), a taxa de aborto completo foi maior no grupo MVA (OR = 0,16; IC95% = 0,07­0,36). Hemorragia ou sangramento intenso foi mais comum no grupo do misoprostol (OR = 3,00; 95%CI = 1,96­4,59), mas a dor após o tratamento foi mais comum em pacientes tratados com MVA (OR = 0,65; 95%CI = 0,52­0,80). Não foram observadas diferenças estatisticamente significativas na aceitabilidade geral dos tratamentos. CONCLUSãO: O misoprostol tem se mostrado uma opção segura e com boa aceitação pelos pacientes.

Efficacy, Safety, and Acceptability of Misoprostol in the Treatment of Incomplete Miscarriage: A Systematic Review and Meta-analysis / Eficácia, segurança e aceitabilidade do misoprostol no tratamento do aborto incompleto: Uma revisão sistemática e metanálise

Abstract Objective To assess the efficacy, safety, and acceptability of misoprostol in the treatment of incomplete miscarriage. Data sources The PubMed, Scopus, Embase, Web of Science, Cochrane Library, and Clinical Trials databases (clinicaltrials.gov) were searched for the relevant articles, and search strategies were developed using a combination of thematic Medical Subject Headings terms and text words. The last search was conducted on July 4, 2022. No language restrictions were applied. Selection of studies Randomized clinical trials with patients of gestational age up to 6/7 weeks with a diagnosis of incomplete abortion and who were managed with at least 1 of the 3 types of treatment studied were included. A total of 8,087 studies were screened. Data collection Data were synthesized using the statistical package Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). For dichotomous outcomes, the odds ratio (OR) and 95% confidence interval (CI) were derived for each study. Heterogeneity between the trial results was evaluated using the standard test, I2 statistic. Data synthesis When comparing misoprostol with medical vacuum aspiration (MVA), the rate of complete abortion was higher in the MVA group (OR = 0.16; 95%CI = 0.07-0.36). Hemorrhage or heavy bleeding was more common in the misoprostol group (OR = 3.00; 95%CI = 1.96-4.59), but pain after treatment was more common in patients treated with MVA (OR = 0.65; 95%CI = 0.52-0.80). No statistically significant differences were observed in the general acceptability of the treatments. Conclusion Misoprostol has been determined as a safe option with good acceptance by patients.

Resumo Objetivo Avaliar a eficácia, segurança e aceitabilidade do misoprostol no tratamento do aborto incompleto. Fontes de dados Os bancos de dados PubMed, Scopus, Embase, Web of Science, Cochrane Library e bancos de dados de Ensaios Clínicos (clinicaltrials.gov) foram pesquisados para os artigos relevantes, e estratégias de busca foram desenvolvidas usando uma combinação de termos temáticos de Medical Subject Headings e palavras de texto. A última pesquisa foi realizada em 4 de julho de 2022. Nenhuma restrição de idioma foi aplicada. Seleção dos estudos Foram incluídos ensaios clínicos randomizados com pacientes com idade gestacional até 6/7 semanas com diagnóstico de aborto incompleto e que foram manejadas com pelo menos um dos três tipos de tratamento estudados. Um total de 8.087 estudos foram selecionados. Coleta de dados Os dados foram sintetizados usando o pacote estatístico Review Manager V.5.1 (The Cochrane Collaboration, Oxford, United Kingdom). Para resultados dicotômicos, o odds ratio (OR, na sigla em inglês) e o intervalo de confiança (IC) de 95% foram derivados para cada estudo. A heterogeneidade entre os resultados do ensaio foi avaliada usando o teste padrão, estatística I2. Síntese dos dados Ao comparar misoprostol com aspiração a vácuo médico (MVA, na sigla em inglês), a taxa de aborto completo foi maior no grupo MVA (OR = 0,16; IC95% = 0,07-0,36). Hemorragia ou sangramento intenso foi mais comum no grupo do misoprostol (OR = 3,00; 95%CI = 1,96-4,59), mas a dor após o tratamento foi mais comum em pacientes tratados com MVA (OR = 0,65; 95%CI = 0,52-0,80). Não foram observadas diferenças estatisticamente significativas na aceitabilidade geral dos tratamentos. Conclusão O misoprostol tem se mostrado uma opção segura e com boa aceitação pelos pacientes.

