Alteration in the Expression of Circular Rnas and its association with the Development and Progression of Osteosarcoma, an Integrative Review with High Sensitivity Research.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor, mainly affecting children, young adults, and the elderly. It is an aggressive cancer with a poor prognosis, exhibiting low survival rates even with standard treatment. Recently, circular RNA molecules capable of influencing gene expression through various functions, with their main role being acting as microRNA sponges and reducing their intracellular expression, have been identified. Recent studies have linked circular RNAs to osteosarcoma development and progression. Therefore, the present study aimed to investigate the alteration in circular RNA expression during osteosarcoma development and progression. METHODS: An integrative literature review was conducted from September 10th to November 12th, 2021, using the following databases: PubMed/MEDLINE, SCOPUS, Web of Science, OVID, and EMBASE. 129 full articles were included in the review. The obtained data were organized using a standardized data collection instrument, which included the following information: altered expression profile of circular RNAs, associated cancer hallmarks, clinical-pathological relationships of circular RNAs, and perspectives on the studied circular RNAs. RESULTS: A total of 94 distinct circular RNAs were identified, predominantly showing an increased expression pattern. Approximately 91% of the studies that aimed to identify the mechanisms of action of circular RNAs highlighted the function of circular RNAs as microRNA sponges. The most associated cancer hallmarks with the identified circular RNAs were proliferative signaling induction, invasion and metastasis, and resistance to cell death. The altered expression of these circular RNAs generally correlated with a worse prognosis for patients, as evidenced by clinical features such as shorter survival, advanced Enneking and/or TNM stage, higher incidence of metastasis, larger tumor size, and increased chemoresistance. CONSLUSION: These findings indicate the significance of circular RNA molecules in osteosarcoma carcinogenesis, suggesting their potential as new prognostic and/or diagnostic biomarkers, as well as alternative therapeutic targets in the fight against osteosarcoma.

Viruses as a potential environmental trigger of type 1 diabetes mellitus (Review).

The etiopathogenesis of type 1 diabetes mellitus (T1DM) is a complex multifactorial process that involves an intricate network of genetic, epigenetic, immunological, and environmental factors. Despite the advances in recent years, some aspects of the mechanisms involved in triggering the disease are still unclear. Infections with certain viruses have been suggested as possible environmental triggers for the autoimmune process that leads to selective and progressive destruction of pancreatic ß-cells and insufficiency of insulin production, which is its hallmark. In this review, advances in knowledge and evidence that suggest the participation of certain viruses in the mechanisms of disease initiation and progression are described. It has been accepted that environmental factors, including viruses, can initiate and possibly sustain, accelerate, or slow down the autoimmune process and consequently damage insulin-producing pancreatic ß-cells. Although the role of these agents, especially human enteroviruses, has been exhaustively studied as the most likely triggers of the activation of autoimmunity that destroys pancreatic islets and leads to T1DM, certain doubts remain. Clinical epidemiological and experimental studies in humans and animals provide consistent and increasing evidence that persistent viral infections, especially with human enteroviruses and rotavirus infections, are associated with an increased risk of the disease in individuals genetically predisposed to autoimmunity.

Perfil das infecções relacionadas à assistência à saúde na unidade de terapia intensiva de um hospital de referência na mesorregião oeste do Rio Grande do Norte / Profile of health care-related infections in the intensive care unit of a reference hospital in the west mesoregion of Rio Grande do Norte / Perfil de las infecciones relacionadas con la atención a la salud en la unidad de cuidados intensivos de un hospital de referencia en la mesoregión oeste del Rio Grande del Norte

