Transactivator of Transcription (Tat)-Induced Neuroinflammation as a Key Pathway in Neuronal Dysfunction: A Scoping Review.

The activity of HIV-1 and its viral proteins within the central nervous system (CNS) is responsible for a wide array of neuropathological effects, resulting in a spectrum of neurocognitive deficits defined as HIV-associated neurocognitive disorders (HAND). Amongst the various viral proteins, the transactivator of transcription (Tat) remains detectable even with effective antiretroviral therapy (ART) and suppressed viremia, highlighting the significance of this protein in the modern ART era. Tat has been extensively researched in both fundamental and clinical settings due to its role in neuroinflammation, neuronal damage, and neurocognitive impairment amongst people living with HIV (PLHIV). To date, numerous fundamental studies have explored Tat-induced neuroinflammation. However, there is no clear consensus on the most frequently studied inflammatory markers or the consistency in the levels of these Tat-induced inflammatory marker levels across different studies. Therefore, we conducted a scoping review of studies investigating Tat-induced neuroinflammation. We conducted searches in PubMed, Scopus, and Web of Science databases using a search protocol tailored specifically to adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews (PRISMA-ScR) guidelines. From the 22 included studies, findings suggest that the HIV-1 Tat protein amplifies levels of neuroinflammatory markers. Amongst the vast array of inflammatory markers explored in the included studies, consistent results point to higher levels of CCL2, IL-6, IL-8, and TNF-α in primary cells and cell lines exposed to or transfected with HIV-1 Tat. These markers are regulated by key inflammatory pathways, such as the extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein kinase (MAPK) pathway, the phosphatidylinositol 3-kinase (PI3K) pathway, the p38 MAPK pathway, and nuclear factor-kB (NF-kB). Furthermore, Tat has been shown to induce neuronal apoptosis, both directly and indirectly. With regards to study designs, utilizing full-length Tat101 at concentrations ranging from 100 to 1000 ng/ml and durations of 24 and 48 h appears optimal for investigating Tat-induced neuroinflammation. In this context, we highlight specific inflammatory markers and pathways that are potentially pivotal in Tat-induced neuroinflammation and subsequent neuronal damage. A deeper investigation into these markers and pathways is crucial to better understand their roles in the development of HAND.

Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review.

HIV-associated neurocognitive disorders (HAND) are the result of the activity of HIV-1 within the central nervous system (CNS). While the introduction of antiretroviral therapy (ART) has significantly reduced the occurrence of severe cases of HAND, milder cases still persist. The persistence of HAND in the modern ART era has been linked to a chronic dysregulated inflammatory profile. There is increasing evidence suggesting a potential role of Viral protein R (Vpr) in dysregulating the neuroinflammatory processes in people living with HIV (PLHIV), which may contribute to the development of HAND. Since the role of Vpr in neuroinflammatory mechanisms has not been clearly defined, we conducted a scoping review of fundamental research studies on this topic. The review aimed to assess the size and scope of available research literature on this topic and provide commentary on whether Vpr contributes to neuroinflammation, as highlighted in fundamental studies. Based on the specified selection criteria, 10 studies (6 of which were cell culture-based and 4 that included both animal and cell culture experiments) were eligible for inclusion. The main findings were that (1) Vpr can increase neuroinflammatory markers, with studies consistently reporting higher levels of TNF-α and IL-8, (2) Vpr induces (neuro)inflammation via specific pathways, including the PI3K/AKT, p38-MAPk, JNK-SAPK and Sur1-Trpm4 channels in astrocytes and the p38 and JNK-SAPK in myeloid cells, and (3) Vpr-specific protein amino acid signatures (73R, 77R and 80A) may play an important role in exacerbating neuroinflammation and the neuropathophysiology of HAND. Therefore, Vpr should be investigated for its potential contribution to neuroinflammation in the development of HAND.

The metabolic consequences of HIV/TB co-infection.

