AIM OF STUDY: The overall aim of this study was to investigate the gene expression profile of Ligno TG-K via de novo RNA-seq and pathway analysis. We also aimed to identify highly expressed genes encoding compounds that contribute to its cytotoxic and antioxidant properties, as well as perform a comparative transcriptomics analysis between Ligno TG-K and its sister species, L. rhinocerus TM02®.
MATERIALS AND METHODS: Total RNA from fresh 3-month-old cultivated L. tigris sclerotia (Ligno TG-K) was extracted and analyzed via de novo RNA sequencing. Expressed genes were analyzed using InterPro and NCBI-Nr databases for domain identification and homology search. Functional categorization based on gene functions and pathways was performed using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Clusters of Orthologous Genes (COG) databases. Selected genes were subsequently subjected to phylogenetic analysis.
RESULTS: Our transcriptomics analysis of Ligno TG-K revealed that 68.06% of its genes are expressed in the sclerotium; 80.38% of these were coding transcripts. Our analysis identified highly expressed transcripts encoding proteins with prospective medicinal properties. These included serine proteases (FPKM = 7356.68), deoxyribonucleases (FPKM = 3777.98), lectins (FPKM = 3690.87), and fungal immunomodulatory proteins (FPKM = 2337.84), all of which have known associations with anticancer activities. Transcripts linked to proteins with antioxidant activities, such as superoxide dismutase (FPKM = 1161.69) and catalase (FPKM = 1905.83), were also highly expressed. Results of our sequence alignments revealed that these genes and their orthologs can be found in other mushrooms. They exhibit significant sequence similarities, suggesting possible parallels in their anticancer and antioxidant bioactivities.
CONCLUSION: This study is the first to provide a reference transcriptome profile of genes expressed in the sclerotia of L. tigris. The current study also presents distinct COG profiles of highly expressed genes in Ligno TG-K and L. rhinocerus TM02®, highlighting that any distinctions uncovered may be attributed to their interspecies variations and inherent characteristics that are unique to each species. Our findings suggest that Ligno TG-K contains bioactive compounds with prospective medicinal properties that warrant further investigations.
CLASSIFICATION: Systems biology and omics.
METHODS: All adults aged 18-70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation.
RESULTS: Among 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05).
CONCLUSIONS: Agile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.
METHODS: Longitudinal data from two different sources were analysed: a pre-post study of an online parenting programme conducted across six countries - the ePLH Evaluation Study, and a prospective cohort study in the United States - LONGSCAN. Cross-lagged panel model on parenting stress and child maltreatment was used in each dataset.
RESULTS: Based on repeatedly measured data of 484 caregivers in the ePLH study across five time points (every two weeks), we found that parenting stress at an earlier time point predicted later child maltreatment (IRR = 1.14, 95 % CI: 1.10,1.18). In addition, the occurrence of child maltreatment was associated with higher subsequent short-term parenting stress (IRR = 1.04, 95 % CI: 1.01,1.08) and thus could form a vicious circle. In the LONGSCAN analysis with 772 caregivers who were followed up from child age of 6 to child age of 16, we also found parenting stress at an earlier time point predicted later child maltreatment (β = 0.11, 95 % CI: 0.01,0.20), but did not observe an association between child maltreatment and subsequent long-term parenting stress.
LIMITATIONS: Potential information bias on the measurements.
CONCLUSIONS: This study provides evidence for a bidirectional temporal relationship between parenting stress and child maltreatment, which should be considered in parenting intervention programmes.
METHODS AND RESULTS: The MY-HF Registry is a 3-year prospective, observational study comprising 2717 Malaysian patients admitted for acute HF. We report the description of baseline data at admission and outcomes of index hospitalization of these patients. The mean age was 60.2 ± 13.6 years, 66.8% were male, and 34.3% had de novo HF. Collectively, 55.7% of patients presented with New York Heart Association (NYHA) Class III or IV; ischaemic heart disease was the most frequent aetiology (63.2%). Most admissions (87.3%) occurred via the emergency department, with 13.7% of patients requiring intensive care, and of these, 21.8% needed intubation. The proportion of patients receiving guideline-directed medical therapy increased at discharge (84.2% vs. 93.6%). The median length of stay (LOS) was 5 days, and in-hospital mortality was 2.9%. Predictors of LOS and/or in-hospital mortality were age, NYHA class, estimated glomerular filtration rate, and comorbid anaemia. LOS and in-hospital mortality were similar regardless of ejection fraction.
