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BackgroundAs the public increasingly uses the internet to search for resources and information regarding health and medicine, it is important that health care organizations provide adequate web resources. Website usability refers to the ease of user experience on a website. In this study, we conducted usability analyses on digital health center websites. ObjectiveThe primary aims of this study were to (1) replicate a preexisting usability scoring methodology for digital health centers; (2) apply and test this replicated usability scoring methodology on a sample set of digital health center websites; and (3) derive recommendations from the results on potential areas of improvements for our sample of digital health center websites. MethodsWebsite usability testing was conducted from March 1, 2020, to March 15, 2020. We replicated a methodology and scoring system from previous literature and applied them to digital health center websites. Our sample included 67 digital health centers that were affiliated with US universities or hospital systems. Usability was split into the following four broad categories: accessibility, marketing, content quality, and technology. Usability tools were used to score websites in each of the four categories. The composite of the key factors of each category was used to generate a general usability and overall usability score for each website. ResultsThe category with the highest average score (6.3) was content quality. The content quality score also had the highest SD (2.18) and an SE of 0.27. The lowest performing category was technology, which had an average score of 0.9. The technology score also had the smallest SD (0.07) and an SE of 0.01. ConclusionsOur data suggest that content quality, on average, was the highest scoring variable among digital health center websites. As content is crucial to digital health knowledge, it is justified that digital health centers invest more resources into creating quality content. The overall lowest scoring variable was technology. Potential reasons for this finding include designated funding for servers, a lack of regulatory frameworks for social media presence and liability, and infrequent website audits. An easy approach for improving this variable is increasing website speed. Accessibility is another area that organizations can potentially improve. We recommend that these organizations perform periodic audits of their web presence with usability tools.

Physicians, nurses, and other health care providers initiated the #GetMePPE movement on Twitter to spread awareness of the shortage of personal protective equipment (PPE) during the coronavirus disease (COVID-19) pandemic. Dwindling supplies, such as face masks, gowns and goggles, and inadequate production to meet increasing demand have placed health care workers and patients at risk. The momentum of the #GetMePPE Twitter hashtag resulted in the creation of a petition to urge public officials to address the PPE shortage through increased funding and production. Simultaneously, the GetUsPPE.org website was launched through the collaboration of physicians and software engineers to develop a digital platform for the donation, request, and distribution of multi-modal sources of PPE. GetUsPPE.org and #GetMePPE were merged in an attempt to combine public engagement and advocacy on social media with the coordination of PPE donation and distribution. Within 10 days, over 1800 hospitals and PPE suppliers were registered in a database that enabled the rapid coordination and distribution of scarce and in-demand materials. One month after its launch, the organization had distributed hundreds of thousands of PPE items and had built a database of over 6000 PPE requesters. The call for action on social media and the rapid development of this digital tool created a productive channel for the public to contribute to the health care response to COVID-19 in meaningful ways. #GetMePPE and GetUsPPE.org were able to mobilize individuals and organizations outside of the health care system to address the unmet needs of the medical community. The success of GetUsPPE.org demonstrates the potential of digital tools as a platform for larger health care institutions to rapidly address urgent issues in health care. In this paper, we outline this process and discuss key factors determining success.

Abstract Background Childhood obesity is a growing concern, and non-alcoholic fatty liver disease (NAFLD) is a significant consequence. Currently, there are no approved drugs to treat NAFLD in children. However, a recent study explored the potential of vitamin E enriched with tocotrienol (TRF) as a powerful antioxidant for NAFLD. The aims of the present study were to investigate the effectiveness and safety of TRF in managing children with obesity and NAFLD. Methods A total of 29 patients aged 10 to 18 received a daily oral dose of 50 mg TRF for six months (January 2020 to February 2022), and all had fatty liver disease were detected by ultrasonography and abnormally high alanine transaminase levels (at least two-fold higher than the upper limits for their respective genders). Various parameters, including biochemical markers, FibroScan, LiverFASt, DNA damage, and cytokine expression, were monitored. Results APO-A1 and AST levels decreased significantly from 1.39 ± 0.3 to 1.22 ± 0.2 g/L (P = 0.002) and from 30 ± 12 to 22 ± 10 g/L (P = 0.038), respectively, in the TRF group post-intervention. Hepatic steatosis was significantly reduced in the placebo group from 309.38 ± 53.60 db/m to 277.62 ± 39.55 db/m (p = 0.048), but not in the TRF group. Comet assay analysis showed a significant reduction in the DNA damage parameters in the TRF group in the post-intervention period compared to the baseline, with tail length decreasing from 28.34 ± 10.9 to 21.69 ± 9.84; (p = 0.049) and with tail DNA (%) decreasing from 54.13 ± 22.1to 46.23 ± 17.9; (p = 0.043). Pro-inflammatory cytokine expression levels were significantly lower in the TRF group compared to baseline levels for IL-6 (2.10 6.3 to 0.7 1.0 pg/mL; p = 0.047 pg/mL) and TNF-1 (1.73 5.5 pg/mL to 0.7 0.5 pg/mL; p = 0.045). Conclusion The study provides evidence that TRF supplementation may offer a risk-free treatment option for children with obesity and NAFLD. The antioxidant and anti-inflammatory properties of TRF offer a promising adjuvant therapy for NAFLD treatment. In combination with lifestyle modifications such as exercise and calorie restriction, TRF could play an essential role in the prevention of NAFLD in the future. However, further studies are needed to explore the long-term effects of TRF supplementation on NAFLD in children. Trial registration The study has been registered with the International Clinical Trial Registry under reference number (NCT05905185) retrospective registration on (15/06/2023).

Objective: Use of bedside emergency department (ED) ultrasound has become increasingly important for the clinical practice of emergency medicine (EM). We sought to evaluate differences in the availability of immediate bedside ultrasound based on basic ED characteristics and physician staffing.Methods: We surveyed ED directors in all 351 EDs in Colorado, Georgia, Massachusetts, and Oregon between January and April 2009. We assessed access to bedside ED ultrasound by the question: “Is bedside ultrasound available immediately in the ED?” ED characteristics included location, visit volume, admission rate, percent uninsured, total emergency physician full-time equivalents and proportion of EM board-certified (BC) or EM board-eligible (BE) physicians. Data analysis used chi-square tests and multivariable logistical regression to compare differences in access to bedside ED ultrasound by ED characteristics and staffing.Results: We received complete responses from 298 (85%) EDs. Immediate access to bedside ultrasound was available in 175 (59%) EDs. ED characteristics associated with access to bedside ultrasound were: location (39% for rural vs. 71% for urban, P20%] rates, P

Objectives: Financial conflicts of interest have come under increasing scrutiny in medicine, but their impact has not been quantified. Our objective was to use the results of a national survey of academic emergency medicine (EM) faculty to determine if an association between money and personal opinion exists.Methods: We conducted a web-based survey of EM faculty. Opinion questions were analyzed with regard to whether the respondent had either 1) received research grant money or 2) received money from industry as a speaker, consultant, or advisor. Responses were unweighted, and tests of differences in proportions were made using Chi-squared tests, with p

Abstract Irritable bowel syndrome (IBS) is frequently linked with coexisting mental illnesses. Our previous study discovered that 32.1% of IBS patients had subthreshold depression (SD), placing them at higher risk of developing major depression. Gut microbiota modulation through psychobiotics was found to influence depression via the gut-brain axis. However, the efficacy of lessening depression among IBS patients remains ambiguous. The study’s aim was to investigate the roles of cultured milk drinks containing 109 cfu Lactobacillus acidophilus LA-5 and Lactobacillus paracasei L. CASEI-01 on depression and related variables among IBS participants with SD. A total of 110 IBS participants with normal mood (NM) and SD, were randomly assigned to one of four intervention groups: IBS-NM with placebo, IBS-NM with probiotic, IBS-SD with placebo, and IBS-SD with probiotic. Each participant was required to consume two bottles of cultured milk every day for a duration of 12 weeks. The following outcomes were assessed: depression risk, quality of life, the severity of IBS, and hormonal changes. The depression scores were significantly reduced in IBS-SD with probiotic and placebo from baseline (p

