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BACKGROUND: Antipsychotic medications (AP) are inappropriately prescribed to young people. The goal of this pragmatic trial was to test a four-component approach to improved targeting of antipsychotic prescribing to people aged ≥3 and <18 years. METHODS: Clinicians in four health systems were cluster randomized by the number of previous AP orders and service line - specialty mental health and all others. Intervention arm clinicians received a best practice alert and child psychiatrist consultation and feedback. Families received system navigation and expedited access to psychotherapy. Primary outcomes were total days' supply of AP medication and proportion of youth with any AP supply at 6 months. We estimated the log-odds of AP use at 6 months and the relative rate of AP over 6 months. The Safer and Targeted Use of Antipsychotics in Youth (SUAY) trial took place between 3/2018 and 12/2020. RESULTS: The trial enrolled 733 patients. The odds ratio (OR) comparing use at 6 months was 0.75 (95% CI: 0.52, 1.09). The mean number of days using AP was 118.5 for intervention patients and 128.2 for control patients (relative risk [RR] = 0.92; 95% CI: 0.81-1.04). Exploratory heterogeneity of treatment effects (HTE) was not detected in groups defined by age, gender, provider specialty, and insurance type. HTE by race/ethnicity was present: among youth of color, mean days' supply was 103.2 for intervention arm and 131.2 for the control arm (RR 0.79, 95% CI: 0.67-0.93). Among secondary outcomes, only new psychotherapy referrals differed with 44.3% (n = 154) of intervention participants having a new order for psychotherapy compared to 33.5% (n = 129) in the control arm (OR 1.47: 95% CI: 1.01-2.14). CONCLUSIONS: This intervention did not result in less AP use at 6 months or a reduction in the days' supply of AP medication, although psychotherapy orders increased. The intervention may be effective for some subgroups.
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BACKGROUND: Delivering prescription digital therapeutics (ie, evidence-based interventions designed to treat, manage, or prevent disorders via websites or smartphone apps) in primary care could increase patient access to substance use disorder (SUD) treatments. However, the optimal approach to implementing prescription digital therapeutics in primary care remains unknown. OBJECTIVE: This pilot study is a precursor to a larger trial designed to test whether implementation strategies (practice facilitation [PF] and health coaching [HC]) improve the delivery of prescription digital therapeutics for SUDs in primary care. This mixed methods study describes outcomes among patients in the 2 pilot clinics and presents qualitative findings on implementation. METHODS: From February 10 to August 6, 2021, a total of 3 mental health specialists embedded in 2 primary care practices of the same integrated health system were tasked with offering app-based prescription digital therapeutics to patients with SUD. In the first half of the pilot, implementation activities included training and supportive tools. PF (at 1 clinic) and HC (at 2 clinics) were added in the second half. All study analyses relied on secondary data, including electronic health records and digital therapeutic vendor data. Primary outcomes were the proportion of patients reached by the prescription digital therapeutics and fidelity related to ideal use. We used qualitative methods to assess the adherence to planned activities and the barriers and facilitators to implementing prescription digital therapeutics. RESULTS: Of all 18 patients prescribed the apps, 10 (56%) downloaded the app and activated their prescription, and 8 (44%) completed at least 1 module of content. Patients who activated the app completed 1 module per week on average. Ideal use (fidelity) was defined as completing 4 modules per week and having a monthly SUD-related visit; 1 (6%) patient met these criteria for 10 weeks (of the 12-week prescription period). A total of 5 (28%) patients had prescriptions while HC was available, 2 (11%) were successfully contacted, and both declined coaching. Clinicians reported competing clinical priorities, technical challenges, and logistically complex workflows in part because the apps required a prescription. Some pilot activities were impacted by staff turnover that coincided with the COVID-19 pandemic. The facilitators to implementation were high engagement and the perception that the apps could meet patient needs. CONCLUSIONS: The pilot study encountered the barriers to implementing prescription digital therapeutics in a real-world primary care setting, especially staffing shortages, turnover, and competing priorities for clinic teams. The larger randomized trial will clarify the extent to which PF and HC improve the implementation of digital therapeutics. TRIAL REGISTRATION: ClinicalTrials.gov NCT04907045; https://clinicaltrials.gov/study/NCT04907045.
