RESUMEN
INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a rare central vestibular disorder characterised by a constant sensation of motion (rocking, swaying, bobbing), which typically arises after motion experiences (e.g. sea, air, and road travel), though can be triggered by non-motion events. The current standard of care is non-specific medications and interventions that only result in mild-to-moderate improvements. The vestibular ocular reflex (VOR) rehabilitation protocol, a specialised form of rehabilitation, has shown promising results in reducing symptoms amongst people with MdDS. Accumulating evidence suggests that it may be possible to augment the effects of VOR rehabilitation via non-invasive brain stimulation protocols, such as theta burst stimulation (TBS). METHODS: The aim of this randomised controlled trial was to evaluate the effectiveness of intermittent TBS (iTBS) over the dorsolateral prefrontal cortex in enhancing the effectiveness of a subsequently delivered VOR rehabilitation protocol in people with MdDS. Participants were allocated randomly to receive either Sham (n = 10) or Active (n = 10) iTBS, followed by the VOR rehabilitation protocol. Subjective outcome measures (symptom ratings and mental health scores) were collected 1 week pre-treatment and for 16 weeks post-treatment. Posturography (objective outcome) was recorded each day of the treatment week. RESULTS: Significant improvements in subjective and objective outcomes were reported across both treatment groups over time, but no between-group differences were observed. DISCUSSION: These findings support the effectiveness of the VOR rehabilitation protocol in reducing MdDS symptoms. Further research into iTBS is required to elucidate whether the treatment has a role in the management of MdDS. TRN: ACTRN12619001519145 (Date registered: 04 November 2019).
Asunto(s)
Reflejo Vestibuloocular , Estimulación Magnética Transcraneal , Humanos , Masculino , Femenino , Estimulación Magnética Transcraneal/métodos , Persona de Mediana Edad , Adulto , Reflejo Vestibuloocular/fisiología , Terapia Combinada , Enfermedad Relacionada con los Viajes , Corteza Prefrontal/fisiopatología , Anciano , Evaluación de Resultado en la Atención de Salud , Ritmo Teta/fisiologíaRESUMEN
BACKGROUND: Health education interventions are considered critical for the prevention and management of conditions of public health concern. Although the burden of these conditions is often greatest in socio-economically disadvantaged populations, the effectiveness of interventions that target these groups is unknown. We aimed to identify and synthesize evidence of the effectiveness of health-related educational interventions in adult disadvantaged populations. METHODS: We pre-registered the study on Open Science Framework https://osf.io/ek5yg/ . We searched Medline, Embase, Emcare, and the Cochrane Register from inception to 5/04/2022 to identify studies evaluating the effectiveness of health-related educational interventions delivered to adults in socio-economically disadvantaged populations. Our primary outcome was health related behaviour and our secondary outcome was a relevant biomarker. Two reviewers screened studies, extracted data and evaluated risk of bias. Our synthesis strategy involved random-effects meta-analyses and vote-counting. RESULTS: We identified 8618 unique records, 96 met our criteria for inclusion - involving more than 57,000 participants from 22 countries. All studies had high or unclear risk of bias. For our primary outcome of behaviour, meta-analyses found a standardised mean effect of education on physical activity of 0.05 (95% confidence interval (CI) = -0.09-0.19), (5 studies, n = 1330) and on cancer screening of 0.29 (95% CI = 0.05-0.52), (5 studies, n = 2388). Considerable statistical heterogeneity was present. Sixty-seven of 81 studies with behavioural outcomes had point estimates favouring the intervention (83% (95% CI = 73%-90%), p < 0.001); 21 of 28 studies with biomarker outcomes showed benefit (75% (95%CI = 56%-88%), p = 0.002). When effectiveness was determined based on conclusions in the included studies, 47% of interventions were effective on behavioural outcomes, and 27% on biomarkers. CONCLUSIONS: Evidence does not demonstrate consistent, positive impacts of educational interventions on health behaviours or biomarkers in socio-economically disadvantaged populations. Continued investment in targeted approaches, coinciding with development of greater understanding of factors determining successful implementation and evaluation, are important to reduce inequalities in health.
Asunto(s)
Educación en Salud , Poblaciones Vulnerables , Adulto , Humanos , Promoción de la Salud , Sesgo , Conductas Relacionadas con la SaludRESUMEN
AIMS/HYPOTHESIS: Presentation of peptide epitopes derived from beta-cell autoantigens, such as insulin and its precursor molecules, by MHC class II molecules to autoreactive T-cells is believed to play a role in the development of Type 1 diabetes. However, little is known about the interaction between peptides of (prepro)insulin and MHC class II molecules permissive and protective for Type 1 diabetes. In this study therefore, peptides spanning the human preproinsulin sequence were assessed for their binding characteristics to Type 1 diabetes-protective and -permissive HLA molecules. METHODS: HLA-DR2, -DQ6.2 (Type 1 diabetes-protective) and HLA-DR4, -DQ8 (Type 1 diabetes permissive) molecule binding affinity for overlapping synthetic 20mer peptides spanning human preproinsulin was measured in a direct competition binding assay against a biotinylated indicator peptide. RESULTS: All HLA molecules tested showed similarity in their binding characteristics across the preproinsulin molecule, with regions of the insulin A-chain showing the highest affinity and C-peptide regions the lowest affinity for all HLA molecules tested. Furthermore, an insulin peptide implicated as a major CD4+ T-cell target in disease pathogenesis (B9-23) had high affinity binding to both protective and permissive HLA molecules but did not represent the highest affinity region of (prepro)insulin identified in either case. CONCLUSION/INTERPRETATION: The results suggest that peptide binding affinity alone is unlikely to be the major determinant of disease susceptibility in relation to interactions between (prepro)insulin epitopes and HLA molecules. The identification of epitopes derived from beta-cell autoantigens that bind promiscuously to diabetes-permissive HLA molecules could be important in the design of peptide-based immunotherapeutic strategies for the prevention of Type 1 diabetes.
Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Proinsulina/metabolismo , Unión Proteica/fisiología , Diabetes Mellitus Tipo 1/inmunología , Susceptibilidad a Enfermedades , Antígenos HLA-DQ/inmunología , Antígenos HLA-DQ/metabolismo , Antígeno HLA-DR2/inmunología , Antígeno HLA-DR2/metabolismo , Antígeno HLA-DR4/inmunología , Antígeno HLA-DR4/metabolismo , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Proinsulina/inmunología , Unión Proteica/inmunología , Precursores de Proteínas/inmunologíaRESUMEN
We studied how combination antiviral therapy affects B cell abnormalities associated with HIV-1 infection, namely elevated circulating immunoglobulin (Ig)G antibody-secreting cell (ASC) frequencies and hypergammaglobulinemia. Within a few weeks of starting antiviral therapy, there is a marked decline in IgG-ASC frequency in both acutely and chronically infected people, whereas the hypergammaglobulinemia often present during chronic infection is more gradually resolved. These reductions are sustained while HIV-1 replication is suppressed. HIV-1 antigen-specific B cell responses are also affected by therapy, manifested by a rapid decline in circulating gp120-specific ASCs. Anti-gp120 titers slowly decrease in chronically infected individuals and usually fail to mature in acutely infected individuals who were promptly treated with antiretroviral therapy. Long-term nonprogressors have high titer antibody responses to HIV-1 antigens, but no detectable gp120-specific IgG-ASC, and normal (or subnormal) levels of total circulating IgG-ASC. Overall, we conclude that HIV-1 infection drives B cell hyperactivity, and that this polyclonal activation is rapidly responsive to decreases in viral replication caused by combination antiviral therapy.