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Background: Epidemiological data on pediatric inflammatory bowel disease (PIBD) have been reported in Asian countries. However, short-term follow-up data, especially in Southeast Asian countries, are limited., Purpose: Analyze and compare the baseline and 1-year follow-up (1FU) data for PIBD in Asian children., Methods: The multinational network included patients with PIBD (aged <19 years) in five Asian countries (Malaysia, Philippines, Singapore, Sri Lanka, and Thailand). The diagnosis of PIBD requires gastrointestinal endoscopy. The patients' demographics, clinical information, disease-related outcomes, and treatment data at 1FU were collected., Results: In 1995-2021, 368 patients were enrolled (CD, 56.8%; UC, 38%; and IBD-unclassified, 5.2%). At 1FU, symptoms including diarrhea, bloody stools, and nausea/vomiting subsided in <3%, while abdominal pain persisted in 10.5% of patients with CD and 7.1% of patients with UC. Assessment endoscopy was performed at 1FU in 38% of CD and 31% of UC cases, of which 21% and 23% showed mucosal healing, respectively. Oral prednisolone was administered to 55.3% of patients at diagnosis and 26.8% at 1FU, while infliximab was administered to 2.5% and 7.2% of patients at diagnosis and 1FU, respectively. Independent factors of 1-year clinical remission for CD were oral prednisolone (odds ratio [OR], 0.20; 95% confidence interval [CI], 0.06-0.68), antibiotic use (OR, 0.09; 95% CI, 0.01-0.54), and immunomodulator use (OR, 5.26; 95% CI, 1.52-18.22). A history of weight loss at diagnosis was the only independent risk factor of an IBD flare by 1FU (OR, 2.01; 95% CI, 1.12-3.63)., Conclusion: The proportion of children with PIBD and abdominal pain at 1FU remained high. The rates of repeat endoscopy and infliximab use were suboptimal with high rates of systemic corticosteroid use. Quality improvement based on the aforementioned predictors may enhance PIBD care in this geographic region or similar settings.

The most important factor that complicates the work of dysmorphologists is the significant phenotypic variability of the human face. Next-Generation Phenotyping (NGP) tools that assist clinicians with recognizing characteristic syndromic patterns are particularly challenged when confronted with patients from populations different from their training data. To that end, we systematically analyzed the impact of genetic ancestry on facial dysmorphism. For that purpose, we established the GestaltMatcher Database (GMDB) as a reference dataset for medical images of patients with rare genetic disorders from around the world. We collected 10,980 frontal facial images - more than a quarter previously unpublished - from 8,346 patients, representing 581 rare disorders. Although the predominant ancestry is still European (67%), data from underrepresented populations have been increased considerably via global collaborations (19% Asian and 7% African). This includes previously unpublished reports for more than 40% of the African patients. The NGP analysis on this diverse dataset revealed characteristic performance differences depending on the composition of training and test sets corresponding to genetic relatedness. For clinical use of NGP, incorporating non-European patients resulted in a profound enhancement of GestaltMatcher performance. The top-5 accuracy rate increased by +11.29%. Importantly, this improvement in delineating the correct disorder from a facial portrait was achieved without decreasing the performance on European patients. By design, GMDB complies with the FAIR principles by rendering the curated medical data findable, accessible, interoperable, and reusable. This means GMDB can also serve as data for training and benchmarking. In summary, our study on facial dysmorphism on a global sample revealed a considerable cross ancestral phenotypic variability confounding NGP that should be counteracted by international efforts for increasing data diversity. GMDB will serve as a vital reference database for clinicians and a transparent training set for advancing NGP technology.

Introduction: The practice of Do-Not-Attempt-Resuscitation (DNAR) aims to respect patient autonomy and acknowledge medical futility. Despite its global acceptance, there is limited research on DNAR in many Asian countries, including Malaysia. This study addressed this gap by exploring DNAR decision-making processes in a Malaysian tertiary hospital., Materials and Methods: A mixed-method retrospective study was conducted in the emergency and trauma department (ETD) of Sarawak General Hospital, Malaysia, from February to July 2023. Data were collected from 115 DNAR cases using a surveillance form to document the patient demographics, types of DNAR orders, initiating physicians, reasons for DNAR, surrogate decision-makers, specific types of procedures withheld or withdrawn and outcomes. Thematic analysis was used for qualitative data, while inferential statistical analysis was applied to quantitative data., Results: The mean age of patients was 71.32 years, with a male predominance (63.5%). The primary reasons for DNAR included "critical illness with poor prognosis" (33.9%), "advanced age with frailty and poor prognosis" (20.9%) and "massive haemorrhagic or ischemic stroke" (16.5%). Most DNAR decisions involved withholding resuscitation (90.4%) and were initiated mainly by internal medicine (52.2%) and emergency medicine teams (34.8%). Surrogate decisionmakers were predominantly adult children (63.5%). Only one case had an advance directive. Majority of patients (80.9%) were admitted to wards, while 16.5% died in the emergency department. The median age of patients was significantly older when adult children (78 years) and spouses (76 years) were the surrogates, compared to when they were not involved (64.5 years and 62.5 years, respectively; p < 0.001 and p = 0.003, respectively). Conversely, the median age was significantly younger when parents (41.5 years) and siblings (64 years) were the surrogates, compared to when they were not involved (75 years and 74 years, respectively; p < 0.001 for both)., Conclusion: Advanced directives are rarely applied in Malaysia. DNAR decisions are typically made by surrogates when patients are critically ill, which is a common trend in many Asian cultures where discussing death is taboo. Cultural norms often lead families to withhold terminal diagnoses from patients, posing challenges for end-of-life care. The most frequent surrogates were adult children, who face dilemmas balancing aggressive treatment and their parents' wishes. The study underscores the need for better communication and decision-making support in emergency departments.

Antisense oligonucleotides (ASOs) are promising therapeutics for treating various neurological disorders. However, ASOs are unable to readily cross the mammalian blood-brain barrier (BBB) and therefore need to be delivered intrathecally to the central nervous system (CNS). Here, we engineered a human transferrin receptor 1 (TfR1) binding molecule, the oligonucleotide transport vehicle (OTV), to transport a tool ASO across the BBB in human TfR knockin (TfR mu/hu KI) mice and nonhuman primates. Intravenous injection and systemic delivery of OTV to TfR mu/hu KI mice resulted in sustained knockdown of the ASO target RNA, Malat1 , across multiple mouse CNS regions and cell types, including endothelial cells, neurons, astrocytes, microglia, and oligodendrocytes. In addition, systemic delivery of OTV enabled Malat1 RNA knockdown in mouse quadriceps and cardiac muscles, which are difficult to target with oligonucleotides alone. Systemically delivered OTV enabled a more uniform ASO biodistribution profile in the CNS of TfR mu/hu KI mice and greater knockdown of Malat1 RNA compared with a bivalent, high-affinity TfR antibody. In cynomolgus macaques, an OTV directed against MALAT1 displayed robust ASO delivery to the primate CNS and enabled more uniform biodistribution and RNA target knockdown compared with intrathecal dosing of the same unconjugated ASO. Our data support systemically delivered OTV as a potential platform for delivering therapeutic ASOs across the BBB.