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Aplicativos Móveis , Atenção Primária à Saúde , Transtornos Relacionados ao Uso de Substâncias , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pesquisa Qualitativa , Transtornos Relacionados ao Uso de Substâncias/terapia , Telemedicina , Adulto JovemRESUMO
ABSTRACT: Stahl, CA, Regni, G, Tanguay, J, McElfresh, M, Trihy, E, Diggin, D, and King, DL. A biomechanical comparison of the back squat and hexagonal barbell deadlift. J Strength Cond Res 38(5): 815-824, 2024-Coaches often use different exercises to encourage similar strength adaptations and limit monotony. Anecdotally, the hexagonal barbell deadlift (HBD) exhibits similarities to the back squat (BS). To date, research has not examined the empirical differences between these exercises. This study examined kinematic and kinetic differences between the BS and the HBD across different loads. Sixteen resistance-trained individuals (6 men and 10 women) volunteered to participate. Subjects performed 1-repetition maximum (1RM) testing under BS and HBD conditions. Kinematic and kinetic data were collected during performance of both exercises at submaximal (warm-up sets) and maximal (1RM) loads using a 3D motion capture and force-plate system. Results showed that subjects lifted greater 1RM loads in the HBD relative to the BS (p < 0.05; d = -1.75). Kinematic data indicated that subjects exhibited greater maximum forward lean of the trunk and decreased maximum knee flexion while performing the HBD compared with the BS. The BS resulted in higher maximum extension moments at the hip joint than the HBD. Maximum extension moments at the knee joint showed no difference between the exercises. Data suggest that bar design and position facilitate balanced moment arm length at hip and knee joints during performance of the HBD. By contrast, bar position during performance of the BS increases moment arm length at the hip joint, making it a hip-dominant exercise. The present data have implications for the programming of both exercises. Future research should examine differences in muscle-activation strategies between the 2 exercises.
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Treinamento Resistido , Levantamento de Peso , Humanos , Fenômenos Biomecânicos , Masculino , Feminino , Treinamento Resistido/métodos , Levantamento de Peso/fisiologia , Adulto Jovem , Adulto , Força Muscular/fisiologia , Músculo Esquelético/fisiologia , Articulação do Quadril/fisiologiaRESUMO
In February 2023, a meeting about correlates of protection (CoPs) against COVID-19 was organized by the International Alliance for Biological Standardization, the European Plotkin Institute for Vaccinology, and Vaccinopolis. The meeting aimed at reviewing the evidence, drawing conclusions, and identifying knowledge gaps. Collection of evidence is not straightforward. Neutralizing antibodies correlate with protection and are used for immunobridging studies within and between vaccine platforms for approval of new COVID-19 vaccines. In preparation for the next pandemic, it is vital that rapidly authorized initial vaccines are available to perform immunobridging studies very early. Additional components of the immune response likely contribute to protection against symptomatic infection. Current evidence is strongest for T lymphocytes and binding antibodies. Further studies are needed to consolidate this evidence and define their potential role in the evaluation of vaccines. For evaluation of mucosal vaccines, identifying CoPs against infection and transmission is key; further research is needed to identify and standardize methods suitable for clinical studies. CoPs for broadly protective beta-coronavirus vaccines remain a critical area of research. The knowledge, expertise, and capacity exist to conduct clinical studies using different designs in different populations to discover and validate CoPs, facilitating and accelerating evaluation of novel vaccines/vaccination platforms.
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Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Pandemias/prevenção & controle , Vacinação , Anticorpos AntiviraisRESUMO
BACKGROUND: About half of people living with dementia have not received a diagnosis, delaying access to treatment, education, and support. We previously developed a tool, eRADAR, which uses information in the electronic health record (EHR) to identify patients who may have undiagnosed dementia. This paper provides the protocol for an embedded, pragmatic clinical trial (ePCT) implementing eRADAR in two healthcare systems to determine whether an intervention using eRADAR increases dementia diagnosis rates and to examine the benefits and harms experienced by patients and other stakeholders. METHODS: We will conduct an ePCT within an integrated healthcare system and replicate it in an urban academic medical center. At primary care clinics serving about 27,000 patients age 65 and above, we will randomize primary care providers (PCPs) to have their patients with high eRADAR scores receive targeted outreach (intervention) or usual care. Intervention patients will be offered a "brain health" assessment visit with a clinical research interventionist mirroring existing roles within the healthcare systems. The interventionist will make follow-up recommendations to PCPs and offer support to newly-diagnosed patients. Patients with high eRADAR scores in both study arms will be followed to identify new diagnoses of dementia in the EHR (primary outcome). Secondary outcomes include healthcare utilization from the EHR and patient, family member and clinician satisfaction assessed through surveys and interviews. CONCLUSION: If this pragmatic trial is successful, the eRADAR tool and intervention could be adopted by other healthcare systems, potentially improving dementia detection, patient care and quality of life.
