A Proteogenomic Pipeline for the Analysis of Protein Biosynthesis Errors in the Human Pathogen Candida albicans.

Candida albicans is a diploid pathogen known for its ability to live as a commensal fungus in healthy individuals but causing both superficial infections and disseminated candidiasis in immunocompromised patients where it is associated with high morbidity and mortality. Its success in colonizing the human host is attributed to a wide range of virulence traits that modulate interactions between the host and the pathogen, such as optimal growth rate at 37 °C, the ability to switch between yeast and hyphal forms, and a remarkable genomic and phenotypic plasticity. A fascinating aspect of its biology is a prominent heterogeneous proteome that arises from frequent genomic rearrangements, high allelic variation, and high levels of amino acid misincorporations in proteins. This leads to increased morphological and physiological phenotypic diversity of high adaptive potential, but the scope of such protein mistranslation is poorly understood due to technical difficulties in detecting and quantifying amino acid misincorporation events in complex protein samples. We have developed and optimized mass spectrometry and bioinformatics pipelines capable of identifying rare amino acid misincorporation events at the proteome level. We have also analyzed the proteomic profile of an engineered C. albicans strain that exhibits high level of leucine misincorporation at protein CUG sites and employed an in vivo quantitative gain-of-function fluorescence reporter system to validate our LC-MS/MS data. C. albicans misincorporates amino acids above the background level at protein sites of diverse codons, particularly at CUG, confirming our previous data on the quantification of leucine incorporation at single CUG sites of recombinant reporter proteins, but increasing misincorporation of Leucine at these sites does not alter the translational fidelity of the other codons. These findings indicate that the C. albicans statistical proteome exceeds prior estimates, suggesting that its highly plastic phenome may also be modulated by environmental factors due to translational ambiguity.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression.

BACKGROUND: Aging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual "omics" signature that distinguishes subjects with varying cognitive profiles. RESULTS: We found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging. CONCLUSIONS: These findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Myocardial RNA Sequencing Reveals New Potential Therapeutic Targets in Heart Failure with Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) represents a global health challenge, with limited therapies proven to enhance patient outcomes. This makes the elucidation of disease mechanisms and the identification of novel potential therapeutic targets a priority. Here, we performed RNA sequencing on ventricular myocardial biopsies from patients with HFpEF, prospecting to discover distinctive transcriptomic signatures. A total of 306 differentially expressed mRNAs (DEG) and 152 differentially expressed microRNAs (DEM) were identified and enriched in several biological processes involved in HF. Moreover, by integrating mRNA and microRNA expression data, we identified five potentially novel miRNA-mRNA relationships in HFpEF: the upregulated hsa-miR-25-3p, hsa-miR-26a-5p, and has-miR4429, targeting HAPLN1; and NPPB mRNA, targeted by hsa-miR-26a-5p and miR-140-3p. Exploring the predicted miRNA-mRNA interactions experimentally, we demonstrated that overexpression of the distinct miRNAs leads to the downregulation of their target genes. Interestingly, we also observed that microRNA signatures display a higher discriminative power to distinguish HFpEF sub-groups over mRNA signatures. Our results offer new mechanistic clues, which can potentially translate into new HFpEF therapies.

Effect of excess weight and insulin resistance on DNA methylation in prepubertal children.

