An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis.

BACKGROUND: ERK5 (extracellular signal-regulated kinase 5) is a dual kinase transcription factor containing an N-terminal kinase domain and a C-terminal transcriptional activation domain. Many ERK5 kinase inhibitors have been developed and tested to treat cancer and inflammatory diseases. However, recent data have raised questions about the role of the catalytic activity of ERK5 in proliferation and inflammation. We aimed to investigate how ERK5 reprograms myeloid cells to the proinflammatory senescent phenotype, subsequently leading to atherosclerosis. METHODS: A ERK5 S496A (dephosphorylation mimic) knock in (KI) mouse model was generated using CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeat-associated 9), and atherosclerosis was characterized by hypercholesterolemia induction. The plaque phenotyping in homozygous ERK5 S496A KI and wild type (WT) mice was studied using imaging mass cytometry. Bone marrow-derived macrophages were isolated from hypercholesterolemic mice and characterized using RNA sequencing and functional in vitro approaches, including senescence, mitochondria reactive oxygen species, and inflammation assays, as well as by metabolic extracellular flux analysis. RESULTS: We show that atherosclerosis was inhibited in ERK5 S496A KI mice. Furthermore, ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype and senescence-associated stemness by upregulating AHR (aryl hydrocarbon receptor) in plaque and bone marrow-derived macrophages isolated from hypercholesterolemic mice. We also discovered that ERK5 S496 phosphorylation could induce NRF2 (NFE2-related factor 2) SUMOylation at a novel K518 site to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity and mediates oxidized LDL (low-density lipoprotein)-induced senescence-associated secretory phenotype. Specific ERK5 kinase inhibitors (AX15836 and XMD8-92) also inhibited ERK5 S496 phosphorylation, suggesting the involvement of ERK5 S496 phosphorylation in the anti-inflammatory effects of these ERK5 kinase inhibitors. CONCLUSIONS: We discovered a novel mechanism by which the macrophage ERK5-NRF2 axis develops a unique senescence-associated secretory phenotype/stemness phenotype by upregulating AHR to engender atherogenesis. The finding of senescence-associated stemness phenotype provides a molecular explanation to resolve the paradox of senescence in proliferative plaque by permitting myeloid cells to escape the senescence-induced cell cycle arrest during atherosclerosis formation.

Improving health outcomes of people with diabetes: target setting for the WHO Global Diabetes Compact.

The Global Diabetes Compact is a WHO-driven initiative uniting stakeholders around goals of reducing diabetes risk and ensuring that people with diabetes have equitable access to comprehensive, affordable care and prevention. In this report we describe the development and scientific basis for key health metrics, coverage, and treatment targets accompanying the Compact. We considered metrics across four domains: factors at a structural, system, or policy level; processes of care; behaviours and biomarkers such as glycated haemoglobin (HbA1c); and health events and outcomes; and three risk tiers (diagnosed diabetes, high risk, or whole population), and reviewed and prioritised them according to their health importance, modifiability, data availability, and global inequality. We reviewed the global distribution of each metric to set targets for future attainment. This process led to five core national metrics and target levels for UN member states: (1) of all people with diabetes, at least 80% have been clinically diagnosed; and, for people with diagnosed diabetes, (2) 80% have HbA1c concentrations below 8·0% (63·9 mmol/mol); (3) 80% have blood pressure lower than 140/90 mm Hg; (4) at least 60% of people 40 years or older are receiving therapy with statins; and (5) each person with type 1 diabetes has continuous access to insulin, blood glucose meters, and test strips. We also propose several complementary metrics that currently have limited global coverage, but warrant scale-up in population-based surveillance systems. These include estimation of cause-specific mortality, and incidence of end-stage kidney disease, lower-extremity amputations, and incidence of diabetes. Primary prevention of diabetes and integrated care to prevent long-term complications remain important areas for the development of new metrics and targets. These metrics and targets are intended to drive multisectoral action applied to individuals, health systems, policies, and national health-care access to achieve the goals of the Global Diabetes Compact. Although ambitious, their achievement can result in broad health benefits for people with diabetes.

