Immunogenicity of mRNA-1273 and BNT162b2 in Immunocompromised Patients: Systematic Review and Meta-analysis Using GRADE.

INTRODUCTION: Immunocompromised (IC) patients mount poor immune responses to vaccination. Higher-dose coronavirus disease 2019 (COVID-19) vaccines may offer increased immunogenicity. METHODS: A pairwise meta-analysis of 98 studies reporting comparisons of mRNA-1273 (50 or 100 mcg/dose) and BNT162b2 (30 mcg/dose) in IC adults was performed. Outcomes were seroconversion, total and neutralizing antibody titers, and cellular immune responses. RESULTS: mRNA-1273 was associated with a significantly higher seroconversion likelihood [relative risk, 1.11 (95% CI, 1.08, 1.14); P < 0.0001; I2 = 66.8%] and higher total antibody titers [relative increase, 50.45% (95% CI, 34.63%, 66.28%); P < 0.0001; I2 = 89.5%] versus BNT162b2. mRNA-1273 elicited higher but statistically nonsignificant relative increases in neutralizing antibody titers and cellular immune responses versus BNT162b2. CONCLUSION: Higher-dose mRNA-1273 had increased immunogenicity versus BNT162b2 in IC patients.

Comparative Effectiveness of mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Older Adults: Systematic Literature Review and Meta-Analysis Using the GRADE Framework.

INTRODUCTION: The mRNA vaccines mRNA-1273 and BNT162b2 demonstrated high efficacy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in phase 3 clinical trials, including among older adults. To inform coronavirus disease 2019 (COVID-19) vaccine selection, this systematic literature review (SLR) and meta-analysis assessed the comparative effectiveness of mRNA-1273 versus BNT162b2 in older adults. METHODS: We systematically searched for relevant studies reporting COVID-19 outcomes with mRNA vaccines in older adults aged ≥ 50 years by first cross-checking relevant published SLRs. Based on the cutoff date from a previous similar SLR, we then searched the WHO COVID-19 Research Database for relevant articles published between April 9, 2022, and June 2, 2023. Outcomes of interest were SARS-CoV-2 infection, symptomatic SARS-CoV-2 infection, severe SARS-CoV-2 infection, COVID-19-related hospitalization, and COVID-19-related death following ≥ 2 vaccine doses. Random effects meta-analysis models were used to pool risk ratios (RRs) across studies. Heterogeneity was evaluated using chi-square testing. Evidence certainty was assessed per GRADE framework. RESULTS: Twenty-four non-randomized real-world studies reporting clinical outcomes with mRNA vaccines in individuals aged ≥ 50 years were included in the meta-analysis. Vaccination with mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR 0.72 [95% confidence interval (CI) 0.64‒0.80]), symptomatic SARS-CoV-2 infection (RR 0.72 [95% CI 0.62‒0.83]), severe SARS-CoV-2 infection (RR 0.67 [95% CI 0.57‒0.78]), and COVID-19-related hospitalization (RR 0.65 [95% CI 0.53‒0.79]) but not COVID-19-related death (RR 0.80 [95% CI 0.64‒1.00]) compared with BNT162b2. There was considerable heterogeneity between studies for all outcomes (I2 > 75%) except death (I2 = 0%). Multiple subgroup and sensitivity analyses excluding specific studies generally demonstrated consistent results. Certainty of evidence across outcomes was rated as low (type 3) or very low (type 4), reflecting the lack of randomized controlled trial data. CONCLUSION: Meta-analysis of 24 observational studies demonstrated significantly lower risk of asymptomatic, symptomatic, and severe infections and hospitalizations with the mRNA-1273 versus BNT162b2 vaccine in older adults aged ≥ 50 years.

Social Media in Health Science Education: An International Survey.

BACKGROUND: Social media is an asset that higher education students can use for an array of purposes. Studies have shown the merits of social media use in educational settings; however, its adoption in health science education has been slow, and the contributing reasons remain unclear. OBJECTIVE: This multidisciplinary study aimed to examine health science students' opinions on the use of social media in health science education and identify factors that may discourage its use. METHODS: Data were collected from the Universitas 21 "Use of social media in health education" survey, distributed electronically among the health science staff and students from 8 universities in 7 countries. The 1640 student respondents were grouped as users or nonusers based on their reported frequency of social media use in their education. RESULTS: Of the 1640 respondents, 1343 (81.89%) use social media in their education. Only 462 of the 1320 (35.00%) respondents have received specific social media training, and of those who have not, the majority (64.9%, 608/936) would like the opportunity. Users and nonusers reported the same 3 factors as the top barriers to their use of social media: uncertainty on policies, concerns about professionalism, and lack of support from the department. Nonusers reported all the barriers more frequently and almost half of nonusers reported not knowing how to incorporate social media into their learning. Among users, more than one fifth (20.5%, 50/243) of students who use social media "almost always" reported sharing clinical images without explicit permission. CONCLUSIONS: Our global, interdisciplinary study demonstrates that a significant number of students across all health science disciplines self-reported sharing clinical images inappropriately, and thus request the need for policies and training specific to social media use in health science education.