Epigenetic mechanisms, such as DNA methylation, regulate gene expression and play a role in the development of insulin resistance. This study evaluates how the BMI z-score (BMIz) and the homeostatic model assessment of insulin resistance (HOMA-IR), alone or in combination, relate to clinical outcomes and DNA methylation patterns in prepubertal children. DNA methylation in peripheral blood mononuclear cells (PBMCs) and clinical outcomes were measured in a cohort of 41 prepubertal children. Children with higher HOMA-IR had higher blood pressure and plasma lactate levels while children with higher BMIz had higher triglycerides levels. Moreover, the DNA methylation analysis demonstrated that a 1 unit increase in the BMIz was associated with a 0.41 (95% CI: 0.29, 0.53) increase in methylation of a CpG near the PPP6R2 gene. This gene is important in the regulation of NF-kB expression. However, there was no strong evidence that the BMIz and the HOMA-IR were synergistically related to any clinical or DNA methylation outcomes. In summary, the results suggest that obesity and insulin resistance may impact metabolic health both independently in prepubertal children. In addition, obesity also has an impact on the DNA methylation of the PPP6R2 gene. This may be a novel underlying starting point for the systemic inflammation associated with obesity and insulin resistance, in this population.

The Role of MicroRNAs in Proteostasis Decline and Protein Aggregation during Brain and Skeletal Muscle Aging.

Aging can be defined as the progressive deterioration of cellular, tissue, and organismal function over time. Alterations in protein homeostasis, also known as proteostasis, are a hallmark of aging that lead to proteome imbalances and protein aggregation, phenomena that also occur in age-related diseases. Among the various proteostasis regulators, microRNAs (miRNAs) have been reported to play important roles in the post-transcriptional control of genes involved in maintaining proteostasis during the lifespan in several organismal tissues. In this review, we consolidate recently published reports that demonstrate how miRNAs regulate fundamental proteostasis-related processes relevant to tissue aging, with emphasis on the two most studied tissues, brain tissue and skeletal muscle. We also explore an emerging perspective on the role of miRNA regulatory networks in age-related protein aggregation, a known hallmark of aging and age-related diseases, to elucidate potential miRNA candidates for anti-aging diagnostic and therapeutic targets.

Redox Imbalance and Methylation Disturbances in Early Childhood Obesity.

Obesity is increasing worldwide in prepubertal children, reducing the age of onset of associated comorbidities, including type 2 diabetes. Sulfur-containing amino acids, methionine, cysteine, and their derivatives play important roles in the transmethylation and transsulfuration pathways. Dysregulation of these pathways leads to alterations in the cellular methylation patterns and an imbalanced redox state. Therefore, we tested the hypothesis that one-carbon metabolism is already dysregulated in prepubertal children with obesity. Peripheral blood was collected from 64 children, and the plasma metabolites from transmethylation and transsulfuration pathways were quantified by HPLC. The cohort was stratified by BMI z-scores and HOMA-IR indices into healthy lean (HL), healthy obese (HO), and unhealthy obese (UHO). Fasting insulin levels were higher in the HO group compared to the HL, while the UHO had the highest. All groups presented normal fasting glycemia. Furthermore, high-density lipoprotein (HDL) was lower while triglycerides and lactate levels were higher in the UHO compared to HO subjects. S-adenosylhomocysteine (SAH) and total homocysteine levels were increased in the HO group compared to HL. Additionally, glutathione metabolism was also altered. Free cystine and oxidized glutathione (GSSG) were increased in the HO as compared to HL subjects. Importantly, the adipocyte secretory function was already compromised at this young age. Elevated circulating leptin and decreased adiponectin levels were observed in the UHO as compared to the HO subjects. Some of these alterations were concomitant with alterations in the DNA methylation patterns in the obese group, independent of the impaired insulin levels. In conclusion, our study informs on novel and important metabolic alterations in the transmethylation and the transsulfuration pathways in the early stages of obesity. Moreover, the altered secretory function of the adipocyte very early in life may be relevant in identifying early metabolic markers of disease that may inform on the increased risk for specific future comorbidities in this population.

Integration of segmented regression analysis with weighted gene correlation network analysis identifies genes whose expression is remodeled throughout physiological aging in mouse tissues.

