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Abstract Background Presently, where inactivity is an overarching problem globally, participation in recreational sports activities has become an important outlet for promoting healthy lifestyles. However, there is a lack of instruments to evaluate the commitment of recreational and leisure sports users. This study aimed to adapt, develop and provide preliminary validation of the Recreational Sport Commitment Questionnaire (RESQ). Methods The development and validation process in this study consisted of four stages: Stage One involved item pool generation, Stage Two focused on content and face validation, Stage Three encompassed data collection, and Stage Four included the assessment of the psychometric properties of the RESQ. This final stage was conducted through Exploratory Factor Analysis (EFA; n = 275) and Confirmatory Factor Analysis (CFA; n = 313) to evaluate convergent validity, discriminant validity, and composite reliability. Results The initial item pool generated 60 items, whereby 42 items were retained after the content validity evaluation process by the panel of experts. Next, EFA analysis suggested 31 items distributed across seven factors. Lastly, psychometric properties of RESQ with 26 items were established through CFA (GFI = 0.91, CFI = 0.97, RMSEA = 0.04, TLI = 0.96, X²/df = 1.52) and other psychometrics evidence. Conclusion Based on the collected psychometrics evidence, RESQ is a valid questionnaire to evaluate the commitment of recreational sports users. The newly developed questionnaire allows sports organizations to assess the factors influencing sport commitment among recreational sports users. Based on the results of RESQ, sport programmes can be tailored made to optimize sports engagement and promote continued commitment.

Abstract Cancer cells are constantly evolving to adapt to environmental changes, particularly during exposure to drug treatment. In this work, we aimed to characterize genetic and epigenetic changes in mitochondrial DNA (mtDNA) that may increase the resistance of oral squamous cell carcinoma (OSCC) to cisplatin. We first derived drug-resistant cells from two human OSCC cell lines, namely SAS and H103, by continual cisplatin treatments for about 4 months. To determine mtDNA changes induced by cisplatin, we performed nanopore sequencing and quantitative polymerase chain reaction analysis of mtDNA extracted from the cells pre- and post-treatment. We also assessed the mitochondrial functions of the cells and their capacity to generate intracellular reactive oxygen species (ROS). We found that in the cisplatin-resistant cells derived from SAS, there was a reduction in mtDNA content and significant enrichment of a m.3910G > C mutation in the MT-ND1 gene. However, such changes were not detected in cisplatin-resistant H103 cells. The cisplatin treatment also altered methylation patterns in both SAS and H103 cells and decreased their sensitivity to ROS-induced cytotoxicity. We suggest that the sequence alterations and epigenetic changes in mtDNA and the reduction in mtDNA content could be key drivers of cisplatin resistance in OSCC. These mtDNA alterations may participate in cellular adaptation that serves as a response to adverse changes in the environment, particularly exposure to cytotoxic agents. Importantly, the observed mtDNA changes may be influenced by the distinct genetic landscapes of various cancer subtypes. Overall, this study reveals significant insights into cisplatin resistance driven by complex mtDNA dynamics, particularly in OSCC. This underscores the need for targeted therapies tailored to the genetic profiles of individual OSCC patients to improve disease prognosis.

Abstract Single nucleotide polymorphisms (SNPs) could increase the susceptibility of individuals to develop obesity and type 2 diabetes (T2DM). Obesity and T2DM are closely related pathophysiologically, thus similar SNPs could mediate both these diseases, but this is rarely reported. Furthermore, limited studies have been performed to summarize SNP data in the Asian population compared to the Western population. In this study, we aimed to summarize SNPs that are associated with the development of obesity and T2DM among Asian populations. We searched six literature databases and Review Manager (RevMan) was used for meta-analysis. The pooled odds ratios (ORs) and 95% CIs were calculated with a random effects model for the heterogeneity among studies. The pooled analysis showed that rs9939609 (FTO gene) and rs17782313 and rs571312 (MC4R gene) are associated with obesity with an odd ratio (OR) of 1.37, 1.36 and 1.29 respectively. For T2DM, five SNPs, rs7903146 and rs12255372 (TCF7L2 gene), rs13266634 and rs11558471 (SLC30A8 gene) and rs2283228 (KCNQ1 gene) have also shown strong associations with T2DM at OR of 1.64, 1.61, 1.22, 1.29 and 1.60 respectively. This data could be used to develop a gene screening panel for assessing obesity and T2DM susceptibility.

