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BACKGROUND: The COVID-19 pandemic (March 2020-May 2023) had a profound effect around the world with vulnerable people being particularly affected, including worsening existing health inequalities. This article explores the impact of the pandemic on health services for First Nations people living with HIV (FN-PWLE) in Manitoba, Canada. This study investigated perceptions of both health care providers and FN-PWLE through qualitative interviews occurring between July 2020 and February 2022 to understand their experience and identify lessons learned that could be translated into health system changes. METHODS: Using a qualitative, participatory-action, intentional decolonizing approach for this study we included an Indigenous knowledge keeper and Indigenous research associates with lived experience as part of the study team. A total of twenty-five [25] in-depth semi-structured interviews were conducted with eleven healthcare providers (HCPs) and fourteen First Nation people with lived HIV experience (FN-PWLE). In total, 18/25 or 72% of the study participants self-identified as First Nation people. RESULTS: The COVID-19 pandemic negatively impacted health services access for FN-PWLE, a) disrupted relationships between FN-PWLE and healthcare providers, b) disrupted access to testing, in-person appointments, and medications, and c) intersectional stigma was compounded. Though, the COVID-19 pandemic also led to positive effects, including the creation of innovative solutions for the health system overall. CONCLUSIONS: The COVID-19 pandemic exaggerated pre-existing barriers and facilitators for Manitoba FN-PWLE accessing and using the healthcare system. COVID-19 impacted health system facilitators such as relationships and supports, particularly for First Nation people who are structurally disadvantaged and needing more wrap-around care to address social determinants of health. Innovations during times of crisis, included novel ways to improve access to care and medications, illustrated how the health system can quickly provide solutions to long-standing barriers, especially for geographical barriers. Lessons learned from the COVID-19 pandemic should be considered for improvements to the health system's HIV cascade of care for FN-PWLE and other health system improvements for First Nations people with other chronic diseases and conditions. Finally, this study illustrates the value of qualitative and First Nation decolonizing research methods. Further studies are needed, working together with First Nations organizations and communities, to apply these recommendations and innovations to change health care and people's lives.
Subject(s)
COVID-19 , HIV Infections , Humans , Manitoba/epidemiology , Pandemics , COVID-19/epidemiology , Canada , Indigenous Peoples , HIV Infections/epidemiology , HIV Infections/therapyABSTRACT
Gardnerella species are associated with bacterial vaginosis (BV) and have been investigated as etiological agents of the condition. Nonetheless, the isolation of this taxon from healthy individuals has raised important questions regarding its etiological role. Recently, using advanced molecular approaches, the Gardnerella genus was expanded to include several different species that exhibit differences in virulence potential. Understanding the significance of these different species with respect to mucosal immunity and the pathogenesis and complications of BV could be crucial to solving the BV enigma. Here, we review key findings regarding the unique genetic and phenotypic diversity within this genus, virulence factors, and effects on mucosal immunity as they stand. We also comment on the relevance of these findings to the proposed role of Gardnerella in BV pathogenesis and in reproductive health and identify key gaps in knowledge that should be explored in the future.
Subject(s)
Vaginosis, Bacterial , Humans , Female , Vaginosis, Bacterial/microbiology , Gardnerella , Immunity, Mucosal , Virulence Factors/genetics , Gardnerella vaginalis/genetics , Vagina/microbiologyABSTRACT
BACKGROUND: The microbiota of the lower female genital tract plays an important role in women's health. Microbial profiling using the chaperonin60 (cpn60) universal target (UT) improves resolution of vaginal species associated with negative health outcomes compared to the more commonly used 16S ribosomal DNA target. However, the choice of DNA extraction and PCR product purification methods may bias sequencing-based microbial studies and should be optimized for the sample type and molecular target used. In this study, we compared two commercial DNA extraction kits and two commercial PCR product purification kits for the microbial profiling of cervicovaginal samples using the cpn60 UT. METHODS: DNA from cervicovaginal secretions and vaginal lavage samples as well as mock community standards were extracted using either the specialized QIAamp DNA Microbiome Kit, or the standard DNeasy Blood & Tissue kit with enzymatic pre-treatment for enhanced lysis of gram-positive bacteria. Extracts were PCR amplified using well-established cpn60 primer sets and conditions. Products were then purified using a column-based method (QIAquick PCR Purification Kit) or a gel-based PCR clean-up method using the QIAEX II Gel Extraction Kit. Purified amplicons were sequenced with the MiSeq platform using standard procedures. The overall quality of each method was evaluated by measuring DNA yield, alpha diversity, and microbial composition. RESULTS: DNA extracted from cervicovaginal samples using the DNeasy Blood and Tissue kit, pre-treated with lysozyme and mutanolysin, resulted in increased DNA yield, bacterial diversity, and species representation compared to the QIAamp DNA Microbiome kit. The column-based PCR product purification approach also resulted in greater average DNA yield and wider species representation compared to a gel-based clean-up method. In conclusion, this study presents a fast, effective sample preparation method for high resolution cpn60 based microbial profiling of cervicovaginal samples.