Gene expression alterations occurring with aging have been described for a multitude of species, organs, and cell types. However, most of the underlying studies rely on static comparisons of mean gene expression levels between age groups and do not account for the dynamics of gene expression throughout the lifespan. These studies also tend to disregard the pairwise relationships between gene expression profiles, which may underlie commonly altered pathways and regulatory mechanisms with age. To overcome these limitations, we have combined segmented regression analysis with weighted gene correlation network analysis (WGCNA) to identify high-confidence signatures of aging in the brain, heart, liver, skeletal muscle, and pancreas of C57BL/6 mice in a publicly available RNA-Seq dataset (GSE132040). Functional enrichment analysis of the overlap of genes identified in both approaches showed that immune- and inflammation-related responses are prominently altered in the brain and the liver, while in the heart and the muscle, aging affects amino and fatty acid metabolism, and tissue regeneration, respectively, which reflects an age-related global loss of tissue function. We also explored sexual dimorphism in the aging mouse transcriptome and found the liver and the muscle to have the most pronounced gender differences in gene expression throughout the lifespan, particularly in proteostasis-related pathways. While the data showed little overlap among the age-dysregulated genes between tissues, aging triggered common biological processes in distinct tissues, which we highlight as important features of murine tissue physiological aging.

tRNA-modifying enzyme mutations induce codon-specific mistranslation and protein aggregation in yeast.

Protein synthesis rate and accuracy are tightly controlled by the cell and are essential for proteome homoeostasis (proteostasis); however, the full picture of how mRNA translational factors maintain protein synthesis accuracy and co-translational protein folding are far from being fully understood. To address this question, we evaluated the role of 70 yeast tRNA-modifying enzyme genes on protein aggregation and used mass spectrometry to identify the aggregated proteins. We show that modification of uridine at anticodon position 34 (U34) by the tRNA-modifying enzymes Elp1, Elp3, Sml3 and Trm9 is critical for proteostasis, the mitochondrial tRNA-modifying enzyme Slm3 plays a fundamental role in general proteostasis and that stress response proteins whose genes are enriched in codons decoded by tRNAs lacking mcm5U34, mcm5s2U34, ncm5U34, ncm5Um34, modifications are overrepresented in protein aggregates of the ELP1, SLM3 and TRM9 KO strains. Increased rates of amino acid misincorporation were also detected in these strains at protein sites that specifically mapped to the codons sites that are decoded by the hypomodified tRNAs, demonstrating that U34 tRNA modifications safeguard the proteome from translational errors, protein misfolding and proteotoxic stress.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019.

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Genomic detection of a virus lineage replacement event of dengue virus serotype 2 in Brazil, 2019

BACKGROUND Despite efforts to mitigate the impact of dengue virus (DENV) epidemics, the virus remains a public health problem in tropical and subtropical regions around the world. Most DENV cases in the Americas between January and July 2019 were reported in Brazil. São Paulo State in the southeast of Brazil has reported nearly half of all DENV infections in the country. OBJECTIVES To understand the origin and dynamics of the 2019 DENV outbreak. METHODS Here using portable nanopore sequencing we generated20 new DENV genome sequences from viremic patients with suspected dengue infection residing in two of the most-affected municipalities of São Paulo State, Araraquara and São José do Rio Preto. We conducted a comprehensive phylogenetic analysis with 1,630 global DENV strains to better understand the evolutionary history of the DENV lineages that currently circulate in the region. FINDINGS The new outbreak strains were classified as DENV2 genotype III (American/Asian genotype). Our analysis shows that the 2019 outbreak is the result of a novel DENV lineage that was recently introduced to Brazil from the Caribbean region. Dating phylogeographic analysis suggests that DENV2-III BR-4 was introduced to Brazil in or around early 2014, possibly from the Caribbean region. MAIN CONCLUSIONS Our study describes the early detection of a newly introduced and rapidly-expanding DENV2 virus lineage in Brazil.

Performance of CDC Trioplex qPCR during a dengue outbreak in Brazil.

