A Randomized, Controlled, Noninferiority, Multicenter Trial of Systemic vs Intralesional Treatment With Meglumine Antimoniate for Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Meglumine antimoniate (MA) remains the main treatment for cutaneous leishmaniasis (CL). Uncontrolled studies suggest that intralesional MA (IL-MA) may be noninferior and safer than systemic MA (S-MA). METHODS: Multicenter, randomized, controlled, open-label, phase 3 clinical trial to evaluate the efficacy and toxicity of IL-MA in 3 infiltrations at 14-day intervals compared with S-MA (10-20 mg Sb5+/kg/day, 20 days) for CL, with noninferiority margin of 20%. Primary and secondary outcomes were definitive cure at day 180 and epithelialization rate at day 90 of treatment, respectively. A 2-year follow-up was performed to assess relapses and emergence of mucosal lesions. Adverse events (AEs) were monitored according to the Division of AIDS AE grading system. RESULTS: We evaluated 135 patients. The cure rates (95% confidence interval) for IL-MA and S-MA treatment were, respectively, 82.8% (70.5-91.4) and 67.8% (53.3-78.3) per protocol (PP) and 70.6% (58.3-81.0) and 59.7% (47.0-71.5) per intention to treat (ITT). The epithelialization rates of the IL-MA and S-MA treatment were, respectively, 79.3% (66.6-88 + 8) and 71.2% (57.9-82.2) PP and 69.1% (55.2-78.5) and 64.2% (50.0-74.2) ITT. AEs in the IL-MA and S-MA groups were, respectively, clinical, 45.6% and 80.6%; laboratory, 26.5% and 73.1%; and electrocardiogram, 8.8% and 25.4%. Ten participants in the S-MA group and 1 in the IL-MA group were discontinued due to severe or persistent AEs. CONCLUSIONS: IL-MA provides a similar cure rate and results in less toxicity compared with S-MA and may be used as first-line therapy for CL patients. CLINICAL TRIALS REGISTRATION: REBEC: RBR-6mk5n4.

Rational Design of Profile HMMs for Sensitive and Specific Sequence Detection with Case Studies Applied to Viruses, Bacteriophages, and Casposons.

Profile hidden Markov models (HMMs) are a powerful way of modeling biological sequence diversity and constitute a very sensitive approach to detecting divergent sequences. Here, we report the development of protocols for the rational design of profile HMMs. These methods were implemented on TABAJARA, a program that can be used to either detect all biological sequences of a group or discriminate specific groups of sequences. By calculating position-specific information scores along a multiple sequence alignment, TABAJARA automatically identifies the most informative sequence motifs and uses them to construct profile HMMs. As a proof-of-principle, we applied TABAJARA to generate profile HMMs for the detection and classification of two viral groups presenting different evolutionary rates: bacteriophages of the Microviridae family and viruses of the Flavivirus genus. We obtained conserved models for the generic detection of any Microviridae or Flavivirus sequence, and profile HMMs that can specifically discriminate Microviridae subfamilies or Flavivirus species. In another application, we constructed Cas1 endonuclease-derived profile HMMs that can discriminate CRISPRs and casposons, two evolutionarily related transposable elements. We believe that the protocols described here, and implemented on TABAJARA, constitute a generic toolbox for generating profile HMMs for the highly sensitive and specific detection of sequence classes.

Telehealth for Parkinson disease patients during the COVID-19 pandemic: the TeleParkinson study.

BACKGROUND: Telemedicine allows Parkinson disease (PD) patients to overcome physical barriers to access health care services and increases accessibility for people with mobility impairments. OBJECTIVE: To investigate the feasibility indicators of a telehealth intervention for PD patients, including patient recruitment, attendance, technical issues, satisfaction, and benefits on levels of physical activity and sleep. METHODS: We conducted a single-center, single-arm study of telehealth video consultations using WhatsApp (Meta Platforms, Inc., Menlo Park, CA, USA). Also, we collected the feasibility indicators as the primary endpoints. All the patients in the study were previously evaluated in person by the same team. RESULTS: Patient recruitment, attendance, and technical issues rates were 61.3%, 90.5%, and 13.3%, respectively, with good scores of patient acceptance and satisfaction with the study intervention. The telehealth intervention improved physical activity, including the number of walks for at least 10 continuous minutes (p = 0.009) and the number of moderate-intensity activities lasting at least 10 continuous minutes (p = 0.001). The Pittsburgh sleep quality index (PSQI) scores also improved for one of its components: perceived sleep duration (p < 0.001) and for total Pittsburgh score (p < 0,001). The average travel time saving was 289.6 minutes, and money-saving was R$106.67 (around USD 18; almost 10% of the current minimum wage in Brazil). CONCLUSIONS: Direct-to-patient telehealth video consultations proved to be feasible and effective and had a positive impact on physical activity levels and sleep in PD patients.