BACKGROUND: The synergy between the human immunodeficiency virus (HIV) and Mycobacterium tuberculosis during co-infection of a host is well known. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms that contribute to the associated disease burden experienced during HIV/tuberculosis (TB) co-infection remain poorly understood. Furthermore, while anti-HIV treatments suppress viral replication, these therapeutics give rise to host metabolic disruption and adaptations beyond that induced by only infection or disease. METHODS: In this study, the serum metabolic profiles of healthy controls, untreated HIV-negative TB-positive patients, untreated HIV/TB co-infected patients, and HIV/TB co-infected patients on antiretroviral therapy (ART), were measured using two-dimensional gas chromatography time-of-flight mass spectrometry. Since no global metabolic profile for HIV/TB co-infection and the effect of ART has been published to date, this pilot study aimed to elucidate the general areas of metabolism affected during such conditions. RESULTS: HIV/TB co-infection induced significant changes to the host's lipid and protein metabolism, with additional microbial product translocation from the gut to the blood. The results suggest that HIV augments TB synergistically, at least in part, contributing to increased inflammation, oxidative stress, ART-induced mitochondrial damage, and its detrimental effects on gut health, which in turn, affects energy availability. ART reverses these trends to some extent in HIV/TB co-infected patients but not to that of healthy controls. CONCLUSION: This study generated several new hypotheses that could direct future metabolic studies, which could be combined with other research techniques or methodologies to further elucidate the underlying mechanisms of these changes.

Tuberculous Granuloma: Emerging Insights From Proteomics and Metabolomics.

Mycobacterium tuberculosis infection, which claims hundreds of thousands of lives each year, is typically characterized by the formation of tuberculous granulomas - the histopathological hallmark of tuberculosis (TB). Our knowledge of granulomas, which comprise a biologically diverse body of pro- and anti-inflammatory cells from the host immune responses, is based mainly upon examination of lungs, in both human and animal studies, but little on their counterparts from other organs of the TB patient such as the brain. The biological heterogeneity of TB granulomas has led to their diverse, relatively uncoordinated, categorization, which is summarized here. However, there is a pressing need to elucidate more fully the phenotype of the granulomas from infected patients. Newly emerging studies at the protein (proteomics) and metabolite (metabolomics) levels have the potential to achieve this. In this review we summarize the diverse nature of TB granulomas based upon the literature, and amplify these accounts by reporting on the relatively few, emerging proteomics and metabolomics studies on TB granulomas. Metabolites (for example, trimethylamine-oxide) and proteins (such as the peptide PKAp) associated with TB granulomas, and knowledge of their localizations, help us to understand the resultant phenotype. Nevertheless, more multidisciplinary 'omics studies, especially in human subjects, are required to contribute toward ushering in a new era of understanding of TB granulomas - both at the site of infection, and on a systemic level.

Metabolomics as a Tool to Investigate HIV/TB Co-Infection.

The HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and tuberculosis (TB) pandemics are perpetuated by a significant global burden of HIV/TB co-infection. The synergy between HIV and Mycobacterium tuberculosis (Mtb) during co-infection of a host is well established. While this synergy is known to be driven by immunological deterioration, the metabolic mechanisms thereof remain poorly understood. Metabolomics has been applied to study various aspects of HIV and Mtb infection separately, yielding insights into infection- and treatment-induced metabolic adaptations experienced by the host. Despite the contributions that metabolomics has made to the field, this approach has not yet been systematically applied to characterize the HIV/TB co-infected state. Considering that limited HIV/TB co-infection metabolomics studies have been published to date, this review briefly summarizes what is known regarding the HIV/TB co-infection synergism from a conventional and metabolomics perspective. It then explores metabolomics as a tool for the improved characterization of HIV/TB co-infection in the context of previously published human-related HIV infection and TB investigations, respectively as well as for addressing the gaps in existing knowledge based on the similarities and deviating trends reported in these HIV infection and TB studies.

Metabolomics as an Approach to Characterise the Contrasting Roles of CCR5 in the Presence and Absence of Disease.