Background: Motivational interviewing (MI) is a person-centred approach focused on empowering and motivating individuals for behavioural change. Medical students can utilize MI in patient education to engage with patients' chronic health ailments and maladaptive behaviours. A current scoping review was conducted to 1) determine the types of MI (conventional, adapted, brief and group MI) education programs in medical schools, delivery modalities and teaching methods used; 2) classify educational outcomes on the basis of Kirkpatrick's hierarchy; and 3) determine the key elements of MI education via the FRAMES (feedback, responsibility, advice, menu of options, empathy, self-efficacy) model., Methods: This scoping review was conducted via the framework outlined by Arksey and O'Malley. Two online databases, CINAHL and MEDLINE Complete, were searched to identify MI interventions in medical education. Further articles were selected from bibliography lists and the Google Scholar search engine., Results: From an initial yield of 2019 articles, 19 articles were included. First, there appears to be a bimodal distribution of most articles published between the two time periods of 2004--2008 and 2019--2023. Second, all the studies included in this review did not use conventional MI but instead utilized a variety of MI adaptation techniques. Third, most studies used face-to-face training in MI, whereas only one study used online delivery. Fourth, most studies have used a variety of interactive experiences to teach MI. Next, all studies reported outcomes at Kirkpatrick's Level 2, but only 4 studies reported outcomes at Kirkpatrick's Level 3. According to the FRAMES model, all studies (n=19; 100%) reported the elements of responsibility and advice. The element that was reported the least was self-efficacy (n = 12; 63.1%)., Conclusion: Our findings suggest that motivational interviewing can be taught effectively in medical schools via adaptations to MI and a variety of teaching approaches. However, there is a need for further research investigating standardized MI training across medical schools, the adequate dose for training in MI and the implementation of reflective practices. Future studies may benefit from exploring and better understanding the relationship between MI and self-efficacy in their MI interventions., (© 2024. The Author(s).)

One Stop Crisis Center (OSCC) is a multi-sectorial center aimed to provide medical, social, legal, police and shelter services to survivors of domestic violence, rape, sexual assault, sodomy and child abuse. Although OSCCs have been established for almost three decades in different parts of the world including in Malaysia, there is a lack of a validated instrument to measure the service quality rendered in OSCCs. A validated instrument known as OSCC-Qual was developed using a 5-stage approach where (1) in stage 1, group discussions were conducted among all authors to identify potential items for the instrument; (2) in stage 2, content validation was performed by 13 experts using content validity index and modified kappa; (3) in stage 3, exploratory factor analysis was performed by 141 healthcare staff with experience in managing OSCC cases to validate the items as well as to identify the number of factors in the instrument; (4) in stage 4, confirmatory factor analysis was performed by 110 domestic violence survivors to ascertain the validity of the factors and items retained in stage 3 and (5) in stage 5, forward and backward translation into local Malay and Chinese languages was performed. Results: In stage 1, a total of 42 items were identified. No item was deleted in stage 2. In stage 3, a total of 7 factors (i.e., "information provision", "competency of staff", "professionalism", "supportive environment", "attitude of staff", "multi-sectorial coordination" and "tangibles") were identified. Four items were deleted due to poor factor loading. In stage 4, another 3 items were iteratively removed due to poor factor loading. Discriminant validity was good. Conclusion: With the availability of the 7-factor and 35-item OSCC-Qual instrument, it is hoped that the efficiency of OSCC in achieving its philosophical objectives after three decades of implementation can be unraveled and remedial actions can be taken, if necessary., (© 2024. The Author(s).)

Introduction: Domestic violence (DV) is a pervasive social and public health issue affecting millions globally, regardless of age, gender or socioeconomic background. Understanding victim and perpetrators' characteristics as well as the DV injury patterns are essential for developing targeted interventions and prevention strategies. Although past DV studies have often focused on female victims, it is increasingly recognised that DV affects a significant proportion of male victims as well. This study aimed to comprehensively examine both male and female DV victims and perpetrators, as well as the anatomical regions affected in DV cases in Kuching, Sarawak, so that a deeper understanding of DV within this community can be enhanced., Materials and Methods: This prospective, observational study was conducted from March 2021 to March 2023, involving adult DV victims aged 18 years and above admitted to the One Stop Crisis Center (OSCC) of Sarawak General Hospital. Data were collected from the OSCC clerking sheet, focusing on the victims, perpetrators and the violence characteristics., Results: A total of 133 DV victims were analysed, with 25.6% being male victims. Although majority of the perpetrators in cases involving male victims were male perpetrators, there was a significantly higher number of female perpetrators in these male DV cases (i.e., 5 out of 34 cases,14.7%) compared to in female DV cases (4 out of 99 cases, 4.0%) (p = 0.05). The commonest type of relationship between the victims and perpetrators was spouses or ex-spouses (56.4%). Male victims had more cases involving weapons (67.6%) compared to female victims (26.3%), p < 0.001. The most affected anatomical region was the head and neck (63.9%) region although no significant differences were observed., Conclusion: The study reveals that DV affects individuals across all societal classes and income groups. Although weapons were used more frequently in male DV cases, other injury characteristics and affected anatomical regions were not significantly different between genders, suggesting female perpetrators can inflict similar injuries as male perpetrators. Subgroup analysis showed that the majority of male victims faced abuse from their children or grandchildren, hinting at hidden geriatric abuse, that should be unmasked and treated as a separate entity.

Background: ATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis., Objectives: To perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features., Methods: Literature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (OR P ) and 95% CI were calculated under the random effects model., Results: Our analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (OR P : 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (OR P : 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (OR P : 1.21, 95% CI: 1.07-1.38, p-value: 0.003)., Conclusions: ATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Conventional cognitive interventions to reduce medication errors have been found to be less effective as behavioural change does not always follow intention change. Nudge interventions, which subtly steer one's choices, have recently been introduced., Methods: Conducted from February to May 2023, this study aimed to determine the relationships between perceived effectiveness and perceived ease of implementation of six nudge interventions to reduce medication errors, i.e., provider champion, provider's commitment, peer comparison, provider education, patient education and departmental feedback, and the moderating effects of seniority of job positions and clinical experience on nudge acceptability. Partial Least Square Structural Equation Modelling was used for data analysis., Results and Discussion: All six nudge strategies had significant positive relationships between perceived effectiveness and acceptability. In three out of six interventions, perceived ease of implementation was shown to have positive relationships with perceived acceptability. Only seniority of job position had a significant moderating effect on perceived ease of implementation in peer comparison intervention. Interventions that personally involve senior doctors appeared to have higher predictive accuracy than those that do not, indicating that high power-distance culture influence intervention acceptability., Conclusion: For successful nudge implementations, both intrinsic properties of the interventions and the broader sociocultural context is necessary., (© 2023. The Author(s).)