Colorectal cancer poses a significant threat to global health, necessitating the development of effective early detection techniques. However, the potential of the fungal microbiome as a putative biomarker for the detection of colorectal adenocarcinoma has not been extensively explored. We analyzed the viability of implementing the fungal mycobiome for this purpose. Biopsies were collected from cancer and polyp patients. The total genomic DNA was extracted from the biopsy samples by utilizing a comprehensive kit to ensure optimal microbial DNA recovery. To characterize the composition and diversity of the fungal mycobiome, high-throughput amplicon sequencing targeting the internal transcribed spacer 1 (ITS1) region was proposed. A comparative analysis revealed discrete fungal profiles among the diseased groups. Here, we also proposed pipelines based on a predictive model using statistical and machine learning algorithms to accurately differentiate colorectal adenocarcinoma and polyp patients from normal individuals. These findings suggest the utility of gut mycobiome as biomarkers for the detection of colorectal adenocarcinoma. Expanding our understanding of the role of the gut mycobiome in disease detection creates novel opportunities for early intervention and personalized therapeutic strategies for colorectal cancer. • Detailed method to identify the gut mycobiome in colorectal cancer patients using ITS-specific amplicon sequencing. • Application of machine learning algorithms to the identification of potential mycobiome biomarkers for non-invasive colorectal cancer screening. • Contribution to the advancement of innovative colorectal cancer diagnostic methods and targeted therapies by applying gut mycobiome knowledge.

Abstract Background Studies on the relationship between diet and colorectal cancer (CRC) risk using single food or nutrient approach are widely conducted as opposed to dietary pattern approach. Therefore, this study aimed to determine the major dietary patterns and their association with CRC risk among Malaysians. Methods Patients aged between 18 and 80 years old from two teaching hospitals in Peninsular Malaysia were recruited through purposive sampling. Socio-demographic information and anthropometry data were assessed before the colonoscopy procedure, and dietary intake was also recorded using a validated semi-quantitative food frequency questionnaire (FFQ). Cases were those patients having histopathologically proven CRC, while controls were those without. Results Four major dietary patterns were identified: the allergenic diet, plant-based diet, processed diet, and energy-dense diet pattern. After adjusting for potential covariates, the processed diet pattern was consistently associated with CRC (OR = 3.45; 95% CI = 1.25–9.52; P = 0.017) while the plant-based diet, energy-dense diet, and allergenic diet were not associated with CRC risk. Conclusions The processed diet pattern attributed to a diet high in confectionaries and fast foods was associated with an increased risk of CRC in the Malaysian population. In order to give prevention measures through lifestyle change, more research could be done on the effect of food patterns on faecal microbiota associated with CRC.

Background: Primary dysmenorrhea is associated with poorer quality of life; however, the causal mechanism remains unclear. A vast body of literature supports the use of oral probiotics for relief from the symptoms of endometriosis; however, to our knowledge, no study has prescribed probiotics for primary dysmenorrhea. Objective: The aim of this study is to investigate the effects of 3-month supplementation with oral probiotics on quality of life and inflammatory markers in women with primary dysmenorrhea. Design: Randomized placebo-controlled trial. Methods: A total of 72 patients (36 patients in each arm) were randomized to receive either oral sachets containing 5 billion colony-forming units each of Lactobacillus acidophilus BCMC (BCrobes Microbial Cells) 12130, Lactobacillus casei subsp BCMC 12313, Lactobacillus lactis BCMC 12451, Bifidobacterium bifidum BCMC 02290, Bifidobacterium longum BCMC 02120, and Bifidobacterium infantis BCMC 02129 each or placebo twice daily for 3 months. Main outcome measures were visual analog scale, verbal rating scale, physical and mental health scores using Short-Form 12-Item version 2 questionnaire, frequency of nonsteroidal anti-inflammatory drug use, and changes in inflammatory markers (interleukin-6, interleukin-8, and tumor necrosis factor alpha) before and after treatment. Results: There was no significant difference in the quality of life scores between the probiotic and placebo groups. Both groups showed significant improvement in pain (visual analog scale) and severity (verbal rating scale) scores but the probiotic group had much lower nonsteroidal anti-inflammatory drug use (odds ratio: 0.69, 95% confidence interval: 0.26–1.83) and better mental health scores (mean change: 6.5, p = 0.03 versus 6.1, p = 0.08) than the placebo group. There was a significant confounding effect of nonsteroidal anti-inflammatory drug use on quality of life scores. No significant difference was found in inflammatory cytokines. Conclusion: Tested oral probiotics improved mental health and potentially reduced the use of nonsteroidal anti-inflammatory drugs; however, there was no significant change in inflammatory markers. Further research with a larger sample size is needed to confirm the findings. Registration: This study is registered under ClinicalTrials.gov (NCT04119011).

Abstract Background There is a rapid increase in the incidence of inflammatory bowel diseases (IBD) in newly industrialized countries, yet epidemiological data is incomplete. We herein report the methodology adopted to study the incidence of IBD in newly industrialized countries and to evaluate the effect of environmental factors including diet on IBD development. Methods Global IBD Visualization of Epidemiology Studies in the 21st Century (GIVES-21) is a population-based cohort of newly diagnosed persons with Crohn’s disease and ulcerative colitis in Asia, Africa, and Latin America to be followed prospectively for 12 months. New cases were ascertained from multiple sources and were entered into a secured online system. Cases were confirmed using standard diagnostic criteria. In addition, endoscopy, pathology and pharmacy records from each local site were searched to ensure completeness of case capture. Validated environmental and dietary questionnaires were used to determine exposure in incident cases prior to diagnosis. Results Through November 2022, 106 hospitals from 24 regions (16 Asia; 6 Latin America; 2 Africa) have joined the GIVES-21 Consortium. To date, over 290 incident cases have been reported. All patients have demographic data, clinical disease characteristics, and disease course data including healthcare utilization, medication history and environmental and dietary exposures data collected. We have established a comprehensive platform and infrastructure required to examine disease incidence, risk factors and disease course of IBD in the real-world setting. Conclusions The GIVES-21 consortium offers a unique opportunity to investigate the epidemiology of IBD and explores new clinical research questions on the association between environmental and dietary factors and IBD development in newly industrialized countries.

Abstract Helicobacter pylori is one of the most common chronic bacterial infections in humans and responsible for 90% of duodenal ulcers and 70–90% of gastric ulcers. Despite this, many misconceptions regarding the appropriate diagnostic method and treatment strategies still exist in the Malaysian clinical practice. Under the initiative of the steering committee, an expert panel consisting of nine key opinion leaders in the field of gastroenterology convened to develop a set of consensus statements that are relevant to the Malaysian healthcare practice. The panel members reviewed the current evidence on the management of H. pylori infection, focusing on the best practices that are relevant to the Malaysian population based on clinical experience and published clinical evidence. Using the modified Delphi method, the panel achieved consensus in three areas of H. pylori infection management: indications for testing, diagnosis, and treatment. The panel proposed a set of 19 consensus statements, which were synthesized via two rounds of blinded voting and group discussions. The recommendations provided are relevant to the Malaysian population and can be used as a guide by physicians across various healthcare settings to facilitate appropriate diagnostic testing and treatment of H. pylori infection.

As we progress deeper into the digital age, the robust development and application of advanced artificial intelligence (AI) technology, specifically generative language models like ChatGPT (OpenAI), have potential implications in all sectors including medicine. This viewpoint article aims to present the authors’ perspective on the integration of AI models such as ChatGPT in clinical medicine and medical education. The unprecedented capacity of ChatGPT to generate human-like responses, refined through Reinforcement Learning with Human Feedback, could significantly reshape the pedagogical methodologies within medical education. Through a comprehensive review and the authors’ personal experiences, this viewpoint article elucidates the pros, cons, and ethical considerations of using ChatGPT within clinical medicine and notably, its implications for medical education. This exploration is crucial in a transformative era where AI could potentially augment human capability in the process of knowledge creation and dissemination, potentially revolutionizing medical education and clinical practice. The importance of maintaining academic integrity and professional standards is highlighted. The relevance of establishing clear guidelines for the responsible and ethical use of AI technologies in clinical medicine and medical education is also emphasized.