CONCLUSIONS: The MY-HF Registry showed that the HF population in Malaysia is younger, predominantly male, and ischaemic-driven and has good prospects with hospitalization for optimization of treatment. These findings suggest a need to reassess current clinical practice and guide resource allocation to improve patient outcomes.
DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter.
PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries.
INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration.
MAIN OUTCOME MEASURES: Enucleation and death.
RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively.
CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia.
FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
OBJECTIVES: This study investigated DNAm differences associated with prenatal nitrogen dioxide (NO2) exposure (a surrogate measure of traffic-related air pollution) at birth and 1 y of age and examined their role in atopic disease. We focused on regions showing persistent DNAm differences from birth to 1 y of age and regions uniquely associated with postnatal NO2 exposure.
METHODS: Microarrays measured DNAm at birth and at 1 y of age for an atopy-enriched subset of Canadian Health Infant Longitudinal Development (CHILD) study participants. Individual and regional DNAm differences associated with prenatal NO2 (n=128) were identified, and their persistence at age 1 y were investigated using linear mixed effects models (n=124). Postnatal-specific DNAm differences (n=125) were isolated, and their association with NO2 in the first year of life was examined. Causal mediation investigated whether DNAm differences mediated associations between NO2 and age 1 y atopy or wheeze. Analyses were repeated using biological sex-stratified data.
RESULTS: At birth (n=128), 18 regions of DNAm were associated with NO2, with several annotated to HOX genes. Some of these regions were specifically identified in males (n=73), but not females (n=55). The effect of prenatal NO2 across CpGs within altered regions persisted at 1 y of age. No significant mediation effects were identified. Sex-stratified analyses identified postnatal-specific DNAm alterations.
DISCUSSION: Regional cord blood DNAm differences associated with prenatal NO2 persisted through at least the first year of life in CHILD participants. Some differences may represent sex-specific alterations, but replication in larger cohorts is needed. The early postnatal period remained a sensitive window to DNAm perturbations. https://doi.org/10.1289/EHP13034.
METHODS: Prospective, multicenter, international registry on the management of H. pylori (European Registry on H. pylori Management). All infected and culture-diagnosed adult patients registered in the Spanish Association of Gastroenterology-Research Electronic Data Capture from 2013 to 2021 were included.
RESULTS: A total of 2,852 naive patients with culture results were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 22%, 27%, and 18%, respectively. The most effective treatment, regardless of resistance, were the 3-in-1 single capsule with bismuth, metronidazole, and tetracycline (91%) and the quadruple with bismuth, offering optimal cure rates even in the presence of bacterial resistance to clarithromycin or metronidazole. The concomitant regimen with tinidazole achieved an eradication rate of 99% (90/91) vs 84% (90/107) with metronidazole. Triple schedules, sequential, or concomitant regimen with metronidazole did not achieve optimal results. A total of 1,118 non-naive patients were analyzed. Resistance to clarithromycin, metronidazole, and quinolones was 49%, 41%, and 24%, respectively. The 3-in-1 single capsule (87%) and the triple therapy with levofloxacin (85%) were the only ones that provided encouraging results.
DISCUSSION: In regions where the antibiotic resistance rate of H. pylori is high, eradication treatment with the 3-in-1 single capsule, the quadruple with bismuth, and concomitant with tinidazole are the best options in naive patients. In non-naive patients, the 3-in-1 single capsule and the triple therapy with levofloxacin provided encouraging results.
