Jia Yi Hee

Objective: In the first year after onset of the autoimmune disease RA (RA), 40-60% do not achieve remission on conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs). To understand how autoreactive T cells may contribute to unstable or non-remission, we studied CD4+ T cells, including those recognising citrullinated (Cit) vimentin in participants with RA. Methods: Two cohorts of drug-naïve new-onset participants with RA were treated with csDMARDs. Disease activity score (DAS28-CRP) and peripheral blood (PB) mononuclear cells were collected longitudinally. In HLA-DR-shared epitope+ cohort 1 (n=21), T cells were assessed with a 17-marker spectral flow panel, incorporating HLA-DRB1*04:01/01:01- VimentinCit64 _59-71 or HLA-DRB1*04:04-VimentinCit71 _66-78 tetramers. Changes in T cell subsets over time were assessed in remitting and non-remitting participants using a generalized linear mixed model with a negative binomial distribution. In cohort 2 (n=26), the transcriptome of disaggregated synovial tissue (ST) and PB CD4+ T cells were analysed at baseline, and ST biopsy spatial proteomics at baseline and 6 months. Results: CD4⁺CXCR5 ^- PD1 ⁺ peripheral helper T cells (Tph), including Cit-vimentin-reactive Tph, CD4⁺CCR7 ⁺ CXCR5 ^- PD1 ⁺ stem-like Tph and TIGIT+PD1+ Tph were increased with moderate/high DAS28-CRP at any time point. Remission outcome was associated with low CD4⁺ follicular helper T cell (Tfh) and Cit-vimentin-reactive Tfh. In non-remitting participants, Tph/fh infiltrated germinal-centre-like ST aggregates. This decreased in remission. Circulating TIGIT ⁺ Tph genes reflected B lymphoid activation and lymph node egress, while in ST they reflected local differentiation. Conclusion: Persistently high circulating TIGIT ⁺ Tph and Tfh, including Cit-vimentin specificities, reflecting antigen-presenting B-cell interactions, are associated with reduced response to csDMARDs in recent-onset RA. Key messages: What is already known on this topic: Tph and Tfh cells interacting with B cells are implicated in active ACPA+ RA Citrullinated (Cit)-vimentin is an important neutrophil extracellular trap-derived target of ACPA What this study adds: High circulating TIGIT+ Tph, Cit-vimentin-autoreactive Tph and Tfh associate with failure to reach remission on conventional synthetic DMARDs within the first year in early HLA-DR shared-epitope+ RA Tph/Tfh and adjacent regulatory T cells surround follicular B-cells in lymphoid aggregates in synovial tissue in non-remission Circulating TIGIT+ Tph bear a transcriptional signature of lymphoid tissue expansion and lymph node egress as compared to functional differentiation and antigen experience in synovial tissue How this study might affect research, practice or policy: When a remission target is not achieved in HLA-DR shared-epitope+ RA patients during the first year of treatment, high circulating TIGIT+ Tph implicate autoreactive T-B-lymphoid expansion in synovial tissue.

Background: Environmental factors contribute to approximately 41% of the risk of rheumatoid arthritis (RA). Previous studies have focused on anthropogenic environmental factors, while much less attention has been given to natural environmental factors. Our study explored the potential influence of natural environmental factors at birth on the risk of RA. Methods: This large retrospective study utilized data from the China Kadoorie Biobank. A restricted cubic spline (RCS) model was employed to explore nonlinear relationships between natural environmental factors and the risk of RA. Additionally, a multivariable Cox regression model, adjusted for confounding factors, was used to examine correlations between season of birth, geographic, climate, and the risk of RA. Results: A total of 512,715 participants were included in this study, of which 2889 (0.56%) were diagnosed with RA. The RCS analysis revealed that the monthly average temperature at birth (p < 0.001), the latitude (p = 0.027) of the birthplace, and the sunshine rate (p < 0.001) exhibited a nonlinear relationship with the risk of RA. Multivariable Cox regression analysis revealed that participants born in Spring and Summer (HR 1.13, 95% CI 1.05–1.23) had an increased risk of RA compared to those born in Autumn and Winter. Additionally, participants born at latitudes ≤ 24°N (HR 1.49, 95% CI 1.32–1.68), with sunshine rate ≤ 28% (HR 2.00, 95% CI 1.75–2.29) or ≥ 60% (HR 1.22, 95% CI 1.08–1.38) had an increased risk of RA. Being born in regions with a monthly average temperature ≥ 27 °C (HR 0.82, 95% CI 0.72–0.95) was associated with a decreased risk of RA. Conclusion: Being born in Spring and Summer, as well as early-life exposure to low-latitude regions and extreme sunlight environments increases the risk of RA. Our study revealed significant associations between the risk of RA and natural environmental factors at birth, emphasizing the impact of the early-life environment on the onset of RA.