BACKGROUND: In recent years real­time reverse transcription polymerase chain reaction (real-time RT-PCR) has become a leading technique for nucleic acid detection and quantification of flaviviruses, including Dengue virus (DENV). Trioplex real-time RT-PCR has the advantages of providing the concurrent detection of Zika virus (ZIKV), DENV, and Chikungunya virus (CHIKV) RNA in human serum. OBJECTIVE: This study sought to compare the sensitivity and specificity of the Trioplex real-time RT-PCR assay to those provided by CDC DENV TaqMan® RT-qPCR assay and conventional PCR when used for DENV detection in the context of a dengue epidemic. STUDY DESIGN: We analyzed 1656 serum samples from symptomatic patients with acute febrile disease for 5 days less between December 2018 and May 2019. The samples were tested using the various PCR-based assays. RESULTS: Of the 1656 serum samples analyzed, 713 (43%) were laboratory-confirmed as arboviruses: 99.86% (712/713) were confirmed as DENV and 0.14% (1/713) were confirmed as ZIKV. Next, 590 samples were selected, and of these, 331 samples (56.1%) were determined to be positive (Ct < 38) and 259 samples (43.9%) were determined to be negative (Ct > 38) using the Trioplex real-time RT-PCR assay. The multiplex method found that the test exhibits 95% sensitivity and 100% specificity. CONCLUSION: This evaluation demonstrates the capacity of the Trioplex real-time RT-PCR assay to detect DENV at a high sensitivity and specificity in a geographic area with a current dengue outbreak and a lower co-circulation of other arboviruses - such as ZIKV and CHIKV, and the results prove it´s applicability as clinical screening test that can serve as a confirmatory test.

[Augmented reality in urology : present and future]. / Réalité augmentée en urologie : actualité et avenir.

Minimally invasive surgery has recently gained popularity. This paradigm shift involves a series of potential difficulties from the surgeon's perspective. With recent developments these obstacles are gradually being overcomed. Recent navigation systems offer major improvements in the way information is acquired, displayed, and integrated into the surgical workflow through augmented reality. Finally, the progress of robotics has helped to improve the minimally invasive dexterity and competence of the surgeon. This article sumarizes the main and most recent developments in the areas mentionned above, analyzes the current limits that still need to be addressed, and suggests possible future directions.

La réalité augmentée en urologie a gagné en popularité ces dernières années. Des systèmes de navigation récents offrent des améliorations majeures en termes d'information acquise, qui est affichée et intégrée dans le flux de travail chirurgical, grâce à la réalité augmentée. De même, le progrès de la robotique a contribué à améliorer la dextérité et la compétence mini-invasives du chirurgien. Cet article résume les principaux et les plus récents développements dans les domaines susmentionnés, analyse les limites actuelles qui doivent encore être abordées et suggère des orientations futures possibles.

Evidence of natural Zika virus infection in neotropical non-human primates in Brazil.

In Africa, Old World Primates are involved in the maintenance of sylvatic circulation of ZIKV. However, in Brazil, the hosts for the sylvatic cycle remain unknown. We hypothesized that free-living NHPs might play a role in urban/periurban ZIKV dynamics, thus we undertook an NHP ZIKV investigation in two cities in Brazil. We identified ZIKV-positive NHPs and sequences obtained were phylogenetically related to the American lineage of ZIKV. Additionally, we inoculated four C. penicillata with ZIKV and our results demonstrated that marmosets had a sustained viremia. The natural and experimental infection of NHPs with ZIKV, support the hypothesis that NHPs may be a vertebrate host in the maintainance of ZIKV transmission/circulation in urban tropical settings. Further studies are needed to understand the role they may play in maintaining the urban cycle of the ZIKV and how they may be a conduit in establishing an enzootic transmission cycle in tropical Latin America.

