Alterations In Vitamin D Metabolism With Chronic Inflammation: Potential Implications In Inflammation-Induced Bone Loss

Inflammatory conditions are often associated with compromised serum 25-(OH)D3 status and previous in vitro studies have shown that inflammatory cytokines may be involved. The objective of this study was to examine the effects of low dose LPS in vivo on inflammatory mediators and gene expression of VDR and hydroxylation enzymes involved in vitamin D metabolism. In experiment 1, 12-week-old male C57BL/6J mice (n=12/group) were randomly assigned to LPS (0, 0.01, and 0.1 mg/kg bw/d) delivered by slow release pellets over 30 and 90 days. In experiment 2, 16-week-old male C57BL/6J mice (n=10/group) were administered (i.p.) LPS (0, 0.1, 0.2 mg/kg bw/d) for 14 days. Body weight was not altered during either study. Low dose LPS increased hepatic TLR4, CD14, and IL-10 after 14 days. No alterations were observed in hepatic genes of interest after 30 days, but IL-10 and IL-1?; were decreased after 90 days. Splenic IL-1?; tended to increase (p = 0.05) after 14 days and IL-6 was increased in low dose LPS after 90 days. Hepatic CYP27A1 gene expression was decreased after 90 days, but not after 14 and 30 days. High dose LPS tended to decrease (p=0.08) splenic VDR after 14 days, and decreased CYP27B1 after 90 days. Renal CYP27B1 was decreased and CYP24A1 was increased after 14 days. A significant increased in plasma 25-(OH)D 3 was observed after 14 days, but not 30 days. Our data suggest that chronic low dose LPS has modest effects on VDR, decreases renal CYP27B1, and increases renal CYP24A1. Further studies should further explore how LPS alters renal gene expression of cytochrome P450 enzymes involved in vitamin D metabolism over time.Department of Nutritional Science

Consumer adoption of on-demand digital platforms: An integrated model

On-demand digital platforms are omnipresent in the contemporary marketplace of the digital era. The purpose of this study was to assess the factors influencing consumers’ intention to adopt on-demand digital platforms in the context of a developing country. Based on a modified integration of the unified theory of acceptance and use of technology (UTAUT) and the social influence theory, this study contended that electronic word-of-mouth (eWOM) about on-demand digital platforms shapes consumers’ perceived risk and subjective norms, which, along with the other elements of UTAUT, influence their intention to use OnDemand digital platforms. A self-administered questionnaire was developed and distributed online, yielding a total of 226 responses, which were analyzed using partial least squares structural equation modelling. The findings revealed that performance expectancy, effort expectancy, subjective norms, and perceived risk significantly affect consumers’ intention, wherein eWOM reduces perceived risk and shapes subjective norms to adopt on-demand digital platforms. Therefore, this study contributes to the literature on consumer adoption of new-age digital products, and in this case, on-demand digital platforms, with implications for theory and practice in this space

Factors Influencing COVID-19 Vaccination Intention among University Students : A Cross-Sectional Study in Malaysia

Vaccination is crucial in controlling the spread of the coronavirus disease 2019 (COVID-19) that triggered the pandemic, but herd immunity can only work with high vaccination coverage in the population. This study aims to measure the COVID-19 knowledge level and determine the factors influencing COVID-19 vaccination intention among university students in Malaysia. A cross-sectional online survey was carried out with 1,274 Malaysian university students in July 2021. Univariate and multivariate analyses were employed to examine the relationships between the study variables. Results showed that the majority of university students had an acceptable level of knowledge of COVID-19. The knowledge, risk perception of COVID-19, social norms, and perceived benefit of COVID-19 vaccination were positively associated with vaccination intention. However, perceived trust in information sources of COVID-19 vaccination and the government's response to COVID-19 did not affect the university students’ desire to receive the vaccination. These findings are essential for health policymakers and healthcare providers to implement evidence-based interventions to increase COVID-19 vaccination uptake among university students

Modifiable Risk Factor Score and Fecundability in a Preconception Cohort in Singapore