ANTECEDENTES: A telemedicina permite que pacientes com doença de Parkinson (DP) superem barreiras físicas para acessar serviços de saúde e aumenta a acessibilidade para pessoas com mobilidade reduzida. OBJETIVO: Investigar indicadores de viabilidade de uma intervenção em telessaúde para pacientes com DP, incluindo recrutamento, atendimento, aderência, problemas técnicos, satisfação e benefícios nos níveis de atividade física e sono. MéTODOS: Foi conduzido um estudo de centro e braço únicos baseado em consultas por telessaúde com utilização do WhatsApp (Meta Platforms, Inc., Menlo Park, CA, EUA). Foram calculados indicadores de viabilidade como desfechos primários. RESULTADOS: As taxas de recrutamento, atendimento e problemas técnicos foram 61,3%, 90,5% e 13,3%, respectivamente, com bons escores de aceitação e satisfação com a intervenção. A intervenção melhorou os níveis de atividade física, incluindo o número de passos por pelo menos 10 minutos contínuos (p = 0,009) e o número de atividades intensas e moderadas com duração de pelo menos 10 minutos contínuos (p = 0,001). O Índice de Qualidade do Sono de Pittsburgh melhorou nos seguintes componentes: duração percebida do sono (p < 0,001) e escore total (p < 0,001). A média do tempo de viagem médio poupado foi de 289,6 minutos, e a economia financeira foi de R$ 106,67 reais (por volta de USD 18; quase 10% do salário mínimo atual do Brasil). CONCLUSõES: As consultas por vídeo provaram ser viáveis e efetivas, com impacto positivo nos níveis de atividade física e sono de pacientes com DP.

Telehealth for Parkinson disease patients during the COVID-19 pandemic: the TeleParkinson study / Telesaúde para pacientes com doença de Parkinson durante a pandemia de COVID-19: o estudo TeleParkinson

Abstract Background Telemedicine allows Parkinson disease (PD) patients to overcome physical barriers to access health care services and increases accessibility for people with mobility impairments. Objective To investigate the feasibility indicators of a telehealth intervention for PD patients, including patient recruitment, attendance, technical issues, satisfaction, and benefits on levels of physical activity and sleep. Methods We conducted a single-center, single-arm study of telehealth video consultations using WhatsApp (Meta Platforms, Inc., Menlo Park, CA, USA). Also, we collected the feasibility indicators as the primary endpoints. All the patients in the study were previously evaluated in person by the same team. Results Patient recruitment, attendance, and technical issues rates were 61.3%, 90.5%, and 13.3%, respectively, with good scores of patient acceptance and satisfaction with the study intervention. The telehealth intervention improved physical activity, including the number of walks for at least 10 continuous minutes (p = 0.009) and the number of moderate-intensity activities lasting at least 10 continuous minutes (p = 0.001). The Pittsburgh sleep quality index (PSQI) scores also improved for one of its components: perceived sleep duration (p < 0.001) and for total Pittsburgh score (p < 0,001). The average travel time saving was 289.6 minutes, and money-saving was R$106.67 (around USD 18; almost 10% of the current minimum wage in Brazil). Conclusions Direct-to-patient telehealth video consultations proved to be feasible and effective and had a positive impact on physical activity levels and sleep in PD patients.

Resumo Antecedentes A telemedicina permite que pacientes com doença de Parkinson (DP) superem barreiras físicas para acessar serviços de saúde e aumenta a acessibilidade para pessoas com mobilidade reduzida. Objetivo Investigar indicadores de viabilidade de uma intervenção em telessaúde para pacientes com DP, incluindo recrutamento, atendimento, aderência, problemas técnicos, satisfação e benefícios nos níveis de atividade física e sono. Métodos Foi conduzido um estudo de centro e braço únicos baseado em consultas por telessaúde com utilização do WhatsApp (Meta Platforms, Inc., Menlo Park, CA, EUA). Foram calculados indicadores de viabilidade como desfechos primários. Resultados As taxas de recrutamento, atendimento e problemas técnicos foram 61,3%, 90,5% e 13,3%, respectivamente, com bons escores de aceitação e satisfação com a intervenção. A intervenção melhorou os níveis de atividade física, incluindo o número de passos por pelo menos 10 minutos contínuos (p = 0,009) e o número de atividades intensas e moderadas com duração de pelo menos 10 minutos contínuos (p = 0,001). O Índice de Qualidade do Sono de Pittsburgh melhorou nos seguintes componentes: duração percebida do sono (p < 0,001) e escore total (p < 0,001). A média do tempo de viagem médio poupado foi de 289,6 minutos, e a economia financeira foi de R$ 106,67 reais (por volta de USD 18; quase 10% do salário mínimo atual do Brasil). Conclusões As consultas por vídeo provaram ser viáveis e efetivas, com impacto positivo nos níveis de atividade física e sono de pacientes com DP.