Laser and radiofrequency for treating genitourinary syndrome of menopause in breast cancer survivors: a systematic review and meta-analysis protocol.

INTRODUCTION: Breast cancer survivors (BCSs) experience more severe symptoms of genitourinary syndrome of menopause (GSM) than healthy postmenopausal women. As hormonal therapy with oestrogen should be avoided in BCSs, finding an effective and safe therapy to address vaginal symptoms and sexual dysfunction is urgently needed. Physical methods may be promising alternatives for the specificities of this group of women. This review aims to evaluate the efficacy and safety of physical methods (laser and radiofrequency) for treating GSM in BCSs. METHODS AND ANALYSIS: The PubMed, Embase, Web of Science, SciELO, LILACS, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov databases will be searched. A search strategy was developed to retrieve clinical trials that evaluate the efficacy and safety of any physical method (laser or radiofrequency) used for GSM in BCSs. No date or language restrictions will be imposed. Two authors will independently select studies by title, abstract and full text to meet the inclusion criteria. Data will be extracted, and the risk of bias will be evaluated using the Cochrane risk-of-bias tool (RoB 2). Review Manager 5.4.1 will be used for data synthesis. The Grading of Recommendations, Assessment, Development and Evaluation will be used to assess the strength of the evidence. ETHICS AND DISSEMINATION: This study reviews the published data; thus, obtaining ethical approval is unnecessary. The findings of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023387680.

Neurological and vestibular findings in three cases of Multiple Sclerosis. / Achados neurológicos e vestibulares em três casos de Esclerose Múltipla.

Multiple sclerosis (MS) is a chronic and inflammatory autoimmune disease that affects the central nervous system (CNS). Dysfunction of body balance is also a common symptom and may be related to neurological injuries resulting from this disease. The aim of this study was to characterize the neurological and vestibular findings of three clinical cases diagnosed with MS. Data on the neurological evaluation and the magnetic resonance imaging of the skull were collected from the medical records. The patients responded to an initial interview and underwent clinical assessment of body balance and Video Head Impulse Test (vHIT). Vestibular symptoms and alterations were observed in at least one of the clinical tests of body balance and cerebellar function. In vHIT, changes were obtained in oculomotor tests, such as the presence of semi-spontaneous nystagmus and in parameters of the saccade test, and reduced gain in one or more vertical channels. Lesions were found on MRI of the skull in central areas that process vestibular information, such as the cerebellum and brainstem. The association of these findings suggests the presence of central vestibular dysfunction, compatible with the lesions detected in imaging exams.

A Esclerose Múltipla (EM) é uma doença autoimune crônica e inflamatória que afeta o sistema nervoso central (SNC). A disfunção do equilíbrio corporal também é um sintoma comum e pode estar relacionada às lesões neurológicas decorrentes desta doença. O objetivo deste estudo foi caracterizar os achados neurológicos e vestibulares de três casos clínicos com diagnóstico de EM. Dados sobre a avaliação neurológica e do exame de ressonância magnética de crânio foram coletados dos prontuários. Os pacientes responderam a uma entrevista inicial e foram submetidos à avaliação clínica do equilíbrio corporal e ao Video Head Impulse Test (vHIT). Observou-se presença de sintomas vestibulares e alterações em pelo menos uma das provas clínicas do equilíbrio corporal e função cerebelar. No vHIT, obteve-se alterações em testes oculomotores, como presença de nistagmo semi-espontâneo e em parâmetros do teste sacádico, e ganho reduzido em um ou mais canais verticais. Foram verificadas lesões, na ressonância magnética de crânio, em áreas centrais que processam as informações vestibulares, como cerebelo e tronco encefálico. A associação destes achados sugere a presença de disfunção vestibular central, compatível com as lesões detectadas nos exames de imagem.

Effects of feeding diets with zinc-l-selenomethionine on growth performance of broilers subjected to cyclic heat stress.