The United Nations Sustainable Development Goals (SDGs) recognize that ensuring individual health and promoting well-being is important for all people, regardless of age. Maternal health, a key part of SDG 3, is listed as its first target [1]. Recently, substantial progress has been made in reducing maternal deaths worldwide, with a 38% decline in the […]

Considering the female preponderance of rheumatoid arthritis (RA), and disease onset typically after the reproductive years, pregnancy and childbirth may play a role in the aetiology of the disease. Adverse outcomes of pregnancy have been found to precede the diagnosis of autoimmune diseases, including RA, but the evidence is scant and inconsistent. Therefore, we investigate whether pregnancy loss is associated with the risk of RA in Chinese women. Data from the China Kadoorie Biobank, conducted by the University of Oxford and the Chinese Centre for Disease Control and Prevention, of 299,629 Chinese women who had been pregnant were used. Multivariable logistic regression and stratified analyses were employed to analyse the association between types of pregnancy loss with the risk of RA. Pregnancy loss was significantly associated with increased risk of RA (OR 1.12, 95% CI 1.06–1.18), specifically, spontaneous (OR 1.11, 95% CI 1.03–1.20) and induced abortions (OR 1.11, 95% CI 1.06–1.17). There was no significant association between stillbirth and the risk of RA (OR 1.07, 95% CI 0.97–1.18). The risk of developing RA increases with the number of pregnancy losses: one loss confers an OR of 1.09 (95% CI 1.03–1.16), two an OR of 1.13 (95% CI 1.05–1.20), three or more an OR of 1.19 (95% CI 1.10–1.28) and OR of 1.06 (95% CI 1.03–1.08) for each additional. Spontaneous and induced abortions are associated with an increased risk of RA in Chinese women.

Background: The issue of malnutrition in the Democratic Republic of Congo is severe. Meanwhile, the Water, Sanitation, and Hygiene program has been demonstrated to be effective in reducing the rates of growth stunting among children. Objective: We aimed to explore the association between maternal exposure to mass media and stunting in children through water, sanitation, and hygiene behaviors. Methods: Mediation analysis was conducted using data from the 2018 Multiple Indicators Cluster Surveys. Results: Mothers’ exposures to television and the internet in the Democratic Republic of Congo significantly decreases the risk of stunting in children by 5% and 10%, respectively, mediated by household water, sanitation, and hygiene facilities and practices. Conclusions: These findings could inform interventions and policies to reduce the rate of stunting rate children by promoting water, sanitation, and hygiene through mass media, especially through the internet and television.

Introduction Over-expression of common inflammatory mediators in the metabolic syndrome (MetS) and in rheumatoid arthritis (RA) may lead to mutually adverse outcomes. Aim We investigate the prevalence of MetS in a multi-ethnic population of RA patients and its effect on clinical and patient-reported outcomes. Method Six hundred sixty RA (561 women) patients from a public-sector specialist clinic in a hospital in Singapore were assessed for MetS according to the 2009 Joint Consensus (JC) and the 2004 National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) definitions. Univariable and multivariable regression modelling were used to investigate the associations between patients’ demographics with MetS and MetS with RA outcomes. Results The prevalence of MetS in our RA cohort was 49.4% and 44.9% according to the JC and NCEP ATP III definitions, respectively. The diagnosis of MetS was largely due to hypertriglyceridemia, hypertension, and obesity. MetS was associated with older age (OR 1.06 [95% CI 1.04–1.08]), Malay ethnicity (OR 1.78 [95% CI 1.02–3.09]), or Indian ethnicity (OR 3.07 [95% CI 1.68–5.59]). No significant associations between MetS and RA outcomes were observed. RA patients with MetS are more likely to suffer from stroke and ischemic heart disease. Conclusion The prevalence of MetS in RA patients in Singapore was almost double that in the general population. MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease. RA patients, especially those older and of Indian and Malay ethnicities, should be routinely screened for MetS. Any MetS-defining condition should be actively controlled. Key Points • Approximately half of the RA sample from the Singapore RA population can be diagnosed with MetS. • Older patients, and patients of Malay and Indian ethnicities have higher odds of MetS. • MetS does not adversely affect RA outcomes but raises the risks of stroke and heart disease.