Background: The use of intestinal ultrasound (IUS) in the management of inflammatory bowel disease (IBD) is emerging. We aim to determine the performance of IUS in the assessment of disease activity in IBD. Methods: This is a prospective cross-sectional study of IUS performed on IBD patients in a tertiary centre. IUS parameters including intestinal wall thickness, loss of wall stratification, mesenteric fibrofatty proliferation, and increased vascularity were compared with endoscopic and clinical activity indices. Results: Among the 51 patients, 58.8% were male, with a mean age of 41 years. Fifty-seven percent had underlying ulcerative colitis with mean disease duration of 8.4 years. Against ileocolonoscopy, IUS had a sensitivity of 67% (95% confidence interval (CI): 41-86) for detecting endoscopically active disease. It had high specificity of 97% (95% CI: 82-99) with positive and negative predictive values of 92% and 84%, respectively. Against clinical activity index, IUS had a sensitivity of 70% (95% CI: 35-92) and specificity of 85% (95% CI: 70-94) for detecting moderate to severe disease. Among individual IUS parameters, presence of bowel wall thickening (>3 mm) had the highest sensitivity (72%) for detecting endoscopically active disease. For per-bowel segment analysis, IUS (bowel wall thickening) was able to achieve 100% sensitivity and 95% specificity when examining the transverse colon. Conclusions: IUS has moderate sensitivity with excellent specificity in detecting active disease in IBD. IUS is most sensitive in detecting a disease at transverse colon. IUS can be employed as an adjunct in the assessment of IBD.

Background: Personalised nutrition and medicine are the future of healthcare. In relation to cancer, public and healthcare professionals often seek dietary recommendations for cancer prevention. Among the important cancers that can be prevented by diet and lifestyle is colorectal cancer (CRC). CRC is one of the commonest cancers globally, and is a major health concern in Malaysia as it presents with high mortality and morbidity rates, causing a significant socioeconomic burden to the country. While extensive research has been conducted on the treatment and mechanisms of cancer, there have been no reports on the associations between metabolites, novel biomarkers of cancer, and dietary patterns in the context of cancer prevention in the Malaysian multiethnic population. Methods: A case control study will be conducted in Malaysia, involving patients diagnosed with CRC, colorectal adenoma and a group of healthy participants. Multiple endpoints will be analyzed, namely metabolomic signatures, epigenetic marks, inflammatory markers and relationship with dietary patterns will be established. Multiple machine learning models will then be used to develop personalised risk stratification algorithms. Recruitment began in July 2019 and is ongoing due to COVID-19 pandemic. Discussion: This study will be the first to identify alterations in metabolites, inflammatory markers and epigenetic marks associated with dietary patterns and CRC risk in Malaysia. Understanding on how dietary patterns influence CRC risk in the multi-ethnic Malaysian population and identification of novel oncometabolites for CRC risk, will allow for development of personalised evidence-based recommendations in reducing individual risks of CRC.

Binmaeil H, Hanafiah A, Mohamed Rose I, Raja Ali RA. Infect Drug Resist. 2021;14:4129–4145. The authors have advised that Table 1 on page 4132 is incorrect. There is an error in the clarithromycin resistant gene reverse primer and UreA probe sequences. The authors apologize for these errors. The correct Table 1 is as follows. Table 1 Oligonucleotides Sequence Used in This Study

The advent of biologics and biologic therapy has transformed the management of inflammatory bowel disease (IBD) with enhanced early and adequate responses to treatment, fewer hospitalizations, a reduced need for surgery, and unprecedented outcomes including complete mucosal and histologic healing. However, an important issue with the use of anti-tumor necrosis factor (anti-TNF) agents in IBD is the increased risk of tuberculosis (TB). This is compounded by the diagnostic dilemma when differentiating between Crohn’s disease and gastrointestinal TB, and the potentially serious consequences of initiating an incorrect treatment in the case of misdiagnosis. The interplay between IBD and TB is most relevant in Asia, where more than 60% of the 10.4 million new TB cases in 2016 were reported. A number of studies have reported an increased risk of TB with anti-TNF agents, including in patients who had tested negative for TB prior to treatment initiation. The limited evidence currently available regarding adhesion molecule antagonists such as vedolizumab suggests a comparatively lower risk of TB, thus making them a promising option for IBD management in TBendemic regions. This comprehensive review examines the available literature on the risk of TB with the use of biologics in the TB-endemic regions of Asia, focusing on the diagnostic dilemma, the risk of reactivation, and the optimized management algorithms for latent and active disease.

Background/Aims Ulcerative colitis (UC) is a chronic, relapsing and remitting inflammation of the gastrointestinal tract. Little is known about the link between dietary intake, food avoidance, and beliefs among UC patients of different disease severity. Therefore, this study aimed to assess the dietary intake, food avoidance, and beliefs among active and inactive UC patients. Methods A cross-sectional study was conducted among UC patients from a tertiary medical center in Kuala Lumpur, Malaysia. Demographic, anthropometric, dietary intake, food avoidance and beliefs were assessed. Disease activity of UC patients was evaluated using the Powell Tuck Index. Results UC patients were recruited (64.1% inactive UC and 35.9% active UC). As compared to inactive UC patients, active UC patients were likely to lose weight (75.0% vs. 0%), possess certain food beliefs (95.7% vs. 39.0%), and frequently practiced dietary avoidance (95.7% vs. 43.9%). The dietary intake among inactive UC patients was higher than active UC patients. However, neither of them met the standard nutrients recommendation for protein, calcium, iron, folate, zinc, vitamin D, vitamin B12, and vitamin E. Conclusions Active UC patients had poorer dietary intake, were more prone to practicing food avoidance and exhibited certain food beliefs as compared to inactive UC patients. Both macro- and micronutrients intakes were inadequate regardless of patient’s disease status. These findings emphasized the importance for patients to be provided with the nutrition-related knowledge as part of strategies to avoid nutritional inadequacies.

The prevalence of non-alcoholic fatty liver disease (NAFLD) has soared globally. As our understanding of the disease grows, the role of the gut-liver axis (GLA) in NAFLD pathophysiology becomes more apparent. Hence, we focused mainly on the small intestinal area to explore the role of GLA. We looked at how multi-strain probiotics (MCP® BCMC® strains) containing six different Lactobacillus and Bifidobacterium species affected the small intestinal gut microbiota, inflammatory cytokines, and permeability in NAFLD patients. After six months of supplementation, biochemical blood analysis did not show any discernible alterations in either group. Five predominant phyla known as Actinobacteria, Proteobacteria, Firmicutes, Bacteroidota and Fusobacteria were found in NAFLD patients. The probiotics group demonstrated a significant cluster formation of microbiota composition through beta-diversity analysis (p < 0.05). This group significantly reduced three unclassifiable species: unclassified_Proteobacteria, unclassified_Streptococcus, and unclassified_Stenotrophomonas. In contrast, the placebo group showed a significant increase in Prevotella_melaninogenica and Rothia_mucilaginosa, which were classified as pathogens. Real-time quantitative PCR analysis of small intestinal mucosal inflammatory cytokines revealed a significant decrease in IFN-γ (−7.9 ± 0.44, p < 0.0001) and TNF-α (−0.96 ± 0.25, p < 0.0033) in the probiotics group but an increase in IL-6 (12.79 ± 2.24, p < 0.0001). In terms of small intestinal permeability analysis, the probiotics group, unfortunately, did not show any positive changes through ELISA analysis. Both probiotics and placebo groups exhibited a significant increase in the level of circulating zonulin (probiotics: 107.6 ng/mL ± 124.7, p = 0.005 vs. placebo: 106.9 ng/mL ± 101.3, p = 0.0002) and a significant decrease in circulating zonula occluden-1 (ZO-1) (probiotics: −34.51 ng/mL ± 18.38, p < 0.0001 vs. placebo: −33.34 ng/mL ± 16.62, p = 0.0001). The consumption of Lactobacillus and Bifidobacterium suggested the presence of a well-balanced gut microbiota composition. Probiotic supplementation improves dysbiosis in NAFLD patients. This eventually stabilised the expression of inflammatory cytokines and mucosal immune function. To summarise, more research on probiotic supplementation as a supplement to a healthy diet and lifestyle is required to address NAFLD and its underlying causes.

Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.

Background and Objectives: We aim to compare the diagnostic performance of Protein induced by vitamin K absence-II (PIVKA-II), a biomarker for hepatocellular carcinoma (HCC), and alpha-fetoprotein (AFP) in differentiating HCC and non-malignant high-risk (NMHR) groups and to determine their cut-off values. Materials and Methods: A total of 163 patients, including 40 with HCC and 123 with NMHR (100 with liver cirrhosis and 23 with non-cirrhotic high-risk patients) were prospectively enrolled. The levels of AFP and PIVKA-II were measured, and their cut-off values were determined. We calculated and compared the areas under the receiver operating characteristic (AUROC) curves of PIVKA-II, AFP, and their combination. Results: The levels of PIVKA-II and AFP were found to be significantly higher in the HCC compared to NMHR patients (p < 0.0001). For the differentiation of HCC from NMHR, the optimal cutoff values for PIVKA-II and AFP were 36.7 mAU/mL (90% sensitivity; 82.1% specificity) and 14.2 ng/mL (75% sensitivity; 93.5% specificity), respectively. The AUROC of PIVKA-II (0.905, p < 0.0001) was higher compared to AFP (0.869, p < 0.0001), but the combination of PIVKA–II and AFP gave the highest AUROC value (0.911, p < 0.0001). However, their differences were not statistically significant (AFP vs. PIVKA; p = 0.4775, AFP vs. Combination; p = 0.3808, PIVKA vs. Combination; p = 0.2268). Conclusions: PIVKA-II and AFP showed equal performance in detecting HCC in high-risk patients. AFP as a screening marker for HCC may be adequate, and replacing or adding the PIVKA-II test in current clinical practice may be of little value.

Inflammatory bowel disease (IBD), which comprises of Crohn's disease and ulcerative colitis, is an idiopathic relapsing and remitting disease in which the interplay of different environment, microbial, immunological and genetic factors that attribute to the progression of the disease. Numerous studies have been conducted in multiple aspects including clinical, endoscopy and histopathology for the diagnostics and treatment of IBD. However, the molecular mechanism underlying the aetiology and pathogenesis of IBD is still poorly understood. This review tries to critically assess the scientific evidence at the transcriptomic level as it would help in the discovery of RNA molecules in tissues or serum between the healthy and diseased or different IBD subtypes. These molecular signatures could potentially serve as a reliable diagnostic or prognostic biomarker. Researchers have also embarked on the study of transcriptome to be utilized in targeted therapy. We focus on the evaluation and discussion related to the publications reporting the different approaches and techniques used in investigating the transcriptomic changes in IBD with the intention to offer new perspectives to the landscape of the disease.

Continuous adjustment of Propofol in manual delivery of anesthesia for conducting a surgical procedure overburdens the workload of an anesthetist who is working in a multi-tasking scenario. Going beyond manual administration and Target Controlled Infusion, closed-loop control of Propofol infusion has the potential to offer several benefits in terms of handling perturbations and reducing the effect of inter-patient variability. This paper proposes a closed-loop automated drug administration approach to control Depth Of Hypnosis in anesthesia. In contrast with most of the existing research on anesthesia control which makes use of linear control strategies or their improved variants, the novelty of the present research lies in applying robust control strategy i.e. Sliding Mode Control to accurately control drug infusion. Based on the derived patient's model, the designed controller uses measurements from EEG to regulate DOH on Bispectral Index by controlling infusion rate of Propofol. The performance of the controller is investigated and characterized with real dataset of 8 patients undergoing surgery. Results of this in silico study indicate that for all the patients, with 0% overshoot observed, the steady state error lies in between ±5. Clinically, this implies that in all the cases, without any overdose, the controller maintains the desired DOH level for smooth conduction of surgical procedures. Resumo: O ajuste contínuo de propofol na administração manual de anestesia para a realização de um procedimento cirúrgico onera a carga de trabalho de anestesiologistas que trabalham em ambiente multitarefa. Indo além da administração manual e da infusão alvo-controlada (IAC), o controle de circuito fechado da infusão de propofol tem o potencial de oferecer vários benefícios em termos de manejo das perturbações e reduzir o efeito da variabilidade interpaciente. Este artigo propõe uma abordagem para a administração automatizada de drogas em circuito fechado para controlar a profundidade da hipnose (PDH) em anestesia. Em contraste com a maioria das pesquisas existentes sobre o controle da anestesia que usam estratégias de controle linear ou de suas variantes melhoradas, a novidade da presente pesquisa reside na aplicação de uma estratégia de controle robusto; isto é, o Controle por Modos Deslizantes (CMD) para controlar com precisão a infusão da droga. Com base no modelo derivado do paciente, o controlador projetado usa as medições do EEG para regular a PDH no Bispectral Index (BIS), controlando a taxa de infusão de propofol. O desempenho do controlador é investigado e caracterizado com um conjunto de dados reais de oito pacientes submetidos à cirurgia. Os resultados deste estudo in silico indicam que, para todos os pacientes, com 0% de excesso observado, o erro de estado estacionário fica entre ± 5. Clinicamente, isso implica que em todos os casos, sem qualquer sobredosagem, o controlador mantém o nível desejado de PDH para a condução tranquila dos procedimentos cirúrgicos. Keywords: Closed-loop anesthesia, Modern control, Biocontrol, Pharmacodynamics, Pharmacokinetics, Palavras-chave: Anestesia de circuito fechado, Controle moderno, Biocontrole, Farmacodinâmica, Farmacocinética

MicroRNA (miRNA) is a small non-coding RNA with an established function to regulate genes at the post-transcriptional level leading to suppression or degradation of its messenger RNA expression (mRNA). Its dysregulation plays a vital role in a variety of biological and pathological processes including cancer. A lot of algorithms have been established to predict the target sites of miRNA, but experimentally identifying and validating its target region is still lacking. Guidance in experimental procedures is really needed to find genuine miRNA targets. Therefore, in this review, we provide an outline on the workflow in predicting and validating the targeted sites of miRNA using several methods as a guideline for the scientists. The final outcome of this type of experiment is essential to explore the major impact of miRNA-mRNA interaction involved in the biological processes and to assist miRNA-based drug development in the future.

Backgrounds. The aim of this study was to appraise the relationship between serum fragmented cytokeratin-18(CK-18), controlled attenuation parameter (CAP), and liver steatosis assessed by ultrasound (US) in nonalcoholic fatty liver disease (NAFLD) patients. Methods. Patients who underwent abdominal US were recruited, followed with measurement of CAP using Fibroscan® and serum fragmented CK-18 using enzyme-linked immunosorbent assay. The degree of liver steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). Results. A total of 109 patients were included in our study. CAP and fragmented CK-18 level were significantly correlated with liver steatosis grade with rs = 0.56 and 0.68, p=0.001, respectively. NAFLD Fibrosis Score was poorly correlated with liver steatosis grade (rs=-0.096, p=0.318). Using fragmented CK-18 level, area under receiver operating characteristic (AUROC) curves for S≥2 and S≥3 were excellent (0.82 and 0.84, respectively). Using CAP, AUROC curves for detection of S≥2 and S≥3 were good (0.76, 0.77, respectively). We also proposed cut-off value of CAP to detect S≥2 and S≥3 to be 263 and 319db/m, respectively, and fragmented CK-18 level to detect S≥2 and S≥3 (194 and 294 U/L, respectively). Conclusions. Both the fragmented CK-18 level and the CAP, but not NAFLD Fibrosis Score, were well correlated with hepatic steatosis grade as assessed by US.