Background: As breast cancer incidence rises among younger women, there is a knowledge gap regarding the emotional, physical, and social effects of mastectomy, specifically in a crisis-affected country such as Syria. This study aimed to explore these effects on young women with breast cancer in Syria, taking into consideration the cultural significance of a woman's breast as part of her feminine identity., Methods: A qualitative design, using semi-structured in-depth interviews with 10 young women with breast cancer who underwent mastectomy, was conducted between June to December 2022., Results: Thematic analysis was used to analyze the data, and five main themes were identified: (1) psychological and emotional well-being (altered self-esteem and femininity, impact on sexual life and relationships, psychological distress associated with mastectomy, mirror trauma and the need for psychological care); (2) body image and breast reconstruction (the dilemma over reconstruction decision, body image and clothing and lack of access to prosthetic information/services); (3) social and interpersonal factors (lack of marriage choices and society's view and stigma); (4) coping mechanisms with mastectomy effects (family support; faith in god almighty; comparing their situation to others and use of prosthetics) and (5) physical health and functioning (physical effects on mobility and function)., Conclusion: Mastectomy has significant physical, emotional, and social consequences on young women with breast cancer, particularly in crisis-affected Syria where access to breast reconstruction is limited. It is crucial for healthcare professionals to understand these impacts, to raise awareness, encourage early detection, and promote less aggressive treatments to improve women's quality of life., (© 2023. The Author(s).)

Background: Domestic violence is a global public health concern as stated by World Health Organization. We aimed to conduct a textual analysis of tweets associated with domestic violence through keyword identification, word trends and word collocations. The data was obtained from Twitter, focusing on publicly available tweets written in English. The objectives are to find out if the identified keywords, word trends and word collocations can help differentiate between domestic violence-related tweets and non-domestic violence-related tweets, as well as, to analyze the textual characteristics of domestic violence-related tweets and non-domestic violence-related tweets., Methods: Overall, 11,041 tweets were collected using a few keywords over a period of 15 days from 22 March 2021 to 5 April 2021. A text analysis approach was used to discover the most frequent keywords used, the word trends of those keywords and the word collocations of the keywords in differentiating between domestic violence-related or non-domestic violence-related tweets., Results: Domestic violence-related tweets and non-domestic violence-related tweets had differentiating characteristics, despite sharing several main keywords. In particular, keywords like "domestic", "violence" and "suicide" featured prominently in domestic-violence related tweets but not in non-domestic violence-related tweets. Significant differences could also be seen in the frequency of keywords and the word trends in the collection of the tweets., Conclusion: These findings are significant in helping to automate the flagging of domestic-violence related tweets and alert the authorities so that they can take proactive steps such as assisting the victims in getting medical, police and legal help as needed., (Copyright© 2023 Chua et al. Published by Tehran University of Medical Sciences.)

Clinical toxinology is an essential subject that should be included in undergraduate medical curricula. By equipping students with the knowledge and skills to identify and treat venomous animals and use antivenom appropriately reduces the risk of medical negligence and delays in treating and transporting these patients. Unfortunately, given the packed curriculum of undergraduate medical programs, it is important to focus on providing students with essential knowledge and skills to function as competent house officers. Student-centered learning approaches, such as gamification and community service projects, can be effective in enhancing learning and promoting awareness of appropriate toxin-related public measures.

Introduction: : Asian children with cystic fibrosis (CF) managed in Malaysia have significant morbidity with limited access to life-sustaining treatments. We determined the morbidity and treatment cost of CF in a resource-limited country., Methods: This cross-sectional study included all children diagnosed with CF in our centre. Data on clinical presentation, genetic mutation, serial spirometry results and complications were collected. Out-of-pocket (OOP) and healthcare costs over 1 year were retrieved for patients who were alive. Cohen's d and odds ratio (OR) were used to determine the effect size., Results: Twenty-four patients were diagnosed with CF. Five patients died at a median (range) age of 18 (0.3-22) years. F508deletion (c. 1521&#95;1523delCTT) was found in 20% of the alleles, while 89% of the variants were detected in nine patients. Body mass index (BMI) Z score was >-1.96 in 70.6% of patients. Two thirds (68%) were colonised with Pseudomonas aeruginosa, and this was associated with lower weight (P = 0.009) and BMI (P = 0.02) Z scores. Only 18% had FEV 1 Z scores >-1.96. Early symptom onset (d = 0.74), delayed diagnosis (d = 2.07), a low FEF 25-75 Z score (d = 0.82) and a high sweat conductance (d = 1.19) were associated with death. Inpatient cost was mainly from diagnostic tests, while medications contributed to half of the outpatient cost., Healthcare utilisation cost was catastrophic, amounting to 20% of the total income., Conclusion: Asian children with CF suffer significant complications such as low weight, low lung function and shortened lifespan. P. aeruginosa colonisation was frequent and associated with poor growth. Healthcare cost to parents was catastrophic., Competing Interests: None

Brain exposure of systemically administered biotherapeutics is highly restricted by the blood-brain barrier (BBB). Here, we report the engineering and characterization of a BBB transport vehicle targeting the CD98 heavy chain (CD98hc or SLC3A2) of heterodimeric amino acid transporters (TV CD98hc ). The pharmacokinetic and biodistribution properties of a CD98hc antibody transport vehicle (ATV CD98hc ) are assessed in humanized CD98hc knock-in mice and cynomolgus monkeys. Compared to most existing BBB platforms targeting the transferrin receptor, peripherally administered ATV CD98hc demonstrates differentiated brain delivery with markedly slower and more prolonged kinetic properties. Specific biodistribution profiles within the brain parenchyma can be modulated by introducing Fc mutations on ATV CD98hc that impact FcγR engagement, changing the valency of CD98hc binding, and by altering the extent of target engagement with Fabs. Our study establishes TV CD98hc as a modular brain delivery platform with favorable kinetic, biodistribution, and safety properties distinct from previously reported BBB platforms., (© 2023. Springer Nature Limited.)

Background: Although tabletop exercise is a commonly used method for disaster response training, it is labor-intensive, requires a tutor for facilitation and may not be ideal in a pandemic situation. Board game is a low-cost and portable alternative that can be utilized for this purpose. The purpose of this study was to compare the perception of interaction engagement and behavioral intention to use a newly developed board game with tabletop exercise for disaster training., Methods: Using the Mechanics-Dynamics-Aesthetics' (MDA) framework, a new, tutorless educational board game known as the Simulated Disaster Management And Response Triage training ("SMARTriage") was first developed for disaster response training. Subsequently, the perceptions of 113 final year medical students on the "SMARTriage" board game was compared with that of tabletop exercise using a crossover design., Results: Using Wilcoxon signed rank test, it was that found that tabletop exercise was generally rated significantly higher (with p < 0.05) in terms of perceived usefulness, perceived ease of use and behavioral intention compared to tutorless "SMARTriage" board game. However, in terms of attitude and interaction engagement, there was no significant difference between these two learning methods for most of the items., Conclusion: Although a clear preference for tutorless board game was not demonstrated, this study suggests that board game was not inferior to tabletop exercise in fostering interaction engagement suggesting that "SMARTriage" board game could potentially be used as an adjunct for teaching and learning activities., (© 2023. The Author(s).)

