Explicando o significado do WHOQOL-SRPB

BACKGROUND: WHOQOL-SRPB is an instrument developed to evaluate how spirituality, religiosity and personal beliefs (SRPB) are related to quality of life in health and health care. Recently, Moreira-Almeida and Koenig (2006) questioned several aspects concerning WHOQOL-SRPB including de definition of the construct used in the instrument and the fact that its facets are too broad to be considered spirituality and religiosity. The present study is an answer to these questions, based on the clarification of some concepts behind the development of the WHOQOLO-SRPB. OBJECTIVES: To clarify the concepts behind the development of the WHOQOL-SRPB. METHODS: The questions raised by Moreira-Almeida and Koenig (2006) were discussed based on the objectives and conceptual framework of the WHOQOL-SRPB and also on the pertinent literature. RESULTS: 1) WHOQOL-SRPB is not an instrument developed to evaluate SRPB but Quality of Life construct; 2) personal beliefs may function as a strategy to cope with life problems, since they give meaning to human behavior and hypothetically influence quality of life; 3) SRPB is a coherent construct and may be considered an independent construct specially concerning psychological well-being; 4) the concepts included in the WHOQOL project were considered genuine cross-cultural concepts through international consensus and this is one of its major strengths. CONCLUSIONS: WHOQOL-SRPB should be seen as an important contribution to the study of the relationship between quality of life and spirituality, religiosity and personal beliefs.CONTEXTO: O WHOQOL-SRPB é um instrumento que foi desenvolvido para avaliar que forma espiritualidade, religião e crenças pessoais (SRPB, sigla em inglês) estão relacionadas à qualidade de vida (QV) na saúde e na assistência à saúde. Recentemente, Moreira-Almeida e Koenig (2006) questionaram vários aspectos relativos ao WHOQOL-SRPB entre eles a definição do construto utilizado no instrumento, bem como o fato de suas facetas serem muito amplas para serem consideradas espiritualidade e religiosidade. OBJETIVOS: Clarificar os conceitos subjacentes ao desenvolvimento do WHOQOL-SRPB. MÉTODO: As questões levantadas por Moreira-Almeida e Koenig (2006) foram discutidas baseados nos objetivos e marco conceitual do WHOQOL-SRPB, bem como, a literatura pertinente. RESULTADOS: 1) o WHOQOL-SRPB não é um instrumento desenvolvido com o objetivo de avaliar o construto SRPB, mas sim qualidade de vida; 2) crenças pessoais podem funcionar como uma estratégia para se conseguir lidar com os problemas, pois dão significado ao comportamento humano e, hipoteticamente, influenciam a QV; 3) SRPB é um construto coerente e pode ser considerado um construto independente de bem-estar psicológico, 4) os conceitos incluídos no projeto WHOQOL foram considerados genuinamente transculturais por consenso e isso é um de seus pontos fortes mais relevantes. CONCLUSÕES: O WHOQOL-SRPB deve ser visto como uma importante contribuição ao estudo da relação entre qualidade de vida e espiritualidade, religiosidade e crenças pessoais

The Safety and Immunogenicity of GTU®MultiHIV DNA Vaccine Delivered by Transcutaneous and Intramuscular Injection With or Without Electroporation in HIV-1 Positive Subjects on Suppressive ART

International audiencePrevious studies have shown targeting different tissues via the transcutaneous (TC) and intramuscular injection (IM) with or without electroporation (EP) has the potential to trigger immune responses to DNA vaccination. The CUTHIVTHER 001 Phase I/II randomized controlled clinical trial was designed to determine whether the mode of DNA vaccination delivery (TC+IM or EP+IM) could influence the quality and function of induced cellular immune responses compared to placebo, in an HIV positive clade B cohort on antiretroviral therapy (ART). The GTU®MultiHIV B DNA vaccine DNA vaccine encoded a MultiHIV B clade fusion protein to target the cellular response. Overall the vaccine and regimens were safe and well-tolerated. There were robust pre-vaccination IFN-γ responses with no measurable change following vaccination compared to placebo. However, modest intracellular cytokine staining (ICS) responses were seen in the TC+IM group. A high proportion of individuals demonstrated potent viral inhibition at baseline that was not improved by vaccination. These results show that HIV positive subjects with nadir CD4+ counts ≥250 on suppressive ART display potent levels of cellular immunity and viral inhibition, and that DNA vaccination alone is insufficient to improve such responses. These data suggest that more potent prime-boost vaccination strategies are likely needed to improve pre-existing responses in similar HIV-1 cohorts (This study has been registered at http://ClinicalTrials.gov under registration no. NCT02457689)

