Genotypic and phenotypic correlations in tooth agenesis: insights from WNT10A and EDA mutations in syndromic and non-syndromic forms.

Tooth agenesis (TA) occurs when tooth development is disrupted at the initiation stage. It can be classified into non-syndromic and syndromic forms (named NSTA and STA), depending on whether it is accompanied by abnormalities of other organs and systems. Genetic factors play a predominant role in the pathogenesis of tooth agenesis, with dozens of genes implicated in both forms. Several genes have been identified, mutations in which can lead to both forms of TA. Among these, WNT10A and EDA are frequently mutated genes in this context, representing extensively researched and documented genes in human non-syndromic selective agenesis of permanent teeth and their association with ectodermal dysplasia syndromes. In this review, we present an overview of the current knowledge regarding genes associated with NSTA and STA, focusing on the distribution and nature of WNT10A and EDA gene mutations. We also explore how these mutations relate to the condition's both forms, including their association with the number of missing permanent teeth.

The Effects of Ketogenic Diets and Ketone Supplements on the Aerobic Performance of Endurance Runners: A Systematic Review.

CONTEXT: Ketogenic diets and ketone supplements have gained popularity among endurance runners given their purported effects: potentially delaying the onset of fatigue by enabling the increased utilization of the body's fat reserve or external ketone bodies during prolonged running. OBJECTIVE: This systematic review was conducted to evaluate the effects of ketogenic diets (>60% fat and <10% carbohydrates/<50 g carbohydrates per day) or ketone supplements (ketone esters or ketone salts, medium-chain triglycerides or 1,3-butadiol) on the aerobic performance of endurance runners. DATA SOURCES: A systematic search was conducted in PubMed, Web of Science, Pro Quest, and Science Direct for publications up to October 2023. STUDY SELECTION: Human studies on the effects of ketogenic diets or ketone supplements on the aerobic performance of adult endurance runners were included after independent screening by 2 reviewers. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: Primary outcomes were markers of aerobic performance (maximal oxygen uptake [VO2max], race time, time to exhaustion and rate of perceived exertion). RESULTS: VO2max was assessed by incremental test to exhaustion. Endurance performance was assessed by time trials, 180-minute running trials, or run-to-exhaustion trials; 5 studies on ketogenic diets and 7 studies on ketone supplements involving a total of 132 endurance runners were included. Despite the heterogeneity in study design and protocol, none reported benefits of ketogenic diets or ketone supplements on selected markers of aerobic performance compared with controls. Reduction in bodyweight and fat while preserving lean mass and improved glycemic control were reported in some included studies on ketogenic diets. CONCLUSION: This review did not identify any significant advantages or disadvantages of ketogenic diets or ketone supplements for the aerobic performance of endurance runners. Further trials with larger sample sizes, more gender-balanced participants, longer ketogenic diet interventions, and follow-up on metabolic health are warranted.

An economic evaluation on sub-optimal breastfeeding in Hong Kong: Infant health outcomes and costs.

AIM: This study estimated the healthcare cost savings for the government due to the prevention of gastroenteritis (GE) infections and lower respiratory tract infections (LRTI) in the first year of life, attributed to an increase in the exclusive breastfeeding rate at 4 months in Hong Kong. METHODS: The model used the best available data inputs, with uncertainty considered using probabilistic sensitivity analysis. We additionally assessed the impact of neonatal jaundice (NNJ) on the economic benefits of increasing exclusive breastfeeding rates. RESULTS: During 2010-2019, five admissions for GE and three admissions for LRTI per 1000 births would have been prevented in the first year of life if the exclusive breastfeeding rate at 4 months increased from the actual levels (~15-30%) to 50%, resulting in annual healthcare cost savings of USD1.05 (95% CI 1.03-1.07) million/year. The cost saving would reach USD1.89 (95% CI 1.86-1.92) million/year if the exclusive breastfeeding rate at 4 months increase to 70%. However, if higher NNJ admissions during 7-90 days related to more exclusive breastfeeding are considered, the cost saving would reduce by 60%. CONCLUSION: Our findings can guide policymakers in allocating budget and resources for breastfeeding promotion in Hong Kong. The prevention of unnecessary NNJ admissions would maximise the economic benefits of exclusive breastfeeding at 4 months.