Increasing evidence suggests excess skin Na+ accumulation in hypertension; however, the role of skin-specific mechanisms of local Na+/water regulation remains unclear. We investigated the association between measures of sweat and trans-epidermal water loss (TEWL) with Na+ content in the skin ([Na+]skin) and clinical characteristics in consecutive hypertensive patients. We obtained an iontophoretic pilocarpine-induced sweat sample, a skin punch biopsy for chemical analysis, and measures of TEWL from the upper limbs. Serum vascular endothelial growth factor-c (VEGF-c) and a reflectance measure of haemoglobin skin content served as surrogates of skin microvasculature. In our cohort (n = 90; age 21-86 years; females = 49%), sweat composition was independent of sex and BMI. Sweat Na+ concentration ([Na+]sweat) inversely correlated with [K+]sweat and was higher in patients on ACEIs/ARBs (P < 0.05). A positive association was found between [Na+]sweat and [Na+]skin, independent of sex, BMI, estimated Na+ intake and use of ACEi/ARBs (Padjusted = 0.025); both closely correlated with age (P < 0.01). Office DBP, but not SBP, inversely correlated with [Na+]sweat independent of other confounders (Padjusted = 0.03). Total sweat volume and Na+ loss were lower in patients with uncontrolled office BP (Padjusted < 0.005 for both); sweat volume also positively correlated with serum VEGF-c and TEWL. Lower TEWL was paralleled by lower skin haemoglobin content, which increased less after vasodilatory pilocarpine stimulation when BMI was higher (P = 0.010). In conclusion, measures of Na+ and water handling/regulation in the skin were associated with relevant clinical characteristics, systemic Na+ status and blood pressure values, suggesting a potential role of the skin in body-fluid homeostasis and therapeutic targeting of hypertension., (© 2023 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Introduction: Although healthcare service industry has been thriving in Malaysia, the types of healthcare service quality models used in past research as well as their key messages had not been explored. A scoping review was performed to determine the validated healthcare service quality models, the key messages of these past studies and potential research gaps that should be addressed in future studies., Materials and Methods: Relevant, peer-reviewed, Englishlanguage articles on healthcare service quality in Malaysia were independently searched by the authors using the SCOPUS and EMERALD databases. Articles that do not directly address healthcare service quality within the Malaysian setting were excluded. Additional articles were identified from the reference lists of the selected articles and from Google search engine. A total of 43 out of 2,749 articles were selected., Results: Most of these studies (28 out of the 43 articles, 65.1%) in this scoping review used either the original or a modified version of SERVQUAL instrument to measure healthcare service quality. Significant positive relationships between tangibles, assurance and empathy with patient satisfaction were identified. As SERVQUAL primarily measures the functional dimension of service quality, this suggests that past studies on Malaysian healthcare services emphasised heavily on the functional dimension of healthcare service quality. Functional dimension refers to the expressive performance on how the healthcare service is rendered whereas technical dimension refers to the types of services rendered as well as its safety and efficacy., Conclusion: A pertinent research gap identified in this review is the lack of studies that measure both technical and functional dimensions comprehensively. Future research should adopt a more holistic (incorporating both technical dimension and functional dimension) measurement of healthcare service quality.

Objective: Outcome of pediatric acute liver failure (PALF) in countries with limited availability of LT is not well described. We evaluated the outcome and prognostic indicators of PALF in Malaysia where emergency LT for ALF is limited., Methods: In this retrospective review on children < 18 years with PALF, we compared clinical and laboratory parameters between survival after supportive treatment and after LT or succumbed without LT. The predictive values of Liver Injury Unit (LIU; peak laboratory values for international normalized ratio [INR], ammonia, total bilirubin) and upon admission (aLIU) on outcome of PALF was evaluated using receiver operator characteristic (ROC) curves., Results: Of 77 children (39 males [51%]; median age 2.8 years) with PALF, the overall survival was 55% (n = 42); 52% (n = 40) survived with supportive management, 2.6% (n = 2) after LT. As compared to children who survived without LT, children who had LT/died had lower hemoglobin, aspartate transferase, γ-glutamyl transpeptidase (GGT), and higher serum bilirubin, alkaline phosphatase, ammonia, and serum sodium (p < 0.05). On multivariate analysis, significant independent predictor for death or LT were peak bilirubin > 452 μmol/L and peak GGT < 96 IU/L. The C-index of LIU and aLIU score were 0.79 and 0.68, respectively, indicating that LIU score was a good model in predicting outcome of PALF., Conclusions: Overall survival of PALF remained poor. High peak bilirubin and low GGT predict poor outcome of PALF. LIU score is a good model in predicting outcome of PALF and maybe useful in selecting children for emergency LT., (© 2022. Asian Pacific Association for the Study of the Liver.)

Aim: Quality of life (QoL) in children with inflammatory bowel disease (IBD) is often impaired by underlying disease. We evaluated factors affecting health-related QoL (HRQoL) in Malaysian children with IBD., Methods: A cross-sectional study using IMPACT-III questionnaires evaluating HRQoL in children aged 8-17 years with duration of IBD of ≥6 months was conducted. IMPACT-III, a validated instrument designed to measure HRQoL in children with IBD, was used. Higher IMPACT-III (maximum = 100) score indicates better HRQoL. Impact of socio-demographic and clinical factors of IBD on the HRQoL was evaluated. Paediatric Crohn's disease (CD) and ulcerative colitis (UC) activity indices were used to classify disease severity., Results: A total of 75 children (UC = 44, CD = 41; mean (SD) age at diagnosis 8.2 (3.5) years) were interviewed at mean age of 12.8 (2.7) years. Mean IMPACT-III score was significantly lower in children with more severe disease (mild: 71.8 (13.6) vs. moderate: 65.5 (10.9) vs. severe: 46.3 (14.5); P < 0.001), history of hospitalisation (yes: 64.0 (14.0) vs. none: 74.1 (12.2), P = 0.034) and a higher number of admissions (r = -0.352, P = 0.041) in preceding 6 months. Diagnosis at a younger age (r = -0.31, P = 0.007) and a longer duration of disease (r = 0.286, P = 0.013) was associated with higher score. A higher weight-for-age (r = 0.261, P = 0.023) or body mass index-for-age z-score (r = 0.235, P = 0.042) was correlated with a better body image domain score, respectively., Conclusions: In Malaysian children with IBD, HRQoL was adversely affected by a more severe disease. Better control of disease activity and maintaining long-term remission are important to improve the HRQoL in childhood IBD., (© 2022 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background and Aims: Thiopurines, which are immunosuppressive drugs for maintaining remission for inflammatory bowel disease, are known to cause myelotoxicity in patients with Nudix Hydroxylase 15 ( NUDT15 ) genetic variants in some Asian countries with monoethnic populations. We aimed to investigate the association of NUDT15 variants with leukopenia in a multiethnic population in Southeast Asia., Methods: Patients with a confirmed diagnosis of inflammatory bowel disease were recruited. We collected demographic and clinical characteristics and whole blood counts before and after initiating thiopurines. Thiopurine S-methyltransferase ( TPMT ) and NUDT15 genotypes were analyzed with the single nucleotide polymorphisms (SNPs) genotyping assay. Leukopenia was defined as a white blood cell (WBC) count < 3,000/μl., Results: In this study, 19 (18.6%) of the 102 patients who had adequate thiopurine therapy experienced leukopenia, 11 patients (57.9%) had NUDT15 c.415C > T variants, 2 patients (10.5%) had NUDT15 c.52G > A variants while one (5.3%) had a TPMT variation. Individually, NUDT15 c.415C > T had a sensitivity and specificity of 57.9% and 94.0% (odds ratio [ OR ] = 21.45, 95% CI 5.94-77.41, p < 0.001), respectively, for predicting thiopurine-induced leukopenia, while NUDT15 c.52G > A was only observed in patients with leukopenia. As compared with patients with wild-type NUDT15 , both NUDT15 variations had a combined sensitivity and specificity of 68.4% and 94%, respectively ( OR = 33.80, 95% CI 8.99-127.05, p < 0.001), for predicting thiopurine-induced leukopenia as well as a shorter onset to leukopenia (median onset [months] 2.0 vs. 5.5; p = 0.045). Sub-group analysis showed that both NUDT15 variations were strongly associated with leukopenia among the Chinese and Indians but not among the Malays., Conclusion: Nudix Hydroxylase 15 variants strongly predicted thiopurine-induced leukopenia across a multiethnic Southeast Asian population, particularly among the Chinese and Indians., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoo, Wong, Ibrahim, Ng, Chew, Lee, Wong, Raja Ali, Shahrani, Leow and Hilmi.)