Zika detection: comparison of methodologies

ABSTRACT Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays. One hundred serum samples from patients presenting with acute febrile symptoms were tested using a previously reported TaqMan® RT-qPCR assay. We used a SYBR® Green RT-qPCR and a conventional PCR methodologies to compare the results. Of the samples that were determined to be negative by the TaqMan® RT-qPCR assay, 100% (Kappa = 0.670) were also found to be negative by SYBR® Green RT-qPCR based on Tm comparison; however, 14% (Kappa = 0.035) were found to be positive by conventional PCR followed by agarose gel electrophoresis. The differences between the ZIKV strains circulating worldwide and the low viremia period can compromise diagnostic accuracy and thereby the accuracy of outbreak data. Therefore, improved assays are required to improve the diagnosis and surveillance of arbovirus.

Zika detection: comparison of methodologies.

Many countries in the Americas have detected local transmission of multiple arboviruses that cause febrile illnesses. Therefore, laboratory testing has become an important tool for confirming the etiology of these diseases. The present study aimed to compare the sensitivity and specificity of three different Zika virus detection assays. One hundred serum samples from patients presenting with acute febrile symptoms were tested using a previously reported TaqMan® RT-qPCR assay. We used a SYBR® Green RT-qPCR and a conventional PCR methodologies to compare the results. Of the samples that were determined to be negative by the TaqMan® RT-qPCR assay, 100% (Kappa=0.670) were also found to be negative by SYBR® Green RT-qPCR based on Tm comparison; however, 14% (Kappa=0.035) were found to be positive by conventional PCR followed by agarose gel electrophoresis. The differences between the ZIKV strains circulating worldwide and the low viremia period can compromise diagnostic accuracy and thereby the accuracy of outbreak data. Therefore, improved assays are required to improve the diagnosis and surveillance of arbovirus.

Clinical, laboratory and virological data from suspected ZIKV patients in an endemic arbovirus area.

BACKGROUND: The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between the diseases caused by ZIKV, dengue (DENV) and chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Brazilian authorities largely rely on clinical and epidemiological data for the epidemiological and clinical classifications of most ZIKV cases. OBJECTIVE: To report the laboratory and clinical profiles of patients diagnosed with Zika fever based only on clinical and epidemiological data. STUDY DESIGN: We analyzed 433 suspected cases of ZIKV identified by the attending physician based on proposed clinical criteria. The samples were also screened for ZIKV, DENV and CHIKV using PCR. RESULTS: Of the 433 patients analyzed, 168 (38.8%) were laboratory-confirmed for arboviruses: 96 were positive for ZIKV, 67 were positive for DENV (56 for DENV-2, 9 for DENV-1, and 2 for DENV-4), four were positive for co-infection with ZIKV/DENV-2, and one was positive for CHIKV. The most common signs or symptoms in the patients with laboratory-confirmed ZIKV were rash (100%), arthralgia (77.1%), fever (74.0%), myalgia (74.0%) and non-purulent conjunctivitis (69.8%). In patients with laboratory-confirmed DENV infections, the most frequently observed symptoms were rash (100%), fever (79.1%), myalgia (74.6%), headache (73.1%) and arthralgia (70.1%). The measure of association between clinical manifestations and laboratory manifestations among patients with ZIKV and DENV detected a statistically significant difference only in abdominal pain (p=0.04), leukopenia (p=0.003), and thrombocytopenia (p=0.01). CONCLUSION: Our data suggests that clinical and epidemiological criteria alone are not a good tool for ZIKV and DENV differentiation, and that laboratory diagnosis should be mandatory.

