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Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.
An increasing number of studies have described the relationship between celiac disease and schizophrenia. Based on the reported correlations and the overlapping linkage regions on 19p13, the myosin IXB gene (MYO9B) can be considered a highly relevant positional and functional candidate gene for schizophrenia. The present work was undertaken to investigate the association of the MYO9B gene with schizophrenia in a Chinese population.
A total of 329 patients with schizophrenia and 350 healthy control subjects in a Chinese population were recruited. A PCR-based RFLP protocol was applied to genotype 7 single nucleotide polymorphisms (SNPs), including rs7249490, rs7256689, rs2279007, rs8113494, rs2305767, rs1545620 and rs2305764, in the MYO9B gene to investigate their association with schizophrenia.
The X2 goodness-of-fit test showed that the genotypic distributions of all 7 SNPs were in Hardy-Weinberg equilibrium in both the patient group and the control group. Disease association was shown for rs8113494 (X2=12.77, P=0.0003, OR=1.89, 95% CI 1.33-2.68) and rs1545620 (X2=15.44, P=8.379e-5, OR=1.65, 95% CI 1.29-2.12), while rs2279007 was associated with schizophrenia in the female subjects (X2=4.637, P=0.031, OR=0.69, 95% CI 0.49-0.97) but not in the male subjects (X2=1.082, P=0.299, OR=0.85, 95% CI 0.63-1.15).
The present work shows that the polymorphisms of the MYO9B gene are likely to confer susceptibility to schizophrenia. Because the MYO9B gene has been found to be highly expressed in the tight junction gate, it could be considered as a meeting point for the interaction between environmental and genetic factors in the pathogenesis of schizophrenia.
An increasing number of studies have described the relationship between velo-cardio-facial syndrome (VCFS) and schizophrenia. in a family-based study, we found that rs10314, a single nucleotide polymorphism (SNP) present in the 3’-flanking region of the CLDN5 gene, was associated with schizophrenia among a Chinese population. High false positive rate is a common problem with the association study of human diseases. It is very important to replicate an initial finding with different samples and experimental designs.
A total of 749 patients with schizophrenia and 383 age and sex matched healthy control subjects in Chinese population were recruited. PCR-based RFLP protocol was applied to genotype rs10314 to see its disease association.
The χ2 goodness-of-fit test showed that the genotypic distributions of rs10314 were in Hardy-Weinberg equilibrium in both the patient group (χ2=1.12, P=0.289) and the control group (χ2=0.22, P=0.639). rs10314 was associated with schizophrenia with an odds ratio (OR) of 1.32 in the male subjects (χ2=5.45, P=0.02, 95% CI 1.05-1.67) but not in the female subjects (χ2=0.64, P=0.425, OR=1.14, 95% CI 0.83-1.57). the χ2 test showed a genotypic association only for combined samples (χ2=7.80, df=2, P=0.02). SNP rs10314 is a G to C base change. Frequency of the genotypes containing the C allele was significantly higher in the patient group than in the control group.
The present work shows that the CLDN5 gene polymorphism is more likely to be involved in schizophrenic men than women, suggesting that this gene may contribute to the gender differences in schizophrenia.
The aim of this study was to develop and externally validate a simple-to-use nomogram for predicting the survival of hospitalised human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients (hospitalised person living with HIV/AIDS (PLWHAs)). Hospitalised PLWHAs (n = 3724) between January 2012 and December 2014 were enrolled in the training cohort. HIV-infected inpatients (n = 1987) admitted in 2015 were included as the external-validation cohort. The least absolute shrinkage and selection operator method was used to perform data dimension reduction and select the optimal predictors. The nomogram incorporated 11 independent predictors, including occupation, antiretroviral therapy, pneumonia, tuberculosis, Talaromyces marneffei, hypertension, septicemia, anaemia, respiratory failure, hypoproteinemia and electrolyte disturbances. The Likelihood χ2 statistic of the model was 516.30 (P = 0.000). Integrated Brier Score was 0.076 and Brier scores of the nomogram at the 10-day and 20-day time points were 0.046 and 0.071, respectively. The area under the curves for receiver operating characteristic were 0.819 and 0.828, and precision-recall curves were 0.242 and 0.378 at two time points. Calibration plots and decision curve analysis in the two sets showed good performance and a high net benefit of nomogram. In conclusion, the nomogram developed in the current study has relatively high calibration and is clinically useful. It provides a convenient and useful tool for timely clinical decision-making and the risk management of hospitalised PLWHAs.