Importance: Although multiple modifiable risk factors have been identified for reduced fecundability (defined as lower probability of conception within a menstrual cycle), no scoring system has been established to systematically evaluate fecundability among females who are attempting to conceive. Objective: To examine the association of a risk score based on 6 modifiable factors with fecundability, and to estimate the percentage reduction in incidence of nonconception if all study participants achieved a minimal risk score level. Design, Setting, and Participants: This population-based cohort study obtained data from the S-PRESTO (Singapore Preconception Study of Long-Term Maternal and Child Outcomes) prospective cohort study. Females of reproductive age who were trying to conceive were enrolled from February 2015 to October 2017 and followed for 1 year, ending in November 2018. Data were analyzed from March to May 2022. Exposures: A reduced fecundability risk score was derived by giving participants 1 point for each of the following factors: unhealthy body mass index, unhealthy diet, smoking, alcohol intake, folic acid supplement nonuser, and older maternal age. Total scores ranged from 0 to 6 and were classified into 5 levels: level 1 (score of 0 or 1), level 2 (score of 2), level 3 (score of 3), level 4 (score of 4), and level 5 (score of 5 or 6). Main Outcomes and Measures: Fecundability, measured by time to conception in cycles, was analyzed using discrete-time proportional hazards models with confounder adjustment. Results: A total of 937 females (mean [SD] age, 30.8 [3.8] years) were included, among whom 401 (42.8%) spontaneously conceived within 1 year of attempting conception; the median (IQR) number of cycles before conception was 4 (2-7). Compared with participants with a level 1 risk score, those with level 2, 3, 4, and 5 risk scores had reductions in fecundability of 31% (adjusted fecundability ratio [FR], 0.69; 95% CI, 0.54-0.88), 41% (FR, 0.59; 95% CI, 0.45-0.78), 54% (FR, 0.46; 95% CI, 0.31-0.69) and 77% (FR, 0.23; 95% CI, 0.07-0.73), respectively. Assessment of the population attributable fraction showed that all participants achieving a minimal (level 1) risk level would be associated with a reduction of 34% (95% CI, 30%-39%) in nonconception within a year. Conclusions and Relevance: Results of this study revealed the co-occurrence of multiple modifiable risk factors for lowered fecundability and a substantially higher conception rate among participants with no or minimal risk factors. The risk assessment scoring system proposed is a simple and potentially useful public health tool for mitigating risks and guiding those who are trying to conceive.publishedVersionPeer reviewe

A study assessing the association of glycated hemoglobin a1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of asian ancestry

10.1371/journal.pone.0079767PLoS ONE811-POLN

Genetic Variants on Chromosome 1q41 Influence Ocular Axial Length and High Myopia

As one of the leading causes of visual impairment and blindness, myopia poses a significant public health burden in Asia. The primary determinant of myopia is an elongated ocular axial length (AL). Here we report a meta-analysis of three genome-wide association studies on AL conducted in 1,860 Chinese adults, 929 Chinese children, and 2,155 Malay adults. We identified a genetic locus on chromosome 1q41 harboring the zinc-finger 11B pseudogene ZC3H11B showing genome-wide significant association with AL variation (rs4373767, β = −0.16 mm per minor allele, Pmeta = 2.69×10−10). The minor C allele of rs4373767 was also observed to significantly associate with decreased susceptibility to high myopia (per-allele odds ratio (OR) = 0.75, 95% CI: 0.68–0.84, Pmeta = 4.38×10−7) in 1,118 highly myopic cases and 5,433 controls. ZC3H11B and two neighboring genes SLC30A10 and LYPLAL1 were expressed in the human neural retina, retinal pigment epithelium, and sclera. In an experimental myopia mouse model, we observed significant alterations to gene and protein expression in the retina and sclera of the unilateral induced myopic eyes for the murine genes ZC3H11A, SLC30A10, and LYPLAL1. This supports the likely role of genetic variants at chromosome 1q41 in influencing AL variation and high myopia

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely