The influence of rs53576 polymorphism in the oxytocin receptor (OXTR) gene on empathy in healthy adults by subtype and ethnicity: a systematic review and meta-analysis

Empathy is essential for navigating complex social environments. Prior work has shown associations between rs53576, a single nucleotide polymorphism (SNP) located in the oxytocin receptor gene (OXTR), and generalized empathy. We undertook a systematic review and meta-analysis to assess the effects of rs53576 on subdomains of empathy, specifically cognitive empathy (CE) and affective empathy (AE), in healthy adults. Twenty cohorts of 8933 participants aged 18-98 were identified, including data from the Sydney Memory and Ageing Study, a cohort of older community adults. Meta-analyses found G homozygotes had greater generalized empathic abilities only in young to middle-aged adults. While meta-analyses of empathy subdomains yielded no significant overall effects, there were differential effects based on ethnicity. G homozygotes were associated with greater CE abilities in Asian cohorts (standardized mean difference; SMD: 0.09 [2.8·10-3-0.18]), and greater AE performance in European cohorts [SMD: 0.12 (0.04-0.21)]. The current literature highlights a need for further work that distinguishes between genetic and ethnocultural effects and explores effects of advanced age on this relationship

Grouping of tooth surfaces by susceptibility to caries: a study in 5–16 year-old children

BACKGROUND: The decline in caries has slowed and this may be indicative of variation in the susceptibility of differing teeth to caries. This study tests the hypothesis that in children, there are groups of tooth sites that exhibit differences in caries susceptibility. METHODS: Probit analysis of caries data collected from a 4-year longitudinal study of 20,000 schoolchildren aged between 5 and 16 years in 10 differing locations in the United States. RESULTS: The development of dental caries within the mouth followed a fixed hierarchy indicating that tooth surfaces show variation in caries susceptibility. Certain teeth and tooth sites have similar susceptibilities and can be grouped, the sizes of the groups vary. The most susceptible group consists of six tooth surfaces: the buccal pits and occlusal fissured surfaces of the first molar teeth. The second group consisted of 12 sites on the second molar and premolar teeth. The group formed by the least susceptible sites included the largest number of tooth surfaces and consists of the majority of the lower anterior teeth and canines. CONCLUSION: Variation in the caries susceptibility of tooth surfaces exists. Surfaces can be grouped according to caries susceptibility. An effect that reduces the cariogenic challenge of one of the sites within a group is likely to affect all the other sites within the particular group

Role of TGF-β1 haplotypes in the occurrence of myocardial infarction in young Italian patients

<p>Abstract</p> <p>Background</p> <p>Transforming growth factor beta 1 (TGF-β1) gene play an important role in the acute myocardial infarction (AMI), however no investigation has been conducted so far in young AMI patients.</p> <p>In this study, we evaluated the influence of TGF-β1 polymorphisms/haplotypes on the onset and progression of AMI in young Italian population.</p> <p>Methods</p> <p>201 cases and 201 controls were genotyped for three TGF-β1 polymorphisms (G-800A, C-509T and Leu10Pro). The main follow-up end-points (mean follow-up, 107 ± 49 months) were death, myocardial infarction or revascularization procedures.</p> <p>Results</p> <p>Significant risk factors were smoking (p < 10^-4), family history for coronary artery disease (p < 10^-4), hypercholesterolemia (p = 0.001) and hypertension (p = 0.002). The C-509T and Leu10Pro polymorphisms showed significant differences (p = 0.026 and p = 0.004) between cases and controls.</p> <p>The most common haplotypes revealed a possible protective effect (GCT, OR 0.75, 95% CI 0.57–0.99, p = 0.042) and an increased risk of AMI (GTC, OR 1.51, 95% CI 1.13–2.02, p = 0.005), respectively.</p> <p>No statistical differences were observed in genotype distribution in the follow-up study between the two groups: 61 patients with subsequent events (13 deaths) and 108 without events.</p> <p>Conclusion</p> <p>Even though our results need to be further confirmed in larger studies, this is the first study reporting on a possible role of TGFβ1 common haplotypes in the onset of AMI in young patients.</p

COVID-19 in Pregnant Women With Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance

OBJECTIVE: To describe coronavirus disease-2019 (COVID-19) and pregnancy outcomes in patients with rheumatic disease who were pregnant at the time of infection. METHODS: Since March 2020 the COVID-19 Global Rheumatology Alliance (GRA) has collected cases of patients with rheumatic disease with COVID-19. We report details of pregnant women at the time of COVID-19 infection, including obstetric details separately ascertained from providers. RESULTS: We report on 39 patients, including 22 with obstetric detail available. The mean and median age was 33 years, range 24-45 years. Rheumatic disease diagnoses included: rheumatoid arthritis (n=9), systemic lupus erythematosus (n=9), psoriatic/other inflammatory arthritides (n=8) and anti-phospholipid antibody syndrome (n=6). Most had a term birth (16/22), with 3 pre-term births, one termination, one miscarriage and one woman yet to deliver at time of report. A quarter (n=10/39) of pregnant women were hospitalised following COVID-19 diagnosis. Two of 39 (5%) required supplemental oxygen (both hospitalised); no patient died. The majority did not receive specific medication treatment for their COVID-19 (n=32/39, 82%), seven patients received some combination of anti-malarials, colchicine, anti-IL-1beta, azithromycin, glucocorticoids, and lopinavir/ritonavir. CONCLUSION: Women with rheumatic diseases who were pregnant at the time of COVID-19 had favourable outcomes. These data have limitations due to the small size and methodology, though they provide cautious optimism for pregnancy outcomes for women with rheumatic disease given the increased risk of poor outcomes that have been reported in other series of pregnant women with COVID-19

Whole-exome sequencing uncovers frequent GNAS mutations in intraductal papillary mucinous neoplasms of the pancreas

Intraductal papillary mucinous neoplasm (IPMN) is a common pancreatic cystic neoplasm that is often invasive and metastatic, resulting in a poor prognosis. Few molecular alterations unique to IPMN are known. We performed whole-exome sequencing for a primary IPMN tissue, which uncovered somatic mutations in KCNF1, DYNC1H1, PGCP, STAB1, PTPRM, PRPF8, RNASE3, SPHKAP, MLXIPL, VPS13C, PRCC, GNAS, KRAS, RBM10, RNF43, DOCK2, and CENPF. We further analyzed GNAS mutations in archival cases of 118 IPMNs and 32 pancreatic ductal adenocarcinomas (PDAs), which revealed that 48 (40.7%) of the 118 IPMNs but none of the 32 PDAs harbored GNAS mutations. G-protein alpha-subunit encoded by GNAS and its downstream targets, phosphorylated substrates of protein kinase A, were evidently expressed in IPMN; the latter was associated with neoplastic grade. These results indicate that GNAS mutations are common and specific for IPMN, and activation of G-protein signaling appears to play a pivotal role in IPMN

MIG and the Regulatory Cytokines IL-10 and TGF-β1 Correlate with Malaria Vaccine Immunogenicity and Efficacy

Malaria remains one of the world's greatest killers and a vaccine is urgently required. There are no established correlates of protection against malaria either for natural immunity to the disease or for immunity conferred by candidate malaria vaccines. The RTS,S/AS02A vaccine offers significant partial efficacy against malaria