Lung cancer as the second most death cancer reported cases is becoming a major threat to the global healthcare system. With the different subtypes of lung cancer and their limited therapy options due to the lack of targetable genes, rising cases of treatment resistance further complicate the management. The majority of the reported lung cancer cases are categorised as non-small cell lung cancer (NSCLC) which is highly associated with tobacco smoking. Tumorigenesis and cancer progression have also been associated with epigenetics. Epigenetics is responsible for cancer gene regulation and its reversible mechanisms attract the current trend of cancer management research. One of the most studied mechanisms is DNA methylation which can influence the cancer gene transcription outcomes. The enzyme, DNA methyltransferases (DNMTs) play a role in regulating the whole process of DNA methylation. Thus, abnormalities in DNMTs can lead to aberrant methylation patterns which then disturb the gene regulation and cellular functions as a whole. In this review, NSCLC subtypes are discussed with the current research trend of studies involving DNA methylation mechanism as a potential diagnostic and prognostic cancer biomarker. As DNMTs expression influences the methylation pattern, our review also outlined the abnormal pattern of DNMTs and its potential therapeutic target for NSCLC to restore the aberrant gene regulation and produce a better prognosis.

Athlete support personnel (ASP) work closely with, treat, or assist an athlete participating in or preparing for sports competition. Their involvement in preventing and eliminating doping is crucial. This study investigated the knowledge, attitudes, and practices related to doping in sports among ASP from Southeast Asian countries. An anonymized self-administered questionnaire assessing knowledge, attitudes, and practices related to doping in sports issues was administered to ASP from Southeast Asian countries. Overall, 596 respondents from eleven countries participated in the study. The majority were male (67.1%), non-healthcare professionals (89.4%), and retired elite athletes (57.7%). Their knowledge was found to be poor, reflected in a mean score of 16.1±5.4 out of 30. Attitudes towards doping, as measured by the Performance Enhancement Attitude Scale (PEAS), scored 18.1±9.4, indicating a negative attitude. While some respondents provided information on medication and supplements use in sports to athletes, only 11.8% reported regular updates on doping in sports topics. Meanwhile, the knowledge and PEAS scores were significantly different between the genders (p = 0.04; p = 0.02). The knowledge score was also negatively correlated with the PEAS (p

Objective: To assess student-athletes’ knowledge and attitudes towards sport-related concussions and to investigate concussion history and reporting behaviours. Method: The cross-sectional, survey-based study was conducted from September 2020 to June 2021 after approval from the research ethics committee of Universiti Malaya, Malaysia, and comprised student-athletes of either gender aged 18 years or above at various universities across Pakistan and who played contact or collision sports for their universities. Data was collected using the Urdu version of the Rosenbaum Concussion Knowledge and Attitudes Survey-Student Version. Data was also gathered about the participants’ self-reported exposure to formal concussion education, previous sport-related concussion history, and reporting behaviours, where applicable. Data was analysed using SPSS 23. Results: Of the 369 participants, 224(60.7%) were males and 145(39.3%) were females. The overall mean age was 19.95±1.75 years. Among the participants, 327(88.6%) had not received formal concussion education. The mean knowledge score was 12.76±2.73 out of a possible 25 points, and the mean attitude score was 38.63±10.30 out of 75 points. Knowledge had a weak positive correlation with attitude towards sport-related concussions SRC (p

Introduction: Low back pain (LBP) is a growing public health problem that can affect anybody. However, little is known regarding the quality of life (QOL) of university students in Malaysia as consequences of LBP, especially among Health Sciences students. The goal of this study was to determine the association between QOL and LBP among Health Sciences students. Methods: Through convenience sampling, 96 Health Sciences students from a Malaysian university were included in this cross-sectional survey. The Oswestry Disability Index (OSW) Questionnaire and the Short-form 36 Questionnaire (SF-36) were used to collect the data. Results: According to the findings of this study, 93.8 percent (n=90) of the students had mild LBP, whereas 6.2 percent (n=6) had moderate LBP. There were no significant mean variations in LBP by gender, age, or course type (p>0.05). This study, however, discovered a significant negative relationship between all dimensions of QOL (general health, physical, and social function) and LBP disability (r=–0.24 to –0.40), p