A pH-Sensitive Stretchable Zwitterionic Hydrogel with Bipolar Thermoelectricity.

Amid growing interest in using body heat for electricity in wearables, creating stretchable devices poses a major challenge. Herein, a hydrogel composed of two core constituents, namely the negatively-charged 2-acrylamido-2-methylpropanesulfonic acid and the zwitterionic (ZI) sulfobetaine acrylamide, is engineered into a double-network hydrogel. This results in a significant enhancement in mechanical properties, with tensile stress and strain of up to 470.3 kPa and 106.6%, respectively. Moreover, the ZI nature of the polymer enables the fabrication of a device with polar thermoelectric properties by modulating the pH. Thus, the ionic Seebeck coefficient (Si) of the ZI hydrogel ranges from -32.6 to 31.7 mV K-1 as the pH is varied from 1 to 14, giving substantial figure of merit (ZTi) values of 3.8 and 3.6, respectively. Moreover, a prototype stretchable ionic thermoelectric supercapacitor incorporating the ZI hydrogel exhibits notable power densities of 1.8 and 0.9 mW m-2 at pH 1 and 14, respectively. Thus, the present work paves the way for the utilization of pH-sensitive, stretchable ZI hydrogels for thermoelectric applications, with a specific focus on harvesting low-grade waste heat within the temperature range of 25-40 °C.

The use of prednisolone during Ramadan fasting in patients with adrenal insufficiency.

OBJECTIVE: Once daily prednisolone taken at predawn has been proposed to be the glucocorticoid replacement of choice in patients with adrenal insufficiency (AI) who intend to fast for the month of Ramadan. However, the effects of prednisolone on metabolic parameters and quality of life during fasting for Ramadan are unknown. DESIGN, PATIENTS AND MEASUREMENTS: Patients with AI on twice-daily hydrocortisone, who had low or moderate risk and intended to fast, were recruited. Patients were converted to prednisolone 5 mg once daily taken at sahur (predawn) and Ramadan education given. Weight, sleep duration, biochemical parameters and quality of life measures (SF-36 questionnaire) were analysed at the end of Ramadan and compared against baseline. RESULTS: Twenty patients (13 men) were recruited, with a mean age of 59.9 ± 15.0 years. All patients were on hydrocortisone 15 mg daily (in divided doses) as pre-Ramadan glucocorticoid replacement. Half had type 2 diabetes with low IDF-DAR risk. Eighty-five percent of patients completed the full 29 days of fasting with no complications. There was a significant reduction in weight (-1.1 ± 1.6 kg, p = .005), with no significant change in blood pressure or sleep duration. There was a significant increase in urea (0.80 ± 1.1 mmol/L, p = .005) and haematocrit, (0.011 ± 0.019 L/L, p = .019) and decrease in serum sodium (-1.6 ± 3.0 mmol/L, p = .028), with no change in serum creatinine or liver function. Quality of life measures were preserved in all domains with significant improvement in role limitation due to physical health (15.3 ± 21.6, p = .005) and bodily pain (8.8 ± 16.3, p = .031). CONCLUSIONS: This study has demonstrated that converting patients with AI who are fasting for Ramadan from twice-daily hydrocortisone to prednisolone 5 mg daily at sahur was safe, with no major short-term adverse effects. Despite the higher equivalent glucocorticoid doses, patients experienced weight loss and no clinically significant change in blood pressure, sleep, biochemical parameters or quality of life. This study paves the way to trial even lower doses of prednisolone once daily in patients fasting for Ramadan with AI.

Artificial intelligence for automated detection and measurements of carpal instability signs on conventional radiographs.