The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear.
Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function.
We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease × COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system).
Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD.
Chlamydia trachomatis (CT) infection has been a major public health threat globally. Monitoring and prediction of CT epidemic status and trends are important for programme planning, allocating resources and assessing impact; however, such activities are limited in China. In this study, we aimed to apply a seasonal autoregressive integrated moving average (SARIMA) model to predict the incidence of CT infection in Shenzhen city, China. The monthly incidence of CT between January 2008 and June 2019 in Shenzhen was used to fit and validate the SARIMA model. A seasonal fluctuation and a slightly increasing pattern of a long-term trend were revealed in the time series of CT incidence. The monthly CT incidence ranged from 4.80/100 000 to 21.56/100 000. The mean absolute percentage error value of the optimal model was 8.08%. The SARIMA model could be applied to effectively predict the short-term CT incidence in Shenzhen and provide support for the development of interventions for disease control and prevention.
Guangxi, a province in southwestern China, has the second highest reported number of HIV/AIDS cases in China. This study aimed to develop an accurate and effective model to describe the tendency of HIV and to predict its incidence in Guangxi. HIV incidence data of Guangxi from 2005 to 2016 were obtained from the database of the Chinese Center for Disease Control and Prevention. Long short-term memory (LSTM) neural network models, autoregressive integrated moving average (ARIMA) models, generalised regression neural network (GRNN) models and exponential smoothing (ES) were used to fit the incidence data. Data from 2015 and 2016 were used to validate the most suitable models. The model performances were evaluated by evaluating metrics, including mean square error (MSE), root mean square error, mean absolute error and mean absolute percentage error. The LSTM model had the lowest MSE when the N value (time step) was 12. The most appropriate ARIMA models for incidence in 2015 and 2016 were ARIMA (1, 1, 2) (0, 1, 2)12 and ARIMA (2, 1, 0) (1, 1, 2)12, respectively. The accuracy of GRNN and ES models in forecasting HIV incidence in Guangxi was relatively poor. Four performance metrics of the LSTM model were all lower than the ARIMA, GRNN and ES models. The LSTM model was more effective than other time-series models and is important for the monitoring and control of local HIV epidemics.
Over a hundred millisecond radio pulsars (MSPs) have been observed in globular clusters (GCs), motivating theoretical studies of the formation and evolution of these sources through stellar evolution coupled to stellar dynamics. Here we study MSPs in GCs using realistic N-body simulations with our Cluster Monte Carlo code. We show that neutron stars (NSs) formed in electron-capture supernovae can be spun up through mass transfer to form MSPs. Both NS formation and spin-up through accretion are greatly enhanced through dynamical interaction processes. We find that our models for average GCs at the present day with masses ≍ 2 × 105M⊙ can produce up to 10 – 20 MSPs, while a very massive GC model with mass ≍ 106M⊙ can produce close to 100. We show that the number of MSPs is anti-correlated with the total number of stellar-mass black holes (BHs) retained in the host cluster. As a result, the number of MSPs in a GC could be used to place constraints on its BH population. Some intrinsic properties of MSP systems in our models (such as the magnetic fields and spin periods) are in good overall agreement with observations.
As self-gravitating systems, dense star clusters exhibit a natural diffusion of energy from their innermost to outermost regions, leading to a slow and steady contraction of the core until it ultimately collapses under gravity. However, in spite of the natural tendency toward “core collapse,” the globular clusters (GCs) in the Milky Way exhibit a well-observed bimodal distribution in core radii separating the core-collapsed and non-core-collapsed clusters. This suggests an internal energy source is at work, delaying the onset of core collapse in many clusters. Over the past decade, a large amount of work has suggested that stellar black holes (BHs) play a dynamically-significant role in clusters throughout their entire lifetimes. Here we review our latest understanding of BH populations in GCs and demonstrate that, through their dynamical interaction with their host cluster, BHs can naturally explain the distinction between core-collapsed and non-core-collapsed clusters through a process we call “black hole burning.”