The Athletic Religious Faith Scale (ARFS) is an instrument measuring religious faith in a sporting context. This study validated the ARFS using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to reach a final version of the scale. Using the EFA, seven domains were classified: religious coping (9 items), religious psychological effects (5 items), dependence on faith (5 items), religious mental healing (6 items), flow (4 items), athletic identity (4 items), and religious dietary practices (7 items). Using CFA, all construct factor loadings were over 0.5. Composite reliability and Cronbach’s alpha values indicated adequate reliability (0.81–0.94) for all ARFS domains. The convergent validity and discriminant validity of all constructs were also established. Overall, the ARFS is a reliable and valid assessment tool for measuring religious faith in athletes. The ARFS could potentially be used with athletes of various religious affiliations in different countries, cultures, and sporting contexts.

Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.

Abstract Objectives Functional genetic variation plays an important role in predicting patients’ response to chemotherapeutic agents. A growing catalogue of mitochondrial DNA (mtDNA) alterations in various cancers point to their important roles in altering the drug responsiveness and survival of cancer cells. In this work, we report the mtDNA sequences, obtained using a nanopore sequencer that can directly sequence unamplified DNA, and the transcriptomes of oral squamous cell carcinoma (OSCC) cell lines with differing responses to cisplatin, to explore the interplay between mtDNA alterations, epigenetic regulation of gene expression, and cisplatin response in OSCC. Data description Two human OSCC cell lines, namely H103 and SAS, and drug-resistant stem-like cells derived from SAS were used in this work. To validate our hypothesis that cisplatin sensitivity is linked to mtDNA changes, we sequenced their mtDNA using a nanopore sequencer, MinION. We also obtained the whole transcriptomic profiles of the cells from a microarray analysis. The mtDNA mutational and whole transcriptomic profiles that we provide can be used alongside other similar datasets to facilitate the identification of new markers of cisplatin sensitivity, and therefore the development of effective therapies for OSCC.

Abstract Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P

The study aimed to determine how a teacher’s competency at the university level related to professional commitment and job satisfaction. This systematic review intends to determine physical education teachers’ competency and job satisfaction. One of the main objectives of physical education programs is to increase various activities of the student, especially physical activities and participation in it. Students who participate in physical activities feel a variety of emotions, and these may enhance their mental and physical well-being. The study concerns the teachers’ satisfaction in effectively influencing and teaching the students. Job satisfaction refers to teachers’ feelings and positive attitudes toward their work. The five components of job satisfaction are pay, promotion, supervision, co-workers, and work itself. Job satisfaction is broken down into these five components. Work as a teacher is one of the most important components of a teacher’s or teacher’s success at work and one of the key criteria for the school’s achievement. Electronic libraries were explored, including Google Scholar, PubMed, Embase, Bing Academic, and Cochrane. Appropriate keywords were used for searching the literature. By applying certain inclusion and exclusion criteria, the final studies were selected for evaluation. The study’s findings showed that physical education instructors had high levels of teaching competence and moderate levels of job satisfaction. The findings demonstrated that job satisfaction and competency rise when degree levels rise, and relatedness, skill, and autonomy self-motivation ensue. Students’ motivation for physical education was greatly influenced by the teachers’ support, motivation, and mastery climate. The self-determination theory positively enhances physical education from the teacher’s perspective on PE, increasing instruction effectiveness.

