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Sulfur treatment for the pesticidal and antibacterial processing of food products has been criticized since it impairs the quality of treated products. The inspection of sulfur-treated products is thus required to achieve the regulation of sulfur treatment. Sulfite assay is currently available for the inspection, but it bears the disadvantages of inaccurate results and complex experimental procedures. Here we report a new chemical marker, namely tryptophan sulfonate, that can be used for the accurate and efficient inspection of sulfur-treated foods. First, the marker was discovered in sulfur-fumigated ginger, yam, and ginseng by untargeted metabolomics. The marker identity was then elucidated using chromatographic separation, nuclear magnetic resonance analysis and chemical synthesis. Finally, to demonstrate its applicability in the inspection, a tryptophan sulfonate assay was developed to test 50 commercial food samples, and the results indicated that it performed better than the sulfite assay in terms of both accuracy and efficiency., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: In the last 15 years, the care provided for individuals born with differences of sex development (DSD) has evolved, with a strong emphasis on interdisciplinary approaches. However, these developments have not convinced some stakeholders to embrace the current model of care. This care model has also paid insufficient attention to socio-cultural differences and global inequalities., Summary: This article is an opinion statement, resulting from in-depth discussions and reflection among clinicians, patients, and family support organizations based in the US and Europe, where we seek areas of common ground and try to identify opportunities to further develop resources. The product of these conversations is summarized in 10 panels. The corresponding sections provide additional discussion on some of the panel items., Key Messages: Participants identified areas of agreement and gained a deeper understanding of the reasons behind disagreements on certain matters and identified the necessary steps to foster future consensus. We offer preliminary recommendations for guiding clinical management and resource allocation. By promoting a broader consensus, we aim to enhance the quality of care and well-being for individuals of all ages who have a DSD., (The Author(s). Published by S. Karger AG, Basel.)

Background: Diabetic foot ulcers (DFUs) are serious complications of diabetes which can lead to lower extremity amputations (LEAs). Risk prediction models can identify high-risk patients who can benefit from early intervention. Machine learning (ML) methods have shown promising utility in medical applications. Explainable modeling can help its integration and acceptance. This study aims to develop a risk prediction model using ML algorithms with explainability for LEA in DFU patients., Methods: This study is a retrospective review of 2559 inpatient DFU episodes in a tertiary institution from 2012 to 2017. Fifty-one features including patient demographics, comorbidities, medication, wound characteristics, and laboratory results were reviewed. Outcome measures were the risk of major LEA, minor LEA and any LEA. Machine learning models were developed for each outcome, with model performance evaluated using receiver operating characteristic (ROC) curves, balanced-accuracy and F1-score. SHapley Additive exPlanations (SHAP) was applied to interpret the model for explainability., Results: Model performance for prediction of major, minor, and any LEA event achieved ROC of 0.820, 0.637, and 0.756, respectively, with XGBoost, XGBoost, and Gradient Boosted Trees algorithms demonstrating best results for each model, respectively. Using SHAP, key features that contributed to the predictions were identified for explainability. Total white cell (TWC) count, comorbidity score and red blood cell count contributed highest weightage to major LEA event. Total white cell, eosinophils, and necrotic eschar in the wound contributed most to any LEA event., Conclusions: Machine learning algorithms performed well in predicting the risk of LEA in a patient with DFU. Explainability can help provide clinical insights and identify at-risk patients for early intervention., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context: Polycystic ovary syndrome (PCOS) has historically been conceptualized as a disorder of the reproductive system in women. However, offspring of women with PCOS begin to show metabolic features of PCOS in childhood, suggestive of childhood manifestations., Objective: To identify childhood manifestations of genetic risk for PCOS., Methods: We calculated a PCOS polygenic risk score (PRS) for 12 350 girls and boys in 4 pediatric cohorts-ALSPAC (UK), COPSAC (Denmark), Project Viva (USA), and The HOLBÆK Study (Denmark). We tested for association of the PRS with PCOS-related phenotypes throughout childhood and with age at pubarche and age at peak height velocity and meta-analyzed effects across cohorts using fixed-effect models., Results: Higher PRS for PCOS was associated with higher body mass index in midchildhood (0.05 kg/m2 increase per 1 SD of PRS, 95% CI 0.03, 0.07, P = 3 × 10-5) and higher risk of obesity in early childhood (OR 1.34, 95% CI 1.13, 1.59, P = .0009); both persisted through late adolescence (P all ≤.03). Higher PCOS PRS was associated with earlier age at pubarche (0.85-month decrease per 1 SD of PRS, 95% CI -1.44, -0.26, P = .005) and younger age at peak height velocity (0.64-month decrease per 1 SD of PRS, 95% CI -0.94, -0.33, P = 4 × 10-5)., Conclusion: Genetic risk factors for PCOS are associated with alterations in metabolic, growth, and developmental traits in childhood. Thus, PCOS may not simply be a condition that affects women of reproductive age but, rather, a possible manifestation of an underlying condition that affects both sexes starting in early life., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Depression is on the rise and has become a significant concern for public health. Limited research has explored the connection between dietary patterns and depression. This investigation aimed to examine how dietary behaviours relate to depression among adolescents attending school in Malaysia., Methods: The study utilized data from the National School-Based Health Survey 2022, a nationwide survey involving school-going adolescents aged 13-17, with a total of 33,523 participants from 239 schools. To assess depression, the study employed the Patient Health Questionnaire (PHQ-9), considering a score of 10 or higher as indicative of depression. Dietary behaviours were assessed using a validated self-administered questionnaire adapted from the World Health Organization's Global School-based Student Health Survey. Descriptive analysis and complex sample logistic regression were carried out using SPSS version 26.0., Results: The study revealed a 26.9% overall prevalence of depression, with higher risks among female adolescents (AOR 2.71, 95% CI 2.51, 2.92) and those in higher grades. Malays (AOR 1.71, 95% CI 1.41, 2.07), Other Bumiputeras (AOR 1.69, 95% CI 1.32, 2.17), and Others (AOR 1.63, 95% CI 1.16, 2.30) had elevated odds of depression compared to Indians. Healthy dietary habits, like consuming less than two servings of fruits daily, correlated with depression (AOR 1.44 95% CI 1.35, 1.54). Additionally, unhealthy dietary behaviours such as fast food consumption (AOR 1.73 [95% CI 1.55, 1.93]) and carbonated soft drink intake (AOR 1.59 [95% CI 1.48, 1.70]) were positively associated with depression., Conclusions: One out of every four Malaysian adolescents was identified to experience depression. Depression was linked to several factors, such as being female, belonging to higher grade levels, identifying as Malays, Other Bumiputeras, or belonging to other ethnicities, and participating in the consumption of fast food, carbonated soft drinks, and fruits. To address these observations, it is crucial to formulate effective public health programmes that prioritize adolescent mental health and encourage the adoption of healthy eating habits., (© 2023. The Author(s).)