Genetic and clinical characteristics of catecholaminergic polymorphic ventricular tachycardia in a Taiwanese nationwide cohort.

BACKGROUND: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare and lethal arrhythmia. Ryanodine receptor 2 (RYR2) mutation accounts for ∼60% of CPVT patients which is inherited in an autosomal dominant pattern. OBJECTIVE: This study aimed to identify CPVT-related mutations and clinical characteristics among Taiwanese CPVT patients and compare to other cohorts worldwide. METHODS: Clinical and genetic data were obtained from the Sudden Arrhythmia Death Syndrome Registry in Taiwan (SADS-TW). Forty clinically diagnosed Taiwanese CPVT patients were included. RESULTS: This is the first nationwide CPVT cohort in Taiwan. Among the 29 Taiwanese patients with CPVT-related gene mutations, 55% had RYR2 mutations, a rate similar to other ethnicities. Three out of 12 RYR2 variants were unreported. Exercise-induced symptoms including syncope and cardiac arrest were more frequent in East Asian cohorts (Taiwanese 79%, Japanese 91%), compared to Caucasian cohorts (59%) (p = 0.002). CONCLUSION: The discovery of diverse RYR2 mutations in the Taiwanese CVPT population demonstrates the importance of genetic testing in different ethnicities.

Sodium-glucose co-transporter 2 Inhibitors Act Independently of SGLT2 to Confer Benefit for Heart Failure with Reduced Ejection Fraction in Mice.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are novel, potent heart failure medications with an unknown mechanism of action. We sought to determine if the beneficial actions of SGLT2i in heart failure were on- or off-target, and related to metabolic reprogramming, including increased lipolysis and ketogenesis. The phenotype of mice treated with empagliflozin and genetically engineered mice constitutively lacking SGLT2 mirrored metabolic changes seen in human clinical trials (including reduced blood glucose, increased ketogenesis, and profound glucosuria). In a mouse heart failure model, SGLT2i treatment, but not generalized SGLT2 knockout, resulted in improved systolic function and reduced pathologic cardiac remodeling. SGLT2i treatment of the SGLT2 knockout mice sustained the cardiac benefits, demonstrating an off-target role for these drugs. This benefit is independent of metabolic changes, including ketosis. The mechanism of action and target of SGLT2i in HF remain elusive.

Predicting impaired cardiopulmonary exercise capacity in patients with atrial fibrillation using a simple echocardiographic marker.

BACKGROUND: Exercise intolerance is a common symptom associated with atrial fibrillation (AF). However, echocardiographic markers that can predict impaired exercise capacity are lacking. OBJECTIVE: This study aimed to investigate the association between echocardiographic parameters and exercise capacity assessed by cardiopulmonary exercise testing in patients with AF. METHODS: This single-center prospective study enrolled patients with AF who underwent echocardiography and cardiopulmonary exercise testing to evaluate exercise capacity at a tertiary center for AF management from 2020 to 2022. Patients with valvular heart disease, reduced left ventricular ejection fraction, or documented cardiomyopathy were excluded. RESULTS: Of the 188 patients, 134 (71.2%) exhibited impaired exercise capacity (peak oxygen consumption ≤85%), including 4 (2.1%) having poor exercise capacity (peak oxygen consumption <50%). Echocardiographic findings revealed that these patients had an enlarged left atrial end-systolic diameter (LA); smaller left ventricular end-diastolic diameter (LVEDD); and increased relative wall thickness, tricuspid regurgitation velocity, and LA/LVEDD and E/e' ratios. In addition, they exhibited lower peak systolic velocity of the mitral annulus and LA reservoir strain. In the multivariate regression model, LA/LVEDD remained the only significant echocardiographic parameter after adjustment for age, sex, and body mass index (P = .020). This significance persisted even after incorporation of heart rate reserve, N-terminal pro-B-type natriuretic peptide level, and beta-blocker use into the model. CONCLUSION: In patients with AF, LA/LVEDD is strongly associated with exercise capacity. Further follow-up and validation are necessary to clarify its clinical implications in patient care.

Normative values of motor performance and their relationship with BMI status in Hong Kong preschoolers.