Caracterização dos idosos internados por doença respiratória aguda em um hospital escola terciário / Characterization of elderly inpatient with acute respiratory disease in a tertiary medical school hospital

Objetivo: Caracterizar o perfil sociodemográfico, clínico e de fatores de risco de idosos internados por Doença Respiratória Aguda (DRA) no Hospital de Base de São José do Rio Preto. Metodologia: Pesquisa quantitativa, descritiva e retrospectiva, com dados coletados através da análise de 94 prontuários médicos de idosos com idade igual ou superior a 60 anos, internados no período de agosto de 2012 a setembro de 2013 por DRA no Hospital de Base de São José do Rio Preto. Resultados: O estudo identificou que entre os 94 idosos internados por DRA, 56,4% eram homens (n=53), com 76 anos de idade ou mais (55,3%), brancos (88,3%), casados (54,2%), com baixa escolaridade (19,1% não alfabetizados e 53,3% com até 4 anos de estudo), portadores de pelo menos uma comorbidade (83%), e apresentavam pelo menos um fator de risco para DRA como tabagismo e/ou desnutrição. Dos classificados com dependência funcional, a maioria eram idosos acima dos 75 anos. Quanto à situação cognitiva, menos da metade dos idosos apresentava algum déficit relatado em prontuário, e entre estes a maioria era maior de 75 anos. Mais de 70% dos pacientes (n=68) receberam alta com melhora, sendo que mais da metade (n=38) tinham 75 anos de idade ou menos. Do total, 17 pacientes evoluíram a óbito, sendo que destes, 88,2% (n=15) tinham acima de 75 anos. Após a alta médica, um pequeno número de pacientes (n=11) foram contra-referenciados às suas Unidades Básicas de Saúde de origem. Conclusão: Os resultados do estudo apontam para a importância de se reforçar as redes de cuidados voltadas aos idosos comprometidos por DRA, especialmente aqueles com idade avançada, fatores de risco presentes, comorbidades associadas, dependência funcional e déficit cognitivo, devido à alta probabilidade de má evolução. A capacitação dos profissionais de saúde dos diferentes níveis de atenção à saúde e a criação de estratégias para educação da população são ações fundamentais para a consolidação destas redes de cuidados e, consequentemente, auxiliar na prevenção e no diagnóstico precoce, visando à redução das internações e a mortalidade por DRA

Objective: To characterize the sociodemographic and clinic profiles and risk factors of elderlies hospitalized by acute respiratory disease (ARD) in Hospital de Base de São José do Rio Preto. Metodology: A quantitative, descriptive and retrospective study, with data collected through the analysis of 94 medical records of elderly inpatient, 60 years or older, hospitalized from August 2012 to September 2013 due to ARD. Results: This study identified that among 94 elderly inpatient with acute respiratory disease, major were men (n = 53), 76 years old or more (n = 52), white (n = 83), and had at least one risk factor for ARDs, such as smoking and/or bad nutrition. Most of the elderly over 75 years were dependent on daily life activities. Less than a half had cognitive deficit reported in their medical records, and most of them were more than 75 years old. More than 70% of the patients were discharged with improvement (n = 68), and more than half were 75 years old or less (n = 38). Among the 94 patients, 17 have died, being 88.2% over 75 years old (n = 15). After discharge, a small number of patients were referred to their Primary Care Unit (n = 11). Conclusions: The results of this study appoint to the importance of increasing care networks for elderly people affected by ARD, especially the oldiest, with risk factors, associated comorbidities, functional dependence and cognitive deficit, due to the high probability of bad prognosis. Training professionals at different levels of health care and creation of strategies to instruct the population about ARD are fundamental actions, in order to consolidate these care networks and, consequently, support prevention and early diagnosis, targeting the reduction of hospitalizations and mortality due to ARD.

Dengue virus surveillance: Detection of DENV-4 in the city of São José do Rio Preto, SP, Brazil.