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Doença de Alzheimer , Prestação Integrada de Cuidados de Saúde , Demência , Idoso , Humanos , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/terapia , Encéfalo , Demência/diagnóstico , Demência/terapia , Registros Eletrônicos de Saúde , Qualidade de Vida , Ensaios Clínicos Pragmáticos como Assunto , AlgoritmosRESUMO
IMPORTANCE: The functionality of CD8+ T cells against human immunodeficiency virus-1 (HIV-1) antigens is indicative of HIV-progression in both animal models and people living with HIV. It is, therefore, of interest to assess CD8+ T cell responses in a prophylactic vaccination setting, as this may be an important component of the immune system that inhibits HIV-1 replication. T cell responses induced by the adenovirus serotype 26 (Ad26) mosaic vaccine regimen were assessed previously by IFN-γ ELISpot and flow cytometric assays, yet these assays only measure cytokine production but not the capacity of CD8+ T cells to inhibit replication of HIV-1. In this study, we demonstrate direct anti-viral function of the clinical Ad26 mosaic vaccine regimen through ex vivo inhibition of replication of diverse clades of HIV-1 isolates in the participant's own CD4+ T cells.
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Vacinas contra a AIDS , Linfócitos T CD8-Positivos , Infecções por HIV , Humanos , Vacinas contra a AIDS/imunologia , Antígenos Virais , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/prevenção & controle , HIV-1 , VacinaçãoRESUMO
BACKGROUND: Experts recommend that treatment for substance use disorder (SUD) be integrated into primary care. The Digital Therapeutics for Opioids and Other SUD (DIGITS) Trial tests strategies for implementing reSET® and reSET-O®, which are prescription digital therapeutics for SUD and opioid use disorder, respectively, that include the community reinforcement approach, contingency management, and fluency training to reinforce concept mastery. This purpose of this trial is to test whether two implementation strategies improve implementation success (Aim 1) and achieve better population-level cost effectiveness (Aim 2) over a standard implementation approach. METHODS/DESIGN: The DIGITS Trial is a hybrid type III cluster-randomized trial. It examines outcomes of implementation strategies, rather than studying clinical outcomes of a digital therapeutic. It includes 22 primary care clinics from a healthcare system in Washington State and patients with unhealthy substance use who visit clinics during an active implementation period (up to one year). Primary care clinics implemented reSET and reSET-O using a multifaceted implementation strategy previously used by clinical leaders to roll-out smartphone apps ("standard implementation" including discrete strategies such as clinician training, electronic health record tools). Clinics were randomized as 21 sites in a 2x2 factorial design to receive up to two added implementation strategies: (1) practice facilitation, and/or (2) health coaching. Outcome data are derived from electronic health records and logs of digital therapeutic usage. Aim 1's primary outcomes include reach of the digital therapeutics to patients and fidelity of patients' use of the digital therapeutics to clinical recommendations. Substance use and engagement in SUD care are additional outcomes. In Aim 2, population-level cost effectiveness analysis will inform the economic benefit of the implementation strategies compared to standard implementation. Implementation is monitored using formative evaluation, and sustainment will be studied for up to one year using qualitative and quantitative research methods. DISCUSSION: The DIGITS Trial uses an experimental design to test whether implementation strategies increase and improve the delivery of digital therapeutics for SUDs when embedded in a large healthcare system. It will provide data on the potential benefits and cost-effectiveness of alternative implementation strategies. CLINICALTRIALS: gov Identifier: NCT05160233 (Submitted 12/3/2021). https://clinicaltrials.gov/ct2/show/NCT05160233.