Alanyl-glutamine (Ala-Gln), a highly soluble and stable glutamine dipeptide, is known to improve gut integrity and function. The aim of this study was to evaluate whether dietary Ala-Gln supplementation could improve growth performance, intestinal development and digestive-absorption function in weaned piglets. A total of 100 purebred Yorkshire piglets weaned at 21 days of age were assigned randomly to four dietary treatment groups and fed a basal diet (control group) or a basal diet containing 0.15%, 0.30% and 0.45% Ala-Gln, respectively. Compared with the control group, piglets fed the Ala-Gln diets had higher average daily gain and lower feed : gain and diarrhea rate (P < 0.05). Moreover, dietary Ala-Gln supplementation increased villous height and villous height : crypt depth ratio in duodenum and jejunum (P < 0.05), as well as the activities of maltase and lysozyme in jejunum mucosa (P < 0.05). In addition, a decrease in serum diamine oxidase activity and crypt depth in duodenum and jejunum was observed in piglets fed the Ala-Gln diets (P < 0.05). Serum cytosolic phospholipase A2 (cPLA2) concentration and gene expression of cPLA2, Na+-dependent glucose transporter 1, glucose transporter 2 and peptide transporter 1 in jejunum were increased by feeding Ala-Gln diets relative to control diet (P < 0.05). These results indicated that feeding Ala-Gln diet has beneficial effects on the growth performance of weaned piglets, which associated with maintaining intestinal morphology and digestive-absorption function.
The association between opportunistic infection (OI) and anaemia among HIV-infected patients remains to be studied. We investigated the prevalence and risk factors of anaemia in hospitalised HIV-infected patients to reveal the association between OI and anaemia. We conducted a retrospective study of HIV-positive hospitalised patients from June 2016 to December 2017 in Mengchao Hepatobiliary Hospital of Fujian Medical University. Patients’ information on socio-demographic and clinical characteristics were carefully collected. The comparison of anaemia prevalence between groups was conducted with χ2 test. A logistic regression model was carried out to analyse the predictors of anaemia. The total prevalence of anaemia in hospitalised HIV-infected patients was 55.15%. The prevalence of mild, moderate and severe anaemia was 41.42%, 11.08% and 2.64%, respectively. Predictors independently associated with anaemia were: CD4 counts <50 cells/μl (odds ratio (OR): 6.376, 95% confidence interval (CI) = 1.916–21.215, P = 0.003), CD4 counts 50–199 cells/μl (OR: 6.303, 95% CI = 1.874–21.203, P = 0.003), co-infection with tuberculosis (TB) (OR: 2.703, 95% CI = 1.349–5.414, P = 0.005) or Penicillium marneffei (PM) (OR: 7.162, 95% CI = 3.147–15.299, P < 0.001). In Fujian, China, more than half inpatients with HIV were anaemic, but severe anaemia is infrequent. Lower CD4 counts, co-infection with TB or PM were independent risk factors for anaemia. Chinese HIV patients especially with TB, PM infection and low CD4 level should be routinely detected for anaemia to improve therapy.
Grounded on the premise that dust particles are charged hard balls, the analysis in Davletov et al. (Contrib. Plasma Phys., vol. 56, 2016, 308) provides an original pseudopotential model of intergrain interaction in complex (dusty) plasmas. This accurate model is engaged herein to consistently treat the finite-size effects from the process of dust particle charging to determination of the thermodynamic quantities and the dust-acoustic wave dispersion in the strongly coupled regime. The orbital motion limited approximation is adopted to evaluate an electric charge of dust grains immersed in a neutralizing background of the buffer plasma. To account for finite dimensions of dust particles, the radial distribution function is calculated within the reference hypernetted-chain (RHNC) approximation to demonstrate a well-pronounced short-range order formation at rather large values of the coupling parameter and the packing fraction. The evaluated excess pressure of the dust component is compared to the available theoretical approaches and the simulation data and is then used to predict the dust-acoustic wave (DAW) dispersion in the strongly coupled regime under the assumption that the dust particles charge varies in the course of propagation. In contrast to many previous investigations, it is demonstrated for the first time ever that for DAWs the charge variation of dust particles should necessarily be taken into account while evaluating the dust isothermal compressibility.
