Virus discovery in cultured portunid crabs: Genomic, phylogenetic, histopathological and microscopic characterization of a reovirus and a new bunyavirus.

Portunid crabs are distributed worldwide and highly valued in aquaculture. Viral infections are the main limiting factor for the survival of these animals and, consequently, for the success of commercial-scale cultivation. However, there is still a lack of knowledge about the viruses that infect cultured portunid crabs worldwide. Herein, the genome sequence and phylogeny of Callinectes sapidus reovirus 2 (CsRV2) are described, and the discovery of a new bunyavirus in Callinectes danae cultured in southern Brazil is reported. The CsRV2 genome sequence consists of 12 dsRNA segments (20,909 nt) encode 13 proteins. The predicted RNA-dependent RNA polymerase (RdRp) shows a high level of similarity with that of Eriocheir sinensis reovirus 905, suggesting that CsRV2 belongs to the genus Cardoreovirus. The CsRV2 particles are icosahedral, measuring approximately 65 nm in diameter, and exhibit typical non-turreted reovirus morphology. High throughput sequencing data revealed the presence of an additional putative virus genome similar to bunyavirus, called Callinectes danae Portunibunyavirus 1 (CdPBV1). The CdPBV1 genome is tripartite, consisting of 6,654 nt, 3,120 nt and 1,656 nt single-stranded RNA segments that each encode a single protein. Each segment has a high identity with European shore crab virus 1, suggesting that CdPBV1 is a new representative of the family Cruliviridae. The putative spherical particles of CdPBV1 measure ∼120 nm in diameter and present a typical bunyavirus morphology. The results of the histopathological analysis suggest that these new viruses can affect the health and, consequently, the survival of C. danae in captivity. Therefore, the findings reported here should be used to improve prophylactic and pathogen control practices and contribute to the development and optimization of the production of soft-shell crabs on a commercial scale in Brazil.

Atomistic Origins of Resurrection of Aged Acetylcholinesterase by Quinone Methide Precursors.

Nerve agents are organophosphates (OPs) that act as potent inhibitors of acetylcholinesterase (AChE), the enzyme responsible for the hydrolysis of acetylcholine. After inhibition, a dealkylation reaction of the phosphorylated serine, known as the aging of AChE, can occur. When aged, reactivators of OP-inhibited AChE are no longer effective. Therefore, the realkylation of aged AChE may offer a pathway to reverse AChE aging. In this study, molecular modeling was conducted to propose new ligands as realkylators of aged AChE. We applied a methodology involving docking and quantum mechanics/molecular mechanics (QM/MM) calculations to evaluate the resurrection kinetic constants and ligand interactions with OP-aged AChE, comparing them to data found in the literature. The results obtained confirm that this method is suitable for predicting kinetic and thermodynamic parameters of ligands, which can be useful in the design and selection of new and more effective ligands for AChE realkylation.

High prevalence of CsRV2 in cultured Callinectes danae: Potential impacts on soft-shell crab production in Brazil.

Crabs can be infected by a variety of pathogenic micro-organisms but the most damaging are viruses. Naturally-occurring Callinectes sapidus reovirus 1 (CsRV1) is thought to contribute to mortality of Callinectes sapidus in soft crab culture in the USA. In Brazil, soft crabs are frequently produced using Callinectes danae, which suffers a similar rate of mortality in culture as C. sapidus. This study investigated whether CsRV1 could be detected in healthy or dead Callinectes danae from Paraná, Brazil and kept in captivity, we also evaluated the relationship between viral infection, and biochemical and behavioral parameters. C. danae from Paranaguá Bay were kept in a recirculation system for 14 days and subjected to weekly biochemical analyses and a reflex action mortality predictors (RAMP) test. RT-qPCR assays for CsRV1 were negative for all samples. However, electrophoretic analysis of extracted RNA from some crabs showed a pattern of 12 dsRNA bands that indicated intense infection by a reovirus with a genome organization different from CsRV1. The banding pattern was indistinguishable from a putative novel reovirus detected in C. sapidus in Rio Grande do Sul, Brazil, provisionally called CsRV2. The prevalence of dsRNA of CsRV2 showed no significant difference between crabs that died and survived. Interestingly, the presence of CsRV2 dsRNA was correlated with a significant reduction in glycogen concentration in hepatopancreas and a decrease in reflex action. The results obtained in this study are an early glimpse of the occurrence of reoviruses in C. danae and their potential effects in soft-shell crab systems in Brazil.

