Sex difference in the associations among secondhand smoke with metabolic syndrome in non-smokers in a large Taiwanese population follow-up study.

Close associations among secondhand smoke (SHS) and metabolic syndrome (MetS) and its components have been demonstrated, however sex differences in these associations remain unclear. We collected 121,364 participants from the Taiwan Biobank, and excluded those with smoking history, the remaining 88,297 participants (male: 18,595; female: 69,702; mean age 50.1 ± 11.0 years) were included. SHS exposure was evaluated based on self-reported questionnaires. SHS was associated with MetS (odds ratio [OR], 1.268, p < 0.001 for males vs. 1.180, p < 0.001 for females), abdominal obesity (OR, 1.234, p < 0.001 for males vs. 1.199, p < 0.001 for females), low high-density lipoprotein cholesterol (OR, 1.183, p = 0.008 for males vs. 1.094, p = 0.011 for females), hyperglycemia (OR, 1.286, p < 0.001 for males vs. 1.234, p < 0.001 for females), but not with hypertriglyceridemia. SHS was associated with high blood pressure (BP) (OR, 1.278, p < 0.001) only in males, but not in females. Furthermore, significant interactions were found between sex x SHS on MetS (p = 0.023), abdominal obesity (p = 0.032), and elevated BP (p < 0.001). Moreover, the participants who were exposed to SHS for ≥1 hour per week were associated with a higher risk (OR = 1.316, p = 0.001 in males vs. OR = 1.220, p < 0.001 in females) of MetS compared to those with no exposure. These results showed an association between SHS and a high OR for MetS in both the males and females. Furthermore, sex differences were identified in the associations between SHS and MetS and its components, and SHS was more closely related to MetS, abdominal obesity, and high BP in males than in females.

Cerebellar atrophy in genetic epileptic encephalopathies: A cohort study and a systematic review.

OBJECTIVE: To analyze cerebellar atrophy in genetic epileptic encephalopathies (EEs). METHODS: This research included a retrospective cohort study conducted from January 2016 to December 2023 and a systematic review on cerebellar atrophy in genetic EEs. Pediatric individuals who were diagnosed with EEs based on electroclinical features, carried causative gene variants, and exhibited cerebellar atrophy were recruited. Electroclinical features, neuroimaging findings, and causative variants of eligible individuals were analyzed. RESULTS: The cohort study showed 10 of 67 pediatric individuals (10/67; 15 %) who were diagnosed with genetic EEs had cerebellar atrophy; and 6 of the 10 individuals (6/10; 60 %) exhibited cerebellar signs. Diagnostic delay between the detection of cerebellar atrophy and the identification of genetic diagnosis existed in 6 individuals (6/10; 60 %) and the median duration was 4.4 years. A total of 32 genes, including 31 genes from the literature review and a newly identified SCN2A gene in this cohort, were reported associated with cerebellar atrophy in genetic EEs. Twenty-six genes (26/32; 81 %) accounted for cerebellar atrophy associated with other brain anomalies and 6 genes (6/32; 19 %) caused isolated cerebellar atrophy. Twenty-five genes (25/32; 78 %) showed late-onset cerebellar atrophy identified after the age of 1 year old. CONCLUSION: Cerebellar atrophy is not uncommon in genetic EEs and may serve as an indicator for molecular diagnosis in clinical practice. To shorten the diagnostic delay, follow-up neuroimaging study is crucial because of high rate of clinico-radiological dissociation and late-onset cerebellar atrophy in this patient group.

Sex difference in the associations among hyperuricemia with self-reported peptic ulcer disease in a large Taiwanese population study.