A Bioinformatics Tool for Efficient Retrieval of High-Confidence Terpene Synthases (TPS) and Application to the Identification of TPS in Coffea and Quillaja.

Terpenoids are a class of compounds that are found in all living organisms. In plants, some terpenoids are part of primary metabolism, but most terpenes found in plants are classified as specialized metabolites, encoded by terpene synthases (TPS). It is not obvious how to assign the putative product of a given TPS using bioinformatics tools. Phylogenetic analyses easily assign TPS into families; however members of the same TPS family can synthetize more than one terpenoid-and, in many biotechnological applications, researchers are more interested in the product of a given TPS rather than its phylogenetic profile. Automated protein annotation can be used to classify TPS based on their products, despite the family they belong to. Here, we implement an automated bioinformatics method, search_TPS, to identify TPS proteins that synthesize mono, sesqui and diterpenes in Angiosperms. We verified the applicability of the method by classifying wet lab validated TPS and applying it to find TPS proteins in Coffea arabica, C. canephora, C. eugenioides, and Quillaja saponaria. Search_TPS is a computational tool based on PERL scripts that carries out a series of HMMER searches against a curated database of TPS profile hidden Markov models. The tool is freely available at https://github.com/liliane-sntn/TPS .

A Phakopsora pachyrhizi Effector Suppresses PAMP-Triggered Immunity and Interacts with a Soybean Glucan Endo-1,3-ß-Glucosidase to Promote Virulence.

Asian soybean rust, caused by the fungus Phakopsora pachyrhizi, is one of the most important diseases affecting soybean production in tropical areas. During infection, P. pachyrhizi secretes proteins from haustoria that are transferred into plant cells to promote virulence. To date, only one candidate P. pachyrhizi effector protein has been characterized in detail to understand the mechanism by which it suppresses plant defenses to enhance infection. Here, we aimed to extend understanding of the pathogenic mechanisms of P. pachyrhizi based on the discovery of host proteins that interact with the effector candidate Phapa-7431740. We demonstrated that Phapa-7431740 suppresses pathogen-associated molecular pattern-triggered immunity (PTI) and that it interacts with a soybean glucan endo-1,3-ß-glucosidase (GmßGLU), a pathogenesis-related (PR) protein belonging to the PR-2 family. Structural and phylogenetic characterization of the PR-2 protein family predicted in the soybean genome and comparison to PR-2 family members in Arabidopsis thaliana and cotton, demonstrated that GmßGLU is a type IV ß-1,3-glucanase. Transcriptional profiling during an infection time course showed that the GmßGLU mRNA is highly induced during the initial hours after infection, coinciding with peak of expression of Phapa-7431740. The effector was able to interfere with the activity of GmßGLU in vitro, with a dose-dependent inhibition. Our results suggest that Phapa-7431740 may suppress PTI by interfering with glucan endo-1,3-ß-glucosidase activity. [Formula: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 "No Rights Reserved" license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2022.

Clinical-epidemiological profile of health users who have undergone a Percutaneous Coronary Intervention / Perfil clínico-epidemiológico de usuários de saúde submetidos à Intervenção Coronária Percutânea

Background: Coronary artery disease represents the condition with the highest prevalence worldwide. The treatment of this disease is through Percutaneous Coronary Intervention (PCI). Aiming: To outline the clinical epidemiological profile of health users who have undergone PCI, in a Hospital in the state of Rio Grande do Sul. Methods: Exploratory research, with a quantitative approach carried out on 188 medical records of health users who were submitted to elective or emergency PCI, with the use of stents or not in the year 2018. Values of p <0.05 represented significant statistical differences. Results: Users with a diagnosis of unstable angina (n = 16; 17.8%), diagnostic symptoms of unstable angina (n = 61; 67.8%) and a diagnosis of angina pectoris (n = 52; 57.8%) presented significantly more likely to be submitted to the PCI in elective way (p <0.001). Users diagnosed with Acute Myocardial Infarction - AMI (n = 59; 60.2%) and symptoms with evolution greater than 24 hours (n = 30; 30.6%) and less than 24 hours (n = 24; 24.5%), with dyslipidemia (n = 38; 38.8%) and who underwent catheterization on the same day (n = 87; 88.8%) are significantly more likely to perform emergency surgery (p <0.05). In addition, the data showed that the diagnosis of unstable angina potentiates new cardiomyopathies (n = 9, 47.4%; p <0.001) and restenosis (n = 5; 26.3%; p = 0.002). Conclusion: It is necessary to create strategies to strengthen the Health Care Network (HCN) with actions for prevention, promotion and rehabilitation to health, aiming quality in diagnosis, treatment and rehabilitation.

ntrodução: A doença arterial coronariana representa a afecção de maior prevalência mundial. O tratamento desta doença se dá pela intervenção coronária percutânea (ICP). Objetivo: Delinear o perfil clínico-epidemiológico dos usuários de saúde submetidos à ICP em um Hospital do estado do Rio Grande do Sul. Métodos: Pesquisa exploratória, de abordagem quantitativa realizada em 188 prontuários de usuários de saúde submetidos à ICP eletiva ou de urgência com uso de stent ou não no ano de 2018. Valores de p< 0,05 representaram diferenças estatísticas significativas. Resultados: Usuários com diagnóstico de angina instável (n=16; 17,8%), sintomas diagnósticos de angina instável (n= 61; 67,8%) e diagnóstico de angina pectoris (n=52; 57,8%) apresentaram significativamente maior probabilidade de serem submetidos à ICP em caráter eletivo (p<0,001). Usuários com diagnóstico para infarto agudo do miocárdio (n=59; 60,2%) e sintomatologia com evolução maior que 24 horas (n=30; 30,6%) e menor que 24 horas (n=24; 24,5%), com dislipidemia (n=38; 38,8%) e que fizeram cateterismo no mesmo dia (n=87; 88,8%) são significativamente mais propensos a realizar cirurgia de urgência (p<0,05). Além disso, os dados evidenciaram que o diagnóstico de angina instável potencializa novas cardiomiopatias (n=9, 47,4%; p<0,001) e reestenose (n=5; 26,3%; p= 0,002). Conclusão: É necessário criar estratégias para fortalecer a Rede de Atenção à Saúde (RAS) com ações de prevenção, promoção e reabilitação à saúde, visando a qualidade no diagnóstico, tratamento e reabilitação.

Clinical-epidemiological profile of health users who have undergone a Percutaneous Coronary Intervention / Perfil clínico-epidemiológico de usuários de saúde submetidos à Intervenção Coronária Percutânea

ABSTRACT: Background: Coronary artery disease represents the condition with the highest prevalence worldwide. The treatment of this disease is through Percutaneous Coronary Intervention (PCI). Aiming: To outline the clinical epidemiological profile of health users who have undergone PCI, in a Hospital in the state of Rio Grande do Sul. Methods: Exploratory research, with a quantitative approach carried out on 188 medical records of health users who were submitted to elective or emergency PCI, with the use of stents or not in the year 2018. Values of p <0.05 represented significant statistical differences. Results: Users with a diagnosis of unstable angina (n = 16; 17.8%), diagnostic symptoms of unstable angina (n = 61; 67.8%) and a diagnosis of angina pectoris (n = 52; 57.8%) presented significantly more likely to be submitted to the PCI in elective way (p <0.001). Users diagnosed with Acute Myocardial Infarction - AMI (n = 59; 60.2%) and symptoms with evolution greater than 24 hours (n = 30; 30.6%) and less than 24 hours (n = 24; 24.5%), with dyslipidemia (n = 38; 38.8%) and who underwent catheterization on the same day (n = 87; 88.8%) are significantly more likely to perform emergency surgery (p <0.05). In addition, the data showed that the diagnosis of unstable angina potentiates new cardiomyopathies (n = 9, 47.4%; p <0.001) and restenosis (n = 5; 26.3%; p = 0.002). Conclusion: It is necessary to create strategies to strengthen the Health Care Network (HCN) with actions for prevention, promotion and rehabilitation to health, aiming quality in diagnosis, treatment and rehabilitation. (AU)