Introduction: Nutrition education is the cornerstone to maintain optimal pregnancy outcomes including gestational weight gain (GWG). Nevertheless, default for appointments is common and often lead to suboptimal achievement of GWG, accompanied with unfavourable maternal and child health outcomes. While mobile health (mHealth) usage is increasing and helps minimising barriers to clinic appointments among pregnant mothers, its effectiveness on health outcomes has been inconclusive. Therefore, this study aimed to address the gap between current knowledge and clinical care, by exploring the effectiveness of mHealth on GWG as the primary outcome, hoping to serve as a fundamental work to achieve optimal health outcomes with the improvement of secondary outcomes such as physical activity, psychosocial well-being, dietary intake, quality of life and sleep quality among pregnant mothers., Methods and Analysis: A total of 294 eligible participants will be recruited and allocated into 3 groups comprising of mHealth intervention alone, mHealth intervention integrated with personal medical nutrition therapy and a control group. Pretested structured questionnaires are used to obtain the respondents' personal information, anthropometry data, prenatal knowledge, physical activity, psychosocial well-being, dietary intake, quality of life, sleep quality and GWG. There will be at least three time points of data collection, with all participants recruited during their first or second trimester will be followed up prospectively (after 3 months or/and after 6 months) until delivery. Generalised linear mixed models will be used to compare the mean changes of outcome measures over the entire study period between the three groups., Ethics and Dissemination: Ethical approvals were obtained from the ethics committee of human subjects research of Universiti Putra Malaysia (JKEUPM-2022-072) and medical research & ethics committee, Ministry of Health Malaysia: NMRR ID-22-00622-EPU(IIR). The results will be disseminated through journals and conferences targeting stakeholders involved in nutrition research., Trial Registration Number: Clinicaltrial.gov ID: NCT05377151., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: The melanocortin 3 receptor (MC3R) has recently emerged as a critical regulator of pubertal timing, linear growth, and the acquisition of lean mass in humans and mice. In population-based studies, heterozygous carriers of deleterious variants in MC3R report a later onset of puberty than noncarriers. However, the frequency of such variants in patients who present with clinical disorders of pubertal development is currently unknown., Objective: This work aimed to determine whether deleterious MC3R variants are more frequently found in patients clinically presenting with constitutional delay of growth and puberty (CDGP) or normosmic idiopathic hypogonadotropic hypogonadism (nIHH)., Methods: We examined the sequence of MC3R in 362 adolescents with a clinical diagnosis of CDGP and 657 patients with nIHH, experimentally characterized the signaling properties of all nonsynonymous variants found and compared their frequency to that in 5774 controls from a population-based cohort. Additionally, we established the relative frequency of predicted deleterious variants in individuals with self-reported delayed vs normally timed menarche/voice-breaking in the UK Biobank cohort., Results: MC3R loss-of-function variants were infrequent but overrepresented in patients with CDGP (8/362 [2.2%]; OR = 4.17; P = .001). There was no strong evidence of overrepresentation in patients with nIHH (4/657 [0.6%]; OR = 1.15; P = .779). In 246 328 women from the UK Biobank, predicted deleterious variants were more frequently found in those self-reporting delayed (aged ≥16 years) vs normal age at menarche (OR = 1.66; P = 3.90E-07)., Conclusion: We have found evidence that functionally damaging variants in MC3R are overrepresented in individuals with CDGP but are not a common cause of this phenotype., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

Purpose: To compare baseline mental health symptoms and gender affirmation between Black/Latine versus White transgender/nonbinary youth (BLTY vs. WTY) and examine relationships between gender affirmation and mental health symptoms, and whether associations differed by race/ethnicity subgroup., Methods: Baseline data were analyzed from the gender-affirming hormone cohort of the Trans Youth Care United States Study-a 4-clinic site, observational study. Mental health symptoms assessed included depression, suicidality, and anxiety. Gender affirmation measures included the parental acceptance subscale from the perceived Parental Attitudes of Gender Expansiveness Scale-Youth Report; non-affirmation, internalized transphobia, and community connectedness subscales from the Gender Minority Stress and Resilience Measure-Adolescent; and self-reported living full time in affirmed gender. Fisher exact tests and independent sample t tests compared mental health symptoms and gender affirmation between subgroups. Logistic regression analyses evaluated associations between gender affirmation and mental health symptoms. Interaction analyses assessed differences in associations between subgroups., Results: The sample (mean age 16 years, range 12-20 years) included 92 BLTY (35%) and 170 WTY (65%). Subgroups had comparable prevalence of depression and anxiety symptoms. WTY had higher prevalence of lifetime suicidality (73% vs. 59%; p = .02). There were no differences in gender affirmation. Among the whole sample, higher parental acceptance decreased odds of depression symptoms. Not living in affirmed gender increased odds of depression symptoms. Higher non-affirmation and internalized transphobia increased odds of depression and anxiety symptoms and suicidality. Associations did not vary by subgroup., Discussion: BLTY and WTY had comparable mental health symptoms. For both subgroups, gender affirmation decreased odds of those symptoms., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Piwi-interacting RNAs (piRNAs) are a new class of small, non-coding RNAs, crucial in the regulation of gene expression. Recent research has revealed links between piRNAs, viral defense mechanisms, and certain human cancers. Due to their clinical potential, there is a great interest in identifying piRNAs from large genome databases through efficient computational methods. However, piRNAs lack conserved structure and sequence homology across species, which makes piRNA detection challenging. Current detection algorithms heavily rely on manually crafted features, which may overlook or improperly use certain features. Furthermore, there is a lack of suitable computational tools for analyzing large-scale databases and accurately identifying piRNAs. To address these issues, we propose LSTM4piRNA, a highly efficient deep learning-based method for predicting piRNAs in large-scale genome databases. LSTM4piRNA utilizes a compact LSTM network that can effectively analyze RNA sequences from extensive datasets to detect piRNAs. It can automatically learn the dependencies among RNA sequences, and regularization is further integrated to reduce the generalization error. Comprehensive performance evaluations based on piRNAs from the piRBase database demonstrate that LSTM4piRNA outperforms current advanced methods and is well-suited for analysis with large-scale databases.

Background: Tai Chi is good for improving the physical fitness of older adults. But few studies have reported the effects of Tai Chi on the postural balance and quality of life of older adults with gait disorders., Objective: This review aimed to assess the influence of tai chi on postural stability and quality of life in older adults with abnormal gait., Method: According to the literature retrieval principles, the works published from the inception date to May 2023 were retrieved, including the following databases: PubMed, Scopus, Web of Science, China National Knowledge Infrastructure, EBSCOhost, and Google Scholar. Subsequently, literature screening and quality assessment were performed., Results: A total of 16 randomized controlled trials were included in this study, Tai Chi intervention can affect populations with Parkinson's disease (PD), no exercise, mild cognitive impairment (MCI), chronic stroke, sedentary, fear of falling, or history of falling. Postural instability is associated with balance, gait, the Unified Parkinson's Disease Rating Scale Motor Subscale 3 (UPDRS III), mobility, lower body strength, and falls. Only two articles looked at quality of life. The Yang style is the most commonly used in the intervention. Nonetheless, most studies were performed on female participants, hence, more research on older male populations is needed., Conclusion: Tai Chi intervention benefits postural balance in patients with gait disorders. 12 weeks is the most common intervention period for patients with gait disorders. The frequency of intervention is seven articles twice a week, and the intervention time is about 60 minutes. The Tai Chi intervention methods in this study involve Yang Style, Sun Style, Taoist Tai Chi, and Health Qigong Tai Chi, but the Yang Style Tai Chi intervention is the most widely used., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: Differences/disorders of sex development (DSDs) are rare, congenital conditions involving discordance between chromosomes, gonads, and phenotypic sex and are often diagnosed in infancy. A key subset of parents of children newly diagnosed with a DSD experience clinically elevated distress. The present study examines the relationship between perinatal factors (i.e., gestational age, delivery method) and trajectories of parental adjustment., Methods: Parent participants (mothers = 37; fathers = 27) completed measures at baseline, 6- and 12-month follow-up. Multilevel linear regression controlled for clustering of the data at three levels (i.e., time point, parent, and family) and examined the relationship between perinatal factors and trajectories of depressive and anxious symptoms. Two-way interactions between perinatal factors and parent type were evaluated., Results: Overall depressive and anxious symptoms decreased over time. There were significant interactions between gestational age and parent type for depressive and anxious symptoms, with younger gestational age having a stronger negative effect on mothers vs. fathers. There was a significant interaction between time and gestational age for depressive symptoms, with 36 weeks' gestational age demonstrating a higher overall trajectory of depressive symptoms across time compared to 38 and 40 weeks. Findings for the delivery method were not significant., Conclusions: Findings uniquely demonstrated younger gestational age was associated with increased depressive symptoms, particularly for mothers compared to fathers. Thus, a more premature birth may predispose parents of infants with DSD to distress. Psychosocial providers should contextualize early diagnosis-related discussions within stressful birth experiences when providing support., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: The incidence of type 2 diabetes mellitus is increasing worldwide. The literature suggests that acupuncture is a possible complementary therapy for type 2 diabetes mellitus. This study aims to determine the effectiveness of acupuncture as an adjunctive therapy on homeostasis model assessment-insulin resistance (HOMA-IR), and health-related quality of life (HRQoL) in patients with type 2 diabetes mellitus., Materials and Methods: This randomized, double-blind, placebo controlled, and parallel design trial will be carried out in a public university teaching hospitals in Malaysia. Eligible type 2 diabetes mellitus subjects will be randomly assigned to receive either acupuncture (n = 30) or a placebo (n = 30). The intervention is carried out using press needle or press placebo on abdomen area (10 sessions of treatment). Both groups will continue with their routine diabetes care. Primary outcome of HOMA-IR will be measured at the time of recruitment (-week 0), and after completion of 10 sessions (week 7) of the treatment. Additionally, secondary outcome of HRQoL will be measured at the time of recruitment (-week 0), after completion of 5 sessions (week 3/4), and 10 sessions (week 7) of the treatment. Any adverse event will be recorded at every visit., Discussion: The findings of this study will provide important clinical evidence for the effect of acupuncture as adjunctive therapy on HOMA-IR, adiposity and HRQoL of type 2 diabetes mellitus., Trial Registration Number: NCT04829045., Competing Interests: The authors have declared that no competing interests exists., (Copyright: © 2023 Cheok et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Post-stroke depression and anxiety, collectively known as post-stroke adverse mental outcome (PSAMO) are common sequelae of stroke. About 30% of stroke survivors develop depression and about 20% develop anxiety. Stroke survivors with PSAMO have poorer health outcomes with higher mortality and greater functional disability. In this study, we aimed to develop a machine learning (ML) model to predict the risk of PSAMO. We retrospectively studied 1780 patients with stroke who were divided into PSAMO vs. no PSAMO groups based on results of validated depression and anxiety questionnaires. The features collected included demographic and sociological data, quality of life scores, stroke-related information, medical and medication history, and comorbidities. Recursive feature elimination was used to select features to input in parallel to eight ML algorithms to train and test the model. Bayesian optimization was used for hyperparameter tuning. Shapley additive explanations (SHAP), an explainable AI (XAI) method, was applied to interpret the model. The best performing ML algorithm was gradient-boosted tree, which attained 74.7% binary classification accuracy. Feature importance calculated by SHAP produced a list of ranked important features that contributed to the prediction, which were consistent with findings of prior clinical studies. Some of these factors were modifiable, and potentially amenable to intervention at early stages of stroke to reduce the incidence of PSAMO.