METHODS: Electronic medical records (EMR) were reviewed and phone surveys performed with parents of CDH survivors who underwent repair at our institution from 2010 to 2019. They completed the following Pediatric Quality of Life Inventory™ (PedsQL™) questionnaires: Generic Core Scales 4.0 (parent-proxy report) and Family Impact (FI) Module 2.0. Age-matched and gender-matched healthy controls from an existing database were used for comparison. Subgroup analysis of CDH patients alone was also performed. Appropriate statistical analysis was used with p
METHODS AND ANALYSIS: REKOVER is a phase-IV, multicountry, multicentre, prospective, real-world observational study. A total of 750 postsurgical and non-surgical patients (male and female, aged 18-80 years) will be recruited from 13 tertiary-care hospitals (15 sites) in Singapore, Thailand, the Philippines and Malaysia. All patients prescribed with TRAM/DKP FDC and willing to participate in the study will be enrolled. The recruitment duration for each site will be 6 months. The severity of pain will be collected using Numeric Pain Rating Scale through the treatment period from day 1 to day 5, while satisfaction with the treatment will be evaluated using Patient Global Evaluation Scale at the end of treatment. Any adverse event reported during the study duration will be recorded for safety analysis (up to day 6). The study data will be entered into the ClaimIt portal and mobile application (app) (ObvioHealth, USA). All the inpatient data will be entered into the portal by the study site and for outpatient it will be done by patients through an app.
ETHICS AND DISSEMINATION: The study has been approved by the local ethics committee from each study sites in Singapore, Thailand, the Philippines and Malaysia. Findings will be disseminated through local and global conference presentations, publications in peer-reviewed scientific journals and continuing medical education.
METHODS AND RESULTS: In a sample of 11 146 adults (51.5% men and 48.5% women) with a mean age of 47.1 years (SD ± 12.3) from a German population-based cohort, we analyzed risk factors and CVD mortality risk associated with an alerting reaction. An alerting reaction was prevalent in 10.2% of the population and associated with sociodemographic, lifestyle, and somatic CVD risk factors. Within a mean follow-up period of 22.7 years (SD ± 7.05 years; max: 32 years; 253 201 person years), 1420 (12.7%) CVD mortality cases were observed. The CVD mortality rate associated with an alerting reaction was significantly higher than in normotension (64 vs. 32 cases/10 000 person-years), but lower than hypertension (118 cases/10 000 person-years). Correspondingly, the alerting reaction was associated with a 23% higher hazard ratio of CVD mortality than normal blood pressure [hazard ratio 1.23 (95% confidence interval 1.02-1.49), P = 0.04]. However, adjustment for antihypertensive medication use attenuated this association [1.19 (0.99-1.44), P = 0.06].
CONCLUSION: The results may warrant monitoring of an alerting reaction as a preventive measure of CVD mortality in untreated individuals with elevated first BP readings, as well as optimized treatment in treated individuals.
METHODS: This prospective cohort study utilized stratified simple random sampling to recruit 1614 participants from the Malaysian Elders Longitudinal Research aged above 55 years within the Klang Valley region from 2013 to 2015. Individual items for the frailty tools, alongside baseline physical and cognitive measures were extracted from the initial survey. Mortality data up to 31 December 2020 were obtained through data linkage from the death registry data obtained from the Malaysian National Registration Department.
RESULTS: Data were available for over 1609 participants, age (68.92 ± 7.52) years and 57 % women, during recruitment. Mortality data revealed 13.4 % had died as of 31 December 2020. Five to 25 % of our study population fulfilled the criteria for frailty using all four frailty tools. This study found an increased risk of mortality with frailty following adjustments for potential factors of falls, total number of illnesses and cognitive impairment, alongside moderate to strong correlation and agreement between frailty tools.
CONCLUSION: Frailty was associated with increased mortality. All four frailty assessment tools can be used to assess frailty within the Malaysian older adult population. The four available tools, however, may not be interchangeable.
AIMS: To determine the prevalence of alcohol abstinence, factors associated with alcohol abstinence and the impact of abstinence on morbidity and overall survival in people with alcohol-associated cirrhosis.
METHODS: We searched Medline and Embase from inception to 15 April 2023 for prospective and retrospective cohort studies describing alcohol abstinence in people with known alcohol-associated cirrhosis. Meta-analysis of proportions for pooled estimates was performed. The method of inverse variance, employing a random-effects model, was used to pool the hazard ratio (HR) comparing outcomes of abstinent against non-abstinent individuals with alcohol-associated cirrhosis.