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Atenção à Saúde , Transtornos Relacionados ao Uso de Opioides , Humanos , Terapia Comportamental , Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Atenção Primária à Saúde , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The 2021 Global Vaccine and Immunization Research Forum highlighted the considerable advances and recent progress in research and development for vaccines and immunization, critically reviewed lessons learned from COVID-19 vaccine programs, and looked ahead to opportunities for this decade. For COVID-19, decades of investments in basic and translational research, new technology platforms, and vaccines targeting prototype pathogens enabled a rapid, global response. Unprecedented global coordination and partnership have played an essential role in creating and delivering COVID-19 vaccines. More improvement is needed in product attributes such as deliverability, and in equitable access to vaccines. Developments in other priority areas included: the halting of two human immunodeficiency virus vaccine trials due to lack of efficacy in preventing infection; promising efficacy results in Phase 2 trials of two tuberculosis vaccines; pilot implementation of the most advanced malaria vaccine candidate in three countries; trials of human papillomavirus vaccines given in single-dose regimens; and emergency use listing of a novel, oral poliomyelitis type 2 vaccine. More systematic, proactive approaches are being developed for fostering vaccine uptake and demand, aligning on priorities for investment by the public and private sectors, and accelerating policy making. Participants emphasized that addressing endemic disease is intertwined with emergency preparedness and pandemic response, so that advances in one area create opportunities in the other. In this decade, advances made in response to the COVID-19 pandemic should accelerate availability of vaccines for other diseases, contribute to preparedness for future pandemics, and help to achieve impact and equity under Immunization Agenda 2030.
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COVID-19 , Vacinas contra a Tuberculose , Vacinas , Humanos , Vacinas contra COVID-19 , Pandemias/prevenção & controle , COVID-19/prevenção & controle , Imunização , Programas de ImunizaçãoRESUMO
Cardiovascular ageing contributes to cognitive impairment. However, the unique and synergistic contributions of multiple cardiovascular factors to cognitive function remain unclear because they are often condensed into a single composite score or examined in isolation. We hypothesized that vascular risk factors, electrocardiographic features and blood pressure indices reveal multiple latent vascular factors, with independent contributions to cognition. In a population-based deep-phenotyping study (n = 708, age 18-88), path analysis revealed three latent vascular factors dissociating the autonomic nervous system response from two components of blood pressure. These three factors made unique and additive contributions to the variability in crystallized and fluid intelligence. The discrepancy in fluid relative to crystallized intelligence, indicative of cognitive decline, was associated with a latent vascular factor predominantly expressing pulse pressure. This suggests that higher pulse pressure is associated with cognitive decline from expected performance. The effect was stronger in older adults. Controlling pulse pressure may help to preserve cognition, particularly in older adults. Our findings highlight the need to better understand the multifactorial nature of vascular aging.
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Transtornos Cognitivos , Disfunção Cognitiva , Humanos , Idoso , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Cognição/fisiologia , Envelhecimento/fisiologia , Pressão Sanguínea/fisiologiaRESUMO
Introduction: Immunological protection against human immunodeficiency virus-1 (HIV-1) infection is likely to require both humoral and cell-mediated immune responses, the latter involving cytotoxic CD8 T-cells. Characterisation of CD8 T-cell mediated direct anti-viral activity would provide understanding of potential correlates of immune protection and identification of critical epitopes associated with HIV-1 control. Methods: The present report describes a functional viral inhibition assay (VIA) to assess CD8 T-cell-mediated inhibition of replication of a large and diverse panel of 45 HIV-1 infectious molecular clones (IMC) engineered with a Renilla reniformis luciferase reporter gene (LucR), referred to as IMC-LucR. HIV-1 IMC replication in CD4 T-cells and CD8 T-cell mediated inhibition was characterised in both ART naive subjects living with HIV-1 covering a broad human leukocyte antigen (HLA) distribution and compared with uninfected subjects. Results & discussion: CD4 and CD8 T-cell lines were established from subjects vaccinated with a candidate HIV-1 vaccine and provided standard positive controls for both assay quality control and facilitating training and technology transfer. The assay was successfully established across 3 clinical research centres in Kenya, Uganda and the United Kingdom and shown to be reproducible. This IMC-LucR VIA enables characterisation of functional CD8 T-cell responses providing a tool for rational T-cell immunogen design of HIV-1 vaccine candidates and evaluation of vaccine-induced T-cell responses in HIV-1 clinical trials.