Abstract Gastroesophageal reflux disease (GERD) is one the most common medical complaints in pregnant women. Some women continue to experience GERD symptoms after delivery. Effective management of GERD symptoms is important to improve productivity and quality of life. Management of heartburn in pregnant and breastfeeding women involves lifestyle modifications, dietary modifications, non-pharmaceutical remedies and pharmaceutical drugs. For most patients, lifestyle/dietary modifications are helpful in reducing GERD symptoms. For patients who require a more intense intervention, various types of pharmaceutical drugs are available. However, the suitability of each treatment for use during pregnancy and lactation must be taken into consideration. This article explores the reported efficacy and safety of these treatment options in pregnant and breastfeeding women. Recommended treatment algorithm in pregnant and breastfeeding women have been developed.

Propofol infusion in anesthesia administration requires continual adjustment in the manual infusion system to regulate the hypnosis level. Hypnotic level is based on Bispectral Index Monitor (BIS) showing the cortical activity of the brain scaled between 0 to 100. The new challenging aspect of automation in anaesthesia is to estimate the concentration of hypnotic drugs in different compartments of the body including primary, rapid peripheral (muscle), slow peripheral (bones, fat) and effect site (brain) compartment based on Pharmacokinetics (PK) and Pharmacodynamics (PD) model. This paper aimed to regulate the hypnosis level with estimating the Propofol concentrations using a linear observer in feedback control strategy based on Integral Super-Twisting Sliding Mode Controller (ISTSMC). The drug concentration in plasma of the silico patients accurately estimated in nominal transient. The results show that tracking errors between the actual output in form of BIS level and linearized output nearly approaches to zero in the maintenance phase of anesthesia to ensure the controller response on sliding phase with optimum performances by achieving desired hypnotic level 50 on BIS. The robustness of control strategy is further ensured by adding measurement noise of electromagnetic environment of operation theatre distracting signal quality index of the output BIS level.

Abstract Food insecurity (FI) has an impact on food intake, and it can make it difficult for people to eat enough nutritious food at all times to sustain an active and healthy lifestyle. The COVID‐19 outbreak has hampered people's capacity to obtain nutritious and affordable food. Although FI has been studied in Malaysia, the extent to which it is linked to gut microbiota has yet to be discovered. This review aimed to compile evidence of the relationship between FI and gut microbial changes and their potential relevance to a multi‐ethnic population in Malaysia. FI is typically associated with cheaper and calorie‐dense foods because of the high cost of quality food and financial constraints that hinder food‐insecure people from adopting healthier dietary choices. As a result, they have started eating low‐quality food such as simple carbohydrates, fats, and processed foods. These poor eating habits can reduce microbial diversity and influence changes in the composition and function of the gut microbiota. This review also explores the impact of ethnicity on the variation in composition of gut microbiota. In conclusion, the findings of this review may be utilized to develop and implement diet‐related intervention programs to ensure that Malaysians get enough nutritious food to maintain a healthy gut microbiota and improve overall health.

Background/Aims Substantial proportions of patients with constipation-predominant irritable bowel syndrome (IBS-C) linked their symptoms with particular intake of foods. However, there is lack of current data regarding the intake among IBS-C patients before any dietary interventions. Thus, this study aimed to evaluate the dietary adequacy among IBS-C against the standard recommended nutrient intake (RNI) and healthy controls. Methods A retrospective case-control study was conducted involving IBS-C patients and healthy control subjects. A validated 126-food items frequency questionnaire was administered to all the subjects to assess their dietary intake, guided by dietitians. The calculated nutrients intake for IBS-C patients was then compared against the standard RNI and healthy controls. Results A total of 306 subjects were recruited, among which 218 were diagnosed with IBS-C and 88 were included as healthy controls. IBS-C patients had significantly lower intake of wholegrain products, fried foods, dairy products, fruits, and vegetables compared to healthy controls. The daily intake of energy, certain macronutrients, and micronutrients among IBS-C patients was significantly lower than the healthy subjects. Less than 5% of IBS-C patients and healthy subjects achieved the standard recommendation for dietary fiber. Also, various vitamin intake (B1, B2, B6, folate, B12, E, K, and potassium) among IBS-C patients did not meet the standard RNI. Conclusions Dietary intakes of IBS-C patients did not meet the recommended intake for Malaysian and showed the nutritional inadequacies compared to the control subjects. Our study highlighted the importance of dietary evaluation prior to planning strategies for dietary intervention targeting IBS-C patients.

Abstract Background The use of simulated patients (SPs) is considered a significant resource for teaching and assessing clinical and communication skills in health professional education. We conducted this study to explore pharmacy students’ perspective towards the utilization of SPs in Qatar and to identify areas that require improvement. Methods An explanatory sequential mixed-methods design was used among students and recent graduates of the College of Pharmacy at Qatar University (QU-CPH). First, their perspectives toward the current utilization of SPs at QU-CPH was explored using a quantitative cross-sectional study design. Following this, we conducted six focus group discussions based on the analysis of the questionnaire results. The findings of the two phases were interpreted through integration of the quantitative and qualitative phases. Results The majority of the participants (> 90%) reported that interactions with SPs are important in building good communication and counseling skills during professional skills course activities. Similarly, most of the respondents (80%) indicated that interactions with SPs prepared them to apply the clinical skills gained during professional skills and patient assessment sessions in real-life. In addition, they reported that interactions with SPs during competency-based assessments were good experiences. The participants disagreed with the notion that interaction with SPs of opposite gender was uncomfortable for them. Themes identified from the focus groups include: interactions with trained SPs compared to faculty SPs, standardization and consistency of SPs’ roles, communication and language barriers, simulations of real-life case scenarios, SPs’ competence and preparedness, psychological impact associated with interaction with SPs, proposed strategies for improving the SP program. Identified areas for improvement include the need for strengthening the SP training and orientation program as well as the SP selection criteria. Conclusion This study showed a positive impact of the utilization of SPs in this pharmacy curriculum as perceived by students and alumni. However, the SP program needs to be optimized in terms of the training and orientation of SPs.

Introduction: Coronary Artery Disease (CAD) is an important extrahepatic cardiovascular complication of Non Alcoholic Fatty Liver Disease (NAFLD). Aim: To determine the prevalence of NAFLD in young (≤45 years) Acute Coronary Syndrome (ACS) patients, and to assess the association between severity of NAFLD and severity of CAD. Materials and Methods: This cross-sectional study was conducted from May 2017-April 2018, with a total of 85 patients. CAD severity was determined by coronary angiogram while its complexity by SYNTAX score. Fatty liver was diagnosed and graded by liver ultrasound examination. Results: The prevalence of NAFLD was 100%. Thirty-three (38.9%) had ST-Elevation Myocardial Infarction (STEMI), 32 (37.6%) had Non STEMI (NSTEMI) and 20 (23.5%) had unstable angina. There was no significant correlation between NAFLD steatosis grades and ACS subtypes (p=0.721), severity of CAD (p=0.822) and SYNTAX score (p=0.982). No association between NAFLD fibrosis score and ACS subtypes (p=0.232), severity of CAD (p=0.445) or SYNTAX score (p=0.839) were observed. Conclusion: The NAFLD was extremely prevalent in young ACS patients. However, no significant association between severity of NAFLD and severity of CAD was found.