During developmental critical periods, circuits are sculpted by a process of activity-dependent competition. The molecular machinery involved in regulating the complex process of responding to different levels of activity is now beginning to be identified. Here, we show that the nonclassical major histocompatibility class I (MHCI) molecule Qa-1 is expressed in the healthy brain in layer 6 corticothalamic neurons. In the visual cortex, Qa-1 expression begins during the critical period for ocular dominance (OD) plasticity and is regulated by neuronal activity, suggesting a role in regulating activity-dependent competition. Indeed, in mice lacking Qa-1, OD plasticity is perturbed. Moreover, signaling through CD94/NKG2, a known cognate Qa-1 heterodimeric receptor in the immune system, is implicated: selectively targeting this interaction phenocopies the plasticity perturbation observed in Qa-1 knockouts. In the cortex, CD94/NKG2 is expressed by microglial cells, which undergo activity-dependent changes in their morphology in a Qa-1–dependent manner. Our study thus reveals a neuron–microglial interaction dependent upon a nonclassical MHCI molecule expressed in L6 neurons, which regulates plasticity in the visual cortex. These results also point to an unexpected function for the Qa-1/HLA-E (ligand) and CD94/NKG2 (receptor) interaction in the nervous system, in addition to that described in the immune system.

Background: There remains a dearth of Asian epidemiological literature for paediatric inflammatory bowel disease (PIBD)., Aim: To describe the presenting features of PIBD from 7 Asia-Pacific pediatric gastroenterology centers via a central standardised electronic data platform., Methods: Clinical, endoscopic and radiologic data at diagnosis from the registry were extracted between 1 st January 1995 to 31 st December 2019. Disease phenotypic characteristics were classified as per the Paris classification system., Results: There was a distinct rise in new PIBD cases: Nearly half (48.6%) of the cohort was diagnosed in the most recent 5 years (2015-2019). The ratio of Crohn's disease (CD):Ulcerative colitis (UC):IBD-Unclassified was 55.9%:38.3%:5.8%. The mean age was 9.07 years with a high proportion of very early onset IBD (VEO-IBD) (29.3%) and EO-IBD (52.7%). An over-representation of the Indian/South Asian ethnic group was observed which accounted for 37.0% of the overall Singapore/Malaysia subcohort (6.8%-9.0% Indians in census). Indian/South Asian CD patients were also most likely to present with symptomatic perianal disease ( P = 0.003). CD patients presented with significantly more constitutional symptoms (fever, anorexia, malaise/fatigue and muscle-wasting) than UC and higher inflammatory indices (higher C-reactive protein and lower albumin levels)., Conclusion: We observed a high incidence of VEO-IBD and an over-representation of the Indian ethnicity. South Asian CD patients were more likely to have symptomatic perianal disease., Competing Interests: Conflict-of-interest statement: All the Authors have no conflict of interest related to the manuscript., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: Early-life environmental exposure, which has important implications in the pathogenesis of inflammatory bowel disease (IBD), is not well understood in Asian children. We examined environmental factors prior to the development of childhood IBD in a Southeast Asian population., Methods: We conducted a case control study in IBD diagnosed before 18 years of age and controls matched by gender, age and ethnicity. A questionnaire recording medical, family, dietary and social histories, home environment, childhood diseases and immunisation status was used., Results: In a multivariate analysis involving 70 children with IBD (Crohn's disease (CD) = 38; ulcerative colitis (UC) = 32) and 140 controls, childhood acute gastroenteritis (odds ratio (OR): IBD 6.9; CD 7.8; UC 5.8) and excessive antibiotic usage in early childhood (OR: IBD 5.3; CD 4.2; UC 4.8) were significantly associated with IBD, CD and UC. Having a fish or turtle aquarium (OR 6.0), major stressful life events (OR 5.6) and attending the same school concurrently with a sibling (OR 2.9) were significant risk factors for IBD. Duration of breastfeeding >6 months (OR: IBD 0.4; UC 0.2) and safe water consumption (OR: IBD 0.2; UC 0.2) reduced the odds of having IBD and UC, respectively. Being vaccinated for rotavirus reduced the odds of developing IBD (OR 0.1)., Conclusions: Several risk and protective factors were identified in this environmental risk study in Southeast Asian children with IBD. This knowledge has important implications in understanding disease aetiology and future prevention strategies to reduce the development of IBD in Southeast Asian children., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background and Aim: Inflammatory bowel diseases (IBD) are chronic gastrointestinal inflammatory conditions comprising two major subtypes: Crohn's disease (CD) and ulcerative colitis (UC). The incidence of IBD is increasing in Asian countries including Malaysia. The aim of this study was to determine whether 32 single nucleotide polymorphisms (SNPs) strongly associated with IBD from genome-wide association studies, performed mainly in Caucasian populations, are associated with IBD in a Malaysian population, correlating these findings with local and systemic inflammation., Methods: Selected SNPs were investigated in a Malaysian cohort comprising 36 IBD patients and 75 controls using customized matrix-assisted laser desorption ionization time-of-flight genotyping. Local mRNA and/or systemic protein levels of IL-10, IL-12, IL-22, IL-23, and TNF-α were measured in these same subjects., Results: ATG16L2 rs11235667 and LINC00824 rs6651252 was significantly associated with increased CD risk while IL12B rs56167332 was a significant protective factor. Three SNPs (SBNO2 rs2024092, CARD9 rs10781499, and rs17085007 between GPR12-USP12) were significantly associated with increased UC risk while NKX2-3 rs4409764 was a significant protective factor. After adjusting for age, gender, and ethnicity, SBNO2 rs2024092, ATG16L2 rs11235667, CARD9 rs10781499, and LINC00824 rs6651252 remained associated with IBD. Interestingly, the risk alleles of IL10 rs3024505, CARD9 rs1078149, and IL12 rs6556412 were associated with higher levels of IL-10, IL-22, and IL-23 in these same subjects, respectively., Conclusions: This study identified eight SNPs associated with IBD and/or its subtypes in the Malaysia population, significantly advancing our understanding of the genetic contribution to IBD in this understudied population. Three of these SNPs modulated relevant cytokine levels and thus, may directly contribute to IBD pathogenesis., (© 2021 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: A scoping review was conducted to map out the common research focusses on ambulance accidents, their key findings and some of the major knowledge gaps in this area., Materials and Methods: Relevant, peer-reviewed, Englishlanguage articles on land ambulance accidents were independently searched by the authors using the MEDLINE and CINAHL databases. Anecdotal reports, testimonies and stories in trade or popular magazines and other grey literature were excluded. Articles that do not directly address ambulance accidents were also excluded. Additional articles were identified from the reference lists of the selected articles and from Google search engine., Results: From an initial yield of 879 articles, 19 articles were included. Most of these articles were published from 2001 - 2005 (5 articles, 26.3%) and 2006 - 2010 (5 articles, 26.3%). Eighteen articles (78.3%) are original articles (18 articles, 78.3%) and another one article is a review article. Most of these articles focused on (1) the types of collisions and (2) the risk factors of ambulance accidents. Nine risk factors were identified to have contributed to ambulance accidents: (1) driving in urban areas (2) driving on dry road (3) the use of lights & sirens (4) the failure to use restraints (5) driving for emergency use (6) back seating (7) at road intersection (8) driver's previous records of accidents and (9) interfacility transfer. The two most common risk factors studied were (1) the use of lights & sirens and (2) driving at intersection., Conclusions: Most of the above risk factors can be mapped into three categories of risk factors: task-related factors, vehicle-related factors and environment-related factors. The category of risk factors least studied is the category of driver-related factors.