As Infecções Relacionadas à Assistência à Saúde (IRAS) ocorrem com mais frequência em Unidade de Terapia Intensiva (UTI) devido a exposição maior dos pacientes a procedimentos e dispositivos invasivos, quadro clínico debilitado e sua manipulação pela equipe assistencial exigindo uso elevado de antimicrobianos, o que pode promover um risco de desenvolvimento de resistência bacteriana a estes, cujas consequências podem ser a dificuldade de tratamento, internamento prolongado, risco de óbito e maior custo associado. Tem como objetivo descrever as IRAs relacionando os agentes etiológicos e o tratamento antimicrobiano em uma UTI de um hospital de referência da mesorregião do Rio Grande do Norte. Trata-se de um estudo descritivo, retrospectivo e transversal de abordagem quantitativa. Foram inseridos 1.682 pacientes internados na UTI geral do hospital estudado entre 2017-2020. Os dados foram coletados a partir de fichas de registro que foram tabuladas e analisadas nos softwares Microsoft Office Excel® e Statistical Package for the Social Sciences utilizando estatística descritiva simples com apresentação de frequências, tendências e dispersão. A análise dos resultados revelou mediana de idade de 57 anos, prevalência do sexo masculino e existência de comorbidades em 57,9% dos casos, especialmente infecção prévia a admissão na UTI. O tempo médio de permanência na UTI foi 11,4 dias e taxa de mortalidade de 52%. Quanto aos dispositivos invasivos, observou-se uso de sonda vesical de demora (96,8%), ventilação mecânica (79,4%) e cateter venoso central (83,7%). Constatou-se 790 IRAS da UTI com crescimento bacteriano em 48,2%. As principais densidades de incidência (DI) de IRAS/1.000 pacientes-dia foram: IPCSL-CVC 1,8; PAV 27 e ITU-AC 22,3. Quanto aos antibióticos, observou-se Lenght of therapy de 872,5/1.000 pacientes-dia, sendo os mais prescritos: vancomicina (N=633), meropenem (N=625), ceftriaxona (N=479), amicacina (N=463) e polimixina B (N=448). Os valores destaques de Days of therapy/1.000 pacientes-dia: meropenem (N=305,7), amicacina (N=260,4), polimixina B (N=256,4), vancomicina (N=229,3) e imipenem (N=165,3). As bactérias mais isoladas nas culturas foram: Acinetobacter spp., Pseudomonas spp. e Klebsiella spp., as quais apresentaram resistência, principalmente, a: ceftazidima (51,5% - 87,3%); cefepima (61,6% - 85,3%); ciprofloxacino (56% - 84,6%) e meropenem (31,7% - 80,3%). Identificou-se não conformidades no tratamento com antibióticos em 455 pacientes, que envolvem principalmente polimixina B, vancomicina, meropenem e ceftriaxona. Conclui-se que há elevados níveis de tempo de permanência na UTI e uso de dispositivos invasivos, assim como DI de IRAS alta com identificação microbiológica de bactérias importantes, especialmente por seu perfil de resistência acentuado com destaque para antibióticos da classe dos carbapenêmicos e cefalosporinas de 3a e 4a geração. Destaca-se também a presença de não conformidades na administração de antibióticos que podem contribuir para a seleção de bactérias multirresistentes.

Health Care-Related Infections (HAI) occur more frequently in the Intensive Care Unit (ICU) due to the greater exposure of patients to invasive procedures and devices, weakened clinical status and their handling by the care team, requiring high use of antimicrobials, which can promote a risk of developing bacterial resistance to these, whose consequences may be difficult treatment, prolonged hospitalization, risk of death and higher associated costs. It aims to describe the IRAS relating the etiological agents and antimicrobial treatment in an ICU of a reference hospital in the mesoregion of Rio Grande do Norte. This is a descriptive, retrospective and cross-sectional study with a quantitative approach. A total of 1,682 patients admitted to the general ICU of the hospital studied between 2017-2020 were included. Data were collected from registration forms that were tabulated and analyzed in Microsoft Office Excel® and Statistical Package for the Social Sciences software using simple descriptive statistics with presentation of frequencies, trends and dispersion. The analysis of the results revealed a median age of 57 years, prevalence of males and the existence of comorbidities in 57.9% of cases, especially infection prior to admission to the ICU. The average length of stay in the ICU was 11.4 days and the mortality rate was 52%. As for invasive devices, the use of an indwelling urinary catheter (96.8%), mechanical ventilation (79.4%) and central venous catheter (83.7%) was observed. There were 790 IRAS in the ICU with bacterial growth in 21.67%. The main HAI incidence densities (DI)/1,000 patient-days were: IPCSL-CVC 1.8; PAV 27 and UTI-AC 22.3. As for antibiotics, a Length of therapy of 872.5/1,000 patient-days was observed, with the most prescribed being: vancomycin (N=633), meropenem (N=625), ceftriaxone (N=479), amikacin (N= 463) and polymyxin B (N=448). The highlighted values of Days of therapy/1000 patient-days: meropenem (N=305.7), amikacin (N=260.4), polymyxin B (N=256.4), vancomycin (N=229.3) and imipenem (N=165.3). The most isolated bacteria in cultures were: Acinetobacter spp., Pseudomonas spp. and Klebsiella spp., which showed resistance mainly to: Ceftazidime (51.5% - 87.3%); cefepime (61.6% - 85.3%); ciprofloxacin (56% - 84.6%) and meropenem (31.7% - 80.3%). Non-compliance was identified in the treatment with antibiotics in 455 patients, which mainly involve polymyxin B, vancomycin, meropenem and ceftriaxone. It is concluded that there are high levels of ICU length of stay and use of invasive devices, as well as high IRAS ID with microbiological identification of important bacteria, especially due to their accentuated resistance profile, with emphasis on antibiotics from the carbapenem class and cephalosporins from 3rd and 4th generation. Also noteworthy is the presence of non-compliance in the administration of antibiotics that may contribute to the selection of multidrug-resistant bacteria.