Structure and validity of Family Harmony Scale: An instrument for measuring harmony.

Culture plays a role in mental health, partly by defining the characteristics that are indicative of positive adjustment. In Chinese cultures, positive family relationships are considered central to well-being. The culturally emphasized characteristic of family harmony may be an important factor associated with psychopathology. This article presents the development and psychometric examination of the Family Harmony Scale (FHS), an indigenously developed 24-item instrument tapping family harmony in 17,461 Hong Kong residents from 7,791 households. A higher-order model with 1 second-order factor and 5 first-order factors fit the data well and showed factorial invariance across sex and participants in different family roles. A 5-item short form (FHS-5) was also developed, with 1 item from each first-order factor. The short scale showed, as expected, a single-factor structure with good fit. Both scales demonstrated high internal consistency, acceptable test-retest reliability, and good convergent and discriminant validity. The 24-item FHS was negatively associated with depressive symptoms after accounting for individual risk factors and general family function. Family harmony moderated the relationship between life stress and depressive symptoms such that those individuals who reported low family harmony had stronger associations between life stress and depressive symptoms. This study adds to the literature a systematically developed, multidimensional measure of family harmony, which may be an important psychological protective factor, in a large urban Chinese sample. The FHS-5 minimizes operational and respondent burdens, making it an attractive tool for large-scale epidemiological studies with Chinese populations in urban settings, where over half of China's 1.4 billion people reside.

Estradiol concentrations in young healthy US versus Chinese men.

OBJECTIVES: The role of estrogens among men has rarely been explicitly considered. We examined differences in total, free, and bioavailable estradiol (Bio E) between young men from the United States (US) and the most economically developed part of China, that is, Hong Kong (HK). METHODS: Cross-sectional analysis was conducted based on 365 young men from the Third National Health and Nutrition Examination Survey in the US and 299 young Chinese men. All participants were aged from 18 to 29 years. Main outcome measures were total estradiol (E2) and calculated Bio E and free estradiol (FE). RESULTS: In both young US and Chinese men, E2 concentrations peaked at ages 25-29 years, at 43.3 pg/ml [95% confidence interval (CI) 41.9-44.8] in US men and 29.0 pg/ml (95% CI 26.2-32.0) in Chinese men. After adjustment for age and ethnicity, in all participants, US men had higher average concentrations of E2 [39.0 (95% CI 38.6-39.4) versus 28.3 (95% CI 28.3-28.4) pg/ml], FE [72.9 (95% CI 72.7-73.7) versus 56.8 (95% CI 56.6-56.9) ng/dl], and Bio E [17.9 (95% CI 17.7-18.1) versus 14.9 (95% CI 14.8-14.9) pg/ml] than HK men. Further adjustment for height or body mass index did not change the results. CONCLUSIONS: Estradiol, and free and Bio E concentrations are much lower in young healthy Chinese men than US men. However, these findings based on comparison between the two assays in the two different locations need further confirmation.

Abnormalities in circulating plasmacytoid dendritic cells in patients with systemic lupus erythematosus.

INTRODUCTION: Dendritic cells (DCs) are capable of inducing immunity or tolerance. Previous studies have suggested plasmacytoid DCs (pDCs) are pathogenic in systemic lupus erythematosus (SLE). However, the functional characteristics of directly isolated peripheral circulating blood pDCs in SLE have not been evaluated previously. METHODS: Peripheral blood pDCs from 62 healthy subjects and 58 SLE patients were treated with apoptotic cells derived from polymorphonuclear cells (PMNs). Antigen loaded or unloaded pDCs were then co-cultured with autologous or allogenous T cells. Changes in T cell proliferation, cell surface CD25 expression, intracellular Foxp3 expression and cytokine production were evaluated. pDCs that had captured apoptotic PMNs (pDCs + apoPMNs were also studied for their cytokine production (interferon (IFN)-alpha, interleukin (IL)-6, IL-10, IL-18) and toll like receptor (TLR) expression. RESULTS: Circulating pDCs from SLE patients had an increased ability to stimulate T cells when compared with control pDCs. Using allogenous T cells as responder cells, SLE pDCs induced T cell proliferation even in the absence of apoptotic PMNs. In addition, healthy pDCs + apoPMNs induced suppressive T regulatory cell features with increased Foxp3 expression in CD4 + CD25 + cells while SLE pDCs + apoPMNs did not. There were differences in the cytokine profile of pDCs that had captured apoptotic PMNs between healthy subjects and patients with SLE. Healthy pDCs + apoPMNs showed decreased production of IL-6 but no significant changes in IL-10 and IL-18. These pDCs + apoPMNs also showed increased mRNA transcription of TLR9. On the other hand, while SLE pDCs + apoPMNs also had decreased IL-6, there was decreased IL-18 mRNA expression and persistent IL-10 protein synthesis. In addition, SLE pDCs lacked TLR9 recruitment. CONCLUSIONS: We have demonstrated that peripheral circulating pDCs in patients with SLE were functionally abnormal. They lacked TLR9 expression, were less capable of inducing regulatory T cell differentiation and had persistent IL-10 mRNA expression following the capture of apoptotic PMNs. We suggest circulating pDCs may be pathogenically relevant in SLE.