OBJECTIVES: To develop and validate an artificial intelligence (AI) system for measuring and detecting signs of carpal instability on conventional radiographs. MATERIALS AND METHODS: Two case-control datasets of hand and wrist radiographs were retrospectively acquired at three hospitals (hospitals A, B, and C). Dataset 1 (2178 radiographs from 1993 patients, hospitals A and B, 2018-2019) was used for developing an AI system for measuring scapholunate (SL) joint distances, SL and capitolunate (CL) angles, and carpal arc interruptions. Dataset 2 (481 radiographs from 217 patients, hospital C, 2017-2021) was used for testing, and with a subsample (174 radiographs from 87 patients), an observer study was conducted to compare its performance to five clinicians. Evaluation metrics included mean absolute error (MAE), sensitivity, and specificity. RESULTS: Dataset 2 included 258 SL distances, 189 SL angles, 191 CL angles, and 217 carpal arc labels obtained from 217 patients (mean age, 51 years ± 23 [standard deviation]; 133 women). The MAE in measuring SL distances, SL angles, and CL angles was respectively 0.65 mm (95%CI: 0.59, 0.72), 7.9 degrees (95%CI: 7.0, 8.9), and 5.9 degrees (95%CI: 5.2, 6.6). The sensitivity and specificity for detecting arc interruptions were 83% (95%CI: 74, 91) and 64% (95%CI: 56, 71). The measurements were largely comparable to those of the clinicians, while arc interruption detections were more accurate than those of most clinicians. CONCLUSION: This study demonstrates that a newly developed automated AI system accurately measures and detects signs of carpal instability on conventional radiographs. CLINICAL RELEVANCE STATEMENT: This system has the potential to improve detections of carpal arc interruptions and could be a promising tool for supporting clinicians in detecting carpal instability.

Earlier diagnosis of peripheral neuropathy in primary care: A call to action.

Peripheral neuropathy (PN) often remains undiagnosed (~80%). Earlier diagnosis of PN may reduce morbidity and enable earlier risk factor reduction to limit disease progression. Diabetic peripheral neuropathy (DPN) is the most common PN and the 10 g monofilament is endorsed as an inexpensive and easily performed test for DPN. However, it only detects patients with advanced neuropathy at high risk of foot ulceration. There are many validated questionnaires to diagnose PN, but they can be time-consuming and have complex scoring systems. Primary care physicians (PCPs) have busy clinics and lack access to a readily available screening method to diagnose PN. They would prefer a short, simple, and accurate tool to screen for PN. Involving the patient in the screening process would not only reduce the time a physician requires to make a diagnosis but would also empower the patient. Following an expert meeting of diabetologists and neurologists from the Middle East, South East Asia and Latin America, a consensus was formulated to help improve the diagnosis of PN in primary care using a simple tool for patients to screen themselves for PN followed by a consultation with the physician to confirm the diagnosis.

Clinical care pathway to detect advanced liver disease in patients with type 2 diabetes through automated fibrosis score calculation and electronic reminder messages: a randomised controlled trial.

OBJECTIVE: We aimed to test the hypothesis that automated fibrosis score calculation and electronic reminder messages could increase the detection of advanced liver disease in patients with type 2 diabetes. DESIGN: In this pragmatic randomised controlled trial at five general medical or diabetes clinics in Hong Kong and Malaysia, we randomly assigned patients in a 1:1 ratio to the intervention group with Fibrosis-4 index and aspartate aminotransferase-to-platelet ratio index automatically calculated based on routine blood tests, followed by electronic reminder messages to alert clinicians of abnormal results, or the control group with usual care. The primary outcome was the proportion of patients with increased fibrosis scores who received appropriate care (referred for hepatology care or specific fibrosis assessment) within 1 year. RESULTS: Between May 2020 and Oct 2021, 1379 patients were screened, of whom 533 and 528 were assigned to the intervention and control groups, respectively. A total of 55 out of 165 (33.3%) patients with increased fibrosis scores in the intervention group received appropriate care, compared with 4 of 131 (3.1%) patients in the control group (difference 30.2% (95% CI 22.4% to 38%); p<0.001). Overall, 11 out of 533 (2.1%) patients in the intervention group and 1 out of 528 (0.2%) patients in the control group were confirmed to have advanced liver disease (difference 1.9% (95% CI 0.61% to 3.5%); p=0.006). CONCLUSION: Automated fibrosis score calculation and electronic reminders can increase referral of patients with type 2 diabetes and abnormal fibrosis scores at non-hepatology settings. TRIAL REGISTRATION NUMBER: NCT04241575.