Las Infecciones Relacionadas con la Atención de la Salud (IRAS) ocurren con mayor frecuencia en la Unidad de Cuidados Intensivos (UCI) debido a la mayor exposición de los pacientes a procedimientos y dispositivos invasivos, el debilitamiento del estado clínico y su manejo por parte del equipo asistencial, requiriendo un alto uso de antimicrobianos , lo que puede promover un riesgo de desarrollar resistencia bacteriana a estos, cuyas consecuencias pueden ser un tratamiento difícil, hospitalización prolongada, riesgo de muerte y mayores costos asociados. Tiene como objetivo describir las IRAs que relacionan los agentes etiológicos y el tratamiento antimicrobiano en una UTI de un hospital de referencia en la mesorregión de Rio Grande do Norte. Se trata de un estudio descriptivo, retrospectivo y transversal con enfoque cuantitativo. Se incluyeron un total de 1.682 pacientes ingresados en la UCI general del hospital estudiado entre 2017-2020. Los datos fueron recolectados a partir de formularios de registro que fueron tabulados y analizados en el software Microsoft Office Excel® y Statistical Package for the Social Sciences utilizando estadística descriptiva simple con presentación de frecuencias, tendencias y dispersión. El análisis de los resultados reveló una mediana de edad de 57 años, predominio del sexo masculino y la existencia de comorbilidades en el 57,9% de los casos, especialmente infección previa al ingreso en UCI. La estancia media en la UCI fue de 11,4 días y la tasa de mortalidad fue del 52%. En cuanto a los dispositivos invasivos, se observó el uso de catéter urinario permanente (96,8%), ventilación mecánica (79,4%) y catéter venoso central (83,7%). Había 790 IRAS en la UCI con crecimiento bacteriano en el 48,2%. Las principales densidades de incidencia (DI) de IRAS/1.000 pacientes-día fueron: IPCSL-CVC 1,8; PAV 27 y UTI-AC 22.3. En cuanto a los antibióticos, se observó una Duración de la terapia de 872,5/1.000 días-paciente, siendo los más prescritos: vancomicina (N=633), meropenem (N=625), ceftriaxona (N=479), amikacina (N= 463) y polimixina B (N=448). Los valores destacados de Días de terapia/1.000 pacientes-día: meropenem (N=305,7), amikacina (N=260,4), polimixina B (N=256,4), vancomicina (N=229,3) e imipenem (N=165,3). Las bacterias más aisladas en cultivos fueron: Acinetobacter spp., Pseudomonas spp. y Klebsiella spp., que mostraron resistencia principalmente a: ceftazidima (51,5% - 87,3%); cefepima (61,6% - 85,3%); ciprofloxacino (56% - 84,6%) y meropenem (31,7% - 80,3%). Se identificó incumplimiento en el tratamiento con antibióticos en 455 pacientes, los cuales involucran principalmente polimixina B, vancomicina, meropenem y ceftriaxona. Se concluye que existen altos índices de estancia en UCI y uso de dispositivos invasivos, así como elevado IRAS ID con identificación microbiológica de bacterias importantes, especialmente por su acentuado perfil de resistencia, con énfasis en antibióticos de la clase carbapenémicos y cefalosporinas de 3ra y 4ta generación. También es destacable la presencia de incumplimiento en la administración de antibióticos que pueden contribuir a la selección de bacterias multirresistentes.

Innate immune response in patients with acute Chikungunya disease.