Venous leg ulceration results in significant morbidity. However, the majority of studies conducted are on Western populations. This study aims to evaluate the wound healing and quality of life for patients with venous leg ulcers (VLUs) in a Southeast Asian population. This is a multi-centre prospective cohort study from Nov 2019 to Nov 2021. All patients were started on 2- or 4-layer compression bandage and were reviewed weekly or fortnightly. Our outcomes were wound healing, factors predictive of wound healing and the EuroQol 5-dimensional 5-level (EQ-5D-5L) health states. Within our cohort, there were 255 patients with VLU. Mean age was 65.2 ± 11.6 years. Incidence of diabetes mellitus was 42.0%. Median duration of ulcer at baseline was 0.30 years (interquartile range 0.136-0.834). Overall, the median time to wound healing was 4.5 months (95% confidence interval [CI]: 3.77-5.43). The incidence of complete wound healing at 3- and 6-month was 47.0% and 60.9%, respectively. The duration of the wound at baseline was independently associated with worse wound healing (Hazard ratio 0.94, 95% CI: 0.89-0.99, P = .014). Patients with healed VLU had a significantly higher incidence of perfect EQ-5D-5L health states at 6 months (57.8% vs 13.8%, P < .001). We intend to present longer term results in subsequent publications., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng., Competing Interests: Declaration of competing interest The authors report no declarations of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In 2020, cervical cancer ranked fourth in terms of both frequency of diagnosis and the leading cause of cancer-related deaths among women globally. Among Malaysian women, it was the third most prevalent form of cancer. Published data on nationally representative cervical cancer screening in Malaysia have been limited. Therefore, this study aimed to determine the prevalence of receiving a Pap smear test in the past three years, its relationship with socio-demographic factors and physical activity., Methods: Using a subset of survey data from the National Health and Morbidity Survey (NHMS) 2019, a secondary data analysis was performed. Trained research assistants collected data through face-to-face method using a mobile tablet questionnaire system application. Logistic regression analysis was performed to examine the relationship between sociodemographic factors, physical activity, and cervical cancer screening. The analyses were conducted using STATA version 14 (Stata Corp, College Station, Texas, USA), accounting for sample weighs and complex sampling design., Results: The analysis included 5,650 female respondents, representing an estimated 10.3 million Malaysian female adults aged 18 and above. Overall, 35.2% (95%CI 33.2, 37.4) respondents had a Pap smear test within the past three years. Respondents who were physically active were 1.41 times more likely to have a Pap smear test. Similarly, respondents aged 35-59 (OR 1.84; 95%CI 1.46, 2.34) and those living in rural localities (OR 1.38; 95%CI 1.13, 1.70) had higher odds of receiving a Pap smear test. Compared to married respondents, single respondents (OR 0.04; 95%CI 0.02, 0.07) and widowed/divorcee respondents (OR 0.72; 95%CI 0.56, 0.82) were less likely to receive a Pap smear test. Educated respondents were more likely to have had a Pap smear test., Conclusions: The overall prevalence of cervical cancer screening in Malaysia remains low (35.2%). Efforts should be made to strengthen health promotion programs and policies in increasing awareness on the significance of cervical cancer screening. These initiatives should specifically target younger women, single women, and widowed/divorced individuals. The higher cervical screening uptake among rural women should be studied further, and the enabling factors in the rural setup should be emulated in urban areas whenever possible., (© 2023. The Author(s).)

Background: In Malaysia, the previous mortality burden has been a significant concern, particularly due to the high prevalence of noncommunicable diseases (NCDs) as the leading cause of death. Estimates of mortality are key indicators for monitoring population health and determining priorities in health policies and health planning. The aim of this study was to estimate the disease burden attributed to 113 major diseases and injuries in Malaysia in 2018 using years of life lost (YLL) method., Methods: This study included all deaths that occurred in Malaysia in 2018. The YLL was derived by adding the number of deaths from 113 specific diseases and multiplying it by the remaining life expectancy for that age and sex group. Data on life expectancy and mortality were collected from the Department of Statistics Malaysia., Results: In 2018, there were 3.5 million YLL in Malaysia. Group II (NCDs) caused 72.2% of total YLL. Ischaemic heart disease was the leading cause of premature mortality among Malaysians (17.7%), followed by lower respiratory infections (9.7%), road traffic injuries (8.7%), cerebrovascular disease (stroke) (8.0%), and diabetes mellitus (3.9%)., Conclusions: NCDs are a significant health concern in Malaysia and are the primary contributor to the overall burden of disease. These results are important in guiding the national health systems on how to design and implement effective interventions for NCDs, as well as how to prioritise and allocate healthcare resources. Key strategies to consider include implementing health promotion campaigns, adopting integrated care models, and implementing policy and regulatory measures. These approaches aim to enhance health outcomes and the managements of NCDs in Malaysia., (© 2023. The Author(s).)