The concomitant use of cannabis and cocaine coexists with increased LPS levels and systemic inflammation in male drug users.

Illicit drug use can cause a variety of effects including alterations in the immune system. The aim of this study was to investigate the effects of illicit drugs on circulating lipopolysaccharide (LPS), systemic inflammation and oxidative stress markers in drug users. We evaluated the levels of soluble CD14 (sCD14), LPS, inflammatory (TNF-α and IL-6) and regulatory (IL-10) cytokines, as well as C-reactive protein (CRP), lipid peroxidation (TBARS) and total thiols in the peripheral blood of 81 men included in groups of cannabis (n = 21), cocaine (n = 12), cannabis-plus-cocaine users (n = 27), and non-drug users (n = 21). The use of cannabis plus cocaine leads to higher systemic levels of LPS, CRP, IL-6 and higher IL-6/IL-10 ratio, characterizing a proinflammatory profile. In contrast, a regulatory profile as viewed by lower systemic TNF-α and IL-6 levels and lower TNF-α/IL-10 ratio were observed in cannabis users compared to the control group. Moreover, cocaine users presented a lower content of non-enzymatic antioxidant thiol compared to control group, cannabis group and cannabis plus cocaine group. In conclusion, our results indicate that the use of cannabis contributes to an anti-inflammatory/or regulatory profile while the concomitant cannabis plus cocaine consumption coexists with increased circulating amounts of LPS and proinflammatory status.

Diversity and classification of reoviruses in crustaceans: A proposal.

A variety of reoviruses have been described in crustacean hosts, including shrimp, crayfish, prawn, and especially in crabs. However, only one genus of crustacean reovirus - Cardoreovirus - has been formally recognized by ICTV (International Committee on Taxonomy of Viruses) and most crustacean reoviruses remain unclassified. This arises in part from ambiguous or incomplete information on which to categorize them. In recent years, increased availability of crustacean reovirus genomic sequences is making the discovery and classification of crustacean reoviruses faster and more certain. This minireview describes the properties of the reoviruses infecting crustaceans and suggests an overall classification of brachyuran crustacean reoviruses based on a combination of morphology, host, genome organization pattern and phylogenetic sequence analysis.

Evaluation of different induced molting methods in Callinectes ornatus (Crustacea, Decapoda, Portunidae) as a tool for the commercial production of soft-shell crabs.

We investigated the effects of eyestalk ablation and cheliped autotomy in inducing molting in Callinectes ornatus. The specimens in intermolt stage were divided into two size classes: 1 (30-50 mm) and 2 (51-70 mm) and were further divided into four experimental groups. In the CA group (Cheliped Autotomy, n=76), crabs were submitted to cheliped autotomy; in the UA group (Unilateral Ablation, n=66) and BA group (Bilateral Ablation, n=66) to unilateral and bilateral eyestalk ablation, respectively. The C group (Control, n=70) was used as control. The animals were individually kept in tanks interconnected to a recirculation system for 30 days. The highest frequency of premolt was recorded in the BA group (32%), followed by the CA group (16%). The premolt frequency of class 1 (28%) was significantly higher (p<0.05) than of class 2 (8%). The mean time until molt in the BA group was significantly lower (p <0.05) than other groups tested. The highest mortality rates were 55% and 25% in crabs from the BA and CA groups, respectively. The results indicate bilateral eyestalk ablation and cheliped autotomy are potentially capable of inducing molt in C. ornatus, but these techniques have limited efficiency for the commercial application of large-scale soft-shell crab.

Predicting postoperative atrial fibrillation after myocardial revascularization without cardiopulmonary bypass: A retrospective cohort study.