Background: This study aimed to evaluate the effects of an internet-based and teacher-facilitated sexuality education package on the sexual knowledge and attitudes of Chinese adolescents. Methods: Six middle schools where no sexuality education had been performed with a total of 501 adolescent students (245 males and 256 females) were included in the trial. In total, 14 classes were randomly assigned to the intervention (internet-based sexuality education package) or the control group (classes were conducted as per normal). Students’ sexual knowledge and attitudes were assessed at the baseline, at the end of the intervention, and 12 months after the intervention. Generalized linear models were employed to assess the effects of the intervention. Results: Positive effects of the intervention were observed on sexual knowledge (β = 4.65, 95% CI: 4.12—5.17) and attitudes (β = 1.25, 95% CI: 1.00—1.50) at the end of the intervention. After 12 months, the effects sustained but the magnitude declined for sexual knowledge (β = 2.39, 95% CI: 1.85—2.93) and attitudes (β = 0.49, 95% CI: 0.23—0.75). There were no significant differences between male and female students. Conclusions: Although further modifications are required, the sexuality education package can increase the accessibility of comprehensive sexuality education to adolescents in rural areas in China.

(1) Background: The empowerment of women contributes to better child health and wellness. This study aimed to examine the association between women’s empowerment and complete vaccination of children, as recommended in the National Expanded Program on Immunization (EPI) in the Democratic Republic of the Congo (DRC). (2) Methods: In this cross-sectional study, a principal component analysis (PCA) was conducted on data from the Multiple-Indicator Cluster Survey 6 (MICS-6) to determine the dimensions of women’s empowerment. Logistic regression analysis was used to assess the association between women’s empowerment and complete vaccination of children stratified by household wealth. In total, 3524 women with children aged 12–23 months were included in the study. (3) Results: Women’s empowerment was defined by three dimensions, namely intrinsic agency, enabling resources, and social independence. Children of women with high levels of empowerment had higher odds of complete vaccination, with values of 1.63 (p = 0.002) and 1.59 (p = 0.012) for intrinsic agency and enabling resources of the empowerment, respectively, compared to the children of women with low levels of empowerment; however, social independence failed to be associated with the vaccination status of children. After stratification by household wealth, the OR of complete vaccination was higher in women from middle-income households with high levels of intrinsic agency (OR: 2.35, p = 0.021) compared to women from poor households with high levels of intrinsic agency (OR: 1.92, p = 0.004). (4) Conclusions: Higher levels of women’s empowerment, especially intrinsic agency and enabling resources, were associated with complete vaccination in children in the DRC. Household wealth status influenced the associations. The empowerment of women is crucial in promoting the complete vaccination of children and providing equal access to vaccines.

BACKGROUND The issue of malnutrition in the Democratic Republic of Congo is severe. Meanwhile, the Water, Sanitation, and Hygiene program has been demonstrated to be effective in reducing the rates of growth stunting among children. OBJECTIVE We aimed to explore the association between maternal exposure to mass media and stunting in children through water, sanitation, and hygiene behaviors. METHODS Mediation analysis was conducted using data from the 2018 Multiple Indicators Cluster Surveys. RESULTS Mothers’ exposures to television and the internet in the Democratic Republic of Congo significantly decreases the risk of stunting in children by 5% and 10%, respectively, mediated by household water, sanitation, and hygiene facilities and practices. CONCLUSIONS These findings could inform interventions and policies to reduce the rate of stunting rate children by promoting water, sanitation, and hygiene through mass media, especially through the internet and television.

Background The Democratic Republic of Congo (DRC) has experienced political unrest, civil insecurity, and military disputes, resulting in extreme poverty and a severely impaired health care system. To reduce the morbidity and mortality in women and children by strengthening healthcare, this study aimed at exploring the relationship between self-reported insecurity of mothers and maternal health-seeking behaviours and diseases in children in the DRC. Method Data collected from 8144 mothers and 14,403 children from the Multiple Indicators Cluster Survey (MICS) conducted by the National Institute of Statistics in 2017–2018, in collaboration with the United Nations Children’s Fund (UNICEF), was used. The severity of the conflict in different provinces was measured using the Uppsala Conflict Data Program (UCDP) reports. Multivariate logistic regression and stratified analysis were utilized to explore the association between conflicts with maternal health-seeking behaviours and diseases among children. Results High self-reported insecurity was positively associated with skilled antenatal care (OR1.93, 95%CI 1.50–2.49), skilled attendants at delivery (OR1.42, 95%CI 1.08–1.87), and early initiation of breastfeeding (OR1.32, 95%CI 1.04–1.68). These associations were more significant in regions with more armed conflict. It was also found that children of mothers with high self-reported insecurity were more likely to suffer from diarrhoea (OR1.47, 95%CI: 1.14–1.88), fever (OR1.23, 95%CI 1.01–1.50), cough (OR1.45, 95%CI 1.19–1.77), and dyspnea (OR2.04, 95%CI 1.52–2.73), than children of mothers with low self-reported insecurity. Conclusions Conflicts increases mothers’ insecurities and negatively affects children’s development. However, high conflict regions have to increase governmental and international assistance to promote the availability and access to maternal and child health services.