Chemokine receptors such as C-C chemokine receptor 5 (CCR5) are activated through interaction with their ligands and are well known for their role in chemotaxis and signal transduction. While serving these roles, cellular responses are effected, hence the immune function of these molecules is established. Given the role of CCR5 in immune function and that the immune and metabolic systems are interlinked, subsequent immune-directed changes should be measurable at a metabolic level. Numerous investigations have reported on metabolic changes associated with CCR5 status in the presence of disease, so as to understand whether specific CCR5 genotypes, frequency and/or levels offer protection to the host or not. However, these metabolic changes were recorded using older conventional techniques. Depending on certain factors such as the disease model, the geography of the samples and/or the ethnic group under study, the role of CCR5 in disease differs. In addition, little is known about CCR5's role in the absence of an enhanced inflammatory state, such as when infection persists. Metabolomics is defined as the study of metabolites and informs on metabolic changes within living organisms as induced by various stimuli, such as the interaction of CCR5 with its ligand. Since metabolomics reflects the underlying biochemical activity and state of cells/tissues, this review proposes it as a tool to clarify the contrasting roles of CCR5.

Relationship of In Vivo MR Parameters to Histopathological and Molecular Characteristics of Newly Diagnosed, Nonenhancing Lower-Grade Gliomas.

The goal of this research was to elucidate the relationship between WHO 2016 molecular classifications of newly diagnosed, nonenhancing lower grade gliomas (LrGG), tissue sample histopathology, and magnetic resonance (MR) parameters derived from diffusion, perfusion, and 1H spectroscopic imaging from the tissue sample locations and the entire tumor. A total of 135 patients were scanned prior to initial surgery, with tumor cellularity scores obtained from 88 image-guided tissue samples. MR parameters were obtained from corresponding sample locations, and histograms of normalized MR parameters within the T2 fluid-attenuated inversion recovery lesion were analyzed in order to evaluate differences between subgroups. For tissue samples, higher tumor scores were related to increased normalized apparent diffusion coefficient (nADC), lower fractional anisotropy (nFA), lower cerebral blood volume (nCBV), higher choline (nCho), and lower N-acetylaspartate (nNAA). Within the T2 lesion, higher tumor grade was associated with higher nADC, lower nFA, and higher Cho to NAA index. Pathological analysis confirmed that diffusion and metabolic parameters increased and perfusion decreased with tumor cellularity. This information can be used to select targets for tissue sampling and to aid in making decisions about treating residual disease.

HIV/HAART-associated oxidative stress is detectable by metabonomics.

Chronic human immunodeficiency virus (HIV) infection, separately and in combination with highly active antiretroviral therapy (HAART) is closely associated with oxidative stress (OS). Most studies demonstrating redox imbalances in HIV-infected individuals have done so using conventional biochemical methodologies. The limited simultaneous detection of multiple OS markers within one sample is a major drawback of these methodologies and can be addressed through the use of metabonomics. HIV-metabonomic studies utilizing biofluids from HAART cohorts as the investigative source, are on the increase. Data from many of these studies identified metabolic markers indicative of HIV-induced OS, usually as an outcome of an untargeted metabonomics study. Untargeted studies cast a wide net for any and all detectable metabolites in complex mixtures. Given the prevalence of OS during HIV infection and antiviral treatment, it is perhaps not surprising that indicators of this malady would become evident during metabolite identification. At times, targeted studies for specific (non-OS) metabolites would also yield OS markers as an outcome. This review examines the findings of these studies by first providing the necessary background information on OS and the main ways in which free radicals/reactive oxygen species (ROS) produced during OS, cause biomolecular damage. This is followed by information on the biomarkers which come about as a result of free radical damage and the techniques used for assaying these stress indicators. The established links between elevated ROS and lowered antioxidants during HIV infection and the subsequent use of HAART is then presented followed by a review of the OS markers detected in HIV metabonomic studies to date. We identify gaps in HIV/HAART-associated OS research and finally suggest how these research gaps can be addressed through metabonomic analysis, specifically targeting the multiple markers of HIV-induced OS.