INTRODUCTION: Considering the threat imposed by postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and the potential benefits of off-pump CABG, the objective of this study was to describe the incidence and identify predictor factors for POAF in patients undergoing CABG without cardiopulmonary bypass (CPB). METHODS: In this retrospective cohort study, we enrolled patients undergoing CABG without CPB between December 2008 and December 2011. The independent variables evaluated in this study were major patients' characteristics (age, sex, and ethnia), associated comorbidities (systemic arterial hypertension, diabetes mellitus, thyroid dysfunction, chronic renal failure (CRF), chronic obstructive pulmonary disease, and ischemic stroke), and the revascularization approach (the number of grafts used, the revascularized branch, and the choice of vascular graft (arterial or venous). The dependent variable was the onset of atrial fibrillation after the procedure. RESULTS: Two hundred and eighty patients were included in the present study. The overall incidence of POAF after off-pump CABG was 5.0%. In the univariate analysis, the presence of chronic renal failure (odds ratio [OR], 3.01 [1.00-9.06], P = .049) and the use of venous-origin graft alone (OR, 9.67 [1.15-81.56], P = .037) were associated with an increased risk or POAF. These findings were confirmed after multivariate analysis, for both CRF (OR, 3.31 [1.05-10.46], P = .042) and the use of venous-origin graft alone (OR, 9.81 [1.13-85.35], P = .039). CONCLUSION: Off-pump coronary artery bypass grafting proved a safe and effective procedure, with low postoperative atrial fibrillation occurrence, for myocardial revascularization. Chronic renal insufficiency and the use of venous-origin graft solely proved to be independent predictor factors for PAOF.

Growth, chain formation, and toxin production by southern Brazilian Pseudo-nitzschia isolates under laboratory conditions.

Pseudo-nitzschia is a diatom genus capable of producing the neurotoxin domoic acid (DA), which has been related to mortalities of marine vertebrates, and the amnesic shellfish poisoning (ASP) in human consumers of contaminated bivalves. This study reports DA production among Pseudo-nitzschia strains isolated from shellfish farming areas in southern Brazil. Twenty-seven cultures of potentially toxigenic Pseudo-nitzschia species were established. Growth, stepped-chain formation, and DA production were evaluated in static, intermittently illuminated (12:12 photoperiod) batch cultures for 12 selected strains, and under continuous light and/or turbulence for a single Pseudo-nitzschia calliantha strain. Growth rate ranged from 0.16 to 0.39 day-1 among the 12 strains. Only P. calliantha and P. cf. multiseries yielded detectable levels of intracellular DA, reaching up to 0.054 fg cell-1 in late exponential and 0.15 pg cell-1 in early stationary phase, respectively. Continuous light impaired cell growth, and turbulence enhanced step-chain formation by threefold during exponential growth phase, but no DA production was detected under both conditions. The effect of turbulence on chain formation should be further evaluated in the field, once particle size is expected to affect the ingestion of toxic cells and thus toxin accumulation by certain DA vectors. The low cell toxicity revealed herein under laboratory conditions is in accordance with the low frequency of DA contamination episodes in south Brazilian waters. Nevertheless, monitoring of Pseudo-nitzschia abundance and DA presence in farming areas is continuously required to assure the quality of local shellfish products.

Enhanced Sampling in Molecular Dynamics Simulations: How Many MD Snapshots can be Needed to Reproduce the Biological Behavior?

Since its early days in the 19th century, medicinal chemistry has concentrated its efforts on the treatment of diseases, using tools from areas such as chemistry, pharmacology, and molecular biology. The understanding of biological mechanisms and signaling pathways is crucial information for the development of potential agents for the treatment of diseases mainly because they are such complex processes. Given the limitations that the experimental approach presents, computational chemistry is a valuable alternative for the study of these systems and their behavior. Thus, classical molecular dynamics, based on Newton's laws, is considered a technique of great accuracy, when appropriated force fields are used, and provides satisfactory contributions to the scientific community. However, as many configurations are generated in a large MD simulation, methods such as Statistical Inefficiency and Optimal Wavelet Signal Compression Algorithm are great tools that can reduce the number of subsequent QM calculations. Accordingly, this review aims to briefly discuss the importance and relevance of medicinal chemistry allied to computational chemistry as well as to present a case study where, through a molecular dynamics simulation of AMPK protein (50 ns) and explicit solvent (TIP3P model), a minimum number of snapshots necessary to describe the oscillation profile of the protein behavior was proposed. For this purpose, the RMSD calculation, together with the sophisticated OWSCA method was used to propose the minimum number of snapshots.

Vanadium complex as a potential modulator of the autophagic mechanism through proteins PI3K and ULK1: development, validation and biological implications of a specific force field for [VO(bpy)2Cl].