Subject(s)
DNA/isolation & purification , Specimen Handling/methods , Vagina/microbiology , Bacteria/genetics , DNA, Bacterial/genetics , Female , Humans , Microbiota/genetics , Nucleic Acid Amplification Techniques , Polymerase Chain Reaction/methods , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA/methodsABSTRACT
Among bilinguals, language-related variables such as first and second language proficiency and balance may be related to important cognitive and academic outcomes, but approaches to characterizing these variables are inconsistent, particularly among at-risk samples of children. The current study employed comprehensive language assessment of English and Spanish language skills and contrasted various approaches to the characterization of language among at-risk ELs in middle school (N = 161). Specifically, we contrasted variable-centered and person-centered approaches, and convergence between objective and self-report measures. Findings support a two-factor structure of English and Spanish language skills in this population, three profiles of students (balanced, moderately unbalanced-higher Spanish, and very unbalanced-higher English), convergence between variable-centered and person-centered approaches, and mixed support for subjective indices of usage. Results provide a foundation from which to examine the roles of L1 and L2 proficiency as well as balance in important cognitive and academic outcomes in this at-risk and understudied population.
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Most cervicovaginal microbiome-immunology studies to date have relied on 16S rDNA microbial profiling which does not resolve the molecular subgroups of Gardnerella, believed to be central to the pathogenesis of bacterial vaginosis (BV) and subsequent risk of HIV acquisition. Here we used the cpn60 universal target which in addition to other microbial taxa, resolves four Gardnerella subgroups, for cervicovaginal microbial profiling in a longitudinal cohort of Kenyan women to examine associations with cellular and soluble markers of inflammation and HIV susceptibility. Participants (N = 41) were sampled, contributing 362 samples for microbiome analysis. All non-Lactobacillus dominant microbial communities were associated with high pro-inflammatory cytokine levels. Divergent associations were observed among different Gardnerella subgroup dominated communities with respect to the chemokine IP-10. Specifically, Gardnerella subgroup A dominant and polymicrobial communities were associated with reduced concentrations of IP-10 in adjusted linear mixed models (p<0.0001), compared to microbial communities dominated by Lactobacillus (non-iners) species. However, these associations did not translate to significant differences in the proportion or absolute number of CCR5, HLA-DR and CD38 expressed on cervical CD4+ T- cells. These findings suggest that some associations between Gardnerella subgroup dominant microbiomes and mucosal immunity differ and are relevant for the study of BV-pathogenesis and understanding the mechanisms of BV-associated HIV risk.
Subject(s)
Gardnerella , Microbiota , Vaginosis, Bacterial , Female , Humans , Chemokine CXCL10 , HIV Infections , Immunity , Kenya/epidemiology , Lactobacillus/genetics , Vagina/immunology , Vagina/microbiologyABSTRACT
Attention is correlated with reading, but the extent to which behavioral ratings and sustained attention relate to reading skills is unclear. We assessed 245 4th and 5th grade struggling readers (mean age = 10.3 years) on behavioral ratings of attention, sustained attention, and reading over a school year. Contributions of behavioral ratings and sustained attention were considered cross-sectionally and longitudinally in the context of other important predictors of reading. Results suggest that sustained measures and behavioral ratings assess distinct, yet overlapping, aspects of attention. Both types of attention accounted for unique variance in comprehension, but not word reading accuracy or fluency, when evaluated cross-sectionally. Results also support the role of behavioral ratings of attention in fluency and in comprehension growth. Findings suggest that multidimensional assessment of attention is useful when considering its relation to reading, and highlights the need to integrate conceptualizations of attention that arise from different theoretical approaches.