Chikungunya disease (CHIKD) is an arbovirose that presents with high morbidity, mainly due to arthralgia. Inflammatory mediators including IL-6, IL-1ß, GM-CSF and others have been implicated in the pathogenesis of CHIKD, whilst type I interferons can be associated with better outcomes. The role of pattern recognition receptors has been studied incompletely. Here, we evaluated the expression of RNA-specific PRRs, their adaptor molecules and downstream cytokines in acute CHIKD patients. Twenty-eight patients were recruited during the 3rd-5th day after the symptoms onset for clinical examination, peripheral blood collection and qRT-PCR analysis of PBMC to compare to the healthy control group (n = 20). We observed common symptoms of acute CHIKD, with fever, arthralgia, headache and myalgia being the most frequent. Compared with uninfected controls, acute CHIKV infection upregulates the expression of the receptors TLR3, RIG-I and MDA5, and also the adaptor molecule TRIF. Regarding cytokine expression, we found an upregulation of IL-6, IL-12, IFN-α, IFN-ß and IFN-γ, which are related directly to the inflammatory or antiviral response. The TLR3-TRIF axis correlated with high expression of IL-6 and IFN-α. Interestingly, greater expression of MDA5, IL-12 and IFN-α was related to lower viral loads in CHIKD acute patients. Together, these findings help to complete the picture of innate immune activation during acute CHIKD, while confirming the induction of strong antiviral responses. Drawing the next steps in the understanding of the immunopathology and virus clearance mechanisms of CHIKD should be of utter importance in the aid of the development of effective treatment to reduce the severity of this debilitating disease.

Identification and evaluation of thermotolerance of yeasts from milk in natura exposed to high temperature and slow and fast pasteurization.

Milk is considered one of the basic raw materials of animal origin; it must present hygienic quality and physical-chemical properties suitable for processing and human consumption. Thus, the ingestion of milk in natura when not properly treated can be characterized as an opportunistic route of transmission of possible microbial pathogens, which can offer risks to public health. The present study aimed the yeast identification, to analyze the thermo-resistance of yeasts isolated from fresh milk, and to trace the susceptibility profile of the isolates to antifungal agents. For this, 23 samples of fresh milk type B, collected by manual or mechanical milking, were stored in collective refrigeration tanks of farms located in the Metropolitan Region of Natal and nearby, State of Rio Grande do Norte (RN), Brazil. Twenty samples of fresh milk commercially traded in the city of Ceará-Mirim RN were also analyzed. The yeasts were quantified by count of colony-forming units (CFU). All isolated species were treated by slow pasteurization (62-64 °C for 30 min) and fast (72-75 °C for 20 s), as well as by boiling (100 °C). Fifty yeast strains were obtained, and the species were identified as Candida tropicalis (28%), Candida parapsilosis (14%), Candida albicans (12%), Candida glabrata (10%), Candida krusei (10%), Kluyveromyces marxianus (10%), Candida guilliermondii (8%), Candida rugosa (2%), Candida orthopsilosis (2%), Pichia manshurica (2%), and Kodamaea ohmeri (2%). Five isolates showed resistance to the antifungal agents tested. Among all the isolates submitted to heat treatment, 80% were resistant to fast pasteurization and 60% to boiling, but none of them resisted the slow pasteurization. The milk collected through mechanical milking and stored in collective cooling tanks, presented higher rates of yeast contamination, compared to milk samples collected by manual milking and kept under the same storage conditions.

Biology and Natural History of Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus is a clinical condition characterized by insufficient insulin production due to progressive loss of pancreatic islet ß-cells mediated by an autoimmune response. This deregulation of the immune system is caused by the action of genetic, epigenetic, and environmental factors in varying combinations for each individual. Although the inflammation of the islets with immune cell infiltration, known as insulitis, is an important element in pathogenesis, other factors are necessary for disease initiation. Associations with variants of HLA and other genes related to immune system function, mainly haplotypes HLA-DR3-DQ2 and HLA-DR4-DQ8, are more evident. The influence of polymorphisms and epigenetic modifications, as well as the microbiome, is convincing proof of the existence of a complex interaction between genetic, immune, and environmental factors in the etiology and pathogenesis of this metabolic disorder. Loss of selftolerance to autoimmunity is a critical point in the development of the disease, and regulatory T cells play a key role in this process. Thus, any failure of these cells, either due to an insufficient number or altered expression of cytokines and transcription factors, may be the trigger for the onset of the disease. The protective action of regulatory T cells is controlled by gene expression that is modulated by epigenetic modifications, including the dysregulation of noncoding RNAs. This review takes an updated approach to the natural history of type 1 diabetes, focusing on the factors involved in the etiology and pathogenesis.

Spirometric values associated with clinical form and risk of death and stroke in chagasic patients.