Phenotypic and functional abnormalities of bone marrow-derived dendritic cells in systemic lupus erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoreactive T and B cells, which are believed to be secondary to deficient dendritic cells (DCs). However, whether DC abnormalities occur during their development in the bone marrow (BM) or in the periphery is not known. METHODS: Thirteen patients with SLE and 16 normal controls were recruited. We studied the morphology, phenotype, and functional abilities of bone marrow-derived dendritic cells (BMDCs) generated by using two culture methods: FMS-like tyrosine kinase 3 (Flt3)-ligand (FL) and granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), respectively. RESULTS: BMDCs induced by FL exhibited both myeloid (mDC) and plasmacytoid DC (pDC) features, whereas GM-CSF/IL-4 induced mDC generation. Substantial phenotypic and functional defects of BMDCs were found from patients with SLE at different stages of cell maturation. When compared with healthy controls, SLE immature BM FLDCs expressed higher levels of CCR7. Both immature and mature SLE BM FLDCs expressed higher levels of CD40 and CD86 and induced stronger T-cell proliferation. SLE BM mDCs expressed higher levels of CD40 and CD86 but lower levels of HLA-DR and a lower ability to stimulate T-cell proliferation when compared with control BM mDCs. CONCLUSIONS: Our data are in accordance with previous reports that suggest that DCs have a potential pathogenic role in SLE. Defects of these cells are evident during their development in BM. BM mDCs are deficient, whereas BM pDCs, which are part of BM FLDCs, are the likely culprit in inducing autoimmunity in SLE.

Intergenerational 'mismatch' and adiposity in a developing population: the Guangzhou biobank cohort study.

Intergenerational 'mismatch' between maternal and adult environments, common in developing economies, has been hypothesized as contributing to obesity. In a rapidly developing population, we examined whether maternal conditions, proxied by maternal literacy, were associated with adult adiposity, proxied by body mass index (BMI) and waist-hip ratio (WHR) and whether these associations were modified by later life conditions, proxied by socio-economic position (SEP) at three life stages. We also examined if maternal conditions had sex-specific associations with adult adiposity. In a cross-sectional study of 19,957 adults (> or =50 years) from the Guangzhou Biobank Cohort Study (phases 2 and 3 in 2005-2008), we used multivariable linear regression to assess the association of maternal literacy with BMI and WHR, and whether the associations varied with sex, age or SEP. The adjusted association of maternal literacy with WHR varied with sex. In women, but not men, maternal illiteracy was associated with higher WHR and BMI, adjusted for age; these associations remained, although attenuated, after adjusting for lifestyle, life course SEP and paternal literacy. There was little evidence that associations varied with SEP at any stage, although continuity of poor conditions into early life may have exacerbated the association of maternal illiteracy with higher WHR in women. Poor maternal conditions in developing populations may increase vulnerability to adiposity in women. Whether such sex-specific intergenerational effects are driven by epigenetics, maternal sex hormones or other mechanisms, remains to be determined. However, mismatched maternal and later life conditions do not appear to be associated with adiposity. Our findings, although preliminary, imply that a transient epidemic of obesity may occur in the first generation of women who experience economic development.

Systemic lupus erythematosus patients have increased number of circulating plasmacytoid dendritic cells, but decreased myeloid dendritic cells with deficient CD83 expression.

Dendritic cells (DCs) are functionally abnormal in systemic lupus erythematosus (SLE). However, previous studies have involved in-vitro cytokine-induced DCs. In this investigation, directly isolated circulating plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) in SLE were studied. Blood dendritic cell antigen (BDCA)-4 and BDCA-1 magnetic isolation kits were used to isolate blood pDCs and mDCs from 30 SLE patients and 36 controls. Their number and surface markers, and their relationship with lupus disease activity were evaluated. The percentage of pDCs per peripheral blood mononuclear cells was higher in SLE (0.33+/-0.14) than in controls (0.16+/-0.09, P<0.01), but that of mDCs was lower in SLE (0.43+/-0.14) than in controls (0.63+/-0.32; P<0.01). In controls, both pDCs and mDCs expressed high levels of MHC-II, however, the expression of CD86, CD83 and CCR7 on pDCs were significantly lower than that on mDCs (all P<0.05). mDCs from patients with SLE, particularly those with active disease, expressed lower CD83 than controls. In health, circulating mDCs may be more efficient than pDCs in stimulating T cells. In SLE, the increased number of circulating pDCs supports a pathogenic role for these cells, and the decreased mDC number and CD83 expression may explain the susceptibility to infections in these patients.