Cross-reactive immune responses to SARS-CoV-2 have been observed in pre-pandemic cohorts and proposed to contribute to host protection. Here we assess 52 COVID-19 household contacts to capture immune ...responses at the earliest timepoints after SARS-CoV-2 exposure. Using a dual cytokine FLISpot assay on peripheral blood mononuclear cells, we enumerate the frequency of T cells specific for spike, nucleocapsid, membrane, envelope and ORF1 SARS-CoV-2 epitopes that cross-react with human endemic coronaviruses. We observe higher frequencies of cross-reactive (p = 0.0139), and nucleocapsid-specific (p = 0.0355) IL-2-secreting memory T cells in contacts who remained PCR-negative despite exposure (n = 26), when compared with those who convert to PCR-positive (n = 26); no significant difference in the frequency of responses to spike is observed, hinting at a limited protective function of spike-cross-reactive T cells. Our results are thus consistent with pre-existing non-spike cross-reactive memory T cells protecting SARS-CoV-2-naïve contacts from infection, thereby supporting the inclusion of non-spike antigens in second-generation vaccines.
To determine oral health literacy (REALD-30) and oral health literacy-related outcome associations, and to calculate if oral health literacy-related outcomes are risk indicators for poor ...self-reported oral health among rural-dwelling Indigenous Australians.
468 participants (aged 17-72 years, 63% female) completed a self-report questionnaire. REALD-30 and oral health literacy-related outcome associations were determined through bivariate analysis. Multivariate modelling was used to calculate risk indicators for poor self-reported oral health.
REALD-30 scores were lower among those who believed teeth should be infrequently brushed, believed cordial was good for teeth, did not own a toothbrush or owned a toothbrush but brushed irregularly. Tooth removal risk indicators included being older, problem-based dental attendance and believing cordial was good for teeth. Poor self-rated oral health risk indicators included being older, healthcare card ownership, difficulty paying dental bills, problem-based dental attendance, believing teeth should be brushed infrequently and irregular brushing. Perceived need for dental care risk indicators included being female and problem-based dental attendance. Perceived gum disease risk indicators included being older and irregular brushing. Feeling uncomfortable about oro-facial appearance risk indicators included problem-based dental attendance and irregular brushing. Food avoidance risk indicators were being female, difficulty paying dental bills, problem-based dental attendance and irregular brushing. Poor oral health-related quality of life risk indicators included difficulty paying dental bills and problem-based dental attendance.
REALD-30 was significantly associated with oral health literacy-related outcomes. Oral health literacy-related outcomes were risk indicators for each of the poor self-reported oral health domains among this marginalised population.
Objective: Research has addressed the experiences of parents, children, and spouses of trans people. The experiences of the siblings of trans people are explored in this study.
Method: Thematic ...analysis was performed on the transcripts of semi-structured interviews with seventeen siblings of trans people.
Results: Evidence was found for an umbrella theme (the responsibility to support and protect) and three themes: ("societal issues", "relationship with their trans sibling", "family and social relationships"). Results indicated that participants engaged in a process of family transition. Challenges participants faced included: lack of knowledge of trans identities, a lack of trans visibility in society, acting as an intermediary between their trans sibling and others, managing conflict, experiencing relational strain and cut-off, holding the knowledge of their sibling's gender identity when others were unaware, witnessing their trans sibling's negative experiences, and suppressing their own negative emotions. Positive experiences included: developing authentic sibling relationships, strengthening family relationships, support from family and social relationships, and developing their understanding of diversity and identity as an advocacy.
Conclusions: Needs were identified as: provision of accessible and accurate information regarding trans identities and issues, increased trans visibility, connection with others in similar situations, and targeted counselling and services.
KEY POINTS
What is already known about this topic:
Family support is associated with positive mental health outcomes and reduced suicide risk in trans populations.
Parental support is not guaranteed for trans populations.
Sibling relationships are often the longest and most influential relationships in life.
What this topic adds:
A description of the experiences of Australians with at least one trans sibling.
An analysis of the positive and challenging aspects of the experiences of people with at least one trans sibling.
An understanding of the support needs of the siblings of trans people.
Abstract
Background
Osteoarthritis is highly heritable and genome-wide studies have identified single nucleotide polymorphisms (SNPs) associated with the disease. One such locus is marked by SNP ...rs11732213 (T > C). Genotype at rs11732213 correlates with the methylation levels of nearby CpG dinucleotides (CpGs), forming a methylation quantitative trait locus (mQTL). This study investigated the regulatory activity of the CpGs to identify a target gene of the locus.
Methods
Nucleic acids were extracted from the articular cartilage of osteoarthritis patients. Samples were genotyped, and DNA methylation was quantified by pyrosequencing at 14 CpGs within a 259-bp interval. CpGs were tested for enhancer effects in immortalised chondrocytes using a reporter gene assay. DNA methylation at the locus was altered using targeted epigenome editing, with the impact on gene expression determined using quantitative polymerase chain reaction.