Influence and implications of the renin-angiotensin-aldosterone system in obstructive sleep apnea: An updated systematic review and meta-analysis.

Obstructive sleep apnea is a chronic, sleep-related breathing disorder, which is an independent risk factor for cardiovascular disease. The renin-angiotensin-aldosterone system regulates salt and water homeostasis, blood pressure, and cardiovascular remodelling. Elevated aldosterone levels are associated with excess morbidity and mortality. We aimed to analyse the influence and implications of renin-angiotensin-aldosterone system derangement in individuals with and without obstructive sleep apnea. We pooled data from 20 relevant studies involving 2828 participants (1554 with obstructive sleep apnea, 1274 without obstructive sleep apnea). The study outcomes were the levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate. Patients with obstructive sleep apnea had higher levels of plasma renin activity (pooled wmd+ 0.25 [95% confidence interval 0.04-0.46], p = 0.0219), plasma aldosterone (pooled wmd+ 30.79 [95% confidence interval 1.05-60.53], p = 0.0424), angiotensin II (pooled wmd+ 5.19 [95% confidence interval 3.11-7.27], p < 0.001), systolic (pooled wmd+ 5.87 [95% confidence interval 1.42-10.32], p = 0.0098) and diastolic (pooled wmd+ 3.40 [95% confidence interval 0.86-5.94], p = 0.0086) blood pressure, and heart rate (pooled wmd+ 3.83 [95% confidence interval 1.57-6.01], p = 0.0009) compared with those without obstructive sleep apnea. The elevation remained significant (except for renin levels) when studies involving patients with resistant hypertension were removed. Sub-group analysis demonstrated that levels of angiotensin II were significantly higher only among the Asian population with obstructive sleep apnea compared with those without obstructive sleep apnea. Body mass index accounted for less than 10% of the between-study variance in elevation of the renin-angiotensin-aldosterone system parameters. Patients with obstructive sleep apnea have higher levels of renin-angiotensin-aldosterone system hormones, blood pressure and heart rate compared with those without obstructive sleep apnea, which remains significant even among patients without resistant hypertension.

Musculoskeletal radiologist-level performance by using deep learning for detection of scaphoid fractures on conventional multi-view radiographs of hand and wrist.

OBJECTIVES: To assess how an artificial intelligence (AI) algorithm performs against five experienced musculoskeletal radiologists in diagnosing scaphoid fractures and whether it aids their diagnosis on conventional multi-view radiographs. METHODS: Four datasets of conventional hand, wrist, and scaphoid radiographs were retrospectively acquired at two hospitals (hospitals A and B). Dataset 1 (12,990 radiographs from 3353 patients, hospital A) and dataset 2 (1117 radiographs from 394 patients, hospital B) were used for training and testing a scaphoid localization and laterality classification component. Dataset 3 (4316 radiographs from 840 patients, hospital A) and dataset 4 (688 radiographs from 209 patients, hospital B) were used for training and testing the fracture detector. The algorithm was compared with the radiologists in an observer study. Evaluation metrics included sensitivity, specificity, positive predictive value (PPV), area under the characteristic operating curve (AUC), Cohen's kappa coefficient (κ), fracture localization precision, and reading time. RESULTS: The algorithm detected scaphoid fractures with a sensitivity of 72%, specificity of 93%, PPV of 81%, and AUC of 0.88. The AUC of the algorithm did not differ from each radiologist (0.87 [radiologists' mean], p ≥ .05). AI assistance improved five out of ten pairs of inter-observer Cohen's κ agreements (p < .05) and reduced reading time in four radiologists (p < .001), but did not improve other metrics in the majority of radiologists (p ≥ .05). CONCLUSIONS: The AI algorithm detects scaphoid fractures on conventional multi-view radiographs at the level of five experienced musculoskeletal radiologists and could significantly shorten their reading time. KEY POINTS: • An artificial intelligence algorithm automatically detects scaphoid fractures on conventional multi-view radiographs at the same level of five experienced musculoskeletal radiologists. • There is preliminary evidence that automated scaphoid fracture detection can significantly shorten the reading time of musculoskeletal radiologists.

