(1) Background: The HIV subtype D is generally associated with a faster decline in CD4+ T cell counts, a higher viral load, and a faster progression to AIDS. However, it is still poorly characterized ...in Brazil. In this study, we used genomics and epidemiological data to investigate the transmission dynamics of HIV subtype D in the state of Bahia, Northeast Brazil. (2) Methods: To achieve this goal, we obtained four novel HIV-1 subtype D partial pol genome sequences using the Sanger method. To understand the emergence of this novel subtype in the state of Bahia, we used phylodynamic analysis on a dataset comprising 3704 pol genome sequences downloaded from the Los Alamos database. (3) Results: Our analysis revealed three branching patterns, indicating multiple introductions of the HIV-1 subtype D in Brazil from the late 1980s to the late 2000s and a single introduction event in the state of Bahia. Our data further suggest that these introductions most likely originated from European, Eastern African, Western African, and Southern African countries. (4) Conclusion: Understanding the distribution of HIV-1 viral strains and their temporal dynamics is crucial for monitoring the real-time evolution of circulating subtypes and recombinant forms, as well as for designing novel diagnostic and vaccination strategies. We advocate for a shift to active surveillance, to ensure adequate preparedness for future epidemics mediated by emerging viral strains.
Staphylococci are one of the most prevalent microorganisms in bovine mastitis. Staphylococcus spp. are widespread in the environment, and can infect animals and humans as opportunistic pathogens. The ...objective of this study was to determine the frequency of methicillin-resistance (MR) among coagulase-negative staphylococci (CoNS) previously obtained from milk of mastitic cows in Brazil and to characterize the antimicrobial resistance phenotype/genotype and the SCCmec type of MRCoNS isolates. Identification of MRCoNS was based on both biochemical and molecular methods. Susceptibility testing for eleven antimicrobials was performed by disk-diffusion agar. Antimicrobial resistance genes and SCCmec were investigated by specific PCRs. Twenty-six MRCoNS were detected (20 % of total CoNS), obtained from 24 animals, and were identified as follows: S. epidermidis (7 isolates), S. chromogenes (7), S. warneri (6), S. hyicus (5) and S. simulans (1). All MRCoNS isolates carried mecA while the mecC gene was not detected in any CoNS. The SCCmec IVa was demonstrated in nine MRCoNS, while the remaining 17 isolates harbored non-typeable SCCmec cassettes. In addition to oxacillin and cefoxitin resistance, MRCoNS showed resistance to tetracycline (n = 7), streptomycin (n = 6), tobramycin (n = 6), and gentamicin (n = 4), and harbored the genes tet(K) (n = 7), str (n = 3), ant(4′) (n = 6) and aac(6′)-aph(2″) (n = 4), respectively. In addition, seven strains showed intermediate resistance to clindamycin and two to streptomycin, of which two harboured the lnu(B) and lsa(E) genes and two the aad(E) gene, respectively. One isolate presented intermediate erythromycin and clindamycin resistance and harbored an erm(C) gene with an uncommon 89-bp deletion rendering a premature stop codon. MRCoNS can be implicated in mastitis of cows and they constitute a reservoir of resistance genes that can be transferred to other pathogenic bacteria.
Resumo: Introdução: As comunidades tradicionais são grupos de indivíduos socialmente organizados que partilham comportamentos econômicos, socioambientais e culturais comuns. Entre elas, destacam-se ...as comunidades indígenas no Brasil, que vêm sofrendo o impacto da urbanização, do crescimento de doenças crônicas e epidemias e do aumento da insegurança alimentar. Relato de experiência: Este estudo teve como objetivo descrever as experiências da equipe de saúde, quanto ao uso de uma ferramenta de gestão de dados na assistência, em uma comunidade indígena no Nordeste brasileiro. Trata-se de um relato de experiência do uso de uma ferramenta digital nas ações assistenciais em uma comunidade tradicional. A equipe de saúde foi dividida em dois grupos: agentes comunitários de saúde e estudantes de Medicina. Discussão: A descrição das experiências e a análise das narrativas resultaram na identificação de 258 citações, que foram classificadas em 12 categorias, relacionadas ao objeto de estudo. Dentre estas, as questões ligadas aos benefícios da ferramenta foram as mais mencionadas (43,41%), em que os subgrupos abordaram diferentes reflexões. A segunda categoria mais citada se referia às limitações da ferramenta (15,11%), sendo a necessidade do sinal de internet o ponto crítico. Ou seja, esta pesquisa mostra vantagens da ferramenta na atenção à saúde, mas também explicita fragilidades inerentes ao seu uso, de modo a trazer questões importantes dessa vivência e estimular práticas semelhantes. Conclusão: Esse relato de experiência, como método científico, traz importantes questões vivenciadas, relacionadas à aplicabilidade prática de uma ferramenta digital em uma comunidade indígena. Apesar de ser inegável que há pontos de fragilidade evidentes, eles não comprometeram o resultado afirmativo da vivência, melhorando a assistência.