The accurate measurement of university students’ motivation to participate in physical activity (PA) is a prerequisite to developing better physical fitness programs. However, motivation driven by government policies, i.e., physical education policies, are often excluded from many existing scales. The purpose of this study was to develop and evaluate a psychometric instrument based on self-determination theory that exclusively measures the motivation of Chinese university students to participate in PA. A total of 1,215 university students who regularly participated in PA at five universities in China constituted the final valid sample. Sample 1 (n = 311) was used to determine the underlying factor structure of the initial Chinese University Students’ Physical Activity Motivation Scale (CUSPAMS) through exploratory factor analysis (EFA). Sample 2 (n = 330) was used to test the model fit of the EFA-derived factor structure and data through confirmatory factor analysis (CFA) and to test the internal consistency of each factor and of the whole scale. Sample 3 (n = 574) was used to confirm the model stability and criterion validity. Finally, 177 individuals were randomly selected from Sample 3 to perform test–retest reliability. Preliminary evidence showed that the nine-factor CUSPAMS, consisting of 32 items, yielded good psychometric characteristics. The development of the CUSPAMS provides an opportunity to improve current theories and practices regarding the assessment of PA motivation. The CUSPAMS is recommended for examining factors that influence motives as well as the impact of motives on PA among Chinese university students.

This study aimed to evaluate the community pharmacists’ knowledge of tackling the issue of inadvertent doping in Malaysia. A cross-sectional survey was conducted among 384 community pharmacists working in Malaysia using a self-administered questionnaire. All the respondents were pharmacists fully registered with the Pharmacy Board of Malaysia and had been working in the community setting for at least one year. Of the 426 community pharmacists approached, 384 community pharmacists participated in this study, giving a response rate of 90.14%. The majority of the respondents were females (63.5%), graduated from local universities (74.9%), with median years of practising as a community pharmacist of six years (interquartile range, IQR = 9 years). The respondents were found to have moderate levels of doping-related knowledge (median score of 52 out of 100). Anabolic steroids (95.8%), stimulants (78.6%) and growth factors (65.6%) were recognised as prohibited substances by most of the respondents. Around 65.9% did not recognise that inadvertent doping is also considered a doping violation. Most of them (90%) also have poor levels of knowledge of doping scenarios in the country. Community pharmacists in Malaysia have limited knowledge in the field of doping. More programmes and activities related to doping and drugs in sports should be held to enhance the community pharmacists’ knowledge on the issue of inadvertent doping.

The purposes are to deepen the understanding of the correlation between learning motivation and learning burnout and thereby stimulate the learning motivation of college students. According to the theory of educational psychology, mechanism of learning motivation, and causes of learning burnout are analyzed. The learning motivation and learning burnout of college students majoring in sports are taken as the breakthrough point. The learning motivation and learning burnout situation of Chinese and Malaysian students majoring in sports are surveyed and compared through questionnaires. In addition, Chinese students majoring in sports are taken as examples to analyze the impact of learning motivation on learning burnout. The correlations between various dimensions are analyzed to determine the impact of learning motivation on learning burnout. The total learning motivation scores of students from the Sport School of Zhengzhou University and the University of Malaya Centre for Sport and Exercise Sciences are 122.3 ± 22.4 and 140.2 ± 23.6, respectively, and their average scores for each question are 3.60 and 4.07, respectively. The total learning burnout scores of students from the Sport School of Zhengzhou University and the University of Malaya Centre for Sport and Exercise Sciences are 58.2 ± 8.95 and 53.6 ± 7.34, respectively. The learning motivation of Malaysian college students majoring in sports is slightly stronger than Chinese students. Compared with Malaysia, the learning burnout of college students majoring in sports in China is extra apparent, mainly exhibited in the two dimensions of depression and a low sense of achievement. The learning motivation and learning burnout of college students majoring in sports are negatively correlated; that is, the stronger the learning motivation, the weaker the learning burnout; on the contrary, the weaker the learning motivation, the more severe the learning burnout. In conclusion, learning burnout of college students can be reduced by correcting and stimulating their learning motivation and improving their learning self-efficacy.