RESUMO: Introdução: A doença arterial coronariana representa a afecção de maior prevalência mundial. O tratamento desta doença se dá pela intervenção coronária percutânea (ICP). Objetivo: Delinear o perfil clínico-epidemiológico dos usuários de saúde submetidos à ICP em um Hospital do estado do Rio Grande do Sul. Métodos: Pesquisa exploratória, de abordagem quantitativa realizada em 188 prontuários de usuários de saúde submetidos à ICP eletiva ou de urgência com uso de stent ou não no ano de 2018. Valores de p< 0,05 representaram diferenças estatísticas significativas. Resultados: Usuários com diagnóstico de angina instável (n=16; 17,8%), sintomas diagnósticos de angina instável (n= 61; 67,8%) e diagnóstico de angina pectoris (n=52; 57,8%) apresentaram significativamente maior probabilidade de serem submetidos à ICP em caráter eletivo (p<0,001). Usuários com diagnóstico para infarto agudo do miocárdio (n=59; 60,2%) e sintomatologia com evolução maior que 24 horas (n=30; 30,6%) e menor que 24 horas (n=24; 24,5%), com dislipidemia (n=38; 38,8%) e que fizeram cateterismo no mesmo dia (n=87; 88,8%) são significativamente mais propensos a realizar cirurgia de urgência (p<0,05). Além disso, os dados evidenciaram que o diagnóstico de angina instável potencializa novas cardiomiopatias (n=9, 47,4%; p<0,001) e reestenose (n=5; 26,3%; p= 0,002). Conclusão: É necessário criar estratégias para fortalecer a Rede de Atenção à Saúde (RAS) com ações de prevenção, promoção e reabilitação à saúde, visando a qualidade no diagnóstico, tratamento e reabilitação. (AU)

Parasite species variation and impact of spatial displacement of the population on cutaneous leishmaniasis in Rio de Janeiro, Brazil.

BACKGROUND: Cutaneous leishmaniasis results from complex interactions between human beings, vectors and the environment. Parasitic species differ in epidemiological and geographical contexts. METHODS: We studied a retrospective cohort of 696 patients with cutaneous leishmaniasis treated at a reference centre in the state of Rio de Janeiro, Brazil, between 2000 and 2015. We analysed displacements due to work, leisure and migrations with identification of Leishmania species. RESULTS: The geographic distribution of autochthonous cases showed that >95% of infections occurred in urban areas. In the state of Rio de Janeiro, most cases were concentrated in the cities surrounding forest parks and nature conservation areas. The same applies to the city of Rio de Janeiro, where these infections occurred in the neighbourhoods surrounding some mountain and forest areas. The non-displacement group included 575 (82.6%) patients and the displacement group included 121 (17.4%) patients. Leishmania (Viannia) braziliensis predominated in both groups. Other species were found in the displacement group. CONCLUSIONS: The disordered urbanization of the state of Rio de Janeiro in recent decades has created conditions for the emergence of urban foci of transmission close to forest areas. Changes in the environment, movement of infected individuals and adaptation of sandflies may have contributed to this.

An old drug and different ways to treat cutaneous leishmaniasis: Intralesional and intramuscular meglumine antimoniate in a reference center, Rio de Janeiro, Brazil.

BACKGROUND: Treatment of cutaneous leishmaniasis (CL) remains challenging since the drugs currently used are quite toxic, thus contributing to lethality unrelated to the disease itself but to adverse events (AE). The main objective was to evaluate different treatment regimens with meglumine antimoniate (MA), in a reference center in Rio de Janeiro, Brazil. METHODOLOGY: A historical cohort of 592 patients that underwent physical and laboratory examination were enrolled between 2000 and 2017. The outcome measures of effectiveness were epithelialization and complete healing of cutaneous lesions. AE were graded using a standardized scale. Three groups were evaluated: Standard regimen (SR): intramuscular (IM) MA 10-20 mg Sb5+/kg/day during 20 days (n = 46); Alternative regimen (AR): IM MA 5 mg Sb5+/kg/day during 30 days (n = 456); Intralesional route (IL): MA infiltration in the lesion(s) through subcutaneous injections (n = 90). Statistical analysis was performed through Fisher exact and Pearson Chi-square tests, Kruskal-Wallis, Kaplan-Meier and log-rank tests. RESULTS: SR, AR and IL showed efficacy of 95.3%, 84.3% and 75.9%, with abandonment rate of 6.5%, 2.4% and 3.4%, respectively. IL patients had more comorbidities (58.9%; p = 0.001), were mostly over 50 years of age (55.6%), and had an evolution time longer than 2 months (65.6%; p = 0.02). Time for epithelialization and complete healing were similar in IL and IM MA groups (p = 0.9 and p = 0.5; respectively). Total AE and moderate to severe AE that frequently led to treatment interruption were more common in SR group, while AR and IL showed less toxicity. CONCLUSIONS/SIGNIFICANCE: AR and IL showed less toxicity and may be good options especially in CL cases with comorbidities, although SR treatment was more effective. IL treatment was an effective and safe strategy, and it may be used as first therapy option as well as a rescue scheme in patients initially treated with other drugs.