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BACKGROUND: The earliest coronavirus disease-2019 (COVID-19) cases in Central Asia were announced in March 2020 by Kazakhstan. Despite the implementation of aggressive measures to curb infection spread, gaps remain in the understanding of the clinical and epidemiologic features of the regional pandemic. METHODS: We did a retrospective, observational cohort study of patients with laboratory-confirmed COVID-19 hospitalized in Kazakhstan between February and April 2020. We compared demographic, clinical, laboratory and radiological data of patients with different COVID-19 severities on admission. Logistic regression was used to assess factors associated with disease severity and in-hospital death. Whole-genome SARS-CoV-2 analysis was performed in 53 patients. FINDINGS: Of the 1072 patients with laboratory-confirmed COVID-19 in March-April 2020, the median age was 36 years (IQR 24-50) and 484 (45%) were male. On admission, 683 (64%) participants had asymptomatic/mild, 341 (32%) moderate, and 47 (4%) severe-to-critical COVID-19 manifestation; 20 in-hospital deaths (1â¢87%) were reported by 5 May 2020. Multivariable regression indicated increasing odds of severe disease associated with older age (odds ratio 1â¢05, 95% CI 1â¢03-1â¢07, per year increase; p<0â¢001), the presence of comorbidities (2â¢34, 95% CI 1â¢18-4â¢85; p=0â¢017) and elevated white blood cell count (WBC, 1â¢13, 95% CI 1â¢00-1â¢27; p=0â¢044) on admission, while older age (1â¢09, 95% CI 1â¢06-1â¢13, per year increase; p<0â¢001) and male sex (5â¢63, 95% CI 2â¢06-17â¢57; p=0â¢001) were associated with increased odds of in-hospital death. The SARS-CoV-2 isolates grouped into seven phylogenetic lineages, O/B.4.1, S/A.2, S/B.1.1, G/B.1, GH/B.1.255, GH/B.1.3 and GR/B.1.1.10; 87% of the isolates were O and S sub-types descending from early Asian lineages, while the G, GH and GR isolates were related to lineages from Europe and the Americas. INTERPRETATION: Older age, comorbidities, increased WBC count, and male sex were risk factors for COVID-19 disease severity and mortality in Kazakhstan. The broad SARS-CoV-2 diversity suggests multiple importations and community-level amplification predating travel restriction. FUNDING: Ministry of Education and Science of the Republic of Kazakhstan.
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OBJECTIVES: Ceftobiprole is an advanced-generation cephalosporin with a favourable safety profile. Published data on the clinical use of ceftobiprole are limited. We report use of ceftobiprole in Canadian patients using data captured by the CLEAR registry. METHODS: The CLEAR registry uses the web-based research data management program REDCap™ (online survey) to facilitate clinicians entering details associated with their clinical experiences using ceftobiprole. RESULTS: Data were available for 38 patients treated with ceftobiprole. The most common infections treated were endocarditis (42.1% of patients), bone and joint infection (23.7%) and hospital-associated bacterial pneumonia (15.8%). 92.1% of patients had bacteraemia and 21.1% were in intensive care. Ceftobiprole was used because of failure of (71.1%), resistance to (18.4%) or adverse effects from (10.5%) previously prescribed antimicrobial agents. Ceftobiprole was primarily used as directed therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections (94.7% of patients). Ceftobiprole susceptibility testing was performed on isolates from 47.4% of patients. It was used concomitantly with daptomycin in 55.3% of patients and with vancomycin in 18.4% of patients. Treatment duration was primarily >10 days (65.8% of patients) with microbiological success in 97.0% and clinical success in 84.8% of patients. 2.6% of patients had gastrointestinal adverse effects. CONCLUSION: In Canada to date, ceftobiprole is used as directed therapy to treat a variety of severe infections caused by MRSA. It is primarily used in patients failing previous antimicrobials, is frequently added to, and thus used in combination with daptomycin or vancomycin with high microbiological and clinical cure rates and an excellent safety profile.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Anti-Bacterial Agents/therapeutic use , Canada , Cephalosporins/therapeutic use , Humans , RegistriesABSTRACT
The present study had two aims. First, we set out to evaluate the structure of processing speed in children by comparing five alternative models: two conceptual models (a unitary model, a complexity model) and three methodological models (a stimulus material model, an output response model, and a timing modality model). Second, we then used the resulting models to predict multiple types of reading, a highly important developmental outcome, using other well-known predictors as covariates. Participants were 844 children enrolled in third through fifth grade in urban public elementary schools who received 16 measures of processing speed that varied in the above dimensions. A two-factor complexity model that differentiated between simple and complex processing speed was the preferred model and fit the data well. Both types of PS predicted reading fluency, and complex (but not simple) PS predicted single word reading and comprehension. Results offer insight to the structure of processing speed, its relation to closely related concepts (such as executive function), and provide nuance to the understanding of the way processing speed influences reading.