Nivel de conocimiento de los licenciados en Enfermería del municipio Boyeros sobre el Programa Materno - Infantil / Level of knowledge of Nursing graduates of municipality Boyeros about Program on Maternal - Child

Introducción: la necesidad de afecto, compañía y de contar con alguien en el momento de ser madre, se ha manifestado a través desde la antigüedad a través de la historia. Objetivo: identificar el nivel de conocimiento de los licenciados en Enfermería sobre el Programa Materno-Infantil en el municipio Boyeros, desde octubre de 2014 hasta junio de 2015. Métodos: el universo estuvo constituido por 312 licenciados en enfermería de la atención primaria y secundaria de salud pertenecientes al municipio Boyeros. Se seleccionó una muestra de 90 licenciados en enfermería de manera intencional. Los métodos y procedimientos utilizados tuvieron un enfoque cuanticualitativo, se aplicaron entrevistas semi-estructurada a 30 directivos y se seleccionaron 20 informantes claves con la técnica cara a cara, se revisó documentación del Plan de Estudio de la carrera en Licenciatura en Enfermería, Programa de la asignatura y Carpeta Metodológica de Enfermería Materno-Infantil Finalmente se realizó la triangulación metodológica, que permitió la identificación información necesaria para identificar las necesidades de aprendizaje y el nivel de conocimientos de los licenciados en Enfermería, la cual fue validada por un grupo de expertos de la especialidad. Resultados: el total de los entrevistados y encuestados plantearon la necesidad de ampliar el sistema de Superación Profesional por medio de Diseño como forma de Superación Profesional Específicos de Enfermería. Conclusiones: el nivel de conocimientos de los licenciados en Enfermería que laboran en el servicio materno-infantil de la atención primaria y secundaria acerca del Programa Materno-Infantil como bajo en temas específicos de la especialidad(AU)

Metabolic Profiling of IDH Mutation and Malignant Progression in Infiltrating Glioma.

Infiltrating low grade gliomas (LGGs) are heterogeneous in their behavior and the strategies used for clinical management are highly variable. A key factor in clinical decision-making is that patients with mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) oncogenes are more likely to have a favorable outcome and be sensitive to treatment. Because of their relatively long overall median survival, more aggressive treatments are typically reserved for patients that have undergone malignant progression (MP) to an anaplastic glioma or secondary glioblastoma (GBM). In the current study, ex vivo metabolic profiles of image-guided tissue samples obtained from patients with newly diagnosed and recurrent LGG were investigated using proton high-resolution magic angle spinning spectroscopy (1H HR-MAS). Distinct spectral profiles were observed for lesions with IDH-mutated genotypes, between astrocytoma and oligodendroglioma histologies, as well as for tumors that had undergone MP. Levels of 2-hydroxyglutarate (2HG) were correlated with increased mitotic activity, axonal disruption, vascular neoplasia, and with several brain metabolites including the choline species, glutamate, glutathione, and GABA. The information obtained in this study may be used to develop strategies for in vivo characterization of infiltrative glioma, in order to improve disease stratification and to assist in monitoring response to therapy.

Factores que influyen en la orientación vocacional de estudiantes en Enfermería. Facultad de Ciencias Médicas "Enrique Cabrera" / Aspects that contribute to the vocational guidance of nursing students. Faculty of Medical Sciences "Enrique Cabrera" / Fatores que influenciam a orientação profissional dos alunos em enfermagem. Faculdade de Ciências Médicas. "Enrique Cabrera"

Introducción: En la actualidad, existen varias teorías que fomentan el desarrollo epistemológico de la ciencia de Enfermería. Profesionales comprometidos en la formación de los recursos humanos en Enfermería, han rediseñado los planes de estudio existentes, para establecer una profesión de excelencia. Objetivo. Identificar los factores que influyen en la orientación vocacional de estudiantes en Enfermería, primer año noveno grado. Método. Se realizó un estudio descriptivo de corte transversal en la Facultad de Ciencias Médicas "Enrique Cabrera", Municipio Boyeros, La Habana, Cuba, en el periodo comprendido de octubre 2014 a junio de 2015. La población estuvo constituida por los 120 estudiantes de primer año de la carrera de Técnicos en Enfermería primer año noveno grado; la muestra se obtuvo mediante el muestreo aleatorio simple con 60 estudiantes, a los cuales se les aplicó una encuesta para la recogida de la información con previo consentimiento informado. Se aplicaron métodos teóricos: análisis-síntesis, inducción-deducción; empíricos: encuesta a estudiantes y estadísticos para la obtención, el procesamiento y análisis de los resultados. Resultados. El 71.1% de los estudiantes obtuvo información acerca de la carrera a través de la familia, el 53.3% presentó un bajo nivel de conocimientos sobre las actividades de orientación vocacional, el 33.3% refirió como motivo para elegir la carrera el gusto por ayudar a las personas. Conclusiones. Se concluye que la familia constituye la vía fundamental por la que los estudiantes obtienen información sobre la carrera de Enfermería, además se constata un bajo nivel de conocimientos en cuanto a las actividades de orientación vocacional. Se identificaron como motivos fundamentales para elegir la carrera el gusto por ayudar a las personas