Hasyanee Binmaeil,1 Alfizah Hanafiah,1,2 Isa Mohamed Rose,3 Raja Affendi Raja Ali2,4 1Department of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia; 2GUT Research Group, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia; 3Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, Malaysia; 4Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, 56000, MalaysiaCorrespondence: Alfizah HanafiahDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur, 56000, MalaysiaEmail alfizah@ppukm.ukm.edu.my; alfizah@ukm.edu.myAims and Objectives: More than half of the world’s population is infected with Helicobacter pylori, which can cause chronic gastritis. WHO has regarded clarithromycin-resistant H. pylori as a high priority pathogen. Hence, accurate diagnosis and detection of clarithromycin- and levofloxacin-resistant H. pylori strains is essential for proper management of infection. The objective of this study was to develop and optimize multiplex quantitative PCR assay for detection of mutations associated with clarithromycin and levofloxacin resistance in H. pylori directly from the gastric biopsies.Materials and Methods: Specific primers and probes were designed to amplify ureA and mutations in 23S rRNA and gyrA genes. Singleplex and triplex qPCR assays were optimized and the assay’s sensitivities and specificities were determined. The optimized multiplex qPCR assay was performed on 571 gastric biopsies.Results: In this study, 14.7% (84/571) of the gastric biopsies were positive for H. pylori by conventional methods and 23.8% (136/571) were positive by the ureA-qPCR with 96.4% sensitivity and 88.5% specificity, while the +LR and −LR were 8.72 and 0.04, respectively. The ureA-positive samples (n=136) were subjected to multiplex qPCR which detected A2142G and A2143G mutations in the 23S rRNA gene (20.6%, 28/136) conferring clarithromycin resistance and gyrA mutations N87K, N87I, D91N, and D91Y (11.8%, 16/136) leading to levofloxacin resistance. The sensitivity and specificity of qPCR of 23S rRNA gene were 100% and 98.7%, respectively, while 100% and 99.8% for qPCR of gyrA, respectively.Conclusion: The effectiveness of this qPCR is that it is sensitive in detecting low bacterial load and will help in timely detection of clarithromycin- and levofloxacin-resistant strains, especially in case of mixed infections. Since it is culture independent, it can inform clinicians about antibiotics to be included in the first-line therapy, thereby improving the management of H. pylori infection at a much greater pace.Keywords: Helicobacter pylori, multiplex qPCR, resistance, mutation, clarithromycin, levofloxacin

Abstract This paper reports the proceedings from the first consensus meeting on the management of mild‐to‐moderate gastroesophageal reflux disease (GERD) in the Southeast Asian (SEA) region. Seventeen statements were drawn up by a steering committee that focused on epidemiology, mechanism of action, diagnostic investigations, and treatment. Voting on the recommendations used the Delphi method with two rounds of voting among the 10 panel members. The consensus panel agreed that GERD is mostly a mild disease in the SEA region with predominantly non‐erosive reflux disease (NERD). Complicated GERD and Barrett's esophagus are infrequently seen. The panel recommended endoscopy in patients with alarm or refractory symptoms but cautioned that the incidence of gastric cancer is higher in SEA. pH and impedance measurements were not recommended for routine assessment. The acid pocket is recognized as an important pathogenic factor in GERD. Lifestyle measures such as weight reduction, avoidance of smoking, reduction of alcohol intake, and elevation of the head of the bed were recommended but strict avoidance of specific foods or drinks was not. Alginates was recommended as the first‐line treatment for patients with mild‐to‐moderate GERD while recognizing that proton‐pump inhibitors (PPIs) remained the mainstay of treatment of GERD. The use of alginates was also recommended as adjunctive therapy when GERD symptoms were only partially responsive to PPIs.

Background and AimsThiopurines, 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.MethodsPatients 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.ResultsIn 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.ConclusionNudix Hydroxylase 15 variants strongly predicted thiopurine-induced leukopenia across a multiethnic Southeast Asian population, particularly among the Chinese and Indians.

Obscure gastrointestinal bleeding is defined as recurrent or persistent gastrointestinal bleeding in the setting of normal upper and lower endoscopies. There are reported use of numerous pharmacological agents to halt the bleeding, including oestrogen. We report a case of middle age gentleman with multiple comorbidities, presented with life threatening gastrointestinal bleeding. He underwent bidirectional endoscopies and mesenteric angiogram, but failed to localise the bleeding. Red blood cell scintigraphy showed numerous bleeding points in small and large bowels. A 5-day oral high dose oestrogen was prescribed in view of difficulty to manage the bleeding, in which the hemostasis was ultimately achieved.

Current treatment for inflammatory bowel disease (IBD) includes the application of anti-inflammatory agents for the induction and remission of IBD. However, prolonged use of anti-inflammatory agents can exert adverse effects on patients. Recently, formulated dietary approach in treating IBD patients is utilized to improve clinical activity scores. An alteration of gastrointestinal microbiota through dietary therapy was found to reduce IBD and is recognized as a promising therapeutic strategy for IBD. One of the recommended formulated diets is an anti-inflammatory diet (AID) that restricts the intake of carbohydrates with modified fatty acids. This diet also contains probiotics and prebiotics that can promote balanced intestinal microbiota composition. However, scientific evidences are limited to support this specific dietary regime in maintaining the remission and prevention relapse of IBD. Therefore, this review aimed to summarize available data from various studies to evaluate the AID diet effectiveness which will be useful for clinicians to manage their IBD patients by application of improved dietary therapy.

Abstract Dysbiosis of the gut microbiome has been associated with the pathogenesis of colorectal cancer (CRC). We profiled the microbiome of gut mucosal tissues from 18 CRC patients and 18 non-CRC controls of the UKM Medical Centre (UKMMC), Kuala Lumpur, Malaysia. The results were then validated using a species-specific quantitative PCR in 40 CRC and 20 non-CRC tissues samples from the UMBI-UKMMC Biobank. Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were found to be over-represented in our CRC patients compared to non-CRC controls. These four bacteria markers distinguished CRC from controls (AUROC = 0.925) in our validation cohort. We identified bacteria species significantly associated (cut-off value of > 5 fold abundance) with various CRC demographics such as ethnicity, gender and CRC staging; however, due to small sample size of the discovery cohort, these results could not be further verified in our validation cohort. In summary, Parvimonas micra, Fusobacterium nucleatum, Peptostreptococcus stomatis and Akkermansia muciniphila were enriched in our local CRC patients. Nevertheless, the roles of these bacteria in CRC initiation and progression remains to be investigated.

Abstract Probiotics comprise a large group of microorganisms, which have different properties and thus confer different benefits. The use of probiotics has shown promising results in the management of diarrheal diseases. While the availability of probiotic products has flourished in the marketplace, there is limited guidance on the selection of probiotics for clinical use. This position paper is aimed at informing clinicians about the proper selection criteria of probiotics based on current evidence on strain‐specific efficacy and safety for the management of diarrheal diseases. Members of the working group discussed issues on probiotic use in clinical practice, which were then drafted into statements. Literature to support or refute the statements were gathered through a search of medical literature from 2011 to 2020. Recommendations were formulated based on the drafted statements and evidence gathered, revised as necessary, and finalized upon agreement of all members. Twelve statements and recommendations were developed covering the areas of quality control in the manufacturing of probiotics, criteria for selection of probiotics, and established evidence for use of probiotics in diarrheal diseases in adults and children. Recommendations for the use of specific probiotic strains in clinical practice were categorized as proven and probable efficacy based on strength of evidence. Robust evidence is available to support the use of probiotics for diarrheal diseases in clinical practice. Based on the results obtained, we strongly advocate the careful evaluation of products, including manufacturing practices, strain‐specific evidence, and contraindications for at‐risk populations when choosing probiotics for use in clinical practice.

Abstract The COVID‐19 pandemic, secondary to SARS‐CoV‐2, has resulted in high mortality and morbidity worldwide. As inflammatory bowel disease (IBD) is a chronic disease, and most patients are on long‐term immunosuppressive agents, there is understandable concern, particularly in terms of therapy. In view of this, experts in IBD across the Asia Pacific region were invited to put together recommendations based on their experience and the currently available data. In general, most IBD therapies (with a few exceptions) can be continued safely, and the general consensus is that maintaining disease control should remain the main principle of management. In addition, social distancing measures and the appropriate use of personal protective equipment should be strictly adhered to. During the current pandemic, face‐to‐face clinic follow ups and non‐urgent procedures should be kept to a minimum.

