Exploring home fall events among infants and toddlers using social media information: an infodemiology study in China.

BACKGROUND: Practical interventions of fall prevention are challenging for infants and toddlers. This study aimed to explore specific details of falls that occurred at home for kids 0-3 years old using key information from social media platforms, which provided abundant data sources for fall events. METHODS: We used internet-based search techniques to collect fall events information from 2013 to 2023. The search was restricted and implemented between 1 and 12 April 2023. Online platforms included Baidu, Weibo, WeChat, TikTok, Toutiao and Little Red Book. A qualitative descriptive approach was used to analyse the fall events and major factors, including the fall event time, child age, environmental factors and behavioural characteristics of children and caregivers. RESULTS: We identified 1005 fall injury cases among infants and toddlers. Fall mechanisms included falls from household furniture (71.2%), falls from height (21.4%) and falls on the same level (7.4%). Environmental risk factors mainly consisted of not using or installing bed rails incorrectly, a gap between beds, unstable furniture, slippery ground and windows without guardrails. Behavioural factors included caregivers leaving a child alone, lapsed attention, turning around to retrieve something, misusing baby products, inadequately holding the child and falling asleep with children. Child behavioural factors included walking or running while holding an object in hand or mouth and underdeveloped walking skills. CONCLUSION: Interventions for preventing falls should be designed specifically for Chinese families, especially considering family function in the context of Chinese culture. Social media reports could provide rich information for researchers.

Global burden of self-harm and interpersonal violence and influencing factors study 1990-2019: analysis of the global burden of disease study.

INTRODUCTION: Widespread concern exists in today's world regarding self-harm and interpersonal violence. This study to analyze the changes in temporal trends and spatial patterns of risk factors and burdens of self-harm and interpersonal violence using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. METHODS: Temporal trends in self-harm and interpersonal violence were initially summarized using the estimated annual percentage change (EAPC). Data were compiled and visualized to delineate changes in disease burden and factors influencing self-harm and interpersonal violence from 1990 to 2019, stratified by gender, age and GBD region. RESULTS: In 2019, the DALY rates of self-harm were 424.7(95% UI 383.25, 466.93). Over the period from 1999 to 2019, self-harm exhibited an overall decreasing trend, with the EAPC of -1.5351 (95% CI -1.6194, -1.4507), -2.0205 (95% CI -2.166, -1.8740) and -2.0605 (95% CI -2.2089, -1.9119), respectively. In contrast, the incidence rate of interpersonal violence was significantly higher than self-harm, with a rate of 413.44 (95% UI 329.88, 502.37) per 100,000 population. Mortality and DALYs of interpersonal violence were lower than those of self-harm, at 5.22 (95% UI 4.87, 5.63) and 342.43 (95% UI 316.61, 371.55). Disease burden of self-harm and interpersonal violence varied by gender, age groups and region. Specific risk factors showed that alcohol use, high temperature and drug use were the main risk factors for self-harm, while alcohol use, intimate partner violence and high temperature were associated with interpersonal violence. Low temperature was a common protective factor for both self-harm and interpersonal violence. The burden of self-harm and interpersonal violence was attributed to different factors influences in different SDI regions. CONCLUSIONS: The study explored temporal trends and spatial distribution of the global disease burden of self-harm and interpersonal violence, emphasizing the significant impact of factors such as alcohol use, temperature, and drug use on disease burden. Further research and policy actions are needed to interpret recent changes of disease burden of self-harm and interpersonal violence, and dedicated efforts should be implemented to devise evidence-based interventions and policies to curtail risk factors and protect high-risk groups.

Influencing factors of length of stay among repeatedly hospitalized patients with mood disorders: a longitudinal study in China.