Limited information exists on the use of zinc-l-selenomethionine (Zn-L-SeMet) in broiler diets and its effects on the growth performance, body temperature, mortality rates, blood profile, and gene expression, especially when animals are reared under cyclic heat stress conditions. This study aimed to investigate the impact of Zn-L-SeMet in broiler diets from 1 to 42 days of age reared under cyclic heat stress and its effects on growth performance, cloacal temperatures, mortality rate, blood parameters, and insulin-like growth factor 1 (IGF-1) and growth hormone receptor (GHR) gene expression in the breast muscle. A total of 1000 male Cobb 500® broiler chicks were randomly assigned to five treatments: 0, 0.15, 0.23, 0.47, and 1.30 mg/kg of Zn-L-SeMet. Each treatment consisted of 10 replicates with 20 birds each. No statistically significant differences in growth performance were observed from 1 to 21 days of age (P > 0.05). However, from 1 to 42 days, feed intake (FI) and feed conversion ratio (FCR) decreased linearly (P < 0.05). Cloacal temperatures showed no significant effects (P > 0.05), while overall mortality rate exhibited a quadratic response (P < 0.05), with the optimal inclusion level predicted to reduce broiler mortality at 0.71 mg/kg. Triglyceride (TRG) levels increased with 0.97 mg/kg (P < 0.05), and gama-glutamil transferase (GGT) levels decreased with the inclusion of 1.19 mg/kg (P < 0.05). No significant effects on IGF-1 and GHR gene expression were found (P > 0.05). In conclusion, the inclusion of 1.30 mg/kg of Zn-L-SeMet in diets of heat-stressed broilers improved growth performance from 1 to 42 days of age. An inclusion of 0.71 mg/kg reduced mortality rate, while 0.97 mg and 1.19 mg increased and reduced TRG and GGT levels, respectively.

(-)-5-Demethoxygrandisin B a New Lignan from Virola surinamensis (Rol.) Warb. Leaves: Evaluation of the Leishmanicidal Activity by In Vitro and In Silico Approaches.

Leishmaniasis is a complex disease caused by infection with different Leishmania parasites. The number of medications used for its treatment is still limited and the discovery of new drugs is a valuable approach. In this context, here we describe the in vitro leishmanicidal activity and the in silico interaction between trypanothione reductase (TryR) and (-)-5-demethoxygrandisin B from the leaves of Virola surinamensis (Rol.) Warb. The compound (-)-5-demethoxygrandisin B was isolated from V. surinamensis leaves, a plant found in the Brazilian Amazon, and it was characterized as (7R,8S,7'R,8'S)-3,4,5,3',4'-pentamethoxy-7,7'-epoxylignan. In vitro antileishmanial activity was examined against Leishmania amazonensis, covering both promastigote and intracellular amastigote phases. Cytotoxicity and nitrite production were gauged using BALB/c peritoneal macrophages. Moreover, transmission electron microscopy was applied to probe ultrastructural alterations, and flow cytometry assessed the shifts in the mitochondrial membrane potential. In silico methods such as molecular docking and molecular dynamics assessed the interaction between the most stable configuration of (-)-5-demethoxygrandisin B and TryR from L. infantum (PDB ID 2JK6). As a result, the (-)-5-demethoxygrandisin B was active against promastigote (IC50 7.0 µM) and intracellular amastigote (IC50 26.04 µM) forms of L. amazonensis, with acceptable selectivity indexes. (-)-5-demethoxygrandisin B caused ultrastructural changes in promastigotes, including mitochondrial swelling, altered kDNA patterns, vacuoles, vesicular structures, autophagosomes, and enlarged flagellar pockets. It reduced the mitochondria membrane potential and formed bonds with important residues in the TryR enzyme. The molecular dynamics simulations showed stability and favorable interaction with TryR. The compound targets L. amazonensis mitochondria via TryR enzyme inhibition.

Cell-free supernatant of probiotic bacteria exerted antibiofilm and antibacterial activities against Pseudomonas aeruginosa: A novel biotic therapy.

