Picture communication symbols and voice symbols: iconicity and preference among healthy older adults in Taiwan.

Purpose.Unaided (e.g., speech and gestures) and aided (e.g., symbol corpuses) communication modes facilitate older adults' expression and comprehension. Adults aged 65 years and above constituted 18.27% of Taiwan's total population in 2023; hence, prioritizing high-quality healthcare for older adults becomes critical. Commercial symbol corpuses, such as Picture Communication Symbols (PCS) and Voice Symbols (VS), play a vital role in aiding older adults with expression and comprehension in Taiwan. Previous studies on iconicity and preference of symbol corpuses have primarily been conducted in Western and South Asian cultural communities. However, these findings may not apply to all Asian communities. Hence, studies investigating these aspects in specific communities are needed. Through quantitative nonexperimental observations, we explored the iconicity of and preference for PCS and VS among 30 healthy older adults in Taiwan.Materials and Methods.A total of 12 practice words and test words each, familiar to the participants and socially and culturally validated, were selected for the developed VS-PCS iconicity and preference measurement. Verbal choices were made to select one line drawing in both measurements.Results & Conclusions.The findings revealed that VS is significantly more transparent and preferred than PCS. Accounting for the iconicity of and preferences for symbol corpuses is pivotal for symbol selection.

Awareness about the learnability of the symbol corpuses being influenced by iconicity and preference, in addition to considering the needs and capabilities of older adults, within Taiwanese cultural communities is raised.Perceptions of iconicity cannot be generalized from one cultural community to another community, but transparency in symbol corpuses leads to higher preferences in similar cultural communities.Healthy older adults in Taiwan believed VS is more transparent and preferred.

Exploring the reduction in aquaporin-4 and increased expression of ciliary neurotrophic factor with the frontal-striatal gliosis induced by chronic high-fat dietary stress.

High-fat diet (HFD)-induced obesity induces peripheral inflammation and hypothalamic pathogenesis linking the activation of astrocytes and microglia. Clinical evidence indicates a positive correlation between obesity and psychiatric disorders, such as depression. The connectivity of the frontal-striatal (FS) circuit, involving the caudate putamen (CPu) and anterior cingulate cortex (ACC) within the prefrontal cortex (PFC), is known for its role in stress-induced depression. Thus, there is a need for a thorough investigation into whether chronic obesity-induced gliosis, characterized by the activation of astrocytes and microglia, in these brain regions of individuals with chronic obesity. The results revealed increased S100ß+ astrocytes and Iba1+ microglia in the CPu and ACC of male obese mice, along with immune cell accumulation in meningeal lymphatic drainage. Activated GFAP+ astrocytes and Iba1+ microglia were observed in the corpus callosum of obese mice. Gliosis in the CPu and ACC was linked to elevated cleaved caspase-3 levels, indicating potential neural cell death by chronic HFD feeding. There was a loss of myelin and adenomatous polyposis coli (APC)+ oligodendrocytes (OLs) in the corpus callosum, an area known to be linked with injury to the CPu. Additionally, reduced levels of aquaporin-4 (AQP4), a protein associated within the glymphatic systems, were noted in the CPu and ACC, while ciliary neurotrophic factor (CNTF) gene expression was upregulated in these brain regions of obese mice. The in vitro study revealed that high-dose CNTF causing a trend of reduced astrocytic AQP4 expression, but it significantly impaired OL maturation. This pathological evidence highlights that prolonged HFD consumption induces persistent FS gliosis and demyelination in the corpus callosum. An elevated level of CNTF appears to act as a potential regulator, leading to AQP4 downregulation in the FS areas and demyelination in the corpus callosum. This cascade of events might contribute to neural cell damage within these regions and disrupt the glymphatic flow.

Prenatal and early childhood infections requiring hospitalization and risk of neurodevelopmental disorders in offspring: a population-based birth cohort study in Taiwan.