BACKGROUND: Patients with mood disorders usually require repeated and prolonged hospitalization, resulting in a heavy burden on healthcare resources. This study aims to identify variables associated with length of stay(LOS) of repeatedly hospitalized patients with mood disorders and to provide information for optimizing psychiatry management and healthcare resource allocation. METHODS: Electronic medical records (EMRs) of repeatedly hospitalized patients with mood disorders from January 2010 to December 2018 were collected and retrospectively analyzed. Chi-square and t-test were adopted to investigate the differences in characteristics between the two groups of short LOS and long LOS. Generalized estimating equation (GEE) was conducted to investigate potential factors influencing LOS. RESULTS: A total of 2,009 repeatedly hospitalized patients with mood disorders were enrolled, of which 797 (39.7%) had a long LOS and 1,212 (60.3%) had a short LOS. Adverse effects of treatment, continuous clinical manifestation, chronic onset type, suicide attempt, comorbidity and use of antidepressants were positively associated with long LOS among all repeatedly hospitalized patients with mood disorders (P < 0.050). For patients with depression, factors associated with long LOS consisted of age, monthly income, adverse effects of treatment, continuous clinical manifestation, suicide attempt and comorbidity (P < 0.050). Whereas, for patients with bipolar disorder (BD), adverse effects of treatment, four or more hospitalizations and use of antidepressants contributed to the long LOS (P < 0.050). Influencing factors of LOS also vary among patients with different effectiveness of treatment. CONCLUSION: The LOS in repeatedly hospitalized patients with mood disorders was influenced by multiple factors. There were discrepancies in the factors affecting LOS in patients with different diagnoses and effectiveness of treatment, and specific factors should be addressed when evaluating the LOS.

Metal Ion Coordination Improves Graphite Nitride Carbon Microwave Therapy in Antibacterial and Osteomyelitis Treatment.

The ability to effectively treat deep bacterial infections while promoting osteogenesis is the biggest treatment demand for diseases such as osteomyelitis. Microwave therapy is widely studied due to its remarkable ability to penetrate deep tissue. This paper focuses on the development of a microwave-responsive system, namely, a zinc ion (Zn2+ ) doped graphite carbon nitride (CN) system (BZCN), achieved through two high-temperature burning processes. By subjecting composite materials to microwave irradiation, an impressive 99.81% eradication of Staphylococcus aureus is observed within 15 min. Moreover, this treatment enhances the growth of bone marrow stromal cells. The Zn2+ doping effectively alters the electronic structure of CN, resulting in the generation of a substantial number of free electrons on the material's surface. Under microwave stimulation, sodium ions collide and ionize with the free electrons generated by BZCN, generating a large amount of energy, which reacts with water and oxygen, producing reactive oxygen species. In addition, Zn2+ doping improves the conductivity of CN and increases the number of unsaturated electrons. Under microwave irradiation, polar molecules undergo movement and generate frictional heat. Finally, the released Zn2+ promotes macrophages to polarize toward the M2 phenotype, which is beneficial for tibial repair.

Ultra-Strong Comprehensive Radiation Effect Tolerance in Carbon Nanotube Electronics.

Carbon nanotube (CNT) field-effect transistors (FETs) have been considered ideal building blocks for radiation-hard integrated circuits (ICs), the demand for which is exponentially growing, especially in outer space exploration and the nuclear industry. Many studies on the radiation tolerance of CNT-based electronics have focused on the total ionizing dose (TID) effect, while few works have considered the single event effects (SEEs) and displacement damage (DD) effect, which are more difficult to measure but may be more important in practical applications. Measurements of the SEEs and DD effect of CNT FETs and ICs are first executed and then presented a comprehensive radiation effect analysis of CNT electronics. The CNT ICs without special irradiation reinforcement technology exhibit a comprehensive radiation tolerance, including a 1 × 104 MeVcm2 mg-1 level of the laser-equivalent threshold linear energy transfer (LET) for SEEs, 2.8 × 1013 MeV g-1 for DD and 2 Mrad (Si) for TID, which are at least four times higher than those in conventional radiation-hardened ICs. The ultrahigh intrinsic comprehensive radiation tolerance will promote the applications of CNT ICs in high-energy solar and cosmic radiation environments.

The prevalence of disability and associated factors among community adults in the baseline of CHCN-BTH Cohort Study.

BACKGROUND: Disability was a major public health problem in China. However, the prevalence of disabilities in community-dwelling adults and their relationships to chronic physical conditions were unclear. We aimed to estimate the prevalence of disabilities and associated factors among a large community-based cohort in China. METHODS: Participants who were local permanent residents aged 18 years or above and completed the disability assessments were selected from the Cohort study on Chronic Disease of Communities Natural Population in Beijing, Tianjin and Hebei (CHCN-BTH) from 2017 to 2019. Disability was assessed using five questions about impairments and activity limitations based on the International Classification of Functioning (ICF), Disability and Health. Univariate, multivariate and multilevel logistic regressions were conducted to estimate the associations between disabilities and associated factors. RESULTS: Totally, 12,871 community-dwelling adults completed the survey. Among of them, 12.9% (95% CI: 12.3%-13.5%) reported having any disability. The prevalence of any disability was significantly higher in participants who were older age, widowed, retired and smokers, had higher BMI, average monthly income < 5000 RMB, lower education level, lower physical exercise frequency and heavy physical labor. Multilevel logistic regressions showed that there were significant associations between disabilities with chronic physical conditions, especially in the vision impairment with lower back pain, and hearing impairment as well as difficulty walking without special equipment with injuries. CONCLUSIONS: Many Chinese adults suffered from disabilities. Sustained efforts should be made to develop specific population-based health promotion and prevention programs for disabilities in China. TRAIL REGISTRATION: ChiCTR1900024725 (25/07/2019).