Real-world usage of sulphonylureas in Asian patients with type 2 diabetes using the Joint Asia Diabetes Evaluation (JADE) register.

AIMS: To explore the patterns of use of oral glucose-lowering drugs (OGLDs) in Asian patients with type 2 diabetes (T2D), focusing on sulphonylureas (SUs), and to describe patient profiles according to treatment regimen. METHODS: We conducted a cross-sectional analysis of data from adults with T2D from 11 Asian countries/regions with structured assessment enrolled in the prospective Joint Asia Diabetes Evaluation (JADE) register between November 2007 and December 2019. Patients receiving insulin and/or injectable glucagon-like peptide-1 receptor agonists were excluded. RESULTS: Amongst 62 512 patients (mean ± standard deviation age: 57.3 ± 11.8 years; 53.6% men), 54 783 (87.6%) were treated with OGLDs at enrolment. Most received one (37.5%) or two (44.2%) OGLDs. In the entire cohort, 59.4% of treated patients received SU-based therapy with variations amongst countries/regions. Overall, 79.5% of SU regimens were based on SUs plus metformin, and 22.1% on SUs plus dipeptidyl peptidase-4 inhibitors. Among SU users, gliclazide was most commonly prescribed (46.7%), followed by glimepiride (40.0%) and glibenclamide (8.1%). More gliclazide users entered the cohort with glycated haemoglobin levels <53 mmol/mol (7%) than non-gliclazide SU users (odds ratio [OR] 1.09, 95% CI 1.02-1.17), with less frequent self-reported hypoglycaemia in the 3 months before registration (OR 0.81, 95% CI 0.72-0.92; adjusted for sociodemographic factors, cardiometabolic risk factors, complications, use of other OGLDs, country/region and year of registration). CONCLUSION: In Asia, SUs are a popular OGLD class, often combined with metformin. Good glycaemic control and safety profiles associated with the use of SUs, including gliclazide, support their position as a key treatment option in patients with T2D.

Direct arene trifluoromethylation enabled by promiscuous activity of fungal laccase.

Laccase from Trametes versicolor was found to oxidize non-phenolic arenes and enable the trifluoromethylation of arenes in the presence of in situ generated CF3 radicals at a catalyst loading as low as 0.0034%. The biocatalytic trifluoromethylation proceeded under mild conditions and could increase the yield by up to 12 fold, compared to the control.

Surface-enhanced Raman scattering (SERS) by gold nanoparticle characterizes dermal thickening by collagen in bleomycin-treated skin ex vivo.