Introduction: Although menstruation is a physiological process, it is shrouded with socio-cultural and religious beliefs. Healthcare providers should be aware that these influences may affect how women perceive their menstrual disorders. The primary objective of this study was to develop a validated questionnaire measuring the sociocultural and religious beliefs during menstruation., Methods: In the first stage, a preliminary list of items measuring socio-cultural and religious beliefs during menstruation was generated. In the second stage, exploratory factor analysis was performed. Finally, confirmatory factor analysis using reflective measurement model and structural equation modelling was performed using partial least squares. The practices of these beliefs were included as mediating effect. Biological symptoms of menstruation were added in as another factor., Results: A total of 400 female students from the Universiti Malaysia Sarawak, Malaysia were recruited. A preliminary list of 22 items was first generated. From the confirmatory factor analysis, two factors were iteratively removed due to poor factor loadings. Four factors were retained, i.e., i) "religious beliefs"; ii) "unpleasant (or dirty) nature of menstruation"; iii) "personal restrictions (dietary and behavior)"; and iv) "restrictions of interactions with male gender". In structural equation modelling, only 2 factors, i.e., the practices of "personal restrictions (dietary and behavioural)" and "restriction of interactions with males" had significant negative impact on quality of life., Conclusion: Menstruation should not be viewed purely from a biological lens as there are layers of sociocultural and religious beliefs surrounding it.

Background: Primary endoscopic prophylaxis in pediatric gastroesophageal varices is not universally practiced. We aimed to determine the role of primary endoscopic prophylaxis in preventing variceal bleeding in gastroesophageal varices in children., Methods: We reviewed all children with gastroesophageal varices seen in our unit from 2000 to 2019. Primary prophylaxis was defined as endoscopic procedure without a preceding spontaneous bleeding and secondary prophylaxis as preceded by spontaneous bleeding. High-risk varices were defined as presence of grade III esophageal varices, cardia gastric varices or cherry red spots on the varices. Outcome measures (spontaneous rebleeding within 3 months after endoscopic procedure, number of additional procedures to eradicate varices, liver transplant [LT], death) were ascertained., Results: Sixteen of 62 (26%) patients (median [± S.D.] age at diagnosis = 5.0 ± 4.3 years) with varices had primary prophylaxis, 38 (61%) had secondary prophylaxis while 8 (13%) had no prophylaxis. No difference in the proportion of patients with high-risk varices was observed between primary (88%) and secondary (92%; P = 0.62) prophylaxis. As compared to secondary prophylaxis, children who had primary prophylaxis were significantly less likely to have spontaneous rebleeding (6% vs. 38%; P = 0.022) and needed significantly fewer repeated endoscopic procedures (0.9 ± 1.0 vs. 3.1 ± 2.5; P = 0.021). After 8.9 ± 5.5 years of follow-up, overall survival was 85%; survival with native liver was 73%. No statistical difference was observed in the eventual outcome (alive with native liver) between primary and secondary (71% vs. 78%, P = 0.78)., Conclusion: Children with PHT who had primary prophylaxis had less subsequent spontaneous rebleeding and needed fewer additional endoscopic procedures as compared to secondary prophylaxis but did not have an improved eventual outcome. Screening endoscopy in all children who have signs of PHT and primary prophylaxis in high-risk esophageal varices should be considered before eventual LT., Competing Interests: Declaration of competing interest None of the authors has any conflict of interest to declare., (Copyright © 2021. Published by Elsevier B.V.)

