Plasma Sphingomyelin Disturbances: Unveiling Its Dual Role as a Crucial Immunopathological Factor and a Severity Prognostic Biomarker in COVID-19.

SARS-CoV-2 infection triggers distinct patterns of disease development characterized by significant alterations in host regulatory responses. Severe cases exhibit profound lung inflammation and systemic repercussions. Remarkably, critically ill patients display a "lipid storm", influencing the inflammatory process and tissue damage. Sphingolipids (SLs) play pivotal roles in various cellular and tissue processes, including inflammation, metabolic disorders, and cancer. In this study, we employed high-resolution mass spectrometry to investigate SL metabolism in plasma samples obtained from control subjects (n = 55), COVID-19 patients (n = 204), and convalescent individuals (n = 77). These data were correlated with inflammatory parameters associated with the clinical severity of COVID-19. Additionally, we utilized RNAseq analysis to examine the gene expression of enzymes involved in the SL pathway. Our analysis revealed the presence of thirty-eight SL species from seven families in the plasma of study participants. The most profound alterations in the SL species profile were observed in patients with severe disease. Notably, a predominant sphingomyelin (SM d18:1) species emerged as a potential biomarker for COVID-19 severity, showing decreased levels in the plasma of convalescent individuals. Elevated SM levels were positively correlated with age, hospitalization duration, clinical score, and neutrophil count, as well as the production of IL-6 and IL-8. Intriguingly, we identified a putative protective effect against disease severity mediated by SM (d18:1/24:0), while ceramide (Cer) species (d18:1/24:1) and (d18:1/24:0)were associated with increased risk. Moreover, we observed the enhanced expression of key enzymes involved in the SL pathway in blood cells from severe COVID-19 patients, suggesting a primary flow towards Cer generation in tandem with SM synthesis. These findings underscore the potential of SM as a prognostic biomarker for COVID-19 and highlight promising pharmacological targets. By targeting sphingolipid pathways, novel therapeutic strategies may emerge to mitigate the severity of COVID-19 and improve patient outcomes.

Adaptive Algorithms as Control Strategies of Smart Upper Limb Orthosis: A Protocol for a Systematic Scoping Review.

Introduction: Adaptive algorithms for controlling orthosis emerged to overcome significant problems with automatic biosignal classification and personalized rehabilitation. Smart orthoses are evolving fast and need a better human-machine interaction performance since biosignals, feedback, and motor control dynamically change and must be adaptive. This manuscript outlines a scoping review protocol to systematically review the smart upper limb (UL) orthoses based on adaptive algorithms and feasibility tests. Materials and Methods: This protocol was developed based on the York framework. A field-specific structure was defined to achieve each phase. Eleven scientific databases (PubMed, Web of Science, SciELO, Koreamed, Jstage, AMED, CENTRAL, PEDro, IEEE, Scopus, and Arxiv) and five patent databases (Patentscope, Patentlens, Google Patents, Kripis, J-platpat) were searched. The developed framework will extract data (i.e., orthosis description, adaptive algorithms, tools used in the usability test, and benefits to the general population) from the selected studies using a rigorous approach. Data will be described quantitatively using frequency and trend analysis methods. Heterogeneity between the included studies will be assessed using the Chi-test and I-statistic. The risk of bias will be summarized using the latest Prediction Model Study Risk of Bias Assessment Tool. Discussion: This review will identify, map, and synthesize the advances about the description of adaptive algorithms for control strategies of smart UL orthosis using data extracted from patents and articles.

High plasma soluble levels of the immune checkpoint HLA-G molecule among bodybuilders.

INTRODUCTION: Studies report that intense physical activity influences the down-regulation of immune function in athletes as well as the interaction between adipose tissue and the immune system. AIM: This study aimed to compare the plasma soluble levels of the immune checkpoint HLA-G (sHLA-G) molecule with the fat mass and muscle mass index among 77 bodybuilders and 64 controls. RESULTS: The comparisons of the percentage of body fat (%BF) revealed that the groups of male and female bodybuilders showed a statistically significant reduction in the percentage of body fat when compared to their control group, (P <0.0001, for both comparisons). Regarding sHLA-G levels, the comparisons showed that the group of male bodybuilders had significantly higher sHLA-G levels compared to the group of female bodybuilders (P = 0.0011). CONCLUSION: Our results showed that in bodybuilders with less body fat, the systemic levels of soluble HLA-G, an immunological molecule with recognized immunosuppressive function, are significantly higher and suggest that this immune mechanism may corroborate the immunosuppressive state in athletes undergoing intense and prolonged physical training.