Background: Hyperuricemia may play a role in various systemic diseases. However, few studies have investigated the relationship between hyperuricemia and the risk of peptic ulcer disease (PUD). Therefore, in this population-based study, we enrolled over 120,000 participants from the Taiwan Biobank (TWB) and examined the risk factors for self-reported PUD. In addition, we investigated sex differences in the association between hyperuricemia and self-reported PUD. Methods: Data of 121,583 participants were obtained from the TWB. Male participants with a serum uric acid level >7 mg/dl and female participants with a serum uric acid level >6 mg/dl were classified as having hyperuricemia. Details of self-reported PUD were obtained by questionnaire. The association between hyperuricemia and self-reported PUD in the male and female participants was examined using multivariable logistic regression analysis. Results: The overall prevalence of self-reported PUD was 14.6%, with a higher incidence in males (16.5%) compared to females (13.5%). After multivariable adjustment, male sex [vs. female sex; odds ratio (OR) = 1.139; 95% confidence interval (CI) = 1.084-1.198; p < 0.001], and hyperuricemia (OR = 0.919; 95% CI = 0.879-0.961; p < 0.001) were significantly associated with self-reported PUD. Further, a significant interaction was found between sex and hyperuricemia on self-reported PUD (p = 0.004). Hyperuricemia was associated with a low risk of self-reported PUD in males (OR = 0.890; 95% CI = 0.837-0.947; p < 0.001) but not in females (p = 0.139). Conclusion: The prevalence of self-reported PUD was higher in the male participants than in the female participants. Hyperuricemia was associated with low prevalence of self-reported PUD in males, but not in females. Further studies are needed to clarify the mechanisms behind these observations and verify the potential protective role of hyperuricemia on the development of self-reported PUD.

Sex differences in the association of long-term exposure to heat stress on kidney function in a large Taiwanese population study.

The incidence and prevalence of dialysis in Taiwan are high compared to other regions. Consequently, mitigating chronic kidney disease (CKD) and the worsening of kidney function have emerged as critical healthcare priorities in Taiwan. Heat stress is known to be a significant risk factor for CKD and kidney function impairment. However, differences in the impact of heat stress between males and females remains unexplored. We conducted this retrospective cross-sectional analysis using data from the Taiwan Biobank (TWB), incorporating records of the wet bulb globe temperature (WBGT) during midday (11 AM-2 PM) and working hours (8 AM-5 PM) periods based on the participants' residential address. Average 1-, 3-, and 5-year WBGT values prior to the survey year were calculated and analyzed using a geospatial artificial intelligence-based ensemble mixed spatial model, covering the period from 2010 to 2020. A total of 114,483 participants from the TWB were included in this study, of whom 35.9% were male and 1053 had impaired kidney function (defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2). Multivariable analysis revealed that in the male participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly positively associated with eGFR < 60 ml/min/1.73 m2 (odds ratio [OR], 1.096, 95% confidence interval [CI] = 1.002-1.199, p = 0.044 for 1 year; OR, 1.093, 95% CI = 1.000-1.196, p = 0.005 for 3 years; OR, 1.094, 95% CI = 1.002-1.195, p = 0.045 for 5 years). However, significant associations were not found for the working hours period. In the female participants, during the midday period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.872, 95% CI = 0.778-0.976, p = 0.018 for 1 year; OR, 0.874, 95% CI = 0.780-0.978, p = 0.019 for 3 years; OR, 0.875, 95% CI = 0.784-0.977, p = 0.018 for 5 years). In addition, during the working hours period, the 1-, 3-, and 5-year average WBGT values per 1 â„ƒ increase were also significantly negatively associated with eGFR < 60 ml/min/1.73 m2 (OR, 0.856, 95% CI = 0.774-0.946, p = 0.002 for 1 year; OR, 0.856, 95% CI = 0.774-0.948, p = 0.003 for 3 years; OR, 0.853, 95% CI = 0.772-0.943, p = 0.002 for 5 years). In conclusion, our results revealed that increased WBGT was associated with impaired kidney function in males, whereas increased WBGT was associated with a protective effect against impaired kidney function in females. Further studies are needed to elucidate the exact mechanisms underlying these sex-specific differences.

Sex difference in the associations among risk factors with gastroesophageal reflux disease in a large Taiwanese population study.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common global health issue. Previous studies have revealed a higher prevalence of GERD in females than in males, however few studies have investigated sex differences in the risk factors associated with GERD. Therefore, the aim of this population-based study was to examine sex differences in the risk factors for GERD in a large cohort of over 120,000 Taiwanese participants. METHODS: We enrolled 121,583 participants (male: 43,698; female: 77,885; mean age 49.9 ± 11.0 years) from the Taiwan Biobank. The presence of GERD was ascertained using self-reported questionnaires. Sex differences in the risk factors associated with GERD were examined using multivariable logistic regression analysis. RESULTS: The overall prevalence of GERD was 13.7%, including 13.0% in the male participants and 14.1% in the female participants (p < 0.001). Multivariable analysis showed that older age, hypertension, smoking history, alcohol history, low fasting glucose, and low uric acid were significantly associated with GERD in the male participants. In the female participants, older age, diabetes, hypertension, smoking history, alcohol history, low systolic blood pressure, low fasting glucose, high hemoglobin, high total cholesterol, low high-density lipoprotein cholesterol (HDL-C), low low-density lipoprotein cholesterol, and low uric acid were significantly associated with GERD. Significant interactions were found between sex and age (p < 0.001), diabetes (p < 0.001), smoking history (p < 0.001), fasting glucose (p = 0.002), triglycerides (p = 0.001), HDL-C (p = 0.001), and estimated glomerular filtration rate (p = 0.002) on GERD. CONCLUSIONS: Our results showed a higher prevalence of GERD among females compared to males. Furthermore, sex differences were identified in the risk factors associated with GERD, and older age, diabetes, smoking history, and low HDL-C were more closely related to GERD in females than in males.

A meta-analysis of the association between RBP4 rs3758539 genotype and metabolic syndrome factors.

AIM: To explore the link between the RBP4 rs3758539 genotype and metabolic syndrome risk factors and whether the impact of this genetic variation displays any potential race discrepancy. MATERIALS AND METHODS: This meta-analysis followed the PRISMA guidelines and was registered with PROSPERO (registration no. CRD42023407999). PubMed, Web of Science, Embase, Cochrane Library, Google Scholar, Airiti Library and CINAHL databases were used for the study search until October 2023. We evaluated the methodological quality using the Joanna Briggs Institute checklist and determined the correlation using a random-effects meta-analysis. RESULTS: The results indicated that individuals with the rs3758539 GA/AA genotype had a higher risk profile, including lower high-density lipoprotein levels [correlation: -0.045, 95% confidence interval (CI): -0.080 to -0.009, p = .015, I2 = 46.9%] and higher body mass index (correlation: 0.117, 95% CI: 0.036-0.197, p = .005, I2 = 82.0%), body fat (correlation: 0.098, 95% CI: 0.004-0.191, p = .041, I2 = 64.0%), and low-density lipoprotein levels (correlation: 0.074, 95% CI: 0.010-0.139, p = .024, I2 = 0%), of developing metabolic syndrome than those with the GG genotype. The subgroup analysis maintained a significantly positive correlation between the rs3758539 GA/AA genotype and body mass index (correlation: 0.163, 95% CI: 0.031-0.289, p = .016, I2 = 88.9%) but a negative correlation with high-density lipoprotein levels (correlation: -0.047, 95% CI: -0.087 to -0.006, p = .025, I2 = 65.7%) in the Asian group only. CONCLUSION: The current meta-analysis supports a significant link between the RBP4 rs3758539 GA/AA genotype and the metabolic syndrome.

The Effectiveness of Parenting Programs in Preventing Abusive Head Trauma: A Systematic Review and Meta-Analysis.

Parenting programs are the most common intervention for preventing the lethal form of child maltreatment, abusive head trauma (AHT). However, certain results of the effects of these programs have not yet been compared across studies. A systematic review with meta-analysis is warranted to quantitively synthesize the available evidence to identify effective elements and strategies of the programs for preventing AHT. This review aims to estimate AHT preventive parenting programs' pooled effect on the reduction of AHT incidence, the improvement of parental knowledge, and the increased use of safe strategies in response to infants' inconsolable crying. Studies published in English and Mandarin were searched and retained if they were randomized control trials (RCTs) or with a quasi-experimental design, included an AHT preventive parenting program, and provided data that quantified targeted outcomes. Eighteen studies were included in this review. AHT preventive parenting programs had a pooled effect on improving parents' knowledge and increasing the use of safe coping strategies in response to inconsolable crying but not on the incidence of AHT and parents' emotional self-regulation. Subgroup analyses showed that the intervention effects were mostly present across study designs or measurements and emerged in the reduction of AHT incidence compared with historical controls. The findings suggest that AHT preventive parenting programs enhance parenting knowledge and skills to provide safe care for infants. Further efforts to evaluate AHT parenting programs on the reduction of AHT incidence are necessary for decision-making on allocating and disseminating interventions.