Increased tissue rigidity is an emerging hallmark of cancer as it plays a critical role in promoting cancer growth. However, the field lacks a defined characterization of tissue rigidity in dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) in vivo. Pre-malignant and malignant lung SCC was developed in BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU). Picro sirius red staining and atomic force microscopy were performed to measure collagen content and collagen (diameter and rigidity), respectively. Then, the expression of tenascin C (TNC) protein was determined using immunohistochemistry staining. Briefly, all tissue rigidity parameters were found to be increased in the Cancer group as compared with the Vehicle group. Importantly, collagen content (33.63 ± 2.39%) and TNC expression (7.97 ± 2.04%) were found to be significantly higher (p < 0.05) in the Malignant Cancer group, as compared with the collagen content (18.08 ± 1.75%) and TNC expression (0.45 ± 0.53%) in the Pre-malignant Cancer group, indicating increased tissue rigidity during carcinogenesis of lung SCC. Overall, tissue rigidity of lung SCC was suggested to be increased during carcinogenesis as indicated by the overexpression of collagen and TNC protein, which may warrant further research as novel therapeutic targets to treat lung SCC effectively.

Hereditary or developmental neurological disorders (HNDs or DNDs) affect the quality of life and contribute to the high mortality rates among neonates. Most HNDs are incurable, and the search for new and effective treatments is hampered by challenges peculiar to the human brain, which is guarded by the near-impervious blood-brain barrier. Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR), a gene-editing tool repurposed from bacterial defense systems against viruses, has been touted by some as a panacea for genetic diseases. CRISPR has expedited the research into HNDs, enabling the generation of in vitro and in vivo models to simulate the changes in human physiology caused by genetic variation. In this review, we describe the basic principles and workings of CRISPR and the modifications that have been made to broaden its applications. Then, we review important CRISPR-based studies that have opened new doors to the treatment of HNDs such as fragile X syndrome and Down syndrome. We also discuss how CRISPR can be used to generate research models to examine the effects of genetic variation and caffeine therapy on the developing brain. Several drawbacks of CRISPR may preclude its use at the clinics, particularly the vulnerability of neuronal cells to the adverse effect of gene editing, and the inefficiency of CRISPR delivery into the brain. In concluding the review, we offer some suggestions for enhancing the gene-editing efficacy of CRISPR and how it may be morphed into safe and effective therapy for HNDs and other brain disorders.

Drug delivery systems have the potential to deliver high concentrations of drug to target areas on demand, while elsewhere and at other times encapsulating the drug, to limit unwanted actions. Here we show proof of concept in vivo and ex vivo tests of a novel drug delivery system based on hollow-gold nanoparticles tethered to liposomes (HGN-liposomes), which become transiently permeable when activated by optical or acoustic stimulation. We show that laser or ultrasound simulation of HGN-liposomes loaded with the GABAA receptor agonist, muscimol, triggers rapid and repeatable release in a sufficient concentration to inhibit neurons and suppress seizure activity. In particular, laser-stimulated release of muscimol from previously injected HGN-liposomes caused subsecond hyperpolarizations of the membrane potential of hippocampal pyramidal neurons, measured by whole cell intracellular recordings with patch electrodes. In hippocampal slices and hippocampal–entorhinal cortical wedges, seizure activity was immediately suppressed by muscimol release from HGN-liposomes triggered by laser or ultrasound pulses. After intravenous injection of HGN-liposomes in whole anesthetized rats, ultrasound stimulation applied to the brain through the dura attenuated the seizure activity induced by pentylenetetrazol. Ultrasound alone, or HGN-liposomes without ultrasound stimulation, had no effect. Intracerebrally-injected HGN-liposomes containing kainic acid retained their contents for at least one week, without damage to surrounding tissue. Thus, we demonstrate the feasibility of precise temporal control over exposure of neurons to the drug, potentially enabling therapeutic effects without continuous exposure. For future application, studies on the pharmacokinetics, pharmacodynamics, and toxicity of HGN-liposomes and their constituents, together with improved methods of targeting, are needed, to determine the utility and safety of the technology in humans.

We report two cases of metoclopramide-induced acute dystonia in pregnant women and consider the role of genetic variation in the pathogenesis of the adverse effect. By whole-gene sequencing, we found that both women were CYP2D6 poor metabolizers. We theorize that CYP2D6 governs the risk of metoclopramide-related acute dystonia through its role in the synthesis of serotonin, which inhibits the dopamine tone. The effect of CYP2D6 poor metabolism is exaggerated by rises in the estrogen levels during pregnancy, as the hormone augments dopamine sensitivity. Together, the two factors may create a hyper-dopaminergic state that is easily upset by metoclopramide, resulting in acute dystonia.

