Trust as a mediator in the relationship between childhood sexual abuse and IL-6 level in adulthood

Childhood sexual abuse (CSA) has been shown to predict the coupling of depression and inflammation in adulthood. Trust within intimate relationships, a core element in marital relations, has been shown to predict positive physical and mental health outcomes, but the mediating role of trust in partners in the association between CSA and inflammation in adulthood requires further study. The present study aimed to examine the impact of CSA on inflammatory biomarkers (IL-6 and IL-1β) in adults with depression and the mediating role of trust. A cross-sectional survey data set of adults presenting with mood and sleep disturbance was used in the analysis. CSA demonstrated a significant negative correlation with IL-6 level (r = -0.28, p<0. 01) in adults with clinically significant depression, while trust showed a significant positive correlation with IL-6 level (r = 0.36, p < .01). Sobel test and bootstrapping revealed a significant mediating role for trust between CSA and IL-6 level. CSA and trust in partners were revealed to have significant associations with IL-6 level in adulthood. Counterintuitively, the directions of association were not those expected. Trust played a mediating role between CSA and adulthood levels of IL-6. Plausible explanations for these counterintuitive findings are discussed

Icosahedral metallacarborane/carborane species derived from 1,1′-bis(o-carborane)

We thank ORSAS (GS) and the EPSRC (DE and DMcK supported by project EP/E02971X/1, WYM supported by project EP/I031545/1) for funding.Examples of singly-metallated derivatives of 1,1[prime or minute]-bis(o-carborane) have been prepared and spectroscopically and structurally characterised. Metallation of [7-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-7,8-nido-C2B9H10]2- with a {Ru(p-cymene)}2+ fragment affords both the unisomerised species [1-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-3-(p-cymene)-3,1,2-closo-RuC2B9H10] (2) and the isomerised [8-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-2-(p-cymene)-2,1,8-closo-RuC2B9H10] (3), and 2 is easily transformed into 3 with mild heating. Metallation with a preformed {CoCp}2+ fragment also affords a 3,1,2-MC2B9-1[prime or minute],2[prime or minute]-C2B10 product [1-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-3-Cp-3,1,2-closo-CoC2B9H10] (4), but if CoCl2/NaCp is used followed by oxidation the result is the 2,1,8-CoC2B9-1[prime or minute],2[prime or minute]-C2B10 species [8-(1[prime or minute]-1[prime or minute],2[prime or minute]-closo-C2B10H11)-2-Cp-2,1,8-closo-CoC2B9H10] (5). Compound 4 does not convert into 5 in refluxing toluene, but does do so if it is reduced and then reoxidised, perhaps highlighting the importance of the basicity of the metal fragment in the isomerisation of metallacarboranes. A computational study of 1,1[prime or minute]-bis(o-carborane) is in excellent agreement with a recently-determined precise crystallographic study and establishes that the {1[prime or minute],2[prime or minute]-closo-C2B10H11} fragment is electron-withdrawing compared to H.Publisher PDFPeer reviewe

Dosage Effects of Histamine-2 Receptor Antagonist on the Primary Prophylaxis of Non-Steroidal Anti-Inflammatory Drug (NSAID)-Associated Peptic Ulcers: A Retrospective Cohort Study

postprin

Expression and reconstitution of the bioluminescent Ca2+ reporter aequorin in human embryonic stem cells, and exploration of the presence of functional IP3 and ryanodine receptors during the early stages of their differentiation into cardiomyocytes

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science China Life Sciences 59 (2016): 811-824, doi:10.1007/s11427-016-5094-6.In order to develop a novel method of visualizing possible Ca2+ signaling during the early differentiation of hESCs into cardiomyocytes and avoid some of the inherent problems associated with using fluorescent reporters, we expressed the bioluminescent Ca2+ reporter, apo-aequorin, in HES2 cells and then reconstituted active holo-aequorin by incubation with f-coelenterazine. The temporal nature of the Ca2+ signals generated by the holo-f-aequorin-expressing HES2 cells during the earliest stages of differentiation into cardiomyocytes was then investigated. Our data show that no endogenous Ca2+ transients (generated by release from intracellular stores) were detected in 1–12-day-old cardiospheres but transients were generated in cardiospheres following stimulation with KCl or CaCl2, indicating that holo-f-aequorin was functional in these cells. Furthermore, following the addition of exogenous ATP, an inositol trisphosphate receptor (IP3R) agonist, small Ca2+ transients were generated from day 1 onward. That ATP was inducing Ca2+ release from functional IP3Rs was demonstrated by treatment with 2-APB, a known IP3R antagonist. In contrast, following treatment with caffeine, a ryanodine receptor (RyR) agonist, a minimal Ca2+ response was observed at day 8 of differentiation only. Thus, our data indicate that unlike RyRs, IP3Rs are present and continually functional at these early stages of cardiomyocyte differentiation.This work was supported by the Hong Kong Theme-based Research Scheme award (T13-706/11-1), the Hong Kong Research Grants Council (RGC) General Research Fund awards (662113, 16101714, 16100115), the ANR/RGC joint research scheme award (A-HKUST601/13), and the Innovation and Technology Commission (ITCPD/17-9). HYSC was supported by a Hong Kong University Grants Council post-graduate studentship (T13-706/11- 11PG)

Efficacy and safety of tofacitinib in the treatment of rheumatoid arthritis: a systematic review and meta-analysis

BACKGROUND: Tofacitinib is a disease-modifying antirheumatic drug (DMARD) which was recently approved by US Food and Drug Administration (FDA). There are several randomised clinical trials (RCTs) that have investigated the efficacy and safety of tofacitinib in adult patients with rheumatoid arthritis (RA). A systematic review with a meta-analysis of RCTs was undertaken to determine the efficacy and safety of tofacitinib in treating patients with RA. METHODS: Electronic and clinical trials register databases were searched for published RCTs of tofacitinib between 2009 and 2013. Outcomes of interest include 20% and 50% improvement in the American College of Rheumatology Scale (ACR20 and ACR50) response rates, rates of infection, the number of immunological/haematological adverse events (AEs), deranged laboratory results (hepatic, renal, haematological tests and lipoprotein level) and the incidence of drug withdrawal. RESULTS: Eight RCTs (n = 3,791) were reviewed. Significantly greater ACR20 response rates were observed in patients receiving tofacitinib 5 and 10 mg bid (twice daily) versus placebo at week 12, with risk ratios (RR) of 2.20 (95% CI 1.58, 3.07) and 2.38 (95% CI 1.81, 3.14) respectively. The effect was maintained at week 24 for 5 mg bid (RR 1.94; 95% CI 1.55, 2.44) and 10 mg bid (RR 2.20; 95% CI 1.76, 2.75). The ACR50 response rate was also significantly higher for patients receiving tofacitinib 5 mg bid (RR 2.91; 95% CI 2.03, 4.16) and 10 mg bid (RR 3.32; 95% CI 2.33, 4.72) compared to placebo at week 12. Patients in the tofacitinib group had significantly lower mean neutrophil counts, higher serum creatinine, higher percentage change of LDL/HDL and a higher risk of ALT/AST > 1 ULN (upper limit of normal) versus placebo. There were no significant differences in AEs and withdrawal due to AEs compared to placebo. CONCLUSION: Tofacitinib is efficacious and well tolerated in patients with MTX-resistant RA up to a period of 24 weeks. However, haematological, liver function tests and lipoproteins should be monitored. Long-term efficacy and pharmacovigilance studies are recommended.published_or_final_versio

An Assessment of Risk of Iodine Deficiency Among Pregnant Women in Sarawak, Malaysia