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Cognitive predictors of reading are well known, but less is understood about the roles of "noncognitive" factors, including emotional variables such as anxiety. While math anxiety has been a focus of study, its analogue in the reading literature is understudied. We assessed struggling fourth and fifth graders (n = 272) on reading anxiety in the context of general anxiety, cognitive predictors (working memory, verbal knowledge), and demographics. Regressions tested for unique contributions to three reading outcomes: word reading accuracy, oral reading fluency, and reading comprehension. Reading anxiety and general anxiety correlated moderately (r = .63) but were differentially related to reading. Reading anxiety predicted comprehension when all other predictors were considered, and predicted oral reading fluency until word reading accuracy was added to the model. Results offer a more nuanced understanding of the nature of reading anxiety, and its implications for struggling readers.
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BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by respiratory system abnormalities, including alveolar hypoventilation and autonomic nervous system dysregulation. CCHS is associated with compromised brain development and neurocognitive functioning. Studies that evaluate cognitive skills in CCHS are limited, and no study has considered cognitive abilities in conjunction with psychosocial and adaptive functioning. Moreover, the roles of pertinent medical variables such as genetic characteristics are also important to consider in the context of neurocognitive functioning. METHODS: Seven participants with CCHS ranging in age from 1 to 20 years underwent neuropsychological evaluations in a clinic setting. RESULTS: Neurocognitive testing indicated borderline impaired neurocognitive skills, on average, as well as relative weaknesses in working memory. Important strengths, including good coping skills and relatively strong social skills, may serve as protective factors in this population. CONCLUSION: CCHS was associated with poor neurocognitive outcomes, especially with some polyalanine repeat expansion mutations (PARMS) genotype. These findings have important implications for individuals with CCHS as well as medical providers for this population.
Subject(s)
Hypoventilation , Sleep Apnea, Central , Adolescent , Adult , Child , Child, Preschool , Homeodomain Proteins/genetics , Humans , Hypoventilation/congenital , Hypoventilation/genetics , Infant , Mutation , Sleep Apnea, Central/diagnosis , Sleep Apnea, Central/genetics , Transcription Factors/genetics , Young AdultABSTRACT
Congenital central hypoventilation syndrome (CCHS) is a rare genetic disorder of an autonomic nervous disorder that affects breathing. It is characterized by respiratory insufficiency secondary to insensitivity to hypoxemia and hypercarbia, particularly during sleep leading to persistent apnea. We report four individuals across two generations harboring heterozygous 25 polyalanine repeats mutations (PARMs) in PHOX2B with a varying degree of phenotypic clinical manifestations. Two family members who reported to be "asymptomatic" were subsequently diagnosed with CCHS, based on genetic testing, obtained because of their family history. Genetic studies in the family including a mother and three offsprings revealed in-frame five amino acid PARMs of PHOX2B consistent with CCHS in addition to full clinical assessment. All affected individuals had evidence of hypercapnia on blood gas analysis with PCO2 in the range of 32-70 (mean; 61). Nocturnal polysomnogram revealed evidence of hypoventilation in two individuals (1 offspring and mother) with the end-tidal CO2 median of 54. Magnetic resonance imaging of brain revealed no abnormalities in the brain stem. There was no evidence of cor pulmonale on echocardiograms in all individuals. Neuropsychological testing was conducted on all four patients; two patients (mother and 1 offspring) had normal results, while the other two offspring exhibited some impairments on neuropsychological testing. This case series emphasizes the importance of screening first-degree relatives of individuals with confirmed CCHS to minimize complications associated with long-term ventilatory impairment. It also suggests that some patients with CCHS should undergo neuropsychological evaluations to assess for cognitive weaknesses secondary to their CCHS.