Abstract: Introduction: Traditional communities are groups of socially organized individuals with common economic, socio-environmental, and cultural behaviors. Brazil’s indigenous communities are a prime example of these groups, suffering the impact of urbanization, the growth of chronic diseases, epidemics, and increased food insecurity. Experience report: To describe the health team’s experiences in the use of a data management tool for care in an indigenous community in northeastern Brazil. Methodology: This is an experience report on the use of a digital tool to assist actions in a traditional community. The health team was divided into community health agents and medical students. Discussion: The description of the experiences and analysis of the narratives resulted in identifying 258 citations, classified into 12 categories related to the study scope. Of these, issues related to benefits of the tool were the most commonly mentioned (43.41%), where the subgroups addressed different reflections. The second most cited category referred to the tool’s limitations (15.11%), with the need for an internet connection being the critical point. This research, therefore, shows the tool’s advantages in health care but also explains weaknesses inherent to its use, raising important issues of this experience and stimulating similar practices. Conclusion: This experience report, as a scientific method, addresses essential experienced issues related to the practical applicability of a digital tool in an indigenous community. Although it is undeniable that there are obvious points of weakness, these did not compromise the positive result of the experience, and care was improved.
Chagas disease, caused by the parasite
(
), remains a serious public health problem for which there is no effective treatment in the chronic stage. Intense cardiac fibrosis and inflammation are ...hallmarks of chronic Chagas disease cardiomyopathy (CCC). Previously, we identified upregulation of circulating and cardiac miR-21, a pro-fibrotic microRNA (miRNA), in subjects with CCC. Here, we explored the potential role of miR-21 as a therapeutic target in a model of chronic Chagas disease. PCR array-based 88 microRNA screening was performed in heart samples obtained from C57Bl/6 mice chronically infected with
and serum samples collected from CCC patients. MiR-21 was found upregulated in both human and mouse samples, which was corroborated by an in silico analysis of miRNA-mRNA target prediction. In vitro miR-21 functional assays (gain-and loss-of-function) were performed in cardiac fibroblasts, showing upregulation of miR-21 and collagen expression upon transforming growth factor beta 1 (TGFβ1) and
stimulation, while miR-21 blockage reduced collagen expression. Finally, treatment of
-infected mice with locked nucleic acid (LNA)-anti-miR-21 inhibitor promoted a significant reduction in cardiac fibrosis. Our data suggest that miR-21 is a mediator involved in the pathogenesis of cardiac fibrosis and indicates the pharmacological silencing of miR-21 as a potential therapeutic approach for CCC.
Structural changes in the spleen have been reported in several infectious diseases. In visceral leishmaniasis (VL), a severe parasitic disease caused by
spp., the loss of white pulp accompanies a ...severe clinical presentation. Hamster model reproduces aspects of human VL progression. In the early stages, a transcriptomic signature of leukocyte recruitment was associated with white pulp hyperplasia. Subsequently, impaired leukocyte chemotaxis with loss of T lymphocytes in the periarteriolar lymphoid sheath occurred. This differential gene expression was subsequently corroborated by transcriptomic profiling of spleens in severe human VL. At the latest stage, spleen disorganization was associated with increasing clinical signs of VL. White pulp disruption was accompanied by decreased
expression. The expression of
and
decreased, likely regulated by
overexpression. Our findings enlighten a pathway implying cell cycle arrest and decreased gene expression involved in spleen organization.
Visceral leishmaniasis is an opportunistic disease in HIV-1 infected individuals, unrecognized as a determining factor for AIDS diagnosis. The growing geographical overlap of HIV-1 and
infections is ...an emerging challenge worldwide, as co-infection increases morbidity and mortality for both infections. Here, we determined the prevalence of people living with HIV (PWH) with a previous or ongoing infection by
and investigated the virological and immunological factors associated with co-infection. We adopted a two-stage cross-sectional cohort (CSC) design (CSC-I,
= 5,346 and CSC-II,
= 317) of treatment-
HIV-1-infected individuals in Bahia, Brazil. In CSC-I, samples collected between 1998 and 2013 were used for serological screening for leishmaniasis by an in-house Enzyme-Linked Immunosorbent Assay (ELISA) with SLA (Soluble
Antigen), resulting in a prevalence of previous or ongoing infection of 16.27%. Next, 317 PWH were prospectively recruited from July 2014 to December 2015 with the collection of sociodemographic and clinical data. Serological validation by two different immunoassays confirmed a prevalence of 15.46 and 8.20% by anti-SLA, and anti-HSP70 serology, respectively, whereas 4.73% were double-positive (DP). Stratification of these 317 individuals in DP and double-negative (DN) revealed a significant reduction of CD4
counts and CD4
/CD8
ratios and a tendency of increased viral load in the DP group, as compared to DN. No statistical differences in HIV-1 subtype distribution were observed between the two groups. However, we found a significant increase of CXCL10 (
= 0.0076) and a tendency of increased CXCL9 (
= 0.061) in individuals with DP serology, demonstrating intensified immune activation in this group. These findings were corroborated at the transcriptome level in independent Leishmania- and HIV-1-infected cohorts (Swiss HIV Cohort and Piaui Northeast Brazil Cohort), indicating that CXCL10 transcripts are shared by the IFN-dominated immune activation gene signatures of both pathogens and positively correlated to viral load in untreated PWH. This study demonstrated a high prevalence of PWH with
seropositivity in Bahia, Brazil, linked to IFN-mediated immune activation and a significant decrease in CD4
levels. Our results highlight the urgent need to increase awareness and define public health strategies for the management and prevention of HIV-1 and
co-infection.