Unrevealed roles of extracellular enolase­1 (ENO1) in promoting glycolysis and pro­cancer activities in multiple myeloma via hypoxia­inducible factor 1α.

The involvement of enolase­1 (ENO1), intracellularly or extracellularly, has been implicated in cancer development. Moreover, anticancer activities of an ENO1­targeting antibody has demonstrated the pathological roles of extracellular ENO1 (surface or secreted forms). However, although ENO1 was first identified as a glycolytic enzyme in the cytosol, to the best of our knowledge, extracellular ENO1 has not been implicated in glycolysis thus far. In the present study, the effects of extracellular ENO1 on glycolysis and other related pro­cancer activities were investigated in multiple myeloma (MM) cells in vitro and in vivo. Knockdown of ENO1 expression reduced lactate production, cell viability, cell migration and surface ENO1 expression in MM cells. Notably, addition of extracellular ENO1 protein in cancer cell culture enhanced glycolytic activity, hypoxia­inducible factor 1­α (HIF­1α) expression, glycolysis­related gene (GRG) expression and pro­cancer activities, such as cell migration, cell viability and tumor­promoting cytokine secretion. Consistently, these extracellular ENO1­induced cellular effects were inhibited by an ENO1­specific monoclonal antibody (mAb). In addition, extracellular ENO1­mediated glycolysis, GRG expression and pro­cancer activities were also reduced by HIF­1α silencing. Lastly, administration of an ENO1 mAb reduced tumor growth and serum lactate levels in an MM xenograft model. These results suggested that extracellular ENO1 (surface or secreted forms) enhanced a HIF­1α­mediated glycolytic pathway, in addition to its already identified roles. Therefore, the results of the present study highlighted the therapeutic potential of ENO1­specific antibodies in treating MM, possibly via glycolysis inhibition, and warrant further studies in other types of cancer.

Irregular Antibody Screening Using a Microdroplet Platform.

The screening procedure for antibodies is considered the most tedious among the three pretransfusion operations, i.e., ABO and Rhesus (Rh) typing, irregular antibody screening/identification, and crossmatching tests. The commonly used screening method for irregular antibodies in clinics at present is a manual polybrene test (MP). The MP test involves numerous reagent replacement and centrifuge procedures, and the sample volume is expected to be relatively less. Herein, screening red blood cells (RBCs) and serum irregular antibodies are encapsulated in microdroplets with a diameter of ~300 µm for a hemagglutination reaction. Owing to the advantage of spatial limitation in microdroplets, screening RBCs and irregular antibodies can be directly agglutinated, thereby eliminating the need for centrifugation and the addition of reagents to promote agglutination, as required by the MP method. Furthermore, the results for a large number of repeated tests can be concurrently obtained, further simplifying the steps of irregular antibody screening and increasing accuracy. Eight irregular antibodies are screened using the proposed platform, and the results are consistent with the MP method. Moreover, the volume of blood samples and antibodies can be reduced to 10 µL and 5 µL, respectively, which is ten times less than that using the MP method.

Risk of rapid progression to dialysis in patients with type 2 diabetes mellitus with and without diabetes-related complications at diagnosis.

Many adults with diabetes mellitus are unaware worldwide. The study objectives aimed to evaluate the risk of dialysis within 5 years of diagnosis between patients with newly diagnosed diabetes with and without diabetes-related complications. A retrospective longitudinal nationwide cohort study was conducted. Patients diagnosed with diabetes between 2005 and 2013 were followed up until 2018. They were categorized based on the presence or absence of complications, the number of complications, and the diabetes complications severity index (DCSI) scores. Dialysis outcomes were determined through the Registry of Catastrophic Illness from the National Health Insurance Research Database. Among the analyzed patients, 25.38% had complications at diagnosis. Patients with complications at diagnosis had a significantly higher risk of dialysis within 5 years (adjusted hazard ratio: 9.55, 95% confidence interval CI 9.02-10.11). Increasing DCSI scores and the number of complications were associated with higher dialysis risks. Patients with one complication had a 7.26-times higher risk (95% CI 6.83-7.71), while those with ≥ 3 complications had a 36.12-times higher risk (95% CI 32.28-40.41). In conclusion, newly diagnosed diabetes patients with complications face an increased risk of dialysis within 5 years. The severity and number of complications are directly linked to the risk of dialysis within this timeframe.