Subject(s)
Epilepsy/complications , Psychotic Disorders/complications , Humans , Male , Seizures/complications , Young AdultABSTRACT
BACKGROUND: Among Indigenous people in Canada the incidence of HIV is 3.5 times higher than other ethnicities. In Manitoba First Nations, Metis and Inuit people are disproportionately represented (40%) among people who are new to HIV care. Northlands Denesuline First Nation (NDFN) identified the need to revisit their level of knowledge and preparedness for responding to the increasing rates of HIV. NDFN piloted a community readiness assessment (CRA) tool to assess its appropriateness for use in northern Manitoba. METHODS: A First Nation and non-First Nation research team trained to administer the CRA tool at NDFN in Manitoba. Five informants were interviewed using the CRA tool and the responses were scored, analysed and reviewed at community workshops and with stakeholders to develop a 1-year action plan. RESULTS: CRA training was best conducted in the community. Using the readiness score of 2.4 along with feedback from two workshops, community members, the research team and stakeholders, we identified priorities for adult education and youth involvement in programmes and planning. CONCLUSIONS: In response to the increasing incidence of HIV, a northern First Nation community successfully modified and implemented a CRA tool to develop an action plan for culturally appropriate interventions and programmes.
Subject(s)
Community Participation/methods , HIV Infections/ethnology , HIV Infections/prevention & control , Health Services, Indigenous/organization & administration , Inuit , Acquired Immunodeficiency Syndrome/prevention & control , Acquired Immunodeficiency Syndrome/therapy , Arctic Regions , Canada , HIV Infections/therapy , Health Knowledge, Attitudes, Practice , Humans , Leadership , Pilot ProjectsABSTRACT
BACKGROUND: Varicella-zoster virus (VZV) is under consideration as a promising recombinant viral vector to deliver foreign antigens including HIV. However, new vectors have come under increased scrutiny, since trials with adenovirus serotype 5-vectored (Ad5-vectored) HIV vaccine demonstrated increased HIV risk in individuals with pre-immunity to the vector that was thought to be associated with mucosal immune activation (IA). Therefore, given the prospect of developing an HIV/VZV chimeric vaccine, it is particularly important to define the impact of VZV vaccination on IA. METHODS: Healthy VZV-seropositive Kenyan women (n = 44) were immunized with high-dose live attenuated VZV vaccine, and we assessed the expression on CD4+ T cells isolated from blood, cervix, and rectum of IA markers including CD38 and HLA-DR and of markers of cell migration and tissue retention, as well as the concentration of genital and intestinal cytokines. A delayed-start group (n = 22) was used to control for natural variations in these parameters. RESULTS: Although immunogenic, VZV vaccination did not result in significant difference in the frequency of cervical activated (HLA-DR+CD38+) CD4+ T cells (median 1.61%, IQR 0.93%-2.76%) at 12 weeks after vaccination when compared with baseline (median 1.58%, IQR 0.75%-3.04%), the primary outcome for this study. VZV vaccination also had no measurable effect on any of the IA parameters at 4, 8, and 12 weeks after vaccination. CONCLUSION: This study provides the first evidence to our knowledge about the effects of VZV vaccination on human mucosal IA status and supports further evaluation of VZV as a potential vector for an HIV vaccine. TRIAL REGISTRATION: ClinicalTrials.gov NCT02514018. FUNDING: Primary support from the Canadian Institutes for Health Research (CIHR). For other sources, see Acknowledgments.