O papel da placenta na transmissão vertical do HIV-1 / The role of the placenta in the vertical transmission of HIV-1

A transmissão vertical (TV) consiste na principal forma de infecção pelo HIV-1 em menores de 13 anos e estimativas apontam que em 25% dos casos a transmissão tenha ocorrido intraútero. Nessas circunstâncias, o vírus de alguma forma ultrapassa a membrana placentária e chega ao sangue fetal. Esta revisão tem como objetivo realizar uma breve descrição sobre os mecanismos presentes na placenta humana que são capazes de gerar susceptibilidade ou proteção à TV do HIV-1. As células placentárias produzem um enorme grupo de citocinas, quimiocinas, hormônios e receptores que podem contribuir com o desfecho da transmissão do vírus ao concepto. Além disso, a capacidade do vírus de infectar as células placentárias também pode contribuir com a sua transmissão. Entretanto, o mecanismo pelo qual o vírus é capaz de sobrepujar a membrana placentária e as consequências dessa infecção no tecido placentário não estão totalmente elucidados. Dessa forma, novas pesquisas nessa área poderão contribuir com o desenvolvimento de estratégias profiláticas eficazes para redução da TV do HIV-1.

Vertical transmission (VT) is the main form of infection by HIV-1 in children under 13 years and estimates show that in 25% of cases intrauterine transmission has occurred. Under these circumstances, the virus somehow overcomes the placental membrane and reaches the fetal blood. This review aims to conduct a brief description of the mechanisms present in human placenta that are capable of generating susceptibility or resistance to VT of HIV-1. Placental cells produces a huge group of cytokines, chemokines, hormones and receptors that may contribute to the outcome of virus transmission to the fetus. Moreover, the ability of the virus to infect placental cells can also contribute to its transmission. However, the mechanism by which the virus is able to overcome the placental tissue is not fully elucidated. Thus, further research in this area may contribute to the development of effective preventive strategies to reduce the VT of HIV-1.

Impact of Strength Training on Bone Mineral Density in Patients Infected With HIV Exhibiting Lipodystrophy.

This study aimed to evaluate the impact of strength training on bone mineral density (BMD) in individuals harboring HIV exhibiting lipodystrophy. The study included 20 subjects (16 men) aged 50.60 ± 6.40 years with reduced BMD, presenting positive serology for HIV, using highly active antiretroviral therapy, and performing no regular practice of physical exercise before being enrolled in the study. Bone mineral density levels were evaluated by dual-energy x-ray absorptiometry in the lumbar spine, femoral neck, and 1/3 radius, before and after 36 sessions (12 weeks) of strength training. Compared with pre-exercise period, the results showed increased BMD in lumbar spine (3.28%; p = 0.012), femoral neck (8.45%; p = 0.044), and 1/3 radius (5.41%; p = 0.035). This is the first study evaluating the impact of strength training in patients living with HIV and exhibiting lipodystrophy, showing an increased BMD in all the regions measured (lumbar spine, femoral neck, and 1/3 radius). This study showed the beneficial impact of the strength training on BMD increase in patients living with HIV as an effective and available approach to improve bone health.

Susceptibility to toxoplasmic retinochoroiditis is associated with HLA alleles reported to be implicated with rapid progression to AIDS.

BACKGROUND/AIMS: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC). METHODS: 98 AIDS patients (25 with TRC, 43 with anti-T. gondii antibodies but without TCR, and 30 without anti-T. gondii antibodies and without TCR) were studied. RESULTS: The HLA-B35 was significantly increased in TRC group (p=0.0038). CONCLUSION: The presence of HLA-B35 may simultaneously predispose to progression to AIDS and TRC.

Mutations in methylenetetrahydrofolate reductase and in cysthationine beta synthase: is there a link to homocysteine levels in peripheral arterial disease?

Peripheral arterial disease (PAD) is an atherosclerotic disturbance characterized by a progressive obstruction of lower limb arteries. Many risk factors associated with PAD development have being reported in the literature. The present study aimed to investigate whether mutations in the methylenetetrahydrofolate reductase (MTHFR) or in the cystathionine beta synthase (CBS) genes are associated with higher levels of homocysteine and the risk of PAD in patients from Brazil. This study analyzed 39 patients with PAD and 32 without PAD in whom risk factors and C677T mutations in the MTHFR gene and both 844ins68 and T833C mutations in the CBS gene were investigated. Although higher levels of homocysteine could be observed in patients with PAD compared to controls, no association between the increase of homocysteine and the frequency of C677T, 844ins68, and T833C mutations could be observed. The results suggest that these mutations do not appear to be related to either homocysteine levels or the development of the disease. However, hyperhomocysteinemia and smoking are important factors in PAD development.

A pilot case-control association study of cytokine polymorphisms in Brazilian women presenting with HPV-related cervical lesions.