Electrically conductive fabrics are achieved by functionalizing with treatments such as graphene; however, these change conventional fabric properties and the treatments are typically not durable. Encapsulation may provide a solution for this, and the present work aims to address these challenges. Next-to-skin wool and cotton knit fabrics functionalized using graphene ink were encapsulated with three poly(dimethylsiloxane)-based products. Properties known to be critical in a next-to-skin application were investigated (fabric structure, moisture transfer, electrical conductivity, exposure to transient ambient conditions, wash, abrasion, and storage). Wool and cotton fabrics performed similarly. Electrical conductivity was conferred with the graphene treatment but decreased with encapsulation. Wetting and high humidity/low temperature resulted in an increase in electrical conductivity, while decreases in electrical conductivity were evident with wash, abrasion, and storage. Each encapsulant mitigated effects of exposures but these effects differed slightly. Moisture transfer changed with graphene and encapsulants. As key performance properties of the wool and cotton fabrics following treatment with graphene and an encapsulant differed from their initial state, use as a patch integrated as part of an upper body apparel item would be acceptable.

Background and objectives: Premenstrual syndrome (PMS) comprises a variety of physical and emotional symptoms that affect women of reproductive age. The distress caused by PMS often leads to self-medication, and many over-the-counter or non-prescription products are available for relieving PMS symptoms. The choice of a suitable product should be based on advice from a health professional, such as a community pharmacist. Hence, we assessed the knowledge, attitude, and practice of Malaysian community pharmacists in providing self-care recommendations for the management of PMS. Materials and Methods: A cross-sectional survey was carried out in Kuala Lumpur, Malaysia from September to November 2018 using a self-administered questionnaire. The respondents were community pharmacists working in Kuala Lumpur and were chosen from a list of Type A license holders in the city. Results: We achieved a response rate of 79% and included 181 questionnaires in the final analysis. Of the 181 respondents, most of them (76.8%; n = 139) had medium to good levels of knowledge of PMS. Likewise, most of the respondents (78.5%; n = 142) had positive attitudes toward their role in PMS management. Having taken courses on managing minor illnesses in women substantially enhanced their levels of knowledge of (p = 0.002), but not their attitude towards, PMS management. Among the PMS-relieving products, the most commonly recommended products were ibuprofen (79%; n = 143), mefenamic acid (74.5%; n = 135), and naproxen (66.9%; n = 121), which are well known for their anti-inflammatory effect. This suggests that the respondents based their product choice on sound evidence. Conclusions: Community pharmacists can play an important role in the management of PMS. In future work, a larger sample can be assembled to obtain more insight into the readiness of community pharmacists to help women in self-managing PMS and establish a specialized service to this end.

Azathioprine and 6-mercaptopurine, often referred to as thiopurine compounds, are commonly used in the management of inflammatory bowel disease. However, patients receiving these drugs are prone to developing adverse drug reactions or therapeutic resistance. Achieving predefined levels of two major thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, is a long-standing clinical practice in ensuring therapeutic efficacy; however, their correlation with treatment response is sometimes unclear. Various genetic markers have also been used to aid the identification of patients who are thiopurine-sensitive or refractory. The recent discovery of novel Asian-specific DNA variants, namely those in the NUDT15 gene, and their link to thiopurine toxicity, have led clinicians and scientists to revisit the utility of Caucasian biomarkers for Asian individuals with inflammatory bowel disease. In this review, we explore the limitations associated with the current methods used for therapeutic monitoring of thiopurine metabolites and how the recent discovery of ethnicity-specific genetic markers can complement thiopurine metabolites measurement in formulating a strategy for more accurate prediction of thiopurine response. We also discuss the challenges in thiopurine therapy, alongside the current strategies used in patients with reduced thiopurine response. The review is concluded with suggestions for future work aiming at using a more comprehensive approach to optimize the efficacy of thiopurine compounds in inflammatory bowel disease.

