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.
METHOD: We collected data on demographics, retention and completion and abstinence between January 2021-August 2023 in MSM using Beyond-66. Using 10-point Likert scales, we compared motivation to remain abstinent and mental wellbeing at the beginning and end of Beyond-66.
RESULTS: 25 MSM have either completed or dropped out/referred out of Beyond-66, 12/25(48%) were living with HIV and the median duration of chemsex use was 5 years (IQR = 4-6). 19 (76%) completed programme; 3 were referred out for a psychiatry assessment and 3 dropped out of the programme. 14 (74%) remain abstinent and 5 relapsed. The median motivation for abstinence scores for the 19 completers increased significantly between the pre-programme and post-programme period (7/10 (IQR = 4-8) to 9/10 (IQR = 5-10), p = .04) and the median mental health score (Likert score out of 10 where 10 is poor mental health) reduced significantly (5/10 (IQR = 4-7) to 2/10 (IQR 1-6), p = .008).
CONCLUSION: This pilot evaluation suggests that MSM using Beyond-66 experience high completion (76%) and abstinence (74%) rates and increased motivation for abstinence and mental wellbeing scores. Further research is needed to design, develop, and deliver peer led interventions for MSM who are chemsex dependant.
METHOD: The study used an online anonymous survey to collect data including demographics, awareness of the term, experience of microaggression, acts and response. The research findings were analyzed using univariate and multivariate analyses using Chi-square test and binary logistic regression respectively.
RESULT: A total of 443 participants (40.9% males, 59.1% females) included 403 physicians (91%), 21 dentists (4.7%), 15 nurses (3.4%) and 4 pharmacists (0.9%). More than half of the participants (59.8%) were aware of the term micro-aggression. The percentage was significantly higher among respondents from the western region of Saudi Arabia than the Gulf/Middle Eastern countries. Approximately 38.1% of the participants experienced microaggression and more than half (55.62%) did not report experiencing microaggression. The most common form of microaggression was passive-aggressive behavior (80.5%) followed by invalidation of an opinion (73.4%). Among those who experienced microaggression, (12.9%) reported anger as the most predominant emotional response.
CONCLUSION: Microaggression is a universal phenomenon. Further research is necessary to determine its prevalence in other countries to establish a comprehensive understanding of its cultural context.
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: We evaluated the performance of machine learning (ML) and non-patented scores for ruling out SF among NAFLD/MASLD patients.
METHODS: Twenty-one ML models were trained (N = 1153), tested (N = 283), and validated (N = 220) on clinical and biochemical parameters of histologically-proven NAFLD/MASLD patients (N = 1656) collected across 14 centres in 8 Asian countries. Their performance for detecting histological-SF (≥F2fibrosis) were evaluated with APRI, FIB4, NFS, BARD, and SAFE (NPV/F1-score as model-selection criteria).
RESULTS: Patients aged 47 years (median), 54.6% males, 73.7% with metabolic syndrome, and 32.9% with histological-SF were included in the study. Patients with SFvs.no-SF had higher age, aminotransferases, fasting plasma glucose, metabolic syndrome, uncontrolled diabetes, and NAFLD activity score (p 140) was next best in ruling out SF (NPV of 0.757, 0.724 and 0.827 in overall, test and validation set).
CONCLUSIONS: ML with clinical, anthropometric data and simple blood investigations perform better than FIB-4 for ruling out SF in biopsy-proven Asian NAFLD/MASLD patients.
METHODS AND RESULTS: Histopathology revealed increased collagen deposition and altered fiber arrangement in the NP and isoproterenol hydrochloride (ISO) groups compared with the blank group. Systolic and diastolic functions were impaired. Western blotting and qRT-PCR demonstrated that the expression of central myofibrosis-related proteins (collagens Ι and ΙΙΙ, MMP2, MMP9, TGF-β1, α-SMA, IL-1β, and TGF-β1) and genes (Collagen Ι, Collagen ΙΙΙ, TGF-β1, and α-SMA mRNA) was upregulated in the NP and ISO groups compared with the blank group. The mRNA-seq analysis indicated differential expression of TGF-β1 signaling pathway-associated genes and proteins. Fibrosis-related protein and gene expression increased in the CFs stimulated with the recombinant human TGF-β1 and NP, which was consistent with the results of animal experiments. According to the immunofluorescence analysis and western blotting, NP exposure activated the TGF-β1/LIMK1 signaling pathway whose action mechanism in NP-induced CFs was further validated using the LIMK1 inhibitor (BMS-5). The inhibitor modulated the TGF-β1/LIMK1 signaling pathway and suppressed the NP-induced increase in fibrosis-related protein expression in the CFs. Thus, the aforementioned pathway is involved in NP-induced fibrosis.
CONCLUSION: We here provide the first evidence that perinatal NP exposure causes myocardial fibrosis in growing male rat pups and reveal the molecular mechanism and functional role of the TGF-β1/LIMK1 signaling pathway in this process.
METHODS: Patients with unexplained pediatric-onset epilepsy were identified from the in-house Severance Neurodevelopmental Disorders and Epilepsy Database. All patients underwent either exome sequencing or multigene panels from January 2017 to December 2019, at Severance Children's Hospital in Korea. Clinical data were extracted from the medical records.