Introduction: Diabetes foot disease (DFD) contributes to poor quality of life, clinical and economic burden. Multidisciplinary diabetes foot teams provide prompt access to specialist teams thereby improving limb salvage. We present a 17-year review of an inpatient multidisciplinary clinical care path (MCCP) for DFD in Singapore., Methods: This was a retrospective cohort study of patients admitted for DFD and enrolled in our MCCP to a 1700-bed university hospital from 2005 to 2021., Results: There were 9279 patients admitted with DFD with a mean of 545 (±119) admissions per year. The mean age was 64 (±13.3) years, 61% were Chinese, 18% Malay and 17% Indian. There was a higher proportion of Malay (18%) and Indian (17%) patients compared to the country's ethnic composition. A third of the patients had end stage renal disease and prior contralateral minor amputation. There was a reduction in inpatient major lower extremity amputation (LEA) from 18.2% in 2005 to 5.4% in 2021 (odds ratio 0.26, 95% confidence interval 0.16-0.40, P  < .001) which was the lowest since pathway inception. Mean time from admission to first surgical intervention was 2.8 days and mean time from decision for revascularization to procedure was 4.8 days. The major-to-minor amputation rate reduced from 1.09 in 2005 to 0.18 in 2021, reflecting diabetic limb salvage efforts. Mean and median length of stay (LOS) for patients in the pathway was 8.2 (±14.9) and 5 (IQR = 3) days, respectively. There was a gradual trend of increase in the mean LOS from 2005 to 2021. Inpatient mortality and readmission rate was stable at 1% and 11%., Conclusion: Since the institution of a MCCP, there was a significant improvement in major LEA rate. An inpatient multidisciplinary diabetic foot care path helped to improve care for patients with DFD.

Background: In epidermolysis bullosa simplex (EBS), epithelial structural fragility results in blisters and erosions. Diacerein 1% ointment has been shown to reduce this blistering., Objective: To evaluate the efficacy and safety of diacerein 1% ointment in the treatment of EBS., Methods: A double-blind study of 54 patients with EBS were randomized to diacerein 1% or vehicle ointment once daily. The primary endpoint ( &ge;60% reduction in body surface area of EBS) and the key secondary endpoint ( &ge;2-point reduction in the Investigator&rsquo;s Global Assessment) were evaluated at 8 weeks., Results: There was no difference in the proportion of patients achieving either key efficacy endpoint between the diacerein 1% and vehicle groups (P&gt;0.05). No difference in treatment emergent adverse events were noted between the groups. In post hoc analysis stratified by EBS subtypes, an IGA score of 0 or 1 was reported in 6 of 13 patients with severe EBS in the diacerein group (46.2%), compared with 2 of 13 patients with severe EBS in the vehicle group (15.4%); (relative risk= 3.08, 95% CI = 0.71, 13.4)., Conclusions: Although there was no significant difference in outcomes between the groups, further study may elucidate the effects of diacerein on EBS lesions, especially in patients with severe EBS. Teng J, Paller AS, Bruckner AL, et al. Diacerein 1% ointment for the treatment of epidermolysis bullosa simplex: a randomized, controlled trial. J Drugs Dermatol. 2023;22(6):599-604. doi:10.36849/JDD.7108.

Purpose: Prior studies have identified a significant relationship between internalized transphobia and poor mental health among transgender and gender-diverse (TGD) adults; however, this relationship has not been extensively examined among youth. Further, little research has sought to explore protective factors, such as identity pride, and their influence on this relationship. We examined the association between internalized transphobia and depression and anxiety symptoms among TGD youth and explored the moderating role of gender identity pride on these associations., Methods: Participants were 315 TGD youth ages 12-20 years (mean = 16; standard deviation = 1.89) seeking gender-affirming hormone treatment at one of four major pediatric hospitals across the United States. At the time of enrollment, participants were naïve to gender-affirming hormone treatment. Participants self-reported mental health, internalized transphobia, and identity pride. Multiple regression models were used with depression and anxiety symptoms as outcomes and age, designated sex at birth, and perceived parental support included as covariates., Results: Greater internalized transphobia was associated with greater depressive symptoms, and gender identity pride moderated this relationship, such that greater gender identity pride was associated with fewer depressive symptoms. Greater internalized transphobia was significantly associated with greater anxiety symptoms; no moderation effect was observed for this relationship., Discussion: Gender identity pride influenced mental health symptoms for youth experiencing internalized transphobia and represents a potential key protective factor. These results support efforts to further develop, test, and implement clinical inventions to bolster identity pride for TGD youth., (Copyright © 2023 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Dioscoreae Rhizoma (Chinese yam; derived from the rhizome of Dioscorea opposita Thunb.) (DR), commonly consumed as a food or supplement, is often sulfur-fumigated during post-harvest handling, but it remains largely unknown if and how sulfur fumigation impacts the chemistry of DR. In this study, we report the impact of sulfur fumigation on the chemical profile of DR and then the molecular and cellular mechanisms potentially involved in the chemical variations induced by sulfur fumigation. The results show that sulfur fumigation significantly and specifically changed the small metabolites (molecular weight lower than 1000 Da) and polysaccharides of DR at both qualitative and quantitative levels. Multifaceted molecular and cellular mechanisms involving chemical transformations (e.g., acidic hydrolysis, sulfonation, and esterification) and histological damage were found to be responsible for the chemical variations in sulfur-fumigated DR (S-DR). The research outcomes provide a chemical basis for further comprehensive and in-depth safety and functional evaluations of sulfur-fumigated DR., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Background: As the RNA secondary structure is highly related to its stability and functions, the structure prediction is of great value to biological research. The traditional computational prediction for RNA secondary prediction is mainly based on the thermodynamic model with dynamic programming to find the optimal structure. However, the prediction performance based on the traditional approach is unsatisfactory for further research. Besides, the computational complexity of the structure prediction using dynamic programming is [Formula: see text]; it becomes [Formula: see text] for RNA structure with pseudoknots, which is computationally impractical for large-scale analysis., Results: In this paper, we propose REDfold, a novel deep learning-based method for RNA secondary prediction. REDfold utilizes an encoder-decoder network based on CNN to learn the short and long range dependencies among the RNA sequence, and the network is further integrated with symmetric skip connections to efficiently propagate activation information across layers. Moreover, the network output is post-processed with constrained optimization to yield favorable predictions even for RNAs with pseudoknots. Experimental results based on the ncRNA database demonstrate that REDfold achieves better performance in terms of efficiency and accuracy, outperforming the contemporary state-of-the-art methods., (© 2023. The Author(s).)

Objective: This study aims to determine the prevalence of poor self-rated health (SRH) in Malaysia and its association with sociodemographic characteristics, lifestyle behavior, chronic diseases, depression, and functional limitations in activities of daily living (ADLs) among older persons., Design: Cross-sectional. Setting, participants, and outcome measures: We used data from the National Health and Morbidity Survey 2018, a nationwide community-based study. This study was conducted using a two-stage stratified cluster sampling design. Older persons were defined as persons aged 60 years and above. SRH was assessed using the question "How do you rate your general health?" and the answers were "very good", "good", "moderate", "not good", and "very bad". SRH was then grouped into two categories; "Good" (very good and good) and "Poor" (moderate, not good, and very bad). Descriptive and logistic regression analyses were conducted using SPSS version 25.0., Results: The prevalence of poor SRH among older persons was 32.6%. Poor SRH was significantly related to physical inactivity, depression, and limitations in activities of daily living (ADLs). Multiple logistic regression revealed that poor SRH was positively associated with those who had depression (aOR 2.92, 95% CI:2.01,4.24), limitations in ADLs (aOR 1.82, 95% CI: 1.31, 2.54), low individual income (aOR 1.66, 95% CI:1.22, 2.26), physical inactivity (aOR 1.40, 95% CI:1.08, 1.82), and hypertension (aOR 1.23, 95% CI:1.02, 1.49)., Conclusions: Older persons with depression, limitations in ADLs, low income, physical inactivity, and hypertension were significantly associated with poor SRH. These findings provide information to aid health personnel and policymakers in the development and implementation of health promotion and disease prevention programs, as well as adequate evidence in planning different levels of care for the older population.

Quality of life (QOL) of older adults is a complex issue that requires an understanding of the intersection between socioeconomic and health factors. A poor quality of life (QOL) is frequently reported as sub-optimal among older adults whereby concerted and collective actions are required through an evidence-based approach. Hence, this cross-sectional study aims to determine the social and health predictors of the QOL of a community-dwelling older adult Malaysian population through a quantitative household survey using multi-stage sampling. A total of 698 respondents aged 60 years old and older were recruited and the majority of them had a good quality of life. Risk of depression, disability, living with stroke, low household income, and lack of social network were identified as the predictors of a poor QOL among the community-dwelling older Malaysians. The identified predictors for QOL provided a list of priorities for the development of policies, strategies, programmes, and interventions to enhance the QOL of the community-dwelling older Malaysians. Multisectoral approaches, especially collective efforts from both social and health sectors, are required to address the complexities of the ageing issues.

Background: Limited prospective outcome data exist regarding transgender and nonbinary youth receiving gender-affirming hormones (GAH; testosterone or estradiol)., Methods: We characterized the longitudinal course of psychosocial functioning during the 2 years after GAH initiation in a prospective cohort of transgender and nonbinary youth in the United States. Participants were enrolled in a four-site prospective, observational study of physical and psychosocial outcomes. Participants completed the Transgender Congruence Scale, the Beck Depression Inventory-II, the Revised Children's Manifest Anxiety Scale (Second Edition), and the Positive Affect and Life Satisfaction measures from the NIH (National Institutes of Health) Toolbox Emotion Battery at baseline and at 6, 12, 18, and 24 months after GAH initiation. We used latent growth curve modeling to examine individual trajectories of appearance congruence, depression, anxiety, positive affect, and life satisfaction over a period of 2 years. We also examined how initial levels of and rates of change in appearance congruence correlated with those of each psychosocial outcome., Results: A total of 315 transgender and nonbinary participants 12 to 20 years of age (mean [±SD], 16±1.9) were enrolled in the study. A total of 190 participants (60.3%) were transmasculine (i.e., persons designated female at birth who identify along the masculine spectrum), 185 (58.7%) were non-Latinx or non-Latine White, and 25 (7.9%) had received previous pubertal suppression treatment. During the study period, appearance congruence, positive affect, and life satisfaction increased, and depression and anxiety symptoms decreased. Increases in appearance congruence were associated with concurrent increases in positive affect and life satisfaction and decreases in depression and anxiety symptoms. The most common adverse event was suicidal ideation (in 11 participants [3.5%]); death by suicide occurred in 2 participants., Conclusions: In this 2-year study involving transgender and nonbinary youth, GAH improved appearance congruence and psychosocial functioning. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.)., (Copyright © 2023 Massachusetts Medical Society.)

Background and Objectives: Evidence for gene-diet interactions is lacking among individuals with specific dietary practices including vegetarians. This study aimed to determine the interactions of rs174547 in the fatty acid desaturase 1 (FADS1) gene with macronutrient such as carbohydrate (particularly fibre), protein and fat intakes on abdominal obesity among middle-aged Malaysian vegetarians of Chinese and Indian ethnicity., Methods and Study Design: The present cross-sectional study was conducted among 163 vegetarians in Kuala Lumpur and Selangor, Malaysia. Dietary intakes of vegetarians were assessed by using a food frequency questionnaire. Waist circumference of vegetarians was measured by using a Lufkin tape W606PM. Genotypes of the rs174547 of vegetarians were determined by using Agena® MassARRAY. A multiple logistic regression model was used to determine the interactions of the rs174547 with macronutrient on abdominal obesity., Results: About 1 in 2 vegetarians (51.5%) had abdominal obesity. Individuals with CT and TT genotype at T3 intake of carbohydrates, protein, fat and fibre as well as individuals with TT genotype at T2 intake of carbohydrates and protein had higher odds of abdominal obesity (pinteration <0.05). The gene-diet interaction remained significant for fibre intake (OR: 4.71, 95% CI: 1.25-17.74, pinteraction=0.022) among vegetarians with TT genotype at T2 intake of fibre after adjusting for age and sex and considering the effects of ethnicity and food groups., Conclusions: The rs174547 significantly interacted with fibre intake on abdominal obesity. A specific dietary fibre recommendation based on genetics is needed among Chinese and Indian middle-aged vegetarians.

Introduction: Children with self-limited delayed puberty (DP) (constitutional delay) enter puberty after variable waiting times, and the factors associated with their eventual pubertal timing are not well understood., Methods: We conducted a retrospective study of 99 girls and 228 boys with self-limited DP at an academic medical center between 2000 and 2015. To define features and potential subtypes of self-limited DP, we performed group-based trajectory modeling on childhood growth and latent-variable factor analysis on clinical characteristics. We then conducted time-to-event analyses to identify associations with pubertal timing., Results: We identified two distinct growth trajectories in individuals with self-limited DP: one with stable and the other with declining height percentiles. Latent-variable factor analysis identified five factors underlying clinical variation that appear to correspond to genetic height potential, body mass index, childhood growth, parental pubertal delay, and medical issues (attention-deficit/hyperactivity disorder and inhaled glucocorticoid use). We observed correlations between pubertal timing and bone age (p = 0.01), childhood height (p = 0.004), and midparental target height (p < 0.001), but not with parental pubertal delay or with testosterone treatment in boys., Conclusions: By illustrating the heterogeneity within self-limited DP and identifying factors underlying this heterogeneity, our study suggests that there may be multiple causes of self-limited DP. However, our ability to determine when puberty will eventually occur remains limited. Dissecting self-limited DP into its component subtypes may inform future studies of the mechanisms contributing to pubertal delay as well as studies of the short- and long-term outcomes of self-limited DP., (© 2022 S. Karger AG, Basel.)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by decreased synaptic transmission and cerebral atrophy with appearance of amyloid plaques and neurofibrillary tangles. Cognitive, functional, and behavioral alterations are commonly associated with the disease. Different pathophysiological pathways of AD have been proposed, some of which interact and influence one another. Current treatment for AD mainly involves the use of therapeutic agents to alleviate the symptoms in AD patients. The conventional single-target treatment approaches do not often cause the desired effect in the disease due to its multifactorial origin. Thus, multi-target strategies have since been undertaken, which aim to simultaneously target multiple targets involved in the development of AD. In this review, we provide an overview of the pathogenesis of AD and the current drug therapies for the disease. Additionally, rationales of the multi-target approaches and examples of multi-target drugs with pharmacological actions against AD are also discussed.

Study Objective: Infants with genital development considered atypical for assigned female sex may undergo feminizing genitoplasty (clitoroplasty and/or vaginoplasty) in early life. We sought to identify factors associated with parent/caregiver decisions regarding genitoplasty for their children with genital virilization., Design: Longitudinal, observational study SETTING: Twelve pediatric centers in the United States with multidisciplinary differences/disorders of sex development clinics, 2015-2020 PARTICIPANTS: Children under 2 years old with genital appearance atypical for female sex of rearing and their parents/caregivers INTERVENTIONS/OUTCOME MEASURES: Data on the child's diagnosis and anatomic characteristics before surgery were extracted from the medical record. Parents/caregivers completed questionnaires on psychosocial distress, experience of uncertainty, cosmetic appearance of their child's genitalia, and demographic characteristics. Urologists rated cosmetic appearance. For 58 patients from the study cohort with genital virilization being raised as girls or gender-neutral, we compared these data across 3 groups based on the child's subsequent surgical intervention: (i) no surgery (n = 5), (ii) vaginoplasty without clitoroplasty (V-only) (n = 15), and (iii) vaginoplasty and clitoroplasty (V+C) (n = 38)., Results: Fathers' and urologists' ratings of genital appearance were more favorable in the no-surgery group than in the V-only and V+C groups. Clitorophallic length was greater in the V+C group compared with the V-only group, with substantial overlap between groups. Mothers' depressive and anxious symptoms were lower in the no-surgery group compared with the V-only and V+C groups., Conclusions: Surgical decisions were associated with fathers' and urologists' ratings of genital appearance, the child's anatomic characteristics, and mothers' depressive and anxious symptoms. Further research on surgical decision-making is needed to inform counseling practices., (Copyright © 2022. Published by Elsevier Inc.)