The aim of the present study was to compare pulmonary function among patients with different clinical forms and scores for risk of death and stroke. Patients were recruited from the Chagas Disease Ambulatory Service at the University of Rio Grande do Norte State (Mossoró, Brazil). The evaluation of pulmonary function was performed through spirometry techniques using a digital spirometer, and information about the clinical forms (cardiac, cardiodigestive, digestive and undetermined) and scores for risk of death (Rassi's risk-of-death score) and stroke was subsequently collected. Upon completion of the evaluation, comparisons of the values obtained between the groups for different clinical forms, risk stratification of stroke and Rassi's risk-of-death were made. The study cohort consisted of 72 patients. Individuals with a low risk of death had significantly higher values in the Tiffeneau index and individuals with a low risk of stroke presented with higher percentage values for forced vital capacity and forced expiratory volume in 1 sec. In addition, individuals with heart disease had worse percentage values for FVC and FEV1. In conclusion, the results showed that spirometry was an effective analytical technique and was associated with clinical forms, and death and stroke risk scores, in patients with Chagas disease, adding an important prognostic tool to those currently available.

Changes in renal function increase the need for advanced ventilatory support and increase the risk of mortality in critically ill patients with COVID-19.

In addition to respiratory failure, another important outcome presented by patients hospitalized with coronavirus disease 2019 (COVID-19) is renal failure, which is related to increased severity of infection and a greater risk of mortality. Severity is often represented by the need for respiratory and/or life support, which can range from oxygen therapy to invasive mechanical ventilation. This study aimed to determine the association between the degree of renal and inflammatory impairment in patients with the need for advanced respiratory support and mortality. Included in the present study were 79 critically ill patients with COVID-19 on different days, who required a nasal cannula and/or orotracheal intubation. Data from laboratory tests, arterial blood gases and information on their clinical evolution were collected. The results obtained showed that the biochemical markers of renal function, as well as the inflammatory markers and the partial pressure of carbon dioxide, were significantly increased in patients who succumbed to the infection. Similarly, these markers were higher amongst patients who required increased respiratory assistance.

Respiratory and functional tests in the assessment and prognosis of patients with chagas disease

Chagas disease causes an important impact on cardiorespiratory system, functional and working capacity of the patient. Performing a functional assessment on these individuals becomes essential, since the impact of physical limitation is an important factor that is related with other life domains, such as risk of cardiovascular events in a brief period and risk of death. The goal of this work was to perform a literature review to present the evaluative and prognostic value of main valid respiratory and functional tests in patients with Chagas disease, as well as their applicability and reproducibility. A literature search was performed from 1981 to 2020 in Scielo, Pubmed/Medline, Science Direct, Scopus and Web of Science databases. Only complete studies published in English, Portuguese or Spanish were analyzed which specifically discussed the respiratory and functional tests used in patients with Chagas disease. In total, 544 articles were retrieved of which 35 were eligible. The main functional tests approached were Cardiopulmonary Exercise Testing, Incremental Exercise Testing and Six-Minute Walk Test. Several studies show themselves as useful markers for predicting quality of life, mortality and functional impairment, in addition to other patients' characteristics. Several tests can be used to assess the respiratory and functional impact to patients' health, as well as its relationship with important domains of their lives

The role of HPV-induced epigenetic changes in cervical carcinogenesis (Review).

Cervical cancer is associated with infection by certain types of human papillomaviruses (HPVs), and this affects women worldwide. Despite the improvements in prevention and cure of HPV-induced cervical cancer, it remains the second most common type of cancer in women in the least developed regions of the world. Epigenetic modifications are stable long-term changes that occur in the DNA, and are part of a natural evolutionary process of necessary adaptations to the environment. They do not result in changes in the DNA sequence, but do affect gene expression and genomic stability. Epigenetic changes are important in several biological processes. The effects of the environment on gene expression can contribute to the development of numerous diseases. Epigenetic modifications may serve a critical role in cancer cells, by silencing tumor suppressor genes, activating oncogenes, and exacerbating defects in DNA repair mechanisms. Although cervical cancer is directly related to a persistent high-risk HPV infection, several epigenetic changes have been identified in both the viral DNA and the genome of the infected cells: DNA methylation, histone modification and gene silencing by non-coding RNAs, which initiate and sustain epigenetic changes. In the present review, recent advances in the role of epigenetic changes in cervical cancer are summarized.

Epidemiologic and clinical investigations during a chikungunya outbreak in Rio Grande do Norte State, Brazil.