RESULTS: Of the 957 patients studied, 947 (99.0%) were Korean and 570 were male (59.6%). The median age at testing was 4.91 years (interquartile range, 1.53-9.39). The overall diagnostic yield was 32.4% (310/957). Clinical exome sequencing yielded a diagnostic rate of 36.9% (134/363), whereas the epilepsy panel yielded a diagnostic rate of 29.9% (170/569). Diagnostic yield differed across epilepsy syndromes. It was high in Dravet syndrome (87.2%, 41/47) and early infantile developmental epileptic encephalopathy (60.7%, 17/28), but low in West syndrome (21.8%, 34/156) and myoclonic-atonic epilepsy (4.8%, 1/21). The most frequently implicated genes were SCN1A (n = 49), STXBP1 (n = 15), SCN2A (n = 14), KCNQ2 (n = 13), CDKL5 (n = 11), CHD2 (n = 9), SLC2A1 (n = 9), PCDH19 (n = 8), MECP2 (n = 6), SCN8A (n = 6), and PRRT2 (n = 5). The recurrent genetic abnormalities included 15q11.2 deletion/duplication (n = 9), Xq28 duplication (n = 5), PRRT2 deletion (n = 4), MECP2 duplication (n = 3), SCN1A, c.2556+3A>T (n = 3), and 2q24.3 deletion (n = 3).
SIGNIFICANCE: Here we present the results of a large-scale study conducted in East Asia, where we identified several common genes and recurrent variants that varied depending on specific epilepsy syndromes. The overall genetic landscape of the Asian population aligns with findings from other populations of varying ethnicities.
METHODS: Data were from population-based studies of aging and their Harmonized Cognitive Assessment Protocols (HCAPs) in the US, South Africa, India, and Mexico (N = 10,037; Age range: 50 to 105 years; 2016 to 2020). Main lifetime occupational skill was classified according to the International Standard Classification of Occupations. Weighted, adjusted regression models estimated pooled and country-specific associations between main lifetime occupational skill and later-life general cognitive function in men and women.
RESULTS: We observed positive gradients between occupational skill and later-life cognitive function for men and women in the US and Mexico, a positive gradient for women but not men in India, and no association for men or women in South Africa.
DISCUSSION: Main lifetime occupations may be a source of later-life cognitive reserve, with cross-national heterogeneity in this association.
HIGHLIGHTS: No studies have examined cross-national differences in the association of occupational skill with cognition. We used data from Harmonized Cognitive Assessment Protocols in the US, Mexico, India, and South Africa. The association of occupational skill with cognitive function varies by country and gender.
MATERIALS AND METHODS: This is a retrospective crosssectional study reviewing the medical records of patients seen by visiting nephrologists from January 2019 to December 2021 in Greentown Health Clinic. The study population are patients with CKD stage 3b, 4 and 5 who are followed up in Greentown Health Clinic. Universal sampling was done, a total of 87 patients reviewed at least once by the visiting nephrologist and with retrievable medical records were included in the study. Those whose medical records were irretrievable were excluded. Blood pressure, urine protein, fasting blood sugar (FBS), glycated haemoglobin (HbA1c), serum creatinine, eGFR and fasting lipid profile (FLP) pre- and post-visits were collected by reviewing patient medical records and laboratory results. The results were then analysed and compared using SPSS version 26.
RESULTS: The median age of patients in this study was 66 years of age, the majority were male patients (54%) and Malay ethnicity (62.1%). Absence of urine microalbuminuria pre and post referral remain the same (n = 11). During prenephrologist visits, a higher percentage of patients exhibited moderate (30-300 mg/g) and severe (>300 mg/g) increase in urine albuminuria (15.7% and 7.2%, respectively) compared to the post-referral period. In patients with significant urine protein pre-referral, patient group with urine protein 3+ showed the highest increment of 30.1% (n = 22), in comparison to 19.3% (n = 16) observed during prereferral. Statistically significant clinical outcomes between pre- and post-referral to the nephrologist include reduction of systolic blood pressure [141±15 mmHg versus 135 ±12 mmHg, p = 0.001] and diastolic blood pressure [median = 80 mmHg (IQR: 10) versus median=71 mmHg (IQR: 17), p < 0.001]. Similarly, total cholesterol [median = 4.4 mmol/L (IQR: 1.4) versus median = 4.0 mmol/L (IQR: 1.5, p = 0.001] and LDL [median = 2.5 mmol/L (IQR: 1.2) versus median = 2.2 mmol/L (IQR: 1.2), p < 0.001)] exhibited statistically significant differences between pre- and post-referral. However, HDL remained unchanged and other outcome variables showed no significant differences.
CONCLUSION: Incorporating nephrologist visits in primary care seems to have positive impact towards patient clinical outcomes. Results shown in this study can aid other primary care clinics in the decision to initiate nephrologist services in the primary care setting as a multidisciplinary approach to managing CKD patients.
OBJECTIVES: Work-related disability is common in persons with spinal cord injury (SCI). The aims of this study are to examine the associations of employment with self-perceived health (SPH) and quality of life (QoL) across 22 countries and to explore the covariates around employment and SPH and QoL.
SETTING: Community.
METHODS: We analyzed 9494 community-dwelling persons with SCI aged 18-65. We performed an adjusted regression and path analysis. The independent variable was 'employment' and the dependent variables were two single items: QoL (very poor to very good) and SPH (excellent to poor). Covariates included the Gross Domestic Product (GDP), education, time since SCI, age, gender, years of employment after SCI, SCI level (paraplegia, tetraplegia), and completeness of SCI.
RESULTS: Participants' mean age was 47, 74% were male, and 63% had paraplegia. We found an association between employment and QoL and SPH. While the magnitude of the effect of employment on QoL did not differ across GDP quartiles, its perceived effect on QoL was found to be significant in the highest GDP quartile. Employment was predictive of good SPH in two GDP quartiles (Q1 and Q4), but significant across all quartiles when predicting poor perceptions, with the magnitude of effect varying significantly.
CONCLUSIONS: Employment is closely related to QoL and SPH depending on the GDP. We may positively influence the QoL and SPH in the SCI population to promote better employment outcomes by considering the infrastructure and economy.