Subject(s)
AIDS Vaccines , CD4-Positive T-Lymphocytes/immunology , HIV-1/physiology , Herpesvirus 3, Human , Virus Activation , AIDS Vaccines/administration & dosage , AIDS Vaccines/immunology , Adult , CD4-Positive T-Lymphocytes/pathology , CD4-Positive T-Lymphocytes/virology , Female , Herpesvirus 3, Human/genetics , Herpesvirus 3, Human/immunology , Humans , Kenya , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/immunology , Varicella Zoster Virus Infection/immunology , Varicella Zoster Virus Infection/pathology , Varicella Zoster Virus Infection/prevention & control , Virus Activation/drug effects , Virus Activation/immunologyABSTRACT
The predictors of developing reading skill are well known, and there is increasing coherence around predictors of developing math as well. These achievement skills share strong relations. Less knowledge is available regarding the extent to which predictors overlap and predict one another, particularly longitudinally, and across different types of reading and math. We followed kindergarten students (n = 193) for one year, evaluating a range of relevant predictor skills in kindergarten, and a range of relevant achievement outcomes (core, fluency, complex) of reading and math in grade 1. Few predictors differentially predicted math versus reading with some exception (phonological awareness and rapid naming for reading; counting knowledge for math). The pattern was more similar for core and fluency outcomes relative to complex ones. A small set of predictors accounted for much of the overlap among math and reading outcomes, regardless of type (core, fluency, or complex). Results have the potential to inform the development of early screening tools to consider both achievement domains simultaneously, and support the importance of following students identified as at-risk in one domain for their performance in both domains.
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Background: Attenuated varicella zoster virus (VZV) is a promising vector for recombinant vaccines. Because human immunodeficiencyvirus (HIV) vaccines are believed to require mucosal immunogenicity, we characterized mucosal VZV-specific humoral immunity following VZVOka vaccination. Methods: Adult Kenyan VZV-seropositive women (n = 44) received a single dose of the live zoster VZVOka vaccine. The anamnestic responses to the virus were followed longitudinally in both plasma and mucosal secretions using an in-house glycoprotein enzyme-linked immunosorbent assay and safety and reactogenicity monitored. VZV seroprevalence and baseline responses to the virus were also characterized in our cohorts (n = 288). Results: Besides boosting anti-VZV antibody responses systemically, vaccination also boosted anti-VZV immunity in the cervicovaginal mucosa with a 2.9-fold rise in immunoglobulin G (P < .0001) and 1.6-fold rise in immunoglobulin A (IgA) (P = .004) from the time before immunization and 4 weeks postvaccination. Baseline analysis demonstrated high avidity antibodies at the gastrointestinal and genital mucosa of VZV-seropositive women. Measurement of VZV-specific IgA in saliva is a sensitive tool for detecting prior VZV infection. Conclusions: VZVOka vaccine was safe and immunogenic in VZV-seropositive adult Kenyan women. We provided compelling evidence of VZV ability to induce genital mucosa immunity. Clinical Trials Registration: NCT02514018.
Subject(s)
Antibodies, Viral/metabolism , Herpesvirus 3, Human/isolation & purification , Immunity, Humoral , Mucous Membrane/immunology , Vagina/immunology , Varicella Zoster Virus Infection/prevention & control , Antibodies, Viral/blood , Female , Herpes Zoster Vaccine/immunology , Humans , Kenya/epidemiology , Vaccines, Attenuated , Varicella Zoster Virus Infection/epidemiology , Varicella Zoster Virus Infection/immunologyABSTRACT
Cell surface expression of α4ß7, α4ß1 and αEß7 integrins play a key role in T cell distribution. Understanding the contribution of integrins to the density and ratios of CD4+: CD4negT cell at the portals of entry for HIV is of fundamental importance for the advance of more effective HIV prevention strategies. We therefore set out to characterize and compare the expression of α4ß7, α4ß1 and αEß7 integrins on systemic, cervical and rectal CD4+ and CD4negT cells isolated from a cohort of healthy Kenyan women at low risk for sexually transmitted infections (STI) (n = 45). Here we show that blood and cervix were enriched in α4+ß1+CD4+T cells and α4+ß7hiCD4+T cells, whereas the rectum had an equal frequency of α4+ß7hiCD4+T cells and αE+ß7hiCD4+T cells. Most cervical and rectal αE+ß7hiCD4+T cells expressed CCR5 as well as CD69. Interestingly, αEß7 was the predominant integrin expressed by CD4negT cells in both mucosal sites, outnumbering αE+ß7hiCD4+T cells approximately 2-fold in the cervix and 7-fold in the rectum. The majority of αE+ß7hiCD4negT cells expressed CD69 at the mucosa. Taken together, our results show unique tissue-specific patterns of integrin expression. These results can help in guiding vaccine design and also the use of therapeutically targeting integrin adhesion as a means to preventing HIV.