Interaction of amisulpride with GLUT1 at the blood-brain barrier. Relevance to Alzheimer’s disease

Blood-brain barrier (BBB) dysfunction may be involved in the increased sensitivity of Alzheimer's disease (AD) patients to antipsychotics, including amisulpride. Studies indicate that antipsychotics interact with facilitated glucose transporters (GLUT), including GLUT1, and that GLUT1 BBB expression decreases in AD. We tested the hypotheses that amisulpride (charge: +1) interacts with GLUT1, and that BBB transport of amisulpride is compromised in AD. GLUT1 substrates, GLUT1 inhibitors and GLUT-interacting antipsychotics were identified by literature review and their physicochemical characteristics summarised. Interactions between amisulpride and GLUT1 were studied using in silico approaches and the human cerebral endothelial cell line, hCMEC/D3. Brain distribution of [3H]amisulpride was determined using in situ perfusion in wild type (WT) and 5xFamilial AD (5xFAD) mice. With transmission electron microscopy (TEM) we investigated brain capillary degeneration in WT mice, 5xFAD mice and human samples. Western blots determined BBB transporter expression in mouse and human. Literature review revealed that, although D-glucose has no charge, charged molecules can interact with GLUT1. GLUT1 substrates are smaller (184.95±6.45g/mol) than inhibitors (325.50±14.40g/mol) and GLUT-interacting antipsychotics (369.38±16.04). Molecular docking showed beta-D-glucose (free energy binding: -15.39kcal/mol) and amisulpride (-29.04kcal/mol) interact with GLUT1. Amisulpride did not affect [14C]D-glucose hCMEC/D3 accumulation. [3H]amisulpride uptake into the brain (except supernatant) of 5xFAD mice compared to WT remained unchanged. TEM revealed brain capillary degeneration in human AD. There was no difference in GLUT1 or P-glycoprotein BBB expression between WT and 5xFAD mice. In contrast, caudate P-glycoprotein, but not GLUT1, expression was decreased in human AD capillaries versus controls. This study provides new details about the BBB transport of amisulpride, evidence that amisulpride interacts with GLUT1 and that BBB transporter expression is altered in AD. This suggests that antipsychotics could potentially exacerbate the cerebral hypometabolism in AD. Further research into the mechanism of amisulpride transport by GLUT1 is important for improving antipsychotics safety

Health, education, and social care provision after diagnosis of childhood visual disability

Aim: To investigate the health, education, and social care provision for children newly diagnosed with visual disability.Method: This was a national prospective study, the British Childhood Visual Impairment and Blindness Study 2 (BCVIS2), ascertaining new diagnoses of visual impairment or severe visual impairment and blindness (SVIBL), or equivalent vi-sion. Data collection was performed by managing clinicians up to 1-year follow-up, and included health and developmental needs, and health, education, and social care provision.Results: BCVIS2 identified 784 children newly diagnosed with visual impairment/SVIBL (313 with visual impairment, 471 with SVIBL). Most children had associated systemic disorders (559 [71%], 167 [54%] with visual impairment, and 392 [84%] with SVIBL). Care from multidisciplinary teams was provided for 549 children (70%). Two-thirds (515) had not received an Education, Health, and Care Plan (EHCP). Fewer children with visual impairment had seen a specialist teacher (SVIBL 35%, visual impairment 28%, χ2p < 0.001), or had an EHCP (11% vs 7%, χ2p < 0 . 01).Interpretation: Families need additional support from managing clinicians to access recommended complex interventions such as the use of multidisciplinary teams and educational support. This need is pressing, as the population of children with visual impairment/SVIBL is expected to grow in size and complexity.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited

Prevalence of malaria and helminth infections in rural communities in northern Sierra Leone, a baseline study to inform Ebola vaccine study protocols.