Sex Difference in the Associations among Obesity-Related Indices with Hyperuricemia in a Large Taiwanese Population Study.

Hyperuricemia has been linked with the development of diabetes, gout, kidney, and cardiovascular diseases. Although obesity is associated with hyperuricemia, data on sex differences in this association are scarce. Therefore, this study was conducted to explore sex differences in the correlations among various indices of obesity with hyperuricemia in Taiwan. Data were obtained from the Taiwan Biobank and included 122,067 participants. After excluding 179 participants with missing data, the remaining 121,888 participants (men: 43,790; women: 78,098) were enrolled. The prevalence rates of hyperuricemia (defined as serum uric acid >7.0/6.0 mg/dL in men/women) were 29.8% and 13.6%, respectively (p < 0.001). Multivariable analysis revealed high values of body shape index (ABSI), waist-to-height ratio (WHtR), waist-hip ratio (WHR), lipid accumulation product (LAP), conicity index (CI), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), body mass index (BMI), and body roundness index (BRI) were significantly associated with hyperuricemia in both the male and female participants (all p < 0.001). The interactions between sex and all 10 of these indices were significant (all p < 0.001) for hyperuricemia. In men, LAP had the highest area under the curve (0.669), followed by BMI (0.655), VAI (0.645), AVI (0.642), BRI (0.640), WHtR (0.633), BAI (0.605), WHR (0.599), CI (0.574), and ABSI (0.510). In women, LAP also had the highest area under the curve (0.754), followed by BMI (0.728), VAI (0.724), WHtR (0.721), BRI (0.720), AVI (0.713), WHR (0.676), BAI (0.673), CI (0.626), and ABSI (0.544). In conclusion, obesity-related indices were associated with hyperuricemia in this large Taiwanese study, and sex differences were found in these associations, with stronger associations in women than in men.

Low Lung Function Is Associated with Low Baseline Calcaneus Ultrasound T-Score but a Slow Decline in T-Score in a Taiwanese Follow-Up Population with No History of Smoking, Bronchitis, Emphysema, or Asthma.

Osteoporosis is a common disease, and the prevalence is increasing in patients with chronic respiratory diseases, with important implications with regard to fractures, hospitalization, and death. Due to inconsistent data and a lack of large cohort follow-up studies on the association between lung function and osteoporosis, the aim of this study was to investigate this issue. We enrolled and followed for a median of 4 years a total of 9059 participants with no history of smoking, bronchitis, emphysema, or asthma from the Taiwan Biobank. Spirometry data, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were used to assess lung function. Changes in the calcaneus ultrasound T-score (ΔT-score) were calculated as follow-up T-score-baseline T-score. A ΔT-score ≤ -3 (median value of ΔT-score) meant a fast decline in T-score. Multivariable analysis showed that lower values of FEV1 (ß, 0.127, p < 0.001), FVC (ß, 0.203, p < 0.001), and FEV1/FVC (ß, 0.002, p = 0.013) were significantly associated with a low baseline T-score. In addition, after follow-up, higher values of FEV1 (odds ratio (OR), 1.146, p = 0.001), FVC (OR, 1.110, p = 0.042), and FEV1/FVC (OR, 1.004, p = 0.002) were significantly associated with ΔT-score ≤ -3. FEV1/FVC < 70% (OR, 0.838, p < 0.001) was significantly associated with ΔT-score ≤ -3. In conclusion, lower FEV1, FVC, and FEV1/FVC were associated with a low baseline T-score, and higher FEV1, FVC, and FEV1/FVC were associated with a rapid decline in T-score in follow-up. This suggests that lung disease may be associated with bone mineral density in the Taiwanese population with no history of smoking, bronchitis, emphysema, or asthma. Further research is needed to establish causality.

Daily association between parent-adolescent relationship and life satisfaction: The moderating role of emotion dysregulation.