In utero and early childhood infections have been associated with an increased risk of neurodevelopmental disorders; however, the observed associations may be confounded by familial predispositions. This study examined the neurodevelopmental disorders attributable to maternal infections during pregnancy and early childhood infections during the first year of life, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), tic disorders, and mental retardation (MR). We performed population and sibling comparison analyses to account for unmeasured familial confounding factors. We conducted a register-based cohort study with 2,885,662 individuals (comprising 1,864,660 full siblings) born in Taiwan between 2001 and 2018 and followed up until 2021. We employed Cox regression analysis to assess the association between in utero and early childhood infections requiring hospitalization and the subsequent risk of neurodevelopmental disorders. In the population analyses, an offspring exposed to maternal infection had an increased risk for ASD (hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.13-1.26), ADHD (HR = 1.14, 95% CI: 1.11-1.18), and MR (HR = 1.21, 95% CI: 1.13-1.30). These associations attenuated toward null in the sibling analyses. Individuals exposed to early childhood infection had an increased risk for ASD (HR = 1.13, 95% CI: 1.10-1.16), ADHD (HR = 1.16, 95% CI: 1.15-1.18), tic disorders (HR = 1.12, 95% CI: 1.09-1.15), and MR (HR = 1.64, 95% CI: 1.60-1.69) in the population analyses; these associations were also significant for ASD (HR = 1.14, 95% CI: 1.07-1.21) and MR (HR = 1.52, 95% CI: 1.44-1.62) in the sibling analyses. The association between maternal infection during pregnancy and offspring neurodevelopmental risk is largely due to familial confounding factors. Conversely, infection in early childhood may be attributable to it being a sensitive period and may play a role in the subsequent risk of ASD and MR.

A population-based study of familial coaggregation and shared genetic etiology of psychiatric and gastrointestinal disorders.

BACKGROUND: It has been proposed that having a psychiatric disorder could increase the risk of developing a gastrointestinal disorder, and vice versa. The role of familial coaggregation and shared genetic loading between psychiatric and gastrointestinal disorders remains unclear. METHODS: This study used the Taiwan National Health Insurance Research Database; 4,504,612 individuals born 1970-1999 with parental information, 51,664 same-sex twins, and 3,322,959 persons with full-sibling(s) were enrolled. Genotyping was available for 106,796 unrelated participants from the Taiwan Biobank. A logistic regression model was used to examine the associations of individual history, affected relatives, and polygenic risk scores (PRS) for schizophrenia (SCZ), bipolar disorder (BPD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD), with the risk of peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD), and vice versa. RESULTS: Here we show that parental psychiatric disorders are associated with gastrointestinal disorders. Full-siblings of psychiatric cases have an increased risk of gastrointestinal disorders except for SCZ/BPD and IBD; the magnitude of coaggregation is higher in same-sex twins than in full-siblings. The results of bidirectional analyses mostly remain unchanged. PRS for SCZ, MDD, and OCD are associated with IBS, PUD/GERD/IBS/IBD, and PUD/GERD/IBS, respectively. PRS for PUD, GERD, IBS, and IBD are associated with MDD, BPD/MDD, SCZ/BPD/MDD, and BPD, respectively. CONCLUSIONS: There is familial coaggregation and shared genetic etiology between psychiatric and gastrointestinal comorbidity. Individuals with psychiatric disorder-affected relatives or with higher genetic risk for psychiatric disorders should be monitored for gastrointestinal disorders, and vice versa.

It has been proposed that people with psychiatric disorders such as depression could have an increased chance of developing gastrointestinal disorders such as irritable bowel syndrome. We looked at whether this was the case in a large number of people from Taiwan. We found that people with a psychiatric disorder, or with relatives having a psychiatric disorder, were more likely to have gastrointestinal disorders, and vice versa. These findings suggest that people who have psychiatric disorders or have psychiatric disorder-affected relatives should be monitored for gastrointestinal disorders, and vice versa, to enable them to benefit from all the treatments they might need to improve their health.

Investigating medication adherence among Taiwanese patient with hypertension, hyperlipidemia, and diabetes: A pilot study using the Chinese version of a Two-Part Medication Nonadherence Scale and the NHI MediCloud system.