Subject(s)
CD4-Positive T-Lymphocytes/immunology , Cervix Uteri/immunology , HIV Infections/transmission , Integrins/physiology , Rectum/immunology , Cervix Uteri/metabolism , Female , Humans , Rectum/metabolismABSTRACT
INTRODUCTION: A protective HIV vaccine would be expected to induce durable effector immune responses at the mucosa, restricting HIV infection at its portal of entry. We hypothesise that use of varicella-zoster virus (VZV) as an HIV delivery vector could generate sustained and robust tissue-based immunity against HIV antigens to provide long-term protection against HIV. Given that HIV uniquely targets immune-activated T cells, the development of human vaccines against HIV must also involve a specific examination of the safety of the vector. Thus, we aim to evaluate the effects of VZV vaccination on the recipients' immune activation state, and on VZV-specific circulating humoral and cellular responses in addition to those at the cervical and rectal mucosa. METHODS AND ANALYSIS: This open-label, randomised, longitudinal crossover study includes healthy Kenyan VZV-seropositive women at low risk for HIV infection. Participants receive a single dose of a commercial live-attenuated VZVOka vaccine at either week 0 (n=22) or at week 12 (n=22) of the study and are followed for 48 and 36 weeks postvaccination, respectively. The primary outcome is the change on cervical CD4+ T-cell immune activation measured by the coexpression of CD38 and HLA-DR 12 weeks postvaccination compared with the baseline (prevaccination). Secondary analyses include postvaccination changes in VZV-specific mucosal and systemic humoral and cellular immune responses, changes in cytokine and chemokine measures, study acceptability and feasibility of mucosal sampling and a longitudinal assessment of the bacterial community composition of the mucosa. ETHICS AND DISSEMINATION: The study has ethical approval from Kenyatta National Hospital/University of Nairobi Ethics and Research Committee, the University of Toronto Research Ethics Board and by Kenyan Pharmacy and Poisons Board. Results will be presented at conferences, disseminated to participants and stakeholders as well as published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02514018. Pre-results.
Subject(s)
Antibodies, Viral/blood , CD4-Positive T-Lymphocytes/immunology , Chickenpox Vaccine/immunology , Herpes Zoster Vaccine/immunology , AIDS Vaccines/immunology , Adolescent , Adult , Chickenpox/prevention & control , Cross-Over Studies , Female , HIV Infections/prevention & control , Herpes Zoster/prevention & control , Herpesvirus 3, Human/immunology , Humans , Immunity, Cellular , Immunity, Humoral , Kenya , Longitudinal Studies , Middle Aged , Research Design , Women's Health , Young AdultABSTRACT
Neuromyths are misconceptions about brain research and its application to education and learning. Previous research has shown that these myths may be quite pervasive among educators, but less is known about how these rates compare to the general public or to individuals who have more exposure to neuroscience. This study is the first to use a large sample from the United States to compare the prevalence and predictors of neuromyths among educators, the general public, and individuals with high neuroscience exposure. Neuromyth survey responses and demographics were gathered via an online survey hosted at TestMyBrain.org. We compared performance among the three groups of interest: educators (N = 598), high neuroscience exposure (N = 234), and the general public (N = 3,045) and analyzed predictors of individual differences in neuromyths performance. In an exploratory factor analysis, we found that a core group of 7 "classic" neuromyths factored together (items related to learning styles, dyslexia, the Mozart effect, the impact of sugar on attention, right-brain/left-brain learners, and using 10% of the brain). The general public endorsed the greatest number of neuromyths (M = 68%), with significantly fewer endorsed by educators (M = 56%), and still fewer endorsed by the high neuroscience exposure group (M = 46%). The two most commonly endorsed neuromyths across all groups were related to learning styles and dyslexia. More accurate performance on neuromyths was predicted by age (being younger), education (having a graduate degree), exposure to neuroscience courses, and exposure to peer-reviewed science. These findings suggest that training in education and neuroscience can help reduce but does not eliminate belief in neuromyths. We discuss the possible underlying roots of the most prevalent neuromyths and implications for classroom practice. These empirical results can be useful for developing comprehensive training modules for educators that target general misconceptions about the brain and learning.