INTRODUCTION: In adolescence, life satisfaction is an early indicator of later psychological well-being. However, researchers know little about how daily family relationships shape adolescent life satisfaction. The current study examined the day-to-day associations between parent-adolescent relationships and life satisfaction, and whether adolescent emotion dysregulation moderated these associations. METHODS: A total of 191 adolescents (Mage = 12.93, SDage = 0.75, 53% female) recruited from junior high schools in Taiwan participated in a 10-day daily diary protocol. We conducted multilevel analyses to examine within-family and between-family processes. RESULTS: At the within-family level, adolescents reported higher life satisfaction on days when parent-adolescent closeness was higher, but lower life satisfaction on days when parent-adolescent conflict was higher. At the between-family level, higher parent-adolescent closeness was associated with greater life satisfaction on average, while parent-adolescent conflict was not related to adolescent life satisfaction. Cross-level interactions indicated that within-family changes in parent-adolescent closeness and conflict were only associated with life satisfaction for adolescents with higher levels of emotion dysregulation, indicating emotion dysregulation may intensify the role of daily parent-adolescent relationships in shaping adolescent life satisfaction. CONCLUSIONS: This study expands current literature and provides novel evidence that changes in day-to-day parent-adolescent relationships have important implications for adolescent life satisfaction, especially for youth higher in emotion dysregulation. The findings underscore the importance of evaluating family and individual characteristics to better support adolescent well-being.

Association and Interaction between Heavy Metals and Hyperuricemia in a Taiwanese Population.

The prevalence of hyperuricemia in Taiwan is high, and hyperuricemia has been associated with a risk of developing several diseases. Although the traditional risk factors for hyperuricemia are well known, the relationship between heavy metals and hyperuricemia is still undefined. Therefore, the aim of this study was to investigate the relationship between hyperuricemia and heavy metals. A total of 2447 participants (977 males and 1470 females) residing in southern Taiwan were enrolled, and levels of the following heavy metals were measured: lead in blood, and nickel, chromium, manganese, arsenic (As), copper, and cadmium in urine. Hyperuricemia was defined as a serum uric acid level greater than 7.0 mg/dL (416.5 µmol/L) in men and 6.0 mg/dL (357 µmol/L) in women. The participants were divided into two groups: those without hyperuricemia (n = 1821; 74.4%) and those with hyperuricemia (n = 626; 25.6%). Multivariate analysis showed that only high urine As (log per 1 µg/g creatinine; odds ratio, 1.965; 95% confidence interval, 1.449 to 2.664; p < 0.001), young age, male sex, high body mass index, high hemoglobin, high triglycerides, and low estimated glomerular filtration rate were significantly associated with hyperuricemia. In addition, the interactions between Pb × Cd (p = 0.010), Ni × Cu (p = 0.002), and Cr × Cd (p = 0.001) on hyperuricemia were statistically significant. Increasing levels of Pb and Cr yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cd. Moreover, increasing levels of Ni yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cu. In conclusion, our results show that high urine As is associated with hyperuricemia, and some interactions of heavy metals on hyperuricemia are noted. We also found that young age, male sex, high BMI, high hemoglobin, high triglycerides, and low eGFR were significantly associated with hyperuricemia.

Klotho Null Mutation Involvement in Adenosine A2B Receptor-Related Skeletal Muscle Degeneration.

Klotho is known for its age-suppressing function and has been implicated in sarcopenia pathology. It has recently been proposed that the adenosine A2B receptor plays a crucial role in skeletal muscle energy expenditure. However, the association between Klotho and A2B remains elusive. In this study, Klotho knockout mice, aged 10 weeks, and wild-type mice, aged 10 and 64 weeks, were used for comparison in indicators of sarcopenia (n = 6 for each group). PCR was performed to confirm the mice genotypes. Skeletal muscle sections were analyzed using hematoxylin and eosin staining as well as immunohistochemistry staining. The skeletal muscle cross-sectional area was significantly reduced in Klotho knockout mice and wild-type mice, aged 64 weeks, when compared with wild-type mice, aged 10 weeks, with a decreased percentage of type IIa and IIb myofibers. Likely impaired regenerative capacity, as reflected by the reduction of paired box 7 (Pax7)- and myogenic differentiation protein 1 (MyoD)-positive cells, was also observed in Klotho knockout mice and aged wild-type mice. 8-Hydroxy-2-deoxyguanosine expression was enhanced with Klotho knockout and aging, indicating higher oxidative stress. Adenosine A2B signaling was impaired, with a lower expression of the A2B receptor and the cAMP-response element binding protein in Klotho knockout and aged mice. The present study provides the novel finding that sarcopenia involves adenosine signaling under the influence of Klotho knockout.