BACKGROUND: This pilot study aimed to investigate medication nonadherence among Taiwanese patients with diabetes, hypertension, and hyperlipidemia using the Chinese version of the Two-Part Medication Nonadherence Scale (C-TPMNS) and the National Health Insurance (NHI) Medicloud system. The study revealed insights into the factors contributing to nonadherence and the implications for improving patient adherence to medications for chronic conditions. However, the small sample size limits the generalizability of the findings. Additionally, the study identified the need for further research with larger and more diverse samples to validate the preliminary findings. METHODS: The study conducted surveys individuals in central Taiwan who received three-high medications and those who returned expired medications from chain pharmacies. A structured questionnaire including the C-TPMNS was administered, and additional data on medical history and HbA1c, LDL, and blood pressure levels were collected from the NHI Medicloud system. Data analysis was performed using multiple ordered logistic regression and Wald test methods. Setting interpretation cutoff point to determine medication nonadherence. RESULTS: The study found that 25.8% of participants were non-adherent to prescribed medications. Non-adherent individuals had significantly higher systolic blood pressure (SBP ≥ 140 mmHg) than adherent participants. Non-adherence was also associated with factors such as lower education, single status, living alone, abnormal glucose postprandial concentration, and triglyceride levels. The C-TPMNS demonstrated good reliability (Cronbach's alpha = 0.816) and validity (area under the ROC curve = 0.72). CONCLUSION: The study highlighted the complexity of medication nonadherence with diverse determinants and emphasized the importance of tailored interventions. The findings underscored the need for region-specific research to comprehensively address medication nonadherence, especially focusing on adherence to medications for hypertension, hyperlipidemia, and diabetes. The study also identified the need for larger, more diverse studies to validate and expand upon the initial findings and emphasized the importance of pharmacist interventions and patient empowerment in managing chronic conditions and improving overall health outcomes.

Cancer and pulmonary fibrosis risks in patients with dermatomyositis and polymyositis: A retrospective cohort study.

Background: This study assessed the risks of developing pulmonary fibrosis and cancer and whether patients are at risk of acquiring subsequent cancer after pulmonary fibrosis development. Methods: From the claims data of 22 million insured people, we identified 1461 patients with dermatomyositis (DM) and 1058 with polymyositis (PM) diagnosed in 1996-2016 and 50,380 comparison individuals without pulmonary fibrosis and cancer at baseline, matched by sex and age. Incident pulmonary fibrosis and cancer in each cohort were assessed at the end of 2016. We further followed up individuals with and without pulmonary fibrosis to assess the subsequent development of cancer. Results: The cancer incidence was 2.6-fold higher in the DM/PM groups combined than in comparisons (135.3 vs. 52.1 per 10,000 person-years), with an adjusted hazard ratio (aHR) of 3.11 (95 % confidence interval [CI] = 2.71-3.58). The incidence was lower in patients with PM than in those with DM (81.3 vs. 176 per 10,000 person-years), with an aHR of 0.39 (95 % CI = 0.29-0.54). The likelihood of developing pulmonary fibrosis was 92 times higher in the PM/DM groups combined than in comparisons (37.9 vs. 0.41 per 10,000 person-years; aHR 84.0 (95 % CI = 49.5-143). The incidence was 1.44-fold higher in patients with PM than in those with DM (46.1 vs. 32.0 per 10,000 person-years), but the difference was not significant. Further analysis showed that in 2452 patients with myositis without pulmonary fibrosis, 234 (9.5 %) had cancer, whereas no cancer was identified in 67 patients with pulmonary fibrosis (p = 0.019). Conclusion: Patients with PM and DM are at great risk of developing cancer and pulmonary fibrosis. Patients who develop pulmonary fibrosis might be at low risk of developing cancer. The complexity of cancer risk interplaying between patients with and without pulmonary fibrosis has clinical relevance and deserves further investigation. Patients who are free of pulmonary fibrosis deserve close monitoring to reduce subsequent cancer risk.

Meteorological factors and risk of ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage: A time-stratified case-crossover study.