CIC de novo loss of function variants contribute to cerebral folate deficiency by downregulating FOLR1 expression.

Background Cerebral folate deficiency (CFD) syndrome is characterised by a low concentration of 5-methyltetrahydrofolate in cerebrospinal fluid, while folate levels in plasma and red blood cells are in the low normal range. Mutations in several folate pathway genes, including FOLR1 (folate receptor alpha, FRα), DHFR (dihydrofolate reductase) and PCFT (proton coupled folate transporter) have been previously identified in patients with CFD. Methods In an effort to identify causal mutations for CFD, we performed whole exome sequencing analysis on eight CFD trios and identified eight de novo mutations in seven trios. Results Notably, we found a de novo stop gain mutation in the capicua (CIC) gene. Using 48 sporadic CFD samples as a validation cohort, we identified three additional rare variants in CIC that are putatively deleterious mutations. Functional analysis indicates that CIC binds to an octameric sequence in the promoter regions of folate transport genes: FOLR1, PCFT and reduced folate carrier (Slc19A1; RFC1). The CIC nonsense variant (p.R353X) downregulated FOLR1 expression in HeLa cells as well as in the induced pluripotent stem cell (iPSCs) derived from the original CFD proband. Folate binding assay demonstrated that the p.R353X variant decreased cellular binding of folic acid in cells. Conclusion This study indicates that CIC loss of function variants can contribute to the genetic aetiology of CFD through regulating FOLR1 expression. Our study described the first mutations in a non-folate pathway gene that can contribute to the aetiology of CFD.

Incidence of post-traumatic stress disorder in survivors of traumatic fracture: a systematic review and meta-analysis.

Post-traumatic stress disorder (PTSD) is prevalent in traumatic events. It is a great hazard of physical and mental health due to their severity and frequency. Traumatic fractures are one of the major causes of PTSD. The incidence of traumatic fractures has been high in recent years, which will directly or indirectly result in PTSD. Our target is to estimate the pooled incidence of PTSD in fracture patients after traumatic events and to explore possible influencing factors by a meta-analysis.The systematic searches in the electronic bibliographic databases of Web of Science, ScienceDirect, Ovid MEDLINE, PubMed, CNKI (China National Knowledge Infrastructure), Wangfang , and Veipu Databases. Not only were heterogeneity and 95% confidence interval (CI) used for comprehensive assessing each pooled, but also was the P value. Subgroup analyses for some sample characteristics were calculated the pooled incidence of PTSD among patients suffered from fractures.In total, 2619 patients suffered from fracture, and were assessed PTSD in the 12 eligible studies. The heterogeneity was not low (I2 = 97.6%, P < 0.001) in the 12 eligible studies. The pooled incidence of PTSD in fracture patients was 29% (95% CI, 20% to 39%) using random-effects model. Subgroup analyses revealed that the pooled incidence of PTSD among patients after traumatic fracture was statistically significant differences according to the study design, the study location, tools to assess the symptoms of PTSD, the mean age and injury mechanism (all P < 0.001). Fracture sites, injury mechanism and pain were the main influencing factors of PTSD in fracture patients.Our results highlight the phenomenon that high incidence of PTSD in patients after fracture and they should be followed up regularly and be provided effective interventions. Future efforts to improve and control the main influencing factors of PTSD for this population still needed.

The TFAP2A-IRF6-GRHL3 genetic pathway is conserved in neurulation.