Aim: This study aims to verify the antibacterial and antibiofilm action of cell-free spent medium (CFSM) from four lactic acid bacteria with potential probiotic characteristics (Lactiplantibacillus plantarum, Lactobacillus acidophilus, Lactobacillus johnsonii, and Lactobacillus delbrueckii) against two Pseudomonas aeruginosa strains. Main methods: The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the CFSM, antibacterial activity by analysing the formation of inhibition zones, and inhibition of planktonic cultures were determined. Whether an increase in the concentration of CFSM influenced the growth of pathogenic strains and the anti-adhesive activity of the CFSM in biofilm formation (crystal violet and MTT assays) were determined, which were all corroborated by using scanning electron microscopy. Key findings: The relationship between the MIC and MBC values showed a bactericidal or bacteriostatic effect for all the cell-free spent media (CFSMs) tested for P. aeruginosa 9027™ and 27853™ strains. The CFSM supplemental doses of 18 or 22%, 20 or 22%, 46 or 48%, and 50 or 54% of L. acidophilus, L. delbrueckii, L. plantarum, and L. johnsonii, respectively, could completely inhibit the growth of both pathogen strains. The antibiofilm activity of the CFSM in three biofilm conditions (pre-coated, co-incubated, and preformed) demonstrated values ranging between 40% and 80% for biofilm inhibition, and similar results were observed for cell viability. Significance: This work provides strong evidence that the postbiotic derived from different Lactobacilli could be practical as an adjuvant therapy for reducing the use of antibiotics, being a good candidate to overcome the growing challenge of hospital infections due to this pathogen.

From Acute Phase to Long COVID: A Cross-Sectional Study of the Epidemiological Profile and Clinical Evaluation of SARS-CoV-2 Infection in Employees at a Pediatric Hospital.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic began in Brazil on 26 February 2020. By 6 May 2023, 37.4 million cases had been confirmed, causing 701 thousand deaths in the country. We aimed to describe the epidemiological profile and clinical development of COVID-19 cases among the employees of a health institution, from acute infection to long COVID. METHODS: This was a longitudinal study using a retrospective and prospective approach via questionnaires referring to epidemiological investigation, which was the inclusion criteria, and about long-term symptoms. RESULTS: A total of 809 employees were detected with SARS-CoV-2 infection via RT-PCR, 466 of them answered the epidemiological investigation, and 101 completed the Long COVID Symptom Questionnaire. The most commonly affected employees were women (88.6%) working in patient care (68.6%). Headache, myalgia, cough, odynophagia, and runny nose were the most frequent symptoms. Only three employees (0.6%) required hospitalization, while the other employees required outpatient management due to mild symptoms. We identified 19 (4.1%) cases of reinfection, and 42 (41.6%) employees reported long-term symptoms, such as myalgia, dyspnea, and headache. CONCLUSIONS: Although most cases were mild with good outcomes, long COVID cases identified are noteworthy, as these symptoms may impact quality of life even months after SARS-CoV-2 infection.

Radiation therapy promotes unsaturated fatty acids to maintain survival of glioblastoma.

Radiation therapy (RT) is essential for the management of glioblastoma (GBM). However, GBM frequently relapses within the irradiated margins, thus suggesting that RT might stimulate mechanisms of resistance that limits its efficacy. GBM is recognized for its metabolic plasticity, but whether RT-induced resistance relies on metabolic adaptation remains unclear. Here, we show in vitro and in vivo that irradiated GBM tumors switch their metabolic program to accumulate lipids, especially unsaturated fatty acids. This resulted in an increased formation of lipid droplets to prevent endoplasmic reticulum (ER) stress. The reduction of lipid accumulation with genetic suppression and pharmacological inhibition of the fatty acid synthase (FASN), one of the main lipogenic enzymes, leads to mitochondrial dysfunction and increased apoptosis of irradiated GBM cells. Combination of FASN inhibition with focal RT improved the median survival of GBM-bearing mice. Supporting the translational value of these findings, retrospective analysis of the GLASS consortium dataset of matched GBM patients revealed an enrichment in lipid metabolism signature in recurrent GBM compared to primary. Overall, these results demonstrate that RT drives GBM resistance by generating a lipogenic environment permissive to GBM survival. Targeting lipid metabolism might be required to develop more effective anti-GBM strategies.