OBJECTIVE AND STUDY DESIGN: A case-control study was conducted on 42 Brazilian women presenting with human papilloma virus (HPV) infection and cervical lesion and 87 HPV-negative women to evaluate single nucleotide polymorphisms observed in TNF-alpha, TGF-beta, IL-10, IL-6, and IFN-gamma genes. RESULTS AND CONCLUSION: No significant association was observed on the cytokine polymorphisms analyzed in this series. Larger studies using cytokine polymorphisms may be useful for providing further information regarding their influence or not in HPV-related cervical lesions.

Metabolism genes are among the differentially expressed ones observed in lymphomononuclear cells of recently diagnosed type 1 diabetes mellitus patients.

The large-scale differential gene expression in lymphomononuclear cells of six patients with recently diagnosed type), and six normal individuals matched to patients for sex and age were studied. Glass slides containing 4608 cDNAs from the IMAGE library were spotted using robotic technology. Statistical analysis was carried out by the SAM program, and gene function assessed by the FATIGO program. Thirty differentially expressed genes (21 induced and 9 repressed) were disclosed when DM-1 patients were compared with controls. Although presenting with distinct biological function, most of the induced or repressed genes were related with protein, phosphate, DNA, RNA, carboxylic acid, and fatty acid metabolism. Although some of these genes have been previously associated with the pathogenesis of T1DM, many other genes were identified for further studies.

[Greater survival among patients with immunogenetic markers of rapid progression to AIDS: subsidies for nursing care]. / Maior sobrevida em pacientes com marcadores imunogenéticos de rápida progressão para a AIDS: subsídios para a assistência de enfermagem.

This study sought subsidies for improving nursing care programs for AIDS patients and aimed to verify the influence of changes in sexual behavior, including the adoption of safe sex practices, associated with the survival of AIDS patients with immunogenetic markers of rapid disease progression. 27 AIDS patients were interviewed, with genetic predisposition to rapid progression to AIDS. Genes were typified through the polymerase chain reaction. In spite of the presence of immunogenetic factors, associated with individual predisposition to a rapid evolution of the disease, changes in sexual behavior, including safe sex practices and antiretroviral therapy, may be related to greater survival. This suggests that counseling, detection of risk attitudes and health education, focusing on positive health behavior, are tools nursing must use with HIV-positive patients, with a view to better quality of life and greater survival among these individuals, even among those with genetic predisposition to rapid disease progression.

Lipodistrofia em portadores do HIV / Lipodystrophy in HIV patients

Apesar de aumento da sobrevida, reducao de episodios morbidos e consequente aumento da qualidade de vida, a terapia anti-retroviral prolongada apresenta efeitos indesejaveis em portadores do HIV, como a sindrome da lipodistrofia. Alteracoes na imagem corporal, com as quais se confrontam tais pacientes, podem repercutir a consequencias marcantes para saude afetivo-emocional e, mesmo considerando os beneficios da terapeutica antiretroviral, contraditoriamente parecem reduzir a qualidade de vida. Dada a complexidade e a heterogeneidade da sindrome da lipodistrofia, o presente estudo tem como objetivo descrever os aspectos psicossociais associados as alteracoes corporeas da lipodistrofia e oferecer informacoes atualizadas e sumarizadas que possam ser utilizadas na assistencia a portadores do HIV

Maior sobrevida em pacientes com marcadores imunogenéticos de rápida progressão para a AIDS: subsídios para a assistência de enfermagem / Greater survival among patients with immunogenetic markers of rapid progression to AIDS: subsidies for nursing care

Com enfoque em subsídios para o aperfeiçoamento de programas de enfermagem, direcionados a pacientes com aids, o presente estudo foi realizado com o objetivo de verificar a influência do comportamento sexual na sobrevida de pacientes com aids, portadores de genes associados à rápida progressão da doença. Foram entrevistados 27 pacientes com aids, geneticamente predispostos à rápida progressão da doença. As tipificações dos genes foram realizadas pela reação em cadeia da polimerase. Os resultados sugerem que, apesar da presença de fatores imunogenéticos, associados à predisposição individual para rápida evolução da doença, as mudanças do comportamento sexual, com adoção de práticas de sexo seguro, junto ao uso da terapia anti-retroviral, podem estar relacionadas com maior sobrevida. O aconselhamento, a detecção de atitudes de risco e a educação para saúde, enfocando o comportamento positivo de saúde, são ferramentas que a enfermagem deve utilizar a portadores do HIV, visando à melhor qualidade de vida e maior sobrevida desses indivíduos, mesmo naqueles geneticamente predispostos à rápida progressão da doença

HPV16, HPV18, and HIV infection may influence cervical cytokine intralesional levels.