The modulation of autophagy has been presented as a very useful strategy in anticancer treatments. In this sense, the vanadium complex (VC) bis(2,2'-bipyridine)chlorooxovanadium(IV), [VO(bpy)2Cl], is known for its ability to induce autophagy in triple-negative breast cancer cells (TNBC). An excellent resource to investigate the role of VC in the induction of autophagy is to make use of Molecular Dynamics (MD) simulations. However, until now, the scarcity of force field parameters for the VC prevented a reliable analysis. The autophagy signaling pathway starts with the PI3K protein and ends with ULK1. Therefore, in the first stage of this work, we developed a new AMBER force field for the VC (VCFF) from a quantum structure, obtained by DFT calculations. In the second stage, the VCFF was validated through structural analyses. From this, it was possible to investigate, through docking and MD (200 ns), the performance of the PI3K-VC and ULK1-VC systems (third stage). The analyses of this last stage involved RMSD, hydrogen bonds, RMSF and two pathways for the modulation of autophagy. In general, this work fills in the absence of force field parameters (FF) for VC by proposing an efficient and new FF, in addition to investigating, at the molecular level, how VC is able to induce autophagy in TNBC cells. This study encourages new parameterizations of metallic complexes and contributes to the understanding of the duality of autophagic processes.Communicated by Ramaswamy H. Sarma.

Molecular Dynamics-Assisted Interaction of Vanadium Complex-AMPK: From Force Field Development to Biological Application for Alzheimer's Treatment.

A large part of the world's population is affected by Alzheimer's disease (AD) and diabetes mellitus type 2, which cause both social and economic impacts. These two conditions are associated with one protein, AMPK. Studies have shown that vanadium complexes, such as bis(N',N'-dimethylbiguanidato)-oxovanadium(IV), VO(metf)2·H2O, are potential agents against AD. A crucial step in drug design studies is obtaining information about the structure and interaction of these complexes with the biological targets involved in the process through molecular dynamics (MD) simulations. However, MD simulations depend on the choice of a good force field that could present reliable results. Moreover, general force fields are not efficient for describing the properties of metal complexes, and a VO(metf)2·H2O-specific force field does not yet exist; thus, the proper development of a parameter set is necessary. Furthermore, this investigation is essential and relevant given the importance for both the scientific community and the population that is affected by this neurodegenerative disease. Therefore, the present work aims to develop and validate the AMBER force field parameters for VO(metf)2·H2O since the literature lacks such information on metal complexes and investigate through classical molecular dynamics the interactions made by the complex with the protein. The proposed force field proved to be effective for describing the vanadium complex (VC), supported by different analyses and validations. Moreover, it had a great performance when compared to the general AMBER force field. Beyond that, MD findings provided an in-depth perspective of vanadium complex-protein interactions that should be taken into consideration in future studies.

Parameterization and validation of a new AMBER force field for an oxovanadium (IV) complex with therapeutic potential implications in Alzheimer's disease.

The scarcity of efficient force fields to describe metal complexes may be a problem for new advances in medicinal chemistry. Thus, the development of force fields for these compounds can be valuable for the scientific community, especially when it comes to molecules that show interesting outputs regarding potential treating of diseases. Vanadium complexes, for instance, have shown promising results towards therapeutics of Alzheimer's Disease, most notably the bis(maltolato)oxovanadium (IV). Therefore, the mainly goal of this work is to develop and validate a new set of parameters for this vanadium complex from a minimum energy structure, obtained by DFT calculations, where great results of the new force field are found when confronted with experimental and quantum reference values. Moreover, the new force field showed to be quite effective to describe the molecule of under study whilst GAFF could not describe it effectively. In addition, a case study points out hydrogen bonds in the vanadium complex-PTP1B system.

MD Simulations to Calculate NMR Relaxation Parameters of Vanadium(IV) Complexes: A Promising Diagnostic Tool for Cancer and Alzheimer's Disease.