Modularity in host-parasite mixed networks: interaction configuration shifts based on human perturbation and parasitism form.

Parasitism is an association based on host individual traits and environmental factors. The complexity of this type of interaction is often lost when studying species-by-species interaction networks. Here we analyze changes in modularity - a metric describing groups of nodes interacting much more frequently among themselves than they do with nodes of other modules, considering the host individual variation and the different forms of parasitism: ecto- and endo-parasitism. For this, we studied mixed networks: bipartite networks comprising host individuals and parasite species as two sets of nodes interacting with each other. We used a fish-parasite mixed network from a highly perturbed coastal river to understand how an anthropogenic perturbation gradient influences the modular structure of host-parasite networks. In addition, we tested how host individual traits drove module configuration within host-parasite mixed networks. Our results showed that different forms of parasitism respond differently to the environment: modularity in fish-ectoparasite networks increased with human perturbation, but modularity was not related to human perturbation in fish-endoparasite networks. In addition, mixed network modules were intrinsically related to individual variation, with host intensity of infection being the most important trait, regardless of the parasite's life form. The effect of total abundance over network structure indicates signs of changes in community equilibrium, with an increase in species with opportunistic behaviors. Module composition was also related to host fitness and body size, which were most predictive in more preserved and diverse river sections. Overall, our results indicate that host-parasite networks are sensitive to ecological gradients marked by human perturbation and that host individual fitness helps to determine network structure.

Maternal-fetal outcomes of women with hypertensive disorders of pregnancy.

OBJECTIVE: The objective of this study was to determine adverse maternal and perinatal outcomes in pregnant women with hypertensive disorders of pregnancy. METHODS: An analytical cross-sectional study was conducted on women admitted with hypertensive disorders of pregnancies to a university maternity hospital from August 2020 to August 2022. Data were collected using a pretested structured questionnaire. Variables associated with adverse maternal and perinatal outcomes were compared using multivariable binomial regression. RESULTS: Of 501 women with pregnancies, 2, 35, 14, and 49% had eclampsia, preeclampsia, chronic hypertension, and gestational hypertension, respectively. Women with preeclampsia/eclampsia had significantly higher risks of cesarean section (79.4 vs. 65%; adjusted RR, 2,139; 95%CI, 1,386-3,302; p=0.001) and preterm delivery at <34 weeks' gestation (20.5 vs. 6%; adjusted RR, 2.5; 95%CI, 1.19-5.25; p=0.01) than those of women with chronic/gestational hypertension. Risks of prolonged maternal hospitalization (43.9 vs. 27.1%), neonatal intensive care unit admission (30.7 vs. 19.8%), and perinatal mortality (23.5 vs. 11.2%) were higher among women with preeclampsia/eclampsia. CONCLUSIONS: Women with preeclampsia/eclampsia had a higher risk of adverse maternal and neonatal outcomes than those with chronic or gestational hypertension. This major maternity care center requires strategies for preventing and managing preeclampsia/eclampsia to improve pregnancy outcomes.

Behavioral Components and Context of Antimicrobial Prescription in a Tertiary Hospital in Portugal.