This study aimed to establish sex- and age-specific reference values for motor performance (MP) in Hong Kong preschoolers aged 3-5 years old and examine the relationship between MP and BMI status. A cross-sectional study was conducted among 5579 preschoolers in Hong Kong. Three MP tests were administered, and height and weight information were collected. GAMLSS was used to compute the normative values of the motor tests. Boys outperformed girls in activities requiring muscle strength and power, while girls outperformed boys in activities requiring balance and coordination. The MP scores increased with age for both overarm beanbag throw and standing long jump for both sexes, while the one-leg balance scores showed larger differences between P50 and P95 in older preschoolers. Children with excessive weight performed worse in standing long jump and one-leg balance compared to their healthy weight peers. This study provides valuable information on the MP of preschoolers in Hong Kong, including sex- and age-specific reference values and the association between BMI status and MP scores. These findings can serve as a reference for future studies and clinical practice and highlight the importance of promoting motor skill development in preschoolers, particularly those who are overweight or obese.

Sex-based differences in obstructive sleep apnea and atrial fibrillation: Implication of atrial fibrillation burden.

Background: Obstructive sleep apnea (OSA) is a risk factor for atrial fibrillation (AF); however, it is unclear whether AF increases the risk of OSA. Furthermore, sex differences among patients with both AF and OSA remain unclear. We aimed to determine the association between an increased AF burden and OSA and investigate the differences in clinical characteristics between women and men with AF and OSA. Methods: This was a descriptive, cross-sectional analysis from a prospective cohort study. Patients with non-valvular AF were recruited from the cardiac electrophysiology clinic of a tertiary center; they underwent a home sleep apnea test and 14-day ambulatory electrocardiography. Moderate-to-severe OSA was defined as an apnea-hypopnea index of ≥15. Results: Of 320 patients with AF, 53.4% had moderate-to-severe OSA, and the mean body mass index (BMI) was 25.6 kg/m2. Less women (38.2%) had moderate-to-severe OSA than men (59.3%) (p < 0.001). In the multivariate analysis, age, being a man, and BMI were significantly associated with moderate-to-severe OSA. AF burden was associated with moderate-to-severe OSA only in men (odds ratio: 1.008; 95% confidence interval: 1.001-1.014). Women and men with OSA had similar BMI (p = 0.526) and OSA severity (p = 0.754), but women were older than men (70.1 ± 1.3 vs. 63.1 ± 0.9 years, p < 0.001). Women with moderate-to-severe OSA had a lower AF burden than men did (27.6 ± 7.1 vs. 49.5 ± 3.9%, p = 0.009). Conclusions: AF burden is a sex-specific risk factor for OSA and is limited to men. In contrast, women with both AF and OSA have a lower AF burden than men, despite being older and having similar OSA severity and body habitus. Thus, AF may develop later in women with OSA than in men.

Online ethnography of breastfeeding discussions in social networking sites for Hong Kong mothers.

With the growth of social networking, parents are increasingly sharing their experiences and opinions or seeking help with childcare through online platforms. This study explored breastfeeding-related topics that Hong Kong mothers raise on social networking sites and how other mothers respond; and how these sites could be a facilitator or barrier to breastfeeding. An online ethnographic approach was used to collect breastfeeding-related discussions (posts and responses) among mothers from three sources: two closed moderated Facebook groups with more than 1000 members, and one open unmoderated forum (Baby Kingdom) (26 December 2021-26 May 2022). Posts not related to breastfeeding (e.g., about formula feeding only) were excluded. Data were collected by a nonparticipatory approach to avoid disrupting the dynamics of the groups. In total, 131 original posts and their 802 responses were collected, of which the common topics discussed were breastfeeding technique, breastfeeding-related health issues, breastfeeding mothers returning to work, and COVID-19 vaccination/infection during breastfeeding. The responses to the queries on breastfeeding technique and health issues in the closed groups were mostly about sharing breastfeeding knowledge and health information to provide timely emotional support and practical solutions. Although similar responses were observed in the open forum, sharing experiences in using formula milk were frequently observed in the responses to posts related to breastfeeding. Social networking sites could be facilitators and barriers to breastfeeding. The potential for infant formula promotion in open forums requires further monitoring and evaluation. Moderation and support from trained professionals or peers could be important.

Iron status and non-alcoholic fatty liver disease: A Mendelian randomization study.