Three allele combinations associated with Multiple Sclerosis

BACKGROUND: Multiple sclerosis (MS) is an immune-mediated disease of polygenic etiology. Dissection of its genetic background is a complex problem, because of the combinatorial possibilities of gene-gene interactions. As genotyping methods improve throughput, approaches that can explore multigene interactions appropriately should lead to improved understanding of MS. METHODS: 286 unrelated patients with definite MS and 362 unrelated healthy controls of Russian descent were genotyped at polymorphic loci (including SNPs, repeat polymorphisms, and an insertion/deletion) of the DRB1, TNF, LT, TGFβ1, CCR5 and CTLA4 genes and TNFa and TNFb microsatellites. Each allele carriership in patients and controls was compared by Fisher's exact test, and disease-associated combinations of alleles in the data set were sought using a Bayesian Markov chain Monte Carlo-based method recently developed by our group. RESULTS: We identified two previously unknown MS-associated tri-allelic combinations: -509TGFβ1*C, DRB1*18(3), CTLA4*G and -238TNF*B1,-308TNF*A2, CTLA4*G, which perfectly separate MS cases from controls, at least in the present sample. The previously described DRB1*15(2) allele, the microsatellite TNFa9 allele and the biallelic combination CCR5Δ32, DRB1*04 were also reidentified as MS-associated. CONCLUSION: These results represent an independent validation of MS association with DRB1*15(2) and TNFa9 in Russians and are the first to find the interplay of three loci in conferring susceptibility to MS. They demonstrate the efficacy of our approach for the identification of complex-disease-associated combinations of alleles

Outcomes of COVID-19 in patients with primary systemic vasculitis or polymyalgia rheumatica from the COVID-19 Global Rheumatology Alliance physician registry: a retrospective cohort study

BACKGROUND: Patients with primary systemic vasculitis or polymyalgia rheumatica might be at a high risk for poor COVID-19 outcomes due to the treatments used, the potential organ damage cause by primary systemic vasculitis, and the demographic factors associated with these conditions. We therefore aimed to investigate factors associated with COVID-19 outcomes in patients with primary systemic vasculitis or polymyalgia rheumatica. METHODS: In this retrospective cohort study, adult patients (aged ≥18 years) diagnosed with COVID-19 between March 12, 2020, and April 12, 2021, who had a history of primary systemic vasculitis (antineutrophil cytoplasmic antibody [ANCA]-associated vasculitis, giant cell arteritis, Behçet's syndrome, or other vasculitis) or polymyalgia rheumatica, and were reported to the COVID-19 Global Rheumatology Alliance registry were included. To assess COVID-19 outcomes in patients, we used an ordinal COVID-19 severity scale, defined as: (1) no hospitalisation; (2) hospitalisation without supplemental oxygen; (3) hospitalisation with any supplemental oxygen or ventilation; or (4) death. Multivariable ordinal logistic regression analyses were used to estimate odds ratios (ORs), adjusting for age, sex, time period, number of comorbidities, smoking status, obesity, glucocorticoid use, disease activity, region, and medication category. Analyses were also stratified by type of rheumatic disease. FINDINGS: Of 1202 eligible patients identified in the registry, 733 (61·0%) were women and 469 (39·0%) were men, and their mean age was 63·8 years (SD 17·1). A total of 374 (31·1%) patients had polymyalgia rheumatica, 353 (29·4%) had ANCA-associated vasculitis, 183 (15·2%) had giant cell arteritis, 112 (9·3%) had Behçet's syndrome, and 180 (15·0%) had other vasculitis. Of 1020 (84·9%) patients with outcome data, 512 (50·2%) were not hospitalised, 114 (11·2%) were hospitalised and did not receive supplemental oxygen, 239 (23·4%) were hospitalised and received ventilation or supplemental oxygen, and 155 (15·2%) died. A higher odds of poor COVID-19 outcomes were observed in patients who were older (per each additional decade of life OR 1·44 [95% CI 1·31–1·57]), were male compared with female (1·38 [1·05–1·80]), had more comorbidities (per each additional comorbidity 1·39 [1·23–1·58]), were taking 10 mg/day or more of prednisolone compared with none (2·14 [1·50–3·04]), or had moderate, or high or severe disease activity compared with those who had disease remission or low disease activity (2·12 [1·49–3·02]). Risk factors varied among different disease subtypes. INTERPRETATION: Among patients with primary systemic vasculitis and polymyalgia rheumatica, severe COVID-19 outcomes were associated with variable and largely unmodifiable risk factors, such as age, sex, and number of comorbidities, as well as treatments, including high-dose glucocorticoids. Our results could be used to inform mitigation strategies for patients with these diseases. FUNDING: American College of Rheumatology and the European Alliance of Associations for Rheumatology