Early phase diagnosis of human diseases has still been a challenge in the medicinal field, and one of the efficient non-invasive techniques that is vastly used for this purpose is magnetic resonance imaging (MRI). MRI is able to detect a wide range of diseases and conditions, including nervous system disorders and cancer, and uses the principles of NMR relaxation to generate detailed internal images of the body. For such investigation, different metal complexes have been studied as potential MRI contrast agents. With this in mind, this work aims to investigate two systems containing the vanadium complexes [VO(metf)2]·H2O (VC1) and [VO(bpy)2Cl]+ (VC2), being metformin and bipyridine ligands of the respective complexes, with the biological targets AMPK and ULK1. These biomolecules are involved in the progression of Alzheimer's disease and triple-negative breast cancer, respectively, and may act as promising spectroscopic probes for detection of these diseases. To initially evaluate the behavior of the studied ligands within the aforementioned protein active sites and aqueous environment, four classical molecular dynamics (MD) simulations including VC1 + H2O (1), VC2 + H2O (2), VC1 + AMPK + H2O (3), and VC2 + ULK1 + H2O (4) were performed. From this, it was obtained that for both systems containing VCs and water only, the theoretical calculations implied a higher efficiency when compared with DOTAREM, a famous commercially available contrast agent for MRI. This result is maintained when evaluating the system containing VC1 + AMPK + H2O. Nevertheless, for the system VC2 + ULK1 + H2O, there was observed a decrease in the vanadium complex efficiency due to the presence of a relevant steric hindrance. Despite that, due to the nature of the interaction between VC2 and ULK1, and the nature of its ligands, the study gives an insight that some modifications on VC2 structure might improve its efficiency as an MRI probe.

From egg to slaughter: monitoring the welfare of Nile tilapia, Oreochromis niloticus, throughout their entire life cycle in aquaculture.

The primary aim of this study was to comprehensively evaluate the welfare of Nile tilapia (Oreochromis niloticus) throughout their entire life cycle within aquaculture, spanning from reproduction to slaughter. The methodology was structured to identify welfare indicators closely aligned with the principles of animal freedoms defined by the Farm Animal Council, encompassing environmental, health, nutritional, behavioral, and psychological freedom. Notably, psychological freedom was inherently considered within the behavioral and physical analyses of the animals. To accomplish this, an integrative systematic literature review was conducted to define precise indicators and their corresponding reference values for each stage of tilapia cultivation. These reference values were subsequently categorized using a scoring system that assessed the deviation of each indicator from established ideal (score 1), tolerable (score 2), and critical (score 3) ranges for the welfare of the target species. Subsequently, a laboratory experiment was executed to validate the pre-selected health indicators, specifically tailored for the early life stages of tilapia. This test facilitated an assessment of the applicability of these indicators under operational conditions. Building on the insights gained from this experimentation, partial welfare indices (PWIs) were computed for each assessed freedom, culminating in the derivation of a general welfare index (GWI). Mathematical equations were employed to calculate these indices, offering a quantitative and standardized measure of welfare. This approach equips tilapia farmers and processors with the tools necessary for the continuous monitoring and enhancement of their production systems and stimulate the adoption of more sustainable and ethical practices within the tilapia farming.

Non-Invasive Methods for Assessing the Welfare of Farmed White-Leg Shrimp (Penaeus vannamei).

Gradually, concern for the welfare of aquatic invertebrates produced on a commercial/industrial scale is crossing the boundaries of science and becoming a demand of other societal actors. The objective of this paper is to propose protocols for assessing the Penaeus vannamei welfare during the stages of reproduction, larval rearing, transport, and growing-out in earthen ponds and to discuss, based on a literature review, the processes and perspectives associated with the development and application of on-farm shrimp welfare protocols. Protocols were developed based on four of the five domains of animal welfare: nutrition, environment, health, and behaviour. The indicators related to the psychology domain were not considered a separate category, and the other proposed indicators indirectly assessed this domain. For each indicator, the corresponding reference values were defined based on literature and field experience, apart from the three possible scores related to animal experience on a continuum from positive (score 1) to very negative (score 3). It is very likely that non-invasive methods for measuring the farmed shrimp welfare, such as those proposed here, will become a standard tool for farms and laboratories and that it will become increasingly challenging to produce shrimp without considering their welfare throughout the production cycle.

Evaluation of autophagy inhibition to combat cancer: (vanadium complex)-protein interactions, parameterization, and validation of a new force field.

Autophagy has drawn attention from the scientific community, mainly because of its significant advantages over chemotherapeutic processes. One of these advantages is its direct action on cancer cells, avoiding possible side effects, unlike chemotherapy, which reaches tumor cells and affects healthy cells in the body, leading to a great loss in the quality of life of patients. In this way, it is known that vanadium complex (VC) [VO(oda)(phen)] has proven inhibition effect on autophagy process in pancreatic cancer cells. Keeping that in mind, molecular dynamics (MD) simulations can be considered excellent strategies to investigate the interaction of metal complexes and their biological targets. However, simulations of this type are strongly dependent on the appropriate choice of force field (FF). Therefore, this work proposes the development of AMBER FF parameters for VC, having a minimum energy structure as a starting point, obtained through DFT calculations with B3LYP/def2-TZVP level of theory plus ECP for the vanadium atom. An MD simulation in vacuum was performed to validate the developed FF. From the structural analyses, satisfying values of VC bond lengths and angles were obtained, where a good agreement with the experimental data and the quantum reference was found. The RMSD analysis showed an average of only 0.3%. Finally, we performed docking and MD (120 ns) simulations with explicit solvent between VC and PI3K. Overall, our findings encourage new parameterizations of metal complexes with significant biological applications, as well as allow to contribute to the elucidation of the complex process of autophagy.