Infection with oncogenic human papillomavirus (HPV) is considered to be the major risk to cervical cancer. This study analyzed the influence of HPV infection on cytokine intralesional levels in cervical lesion in the presence or not of HIV infection. Cervical biopsies from 42 women were studied. HPV detection and typing were performed using amplified DNA hybridized with sequence-specific primers, and cytokine intralesional levels were detected using ELISA. HPV16+ biopsies exhibited increased IFN-gamma and IL-10 when compared to HPV16- (P = 0.03 and 0.04, respectively). HPV18+ biopsies exhibited decreased TNF-alpha (P = 0.009) and IFN- gamma (P = 0.01) when compared to HPV18-. In accordance to HIV status, HIV-/HPV16+ patients exhibited increased IFN-gamma when compared to those presenting HIV-/HPV16- (P = 0.007). HIV-/HPV18+ patients presented decreased IFN-gamma when compared to HIV-/HPV18- (P = 0.02). These results suggest that the presence of HPV16 infection may influence cervical lesion installation, and irrespective of HIV status, HPV18 infection may be more aggressive than HPV-16.

Overexpression of HLA class I molecules on T cells among type 1 diabetes Brazilian patients.

To evaluate the membrane expression of histocompatibility (HLA) class I (A-C) molecules on lymphomononuclear cells involved in the pathogenesis of type 1 diabetes, we studied 20 newly diagnosed Brazilian patients and 20 matched controls. The coexpression of HLA and cluster of differentiation (CD) molecules was evaluated by flow cytometry. Compared to controls, patients presented increased fluorescence intensity of HLA class I molecules on CD3+, CD4+ and CD8+ cells. Patients exhibiting the HLA-DQB1*0201 and/or DQB1*0302 alleles presented increased expression of class I molecules in relation to HLA-matched healthy controls. The increased HLA class I expression in subsets of T cells may be due to the proinflammatory profile of the disease as well as to the presence of diabetes susceptibility alleles.

Influência da infecção pelo HIV-1 sobre a presença do HPV em lesões do colo uterino / Influence of HIV-1 infection on the presence of HPV in uterine cervix lesions

Analisa a influência da infecção pelo HIV-1 sobre a presença e persistência da infecção pelos HPV16 e HPV18 em mulheres apresentando NIC

Influência do HPV-16 sobre a produção intralesional de IL-10 em mulheres imunogeneticamente responsivas e portadoras do HIV-1 / Influence of the HPV-16 on IL-10 intralesional production in immunogenetically responsive women carrying HIV-1 infection

A infecção pelo papilomavirus humano do tipo 16 - HPV 16, constitui importante fator de risco para o desenvolvimento do câncer cervical. Citocinas são importantes na resposta imune contra infecções virais. Geneticamente determinadas, podem apresentar predomínio para padrão associado com a eliminação do HPV, ou associadas com a persistência da infecção e progressão para lesões cervicais, como a interleucina 10. Além disso, a infecção pelo vírus da imunodeficiência humana do tipo 1, parece ser uma co-morbidade para o desenvolvimento das lesões cervicais

Como entender a associaçäo entre o sistema HLA e as doenças auto-imunes endócrinas / How to understand the association of the HLA system and autoimmune endocrine disorders

A introduçäo de nova nomenclatura para os componentes do complexo principal de histocompatibilidade (Major Histocompatibility Complex - MHC) e a descriçäo de novos métodos moleculares para a tipificaçäo dos alelos do MHC contribuíram, grandemente, para o entendimento e identificaçäo do extenso polimorfismo do sistema. No entanto, para o näo especialista, essas novas aquisições têm dificultado o entendimento do papel do MHC em associaçäo com as doenças. Assim, neste artigo, foram revisados os conceitos atuais acerca dos genes e moléculas do MHC, os métodos de tipificaçäo desses marcadores de histocompatibilidade e a nomenclatura vigente para os componentes do sistema. Esses aspectos säo extremamente importantes para o entendimento do polimorfismo do MHC, dando embasamento para a compreensäo dos mecanismos propostos de associaçäo desses marcadores com as doenças auto-imunes endócrinas como diabetes mellitus do tipo 1, doença de Graves e tireoidite de Hashimoto, doença de Addison, síndrome poliglandular auto-imune e insuficiência ovariana prematura

Fatores imunogenéticos envolvidos na progressäo para a AIDS / Immunogenetic factors involved in the progression to AIDS

A síndrome da Imunodeficiência Adquirida - AIDS - é uma doença caracterizada pela progressäo para graves infecçöes oportunistas e neoplasias resultantes da progressiva imunossupressäo adquirida após a infecçäo pelo HIV. A variedade de padröes temporais para iniciaçäo e progressäo para a AIDS leva-nos à hipótese da existência de vários fatores desencadeadores da doença