Much has been claimed on the health benefits of alkaline water including metabolic syndrome (MetS) and its features with scarcity of scientific evidence. Methods: This cross-sectional comparative study was conducted to determine whether regular consumption of alkaline water confers health advantage on blood metabolites, anthropometric measures, sleep quality and muscle strength among postmenopausal women. A total of 304 community-dwelling postmenopausal women were recruited with comparable proportion of regular drinkers of alkaline water and non-drinkers. Participants were ascertained on dietary intake, lifestyle factors, anthropometric and biochemical measurements. Diagnosis of MetS was made according to Joint Interim Statement definition. A total of 47.7% of the participants met MS criteria, with a significant lower proportion of MetS among the alkaline water drinkers. The observed lower fasting plasma glucose (F(1,294) = 24.20, p = 0.025, partial η2 = 0.435), triglyceride/high-density lipoprotein concentration ratio (F(1,294) = 21.06, p = 0.023, partial η2 = 0.360), diastolic blood pressure (F(1,294) = 7.85, p = 0.046, partial η2 = 0.258) and waist circumference (F(1,294) = 9.261, p = 0.038, partial η2 = 0.263) in the alkaline water drinkers could be considered as favourable outcomes of regular consumption of alkaline water. In addition, water alkalization improved duration of sleep (F(1,294) = 32.05, p = 0.007, partial η2 = 0.451) and handgrip strength F(1,294) = 27.51, p = 0.011, partial η2 = 0.448). Low density lipoprotein cholesterol concentration (F(1,294) = 1.772, p = 0.287, partial η2 = 0.014), body weight (F(1,294) = 1.985, p = 0.145, partial η2 = 0.013) and systolic blood pressure (F(1,294) = 1.656, p = 0.301, partial η2 = 0.010) were comparable between the two different water drinking behaviours. In conclusion, drinking adequate of water is paramount for public health with access to good quality drinking water remains a critical issue. While consumption of alkaline water may be considered as a source of easy-to implement lifestyle to modulate metabolic features, sleep duration and muscle strength, further studies are warranted for unravelling the precise mechanism of alkaline water consumption on the improvement and prevention of MetS and its individual features, muscle strength and sleep duration as well as identification of full spectrum of individuals that could benefit from its consumption., Competing Interests: The authors have declared that no competing interests exist.

We previously found that sulfur fumigation, a commonly used controversial method for the post-harvest handling of ginger, induces the generation of a compound in ginger, which was speculated to be a sulfur-containing derivative of 6-shogaol based on its mass data. However, the chemical and biological properties of the compound remain unknown. As a follow-up study, here we report the chemical structure, systemic exposure, and anticancer activity of the compound. Chromatographic separation, nuclear magnetic resonance analysis, and chemical synthesis structurally elucidated the compound as 6-gingesulfonic acid. Pharmacokinetics in rats found that 6-gingesulfonic acid was more slowly absorbed and eliminated, with more prototypes existing in the blood than 6-shogaol. Metabolism profiling indicated that the two compounds produced qualitatively and quantitatively different metabolites. It was further found that 6-gingesulfonic acid exerted significantly weaker antiproliferative activity on tumor cells than 6-shogaol. The data provide chemical and biological evidence that sulfur fumigation may impair the healthcare functions of ginger.

This study aimed to investigate the association between socio-demographic factors and designated healthy lifestyle behaviours in a nationally-representative sample of Malaysian adults aged 18 years and above. Secondary data involving 7388 participants aged 18-96 years from the National Health and Morbidity Survey 2019, a national cross-sectional survey, was used in this study. A healthy lifestyle score (0-5 points) was calculated based on five modifiable lifestyle factors: non-smoker, body mass index < 25 kg/m 2 , physically active, moderate (or less) alcohol intake, and daily consumption of ≥ 5 servings of fruits and vegetables. Associations between socio-demographic factors and healthy lifestyle behaviours were examined using multinomial logistic regression adjusted for sampling design. About 30.6% of the participants met at least four out of the five healthy lifestyle factors. In multinomial model, subjects who were female (aOR = 3.26, 95%CI = 2.58, 4.12), of Chinese (aOR = 2.31, 95%CI = 1.62, 3.30 or other ethnicity (aOR = 1.44, 95%CI = 1.05, 1.98), and aged 18-30 years (aOR = 1.74, 95% CI = 1.12, 2.71) showed significant association with achieving healthy lifestyle compared to male, Malay and ≥ 61 years old as reference categories. Our results indicated that gender, age and ethnicity associated with healthy lifestyle behaviours. Information on the influence of socio-demographic factors on the prevalence of healthy lifestyles will facilitate the development of effective intervention strategies to improve the adaptation of healthy lifestyle practices., (© 2022. The Author(s).)

Objective: The impact of parent-reported stigma due to their child's disorder/difference of sex development (DSD) on parent psychosocial adjustment is poorly understood. In other pediatric populations, perceived interference of medical conditions into daily activities (i.e., illness intrusiveness ) mediates the relationship of stigma to adjustment. This study assessed relationships between parent-focused and child-focused stigma → illness intrusiveness → depressive and anxious symptoms . Exploratory analyses sought to identify patient characteristics associated with stigma., Method: Caregivers (59 women and 43 men) of 63 children diagnosed with a DSD up to age 4 years completed measures of demographics, parent-focused and child-focused stigma, illness intrusiveness, and depressive and anxious symptoms., Results: Increased parent-focused and child-focused stigma were associated with increased illness intrusiveness, which, in turn, was associated with increased depressive and anxious symptoms for parents nested within dyads. Among children with DSD family histories, parents reported greater child-focused stigma., Conclusion: Parents who experience DSD-related stigma report greater interference of their child's DSD into their daily activities, which is associated with poorer psychosocial adjustment. Findings support developing clinical interventions related to parents' perceptions of stigma and illness intrusiveness to improve parent adjustment., Competing Interests: Disclosure: P. F. Austin is a clinical investigator and member of the pediatric advisory group for Allergan. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Equations for estimated glomerular filtration rate (eGFR) based on serum creatinine include terms for sex/gender. For transgender and gender-diverse (TGD) youth, gender-affirming hormone (GAH) treatment may affect serum creatinine and in turn eGFR., Methods: TGD youth were recruited for this prospective, longitudinal, observational study prior to starting GAH treatment. Data collected as part of routine clinical care were abstracted from the medical record., Results: For participants designated male at birth (DMAB, N = 92), serum creatinine decreased within 6 months of estradiol treatment (mean ± SD 0.83 ± 0.12 mg/dL to 0.76 ± 0.12 mg/dL, p < 0.001); for participants designated female at birth (DFAB, n = 194), serum creatinine increased within 6 months of testosterone treatment (0.68 ± 0.10 mg/dL to 0.79 ± 0.11 mg/dL, p < 0.001). Participants DFAB treated with testosterone had serum creatinine similar to that of participants DMAB at baseline, whereas even after estradiol treatment, serum creatinine in participants DMAB remained higher than that of participants DFAB at baseline. Compared to reference groups drawn from the National Health and Nutritional Examination Survey, serum creatinine after 12 months of GAH was more similar when compared by gender identity than by designated sex., Conclusion: GAH treatment leads to changes in serum creatinine within 6 months of treatment. Clinicians should consider a patient's hormonal exposure when estimating kidney function via eGFR and use other methods to estimate GFR if eGFR based on serum creatinine is concerning., (© 2022. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

This study provides an accurate and efficient method to reconstruct detailed and high-resolution digital 3D models of carpological materials by photogrammetric method, in which only about 100 to 150 images are required for each model reconstruction. The 3D models reflect the realistic morphology and genuine color of the carpological materials. The 3D models are scaled to represent the true size of the materials even as small as 3 mm in diameter. The interfaces are interactive, in which the 3D models can be rotated in 360° to observe the structures and be zoomed to inspect the macroscopic details. This new platform is beneficial for developing a virtual herbarium of carpological collection which is thus the most important to botanical authentication and education., Competing Interests: The authors have declared that no competing interests exist.