PURPOSE: Current skin imaging modalities, including optical, electron, and confocal microscopy, mostly require tissue fixations that could damage proteins and biological molecules. Live tissue or cell imaging such as ultrasonography and optical coherent microscope may not adequately measure the dynamic spectroscopical changes. Raman spectroscopy has been adopted for skin imaging in vivo, mostly for skin cancer imaging. However, whether the epidermal and dermal thickening in skin could be measured and distinguished by conventional Ramen spectroscopy or the surface-enhanced Raman scattering (SERS), a rapid and label-free method for noninvasive measurement remains unknown. METHODS: Human skin sections from patients of atopic dermatitis and keloid, which represent epidermal and dermal thickening, respectively, were measured by conventional Ramen spectroscopy. In mice, skin sections from imiquimod (IMQ)- and bleomycin (BLE)-treated mice, which reflect the epidermal and dermal thickening, respectively, were measured by SERS, that incorporates gold nanoparticles to generate surface plasma and enhance Raman signals. RESULTS: Conventional Ramen spectroscopy failed to consistently show the Raman shift in human samples among the different groups. SERS successfully revealed a prominent peak around 1300 cm-1 in the IMQ-treated skin; and two significant peaks around 1100 and 1300 cm-1 in BLE-treated group. Further quantitative analysis showed 1100 cm-1 peak was significantly accentuated in the BLE-treated skin than that in control skin. SERS identified in vitro a similar 1100 cm-1 peak in solutions of collagen, the major dermal biological molecules. CONCLUSION: SERS distinguishes the epidermal or dermal thickening in mouse skin with rapid and label-free measures. A prominent 1100 cm-1 SERS peak in the BLE-treated skin may result from collagen. SERS might help precision diagnosis in the future.

Practical considerations for the use of SGLT-2 inhibitors in the Asia-Pacific countries-An expert consensus statement.

Recent clinical studies have demonstrated the effectiveness of SGLT-2 inhibitors in reducing the risks of cardiovascular and renal events in both patients with and without type 2 diabetes mellitus. Consequently, many international guidelines have begun advocating for the use of SGLT-2 inhibitors for the purpose of organ protection rather than as simply a glucose-lowering agent. However, despite the consistent clinical benefits and available strong guideline recommendations, the utilization of SGLT-2 inhibitors have been unexpectedly low in many countries, a trend which is much more noticeable in low resource settings. Unfamiliarity with the recent focus in their organ protective role and clinical indications; concerns with potential adverse effects of SGLT-2 inhibitors, including acute kidney injury, genitourinary infections, euglycemic ketoacidosis; and their safety profile in elderly populations have been identified as deterring factors to their more widespread use. This review serves as a practical guide to clinicians managing patients who could benefit from SGLT-2 inhibitors treatment and instill greater confidence in the initiation of these drugs, with the aim of optimizing their utilization rates in high-risk populations.

Improving population-level refractive error monitoring via mixture distributions.

INTRODUCTION: Sampling and describing the distribution of refractive error in populations is critical to understanding eye care needs, refractive differences between groups and factors affecting refractive development. We investigated the ability of mixture models to describe refractive error distributions. METHODS: We used key informants to identify raw refractive error datasets and a systematic search strategy to identify published binned datasets of community-representative refractive error. Mixture models combine various component distributions via weighting to describe an observed distribution. We modelled raw refractive error data with a single-Gaussian (normal) distribution, mixtures of two to six Gaussian distributions and an additive model of an exponential and Gaussian (ex-Gaussian) distribution. We tested the relative fitting accuracy of each method via Bayesian Information Criterion (BIC) and then compared the ability of selected models to predict the observed prevalence of refractive error across a range of cut-points for both the raw and binned refractive data. RESULTS: We obtained large raw refractive error datasets from the United States and Korea. The ability of our models to fit the data improved significantly from a single-Gaussian to a two-Gaussian-component additive model and then remained stable with ≥3-Gaussian-component mixture models. Means and standard deviations for BIC relative to 1 for the single-Gaussian model, where lower is better, were 0.89 ± 0.05, 0.88 ± 0.06, 0.89 ± 0.06, 0.89 ± 0.06 and 0.90 ± 0.06 for two-, three-, four-, five- and six-Gaussian-component models, respectively, tested across US and Korean raw data grouped by age decade. Means and standard deviations for the difference between observed and model-based estimates of refractive error prevalence across a range of cut-points for the raw data were -3.0% ± 6.3, 0.5% ± 1.9, 0.6% ± 1.5 and -1.8% ± 4.0 for one-, two- and three-Gaussian-component and ex-Gaussian models, respectively. CONCLUSIONS: Mixture models appear able to describe the population distribution of refractive error accurately, offering significant advantages over commonly quoted simple summary statistics such as mean, standard deviation and prevalence.