OBJECTIVES: The aim of this study was to assess the association of genetically determined iron status with the risk for non-alcoholic fatty liver disease (NAFLD) using two-sample Mendelian randomization (MR) analysis. METHODS: We applied single nucleotide polymorphisms (SNPs) associated at genome-wide significance with iron status proxied by serum iron, ferritin, transferrin, and transferrin saturation from the Genetics of Iron status Consortium (N = 48 793), in a genome-wide association study of 1664 NAFLD cases and 400 055 controls from the United Kingdom Biobank. A SNP associated with multiple markers of iron status was only applied to one marker with the strongest association in the main analysis. Their effects on NAFLD were calculated using inverse variance weighting after excluding SNPs associated with alkaline phosphatase and lipid metabolism. RESULTS: The risk for NAFLD is negatively associated with genetically predicted serum transferrin level with a 20% reduction in NAFLD risk per SD (0.65g/L) increase in transferrin (95% confidence interval [CI], 0.66-0.97), and trending positive association with transferrin saturation (odds ratio [OR], 1.50; 95% CI, 0.96-2.35) but it was not associated with serum iron (OR, 0.90; 95% CI, 0.63-1.29) and ferritin (OR, 1.33; 95% CI, 0.54-3.30). CONCLUSIONS: MR analysis provided evidence that genetically predicted higher serum transferrin, indicating lower iron status, may be protective against NAFLD, whereas higher transferrin saturation, indicating higher iron status, might increase the risk for NAFLD and its pathogenesis.

Probable endometrial tuberculosis in a patient with rhupus.

Endometrial tuberculosis (TB) is an uncommon manifestation of disseminated TB. Rhupus is the coexistence of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We describe a case of endometrial TB in rhupus patient an immunosuppressed. Contribution: We describe an uncommon presentation of disseminated TB, endometrial TB, in a rare rheumatic disease, rhupus. A high index of suspicion for TB is imperative in immunocompromised patients presenting with chronic urogenital symptoms especially in an endemic area.

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.

Osteoporosis in Black South Africans With Rheumatoid Arthritis.

Background Osteoporosis is a common comorbidity associated with rheumatoid arthritis (RA). The aim of this study was to determine the risk factors and possible predictors of osteoporosis in black patients with RA. Methods A retrospective study of 120 randomly selected RA patients attending an arthritis clinic in Johannesburg, South Africa, was carried out, in which 60 patients were with and 60 without osteoporosis. The demographics, disease activity, American College of Rheumatology (ACR) functional status, treatment, and dual-energy X-ray absorptiometry (DEXA) characteristics were compared. Statistical analysis was performed using SPSS version 25.0 (IBM Corp, Armonk, NY). Bivariate comparisons of demographic factors, disease factors, and T-scores between patients with and without osteoporosis were performed, using two-sided t-tests for continuous variables and chi-squared tests for categorical variables. Possible predictors of osteoporosis were subsequently entered into a multivariate logistic regression model with osteoporosis being the dependent variable. The level of significance for all analyses was set at p < 0.05. Results The median (IQR) age of the overall cohort was 67 (61.0, 72.8) years, the majority (95.5%) were female, of which 97.4% were postmenopausal. The mean disease duration from diagnosis to the DEXA was 8.6 ± 6.2 years. Rheumatoid factor (RF) positivity was 89.2% and anti-cyclic citrullinated peptide (ACCP) positivity was 82.7%. The median (IQR) for disease activity score 28 swollen and tender joint count using the erythrocyte sedimentation rate (DAS-28 ESR) was 3.4 (2.8-4.7) and the median (IQR) for ESR was 41 (22, 64.3) mm/h. There were significantly more patients treated with triple therapy in the no osteoporosis group, 38 (63.3%), than in the osteoporosis group, 21 (35%) (p = 0.00). The ACR functional class was significantly worse in the RA patients with osteoporosis than in the RA patients without osteoporosis [median (IQR), 2 (2, 3) vs 2 (1, 2), (p = 0.03)], respectively. Conclusion This study found that a worse ACR functional class was significantly associated with osteoporosis. In addition, the use of triple therapy had a protective effect. Early recognition of the risk factors for osteoporosis should be sought, with prompt preventative measures, screening, and treatment.

Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.