INTRODUCTION: Recurrent parasitic infections may influence the immune response to vaccines. In the Partnership for Research on Ebola VACcinations extended follow-UP and clinical research capacity build-UP (PREVAC-UP) study being undertaken in Mambolo, northern Sierra Leone, participants are being followed up to assess the potential impact of exposure to malaria and/or helminth infections on long-term immune response to two Ebola vaccines. To support the development of the assays that will be used in this evaluation, a parasitological survey was conducted in Mambolo between November 2019 and February 2020. METHODS: Healthy individuals aged ≥1 year who were resident in Mambolo Chiefdom were selected using a stratified sampling approach and questionnaires were administered to explore their sociodemographic characteristics. Microscopy was used to detect malaria parasites, intestinal helminths and urinary schistosome infections. Rapid blood tests were used to detect infections with Onchocerca volvulus and Wuchereria bancrofti. We estimated the overall prevalence of these infections and used adjusted logistic regression models to explore risk factors for malaria and hookworm infection. RESULTS: Eight hundred and fifteen (815) residents, 50.9% of whom were female were surveyed. Overall, 309 (39.1%) of 791 persons tested for malaria had a positive blood slide; Plasmodium falciparum was the dominant species. Helminth infection was detected in 122 (15.0%) of 815 stool samples including three mixed infections. The helminth infections comprised 102 (12.5%) cases of hookworm, 11 (1.3%) cases of Trichuris trichiura, 10 (1.2%) cases of Schistosoma mansoni and two (0.2%) cases of Ascaris lumbricoides. Being male (OR = 2.01, 95% CI 1.15-3.50) and residing in a non-riverine community (OR = 4.02, 95%CI 2.32-6.98) were the factors associated with hookworm infection. Onchocerca volvulus and Wuchereria bancrofti infections were found in 3.3% and 0.4% of participants respectively. CONCLUSION: Malaria and hookworm are the most prevalent parasite infections and those most likely to influence long-term immune response to Ebola vaccines among the trial participants

Interaction of amisulpride with GLUT1 at the blood-brain barrier. Relevance to Alzheimer's disease

Blood-brain barrier (BBB) dysfunction may be involved in the increased sensitivity of Alzheimer's disease (AD) patients to antipsychotics, including amisulpride. Studies indicate that antipsychotics interact with facilitated glucose transporters (GLUT), including GLUT1, and that GLUT1 BBB expression decreases in AD. We tested the hypotheses that amisulpride (charge: +1) interacts with GLUT1, and that BBB transport of amisulpride is compromised in AD. GLUT1 substrates, GLUT1 inhibitors and GLUT-interacting antipsychotics were identified by literature review and their physicochemical characteristics summarised. Interactions between amisulpride and GLUT1 were studied using in silico approaches and the human cerebral endothelial cell line, hCMEC/D3. Brain distribution of [3H]amisulpride was determined using in situ perfusion in wild type (WT) and 5xFamilial AD (5xFAD) mice. With transmission electron microscopy (TEM) we investigated brain capillary degeneration in WT mice, 5xFAD mice and human samples. Western blots determined BBB transporter expression in mouse and human. Literature review revealed that, although D-glucose has no charge, charged molecules can interact with GLUT1. GLUT1 substrates are smaller (184.95±6.45g/mol) than inhibitors (325.50±14.40g/mol) and GLUT-interacting antipsychotics (369.38±16.04). Molecular docking showed beta-D-glucose (free energy binding: -15.39kcal/mol) and amisulpride (-29.04kcal/mol) interact with GLUT1. Amisulpride did not affect [14C]D-glucose hCMEC/D3 accumulation. [3H]amisulpride uptake into the brain (except supernatant) of 5xFAD mice compared to WT remained unchanged. TEM revealed brain capillary degeneration in human AD. There was no difference in GLUT1 or P-glycoprotein BBB expression between WT and 5xFAD mice. In contrast, caudate P-glycoprotein, but not GLUT1, expression was decreased in human AD capillaries versus controls. This study provides new details about the BBB transport of amisulpride, evidence that amisulpride interacts with GLUT1 and that BBB transporter expression is altered in AD. This suggests that antipsychotics could potentially exacerbate the cerebral hypometabolism in AD. Further research into the mechanism of amisulpride transport by GLUT1 is important for improving antipsychotics safety

Prevalence of malaria and helminth infections in rural communities in northern Sierra Leone, a baseline study to inform Ebola vaccine study protocols. S1 Data

Data for: "Prevalence of malaria and helminth infections in rural communities in northern Sierra Leone, a baseline study to inform Ebola vaccine study protocols"