This study aimed to investigate the relationship between adequate fruit and vegetable intake, and cardiovascular diseases (CVDs)-associated risk factors (i.e., diabetes, hypertension and hypercholesterolemia) among Malaysian adults without history of chronic diseases. We analyzed the data from 11,172 Malaysian adults (i.e., 5554 male and 5618 female), who participated in the population-based National Health and Morbidity Survey 2015. Multiple logistic regression was employed to determine the relationship between adequate daily intake of fruit and vegetables (i.e., ≥5 servings per day) and undiagnosed diabetes, undiagnosed hypertension, and undiagnosed hypercholesterolemia, after adjustment for sociodemographic characteristics and lifestyle risk factors. The mean age (±SE) of these participants was 40.79 (±0.17) years old. Our data demonstrated an adequate daily intake of fruit and vegetables was inversely associated with undiagnosed hypercholesterolemia (adjusted OR: 0.71; 95% CI: 0.51-0.98). Further analyses demonstrated an inverse association between the adequate daily intake of vegetables alone and undiagnosed hypertension (adjusted OR: 0.71; 95% CI: 0.51-0.98). The findings from this study suggest the need for a holistic public health approach to reinforce public awareness about diet-related diseases, which will eventually aid in the prevention of CVDs among Malaysian adults in the long run.

Objective: Cardiovascular disease (CVD) is the leading cause of disability and death in many countries. Together with CVD, Type 2 diabetes mellitus (T2DM) accounts for more than 80% of all premature non-communicable disease deaths. The protective effect of the Mediterranean diet (MedDiet) on CVD and its risk factors, including T2DM, has been a constant topic of interest. Notwithstanding, despite the large body of evidence, scientists are concerned about the challenges and difficulties of the application of MedDiet. This review aims to explore the motivations and challenges for using MedDiet in patients with CVD and T2DM., Design: An electronic search was conducted for articles about MedDiet published in PubMed, ScienceDirect, Scopus, and Web of Science up to December 2021, particularly on CVD and T2DM patients. From a total of 1536 studies, the final eligible set of 108 studies was selected. Study selection involved three iterations of filtering., Results: Motivation to apply MedDiet was driven by the importance of studying the entire food pattern rather than just one nutrient, the health benefits, and the distinct characteristics of MedDiet. Challenges of the application of MedDiet include lacking universal definition and scoring of MedDiet. Influences of nutritional transition that promote shifting of traditional diets to Westernized diets further complicate the adherence of MedDiet. The challenges also cover the research aspects, including ambiguous and inconsistent findings, the inexistence of positive results, limited evidence, and generalization in previous studies. The review revealed that most of the studies recommended that future studies are needed in terms of health benefits, describing the potential benefits of MedDiet, identifying the barriers, and mainly discussing the effect of MedDiet in different populations., Conclusions: In general, there is consistent and strong evidence that MedDiet is associated inversely with CVD risk factors and directly with glycemic control. MedDiet is the subject of active and diverse research despite the existing challenges. This review informs the health benefits conferred by this centuries-old dietary pattern and highlights MedDiet could possibly be revolutionary, practical, and non-invasive approach for the prevention and treatment CVD and T2DM.

Background: The populations of many countries-including Malaysia-are rapidly growing older, causing a shift in leading causes of disease and death. In such rapidly ageing populations, it is critical to monitor trends in burden of disease and health of older adults by identifying the leading causes of premature mortality and measuring years of life lost (YLL) to these. The objective of this study, therefore, is to describe the burden (quantified by YLL) associated with major causes of premature mortality among older adults in Malaysia in 2019., Methods: All deaths that occurred in older adults aged 60 and above in Malaysia in the year 2019 were included in this study. YLL was calculated by summing the number of deaths for the disease category at 5-year age intervals, multiplied by the remaining life expectancy for the specific age and sex group. Both life expectancy and mortality data were obtained from the Department of Statistics Malaysia., Results: In 2019, older adults accounted for 67.4% of total deaths in Malaysia (117,102 out of 173,746). The total number of YLL among older adults in Malaysia in 2019 was estimated at 1.36 million YLL, accounting for 39.6% of the total YLL (3.44 million) lost to all premature deaths in that year. The major causes of premature mortality among older adults were ischaemic heart disease (29.5%) followed by cerebrovascular disease (stroke) (20.8%), lower respiratory infections (15.9%), diabetes mellitus (8.1%) and trachea, bronchus and lung cancers (5.0%)., Conclusions: Non-communicable diseases (NCD) remained the largest contributor to premature mortality among older adults in Malaysia. Implementation of population-level NCD health promotion programmes, screening programmes among high-risk groups and holistic intervention programmes among populations living with NCD are critical in reducing the overall burden of premature mortality., (© 2022. The Author(s).)

Objectives: Measurement comparability between blood gas analyzers within a laboratory is of utmost importance. This study analyzed the data obtained from a three-year period., Design and Methods: For quality monitoring one blood sample was tested on two identical blood gas analyzers at each of three shifts/day for three years. Deming regression analysis was used to determine result correlation and statistical identity between the two analyzers for p H, p CO 2 , p O 2 , sodium, potassium, chloride, ionized calcium, glucose, and lactate. Failures in the two-analyzer comparison were determined by the performance limits from the Institute of Quality Management in Healthcare (IQMH) and from the manufacturer respectively., Results: Correlation coefficients were greater than 0.96 (0.9622-0.9975) for all tested analytes. The measurements of every analyte on both analyzers were statistically identical. In the two-analyzer comparison failure numbers/1000 tests for p O 2 and glucose varied with the performance limits (IQMH: 0.6 and 49.2; the manufacturer: 19.3 and 4.4, respectively). In addition, persistent glucose failures (>5/week) between the two analyzers occurred occasionally., Conclusions: Results of all tested analytes between the two blood gas analyzers were interchangeable. Recurring glucose discrepancies might be a result of different lots of cartridges used on each analyzer, which were not identified during the initial installation., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© 2022 The Authors.)

Background: Surgical intervention in youth with differences of sex development (DSD) is a controversial topic. Historically, evidence suggests that genital surgery in DSD is associated with mixed patient satisfaction. However, less is known about surgical outcomes under therapeutic advancements in the past several decades., Objective: The purpose of the current study is to provide an updated and empirical qualitative examination of the surgical experiences and responses to care of adolescents and young adults (AYA) with DSD in order to fill this gap in the literature and inform patient care., Methods: Qualitative interviews were conducted with 37 AYA (ages 12-26) with DSD. Interviews were transcribed, coded, and analyzed thematically., Results: Three major themes were identified: 1) knowledge related to surgery; 2) surgical and medical experience; and 3) psychosocial factors related to surgery. Results demonstrated that most AYA were not involved in the decision to pursue surgery and were observed to have varying levels of knowledge regarding their surgeries. Most participants in the current study had received a DSD-related surgery and the majority described having positive surgical experiences and few regrets. Nonetheless, AYA described both medical and psychosocial challenges related to their surgeries and recoveries and offered feedback on ways to improve the surgical process., Discussion: The current study provides a qualitative examination of the surgical experiences of 37 AYA with DSD. Findings highlight the importance of regular and ongoing communication with providers to improve knowledge related to surgery during the decision-making process as well as after surgical intervention. Results underscore the benefits of multidisciplinary teams and the value of patient handouts and decision aids in assisting AYA in the decision to pursue surgical intervention. Other specific recommendations for providers include increased patient privacy during genital exams, greater emphasis on psychoeducation and pain management strategies, and the use of behavioral health services to assist with challenges and social support., Conclusions: The decision to pursue surgical intervention in youth with DSD remains a complex and controversial issue, and more information regarding patients' perspectives on surgery is needed. The current study provides novel insights into patient experiences of surgical intervention and highlights the need for psychosocial support throughout the shared decision-making process., Competing Interests: Conflicts of interest The authors of this manuscript declare no conflicts of interest., (Copyright © 2022 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Visual snow syndrome is a neurological condition characterized by a persistent visual disturbance, visual snow, in conjunction with additional visual symptoms. Cortical hyperexcitability is a potential pathophysiological mechanism, which could be explained by increased gain in neural responses to visual input. Alternatively, neural noise in the visual pathway could be abnormally elevated. We assessed these two potential competing neural mechanisms in our studies of visual contrast perception. Cortical hyperexcitation also occurs in migraine, which commonly co-occurs with visual snow syndrome. Therefore, to determine whether the effect of visual snow syndrome can be distinguished from interictal migraine, we recruited four participant groups: controls, migraine alone, visual snow syndrome alone and visual snow syndrome with migraine. In the first experiment, we estimated internal noise in 20 controls, 21 migraine participants and 32 visual snow syndrome participants (16 with migraine) using a luminance increment detection task. In the second experiment, we estimated neural contrast gain in 21 controls, 22 migraine participants and 35 visual snow syndrome participants (16 with migraine) using tasks assessing sensitivity to changes in contrast from a reference. Contrast gain and sensitivity were measured for the putative parvocellular and 'on' and 'off' magnocellular pathways, respectively. We found that luminance increment thresholds and internal noise estimates were normal in both visual snow syndrome and migraine. Contrast gain measures for putative parvocellular processing and contrast sensitivity for putative off magnocellular processing were abnormally increased in visual snow syndrome, regardless of migraine status. Therefore, our results indicate that visual snow syndrome is characterized by increased neural contrast gain but not abnormal neural noise within the targeted pathways., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Present guidelines recommend a multidisciplinary team (MDT) approach to diabetic foot ulcer (DFU) care, but relevant data from Asia are lacking. We aim to evaluate the clinical and economic outcomes of an MDT approach in a lower extremity amputation prevention programme (LEAPP) for DFU care in an Asian population. We performed a case-control study of 84 patients with DFU between January 2017 and October 2017 (retrospective control) vs 117 patients with DFU between December 2017 and July 2018 (prospective LEAPP cohort). Comparing the clinical outcomes between the retrospective cohort and the LEAPP cohort, there was a significant decrease in mean time from referral to index clinic visit (38.6 vs 9.5 days, P < .001), increase in outpatient podiatry follow-up (33% vs 76%, P < .001), decrease in 1-year minor amputation rate (14% vs 3%, P = .007), and decrease in 1-year major amputation rate (9% vs 3%, P = .05). Simulation of cost avoidance demonstrated an annualised cost avoidance of USD $1.86m (SGD $2.5m) for patients within the LEAPP cohort. In conclusion, similar to the data from Western societies, an MDT approach in an Asian population, via a LEAPP for patients with DFU, demonstrated a significant reduction in minor and major amputation rates, with annualised cost avoidance of USD $1.86m., (© 2021 The Authors. International Wound Journal published by Medicalhelplines.com Inc (3M) and John Wiley & Sons Ltd.)