Hemolacria is a rare condition that causes a person to produce tears that are partially composed of blood. It can be a presenting feature of certain ocular and systemic conditions. Here, the authors describe an interesting case of a 12-year-old boy with an underlying beta-thalassemia trait, who presented with a 2-day history of bilateral blood-stained tears, and an episode of epistaxis. Ocular examination was normal, and syringing showed no nasolacrimal duct blockage. Systemic examination was unremarkable. Laboratory investigations confirmed type 2 von Willebrand disease. Management of hemolacria remains a clinical challenge given the rare occurrence of the disease. In this case report, the authors discuss the differential diagnosis and management approach to hemolacria., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: We aimed to ascertain the efficacy and feasibility of exclusive enteral nutrition (EEN) as an induction and re-induction therapy in Asian children with Crohn's disease (CD)., Methods: All children diagnosed with CD between 1995 and 2019 were reviewed. Response to induction was compared between EEN and standard immunosuppression (IS) using Paediatric Crohn's Disease Activity Index, growth failure, perianal disease and extra-intestinal manifestations. Two study groups were analysed: (i) primary induction and (ii) re-induction for relapses., Results: Twenty-nine children (mean age (± standard deviation) at diagnosis 9.4 ± 8.5 years old, ileo-colonic 35%, non-stricturing 79%) were studied. At primary induction (group 1; n = 18), no difference was observed in remission rates (9/13 vs. 5/5; P = 0.278), efficacy for improving growth failure (6/8 vs. 0/1; P > 0.999), perianal disease (4/6 vs. 0/2; P > 0.999) and extra-intestinal manifestations (2/2 vs. 0/0; P > 0.999) with EEN or standard IS. Group 2 (n = 38 relapses), no difference was observed in remission rates (16/19 vs. 15/19, P > 0.999), growth failure (0/7 vs. 4/14; P = 0.328), perianal disease (1/10 vs. 7/7; P > 0.999) and extra-intestinal manifestations (0/0 vs. 1/1; P > 0.999) with EEN or standard IS. Both treatment modalities were equally effective as re-induction in relapses in patients previously treated with EEN (P = 0.191)., Conclusion: As compared to standard IS, EEN was equally effective in primary induction and re-induction for relapse in Asian children with CD and can be repeatedly used for recurrent relapses., (© 2020 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: Concerns over high transmission risk of SARS-CoV-2 have led to innovation and usage of an aerosol box to protect healthcare workers during airway intubation in patients with COVID-19. Its efficacy as a barrier protection in addition to the use of a standard personal protective equipment (PPE) is not fully known. We performed a simulated study to investigate the relationship between aerosol box usage during intubation and contaminations on healthcare workers pre-doffing and post-doffing of PPE., Methods: This was a randomised cross-over study conducted between 9 April to 5 May 2020 in the ED of University Malaya Medical Centre. Postgraduate Emergency Medicine trainees performed video laryngoscope-assisted intubation on an airway manikin with and without an aerosol box in a random order. Contamination was simulated by nebulised Glo Germ. Primary outcome was number of contaminated front and back body regions pre-doffing and post-doffing of PPE of the intubator and assistant. Secondary outcomes were intubation time, Cormack-Lehane score, number of intubation attempts and participants' feedback., Results: Thirty-six trainees completed the study interventions. The number of contaminated front and back body regions pre-doffing of PPE was significantly higher without the aerosol box (all p values<0.001). However, there was no significant difference in the number of contaminations post-doffing of PPE between using and not using the aerosol box, with a median contamination of zero. Intubation time was longer with the aerosol box (42.5 s vs 35.5 s, p<0.001). Cormack-Lehane scores were similar with and without the aerosol box. First-pass intubation success rate was 94.4% and 100% with and without the aerosol box, respectively. More participants reported reduced mobility and visibility when intubating with the aerosol box., Conclusions: An aerosol box may significantly reduce exposure to contaminations but with increased intubation time and reduced operator's mobility and visibility. Furthermore, the difference in degree of contamination between using and not using an aerosol box could be offset by proper doffing of PPE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Functional gastrointestinal disorders (FGIDs) are common in children. The prevalence of FGIDs varies across the world but is unknown in Malaysia. We aimed to investigate the prevalence of FGIDs in healthy Malaysian infants., Methods: This was a cross-sectional study involving healthy infants younger than 12 months of age who attended a well-baby clinic. A universal sampling method was adopted. Children with congenital disorders potentially affecting gastrointestinal functions, chronic debilitating diseases and hypothyroidism were excluded. Rome IV criteria were used to define FGIDs., Results: Of the total 534 infants recruited (54% males), 92% were born at term; 85% had normal birth weight [range 2.5-4.0 kg], and the mean (±S.D.) age at interview was 6.8 (±3.4) months. Thirty-six percent were breastfed, 29% were formula-fed, and 35% had mixed feeding. Prevalence of infant regurgitation and rumination syndrome was 10.5% and 1.7%, respectively. Prevalence of infant colic was 1.9% (3/160) (infant < 5 months old) while infant dyschezia, functional constipation and diarrhoea were 1.3%, 1.1% and 0.3%, respectively. No subjects fulfilled diagnostic criteria for cyclic vomiting syndrome. Breastfed infants were less likely to regurgitate, after adjustment for age, gender, ethnicity, birth weight and gestation (adjusted OR 0.25 [95% CI 0.12-0.54]; p < 0.001). No significant differences among other factors (gender, Malays vs. non-Malays, premature vs. term, and birthweight) were noted for other FGIDs., Conclusion: With the exception of the lower prevalence of infant colic and functional constipation, the prevalence rates of other FGIDs observed in the present study were similar to those published in the literature. Breastfeeding protects against infant regurgitation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article., (Copyright © 2020. Published by Elsevier B.V.)

Background: Patient's financial ability is always the most critical imputes to treatment choice and adherence; as it translates into health outcomes such as survival rate and quality of life. Cancer care is likely to affect the patient's financial well-being, putting huge financial pressure to the families. Therefore, it is imperative to understand the confounding factors of financial toxicity among cancer survivors along the course of survivorship., Methods: This study was designed in the form of cross-sectional analysis, in which, cancer survivors were recruited from the Sarawak General Hospital, the largest tertiary and referral public hospital in Sarawak. To capture the financial toxicity of the cancer survivors, the Comprehensive Score for Financial Toxicity (COST) instrument in its validated form was adopted. Multivariable logistic regression analysis was applied to determine the relationship between financial toxicity (FT) and its predictors., Results: The median age of the 461 cancer survivors was 56 while the median score of COST was 22.0. Besides, finding from multivariable logistic regression revealed that low income households (OR: 6.893, 95% CI, 3.109-15.281) were susceptible to higher risk of financial toxicity, while elderly survivors above 50 years old reported a lower risk in financial toxicity. Also, survivors with secondary schooling (OR:0.240; 95%CI, 0.110-0.519) and above [College or university (OR: 0.242; 95% CI, 0.090-0.646)] suffer a lower risk of FT., Conclusion: Financial toxicity was found to be associated with survivors age, household income and educational level. In the context of cancer treatment within public health facility, younger survivors, households from B40 group and individual with educational attainment below the first level schooling in the Malaysian system of education are prone to greater financial toxicity. Therefore, it is crucial for healthcare policymakers and clinicians to deliberate the plausible risk of financial toxicity borne by the patient amidst the treatment process.

Our understanding of Na + homeostasis has recently been reshaped by the notion of skin as a depot for Na + accumulation in multiple cardiovascular diseases and risk factors. The proposed water-independent nature of tissue Na + could induce local pathogenic changes, but lacks firm demonstration. Here, we show that tissue Na + excess upon high Na + intake is a systemic, rather than skin-specific, phenomenon reflecting architectural changes, i.e. a shift in the extracellular-to-intracellular compartments, due to a reduction of the intracellular or accumulation of water-paralleled Na + in the extracellular space. We also demonstrate that this accumulation is unlikely to justify the observed development of experimental hypertension if it were water-independent. Finally, we show that this isotonic skin Na + excess, reflecting subclinical oedema, occurs in hypertensive patients and in association with aging. The implications of our findings, questioning previous assumptions but also reinforcing the importance of tissue Na + excess, are both mechanistic and clinical.