Introduction: Currently, there are several theories that promote the development of science epistemological Nursing. Professionals engaged in the training of human resources in nursing, have redesigned the existing curricula, to establish a career of excellence. Objective. Identify the factors influencing vocational guidance of students in Nursing, first ninth grade year. Method. A descriptive study of transversal cut was made at the Faculty of Medical Sciences "Enrique Cabrera" Municipality Boyeros, Havana, in the period from October 2014 to June 2015. The study population consisted of 120 freshmen of Nursing career Technical freshmanninth grade; the sample was obtained by simple random sampling with 60 students, which was applied a survey to collect information prior informed consent. theoretical methods were applied: analysis-synthesis, induction-deduction; Empirical: student survey and statistics for the collection, processing analysis results. Results. 71.1% of students obtained information about the race through the family, 53.3% had a low level of knowledge about the activities of vocational guidance, 33.3% he reported as a reason to choose the race taste for help people. Conclusions. Se concludes that the family is the fundamental way in which students get information about nursing career, plus a low level of knowledge is found in terms of orientation activities vocacional.Se identified as key reasons for choosing the race taste for helping people

Introdução: Atualmente, existem várias teorias que promovam o desenvolvimento de Enfermagem de ciência epistemológica. Profissionais que trabalham na formação de recursos humanos em enfermagem, ter redesenhado o currículo existente, estabelecer uma carreira de excelência.Target. Identificar os fatores que influenciam a orientação profissional dos alunos em Enfermagem, primeiro ano da nona série. Métodos. Um estudo descritivo de corte transversal foi feito na Faculdade de Ciências Médicas "Enrique Cabrera" município Boyeros, em Havana, no período de outubro de 2014 a junho de 2015. A população do estudo consistiu de 120 calouros de carreira de enfermagem calouro técnico nona série; a amostra foi obtida por amostragem aleatória simples com 60 alunos, o que foi aplicada uma pesquisa para coletar informações consentimento prévio informado. Foram aplicados métodos teóricos: análise-síntese, de indução de dedução; Empírica: pesquisa do aluno e estatísticas para a recolha, tratamento resultados da análise. Resultados. 71,1% dos alunos obtiveram informações sobre a corrida através da família, 53,3% tinham um baixo nível de conhecimento sobre as atividades de orientação profissional, 33,3% relatou como uma razão para escolher o sabor de corrida para obter ajuda pessoas. Conclusões. Se conclui que a família é o caminho fundamental em que os estudantes obter informações sobre a carreira de enfermagem, além de um baixo nível de conhecimento é encontrado em termos de atividades de orientação vocacional.Se identificado como principais razões para a escolha da raça gosto de ajudar as pessoas

Efectos nocivos de la contaminación ambiental sobre la embarazada / Harmful effects of environmental pollution on pregnant women

Este trabajo se basa esencialmente en el análisis de los efectos nocivos de la contaminación ambiental en las embarazadas. Se mencionan los factores que influyen en la calidad de vida relacionados con los problemas ambientales, y se proponen algunas medidas que puedan contribuir a la disminución de los efectos nocivos y la morbimortalidad materno-fetal. Se han tenido en cuenta materiales bibliográficos actualizados y el protocolo de intervención nacional materno-infantil. Los análisis expuestos confirman la necesidad de desarrollar acciones de prevención conjuntas entre las diversas instituciones, empresas y comunidad, con la finalidad de eliminar o disminuir los factores de riesgo ambiental adversos a la salud de las embarazadas(AU)