OBJECTIVES/SPECIFIC AIMS: We hypothesize that both NGF and TNF-α contribute to oral cancer pain by upregulating pro-nociceptive inflammatory cytokines. METHODS/STUDY POPULATION: In total, 48 oral cancer patients were evaluated and their pain scores were measured using a validated oral cancer pain questionnaire. Presence of perineural invasion (PNI) was identified from patients’ pathology reports. We utilized The NIH Cancer Genome Atlas (TCGA) Head and Neck Cancer cohort to investigate the association between pain and genes related to NGF, TNF-α, and their receptors (TRKA, P75, TNF-α receptor 1, and TNF-α receptor 2) in oral cancer samples by employing PNI as a surrogate for pain. Demographic characteristics, clinical characteristics, and genes were analyzed using logistic regression models. A xenograft cancer pain model was created by inoculating human oral cancer cells (HSC-3) into the mouse hind paw. Mice (n=6 per group) were treated with anti-NGF alone, anti-TNF-α alone, a combination of anti-NGF and anti-TNF-α, or PBS (vehicle control). Nociceptive behaviors were measured using an electronic paw withdrawal assay. Paw volume was measured using a plethysmometer. Cytokines in the paw tissues were measured using a multiplex assay kit with 28 cytokines. RESULTS/ANTICIPATED RESULTS: Oral cancer patients with PNI report significantly more pain compared with patients without PNI in our patient cohort (p<0.05). From analysis of TCGA data, we found that PNI is significantly associated with lymphovascular invasion, pathological nodal invasion, and pathological tumor staging (all p<0.05). In adjusted models, we observed that the NGF receptor p75NTR (NGFR) and the TNF-α receptor 1 (TNFRSF1A) were associated with PNI (both p<0.05) and significantly correlated to each other (r=0.25, p<0.001). High levels of TNF-α were present in HSC-3 cell lines and the mouse xenograft cancers. In mice with cancer pain, combined treatment with anti-NGF and anti-TNF-α together provided more effective pain control compared with either anti-NGF or anti-TNF-α treatment alone (p<0.05). We found significantly increased levels of MIP3a, IL-1b, IL-2, IL-4, IL-28b, IL-23, IL17a, IL-31, and IL-33 in cancer mice compared with normal mice (all p<0.05). The combination therapy significantly reduced cytokines MIP3a, IL-1b, IL-4, IL-28b, IL-31, and IL-33 (all p<0.05). DISCUSSION/SIGNIFICANCE OF IMPACT: We show that targeting both NGF and TNF-α provides more effective pain relief in an oral cancer model. These results suggest that therapeutic strategies aimed at both pathways could yield improved pain management for oral cancer patients.
Diarrhea is a common cause of morbidity and mortality and the incidence of diarrhea in the world has changed little over the past four decades. To assess the prevalence of and healthcare practices for diarrhea, a cross-sectional study was conducted in Pudong, Shanghai, China. In October 2014, a total of 5324 community residents were interviewed. Respondents were asked if they had experienced diarrhea (defined as ⩾3 passages of watery, loose, bloody, or mucoid stools within a 24-h period) in the previous month prior to the interview. The monthly prevalence of diarrhea was 4·1% (95% CI: 3·3–4·8), corresponding to an incidence rate of 0·54 episodes per person-year. The proportion of individuals with diarrhea who sought healthcare was 21·2% (95% CI: 13·4–29·0). Diarrhea continues to impose a considerable burden on the community and healthcare system in Pudong. Young age and travel were identified as predictors of increased diarrhea occurrence.