BACKGROUND: Stroke risks associated with rapid climate change remain controversial due to a paucity of evidence. AIMS: To examine the risk of subarachnoid hemorrhage (SAH), intracranial hemorrhage (ICH), and ischemic stroke (IS) associated with meteorological parameters. METHODS: In this time-stratified case-crossover study, adult patients hospitalized for their first stroke between 2011 and 2020 from the insurance claims data in Taiwan were identified. The hospitalization day was designated as the case period, and three or four control periods were matched by the same day of the week and month of each case period. Daily mean and 24-h variations in ambient temperature, relative humidity, air pressure, and apparent temperature were measured. Conditional logistic regression models were applied to assess the risk of stroke associated with exposure to weather variables, using the third quintile as a reference, controlling for air pollutant levels. RESULTS: There were 7161 patients with SAH, 40,426 patients with ICH, and 107,550 patients with IS. There was an inverse linear relationship between mean daily temperature and apparent temperature with ICH. Elevated mean daily atmospheric pressure was associated with an increased risk of ICH. A greater decrease in apparent temperature over a 24-h period was associated with increased risk of ICH but decreased risk of IS (odds ratio (95% confidence interval) for the first vs. third quintile of changes in apparent temperature, 1.141 (1.053-1.237) and 0.946 (0.899-0.996), respectively). CONCLUSIONS: There were considerable differences in short-term associations between meteorological parameters and three main pathological types of strokes. DATA ACCESS STATEMENT: The authors have no permission to share the data.

Risk of chronic kidney disease in patients with a hyperglycemic crisis as the initial presentation of type 2 diabetes.

Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan's insurance claims from adults newly diagnosed with type 2 diabetes during 2006-2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018's end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91-2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59-1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33-2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29-2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

Central Channelopathies in Obesity.

As obesity has raised heightening awareness, researchers have attempted to identify potential targets that can be treated for therapeutic intervention. Focusing on the central nervous system (CNS), the key organ in maintaining energy balance, a plethora of ion channels that are expressed in the CNS have been inspected and determined through manipulation in different hypothalamic neural subpopulations for their roles in fine-tuning neuronal activity on energy state alterations, possibly acting as metabolic sensors. However, a remaining gap persists between human clinical investigations and mouse studies. Despite having delineated the pathways and mechanisms of how the mouse study-identified ion channels modulate energy homeostasis, only a few targets overlap with the obesity-related risk genes extracted from human genome-wide association studies. Here, we present the most recently discovered CNS-specific metabolism-correlated ion channels using reverse and forward genetics approaches in mice and humans, respectively, in the hope of illuminating the prospects for future therapeutic development.

Widowhood and mortality risk in Taiwan: a population-based matched cohort study.

BACKGROUND: Studying the causes of death among deceased spouses and surviving partners may provide insights into the underlying mechanisms of the association between widowhood and mortality. This study investigated the mortality risk of widowhood in Taiwan, examined the association of the cause of death between widowed individuals and their deceased spouses and explored potential modifying effects by age, gender and duration after widowhood. METHODS: This matched cohort study utilized Taiwan's National Health Insurance claims database and National Death Registry. In total, 204 010 widowed men and 596 136 widowed women were identified with a mean follow-up period of 6.9 and 7.9 years, respectively, and 816 040 comparison men and 2 384 544 comparison women were selected. RESULTS: Widowhood was associated with an increased mortality risk, with widowed men having a 1.32 increased risk and widowed women having a 1.27 increased risk. Age at spousal death and duration modified the associations after widowhood. The widowed individuals are more likely to die by the same cause as the deceased spouse if they died by suicide, accident, endocrine, gastrointestinal disorders or infection. CONCLUSIONS: The study suggests that healthcare policies and interventions should be developed to improve widowed individuals' health and overall welfare.