This work is essentially based on the analysis of harmful effects of environmental pollution on pregnant women. Factors that influence on quality of life in relation to environmental problems are related and some measures that can help reduce harmful effects and mother-fetal morbimortality are suggested. Updated bibliographic materials have been considered as well as the mother-child national intervention protocol. The analysis made confirm the need to develop joint prevention actions among different institutions, companies and community with the aim of eliminating or reducing environmental risk factors adverse to the health of pregnant women(AU)

Efectos nocivos de la contaminación ambiental sobre la embarazada / Harmful effects of environmental pollution on pregnant women

Este trabajo se basa esencialmente en el análisis de los efectos nocivos de la contaminación ambiental en las embarazadas. Se mencionan los factores que influyen en la calidad de vida relacionados con los problemas ambientales, y se proponen algunas medidas que puedan contribuir a la disminución de los efectos nocivos y la morbimortalidad materno-fetal. Se han tenido en cuenta materiales bibliográficos actualizados y el protocolo de intervención nacional materno-infantil. Los análisis expuestos confirman la necesidad de desarrollar acciones de prevención conjuntas entre las diversas instituciones, empresas y comunidad, con la finalidad de eliminar o disminuir los factores de riesgo ambiental adversos a la salud de las embarazadas.

This work is essentially based on the analysis of harmful effects of environmental pollution on pregnant women. Factors that influence on quality of life in relation to environmental problems are related and some measures that can help reduce harmful effects and mother-fetal morbimortality are suggested. Updated bibliographic materials have been considered as well as the mother-child national intervention protocol. The analysis made confirm the need to develop joint prevention actions among different institutions, companies and community with the aim of eliminating or reducing environmental risk factors adverse to the health of pregnant women.

Metabonomic analysis of HIV-infected biofluids.

Monitoring the progression of HIV infection to full-blown acquired immune deficiency syndrome (AIDS) and assessing responses to treatment will benefit greatly from the identification of novel biological markers especially since existing clinical indicators of disease are not infallible. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are powerful methodologies used in metabonomic analyses for an approximation of HIV-induced changes to the phenotype of an infected individual. Although early in its application to HIV/AIDS, (biofluid) metabonomics has already identified metabolic pathways influenced by both HIV and/or its treatment. To date, biofluid NMR and MS data show that the virus and highly active antiretroviral treatment (HAART) mainly influence carbohydrate and lipid metabolism, suggesting that infected individuals are susceptible to very specific metabolic complications. A number of well-defined biofluid metabonomic studies clearly distinguished HIV negative, positive and treatment experienced patient profiles from one another. While many of the virus or treatment affected metabolites have been identified, the metabonomics measurements were mostly qualitative. The identities of the molecules were not always validated neither were the statistical models used to distinguish between groups. Assigning particular metabolic changes to specific drug regimens using metabonomics also remains to be done. Studies exist where identified metabolites have been linked to various disease states suggesting great potential for the use of metabonomics in disease prognostics. This review therefore examines the field of metabonomics in the context of HIV/AIDS, comments on metabolites routinely detected as being affected by the pathogen or treatment, explains what existing data suggest and makes recommendations on future research.

The Th1/Th2/Th17 cytokine profile of HIV-infected individuals: a multivariate cytokinomics approach.

HIV infection causes the dysregulation of cytokine production. A cytokinomics approach employing cytometric bead array (CBA) technology, flow cytometry and multivariate analysis was applied to the investigation of HIV-induced T helper cell type 1 (Th1), Th2 and Th17 cytokine changes in the sera of treatment naive individuals. Stepwise linear discriminant analysis (LDA) and logistic regression identified interleukin (IL)-6 to be discriminatory for HIV infection with 74.6% and 71.2% of the cases correctly classified. Analysis of variance (ANOVA) confirmed IL-6 and IL-10 concentrations to be significantly (p=0.001 and p=0.025) different between the groups. A scatter plot of the log IL-6 and IL-10 concentrations for the groups largely overlapped, with improved differentiation where patients were advancing to the acquired immunodeficiency syndrome (AIDS). IL-17A levels were higher than other cytokines but did not significantly distinguish the groups suggesting that the HIV- and HIV+ individuals had similar immune profiles. This possibility was supported by other clinical indicators. Taken together, the measured cytokines (IL-6, 10 and 17) have potential prognostic value.