An experimental investigation into laser ablation of secondary explosives, cyclotetramethylene tetranitramine (HMX), has been carried out by using a solid-state laser at the wavelength of 1064 nm. The ion particles of decomposition were detected by using a time-of-flight mass spectrometer. Possible attributions of both negative ions and positive ions were obtained. Some obvious peaks were found at m/z = 18, 28, 46, 60, and 106, corresponding to H2O, CO/N2/H2CN, NO2, CH2NO2/N2O2, and N(NO2)2/CH2(NO2)2, respectively. According to the distribution of the particles, three possible pathways were proposed to explain the process of particles. The results may shed some light on the possible decomposition mechanism of HMX under laser initiation.
Pig farmers and veterinarians have high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) due to the occupational livestock exposure, while few reported this association on slaughterhouse workers. We conducted this cross-sectional study to explore the phenotypic and molecular characteristics of S. aureus and MRSA in slaughterhouse pig-related workers and control workers in Guangdong Province, China. Participants were interviewed and provided two nasal swabs. Swabs were tested for S. aureus, and isolates were further tested for antimicrobial susceptibility, virulence genes and multi-locus sequence typing. Compared with control workers, pig-related workers have significantly higher prevalence of MRSA carriage (adjusted odd ratio (aOR) 3·70, 95% CI 1·63–8·40). The proportions of MRSA resistant to clindamycin, erythromycin, tetracycline or chloromycetin were significantly higher in pig-related workers than in control workers. The predominant phenotypes of S. aureus were resistant to penicillin, clindamycin, erythromycin and tetracycline. Three MRSA CC9 isolates with livestock-associated characteristics (resistance to tetracycline and absence of immune evasion cluster (IEC) genes) were detected in pig-related workers but not in control workers. For human-associated CCs (CC7, CC59, CC6, and CC188), there was no significant difference in IEC profile or antimicrobial resistance between the groups. These findings reveal that there may be a potential risk for livestock-to-human transmission of LA-MRSA and human-to-human transmission of human-associated MRSA.
Personality may predispose family caregivers to experience caregiving differently in similar situations and influence the outcomes of caregiving. A limited body of research has examined the role of some personality traits for health-related quality of life (HRQoL) among family caregivers of persons with dementia (PWD) in relation to burden and depression.
Data from a large clinic-based national study in South Korea, the Caregivers of Alzheimer's Disease Research (CARE), were analyzed (N = 476). Path analysis was performed to explore the association between family caregivers’ personality traits and HRQoL. With depression and burden as mediating factors, direct and indirect associations between five personality traits and HRQoL of family caregivers were examined.
Results demonstrated the mediating role of caregiver burden and depression in linking two personality traits (neuroticism and extraversion) and HRQoL. Neuroticism and extraversion directly and indirectly influenced the mental HRQoL of caregivers. Neuroticism and extraversion only indirectly influenced their physical HRQoL. Neuroticism increased the caregiver's depression, whereas extraversion decreased it. Neuroticism only was mediated by burden to influence depression and mental and physical HRQoL.
Personality traits can influence caregiving outcomes and be viewed as an individual resource of the caregiver. A family caregiver's personality characteristics need to be assessed for tailoring support programs to get the optimal benefits from caregiver interventions.
The simulations of flow past a two-dimensional circular cylinder are conducted to investigate the feasibility of adaptive mesh refinement applied on curved spectral elements. The nonconforming spectral element method and adaptive meshes technique are used to the curve surfaces and observe whether any discontinuity of the solutions. The adaptive nonconforming spectral element method is implemented to compare with those obtained by conforming mesh method with respect to several existing numerical and experimental studies. Meanwhile, three kinds of estimated error base mesh adaptation are conducted to compare their accuracy and efficiency with conforming mesh method. The results show adaptive nonconforming mesh method is more efficient than the conforming method. Especially, the vorticity error based method performs highest accuracy and fastest convergence. The results show this mesh refinement technique is applicable on the curved elements with satisfactory accuracy. It releases this technique may be applied on the simulations of flow past objects with more general geometries.