Competing Interests: We declare no competing interests.

The genome-editing Cas9 protein uses multiple amino-acid residues to bind the target DNA. Considering only the residues in proximity to the target DNA as potential sites to optimise Cas9's activity, the number of combinatorial variants to screen through is too massive for a wet-lab experiment. Here we generate and cross-validate ten in silico and experimental datasets of multi-domain combinatorial mutagenesis libraries for Cas9 engineering, and demonstrate that a machine learning-coupled engineering approach reduces the experimental screening burden by as high as 95% while enriching top-performing variants by ∼7.5-fold in comparison to the null model. Using this approach and followed by structure-guided engineering, we identify the N888R/A889Q variant conferring increased editing activity on the protospacer adjacent motif-relaxed KKH variant of Cas9 nuclease from Staphylococcus aureus (KKH-SaCas9) and its derived base editor in human cells. Our work validates a readily applicable workflow to enable resource-efficient high-throughput engineering of genome editor's activity., (© 2022. The Author(s).)

Objective: This study aimed to determine whether the visual response to flickering checkerboard patterns measured using electroencephalography (EEG) relate to excitatory or inhibitory metabolite levels measured using ultra-high (7Tesla/7T) magnetic resonance spectroscopy (MRS)., Background: Electrophysiological studies have shown altered visual cortical response amplitudes and contrast gain responses to high contrast flickering patterns in people with migraine. These contrast response anomalies have been argued to represent an imbalance between cortical inhibition and excitation, however the specific mechanism has not been elucidated., Methods: MRS-measured metabolite levels were obtained from the occipital cortex of 18 participants with migraine and 18 non-headache controls. EEG contrast gain response functions were collected on separate days from a subset of 10 participants with migraine and 12 non-headache controls. Case-control outcome measures were statistically compared between groups both before and after checkboard exposure., Results: No significant difference in GABA and glutamate levels were found between groups nor checkerboard timepoint. Glucose levels were significantly reduced after checkerboard exposure in both participant groups. There was no metabolic signature in visual cortex in response to high-contrast flickering checkboards that distinguished those with migraine and without. There was also no correlation between MRS and EEG measurements in response to the flickering checkerboard., Conclusion: Our findings suggest that the mechanisms driving contrast-flickering stimulus aversion are not simplistically reflected by gross changes in metabolic activity in the primary visual cortex., Competing Interests: The authors have declared that no competing interests exist.

Chemistry laboratory experiments are invaluable to students' acquisition of necessary synthetic, analytical, and instrumental skills during their undergraduate studies. However, the COVID-19 pandemic rendered face-to-face (f2f), in-person teaching laboratory experiences impossible from late 2019-2020 and forced educators to rapidly develop new solutions to deliver chemistry laboratory education remotely. Unfortunately, achieving learning and teaching objectives to the same caliber of in-person experiments is very difficult through distance learning. To overcome these hurdles, educators have generated many virtual and remote learning options for not only foundational chemistry courses but also laboratory experiments. Although the pandemic challenged high-level chemistry education, it has also created an opportunity for both students and educators to be more cognizant of virtual learning opportunities and their potential benefits within chemistry curriculum. Irrespective of COVID-19, virtual learning techniques, especially virtual lab experiments, can complement f2f laboratories and offer a cost-efficient, safe, and environmentally sustainable alternative to their in-person counterparts. Implementation of virtual and distance learning techniques-including kitchen chemistry and at-home laboratories, prerecorded videos, live-stream video conferencing, digital lab environment, virtual and augmented reality, and others-can provide a wide-ranging venue to teach chemistry laboratories effectively and encourage diversity and inclusivity in the field. Despite their relevance to real-world applications and potential to expand upon fundamental chemical principles, polymer lab experiments are underrepresented in the virtual platform. Polymer chemistry education can help prepare students for industrial and academic positions. The impacts of polymers in our daily life can also promote students' interests in science and scientific research. Hence, the translation of polymer lab experiments into virtual settings improves the accessibility of polymer chemistry education. Herein, we assess polymer experiments in the emergence of virtual learning environments and provide suggestions for further incorporation of effective polymer teaching and learning techniques into virtual settings., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society and Division of Chemical Education, Inc.)

Context: Polycystic ovary syndrome (PCOS) is characterized by ovulatory dysfunction and hyperandrogenism and can be associated with cardiometabolic dysfunction, but it remains unclear which of these features are inciting causes and which are secondary consequences., Objective: To determine whether ovarian function is necessary for genetic risk factors for PCOS to produce nonreproductive phenotypes., Design, Setting, and Participants: Cohort of 176 360 men in the UK Biobank and replication cohort of 37 348 men in the Estonian Biobank., Main Outcome Measures: We calculated individual PCOS polygenic risk scores (PRS), tested for association of these PRS with PCOS-related phenotypes using linear and logistic regression and performed mediation analysis., Results: For every 1 SD increase in the PCOS PRS, men had increased odds of obesity (odds ratio [OR]: 1.09; 95% CI, 1.08-1.10; P = 1 × 10-49), type 2 diabetes mellitus (T2DM) (OR: 1.08; 95% CI, 1.05-1.10; P = 3 × 10-12), coronary artery disease (CAD) (OR: 1.03; 95% CI, 1.01-1.04; P = 0.0029), and marked androgenic alopecia (OR: 1.03; 95% CI, 1.02-1.05; P = 3 × 10-5). Body mass index (BMI), hemoglobin A1c, triglycerides, and free androgen index increased as the PRS increased, whereas high-density lipoprotein cholesterol and SHBG decreased (all P < .0001). The association between the PRS and CAD appeared to be completely mediated by BMI, whereas the associations with T2DM and marked androgenic alopecia appeared to be partially mediated by BMI., Conclusions: Genetic risk factors for PCOS have phenotypic consequences in men, indicating that they can act independently of ovarian function. Thus, PCOS in women may not always be a primary disorder of the ovaries., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)