Consumption of antimicrobials is an important driver of antimicrobial resistance. There is limited knowledge of the key determinants of antimicrobial prescribing behavior in hospitals. An understanding of these determinants is required for the successful design, adoption, and implementation of quality improvement interventions in Antimicrobial Stewardship Programs (ASP). This study aimed to describe the main factors that influence the doctor's decision on antimicrobials prescribing and to identify the behaviors that drive physicians' decision making. A structured web-based questionnaire focused on behavioral components of antimicrobial prescription was applied to the medical staff of three different departments-Internal Medicine, General Surgery, and Intensive Care Medicine-of a university hospital. All doctors agreed that inadequate use of antimicrobials increases AMR. A total of 77% of the surgeons and 100% of the internists and intensivists perceived antimicrobial prescription as a priority in the department. Full autonomy in antimicrobial prescription was preferred by internists (64%) but not by surgeons (18%) and intensivists (24%). Most physicians were keen to have ASP advice, but most did not want advice from colleagues of the same service. Almost all surgeons ask for advice when prescribing, but only 68% of the internists do it. Less than half of all physicians and only 25% of the surgeons felt free to prescribe contrary to guidelines. Most physicians, particularly in Intensive Care Medicine (94%), adopt the "wait and see" strategy when no microbiologic confirmation is available, but 27% of the surgeons start empirical therapy. In conclusion, the context of antimicrobial prescription, autonomy, and confidence in antimicrobial prescription demonstrated heterogeneity between the three departments and this should be considered when planning ASP.

Quality, opportunity, and treatment of data of tuberculosis and human immunodeficiency virus co-infection / Calidad, oportunidad y manejo de los datos de coinfección tuberculosis y virus de la inmunodeficiencia humana / Qualidade, oportunidade e tratamento de dados de tuberculose e coinfecção com vírus da imunodeficiência humana

Background and Objectives: The identification, evaluation, and use of methodological resources for data quality analysis is important to support planning actions of public policies for the control of tuberculosis (TB) and the co-infection TB and human immunodeficiency virus (HIV). The objective was to analyze the quality and timeliness of notification of TB and TB-HIV co-infection cases from the Notifiable Diseases Information System (SINAN - Sistema de Informação de Agravos de Notificação) in Espírito Santo State, from 2016 to 2018. Methods: This is a cross-sectional study of the quality of SINAN data using the Centers for Disease Control and Prevention (CDC) guidelines to analyze the quality and timeliness of SINAN-TB notification, with emphasis on the description of TB-HIV co-infection in Espírito Santo State, from 2016 to 2018. It considered five methodological steps that included quality analysis, standardization of records, duplicity analysis, the completeness of data through linkage with the SINAN-HIV database and anonymization of data. It obtained ethical approval under the number 4022892 on 12/05/2020. Results: The study showed that 89% of mandatory variables and 91% of essential variables showed satisfactory completeness. In TB-HIV co-infection 73% of the variables were completed, but essential variables related to TB treatment follow-up showed unsatisfactory completeness. The timeliness of reporting was considered regular. Conclusion: Improvements in work processes and the development of a specific methodological process for data treatment are necessary to qualify the information available in SINAN-TB.(AU)

Justificativa e Objetivos: A identificação, avaliação e emprego de recursos metodológicos para análise da qualidade dos dados é importante para fundamentar ações de planejamento das políticas públicas no controle da tuberculose (TB) e da coinfecção TB e o vírus da imunodeficiência humana (HIV). O objetivo é analisar a qualidade e a oportunidade de notificação dos casos de TB e coinfecção TB-HIV do Sistema de Informação de Agravos de Notificação (SINAN) no Espírito Santo, de 2016 a 2018. Métodos: Trata-se de um estudo transversal da qualidade dos dados do SINAN com uso do Guia do Centers for Disease Control and Prevention (CDC) de análise da qualidade e oportunidade de notificação do SINAN-TB, com ênfase na descrição da coinfecção TB-HIV no Espírito Santo, de 2016 a 2018. Considerou-se cinco etapas metodológicas que incluíram análise da qualidade, padronização dos registros, análise de duplicidade, a completitude dos dados por meio de linkage com o banco de dados do SINAN-HIV e anonimização dos dados. Obteve aprovação ética sob parecer de nº 4022892 em 12/05/2020. Resultados: O estudo mostrou que 89% das variáveis obrigatórias e 91% das variáveis essenciais apresentaram completitude satisfatória. Na coinfecção TB-HIV 73% das variáveis foram preenchidas, porém variáveis essenciais relacionadas ao acompanhamento do tratamento para TB apresentaram completitude insatisfatória. A oportunidade de notificação foi considerada regular. Conclusão: Melhorias nos processos de trabalho e elaboração de processo metodológico específico para o tratamento dos dados são necessárias para qualificar as informações disponíveis no SINAN-TB.(AU)