Metabolic syndrome, today affecting more than 20% of the US population, is a group of 5 conditions that often coexist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here, we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism and that lipid droplet accumulation in endothelium suppresses endothelial nitric oxide synthase (eNOS), reduces NO production, elevates blood pressure, and accelerates atherosclerosis. Mechanistically, the accumulation of lipid droplets destabilizes eNOS mRNA and activates an endothelial inflammatory signaling cascade that suppresses eNOS and NO production. Pharmacological prevention of lipid droplet formation reverses the suppression of NO production in cell culture and in vivo and blunts blood pressure elevation in response to a high-fat diet. These results highlight lipid droplets as a critical and unappreciated component of endothelial cell biology, explain how lipids increase blood pressure acutely, and provide a mechanistic account for the epidemiological link between obesity and elevated blood pressure.

Country-level socioeconomic status relates geographical latitude to the onset of RA: a worldwide cross-sectional analysis in the METEOR registry.

OBJECTIVE: Age at rheumatoid arthritis (RA) onset varies by geographical latitude. We have investigated to what extent differences in patient-specific factors and country-level socioeconomic indicators explain this variability. METHODS: Patients with RA from the worldwide METEOR registry were included. Bayesian multilevel structural equation models were used to study the relationship between the absolute value of (hospital) geographical latitude and age at diagnosis (as a proxy for age at RA onset). We examined to what extent this effect is mediated by individual patient characteristics and by country-specific socioeconomic indicators and disentangled whether the observed effects occurred at the patient, hospital, or country levels. RESULTS: We included 37 981 patients from 93 hospitals in 17 geographically widespread countries. Mean age at diagnosis per country ranged from 39 (Iran) to 55 (Netherlands) years. Per degree increase in country latitude (between 9.9° and 55.8°), mean age at diagnosis increased by 0.23 years (95% credibility interval: 0.095 to 0.38) (reflecting >10 years difference in age at RA onset). For hospitals within a country, this latitude effect was negligible. Inclusion of patient-specific factors (eg, gender, anticitrullinated protein antibodies status) in the model augmented the main effect from 0.23 to 0.36 years. Inclusion of country-level socioeconomic indicators (eg, gross domestic product per capita) in the model almost effaced the main effect (from 0.23 to 0.051 (-0.37 to 0.38)). CONCLUSIONS: Patients living closer to the equator get RA at a younger age. This latitude gradient was not explained by individual patient characteristics, but rather by countries' socioeconomic status, providing a direct link between countries' level of welfare and the clinical onset of RA.

GC-MS Coupled with Rate-All-That-Apply (RATA) to Analyse the Volatile Flavor Substances of Yellow Wine during Fermentation.

Yellow glutinous rice wine is a traditional Chinese beverage created by soaking, boiling, and fermenting glutinous rice. The majority of current studies on the flavor of yellow glutinous rice wine are based on instrumental analysis, with sensory analysis being overlooked. In this study, 36 volatile chemicals in the fermentation process of yellow wine were annotated by GC-MS and then an OPLS-DA model was built to screen out 13 distinctive substances (VIP > 1, p < 0.01). The relative odor activity value (ROAV) was calculated using the threshold values of these chemicals and 10 substances, including alcohols, esters, and aldehydes, were found as key contributors to the overall flavor of yellow wine. Following that, consumers quantified the sensory descriptors of yellow wine using rate-all-that-apply (RATA), and correspondence analysis revealed three groups of characteristic flavors and odors. Alcohols and esters were found to be key producers of flowery and fruity scents in yellow wine, according to correlation analysis. We discovered two alcohols that are rarely found in yellow wine: [R,R]-2,3-butanediol and 1-phenylethanol. The former was found to be favorably connected with wine scent and pungent odor, and its specific effect on flavor should be researched further.

Breastfeeding challenges and opportunities during COVID-19 in Hong Kong.

Barriers to sustain breastfeeding could be time and place specific. Here, we summarise new and old challenges to breastfeeding during COVID-19 pandemic in Hong Kong, some of which were obtained from qualitative in-depth interviews with health-care professionals. We document how unnecessary massive mother-baby separations in hospitals and doubts in COVID-19 vaccine safety seriously harm breastfeeding. We also discuss how the trends and increase in acceptance of receiving post-natal care from family doctors, online-antenatal class, work-from-home policy and telemedicine implicate new strategies to protect, promote and support breastfeeding during and after the pandemic. The challenges from the COVID-19 pandemic on breastfeeding have revealed new opportunities to support breastfeeding in Hong Kong and similar settings where exclusive breastfeeding for 6 months is still not the norm.