A Comparative Phenotypic and Genomic Analysis of Methicillin-Resistant Staphylococcus aureus ST45 Isolates From Cellulitis and Osteomyelitis in Taiwan.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) sequence type (ST) 45 is a globally disseminated MRSA lineage. Herein, we investigated whether MRSA ST45 isolates from cellulitis and from osteomyelitis display distinctive phenotypic and genomic characteristics. METHODS: A total of 15 MRSA ST45 isolates from cellulitis (CL-MRSA; n = 6) or osteomyelitis (OM-MRSA; n = 9) were collected in a Taiwan hospital. These MRSA ST45 isolates were characterized for their antimicrobial susceptibility, biofilm-forming ability, cellular infectivity in vitro, and pathogenicity in vivo. Four CL-MRSA and 6 OM-MRSA ST45 isolates were selected for whole-genome sequencing (WGS). RESULTS: Antibiotic resistance tests showed that all OM-MRSA ST45 strains, but not CL-MRSA ST45 strains, were resistant to ciprofloxacin, levofloxacin, gentamicin, and doxycycline. Compared to the CL-MRSA ST45 isolates, the OM-MRSA ST45 isolates had stronger biofilm-forming ability and cellular infectivity and caused more severe disease in mice. WGS analysis revealed that these OM-MRSA ST45 isolates carry multiple common mutations or polymorphisms in genes associated with antibiotic resistance and virulence. Moreover, the transposable elements IS256 and IS257R2 were found only in the OM-MRSA ST45 isolates. CONCLUSIONS: The emergence and spread of the highly pathogenic and multidrug-resistant ST45 MRSAs identified from osteomyelitis may pose a serious threat on public health.

Familial factors rather than paternal age contribute to the aetiology of epilepsy.

BACKGROUND: Whether paternal age associated with offspring's epilepsy risk is a cause of de novo mutation as men age, or just an association due to confounding factors, is still unclear. METHODS: We performed a population-based, multi-generation and sibling comparison study in Taiwan, which included 2 751 232 singletons born in 2001-17 who were followed until 2020. Of these, 819 371/826 087 with information on paternal/maternal grandparents were selected for multi-generation analyses and 1 748 382 with sibling(s) were selected for sibling comparison. Cox proportional hazard regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the total cohort, there was an increased risk of epilepsy in individuals with advanced paternal age, e.g. the HR for paternal age ≥50 was1.36 (95% CI: 1.15-1.61) compared with paternal age 25-29, and fathers older than mothers, e.g. the HR for parental age difference ≥15 years was 1.29 (95% CI: 1.16-1.43). When accounting for parental age difference, the association between paternal age and epilepsy in offspring was attenuated (HR for paternal age ≥50 was 1.11, 95% CI: 0.93-1.34). Multi-generation analyses did not support the association of advanced grand-paternal age at childbirth of the parent with offspring's risk of epilepsy. Sibling comparison analyses did not support the association of older paternal age with increased risk of epilepsy (HR was 0.96 for per year increase in paternal age, 95% CI: 0.96-0.97). CONCLUSIONS: These results do not support the hypothesis that advanced paternal age is associated with epilepsy in offspring. Instead, familial factors may explain the observed paternal age association with the offspring's risk of epilepsy.

An absence of imperfections: A proposed framework for defining, assessing, and achieving skin glow.

BACKGROUND: Skin glow is a subcomponent of skin quality. It has become entrenched in the cosmeceuticals and aesthetics lexicons as a synonym for health and youth, but is not well-defined as a scientific metric. AIMS: To examine the concept of skin glow and determine if it is an objective concept that can be defined and quantified. METHODS: Literature review was used to develop a survey on current concepts relating to skin quality. The survey results were analyzed descriptively and presented to a focus group comprising five dermatologists and four aesthetic physicians. This group then discussed the concept of skin glow, how to define it and what metrics could be used to assess it. RESULTS: Surveyed practitioners (n = 38) ranked skin quality as the fourth most important factor related to a person's overall aesthetic first impression. Almost all (95%) respondents reported routinely assessing skin quality, citing serial photography (83%), and visual inspection (67%) as the main means of achieving this. The focus group defined skin glow as even reflectance from an unaffected papillary and reticular dermal collagen layer, which is created only when skin does not exhibit any characteristics that detract from this even reflectance. Due to its complexity, the focus group proposed a hierarchal framework for assessment, encompassing patient self-rating, practitioner severity rating, and supplemental use of validated measurement devices. CONCLUSIONS: Skin glow can be defined and quantified. More work is warranted to develop a practical skin glow assessment tool suitable for use in the clinic setting.