This study evaluated the relationship between CL features assessed by ultrasound (luteal tissue area and blood flow, BF) or rectal palpation (size), uterine tone (UT), plasma progesterone (P4) ...concentration on Day 7 (D7) and subsequent pregnancy outcomes in bovine embryo recipients. A total of 163 cows and heifers were included in this study. The expected day of ovulation after the synchronization protocol was designated as D0. On D7, ovaries and uterus were examined by ultrasonography and rectal palpation, and subjective scores (1–3 scale) were assigned for CL size, area and BF, and for UT. Blood samples were collected for further P4 analysis. Each embryo recipient then received a grade I frozen–thawed in vivo‐produced blastocyst, which was transferred to the uterine horn ipsilateral to the CL. Pregnancy diagnosis was performed on D35, and the results were retrospectively compared with the assigned scores for CL and UT. We observed a significant (p < .02) interaction between CL size and UT, with a progressive increase in the likelihood of pregnancy for recipients bearing a large CL among those with turgid UT. Ultrasound scoring of the CL using B‐mode and Doppler‐mode did not significantly predict pregnancy rates on D35 (p < .6 and p < .5, respectively). However, logistic regression analysis revealed a trend towards a quadratic effect (p < .08 and p < .06) indicating that the probability of pregnancy varied according to the area of luteal tissue and P4 concentrations, respectively. No significant (p > .05) association was found between the probability of pregnancy and the BF area of the CL. In summary, UT before embryo transfer may reflect successful recipient synchronization. Elevated P4 levels, assessed by CL size, may offset uterine contractility, mitigating adverse effects. Additionally, the CL area may be more important than its vascularization area when evaluating recipients D7 after ovulation.
Purpose
Penile cancer has a high incidence in developing countries. The standard treatment is removal of the primary tumor and, when necessary, inguinal lymphadenectomy. Currently, the most important ...prognostic factor is lymph node disease, however, the available staging methods are inaccurate, and the high morbidity rate of lymphadenectomy has stimulated the study of predictive biomarkers of lymph node metastasis for selecting the patients who need lymphadenectomy. SOX2, STAT3 and CD44
high
/CD24
low
were chosen because they have provided good predictive results in other squamous cell carcinoma (SCC), although there are no studies for penile cancer. Thus, the expression of SOX2, STAT3, CD24+, and CD44+ in the penile cancer tumor microenvironment was investigated for correlation with tumor behavior in SCC.
Methods
This observational, prospective, translational study included 34 men and investigated the expression of SOX2, STAT3, CD24+, and CD44+ in tumor tissue by flow cytometry.
Results
The median age of the 38 evaluated patients with penile cancer was 61 (37–80) years. Most patients presented a tumor located on the glans penis (82.3%), with the usual histological type (79.4%) and 61.7% of patients presented stage pT2. No metastasis was found in 85.3% of patients. The expression of SOX2, STAT3 and CD44
high
/CD24
low
in the microenvironment of penile SCC treated with lymphadenectomy was significantly associated with aggressive tumor behavior (
p
< 0.05). STAT3 expression shows discrepant points when evaluated in context of angiolymphatic vascular invasion.
Conclusion
SOX2, STAT3 and CD44
high
/CD24
low
in penile SCC can be indicators of prognosis, allowing for selection of more aggressive treatment when necessary.
De Faria Guimaraes et al discuss the case study of a child with spastic gait achieved independent walking at the age of 2 years, and 3 years later was referred for investigation. A brain MRI ...demonstrated corpus callosum dysgenesis and peritrigonal white matter abnormality. Whole exome sequencing revealed compound heterozygosity for two novel likely pathogenic variants in NT5C2, consistent with SPG45, of the SPG subtypes with thin corpus callosum.
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