Mutations in IRF6, TFAP2A and GRHL3 cause orofacial clefting syndromes in humans. However, Tfap2a and Grhl3 are also required for neurulation in mice. Here, we found that homeostasis of Irf6 is also required for development of the neural tube and associated structures. Over-expression of Irf6 caused exencephaly, a rostral neural tube defect, through suppression of Tfap2a and Grhl3 expression. Conversely, loss of Irf6 function caused a curly tail and coincided with a reduction of Tfap2a and Grhl3 expression in tail tissues. To test whether Irf6 function in neurulation was conserved, we sequenced samples obtained from human cases of spina bifida and anencephaly. We found two likely disease-causing variants in two samples from patients with spina bifida. Overall, these data suggest that the Tfap2a-Irf6-Grhl3 genetic pathway is shared by two embryologically distinct morphogenetic events that previously were considered independent during mammalian development. In addition, these data suggest new candidates to delineate the genetic architecture of neural tube defects and new therapeutic targets to prevent this common birth defect.

Comparison between the molecular diagnostic test and chest X-ray combined with multi-slice spiral CT in the diagnosis of lobar pneumonia.

Lobar pneumonia is an inflammatory condition of the lung that mainly affects the lobes of the lungs and the alveoli, and it is usually caused by a bacterial infection. There are many ways to diagnosis this disease. But an early and accurate method for lobar pneumonia diagnosis has an important role in its treatment. Therefore, in this study, a comparison between the molecular diagnostic test and chest x-ray combined with multi-slice spiral CT was done to find out better diagnosis of lobar pneumonia. For this purpose, 122 individuals suspected of lobar pneumonia were studied by clinical examination, chest X-ray, and multi-slice spiral CT. For the molecular diagnosis test, the multiplex PCR was used for two main causes of the disease, Streptococcus pneumoniae and Klebsiella pneumoniae. Results showed that the specificity for Chest X-ray + Multi-slice Spiral CT had the highest amount (82.8%), but high sensitivity (100%) belonged to a molecular diagnostic test for both bacteria. On the other hand, the sensitivity and specificity of Streptococcus pneumoniae were better than Klebsiella pneumoniae and the possibility of error in Streptococcus pneumoniae was lower than Klebsiella pneumoniae. In general, although the Chest X-ray + Multi-slice Spiral CT method was better than the molecular diagnosis test, it could not identify the causative agent and did not show a difference between pathogens for better antibiotic treatment, and also the possibility of diagnosis is low at the beginning of the disease. Therefore, according to the results of the current study, the best way to diagnose lobar pneumonia is to use both methods, simultaneously.

[Jiawei Baitouweng Decoction affects intestinal mucosal tight junction proteins in rats with ulcerative colitis through p38 MAPK-MLCK signaling pathway].

The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.

Deliberate self-harm among children with disabilities in China: a matched case-control study.

BACKGROUND: Study about deliberate self-harm (DSH) in children with different types of disabilities was scarce. This study compared the incidence and patterns of DSH between children with and without disabilities aged 6-17 years using a matched case-control study in Beijing. METHODS: A total of 650 pairs of children with and without disabilities were surveyed. Characteristics of latest episode of self-harm within the 12 months were compared. Associations between disability status, sociodemographic factors, smoking, drinking, sleep problems, and self-harm were examined. RESULTS: Children with disabilities showed significant higher incidence of DSH than children without disabilities. Two groups differed significantly in terms of self-harm methods, body parts injured, premeditation, wishing to be known by others and help-seeking behavior. The adjusted OR for self-harm was 4.76 (2.99-7.55) for children with disabilities compared with children without disabilities. Children who slept fewer than 6 h per night, had difficulty falling asleep at night sometimes/often, and went to sleep after midnight 1 to 3 nights per month or at least once a week were at elevated risk of self-harm. CONCLUSION: This study highlights a strong relationship between disability, sleep problems, and DSH. Interventions to reduce self-harm should target disability and sleep problems as important risk factors.

Incidence and Risk Factors of Intrauterine Transmission Among Pregnant Women With Chronic Hepatitis B Virus Infection.