Dengue viruses are the most common arbovirus infection worldwide and are caused by four distinct serotypes of the dengue virus (DENV). In the present study, we assessed DENV transmission in São José do Rio Preto (SJRP) from 2010 to 2014. We analyzed blood samples from febrile patients who were attended at health care centers in SJRP. DENV detection was performed using multiplex RT-PCR, using flavivirus generic primers, based on the genes of the non-structural protein (NS5), followed by nested-PCR assay with species-specific primers. We analyzed 1549 samples, of which 1389 were positive for NS1 by rapid test. One thousand and eight-seven samples (78%) were confirmed as positive by multiplex RT-PCR: DENV-4, 48.5% (528/1087); DENV-1, 41.5% (449/1087); DENV-2, 9.5% (104/1087); and co-infection (5 DENV-1/DENV-4, 1 DENV-1/DENV-2), 0.5% (6/1087). Phylogenetic analysis of the DENV-4 grouped the isolates identified in this study with the American genotype and the showed a relationship between isolates from SJRP and isolates from the northern region of South America. Taken together, our data shows the detection and emergence of new dengue genotype in a new region and reiterate the importance of surveillance programs to detect and trace the evolution of DENV.

Fatores de risco e complicações em usuários cadastrados no hiperdia de São José do Rio Preto / Risk factors and complications among patients registered in the hiperdia in São José do Rio Preto

As condições crônicas ocupam lugar de destaque entre os problemas de saúde pública, representando as principais causas de internações e mortalidade. O objetivo deste estudo foi identificar variáveis sociodemográficas, fatores de risco e complicações dos usuários cadastrados no Sistema de Cadastramento e Acompanhamento de Hipertensos e Diabéticos (HIPERDIA) de São José do Rio Preto.Trata-se de estudo descritivo transversal que utilizou dados secundários,no qual foram estudados 45.723 cadastrados no HIPERDIA de 2002 a 2012. A análise estatística foi realizada de forma univariada (teste qui quadrado).Destes, 31.547(69%) eram hipertensos, 2867(6,27%) diabéticos e 11.309 (24,73%) hipertensos e diabéticos. A maioria era feminina, idade média 59 ± 13,8 anos, ensino fundamental incompleto, branca, e conviviam com companheiro(a) e filhos. Observou-se associação estatisticamente significante das condições clinicas com: fatores de risco; tabagismo e Sedentarismo (p<0,0001) com Diabetes e Hipertensão com diabetes; Sobrepeso (p<0,0001) nas três condições clínicas e antecedentes Familiares (p<0,0001) com hipertensão e diabetes; com as complicações: Outras coronariopatias, Infarto Agudo do Miocárdio e Doença Renal (p < 0,01) com as três condições clínicas; e Acidente Vascular Cerebral (p<0,0001) na diabetes e diabetes com hipertensão. 59,57% apresentavam fator de risco e 16,58% complicações. Os dados deste estudo darão subsídios para elaborar estratégias de intervenções na melhoria do atendimento aos hipertensos e diabeticos prevenindo assim as complicações.

Chronic conditions stand out among public health problems, representing the primary cause of hospitalizations and mortality. This study's objective was to identify sociodemographic variables, risk factors and complications among patients enrolled in the HIPERDIA (Registration and Monitoring System of Hypertensive and Diabetic Patients) in São José do Rio Preto, SP, Brazil. A descriptive and cross-sectional study was conducted including 45,723 patients enrolled in the HIPERDIA between 2002 and 2012: 31,547 (69%) were hypertensive, 2,867 (6.27%) were diabetic, and the remaining 11,309 (24.73%) had hypertension and diabetes. Most were women aged 59 ± 13.8 years old on average, had incomplete primary education, were Caucasians and lived with a partner and children. Statistically significant associations were observed between clinical conditions and risk factors: smoking (p<0.0001) and diabetes, and hypertension with diabetes; being overweight (p<0.0001) in the three clinical conditions; and family history and sedentariness (p<0.0001) with hypertension and diabetes and withthe following complications: other heart diseases, Acute Myocardial Infarction and Kidney Disease (p < 0.01) with the three clinical conditions; and stroke (p<0.0001) with diabetes, and diabetes with hypertension. Among the patients, 59.57% presented a risk factor and 16.58% experienced complications. The study's results support interventions intended to decrease risk factors among hypertensive and diabetic patients, consequently preventing complications.