Access to school-based eye health programs in Central Region, Malawi: a qualitative case study.

Vision impairment among children is associated with lower levels of educational attainment. School-based eye health programs have the potential to provide high-quality and cost-effective services that assist in the prevention of blindness and uncorrected vision impairment, particularly in low-resources settings. The aim of this study was to identify key factors that inhibit or facilitate the provision of school-based eye health programs, including referral to eye care services, for Malawian children in the Central Region. In-depth interviews (n = 10) and focus groups (n = 5) with children, parents, school staff, eye care practitioners, government and NGO workers (total participants n = 44) in rural and urban contexts within central region, Malawi, were conducted. Taking a rights-based approach, we used the AAAQ (availability, accessibility, acceptability, quality) framework to identify barriers and enablers to school eye health programs. Complex factors shape access to school-based eye health programs. While intersectoral collaboration between ministries was present, infrastructure and resourcing restricted the delivery of school eye health programs. School staff were supportive of being trained as vision screeners. Parents voiced geographic access to follow up eye care, and spectacle cost as a barrier; and children revealed experiences of stigma related to spectacle as barriers to uptake. School-based eye care may be facilitated through teachers, community informants and health workers through; the provision of school vision screening; increased awareness of the impact of vision impairment on education and future employment; and through educational approaches that seek to decrease stigma and misconceptions associated with wearing spectacles.

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

BACKGROUND: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. METHODS: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG). RESULTS: Among 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8-48.0) vs. 52.5 (52.4-52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5-44.8)], followed by affected single parent [47.7 (47.6-47.8)] and affected siblings only [51.5 (51.3-51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1-48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8-50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050-0.001). CONCLUSIONS: In Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management  was associated with better control of  cardiometabolic risk factors especially in those with FamH.

Predicting vasovagal reactions to a virtual blood donation using facial image analysis.

BACKGROUND: People with needle fear experience not only anxiety and stress but also vasovagal reactions (VVR), including nausea, dizziness, sweating, pallor changes, or even fainting. However, the mechanism behind needle fear and the VVR response are not yet well understood. The aim of our study was to explore whether fluctuations in facial temperature in several facial regions are related to the level of experienced vasovagal reactions, in a simulated blood donation. STUDY DESIGN AND METHODS: We recruited 45 students at Tilburg University and filmed them throughout a virtual blood donation procedure using an Infrared Thermal Imaging (ITI) camera. Participants reported their fear of needles and level of experienced vasovagal reactions. ITI data pre-processing was completed on each video frame by detecting facial landmarks and image alignment before extracting the mean temperature from the six regions of interest. RESULTS: Temperatures of the chin and left and right cheek areas increased during the virtual blood donation. Mixed-effects linear regression showed a significant association between self-reported vasovagal reactions and temperature fluctuations in the area below the nose. DISCUSSION: Our results suggest that the area below the nose may be an interesting target for measuring vasovagal reactions using video imaging techniques. This is the first in a line of studies, which assess whether it is possible to automatically detect levels of fear and vasovagal reactions using facial imaging, from which the development of e-health solutions and interventions can benefit.

Surgical Management of Patients with Snakebite-Related Musculoskeletal Complication-A Single Institution Experience in Cambodia.