Previous findings from a state-wide Iodine Deficiency Disorders (IDD) study among pregnant women (PW) in Sarawak indicated that PW are at risk of IDD and further assessment is needed. This paper describes the methodology used in conducting this study for an assessment of risk of iodine deficiency among pregnant women in Sarawak, Malaysia. A total of 30 maternal child health care clinics (MCHCs) were selected using probability proportional to population size (PPS) sampling technique. The PW sample size was calculated based on 95% confidence interval (CI), relative precision of 5%, design effect of 2, anticipated IDD prevalence of 65.0% and non-response rate of 20%. Thus, the total sample size required was 750 (25 respondents per selected MCHC). The WHO Expanded Programme on Immunization (EPI) surveys approach was used to randomly select the first respondent and subsequent respondents were chosen until the required number of PW was met. The required data were obtained through: face-to-face interviews (socio-demographic and food frequency questionnaire), clinical assessments (thyroid size, and hyper/hypothyroidism) and biochemical analysis (urine and blood serum). A total of 677 PW responded in the study with a response rate of 90.2%. Majority of the PW were at second gravida, aged 25-29 years old and of Malay ethnicity. The methodology used in this study was based on International guidelines which may provide state's estimates. All the necessary steps were taken into consideration to ensure valid and reliable findings on current iodine status among PW

Universality class of the restricted solid-on-solid model with hopping

We study the restricted solid-on-solid (RSOS) model with finite hopping distance $l_{0}$, using both analytical and numerical methods. Analytically, we use the hard-core bosonic field theory developed by the authors [Phys. Rev. E {\bf 62}, 7642 (2000)] and derive the Villain-Lai-Das Sarma (VLD) equation for the $l_{0}=\infty$ case which corresponds to the conserved RSOS (CRSOS) model and the Kardar-Parisi-Zhang (KPZ) equation for all finite values of $l_{0}$. Consequently, we find that the CRSOS model belongs to the VLD universality class and the RSOS models with any finite hopping distance belong to the KPZ universality class. There is no phase transition at a certain finite hopping distance contrary to the previous result. We confirm the analytic results using the Monte Carlo simulations for several values of the finite hopping distance.Comment: 13 pages, 3 figure

Do people feel they belong? Socio‐political factors shaping the place attachment of Hong Kong citizens

Hong Kong citizens’ sense of belonging has gone through a period of fluctuation during the period of rapid socio‐political and legal change since the outbreak of the Anti‐Extradition Law Amendment Bill Movement in 2019. This study explored how multiple dimensions of the place attachment of Hong Kong citizens have been shaped by factors associated with these changes. Six socio‐political variables were incorporated into the three dimensions of the person–process–place (PPP) framework. Based on a representative survey of the local population (n = 768), we found that political inclination and identity were significantly associated with the sense of place, with citizens identifying as Chinese and aligning with the pro‐establishment camp showing higher levels of place attachment. Mobility was negatively associated with place attachment, whereas the correlation between attachment and perceptions of the law and legal system was positive. The study has implications for Hong Kong’s current socio‐political and institutional environment and for emigration. It also demonstrates the wider applicability of the PPP framework for identifying and clarifying the various predictors of different dimensions of place attachment

Frequent epigenetic inactivation of secreted frizzled-related protein 2 (SFRP2) by promoter methylation in human gastric cancer

The role of secreted frizzled-related protein (SFRP) genes in gastric cancer remains largely unknown. We determined the frequency and functional significance of SFRPs hypermethylation in human gastric cancer. The expression and methylation status of four SFRP members (SFRP1, 2, 4, and 5) in primary gastric cancer samples was screened. The biological effects of SFRP were analysed by flow cytometry, cell viability assay and in vivo tumour growth in nude mice. Among the four SFRPs, only SFRP2 was significantly downregulated in gastric cancer as compared to adjacent non-cancer samples (P<0.01). Promoter hypermethylation of SFRP2 was detected in 73.3% primary gastric cancer tissues, 37.5% of samples showing intestinal metaplasia and 20% adjacent normal gastric tissues. Bisulphite DNA sequencing confirmed the densely methylated SFRP2 promoter region. Demethylation treatment restored the expression of SFRP2 in gastric cancer cell lines. Forced expression of SFRP2 induced cell apoptosis, inhibited proliferation of gastric cancer cells and suppressed tumour growth in vivo. Moreover, methylated SFRP2 was detected in 66.7% of serum samples from cancer patients but not in normal controls. In conclusion, epigenetic inactivation of SFRP2 is a common and early event contributing to gastric carcinogenesis and may be a potential biomarker for gastric cancer