The first autochthonous case of chikungunya virus (CHIKV) infection in Brazil was in September 2014 in the State of Amapá, and from there it rapidly spread across the country. The present study was conducted in 2016 in the state of Rio Grande do Norte, and the aims were to describe the epidemiological and the clinical aspects of the CHIKV outbreak. Biological samples from 284 chikungunya suspected cases were screened for CHIKV and Flavivirus (FV) RNA using qRT-PCR. Negative PCR samples were also screened for anti-CHIKV and anti-FVIgM by ELISA. CHIKV RNA were detected in 125 samples mostly occurring from January through March (46%), mainly affecting adults and older adults. We found a gradual decrease in viral RNA over the disease time. Anti-CHIKV IgM was found in 47.5% after negative CHIKV qRT-PCR. Interestingly, 45.0% simultaneously had positive results for CHIKV and FV IgM, suggesting the occurrence of virus co-circulation. The most frequent symptom was fever (91%). Women presented more chance to develop nausea and abdominal pain compared to men. Our data described and allows us to better understand the clinical and epidemiological aspects of the 2016 chikungunya outbreak in Rio Grande do Norte and can help in the early clinical diagnosis of the virus.

Biology and pathogenesis of human osteosarcoma.

Osteosarcoma (OS) is a bone tumor of mesenchymal origin, most frequently occurring during the rapid growth phase of long bones, and usually located in the epiphyseal growth plates of the femur or the tibia. Its most common feature is genome disorganization, aneuploidy with chromosomal alterations, deregulation of tumor suppressor genes and of the cell cycle, and an absence of DNA repair. This suggests the involvement of surveillance failures, DNA repair or apoptosis control during osteogenesis, allowing the survival of cells which have undergone alterations during differentiation. Epigenetic events, including DNA methylation, histone modifications, nucleosome remodeling and expression of non-coding RNAs have been identified as possible risk factors for the tumor. It has been reported that p53 target genes or those genes that have their activity modulated by p53, in addition to other tumor suppressor genes, are silenced in OS-derived cell lines by hypermethylation of their promoters. In osteogenesis, osteoblasts are formed from pluripotent mesenchymal cells, with potential for self-renewal, proliferation and differentiation into various cell types. This involves complex signaling pathways and multiple factors. Any disturbance in this process can cause deregulation of the differentiation and proliferation of these cells, leading to the malignant phenotype. Therefore, the origin of OS seems to be multifactorial, involving the deregulation of differentiation of mesenchymal cells and tumor suppressor genes, activation of oncogenes, epigenetic events and the production of cytokines.

Strength training improves body composition, muscle strength and increases CD4+ T lymphocyte levels in people living with HIV/AIDS.

The establishment of physical training programs for people living with HIV/AIDS (PLWHA) has several benefits. The study aimed to analyze the effect of resistance training using prediction of intensity by subjective perception of effort (SPE) on body composition, muscle strength, and TCD4+ lymphocyte levels in PLWHA. This a randomized controlled trial study. Participants (11 men and 8 women), were divided in two groups: exercise group (EG) and control group (CG). The EG was submitted to 12 weeks of a resistance-training program based in the prediction of intensity by SPE. Body mass percentages were evaluated using tetrapolar bioelectrical impedance and skinfold methods. We used Flow Cytometry to quantify CD4+ T lymphocytes. Patients showed significant changes in Body Fat Percentage (Δ%=-6.23%), Lean Body Mass (Δ%=2.45%), and CD4T lymphocytes levels (Δ%=15.77%). They also showed significant increase in muscular strength presented in the test for one repetition maximum in all the evaluated exercises. Our data suggest that exercising program prescribed by SPE is capable of improving immune function, body composition, and muscular strength in PLWHA.

Innate immune response in patients with acute Zika virus infection.

Innate immunity receptors (Toll-like receptors/TLRs and RIG-like receptors/RLRs) are important for the initial recognition of Zika virus (ZIKV), modulation of protective immune response, and IFN-α and IFN-ß production. Immunological mechanisms involved in protection or pathology during ZIKV infection have not yet been determined. In this study, we evaluated the mRNA expression of innate immune receptors (TLR3, TLR7, TLR8, TLR9, melanoma differentiation-associated protein 5/MDA-5, and retinoic acid inducible gene/RIG-1), its adapter molecules (Myeloid Differentiation Primary Response Gene 88/Myd88, Toll/IL-1 Receptor Domain-Containing Adaptor-Inducing IFN-ß/TRIF), and cytokines (IL-6, IL-12, TNF-α, IFN-α, IFN-ß, and IFN-γ) in the acute phase of patients infected by ZIKV using real-time PCR in peripheral blood. Patients with acute ZIKV infection had high expression of TLR3, IFN-α, IFN-ß, and IFN-γ when compared to healthy controls. In addition, there was a positive correlation between TLR3 expression compared to IFN-α and IFN-ß. Moreover, viral load is positively correlated with TLR8, RIG-1, MDA-5, IFN-α, and IFN-ß. On the other hand, patients infected by ZIKV showed reduced expression of RIG-1, TLR8, Myd88, and TNF-α molecules, which are also involved in antiviral immunity. Similar expressions of TLR7, TLR9, MDA-5, TRIF, IL-6, and IL-12 were observed between the group of patients infected with ZIKV and control subjects. Our results indicate that acute infection (up to 5 days after the onset of symptoms) by ZIKV in patients induces the high mRNA expression of TLR3 correlated to high expression of IFN-γ, IFN-α, and IFN-ß, even though the high viral load is correlated to high expression of TLR8, RIG-1, MDA-5, IFN-α, and IFN-ß in ZIKV patients.