LncRNA HOTAIRM1 functions in DNA double-strand break repair via its association with DNA repair and mRNA surveillance factors.

The eukaryotic exon junction complex component Y14 participates in double-strand break (DSB) repair via its RNA-dependent interaction with the non-homologous end-joining (NHEJ) complex. Using immunoprecipitation-RNA-seq, we identified a set of Y14-associated long non-coding RNAs (lncRNAs). The lncRNA HOTAIRM1 serves as a strong candidate that mediates the interaction between Y14 and the NHEJ complex. HOTAIRM1 localized to near ultraviolet laser-induced DNA damage sites. Depletion of HOTAIRM1 delayed the recruitment of DNA damage response and repair factors to DNA lesions and compromised the efficiency of NHEJ-mediated DSB repair. Identification of the HOTAIRM1 interactome revealed a large set of RNA processing factors including mRNA surveillance factors. The surveillance factors Upf1 and SMG6 localized to DNA damage sites in a HOTAIRM1-dependent manner. Depletion of Upf1 or SMG6 increased the level of DSB-induced non-coding transcripts at damaged sites, indicating a pivotal role for Upf1/SMG6-mediated RNA degradation in DNA repair. We conclude that HOTAIRM1 serves as an assembly scaffold for both DNA repair and mRNA surveillance factors that act in concert to repair DSBs.

Comparative Gut Microbiome Differences between High and Low Aortic Arch Calcification Score in Patients with Chronic Diseases.

Gut dysbiosis can induce chronic inflammation and contribute to atherosclerosis and vascular calcification. The aortic arch calcification (AoAC) score is a simple, noninvasive, and semiquantitative assessment tool to evaluate vascular calcification on chest radiographs. Few studies have discussed the relationship between gut microbiota and AoAC. Therefore, this study aimed to compare the microbiota composition between patients with chronic diseases and high or low AoAC scores. A total of 186 patients (118 males and 68 females) with chronic diseases, including diabetes mellitus (80.6%), hypertension (75.3%), and chronic kidney disease (48.9%), were enrolled. Gut microbiota in fecal samples were analyzed by sequencing of the 16S rRNA gene, and differences in microbial function were examined. The patients were divided into three groups according to AoAC score, including 103 patients in the low AoAC group (AoAC ≤ 3), 40 patients in the medium AoAC group (3 < AoAC ≤ 6), and 43 patients in the high AoAC group (AoAC > 6). Compared to the low AoAC group, the high AoAC group had a significantly lower microbial species diversity (Chao1 index and Shannon index) and increased microbial dysbiosis index. Beta diversity showed that the microbial community composition was significantly different among the three groups (p = 0.041, weighted UniFrac PCoA). A distinct microbial community structure was found in the patients with a low AoAC, with an increased abundance at the genus level of Agathobacter, Eubacterium coprostanoligenes group, Ruminococcaceae UCG-002, Barnesiella, Butyricimonas, Oscillibacter, Ruminococcaceae DTU089, and Oxalobacter. In addition, there was an increased relative abundance of class Bacilli in the high AoAC group. Our findings support the association between gut dysbiosis and the severity of AoAC in patients with chronic diseases.

Long-Term Outcome of Pediatric Patients with Anti-NMDA Receptor Encephalitis in a Single Center.