Debra Nestel,1 Katherine Gray,1 Margaret Simmons,1 Shane A Pritchard,1 Rumana Islam,1 Wan Q Eng,1 Adrian Ng,1 Tim Dornan2 1Gippsland Medical School/School of Rural Health, Monash University, Clayton, Australia; 2School of Health Professions Education, Maastricht University, Maastricht, the Netherlands Background: This paper explores local community perceptions of a relatively new rural medical school. For the purposes of this paper, community engagement is conceptualized as involvement in planning, delivering, and evaluating the medical program. Although there are several reviews of patient involvement in medical curricula development, this study was designed to pilot an approach to exploring the perspectives of well members of the community in the transition of institutional policy on community engagement to one medical school. Methods: An advertisement in the local newspaper invited volunteers to participate in a telephone interview about the new medical school. An independent researcher external to the medical school conducted the interviews using a topic guide. Audio recordings were not made, but detailed notes including verbatim statements were recorded. At least two research team members analyzed interview records for emergent themes. Human research ethics approval was obtained. Results: Twelve interviews were conducted. Participants offered rich imaginings on the role of the school and expectations and opportunities for students. Most participants expressed strong and positive views, especially in addressing long-term health workforce issues. It was considered important that students live, mix, and study in the community. Some participants had very clear ideas about the need of the school to address specified needs, such as indigenous health, obesity, aging, drug and alcohol problems, teenage pregnancy, ethnic diversity, and working with people of low socioeconomic status. Conclusion: This study has initiated a dialogue with potential partners in the community, which can be built upon to shape the medical school's mission and contribution to the society it serves. The telephone interview approach and thematic analysis yielded valuable insights and is recommended for further studies. Our study was limited by its small study size and the single recruitment source. The community is a rich resource for medical education, but there is a dearth of literature on the perspectives of the community and its role in medical education. Keywords: community engagement, medical education, medical school, community-based education, rural, curriculum development

Whole-exome sequencing (WES) has been widely used for analysis of human genetic diseases, but its value for the pharmacogenomic profiling of individuals is not well studied. Initially, we performed an in-depth evaluation of the accuracy of WES variant calling in the pharmacogenes CYP2D6 and CYP2C19 by comparison with MiSeq® amplicon sequencing data (n = 36). This analysis revealed that the concordance rate between WES and MiSeq® was high, achieving 99.60% for variants that were called without exceeding the truth-sensitivity threshold (99%), defined during variant quality score recalibration. Beyond this threshold, the proportion of discordant calls increased markedly. Subsequently, we expanded our findings beyond CYP2D6 and CYP2C19 to include more genes genotyped by the iPLEX® ADME PGx Panel in the subset of twelve samples. WES performed well, agreeing with the genotyping panel in approximately 99% of the selected pass-filter variant calls. Overall, our results have demonstrated WES to be a promising approach for pharmacogenomic profiling, with an estimated error rate of lower than 1%. Quality filters, particularly variant quality score recalibration, are important for reducing the number of false variants. Future studies may benefit from examining the role of WES in the clinical setting for guiding drug therapy.

Direct-to-consumer (DTC) DNA testing has grown from contentious beginnings into a global industry, by providing a wide range of personal genomic information directly to its clients. These companies, typified by the well-established 23andMe, generally carry out a gene-chip analysis of single nucleotide polymorphisms (SNPs) using DNA extracted from a saliva sample. These genetic data are then assimilated and provided direct to the client, with varying degrees of interpretation. Although much debate has focused on the limitations and ethical aspects of providing genotypes for disease risk alleles, the provision of pharmacogenetic results by DTC companies is less studied. We set out to evaluate current DTC pharmacogenetics offerings, and then to consider how these services might best evolve and adapt in order to play a potentially useful future role in delivery of personalized medicine.

In the title compound, C19H34N+·Br−·H2O, the dihedral angle between the trans-planar alkyl side chain and the pyridinium ring is 52.73 (7)°. In the crystal structure, O—H...Br, C—H...Br and C—H...O hydrogen bonds form a network, while the hydrophobic alkyl chains interdigitate, forming bilayers.