Dose of selective serotonin reuptake inhibitors and risk of upper gastrointestinal bleeding in older adults.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been associated with an increased risk of upper gastrointestinal bleeding (UGIB) in older patients but little is known about the risk associated with individual SSRI drugs and doses. AIMS: To quantify the risk of UGIB in relation to individual SSRI use in older adults. METHODS: We conducted a nested case-control study within a cohort of 9565 patients aged ⩾65 years prescribed SSRIs from 2000 to 2013 using claims data of universal health insurance in Taiwan. Incident cases of UGIB during the follow-up period were identified and matched with three control subjects. Conditional logistic regression was used to estimate the odds ratio (OR) of UGIB associated with individual SSRI use and cumulative dose. RESULTS: UGIB risk increased with the increasing cumulative doses of SSRIs (adjusted OR: 1.28, 95% confidence interval (CI): 1.02-1.62 for the highest vs. the lowest tertile). Compared with users of other SSRIs, fluoxetine users were at an increased risk of UGIB (adjusted OR: 1.25, 95% CI: 1.03-1.50) with a dose-response manner, whereas paroxetine users had 29% decreased odds (95% CI: 0.56-0.91). The increased risk was only observed among current fluoxetine users. CONCLUSIONS: Fluoxetine therapy was associated with an increased risk of UGIB in a dose-response manner among older adults.

Obesity indices and the risk of total and cardiovascular mortality among people with diabetes: a long-term follow-up study in Taiwan.

BACKGROUND: The association between obesity indicators and mortality in individuals with diabetes remains unclear, and data on cardiovascular mortality are scarce. Therefore, we investigated the associations between the five adiposity indices and both all-cause and cardiovascular mortality in patients with diabetes. METHODS: This cohort study included 34,686 adults with diabetes who underwent a standard health-screening program between 1996 and 2017 in Taiwan. The dates and causes of death till January 2022 were retrieved from the National Death Registry. Cox proportional hazards models were used to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and cardiovascular mortality in relation to body mass index (BMI), waist circumference, waist-hip ratio (WHR), body fat percentage (BF%), and A Body Shape Index (ABSI), using the third quintile as the reference group. RESULTS: During a median follow-up of 15 years, there were 8,324 deaths, of which 1,748 were attributed to cardiovascular disease. After adjusting for demographics, lifestyle factors and comorbidities, ABSI was associated with all-cause mortality in an exposure-response manner; the HR (95% CI) for first and fifth vs. third quintile was 0.78 (0.69-0.89) and 1.24 (1.14-1.35), respectively. A similar but weaker exposure-response relationship was found between WHR and mortality. People with a lower BMI and BF% had an increased risk of mortality (HR [95% CI] for the first vs. third quintiles, 1.33 [1.22, 1.44] and 1.42 [1.30, 1.56], respectively). No association was observed between waist circumference categories and risk of mortality. Similar results were observed for the association of BF%, waist circumference, and ABSI with cardiovascular mortality. However, no significant association was observed between BMI and cardiovascular mortality. The association between WHR and cardiovascular mortality was stronger than that between WHR and all-cause mortality. CONCLUSIONS: ABSI demonstrated a consistent exposure-response relationship with both all-cause and cardiovascular mortality in this Asian cohort with diabetes. Our findings highlight the importance of monitoring ABSI, a surrogate index of central adiposity, in patients with diabetes.

Optimized Sugar-Free Citrus Lemon Juice Fermentation Efficiency and the Lipid-Lowering Effects of the Fermented Juice.

Aging and obesity make humans more prone to cardiovascular and metabolic syndrome diseases, leading to several serious health conditions, including hyperlipidemia, high blood pressure, and sleep disturbance. This study aimed to explore the hypolipidemic effect of fermented citrus lemon juice using a hyperlipidemic hamster model. The sugar-free lemon juice's fermentation was optimized, and the characteristics of fresh and fermented lemon juice (FLJ) were evaluated and compared, which contained polyphenols and superoxide dismutase-like activity. Results showed that the absorption and utilization efficiency of FLJ was higher compared with the unfermented lemon juice. This study's prefermentation efficiency evaluation found that 21-30 days of bacterial DMS32004 and DMS32005 fermentation of fresh lemon juice provided the best fermentation benefits, and 21-day FLJ was applied as a remedy after the efficiency compassion. After six weeks of feeding, the total cholesterol (TC) and triglyceride (TG) values in the blood and liver of the FLJ treatment groups were decreased compared with the high-fat diet (HFD) group. In addition, the blood low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced in the FLJ treatment groups compared with the HFD group. In contrast, the blood high-density lipoprotein (HDL-C) to LDL-C ratio increased considerably in the FLJ treatment groups, and the total to HDL ratio was significantly lower than in the HFD group. Compared with the HFD group, the TC content in the FLJ treatment groups' feces increased significantly. This study demonstrated that the sugar-free fermentation method and fermentation cycle management provided FLJ with the potential to regulate blood lipids. Further research and verification will be carried out to isolate specific substances from the FLJ and identify their mechanisms of action.