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Infecções por HIV , HIV-1 , Humanos , Linfócitos T CD8-Positivos , Luciferases , Células ClonaisRESUMO
BACKGROUND: There is an urgent need for evidence on how interventions can prevent or mitigate cancer-related financial hardship. Our objectives are to compare self-reported financial hardship, quality of life, and health services use between patients receiving a financial navigation intervention versus a comparison group at 12 months follow-up, and to assess patient-level factors associated with dose received of a financial navigation intervention. METHODS: The Cancer Financial Experience (CAFÉ) study is a multi-site randomized controlled trial (RCT) with individual-level randomization. Participants will be offered either brief (one financial navigation cycle, Arm 2) or extended (three financial navigation cycles, Arm 3) financial navigation. The intervention period for both Arms 2 and 3 is 6 months. The comparison group (Arm 1) will receive enhanced usual care. The setting for the CAFÉ study is the medical oncology and radiation oncology clinics at two integrated health systems in the Pacific Northwest. Inclusion criteria includes age 18 or older with a recent cancer diagnosis and visit to a study clinic as identified through administrative data. Outcomes will be assessed at 12-month follow-up. Primary outcomes are self-reported financial distress and health-related quality of life. Secondary outcomes are delayed or foregone care; receipt of medical financial assistance; and account delinquency. A mixed methods exploratory analysis will investigate factors associated with total intervention dose received. DISCUSSION: The CAFÉ study will provide much-needed early trial evidence on the impact of financial navigation in reducing cancer-related financial hardship. It is theory-informed, clinic-based, aligned with patient preferences, and has been developed following preliminary qualitative studies and stakeholder input. By design, it will provide prospective evidence on the potential benefits of financial navigation on patient-relevant cancer outcomes. The CAFÉ trial's strengths include its broad inclusion criteria, its equity-focused sampling plan, its novel intervention developed in partnership with clinical and operations stakeholders, and mixed methods secondary analyses related to intervention dose offered and dose received. The resulting analytic dataset will allow for rich mixed methods analysis and provide critical information related to implementation of the intervention should it prove effective. TRIAL REGISTRATION: ClinicalTrials.gov NCT05018000 . August 23, 2021.
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Estresse Financeiro , Neoplasias , Adolescente , Humanos , Neoplasias/diagnóstico , Qualidade de Vida , Resultado do TratamentoRESUMO
Human infection (or challenge) studies involve the intentional administration of a pathogen (challenge agent) to volunteers. The selection, isolation, development and production of the challenge agent is one of the first steps in developing a challenge study and critical for minimising the risk to volunteers. Regulatory oversight for this production differs globally. Manufacturing agents within a Good Manufacturing Practice (GMP) facility reduces the risk of the manufacturing process by including processes such as confirming the identity of the challenge agent and ascertaining that it's pure and free from impurities. However, in some cases it's not possible or feasible to manufacture to GMP standards, for example where the challenge agent requires an intermediate vector for growth. There is lack of clear guidance on what the minimum requirements for high-quality safe manufacture outside of GMP facilities should be and here we describe the development of a considerations document for the selection and production of challenge agents to meet this need.
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PURPOSE: There is limited knowledge of nursing students' perspectives about engagement with special needs populations. The purpose of this study was to identify the advantages/benefits and disadvantages/challenges of nursing students' engagement experience with children with special mental and physical disabilities. Recommendations to enhance student engagement experiences were also provided. METHODS: A descriptive, qualitative design was employed. Undergraduate nursing students (N = 28) responded to open-ended questions about their civic engagement experiences at a community-based, respite care program for children with special needs. Student accounts underwent directed content analysis, with coding, category and theme development according to the Theory of Planned Behavior. The Atlas.Ti computer program was used to manage the data. RESULTS: Advantages/Benefits: Filling cognitive and experiential learning gaps, rewarding connections/relationships, positive emotions, perceptions and interactions, and fun and stress relief. Disadvantage/challenges: Managing negative/uncomfortable emotions and uncertainty, witnessing and managing disruptive behaviors, negative perceptions of program operations/expectations. CONCLUSIONS: Students experienced cognitive, emotional, interpersonal and educational advantages and/or disadvantages while engaging with this defined population. PRACTICE IMPLICATIONS: To enhance engagement faculty can provide education and anticipatory guidance, detail responsibilities and expectations, and/or utilize simulation for student preparation. Nurses and researchers can utilize community based participatory methods to guide discussions with community-based organizations to collaboratively develop strategies to institute, evaluate and enhance student engagement during service learning experiences with children who have special needs.