BACKGROUND: Anti-N-methyl-D-aspartate (NMDA) receptor encephalitis is the most common autoimmune encephalitis in children. There is a high probability of recovery if treated promptly. We aimed to analyze the clinical features and long-term outcomes of pediatric patients with anti-NMDA receptor encephalitis. METHOD: We conducted a retrospective study with definite diagnoses of anti-NMDA receptor encephalitis in 11 children treated in a tertiary referral center between March 2012 and March 2022. Clinical features, ancillary tests, treatment, and outcomes were reviewed. RESULTS: The median age at disease onset was 7.9 years. There were eight females (72.7%) and three males (27.3%). Three (27.3%) patients initially presented with focal and/or generalized seizures and eight (72.7%) with behavioral change. Seven patients (63.6%) revealed normal brain MRI scans. Seven (63.6%) had abnormal EEG results. Ten patients (90.1%) received intravenous immunoglobulin, corticosteroid, and/or plasmapheresis. After a median follow-up duration of 3.5 years, one patient was lost to follow-up at the acute stage, nine (90%) had an mRS ≤ 2, and only one had an mRS of 3. CONCLUSIONS: With the early recognition of anti-NMDA receptor encephalitis based on its clinical features and ancillary tests, we were able to treat patients promptly with first-line treatment and achieve favorable neurological outcomes.

Sex difference in the associations among obesity-related indices with incidence of diabetes mellitus in a large Taiwanese population follow-up study.

Background: Obesity is a major risk factor for diabetes mellitus (DM), which is in turn a major risk factor for cardiovascular diseases such as coronary artery disease and stroke. As few studies have investigated sex differences in the association between obesity and incidence of DM, the aim of this longitudinal study was to explore this issue in a large group of Taiwanese participants. Methods: A total of 24,346 participants were enrolled in this study, of whom 8,334 (mean age, 50.6 ± 11.0 years) were male and 16,012 (mean age, 50.5 ± 10.1 years) were female. The following obesity-related indices were studied: body mass index, waist-to-height ratio, waist-to-hip ratio (WHR), body roundness index, conicity index (CI), body adiposity index, abdominal volume index, lipid accumulation product (LAP), and visceral adiposity index (VAI). Results: The analysis showed significant associations between all of these indices with incidence of DM (all p < 0.001). In the male participants, the strongest predictors for incidence of DM were LAP (AUC = 0.692), WHtR (AUC = 0.684), and WHR (AUC = 0.683). In the female participants, the strongest predictors were LAP (AUC = 0.744), WHtR (AUC = 0.710) and VAI (AUC = 0.710), followed by BRI (AUC = 0.708). Conclusion: Strong associations were found between the studied obesity-related indices and incidence of DM, and sex differences were found. Hence, to better control DM, reducing body weight may be beneficial in addition to lifestyle modifications, diet control, and pharmacological interventions.

Effect of FADS1 rs174556 Genotype on Polyunsaturated Fatty Acid Status: A Systematic Review and Meta-Analysis.

PUFA status is highly implicated in cognitive development and metabolic disorder-related diseases. Genetic variants of FADS genes encoding enzymes that catalyze the rate-limiting steps of PUFA biosynthesis appear to be associated with n-3 and n-6 PUFA contents. Therefore, we conducted the first systematic review and meta-analysis to explore the association of the A-allele carriers of the FADS1 rs174556 with PUFA status. The PRISMA guidelines were followed. The literature search was conducted up to November 2022 in PubMed, Web of Science, Embase, Cochrane Library, Airiti Library, and CINAHL. The Joanna Briggs Institute checklists were used to assess the methodological quality. The correlation with 95% CIs was determined by a random-effect meta-analysis. Eleven studies that met the inclusion criteria and acceptable quality were included in this systematic review. The data on PUFA contents were collected when they were mainly analyzed using blood samples and breast milk. Results of the meta-analysis on eight studies (one randomized controlled trial, one cohort study, and six cross-sectional studies) showed that the A-allele carriers of rs174556 were significantly negatively correlated with the concentrations of AA (P = 0.001), EPA (P = 0.004), and DHA (P = 0.025). However, ALA and LA were not associated with the A-allele carriers. To clarify the discrepancy, we further divided the studies into blood samples and breast milk subgroups. The subgroup analysis revealed that the A-allele carriers of rs174556 were significantly positively correlated with LA (P = 0.031) and negatively correlated with AA (P = 0.001), EPA (P = 0.036), and DHA (P < 0.001) in the blood sample group, but not in the breast milk group. The current meta-analysis proved that the A-allele carriers of the FADS1 rs174556 appeared to be highly associated with lower concentrations of AA, EPA, and DHA but higher LA in the blood samples. The study has been registered on the International Prospective Register of Systematic Reviews (PROSPERO:CRD42022363978). Adv Nutr 2023;x:xx-xx.