Computational Analysis of Transposable Elements and CircRNAs in Plants.

This chapter provides two main contributions: (1) a description of computational tools and databases used to identify and analyze transposable elements (TEs) and circRNAs in plants; and (2) data analysis on public TE and circRNA data. Our goal is to highlight the primary information available in the literature on circular noncoding RNAs and transposable elements in plants. The exploratory analysis performed on publicly available circRNA and TEs data help discuss four sequence features. Finally, we investigate the association on circRNAs:TE in plants in the model organism Arabidopsis thaliana.

A Practical Guide on Computational Tools and Databases for Transposable Elements in Plants.

In the age of big data, obtaining precise information about the research topic of interesting is extremely important. Keeping this in mind, this chapter focuses on providing a practical knowledge guide about computational tools and databases of transposable elements (TE) in plants. For that, we organize and present this text in three sections: (1) a discussion about tools and databases on this theme; (2) hands-on of how to use a few of them; (3) an exploratory data analysis on public TE data. Finally, we are going deep to present the main challenges and possible solutions to improve resources and tools.

High Gravity and Very High Gravity Fermentation of Sugarcane Molasses by Flocculating Saccharomyces cerevisiae: Experimental Investigation and Kinetic Modeling.

Substantial progress has been made in ethanol fermentation technology under high gravity (HG) and very high gravity (VHG), which offer environmental and economic benefits. HG and VHG processes increase the productivity of ethanol, reduce distillation costs, and enable higher yields. The aim of the present study was to evaluate the use of sugarcane molasses as the medium component along with flocculating yeasts for fermentation in a fed-batch process employing this promising technology. We evaluated fed-batch fermentation, HG, and VHG involving a molasses-based medium with high concentrations of reducing sugars (209, 222, and 250 g/L). Fermentation of 222 g/L of total reducing sugars achieved 89.45% efficiency, with a final ethanol concentration of 104.4 g/L, whereas the highest productivity (2.98 g/(L.h)) was achieved with the fermentation of 209 g/L of total reducing sugars. The ethanol concentration achieved with the fermentation of 222 g/L of total reducing sugars was close to the value obtained for P'max (105.35 g/L). The kinetic model provided a good fit to the experimental data regarding the fermentation of 222 g/L. The results revealed that sugarcane molasses and flocculating yeasts can be efficiently used in HG fermentation to reduce the costs of the process and achieve high ethanol titers.

Characterization of a Novel Mitovirus of the Sand Fly Lutzomyia longipalpis Using Genomic and Virus-Host Interaction Signatures.

Hematophagous insects act as the major reservoirs of infectious agents due to their intimate contact with a large variety of vertebrate hosts. Lutzomyia longipalpis is the main vector of Leishmania chagasi in the New World, but its role as a host of viruses is poorly understood. In this work, Lu. longipalpis RNA libraries were subjected to progressive assembly using viral profile HMMs as seeds. A sequence phylogenetically related to fungal viruses of the genus Mitovirus was identified and this novel virus was named Lul-MV-1. The 2697-base genome presents a single gene coding for an RNA-directed RNA polymerase with an organellar genetic code. To determine the possible host of Lul-MV-1, we analyzed the molecular characteristics of the viral genome. Dinucleotide composition and codon usage showed profiles similar to mitochondrial DNA of invertebrate hosts. Also, the virus-derived small RNA profile was consistent with the activation of the siRNA pathway, with size distribution and 5' base enrichment analogous to those observed in viruses of sand flies, reinforcing Lu. longipalpis as a putative host. Finally, RT-PCR of different insect pools and sequences of public Lu. longipalpis RNA libraries confirmed the high prevalence of Lul-MV-1. This is the first report of a mitovirus infecting an insect host.