GOALS: To identify the potential risk factors of hepatitis B virus (HBV) intrauterine transmission and predict the incidence of HBV intrauterine transmission among hepatitis B surface antigen-positive pregnant women with diverse viral load. BACKGROUND: The intrauterine transmission of HBV significantly contributes to the persistence of a high number of patients infected with HBV. However, its risk factors remain unclear. MATERIALS AND METHODS: A prospective study was performed on hepatitis B surface antigen-positive pregnant women who delivered from June 2012 to December 2016 at Wuhan Medical Care Center for Women and Children, Wuhan, China. RESULTS: In total, 1200 women paired with 1219 infants were enrolled. In total, 11 (0.9%) infants were identified with intrauterine transmission. We observed that all infants with intrauterine transmission were born to hepatitis B e antigen-positive mothers who had serum HBV DNA levels >7 log10 copies/mL. Our study suggested that the HBV DNA levels (for each log10 copies/mL increase, odds ratio=5.43; 95% confidence interval, 1.31-22.43; P=0.019) had independent effects on HBV intrauterine transmission in a multivariate logistic regression model. Moreover, cesarean section (odds ratio=0.18; 95% confidence interval, 0.04-0.74; P=0.018) was associated with a reduced risk of HBV intrauterine transmission. The predictive rates of intrauterine transmission were 0.06%, 0.50%, 2.81%, 8.89% in infants with maternal HBV DNA levels of 10, 10, 10, 10 copies/mL, respectively. CONCLUSIONS: Our data confirmed that increasing maternal viral load has the ability to predict intrauterine HBV transmission. Vaginal delivery increased risk of HBV transmission in infants compared with cesarean section. Further studies are warranted to clarify the possible mechanism underlying these associations.

Maternal Hepatitis B Virus Infection and Pregnancy Outcomes: A Hospital-based Case-control Study in Wuhan, China.

GOALS: To examine the impact of maternal hepatitis B virus infection on pregnancy outcomes. BACKGROUND: Studies regarding hepatitis B virus infection and pregnancy outcomes are limited with inconsistent results, and none of them have evaluated the effect of maternal viral load in pregnancy on pregnancy outcomes. STUDY: A hospital-based case-control study was conducted. In total, 1728 hepatitis B surface antigen (HBsAg)-positive women who delivered consecutively at Wuhan Women and Children Medical and Healthcare Center, Wuhan, China, from June 2008 to May 2015, were compared with 1497 HBsAg-negative women giving birth in the same hospital during the same period who were randomly identified and selected from the computerized medical record database in parallel. Univariate and multivariate logistic regression models were constructed. RESULTS: After adjusting for confounding variables, maternal HBsAg carriage was associated with increased risk of pregnancy-induced hypertension [adjusted odds ratio (aOR)=2.20; 95% confidence interval (CI), 1.30-3.73], fetal distress (aOR=1.40; 95% CI, 1.09-1.78), cesarean delivery (aOR=1.70; 95% CI, 1.45-1.99), and macrosomia (aOR=1.68; 95% CI, 1.19-2.37). Moreover, maternal viral load in the second trimester was significantly associated with risk of preterm birth (aOR for each log10 copy/mL increase, 1.18; 95% CI, 1.01-1.39) among HBsAg carriers after adjustment for maternal age, employment, parity, history of abortion, and prenatal body mass index. CONCLUSIONS: Maternal HBsAg carriage was associated with several adverse pregnancy outcomes. Furthermore, hepatitis B viral activity in pregnancy might have certain effects on pregnancy outcomes. Careful surveillance of maternal HBsAg status as well as viral activity in the second trimester among HBsAg carriers is warranted.

Changes in proteinuria and the risk of myocardial infarction in people with diabetes or pre-diabetes: a prospective cohort study.

BACKGROUND: The relationship between changes in proteinuria and myocardial infarction (MI) remains unclear in people with diabetes or pre-diabetes. We aimed to evaluate the predictive value and independent role of changes in proteinuria over a 2-year period in the incidence of MI in people with diabetes or pre-diabetes. METHODS: Based on the baseline and 2-year dipstick screening results from the Kailuan prospective cohort study, participants were divided into four categories: no proteinuria, remittent proteinuria, incident proteinuria, and persistent proteinuria. Four multivariable Cox proportional hazard models were built to adjust for the effects of different confounding covariates. RESULTS: Among the 17,625 participants in this study, there were a total of 238 incidents of MI during a median follow-up of 6.69 years. After adjusting for demography factors and laboratory indices, the association between persistent proteinuria and MI incidence was maintained (hazard ratio [HR] 2.50, 95% confidence interval [CI] 1.48-4.22). Every decrease of proteinuria from 2006 to 2008 was observed to be responsible for a 21% decline of MI incidence (HR 0.79, 95% CI 0.68-0.90). The interaction between changes in proteinuria and diabetes was confirmed with no effect on MI (P = 0.3371). CONCLUSIONS: Persistent proteinuria is an independent risk factor for MI incidence in the pre-diabetic and diabetic population. These findings may help clinicians to interpret proteinuria changes in the outpatient setting and provide possible preventive approaches for people with pre-diabetes or diabetes.