BACKGROUND: Snakebite-related injury is a serious public health issue. In Cambodia, it is estimated that up to 21,500 cases of envenoming occurs from snakebites annually. Musculoskeletal disability is a major long-term complication associated with the injury. In this study, we aim to describe surgical management and rehabilitation in snakebite-related musculoskeletal injuries at Children's Surgical Centre, Phnom Penh, Cambodia. METHODS: We conducted a retrospective case series analysis of patients with snakebite-related injury who were treated between January 1, 2002 and December 31, 2018. Surgical patients were divided into the early and late presenting groups (= < one year vs. > one year, respectively) based on their time interval from snake bite to time of presentation. RESULTS: There were 88 patients who presented with snakebite-related musculoskeletal injury during the cohort study period. Majority of them were male (n = 62, 71%) and had a median age of 24 years old (IQR 17-44). The injuries were all in the upper and lower limbs though lower limb injury was more common in female patients (81% vs. 48%, Fisher's test p = 0.005). The median time interval from snakebite to time of treatment was 3 years (IQR 3 months-11 years). In this study, 65 patients received surgical interventions. An ulcerated wound was the most common symptom among the early presenting group (78% vs. 24%), while scar contracture was most common among the late group (76% vs. 22%) (Fisher's test p < 0.0001). For management, surgical debridement was the most common primary intervention for the early group (52% vs. 19%), and contracture release was the most common for patients in the late group (62% vs. 15%) (Fisher's test p = 0.0004). Overall, the postoperative complication rate was highest in the late presenting group (34% vs. 3%, Fisher's test p = 0.005). CONCLUSION: More than half of the patients presented with musculoskeletal injury require surgical correction. Our study demonstrated that scar contracture is the most common complaint among the late presenting group and is associated with high postoperative complication rate.

An in vitro study: prebiotic effects of edible palm hearts in batch human fecal fermentation system.

BACKGROUND: Edible palm hearts (EPH), known as palmito, chonta or swamp cabbage in America or umbut in Malaysia, is a type of vegetable harvested from palm tree species. EPH is firm and smooth and described as having a flavor resembling artichoke. It has underlying prebiotic potential that selectively stimulates the growth and activity of beneficial colonic microbiota, thus enhancing the host's health. This study is the first to present results of EPH from local species such as oil palm (Elaeis guineensis), sago palm (Metroxylon sagu) and coconut (Cocos nucifera) using in vitro colonic fermentation with human fecal slurry. Samples obtained at 0, 6, 12 and 24 h were evaluated by bacterial enumeration using fluorescent in situ hybridization (FISH), and short-chain fatty acids (SCFA) were analyzed by high-performance liquid chromatography (HPLC). RESULTS: All EPH samples revealed induction effects towards Bifidobacterium spp., Lactobacillus-Enterococcus and Bacteroidaceae/Prevotellaceae populations similar to those in inulin fermentation. A significant decrease (P ≤ 0.05) in pathogenic Clostridium histolyticum group was observed in the response of raw sago palm hearts. In general, all samples stimulate the production of SCFA. Particularly in the colonic fermentation of sago palm heart, acetate and propionate revealed the highest concentrations of 286.18 and 284.83 mmol L-1 in raw and cooked form, respectively. CONCLUSION: This study concluded that edible palm hearts can be a potential prebiotic ingredient that promotes human gastrointestinal health, as well as discovering a new direction towards an alternative source of functional foods. © 2022 Society of Chemical Industry.

[Reflections on the Prospective Professional Competency of Taiwan Public Health Nurses].

Societal ageing, the rising prevalence of chronic diseases, and the COVID-19 pandemic have changed the global healthcare environment dramatically. These challenges have significantly burdened community medical and healthcare systems and complicated the work of public health nursing. As an important care provider on the frontlines of primary care, public health nurses (PHNs) must keep up with the current state of the medical environment and statistical data interpretation, scientific data translation, community resource sharing, and telehealth applications. These demands have greatly impacted the traditional routines and existing professional core competencies of PHNs. Discussions among 12 Taiwanese public healthcare experts and the definition of public health nursing capacity from World Health Organization were considered in this review. In addition to reflecting on social changes and the professional development of public health nursing, eight prospective recommendations were provided in this review to enhance the professional competence of PHNs and better prepare them for future changes in the health environment and primary healthcare. The suggestions provide a reference for updating the position statement of PHNs.