Th17 response in patients with cervical cancer.

Persistent infection by high-risk human papillomavirus (HR-HPV) is the main risk factor for uterine cervical cancer (UCC). However, viral infection alone is not sufficient for the development and progression of premalignant cervical lesions for cancer. In previous years it has been suggested that the adaptive immune response triggered by the differentiation of naïve helper T cells in Th17 cells may serve an important role in disease development. It has been hypothesized that Th17 cells may be involved in the promotion of UCC, as high levels of interleukin 17 (IL17) expression have been detected in the mucosa of the uterine cervix of patients affected by the disease. However, the role of Th17 cells in the tumor development and progression remains unclear. It is believed that the immune response of the Th17 type during persistent infection of the genital tract with HR-HPV triggers chronic inflammation with a long duration with the production of IL17 and other pro-inflammatory cytokines, creating a favorable environment for tumor development. These cytokines are produced by immune system cells in addition to tumor cells and appear to function by modulating the host immune system, resulting in an immunosuppressive response as opposed to inducing an effective protective immune response, thus contributing to the growth and progression of the tumor. In the present review, the latest advances are presented about the function of Th17 cells and the cytokines produced by them in the development and progression of UCC.

Chikungunya fever: a threat to global public health.

Chikungunya fever is an emerging arbovirus infection, representing a serious public health problem. Its etiological agent is the Chikungunya virus (CHIKV). Transmission of this virus is mainly vector by mosquitoes of the genus Aedes, although transmission by blood transfusions and vertical transmission has also been reported. The disease presents high morbidity caused mainly by the arthralgia and arthritis generated. Cardiovascular and neurological manifestations have also been reported. The severity of the infection seems to be directly associated with the action of the virus, but also with the decompensation of preexisting comorbidities. Currently, there are no therapeutic products neither vaccines licensed to the infection CHIKV control, although several vaccine candidates are being evaluated and human polyvalent immunoglobulins anti-CHIKV had been tested. Antibodies can protect against the infection, but in sub-neutralizing concentrations can augment virus infection and exacerbate disease severity. So, the prevention still depends on the use of personal protection measures and vector control, which are only minimally effective.

Improved reverse transcription-polymerase chain reaction assay for the detection of flaviviruses with semi-nested primers for discrimination between dengue virus serotypes and Zika virus.

BACKGROUND The genus Flavivirus includes a variety of medically important viruses, including dengue virus (DENV) and Zika virus (ZIKV), which are most prevalent in Brazil. Because the clinical profile of patients affected by different DENV serotypes or ZIKV may be similar, the development of new methods that facilitate a rapid and accurate diagnosis is crucial. OBJECTIVES The current study aimed to develop an improved reverse transcription-polymerase chain reaction (RT-PCR) protocol for universal detection of flaviviruses by using semi-nested primers that discriminate between DENV serotypes and ZIKV. METHODS The bioinformatics workflow adopted for primer design included: (1) alignment of 1,442 flavivirus genome sequences, (2) characterisation of 27 conserved regions, (3) generation of a primer set comprising 77 universal primers, and (4) selection of primer pairs with greatest coverage and specificity. Following primer design, the reaction was validated in vitro. The same approach was applied to the design of primers specific for DENV and ZIKV, using a species-specific sequence database. FINDINGS The new assay amplified an 800-806 nt variable region of the NS5 gene and allowed discrimination of virtually all flavivirus species using reference-sequence comparison. The 800-806 nt fragment was validated as a template for a semi-nested multiplex PCR using five additional primers for the detection of DENV and ZIKV. These primers were designed to generate amplicons of different sizes, allowing differentiation of the four serotypes of DENV, and ZIKV using agarose gel electrophoresis. MAIN CONCLUSIONS The bioinformatics pipeline allowed efficient primer design, making it possible to identify the best targets within the coding region of the NS5 protein. The multiplex system proved effective in differentiation of DENV1-4 and ZIKV on a 2% agarose gel. The possibility of discriminating DENV serotypes and ZIKV in the same reaction provided a faster result consuming less sample. In addition, this simplified approach ensured the reduction of the cost per analysis.