Effects of a power strength training using elastic resistance exercises on the motor and non-motor symptoms in patients with Parkinson's disease H&Y 1-3: study protocol for a randomised controlled trial (PARK-BAND Study).

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder in Brazil. Physical activity is a complementary intervention in managing inherent declines associated with the disease like strength, balance, gait, and functionality and benefit health-related outcomes. Here, we report the PARK-BAND Study protocol, which aims to investigate potential benefits of power training using elastic devices in participants with PD. Our intervention will be provided in patients with PD using elastic devices like elastic bands and tubes. Therefore, we used the term Park from Parkinson's disease and band from elastic bands. METHODS AND ANALYSIS: This randomised single-blind single-centre two-arm parallel, superiority trial will include 50 participants with PD attending the clinical setting. Those who meet the eligibility criteria and provide consent to participate will be randomised in a 1:1 ratio to either the exercise group, which will receive power training programme or the health education group, which will receive the education programme. Randomisation will be performed by permuted block randomisation with a block size of eight. Both groups will receive a 12-week intervention. The exercise group will have two sessions per week and the health education group will have one session per week. Changes from baseline in bradykinesia, as assessed by the Unified Parkinson's Disease Rating Scale motor examination subscore and physical functional performance, will be the primary outcomes. Secondary outcomes include other neurological, neurophysiological and physical variables, as well as the quality of life, depression, cognition, sleep quality and disturbances, assessed before and after interventions. We hypothesise that the exercise group will have greater improvement in primary and secondary outcomes than the health education group. ETHICS AND DISSEMINATION: The study is approved by the Research Ethics Committee of Hospital Universitário Walter Cantidio and all participants will provide their written informed consent (register number 91075318.1.0000.5045).Trial results will be disseminated via peer reviewed journal articles and conference presentations, reports for organisations involved with PD and for participants. TRIAL REGISTRATION NUMBER: Registro Brasileiro de Ensaios Clínicos Registry (RBR-5w2sqt); Pre-results.

A single unidirectional piRNA cluster similar to the flamenco locus is the major source of EVE-derived transcription and small RNAs in Aedes aegypti mosquitoes.

Endogenous viral elements (EVEs) are found in many eukaryotic genomes. Despite considerable knowledge about genomic elements such as transposons (TEs) and retroviruses, we still lack information about nonretroviral EVEs. Aedes aegypti mosquitoes have a highly repetitive genome that is covered with EVEs. Here, we identified 129 nonretroviral EVEs in the AaegL5 version of the A. aegypti genome. These EVEs were significantly associated with TEs and preferentially located in repeat-rich clusters within intergenic regions. Genome-wide transcriptome analysis showed that most EVEs generated transcripts although only around 1.4% were sense RNAs. The majority of EVE transcription was antisense and correlated with the generation of EVE-derived small RNAs. A single genomic cluster of EVEs located in a 143 kb repetitive region in chromosome 2 contributed with 42% of antisense transcription and 45% of small RNAs derived from viral elements. This region was enriched for TE-EVE hybrids organized in the same coding strand. These generated a single long antisense transcript that correlated with the generation of phased primary PIWI-interacting RNAs (piRNAs). The putative promoter of this region had a conserved binding site for the transcription factor Cubitus interruptus, a key regulator of the flamenco locus in Drosophila melanogaster Here, we have identified a single unidirectional piRNA cluster in the A. aegypti genome that is the major source of EVE transcription fueling the generation of antisense small RNAs in mosquitoes. We propose that this region is a flamenco-like locus in A. aegypti due to its relatedness to the major unidirectional piRNA cluster in Drosophila melanogaster.

Geo-epidemiology and socioeconomic aspects of human sporotrichosis in the municipality of Duque de Caxias, Rio de Janeiro, Brazil, between 2007 and 2016.

BACKGROUND: Sporotrichosis is usually caused by the traumatic inoculation of pathogenic species of fungi of the genus Sporothrix. The most prevalent species in Brazil is Sporothrix brasiliensis, which is generally associated with transmission involving infected cats. Sporotrichosis is hyperendemic in the state of Rio de Janeiro and Duque de Caxias is one of the most affected municipalities. METHODS: This was a cross-sectional, geo-epidemiological and socioeconomic study of human sporotrichosis in the municipality of Duque de Caxias using geoprocessing information for the construction of thematic maps. RESULTS: Eight hundred and twenty-seven cases of sporotrichosis from Duque de Caxias were reported between 2007 and 2016, most of them in women from 25-59 years. The most affected areas had low per capita income and scarce supply of treated water. Human sporotrichosis expanded throughout the territory of the municipality over time. CONCLUSIONS: An increase in both the number of reported cases and their spatial distribution occurred throughout the studied decade. The concentration of the disease was more intense in areas with greater vulnerability of the population, expressed by low per capita income and deficient provision of basic sanitation services. Sporotrichosis requires measures to better control the disease in Duque de Caxias and in the state of Rio de Janeiro.