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Crianças com Deficiência , Bacharelado em Enfermagem , Estudantes de Enfermagem , Criança , Bacharelado em Enfermagem/métodos , Humanos , Aprendizagem , Aprendizagem Baseada em Problemas , Estudantes de Enfermagem/psicologiaRESUMO
Full characterisation of functional HIV-1-specific T-cell responses, including identification of recognised epitopes linked with functional antiviral responses, would aid development of effective vaccines but is hampered by HIV-1 sequence diversity. Typical approaches to identify T-cell epitopes utilising extensive peptide sets require subjects' cell numbers that exceed feasible sample volumes. To address this, CD8 T-cells were polyclonally expanded from PBMC from 13 anti-retroviral naïve subjects living with HIV using CD3/CD4 bi-specific antibody. Assessment of recognition of individual peptides within a set of 1408 HIV-1 Gag, Nef, Pol and Env potential T-cell epitope peptides was achieved by sequential IFNγ ELISpot assays using peptides pooled in 3-D matrices followed by confirmation with single peptides. A Renilla reniformis luciferase viral inhibition assay assessed CD8 T-cell-mediated inhibition of replication of a cross-clade panel of 10 HIV-1 isolates, including 9 transmitted-founder isolates. Polyclonal expansion from one frozen PBMC vial provided sufficient CD8 T-cells for both ELISpot steps in 12 of 13 subjects. A median of 33 peptides in 16 epitope regions were recognised including peptides located in previously characterised HIV-1 epitope-rich regions. There was no significant difference between ELISpot magnitudes for in vitro expanded CD8 T-cells and CD8 T-cells directly isolated from PBMCs. CD8 T-cells from all subjects inhibited a median of 7 HIV-1 isolates (range 4 to 10). The breadth of CD8 T-cell mediated HIV-1 inhibition was significantly positively correlated with CD8 T-cell breadth of peptide recognition. Polyclonal CD8 T-cell expansion allowed identification of HIV-1 isolates inhibited and peptides recognised within a large peptide set spanning the major HIV-1 proteins. This approach overcomes limitations associated with obtaining sufficient cell numbers to fully characterise HIV-1-specific CD8 T-cell responses by different functional readouts within the context of extreme HIV-1 diversity. Such an approach will have useful applications in clinical development for HIV-1 and other diseases.
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Epitopos de Linfócito T , HIV-1 , Linfócitos T CD8-Positivos , Soropositividade para HIV , Inibição Psicológica , Leucócitos MononuclearesRESUMO
OBJECTIVES: Interleukin-21 (IL-21) has been linked with the generation of virus-specific memory CD8+ T cells following acute infection with HIV-1 and reduced exhaustion of CD8+ T cells. IL-21 has also been implicated in the promotion of CD8+ T-cell effector functions during viral infection. Little is known about the expression of interleukin-21 receptor (IL-21R) during HIV-1 infection or its role in HIV-1-specific CD8+ T-cell maintenance and subsequent viral control. METHODS: We compared levels of IL-21R expression on total and memory subsets of CD8+ T cells from HIV-1-negative and HIV-1-positive donors. We also measured IL-21R on antigen-specific CD8+ T cells in volunteers who were positive for HIV-1 and had cytomegalovirus-responding T cells. Finally, we quantified plasma IL-21 in treatment-naive HIV-1-positive individuals and compared this with IL-21R expression. RESULTS: IL-21R expression was significantly higher on CD8+ T cells (Pâ=â0.0256), and on central memory (Pâ=â0.0055) and effector memory (Pâ=â0.0487) CD8+ T-cell subsets from HIV-1-positive individuals relative to HIV-1-negative individuals. For those infected with HIV-1, the levels of IL-21R expression on HIV-1-specific CD8+ T cells correlated significantly with visit viral load (râ=â0.6667, Pâ=â0.0152, nâ=â13) and inversely correlated with plasma IL-21 (râ=â-0.6273, Pâ=â0.0440, nâ=â11). Lastly, CD8+ T cells from individuals with lower set point viral load who demonstrated better viral control had the lowest levels of IL-21R expression and highest levels of plasma IL-21. CONCLUSION: Our data demonstrates significant associations between IL-21R expression on peripheral CD8+ T cells and viral load, as well as disease trajectory. This suggests that the IL-21 receptor could be a novel marker of CD8+ T-cell dysfunction during HIV-1 infection.