Erratum to: Changes in proteinuria and the risk of myocardial infarction in people with diabetes or pre-diabetes: a prospective cohort study.

Following publication of the original article [1], the authors reported that figure 2 had not been replaced with the correct figure as indicated in the proofs.

Longitudinal Associations between Triglycerides and Metabolic Syndrome Components in a Beijing Adult Population, 2007-2012.

BACKGROUND: Longitudinal associations between triglycerides (TG) and other metabolic syndrome (MetS) components have rarely been reported. The purpose was to investigate the longitudinal association between TG and other MetS components with time. METHODS: The longitudinal study was established in 2007 on individuals who attended health check-ups at Beijing Tongren Hospital and Beijing Xiaotangshan Hospital. Data used in this study was based on 7489 participants who had at least three health check-ups over a period of 5-year follow up. Joint model was used to explore longitudinal associations between TG and other MetS components after adjusted for age. RESULTS: There were positive correlations between TG and other MetS components except for high density lipoprotein (HDL), and the correlations increased with time. A negative correlation was displayed between TG and HDL, and the correlation also increased with time. Among all five pairs of TG and other MetS components, the marginal correlation between TG and body mass index (BMI) was the largest for both men and women. The marginal correlation between TG and fasting plasma glucose was the smallest for men, while the marginal correlation between TG and diastolic blood pressure was the smallest for women. CONCLUSIONS: The longitudinal association between TG and other MetS components increased with time. Among five pairs of TG and other MetS components, the longitudinal correlation between TG and BMI was the largest. It is important to closely monitor subjects with high levels of TG and BMI in health check-up population especially for women, because these two components are closely associated with development of hypertension, diabetes, cardiovascular disease and other metabolic diseases.

Rare LRP6 variants identified in spina bifida patients.

Several single-nucleotide variants (SNVs) in low-density lipoprotein receptor-related protein 6 (Lrp6) cause neural tube defects (NTDs) in mice. We therefore examined LRP6 in 192 unrelated infants from California with the NTD, spina bifida, and found four heterozygous missense SNVs, three of which were predicted to be deleterious, among NTD cases and not in 190 ethnically matched nonmalformed controls. Parents and siblings could not be tested because of the study design. Like Crooked tail and Ringleschwanz mouse variants, the p.Tyr544Cys Lrp6 protein failed to bind the chaperone protein mesoderm development and impaired Lrp6 subcellular localization to the plasma membrane of MDCK II cells. Only the p.Tyr544Cys Lrp6 variant downregulated canonical Wnt signaling in a TopFlash luciferase reporter in vitro assay. In contrast, three Lrp6 mutants (p.Ala3Val, p.Tyr544Cys, and p.Arg1574Leu) increased noncanonical Wnt/planar cell polarity (PCP) signaling in an Ap1-luciferase assay. Thus, LRP6 variants outside of YWTD repeats could potentially predispose embryos to NTDs, whereas Lrp6 modulation of Wnt/PCP signaling would be more essential than its canonical pathway role in neural tube closure.

Analysis of archived residual newborn screening blood spots after whole genome amplification.

BACKGROUND: Deidentified newborn screening bloodspot samples (NBS) represent a valuable potential resource for genomic research if impediments to whole exome sequencing of NBS deoxyribonucleic acid (DNA), including the small amount of genomic DNA in NBS material, can be overcome. For instance, genomic analysis of NBS could be used to define allele frequencies of disease-associated variants in local populations, or to conduct prospective or retrospective studies relating genomic variation to disease emergence in pediatric populations over time. In this study, we compared the recovery of variant calls from exome sequences of amplified NBS genomic DNA to variant calls from exome sequencing of non-amplified NBS DNA from the same individuals. RESULTS: Using a standard alignment-based Genome Analysis Toolkit (GATK), we find 62,000-76,000 additional variants in amplified samples. After application of a unique kmer enumeration and variant detection method (RUFUS), only 38,000-47,000 additional variants are observed in amplified gDNA. This result suggests that roughly half of the amplification-introduced variants identified using GATK may be the result of mapping errors and read misalignment. CONCLUSIONS: Our results show that it is possible to obtain informative, high-quality data from exome analysis of whole genome amplified NBS with the important caveat that different data generation and analysis methods can affect variant detection accuracy, and the concordance of variant calls in whole-genome amplified and non-amplified exomes.