A seminested PCR assay for detection and typing of human papillomavirus based on E1 gene sequences.

HPV infection is considered one of the leading causes of cervical cancer in the world. To date, more than 180 types of HPV have been described and viral typing is critical for defining the prognosis of cancer. In this work, a seminested PCR which allow fast and inexpensively detection and typing of HPV is presented. The system is based on the amplification of a variable length region within the viral gene E1, using three primers that potentially anneal in all HPV genomes. The amplicons produced in the first step can be identified by high resolution electrophoresis or direct sequencing. The seminested step includes nine specific primers which can be used in multiplex or individual reactions to discriminate the main types of HPV by amplicon size differentiation using agarose electrophoresis, reducing the time spent and cost per analysis.

Improved reverse transcription-polymerase chain reaction assay for the detection of flaviviruses with semi-nested primers for discrimination between dengue virus serotypes and Zika virus

BACKGROUND The genus Flavivirus includes a variety of medically important viruses, including dengue virus (DENV) and Zika virus (ZIKV), which are most prevalent in Brazil. Because the clinical profile of patients affected by different DENV serotypes or ZIKV may be similar, the development of new methods that facilitate a rapid and accurate diagnosis is crucial. OBJECTIVES The current study aimed to develop an improved reverse transcription-polymerase chain reaction (RT-PCR) protocol for universal detection of flaviviruses by using semi-nested primers that discriminate between DENV serotypes and ZIKV. METHODS The bioinformatics workflow adopted for primer design included: (1) alignment of 1,442 flavivirus genome sequences, (2) characterisation of 27 conserved regions, (3) generation of a primer set comprising 77 universal primers, and (4) selection of primer pairs with greatest coverage and specificity. Following primer design, the reaction was validated in vitro. The same approach was applied to the design of primers specific for DENV and ZIKV, using a species-specific sequence database. FINDINGS The new assay amplified an 800-806 nt variable region of the NS5 gene and allowed discrimination of virtually all flavivirus species using reference-sequence comparison. The 800-806 nt fragment was validated as a template for a semi-nested multiplex PCR using five additional primers for the detection of DENV and ZIKV. These primers were designed to generate amplicons of different sizes, allowing differentiation of the four serotypes of DENV, and ZIKV using agarose gel electrophoresis. MAIN CONCLUSIONS The bioinformatics pipeline allowed efficient primer design, making it possible to identify the best targets within the coding region of the NS5 protein. The multiplex system proved effective in differentiation of DENV1-4 and ZIKV on a 2% agarose gel. The possibility of discriminating DENV serotypes and ZIKV in the same reaction provided a faster result consuming less sample. In addition, this simplified approach ensured the reduction of the cost per analysis.

Chemical composition and evaluation of the antibacterial and Cytotoxic activities of the essential oil from the leaves of Myracrodruon urundeuva.

BACKGROUND: This study evaluated the in vitro activity of essential oil extracted from the leaves of Myracrodruon urundeuva. METHODS: The oil was obtained by hydro-distillation and characterized by Gas Chromatography coupled to Mass Spectrometry (GC-MS) and Gas Chromatography with Flame Ionization Detector (GC-FID). The antibacterial activity was evaluated by the broth microdilution technique and the MIF was determined by using growth indicator CTT (2,3,5-triphenyl-tetrazolium) and CBM in BHI agar. The oil's cytotoxicity was evaluated in HeLa, HEK-293, and Vero E6 cells using MTT, 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium. RESULTS: The oil showed chemical markers, including α-pinene (87.85%), trans-caryophyllene (1.57%), limonene (1.49%) and ß -pinene (1.42%), and activity against all strains: Staphylococcus aureus (MIC = MBC = 0.22 mg/mL), Staphylococcus epidermidis (MIC = 0.11 mg/mL and MBC = 0.22 mg/mL), Escherichia coli (MIC = 0.88 mg/mL and MBC = 1.75 mg/mL), Pseudomonas aeruginosa (MIC = MBC = 7 mg/mL) and Salmonella Enteritidis (MIC = MBC = 0.44 mg/mL). In vitro cytotoxicity tests showed that the oil is not toxic and has slight antitumor activity. CONCLUSIONS: We conclude that the M. urundeuva oil results are promising, with prospects of being pharmacologically viable.