Background: Although gamification increases user engagement, its effectiveness in point-of-care ultrasonographic training has yet to be fully established. This study was conducted with the primary outcome of evaluating its effectiveness in point-of-care ultrasonographic training as compared to conventional approach., Methods: Participants consisting of junior doctors were randomized into either the (1) gamified or the (2) conventional educational approach for ultrasonographic training., Results: A total of 31 junior doctors participated in this study (16 participants in gamified arm, 15 in the conventional arm after one participant from the conventional arm dropped out due to work commitment). Two-way mixed ANOVA test showed that there was no statistically significant interaction between the types of educational approach and time of testing (pre-test, post-test, 2 months post-training) for both theoretical knowledge score and practical skills score, with F(2, 58) = 39.6, p < 0.001, partial η 2  = 0.4 and F(2, 58) = 3.06, p = 0.06, partial η 2  = 0.095, respectively. For theoretical knowledge score, pairwise comparisons showed that the mean 2 months post-training scores (20.28 +/- 0.70, 95% CI 18.87-21.69) and mean post-test scores (20.27 +/- 0.65, 95% CI 18.94-21.60) were better than the pre-test scores (12.99 +/- 0.50, 95% CI 11.97-14.00) with p-values < 0.001 for both comparisons respectively. Similarly, for practical skill score, pairwise comparisons showed that the mean 2 months post-training scores (20.28 +/- 0.70, 95% CI 18.87-21.69) and mean post-test scores (20.27 +/- 0.65, 95% CI 18.94-21.60) were also better than the pre-test scores (12.99 +/- 0.50, 95% CI 11.97-14.00) with p-values < 0.001 for both comparisons respectively. Participants in the gamification arm generally perceived the various game elements and game mechanics as useful in contributing and motivating them to learn ultrasonography., Conclusions: Gamification approach could be an effective alternative to conventional approach in point-of-care ultrasonographic training.

Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the development of a BBB transport vehicle (TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. TVs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (hTfR) without the use of amino acid insertions, deletions, or unnatural appendages. A crystal structure of the TV-TfR complex revealed the TV binding site to be away from transferrin and FcRn binding sites, which was further confirmed experimentally in vitro and in vivo. Recombinant expression of TVs fused to anti-β-secretase (BACE1) Fabs yielded antibody transport vehicle (ATV) molecules with native immunoglobulin G (IgG) structure and stability. Peripheral administration of anti-BACE1 ATVs to hTfR-engineered mice and cynomolgus monkeys resulted in substantially improved CNS uptake and sustained pharmacodynamic responses. The TV platform readily accommodates numerous additional configurations, including bispecific antibodies and protein fusions, yielding a highly modular CNS delivery platform., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Premature infants and children with intestinal failure (IF) or short bowel syndrome are susceptible to intestinal failure-associated liver disease (IFALD, previously referred to as parenteral nutrition-associated liver disease, or PNALD). IFALD in children is characterized by progressive cholestasis and biliary fibrosis, and steatohepatitis in adults, and is seen in individuals dependent upon prolonged administration of PN. Many factors have been proposed as contributing to the pathogenesis of IFALD. In recent years, the focus has been on the potential synergistic roles of the intestinal microbiome, increased intestinal permeability, activation of hepatic innate immune pathways, and the use of intravenous soybean-oil-based intravenous lipid emulsions (SO-ILE). In vitro and in vivo studies have identified stigmasterol, a component of the plant sterols present in SO-ILE, as playing an important role. Although various strategies have been adopted to prevent or reverse IFALD, most suffer from a lack of strong evidence supported by well-designed, prospective clinical trials with clearly defined endpoints. Reduction in the amount of SO-ILEs or replacement with non-SO-ILEs has been shown to reverse IFALD although safety and long-term effectiveness have not been studied. Medical and surgical modalities to increase intestinal adaptation, advance enteral feedings, and prevent central line bloodstream infections are also important preventative strategies. There is a continued need to conduct high-quality, prospective trials with clearly define outcome measures to ascertain the potential benefits of these strategies.

Background: In conjunction with an automated external defibrillator (AED) placement program at various locations within a public university in Malaysia, a series of structured training programs were conducted. The objectives of this study is to (1) evaluate the effectiveness of a structured training program in improving the perception of the importance of AED and cardiopulmonary resuscitation (CPR), (2) evaluate the confidence of the employees in using an AED and performing bystander CPR, (3) identify the fears and concerns of these employees in using AED and performing CPR, and (4) determine the perception of these employees towards the strategy of the AEDs placed at various locations within the university., Methods: In this single-center observational study, a validated questionnaire aimed to assess the university employees' attitude and confidence in handling AED and performing CPR before (pre-test) and immediately after (post-test) the training program was conducted., Results: A total of 184 participants participated in this study. Using the Wilcoxon signed-rank test, the training programs appeared to have improved the perception that "using AED is important for unresponsive victims" (z = 4.32, p < 0.001) and that "AED practice drills should be performed on a regular basis" (z = - 2.41, p = 0.02) as well as increased the confidence to perform CPR (z = - 8.56, p < 0.001), use AED (z = - 8.93, p < 0.001), identify victims with no signs of life (z = - 7.88, p < 0.001), and the willingness to perform CPR and AED without hesitancy (z = - 8.91, p < 0.001). Fears and concerns on performing CPR and using AED also appeared to have been significantly reduced, and the perception on placement strategies of these AEDs was generally positive., Conclusion: Using the theory of planned behavior as the explanatory framework, training programs appear to be helpful in improving the perception and the confidence of the participants towards performing CPR and using AED through the promotion of positive attitude, positive societal expectation, and a positive sense of empowerment. But whether this positive effect will translate into actual CPR performance and AED application in a real cardiac arrest is yet to be seen.

Background: The influence of past familial experiences of receiving cardiopulmonary resuscitation (CPR) and medical help in various cardiac arrest and nonfatal cardiac events toward willingness to "pay it forward" by helping the next cardiac arrest victim was explored., Methods: Using a validated questionnaire, 6248 participants were asked to rate their willingness to perform bystander chest compression with mouth-to-mouth ventilation and chest compression-only CPR. Their past familial experiences of receiving cardiopulmonary resuscitation (CPR) and medical help in various cardiac arrest and nonfatal cardiac events were also recorded., Results: Kruskal-Wallis test with post hoc Dunn's pairwise comparisons showed that the following were significantly more willing to perform CPR with mouth-to-mouth ventilation: familial experience of "nonfatal cardiac events" (mean rank = 447) vs "out-of-hospital cardiac arrest with no CPR" (mean rank = 177), U = 35442.5, z = -2.055, p = 0.04; "in-hospital cardiac arrest and successful CPR" (mean rank = 2955.79) vs "none of these experiences" (mean rank = 2468.38), U = 111903, z = -2.60, p = 0.01; and "in-hospital cardiac arrest with successful CPR" (mean rank = 133.45) vs "out-of-hospital arrest with no CPR" (mean rank = 112.36), U = 4135.5, z = -2.06, p = 0.04. For compression-only CPR, Kruskal-Wallis test with multiple runs of Mann-Whitney U tests showed that "nonfatal cardiac events" group was statistically higher than the group with "none of these experiences" (mean rank = 3061.43 vs 2859.91), U = 1194658, z = -2.588, p = 0.01. The groups of "in-hospital cardiac arrest with successful CPR" and "in-hospital cardiac arrest with transient return of spontaneous circulation" were the most willing groups to perform compression-only CPR., Conclusion: Prior familial experiences of receiving CPR and medical help, particularly among those with successful outcomes in a hospital setting, seem to increase the willingness to perform bystander CPR.