RESULTS: We included 19 studies involving 18,833 people with alcohol-associated cirrhosis. The prevalence of alcohol abstinence was 53.8% (CI: 44.6%-62.7%). Over a mean follow-up duration of 48.6 months, individuals who continued to consume alcohol had significantly lower overall survival compared to those who were abstinent (HR: 0.611, 95% CI: 0.506-0.738). These findings remained consistent in sensitivity/subgroup analysis for the presence of decompensation, study design and studies that assessed abstinence throughout follow-up. Alcohol abstinence was associated with a significantly lower risk of hepatic decompensation (HR: 0.612, 95% CI: 0.473-0.792).
CONCLUSIONS: Alcohol abstinence is associated with substantial improvement in overall survival in alcohol-associated cirrhosis. However, only half of the individuals with known alcohol-associated cirrhosis are abstinent.
MATERIALS AND METHODS: This was a single-centre, evaluatorblinded, split-face, randomised study investigating the effects of thermal spring water (TSW) in improving efficacy and tolerability of standard acne therapy. Total of 31 participants with mild-to-moderate acne were recruited and subjected to TSW spray to one side of the face 4 times daily for 6 weeks in addition to standard therapy. The other side received standard therapy only.
RESULTS: Six (19.4%) males and 25 (80.6%) female with mean age 25.1±6.13 participated, 15 (48.4%) had mild acne while 16 (51.6%) had moderate acne. Seven (22.6%) were on oral antibiotics, 25 (80.6%) used adapalene, 6 (19.4%) tretinoin and 21 (67.7%) benzoyl peroxide. Skin hydration improved and better on spring water treated side with mean difference12.41±30.31, p = 0.04 at the forehead, 39.52±65.14, p < 0.01 at the cheek and 42.172±71.71, p < 0.01 at the jaw at week 6. Participants also report significant reduction in dryness at the treated side at week 6, mean difference 0.93±0.10, p < 0.001. TEWL, sebum and pH were comparable on both sides with no significant differences. Tolerability towards standard therapy improved as early week 2 with reduction of stinging following application of topical therapy (mean difference 0.62±1.43, p = 0.03), increase in skin feeling good (-1.79±1.70, p < 0.001) and skin suppleness (0.62±1.43, p < 0.001). These improvements were significantly maintained till week 6. Cardiff acne disability index significantly improved at week 6 (p<0.001) despite no significant changes in Comprehensive Acne Severity Scale score before and after treatment.
CONCLUSION: TSW may have a role as an adjunct to standard acne therapy by improving hydration, acne disability index and tolerability towards standard topical treatment.
MATERIALS AND METHODS: This is a prospective single centre randomised single blinded comparative study conducted in HUSM. The primary endpoints for this study are the overall complete stone clearance rate and complication rate, while the secondary outcome for this study are duration of procedure and rate of usage of adjunct methods. Objective data analysis is conducted using independent sample t-test and chi-squared test.
RESULTS: A total of 66 patients underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis which is CBD stone. 34 patients were allocated to EST plus EPLBD arm (n=34), and 32 patients were in EST alone arm (n=32) using randomisation method. For intention to treat, patients from EST alone arm that unable to achieve complete stone clearance will be switched to EST plus EPLBD arm. The overall complete stone removal rate for both groups were comparable (EST plus EPLDB: 100% versus EST alone: 93.8%; p= 0.139). The two patients from EST alone group (6.2%) that unable to achieve complete stone clearance were converted to EST plus EPLBD group for intention to treat and able to achieve complete stone clearance by EST plus EPLBD. For procedural time, both arms are comparable as well (EST plus EPLDB: 15.8 minutes vs EST alone: 15.5 minutes; p= 0.860). Complications such as pancreatitis occurred in one patient in EST plus EPLBD arm (EST plus EPLDB: 2.9 % vs EST alone: 0 %; p= 0.328), and bleeding occurred in one patient in EST alone arm (EST plus EPLDB: 0 % vs EST alone: 3.1 %; p= 0.299) , but it is not statistically significant. No perforation or cholangitis complication occurred in both groups. No adjunct usage was observed in both groups.
CONCLUSION: In this study with limited sample size, both EST plus EPLBD and EST alone are effective and has comparable procedural time in removing CBD stone. Even though both methods are equally effective, EPLBD plus EST is an alternative solution if complete stone clearance is unable to achieve via EST alone.