Results
rs11732213 genotype correlated with DNA methylation at nine CpGs, which formed a differentially methylated region (DMR), with the osteoarthritis risk allele T corresponding to reduced levels of methylation. The DMR acted as an enhancer and demethylation of the CpGs altered expression of
TMEM129
. Allelic imbalance in
TMEM129
expression was identified in cartilage, with under-expression of the risk allele.
Conclusions
TMEM129
is a target of osteoarthritis genetic risk at this locus. Genotype at rs11732213 impacts DNA methylation at the enhancer, which, in turn, modulates
TMEM129
expression.
TMEM129
encodes an enzyme involved in protein degradation within the endoplasmic reticulum, a process previously implicated in osteoarthritis.
TMEM129
is a compelling osteoarthritis susceptibility target.
Indigenous Australians suffer substantially poorer oral health than their non-Indigenous counterparts and new approaches are needed to address these disparities. Previous work in Port Augusta, South ...Australia, a regional town with a large Indigenous community, revealed associations between low oral health literacy scores and self-reported oral health outcomes. This study aims to determine if implementation of a functional, context-specific oral health literacy intervention improves oral health literacy-related outcomes measured by use of dental services, and assessment of oral health knowledge, oral health self-care and oral health- related self-efficacy.
This is a randomised controlled trial (RCT) that utilises a delayed intervention design. Participants are Indigenous adults, aged 18 years and older, who plan to reside in Port Augusta or a nearby community for the next two years. The intervention group will receive the intervention from the outset of the study while the control group will be offered the intervention 12 months following their enrollment in the study. The intervention consists of a series of five culturally sensitive, oral health education workshops delivered over a 12 month period by Indigenous project officers. Workshops consist of presentations, hands-on activities, interactive displays, group discussions and role plays. The themes addressed in the workshops are underpinned by oral health literacy concepts, and incorporate oral health-related self-efficacy, oral health-related fatalism, oral health knowledge, access to dental care and rights and entitlements as a patient. Data will be collected through a self-report questionnaire at baseline, at 12 months and at 24 months. The primary outcome measure is oral health literacy. Secondary outcome measures include oral health knowledge, oral health self-care, use of dental services, oral health-related self-efficacy and oral health-related fatalism.
This study uses a functional, context-specific oral health literacy intervention to improve oral health literacy-related outcomes amongst rural-dwelling Indigenous adults. Outcomes of this study will have implications for policy and planning by providing evidence for the effectiveness of such interventions as well as provide a model for working with Indigenous communities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
It is currently unknown how post-COVID-19 syndrome (PCS) may affect those infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This longitudinal study includes ...healthcare staff who tested positive for SARS-CoV-2 between March and April 2020, with follow-up of their antibody titers and symptoms. More than half (21 of 38) had PCS after 7–8 months. There was no statistically significant difference between initial reverse-transcription polymerase chain reaction titers or serial antibody levels between those who did and those who did not develop PCS. This study highlights the relative commonality of PCS in healthcare workers and this should be considered in vaccination scheduling and workforce planning to allow adequate frontline staffing numbers.
In this study, 55% of healthcare workers with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had Post-COVID-19 Syndrome at 7-8 months following symptom onset. Developing the syndrome had no association with antibodies against the receptor binding domain of SARS-CoV-2.
At-home sampling is key to large scale seroprevalence studies. Dried blood spot (DBS) self-sampling removes the need for medical personnel for specimen collection but facilitates specimen referral to ...an appropriately accredited laboratory for accurate sample analysis. To establish a highly sensitive and specific antibody assay that would facilitate self-sampling for prevalence and vaccine-response studies. Paired sera and DBS eluates collected from 439 sero-positive, 382 sero-negative individuals and DBS from 34 vaccine recipients were assayed by capture ELISAs for IgG and IgM antibody to SARS-CoV-2. IgG and IgM combined on DBS eluates achieved a diagnostic sensitivity of 97.9% (95%CI 96.6 to 99.3) and a specificity of 99.2% (95% CI 98.4 to 100) compared to serum, displaying limits of detection equivalent to 23 and 10 WHO IU/ml, respectively. A strong correlation (r = 0.81) was observed between serum and DBS reactivities. Reactivity remained stable with samples deliberately rendered inadequate, (p = 0.234) and when samples were accidentally damaged or 'invalid'. All vaccine recipients were sero-positive. This assay provides a secure method for self-sampling by DBS with a sensitivity comparable to serum. The feasibility of DBS testing in sero-prevalence studies and in monitoring post-vaccine responses was confirmed, offering a robust and reliable tool for serological monitoring at a population level.
The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of heme ...metabolism, with nanomolar affinity. Using cryo-electron microscopy and x-ray crystallography, we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through recruitment of a metabolite.
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