Genotype-phenotype correlation in Taiwanese children with diazoxide-unresponsive congenital hyperinsulinism.

Objective: Congenital hyperinsulinism (CHI) is a group of clinically and genetically heterogeneous disorders characterized by dysregulated insulin secretion. The aim of the study was to elucidate genetic etiologies of Taiwanese children with the most severe diazoxide-unresponsive CHI and analyze their genotype-phenotype correlations. Methods: We combined Sanger with whole exome sequencing (WES) to analyze CHI-related genes. The allele frequency of the most common variant was estimated by single-nucleotide polymorphism haplotype analysis. The functional effects of the ATP-sensitive potassium (KATP) channel variants were assessed using patch clamp recording and Western blot. Results: Nine of 13 (69%) patients with ten different pathogenic variants (7 in ABCC8, 2 in KCNJ11 and 1 in GCK) were identified by the combined sequencing. The variant ABCC8 p.T1042QfsX75 identified in three probands was located in a specific haplotype. Functional study revealed the human SUR1 (hSUR1)-L366F KATP channels failed to respond to intracellular MgADP and diazoxide while hSUR1-R797Q and hSUR1-R1393C KATP channels were defective in trafficking. One patient had a de novo dominant mutation in the GCK gene (p.I211F), and WES revealed mosaicism of this variant from another patient. Conclusion: Pathogenic variants in KATP channels are the most common underlying cause of diazoxide-unresponsive CHI in the Taiwanese cohort. The p.T1042QfsX75 variant in the ABCC8 gene is highly suggestive of a founder effect. The I211F mutation in the GCK gene and three rare SUR1 variants associated with defective gating (p.L366F) or traffic (p.R797Q and p.R1393C) KATP channels are also associated with the diazoxide-unresponsive phenotype.

Phosphate burden induces vascular calcification through a NLRP3-caspase-1-mediated pyroptotic pathway.

AIMS: The aim of this study is to clarify the role of NLRP3 inflammasome in phosphate burden-induced vascular smooth muscle cell (VSMC) calcification. MAIN METHODS: VSMC calcification was induced using a high concentration of inorganic phosphate. After pharmacological inhibition or genetic silencing of the NLRP3 inflammasome, pyroptosis, or potassium efflux, the cells were examined by RT-qPCR, immunofluorescence, and western blotting to identify the NLRP3-mediated pathway for VSMC calcification. KEY FINDINGS: Calcified VSMCs with α-smooth muscle actin (α-SMA) disarray presented features of pyroptosis, including caspase-1 maturation, cleaved gasdermin D (GSDMD), and a high supernatant level of lactate dehydrogenase A. Pharmacological inhibitions of caspase-1 and pyroptosis attenuated VSMC calcification, whereas interleukin-1ß receptor antagonism did not. Unlike canonical NLRP3 activation, osteogenic VSMCs did not upregulate NLRP3 expression. However, NLRP3 genetic silencing or inhibitions, which targets different domains of the NLRP3 protein, could ameliorate VSMC calcification by aborting caspase-1 and GSDMD activation. Furthermore, potassium efflux through the inward-rectifier potassium channel, and not through the P2X7 receptor, triggered NLRP3 inflammasome activation and VSMC calcification. SIGNIFICANCE: In the present study, we identified a potassium efflux-triggered NLRP3-caspase-1-mediated pyroptotic pathway for VSMC calcification that is unique and different from the canonical NLRP3 inflammasome activation. Therefore, targeting this pathway may serve as a novel therapeutic strategy for vascular calcification.