Justificación y Objetivos: La identificación, evaluación y utilización de recursos metodológicos de análisis de la calidad de los datos es importante para apoyar la planificación de políticas públicas de control de la tuberculosis (TB) y la coinfección con el virus de la inmunodeficiencia humana (VIH). El objetivo es analizar la calidad y oportunidad de la notificación de casos de TB y coinfección TB-VIH del Sistema de Informação de Agravos de Notificação (SINAN), en el Estado del Espírito Santo, desde el año 2016 hasta 2018. Métodos: Este es un estudio transversal utilizando el análisis de la Guía de los Centros para el Control y Prevención de Enfermedades (CDC) de la calidad y oportunidad de la notificación en SINAN-TB, con énfasis en la descripción de la coinfección TB-VIH, en el Estado del Espírito Santo, desde el año 2016 hasta 2018. Fueran considerados cinco pasos metodológicos que incluyeron análisis de calidad, estandarización de registros, análisis de duplicidad, vinculación con la base de datos SINAN-VIH y anonimización de datos. Obtuvo aprobación ética bajo dictamen nº 4022892 el 12/05/2020. Resultados: El 89% de las variables obligatorias y el 91% de las variables esenciales se completaron satisfactoriamente. En la coinfección TB-VIH el 73% de las variables fueron completadas, mientras que las variables esenciales relacionadas con el acompañamiento del tratamiento para la TB presentaron una completitud insatisfactoria. La oportunidad de notificación fue considerada regular. Conclusión: Las mejoras en los procesos de trabajo y la elaboración de un proceso metodológico específico para el tratamiento de los datos son necesarias para cualificar la información disponible en el SINAN-TB.(AU)

Physical and mental illness comorbidity among individuals with frequent self-harm episodes: A mixed-methods study.

Background: Research has indicated an increased risk of self-harm repetition and suicide among individuals with frequent self-harm episodes. Co-occurring physical and mental illness further increases the risk of self-harm and suicide. However, the association between this co-occurrence and frequent self-harm episodes is not well understood. The objectives of the study were (a) to examine the sociodemographic and clinical profile of individuals with frequent self-harm (regardless of suicidal intent) episodes and, (b) the association between physical and mental illness comorbidity, self-harm repetition, highly lethal self-harm methods, and suicide intent. Methods: The study included consecutive patients with five or more self-harm presentations to Emergency Departments across three general hospitals in the Republic of Ireland. The study included file reviews (n = 183) and semi-structured interviews (n = 36). Multivariate logistic regression models and independent samples t-tests were used to test the association between the sociodemographic and physical and mental disorders comorbidity on highly lethal self-harm methods and suicidal intent, respectively. Thematic analysis was applied to identify themes related to physical and mental illness comorbidity and frequent self-harm repetition. Findings: The majority of individuals with frequent self-harm episodes were female (59.6%), single (56.1%), and unemployed (57.4%). The predominant current self-harm method was drug overdose (60%). Almost 90% of the participants had history of a mental or behavioral disorder, and 56.8% had recent physical illness. The most common psychiatric diagnoses were alcohol use disorders (51.1%), borderline personality disorder (44.0%), and major depressive disorder (37.8%). Male gender (OR = 2.89) and alcohol abuse (OR = 2.64) predicted the risk of a highly lethal self-harm method. Suicide intent was significantly higher among those with a diagnosis of major depressive disorder (t = 2.43; p = 0.020). Major qualitative themes were (a) the functional meaning of self-harm (b) self-harm comorbidity (c) family psychiatric history and (d) contacts with mental health services. Participants described experiencing an uncontrollable self-harm urge, and self-harm was referred to as a way to get relief from emotional pain or self-punishment to cope with anger and stressors. Conclusion: Physical and mental illness comorbidity was high among individuals with frequent self-harm episodes. Male gender and alcohol abuse were associated with highly lethal self-harm methods. The mental and physical illness comorbidity of individuals with frequent self-harm episodes should be addressed via a biopsychosocial assessment and subsequent indicated treatment interventions.