Value of Contrast-enhanced Magnetic Resonance Imaging (MRI) in the Diagnosis of Breast Cancer.

This review article aims to address the main features of breast cancer. Thus, the general aspects of this disease have been shown since the first evidence of breast cancer in the world until the numbers today. In this way, there are some ways to prevent breast cancer, such as the woman's lifestyle (healthy eating habits and physical activities) that helps to reduce the incidence of this anomaly. The first noticeable symptom of this anomaly is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer are discovered when the woman feels a lump being present and about 90% of the cases, the cancer is noticed by the woman herself. Currently, the most used method for the detection of cancer and other injuries is the Magnetic Resonance Imaging (MRI) technique. This technique has been shown to be very effective, however, for a better visualization of the images, Contrast Agents (CAs) are used, which are paramagnetic compounds capable of increasing the relaxation of the hydrogen atoms of the water molecules present in the body tissues. The most used CAs are Gd3+ complexes, although they are very efficient, they are toxic to the organism. Thus, new contrast agents have been studied to replace Gd3+ complexes; we can mention iron oxides as a promising substitute.

Effectiveness of green tea extract (Camellia sinensis) capsule supplementation for post-exercise muscle recovery in healthy adults: a systematic review protocol.

OBJECTIVE: The objective of the review is to evaluate the effectiveness of green tea extract (Camellia sinensis) capsule supplementation compared with placebo for post-exercise muscle pain and muscle recovery in healthy adults. INTRODUCTION: Green tea extract is popularly consumed by athletes and practitioners of physical activity, as it is easily accessible in supermarkets and health food stores. It is a source of catechins, which assist the endogenous antioxidant system in combating free radicals produced during exercise that can lead to oxidative stress and, therefore, muscle damage and delayed-onset muscle pain. However, there is no consensus on the effect of green tea extract and the ideal and safe dosage to promote muscle recovery. INCLUSION CRITERIA: Studies on the effectiveness of supplementation with green tea extract capsules compared with placebo in post-exercise muscle pain and muscle recovery in healthy adults will be included. Studies that are associated with any other source of polyphenols with green tea extract will be excluded. METHODS: Studies will be identified using the following databases: Cochrane Library, PubMed, Embase, Web of Science, Virtual Health Library, SPORTDiscus, Science Direct, and Scopus. OpenGrey, DART-Europe, and Google Scholar will be used to identify unpublished studies. Studies published in English, French, Spanish, or Portuguese will be included. There will be no restriction on the date of publication. Two authors will independently screen titles and abstracts following previously defined eligibility criteria. After excluding irrelevant studies, the authors will read the full texts of any articles potentially eligible for further evaluation. Any disagreements will be resolved by discussion or by consulting a third author. The included studies will be assessed on their methodological quality using the appropriate JBI critical appraisal checklist, and the data will be extracted by the two authors. A meta-analysis will be performed using a random effects or fixed effects model. The heterogeneity of the data will be calculated. This review will follow the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to classify the certainty of the evidence. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020138772.

Epidemiological and clinical profile of HIV-infected patients from Southwestern Goias State, Brazil.