In diabetes mellitus, the efficient alleviation of hyperglycemia, an elevated glycemic concentration, is quite crucial to avoid persistent complications. Thus, it is of prime importance to have an automated closed-loop insulin delivery system, often termed as an artificial pancreas, in the patient's body. The requisite amount of exogenous insulin bolus must be determined by a control algorithm, which is the primary constituent of the closed-loop system. In this article, a finite-time synergistic control approach, based on a gain-scheduled Luenberger observer (GSLO), is introduced. The proposed control strategy establishes a closed-loop insulin delivery system, which confirms the glycemic regulation that is quite obligatory in type-1 diabetic (T1D) patients. The control law is synthesized by using a recursive backstepping with a sliding mode control (SMC) approach. Besides, the nonlinear terms are incorporated, in the pseudo control inputs, which provide the finite-time convergence of the system's trajectories. Since the proposed control law relies on the system's information, thus, a virtual patient simulator, presented by Bergman minimal model (BMM), is transformed into an equivalent dynamic structure, which facilitates the design of GSLO. The observer's gains, which modify in each iteration, are based on the updated values of the system's states. Also, it endorses the separation principle, thus proving the closed-loop system's stability. The proposed closed-loop insulin delivery system confirms the suppression of postprandial hyperglycemia and hypoglycemic events in T1D patients. The efficacy is demonstrated via in-silico testing, which is executed in MATLAB/Simulink environment.

Colorectal cancer (CRC) is a heterogeneous disease that commonly affects individuals aged more than 50 years old globally. Regular colorectal screening, which is recommended for individuals aged 50 and above, has decreased the number of cancer death toll over the years. However, CRC incidence has increased among younger population (below 50 years old). Environmental factors, such as smoking, dietary factor, urbanization, sedentary lifestyle, and obesity, may contribute to the rising trend of early-onset colorectal cancer (EOCRC) because of the lack of genetic susceptibility. Research has focused on the role of gut microbiota and its interaction with epithelial barrier genes in sporadic CRC. Population with increased consumption of grain and vegetables showed high abundance of Prevotella, which reduces the risk of CRC. Microbes, such as Fusobacterium nucleatum, Bacteroides fragilis and Escherichia coli deteriorate in the intestinal barrier, which leads to the infiltration of inflammatory mediators and chemokines. Gut dysbiosis may also occur following inflammation as clearly observed in animal model. Both gut dysbiosis pre- or post-inflammatory process may cause major alteration in the morphology and functional properties of the gut tissue and explain the pathological outcome of EOCRC. The precise mechanism of disease progression from an early stage until cancer establishment is not fully understood. We hypothesized that gut dysbiosis, which may be influenced by environmental factors, may induce changes in the genome, metabolome, and immunome that could destruct the intestinal barrier function. Also, the possible underlying inflammation may give impact microbial community leading to disruption of physical and functional role of intestinal barrier. This review explains the potential role of the interaction among host factors, gut microenvironment, and gut microbiota, which may provide an answer to EOCRC.

Background The incidence rate of colorectal cancer (CRC) in Asian countries is increasing. Furthermore, recent studies have shown a concerning rise in the incidence of CRC among younger patients aged less than 50 years. This study aimed to analyze the incidence trends and clinicopathological features in patients with early-onset CRC (EOCRC) and later-onset CRC (at age ≥ 50 years). Methods A retrospective analysis was performed on 946 patients with CRC diagnosed from 1997 to 2017 at Universiti Kebangsaan Malaysia Medical Centre. The time trend was assessed by dividing the two decades into four 5-year periods. The mean age-standardized and age-specific incidence rates were calculated by using the 5-year cumulative population of Kuala Lumpur and World Health Organization standard population. The mean incidence was expressed per 100,000 person-years. Results After a stable (all age groups) CRC incidence rate during the first decade (3.00 per 100,000 and 3.85 per 100,000), it sharply increased to 6.12 per 100,000 in the 2008–2012 period before decreasing to 4.54 per 100,000 in the 2013–2017 period. The CRC incidence trend in later-onset CRC showed a decrease in the 2013–2017 period. Contrariwise, for age groups of 40–44 and 45–49 years, the trends showed an increase in the latter 15 years of the study period (40–44 years: 1.44 to 1.92 to 2.3 per 100,000; 45–49 years: 2.87 to 2.94 to 4.01 per 100,000). Malays’ EOCRC incidence rate increased from 2008–2012 to 2013–2017 for both the age groups 40–44 years (1.46 to 2.89 per 100,000) and 45–49 years (2.73 to 6.51 per 100,000). Nearly one-fifth of EOCRC cases were diagnosed at an advanced stage (Dukes D: 19.9%), and the majority of them had rectal cancer (72.8%). Conclusion The incidence of EOCRC increased over the period 1997–2017; the patients were predominantly Malays, diagnosed at a later stage, and with cancer commonly localized in the rectal region. All the relevant stakeholders need to work on the management and prevention of CRC in Malaysia.

Background: The emergence of multidrug-resistant Helicobacter pylori has undermined eradication strategies to prevent the development of gastric cancer. This study was conducted to estimate the prevalence of secondary antibiotic resistance of H. pylori in urban multicultural areas in Malaysia. Methods: From January 2017 to December 2021, gastric biopsies from 218 patients with a history of H. pylori eradication failure were sent to our laboratory for antibiotic susceptibility testing. A minimal inhibitory concentration was determined for six antibiotics, namely metronidazole, clarithromycin, levofloxacin, amoxicillin, tetracycline, and rifampicin using the E-test method. Two multidrug-resistant H. pylori strains identified in this study were subjected to whole genome sequencing. Results: Eradication failure was observed to be significantly higher in the Malaysian Chinese patients than in the Malaysian Indian and Malay patients. H. pylori were successfully isolated from 51 patients (23.4%). Overall, the antibiotic resistance rates of H. pylori to metronidazole, clarithromycin, levofloxacin, and amoxicillin were 82.4% (42/51), 72.5% (37/51), 52.9% (27/51), and 3.9% (2/51), respectively. Resistance to tetracycline and rifampicin were not observed during the study period. Resistance to more than one antibiotic was observed in 82.4% (42/51) of the isolates, of which 42.2% (19/42) were resistant to three antibiotic classes. Resistance to both clarithromycin and metronidazole were most frequently observed in isolates with dual resistance (56.5%; 13/23). Codon substitutions in penicillin-binding protein 1A (V346L, V374L, G595_V596InsG, Y604H, and N608S) were detected in amoxicillin-resistance H. pylori strains. Herein, we report amoxicillin resistance in H. pylori isolated from Malaysian patients, and its resistance mechanism, for the first time. Conclusion: Our results show the increase trend in secondary multidrug resistance in H. pylori isolates, which warrants continuous surveillance.

Obesity has become a worldwide health concern among the pediatric population. The prevalence of non-alcoholic fatty liver disease (NAFLD) is growing rapidly, alongside the high prevalence of obesity. NAFLD refers to a multifactorial disorder that includes simple steatosis to non-alcoholic steatohepatitis (NASH) with or devoid of fibrosis. NAFLD is regarded as a systemic disorder that influences glucose, lipid, and energy metabolism with hepatic manifestations. A sedentary lifestyle and poor choice of food remain the major contributors to the disease. Prompt and timely diagnosis of NAFLD among overweight children is crucial to prevent the progression of the condition. Yet, there has been no approved pharmacological treatment for NAFLD in adults or children. As indicated by clinical evidence, lifestyle modification plays a vital role as a primary form of therapy for managing and treating NAFLD. Emphasis is on the significance of caloric restriction, particularly macronutrients (fats, carbohydrates, and proteins) in altering the disease consequences. A growing number of studies are now focusing on establishing a link between vitamins and NAFLD. Different types of vitamin supplements have been shown to be effective in treating NAFLD. In this review, we elaborate on the potential role of vitamin E with a high content of tocotrienol as a therapeutic alternative in treating NAFLD in obese children.