Clinical features and therapeutic response in adult and pediatric patients with American tegumentary leishmaniasis in Rio de Janeiro.

BACKGROUND: American tegumentary leishmaniasis (ATL) is a neglected disease with wide territorial distribution. Knowledge is scarce in children and adolescents. This study aims to compare the clinical features and response to antimony treatment in pediatric and adult patients with cutaneous leishmaniasis. METHODS: A retrospective cohort study was performed with 659 patients who attended a reference centre in Rio de Janeiro, Brazil, from 2000 to 2015. The pediatric cohort consisted of 131 (20%) patients and the adult cohort consisted of 528 (80%) patients. RESULTS: The epidemiological profile, antimony therapeutic response and incidence of adverse events (AE) were different in the pediatric cohort compared with the adult cohort. Mucosal form was less frequent in the pediatric cohort (RR:0.49, p=0.011). Lesions in the head, neck and trunk were more frequent in the pediatric cohort (RR:1.49, p=0.043). The effectiveness of antimony treatment was superior in the pediatric cohort (88.3% vs 76.6%) with a shorter healing time (RR:0.49, p=0.009). Pediatric patients had lower proportions of moderate to severe AE compared with adults (RR:0.45, p=0.027). Clinical AE predominated in the adult cohort (RR:0.40, p=0.000) and laboratory AE in the pediatric cohort (RR:1.50, p=0.023). CONCLUSIONS: This study adds to the body of knowledge on differences that exist between different age groups in ATL.

Autism spectrum disorder and postnatal factors: a case-control study in brazil / Transtorno do espectro do autismo e fatores pós-natais: um estudo de caso controle no brasil

ABSTRACT Objective: To estimate the magnitude of the association between Autism Spectrum Disorder (ASD) and postnatal factors in a Brazilian population. Methods: A case-control study was performed with 253 individuals diagnosed with ASD and 886 individuals without signs of the disorder. A semi-structured questionnaire and the multiple logistic regression model were adopted in the data analysis. To estimate the magnitude of associations, the crude and adjusted Odds Ratio (OR) was used. Results: An association with the following factors was found: having been born with congenital malformation (OR 4.24; confidence interval of 95% - 95%CI 1.92-9.34), neonatal jaundice (OR 1.43; 95%CI 1.01-2.02), absence of crying at birth and seizure episode in childhood (OR 5.75; 95%CI 3.37-9.81). The magnitude of the association was higher in the children/adolescents who had two or more postnatal complications (OR 6.39; 95%CI 4.10-10.00). Conclusions: The findings of the present study suggest that malformation, neonatal jaundice, absence of crying at birth and seizure episodes in childhood are important factors to be considered when studying the etiology of ASD.

RESUMO Objetivo: Estimar, em uma população brasileira, a magnitude da associação entre o transtorno do espectro do autismo (TEA) e os fatores pós-natais. Métodos: Estudo de caso controle realizado com 253 indivíduos com diagnóstico do TEA e 886 sem sinais do transtorno. Foi aplicado um questionário semiestruturado e adotou-se o modelo de regressão logística múltipla na análise dos dados. Para estimar a magnitude das associações, utilizou-se a razão de chances (Odds Ratio - OR) bruta e ajustada. Resultados: Encontrou-se associação de TEA com os seguintes fatores: ter nascido com má-formação congênita (OR 4,24; intervalo de confiança de 95% - IC95% 1,92-9,34), icterícia neonatal (OR 1,43; IC95% 1,01-2,02), ausência de choro ao nascer (OR 1,97; IC95% 1,20-3,23) e episódio de convulsão na infância (OR 5,75; IC95% 3,37-9,81). A magnitude da associação foi maior nas crianças/adolescentes que tiveram duas ou mais complicações pós-natais (OR 6,39; IC95% 4,10-10,00). Conclusões: Os achados do presente estudo sugerem que má-formação, icterícia neonatal, ausência de choro ao nascer e episódios de convulsão na infância são fatores importantes a serem considerados ao estudar a etiologia do TEA.