An in silico molecular modeling approach of halolactone derivatives as potential inhibitors for human immunodeficiency virus type-1 reverse transcriptase enzyme.

Acquired Immune Deficiency Syndrome (AIDS) is an infectious disease caused by Human Immunodeficiency Virus (HIV) infection and its replication requires the Reverse Transcriptase (RT) enzyme. RT plays a key role in the HIV life cycle, making it one of the most important targets for designing new drugs. Thus, in order to increase therapeutic options against AIDS, halolactone derivatives (D-halolactone) that have been showed as potential non-nucleoside inhibitors of the RT enzyme were studied. In the present work, a series of D-halolactone were investigated by molecular modeling studies, combining Three-dimensional Quantitative Structure-Activity Relationship (3 D-QSAR), molecular docking and Molecular Dynamics (MD) techniques, to understand the molecular characteristics that promote biological activity. The internal and external validation parameters indicated that the 3 D-QSAR model has good predictive capacity and statistical significance. Contour maps provided useful information on the structural characteristics of compounds for anti-HIV-1 activity. The docking results showed that D-halolactone present good complementarity by the RT allosteric site. In MD simulations it was observed that the formation of enzyme-ligand complexes were favorable, and from the free energy decomposition it was found that Leu100, Val106, Tyr181, Try188, and Trp229 are key residues for stabilization in the enzymatic site. Thus, the results showed that the proposed models can be used to design promising HIV-1 RT inhibitors. Communicated by Ramaswamy H. Sarma.

NEOTROPICAL FRESHWATER FISHES: A dataset of occurrence and abundance of freshwater fishes in the Neotropics.

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications.

Achados neurológicos e vestibulares em três casos de Esclerose Múltipla / Neurological and vestibular findings in three cases of Multiple Sclerosis

RESUMO A Esclerose Múltipla (EM) é uma doença autoimune crônica e inflamatória que afeta o sistema nervoso central (SNC). A disfunção do equilíbrio corporal também é um sintoma comum e pode estar relacionada às lesões neurológicas decorrentes desta doença. O objetivo deste estudo foi caracterizar os achados neurológicos e vestibulares de três casos clínicos com diagnóstico de EM. Dados sobre a avaliação neurológica e do exame de ressonância magnética de crânio foram coletados dos prontuários. Os pacientes responderam a uma entrevista inicial e foram submetidos à avaliação clínica do equilíbrio corporal e ao Video Head Impulse Test (vHIT). Observou-se presença de sintomas vestibulares e alterações em pelo menos uma das provas clínicas do equilíbrio corporal e função cerebelar. No vHIT, obteve-se alterações em testes oculomotores, como presença de nistagmo semi-espontâneo e em parâmetros do teste sacádico, e ganho reduzido em um ou mais canais verticais. Foram verificadas lesões, na ressonância magnética de crânio, em áreas centrais que processam as informações vestibulares, como cerebelo e tronco encefálico. A associação destes achados sugere a presença de disfunção vestibular central, compatível com as lesões detectadas nos exames de imagem.

ABSTRACT Multiple sclerosis (MS) is a chronic and inflammatory autoimmune disease that affects the central nervous system (CNS). Dysfunction of body balance is also a common symptom and may be related to neurological injuries resulting from this disease. The aim of this study was to characterize the neurological and vestibular findings of three clinical cases diagnosed with MS. Data on the neurological evaluation and the magnetic resonance imaging of the skull were collected from the medical records. The patients responded to an initial interview and underwent clinical assessment of body balance and Video Head Impulse Test (vHIT). Vestibular symptoms and alterations were observed in at least one of the clinical tests of body balance and cerebellar function. In vHIT, changes were obtained in oculomotor tests, such as the presence of semi-spontaneous nystagmus and in parameters of the saccade test, and reduced gain in one or more vertical channels. Lesions were found on MRI of the skull in central areas that process vestibular information, such as the cerebellum and brainstem. The association of these findings suggests the presence of central vestibular dysfunction, compatible with the lesions detected in imaging exams.