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Infecções por HIV , HIV-1 , Linfócitos T CD8-Positivos , Humanos , Subunidade alfa de Receptor de Interleucina-21 , Receptores de Interleucina-21 , Carga ViralRESUMO
Individuals infected with HIV display varying rates of viral control and disease progression, with a small percentage of individuals being able to spontaneously control infection in the absence of treatment. In attempting to define the correlates associated with natural protection against HIV, extreme heterogeneity in the datasets generated from systems methodologies can be further complicated by the inherent variability encountered at the population, individual, cellular and molecular levels. Furthermore, such studies have been limited by the paucity of well-characterised samples and linked epidemiological data, including duration of infection and clinical outcomes. To address this, we selected 10 volunteers who rapidly and persistently controlled HIV, and 10 volunteers each, from two control groups who failed to control (based on set point viral loads) from an acute and early HIV prospective cohort from East and Southern Africa. A propensity score matching approach was applied to control for the influence of five factors (age, risk group, virus subtype, gender, and country) known to influence disease progression on causal observations. Fifty-two plasma proteins were assessed at two timepoints in the 1st year of infection. We independently confirmed factors known to influence disease progression such as the B*57 HLA Class I allele, and infecting virus Subtype. We demonstrated associations between circulating levels of MIP-1α and IL-17C, and the ability to control infection. IL-17C has not been described previously within the context of HIV control, making it an interesting target for future studies to understand HIV infection and transmission. An in-depth systems analysis is now underway to fully characterise host, viral and immunological factors contributing to control.
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Infecções por HIV/diagnóstico , HIV-1/crescimento & desenvolvimento , Replicação Viral , Proteínas Adaptadoras de Transdução de Sinal/sangue , Adulto , África , Biomarcadores/sangue , Progressão da Doença , Feminino , Infecções por HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , HIV-1/patogenicidade , Antígenos HLA-B/genética , Antígenos HLA-B/imunologia , Humanos , Incidência , Interleucina-17/sangue , Masculino , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Carga Viral , Adulto JovemRESUMO
ABSTRACT: Phillips, J, Diggin, D, King, DL, and Sforzo, GA. Effect of varying self-myofascial release duration on subsequent athletic performance. J Strength Cond Res 35(3): 746-753, 2021-Self-myofascial release (SMR) treatments can enhance joint range-of-motion and restore movement function. The effects of different SMR durations on athletic performance have yet to be examined. Twenty-four volunteers had ankle and knee joint range-of-motion assessed using modified weight-bearing and kneeling lunge (KL) tests. Vertical jump and pro-agility sprint performance were also examined. All tests were conducted before and immediately after 1 (SMR_1) and 5 minutes (SMR_5) of foam rolling, and immediately after a control (CONTR) condition. Results showed KL scores increased after SMR_5 (16.4%; effect size [ES] = 0.85) when compared with SMR_1 (12.5%; ES = 0.58). Weight-bearing lunge scores showed little change after either SMR treatment. The CONTR condition exhibited little effect on joint range-of-motion. Vertical jump performance decreased after SMR_5 (5.1%; ES = 0.26) but changed little after SMR_1 (0.7%; ES = 0.03) and CONTR (1.9%; ES = 0.10) conditions. Pro-agility performance improved slightly after SMR_1 (1.1%) but deteriorated after CONTR (1.2%) and SMR_5 (0.5%). Effect size calculations for changes in pro-agility sprint times were trivial across all conditions (0.06-0.15). Data suggest that extended periods of SMR may be recommended, should improvements in joint range-of-motion be required. If power output is a critical requirement of subsequent exercise/performance tasks, prolonged SMR treatment (i.e., 5 minutes) should be avoided. Practitioners should be cautious when implementing SMR treatments within warm-ups.