Prenatal lipopolysaccharide exposure induces anxiety-like behaviour in male mouse offspring and aberrant glial differentiation of embryonic neural stem cells.

BACKGROUND: Prenatal infection has been implicated in the development of neuropsychiatric disorders in children. We hypothesised that exposure to lipopolysaccharide during prenatal development could induce anxiety-like behaviour and sensorineural hearing loss in offspring, as well as disrupt neural differentiation during embryonic neural development. METHODS: We simulated prenatal infection in FVB mice and mouse embryonic stem cell (ESC) lines, specifically 46C and E14Tg2a, through lipopolysaccharide treatment. Gene expression profiling analyses and behavioural tests were utilized to study the effects of lipopolysaccharide on the offspring and alterations in toll-like receptor (TLR) 2-positive and TLR4-positive cells during neural differentiation in the ESCs. RESULTS: Exposure to lipopolysaccharide (25 µg/kg) on gestation day 9 resulted in anxiety-like behaviour specifically in male offspring, while no effects were detected in female offspring. We also found significant increases in the expression of GFAP and CNPase, as well as higher numbers of GFAP + astrocytes and O4+ oligodendrocytes in the prefrontal cortex of male offspring. Furthermore, increased scores for genes related to oligodendrocyte and lipid metabolism, particularly ApoE, were observed in the prefrontal cortex regions. Upon exposure to lipopolysaccharide during the ESC-to-neural stem cell (NSC) transition, Tuj1, Map2, Gfap, O4, and Oligo2 mRNA levels increased in the differentiated neural cells on day 14. In vitro experiments demonstrated that lipopolysaccharide exposure induced inflammatory responses, as evidenced by increased expression of IL1b and ApoB mRNA. CONCLUSIONS: Our findings suggest that prenatal infection at different stages of neural differentiation may result in distinct disturbances in neural differentiation during ESC-NSC transitions. Furthermore, early prenatal challenges with lipopolysaccharide selectively induce anxiety-like behaviour in male offspring. This behaviour may be attributed to the abnormal differentiation of astrocytes and oligodendrocytes in the brain, potentially mediated by ApoB/E signalling pathways in response to inflammatory stimuli.

Chemoprevention of lotus leaf ethanolic extract through epigenetic activation of the NRF2-mediated pathway in murine skin JB6 P+ cell neoplastic transformation.

Background and aim: Skin is one barrier protecting from environmental risk factors that can make skin cells cancerous through DNA damage and oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) pathway is an anti-stress defense system that can be regulated by DNA methylation and histone modification. Dietary phytochemicals have chemopreventive properties that can inhibit or delay carcinogenesis. The lotus leaf is a traditional medicinal plant containing many polyphenols whose extracts show many biological activities, including antioxidant, anti-obesity, and anti-cancer. This study aim to investigate the effect of lotus leaves on neoplastic transformation in murine skin JB6 P+ cells. Experimental procedure: Lotus leaves were extracted with water (LL-WE) and ethanol (LL-EE), and the LL-WE residues were further extracted with ethanol (LL-WREE). JB6 P+ cells were treated with different extracts. The chemoprotective effect would be evaluated by heme oxygenase 1 (HO-1), NAD(P)H quinone oxidoreductase (NQO1), and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) expression. Results and conclusion: LL-EE contained higher total phenolics and quercetin among extracts. In mouse skin JB6 P+ cells with 12-O-tetradecanoylphorbol-13-acetate treatment, LL-EE showed the greatest potential to suppress skin carcinogenesis. LL-EE activated the NRF2 pathway by upregulating antioxidant and detoxification enzymes upregulates antioxidant and detoxification enzymes, including HO-1, NQO1, and UGT1A1, and downregulates DNA methylation, which might be caused by lower DNA methyltransferase and histone deacetylase levels. Therefore, our results show that LL-EE reduces the neoplastic transformation of skin JB6 P+ cells, potentially by activating the NRF2 pathway and regulating epigenetic DNA methylation and histone acetylation.