Knowledge about epidemiological distribution patterns of HIV infection in different geographic regions is relevant to understand the dynamics of the disease in Brazil. This study aims to characterize the epidemiological and clinical profile of HIV-infected patients from Southwestern Goias State, from 2005 to 2015. A standardized questionnaire was used to collect clinical-epidemiological, virological, and immunological data from the medical records of all HIV-infected patients (n=539) who were followed at the regional reference center of Jatai, Goias State, Brazil, from 2005 to 2015. We detected the prevalence of male patients and the heterosexual route of transmission, as well as an expressive number of young women infected with HIV. The HIV infection was more prevalent in reproductive ages (55.3%). Most patients presented clinical manifestations related to HIV infection at the time of diagnosis. Twenty-four patients presented coinfection with hepatitis C virus, syphilis, hepatitis B virus, leprosy or Chagas disease. Pneumonia caused by Pneumocystis jirovecii was the most common opportunistic infection, followed by neurotoxoplasmosis, tuberculosis, and neurocryptococcosis. Combined antiretroviral therapy improved CD4+ T-cell counts: the mean CD4+ T-cell counts after treatment was twice as high as those found at the first medical appointment; and highly active antiretroviral therapy promoted viral suppression in a significant number of patients. Considering the increasing distribution of HIV infection to the interior of Brazil, this descriptive study outlines the clinical-epidemiological characteristics of HIV infection in Southwestern Goias and contributes to develop local prevention strategies and public service plans.

Mutação de novo no gene DEAF1 e sua relação com o autismo: estudo de caso / De novo mutation in the DEAF1 gene and its relation to autism: a case study / Mutación de nuevo en el gen DEAF1 y su relación con el autismo: estudio de caso

Objetivo: Analisar as implicações, impactos e o desenvolvimento de um indivíduo diagnosticado com TEA e portador da mutação de novo no gene DEAF1, a partir das várias perspectivas de intervenções realizadas. Método: Trata-se de um estudo descritivo com histórico dos tratamentos, resultados laboratoriais e genéticos mais recentes do paciente. Resultados: Sintomas notados aos 2 anos e diagnóstico específico aos 5. Aos 8 anos teve a primeira crise convulsiva tônico-clônica e o Eletroencefalograma alterado. Após obteve o diagnóstico molecular confirmado. Possuía epilepsia refratária de difícil controle, que houve piora com uma tentativa do uso de derivados canabinoides em conjunto com estimulação elétrica transcraniana. No momento, com os tratamentos, atendimentos multidisciplinares, dieta de exclusão de alérgenos e medicações de controle individual, diminuíram a intensidade das crises epiléticas e houve melhor controle do seu estado geral. Conclusão: Este estudo descreve como a mutação de novo no gene DEAF1 está relacionada com o TEA e com o comprometimento do desenvolvimento neurocognitivo. As terapias e métodos devem respeitar cada paciente na sua individualidade.

Objective: To analyze the implications, impacts and development of an individual diagnosed with ASD and carrying a de novo mutation in the DEAF1 gene, from the various perspectives of interventions performed. Method: This is a descriptive study, with the patient's history of treatments, and most recent laboratory and genetic results.Results: Symptoms were noticed at 2 years old and specific diagnosis at 5. At 8 years old he had his first tonic-clonic seizure and the electroencephalogram was altered. After, it was obtained the confirmed molecular diagnosis. He had refractory epilepsy that was difficult to control and aggravated with an attempt to use cannabinoid derivatives in conjunction with transcranial electrical stimulation. At the moment, treatments, multidisciplinary care, allergen exclusion diet and individual control medications, reduced the intensity of epileptic seizures and there was better control of his general condition. Conclusion: This study describes how the de novo mutation in the DEAF1 gene is related to ASD and neurocognitive development impairment. Therapies and methods must respect each patient in their individuality.

Objetivo: Analizar las implicaciones, impactos y desarrollo de un individuo diagnosticado de TEA y portador de una mutación de novo en el gen DEAF1, desde las distintas perspectivas de las intervenciones realizadas. Método: Este es un estudio descriptivo, con el historico de tratamientos del paciente y los resultados genéticos y de laboratorio más recientes. Resultados: Los síntomas se notaron a los 2 años y el diagnóstico específico a los 5. A los 8 años tuvo su primera crisis tónico-clónica y se alteró el electroencefalograma. Posteriormente se obtuvo el diagnóstico molecular confirmado. Tenía epilepsia refractaria que era difícil de controlar y se agravaba con un intento de utilizar derivados cannabinoides junto con estimulación eléctrica transcraneal. En el momento, los tratamientos, la atención multidisciplinar, la dieta de exclusión de alérgenos y los medicamentos de control individual, redujeron la intensidad de las crisis epilépticas y hubo un mejor control de su estado general. Conclusión: Este estudio describe cómo la mutación de novo en el gen DEAF1 se relaciona con el TEA y el deterioro del desarrollo neurocognitivo. Las terapias y los métodos deben respetar a cada paciente en su individualidad.