Alfizah Hanafiah,1 Hasyanee Binmaeil,1 Raja Affendi Raja Ali,2 Isa Mohamed Rose,3 Bruno S Lopes4 1Department of Medical Microbiology and Immunology; 2Department of Medicine; 3Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Cheras, Kuala Lumpur 56000, Malaysia; 4Department of Medical Microbiology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UKCorrespondence: Alfizah HanafiahDepartment of Medical Microbiology and Immunology, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, 16th Floor, Preclinical Building, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur 56000, MalaysiaTel +603 9 145 9539Fax +603 9 145 9524Email alfizah@ppukm.ukm.edu.myBruno S LopesDepartment of Medical Microbiology, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, 0:025 Polwarth Building, Aberdeen AB25 2ZD, UKEmail bruno.lopes@abdn.ac.ukAims and objectives: Helicobacter pylori has been classified as high priority pathogen by the WHO in 2017. The emergence of antibiotic-resistant strains is one of the main causes of treatment failure in H. pylori infection. This study determined and characterized primary and secondary resistances in H. pylori in Malaysia.Materials and methods: Gastric biopsies from antrum (n=288) and corpus (n=283) were obtained from 288 patients who underwent endoscopy at Universiti Kebangsaan Malaysia Medical Center (UKMMC), Kuala Lumpur, Malaysia. Antibiotic susceptibility to six classes of antibiotics was determined by the E-test. Mutations conferring in resistance in functional genes were identified by PCR and sequencing.Results: Overall resistance rates to metronidazole, clarithromycin and levofloxacin were 59.3% (35/59), 35.6% (21/59) and 25.4% (15/59), respectively. Secondary isolates showed significantly higher resistance rates to clarithromycin compared to the primary isolates. Mixed infection with susceptible and resistant isolates was observed in 16.2% (6/37) of cases, of which 83.3% (n=5) had infection with the same strain. 41% (18/44) of isolates were resistant to more than one class of antibiotics of which 50% (9/18) were multidrug-resistant, two being primary and seven being secondary isolates. Mutations in rdxA, 23S rRNA and gyrA genes were associated with resistance to metronidazole, clarithromycin and levofloxacin, respectively.Conclusion: The high level of resistance to metronidazole, clarithromycin and levofloxacin seen in H. pylori isolates in our setting warrants the need for continuous surveillance and highlights caution in use of antibiotics generally used as first-line therapy in H. pylori eradication regimen.Keywords: Helicobacter pylori, antibiotic resistance, clarithromycin, metronidazole, levofloxacin, point mutation

Abstract Background Our study aimed to determine the effect of probiotic consumption containing six viable microorganisms of 30 × 1010 cfu Lactobacillus and Bifidobacteria strains for six months on clinical outcomes and inflammatory cytokines (TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22) in patients with colorectal cancer. Methods Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo (n = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 (n = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit. Results The majority of cases (~ 70%) were in Duke’s C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level (P

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn’s and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn’s disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.

Abstract Background Inflammatory bowel disease (IBD) was once considered as a Western disease. However, recent epidemiological data showed an emerging trend of IBD cases in the Eastern Asia countries. Clinico-epidemiological data of IBD in Malaysia is scarce. This study aimed to address this issue. Methods Retrospective analysis of ulcerative colitis (UC) and Crohn’s disease (CD), diagnosed from January 1980 till June 2018 was conducted at our centre. Results A total of 413 IBD patients (281 UC, 132 CD) were identified. Mean crude incidence of IBD has increased steadily over the first three decades: 0.36 (1980–1989), 0.48 (1990–1999) and 0.63 per 100,000 person-years (2000–2009). In the 2010 to 2018 period, the mean crude incidence has doubled to 1.46 per 100,000 person-years. There was a significant rise in the incidence of CD, as depicted by reducing UC:CD ratio: 5:1 (1980–1989), 5:1 (1990–1999), 1.9:1 (2000–2009) and 1.7:1 (2010–2018). The prevalence rate of IBD, UC and CD, respectively were 23.0, 15.67 and 7.36 per 100,000 persons. Of all IBD patients, 61.5% (n = 254) were males. When stratified according to ethnic group, the highest prevalence of IBD was among the Indians: 73.4 per 100,000 persons, followed by Malays: 24.8 per 100,000 persons and Chinese: 14.6 per 100,000 persons. The mean age of diagnosis was 41.2 years for UC and 27.4 years for CD. Majority were non-smokers (UC: 76.9%, CD: 70.5%). The diseases were classified as follows: UC; proctitis (9.2%), left-sided colitis (50.2%) and extensive colitis (40.6%), CD; isolated ileal (22.7%), colonic (28.8%), ileocolonic (47.7%) and upper gastrointestinal (0.8%). 12.9% of CD patients had concurrent perianal disease. Extra intestinal manifestations were observed more in CD (53.8%) as compared to UC (12%). Dysplasia and malignancy, on the other hand, occurred more in UC (4.3%, n = 12) than in CD (0.8%, n = 1). Over one quarter (27.3%) of CD patients and 3.6% of UC patients received biologic therapy. Conclusion The incidence of IBD is rising in Malaysia, especially in the last one decade. This might be associated with the urbanization and changing diets. Public and clinicians’ awareness of this emerging disease in Malaysia is important for the timely detection and management.

Aberrant gut microbiota dysbiosis in women with a previous history of gestational diabetes mellitus (post-GDM) was comparable to that in adults with type 2 diabetes mellitus (T2DM). Nonetheless, potential relationships between diet, gut microbiota, and metabolic phenotypes in post-GDM women after delivery are yet to be discovered. In this research, we assessed the relationship of the macronutrient intakes, gut microbiota composition, and metabolic phenotypes (i.e., anthropometrics and glycemic control) in post-GDM women with and without postpartum glucose intolerance (GI). About 24 post-GDM women were included in this study, 14 women were grouped in the GI group and 10 women were grouped in the normal glucose tolerance (NGT) group according to oral glucose tolerance test. Macronutrient intake assessment using a 3-day dietary record, anthropometric measurements, biochemical analyses, and fecal sampling were done during 3–6 months postpartum. Gut microbiota profiling was determined using 16S rRNA genes sequencing targeting the V3–V4 regions. The relationships between macronutrient intakes, gut microbiota composition, and metabolic phenotypes were evaluated using Pearson’s correlation coefficient and stepwise regression analyses. In this study, most post-GDM women had significantly poor dietary fiber adherence than the nutritional recommendations. Women from the GI group have significantly higher fasting blood glucose (FBG), HbA1c, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) levels compared to the NGT group. The group also showed significant elevation of high-sensitivity C-reactive protein (hs-CRP) level when compared to the normal value. Specific gut microbial taxa derived from Proteobacteria and Bacteroidetes such as Parasutterella, Aquicella, Haliscomenobacter, and Prevotellaceae_NK3B31_group were significantly abundant in the GI group compared to the NGT group. Prevotellaceae_NK3B31_group was significantly associated with high FBG, HOMA-IR, and HbA1c levels. Low fiber and monounsaturated fatty acids intakes were associated with Lactobacillus. Meanwhile, Lactobacillus was associated with high body mass index, waist circumference, 2-h postprandial blood glucose, and hs-CRP levels. Our study suggested that macronutrient intake is an important predictor of gut microbiota dysbiosis and is associated with obesity, low-grade inflammation, and poor glycemic control in post-GDM women. Hence, dietary intake modification to remodel gut microbiota composition is a promising T2DM preventive strategy in post-GDM women.

Linear Parameter Varying (LPV) systems and their control have gained attraction recently as they approximate nonlinear systems with higher order than ordinary linear systems. On the other hand, time delay is an inherent part of various real-life applications. A supervisory control structure is proposed in this paper for LPV systems subject to time delays. In the proposed control structure, a supervisor selects the most suitable controller from a bank of controllers; which desires to enhance the performance of closed-loop system in contrast with using a single robust controller. The analysis is based on the celebrated Smith predictor for time delay compensation and we provide a sufficient condition to assure the stability of the closed-loop switched system in terms of dwell time. Simulations on blood pressure control of hypertension patients in postoperative scenario are used to exemplify the effectiveness of the utilized technique. The operating region of the system is partitioned into five smaller operating regions to construct corresponding robust controllers and perform hysteresis switching amongst them. Simulation results witnessed that the proposed control scheme demonstrated a pressure undershoot less than the desired value of 10 mmHg while the Mean Arterial Pressure (MAP) remains within ±5 mmHg of the desired value.