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OBJECTIVES/GOALS: Intraocular pressure is the most significant risk factor for glaucoma. Mechanosensitive proteins may have a critical role in transducing mechanical stimuli that ultimately lead to death of retinal ganglion cells. Our goal is to use genetic and functional approaches to discover mechanosensitive ion channels that mediate the progression of glaucoma. METHODS/STUDY POPULATION: Association data, obtained using a logistic regression model that included age, gender and population substructure as co-variates, for 2,576 SNPs located in the PIEZO1 and PIEZO2 genomic regions were extracted from the NEIGHBORHOOD genome-wide association study results for primary open angle glaucoma (POAG) (3,853 cases and 33,480 controls) and the subset of cases with intraocular pressure (IOP) measurements > 21mmHg (high-tension, HTG) (1868 cases and 33,480 controls). Rare coding PIEZO1 and PIEZO2 variants were evaluated using logistic regression and SNP data from the Human Exome array in 2606 POAG cases and 2606 controls and the subset of 1868 HTG cases and 2606 controls. Immunohistochemistry was used to characterize the expression of Piezo1 and Piezo2 in mouse eye sections. RESULTS/ANTICIPATED RESULTS: Exome data analysis identified two protein-altering variants associated with lower glaucoma risk (P<0.05): a PIEZO1 missense allele (Arg1527His; OR= 0.18, P= 0.001) and a variant disrupting a splice donor site (c.1107+1G>C; OR=0.38, P= 0.02), that prematurely truncates the protein. Investigation of the NEIGHBORHOOD GWAS dataset identified nominal association with common PIEZO2 variants (minor allele frequency > 0.3) in POAG overall (top SNP rs264179, P= 0.008) and in the HTG subgroup (top SNP rs264160, P= 0.001). The associated PIEZO2 SNPs are significantly associated with gene expression in lymphocytes (P< 1x10-8) with the risk allele correlated with decreased gene expression. Piezo1 and Piezo2 are expressed in many ocular tissues in the mouse, including cornea, ciliary body and retina. DISCUSSION/SIGNIFICANCE: We identify rare, protein-altering PIEZO1 variants associated with lower glaucoma risk and show that Piezo1 and Piezo2 are broadly expressed in the eye. Common variants influencing PIEZO2 expression also show nominal association with POAG risk. Inhibition of Piezo1 or augmentation of Piezo2 could be novel therapeutic strategies for glaucoma.
Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD.
A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT.
ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group.
ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China.
Previous studies have demonstrated structural and functional changes of the hippocampus in patients with major depressive disorder (MDD). However, no studies have analyzed the dynamic functional connectivity (dFC) of hippocampal subregions in melancholic MDD. We aimed to reveal the patterns for dFC variability in hippocampus subregions – including the bilateral rostral and caudal areas and its associations with cognitive impairment in melancholic MDD.
Forty-two treatment-naive MDD patients with melancholic features and 55 demographically matched healthy controls were included. The sliding-window analysis was used to evaluate whole-brain dFC for each hippocampal subregions seed. We assessed between-group differences in the dFC variability values of each hippocampal subregion in the whole brain and cognitive performance on the MATRICS Consensus Cognitive Battery (MCCB). Finally, association analysis was conducted to investigate their relationships.
Patients with melancholic MDD showed decreased dFC variability between the left rostral hippocampus and left anterior lobe of cerebellum compared with healthy controls (voxel p < 0.005, cluster p < 0.0125, GRF corrected), and poorer cognitive scores in working memory, verbal learning, visual learning, and social cognition (all p < 0.05). Association analysis showed that working memory was positively correlated with the dFC variability values of the left rostral hippocampus-left anterior lobe of the cerebellum (r = 0.338, p = 0.029) in melancholic MDD.
These findings confirmed the distinct dynamic functional pathway of hippocampal subregions in patients with melancholic MDD, and suggested that the dysfunction of hippocampus-cerebellum connectivity may be underlying the neural substrate of working memory impairment in melancholic MDD.
The findings regarding the associations between red meat, fish and poultry consumption, and the metabolic syndrome (Mets) have been inconclusive, and evidence from Chinese populations is scarce. A cross-sectional study was performed to investigate the associations between red meat, fish and poultry consumption, and the prevalence of the Mets and its components among the residents of Suzhou Industrial Park, Suzhou, China. A total of 4424 participants were eligible for the analysis. A logistic regression model was used to estimate the OR and 95 % CI for the prevalence of the Mets and its components according to red meat, fish and poultry consumption. In addition, the data of our cross-sectional study were meta-analysed under a random effects model along with those of published observational studies to generate the summary relative risks (RR) of the associations between the highest v. lowest categories of red meat, fish and poultry consumption and the Mets and its components. In the cross-sectional study, the multivariable-adjusted OR for the highest v. lowest quartiles of consumption was 1·23 (95 % CI 1·02, 1·48) for red meat, 0·83 (95 % CI 0·72, 0·97) for fish and 0·93 (95 % CI 0·74, 1·18) for poultry. In the meta-analysis, the pooled RR for the highest v. lowest categories of consumption was 1·20 (95 % CI 1·06, 1·35) for red meat, 0·88 (95 % CI 0·81, 0·96) for fish and 0·97 (95 % CI 0·85, 1·10) for poultry. The findings of both cross-sectional studies and meta-analyses indicated that the association between fish consumption and the Mets may be partly driven by the inverse association of fish consumption with elevated TAG and reduced HDL-cholesterol and, to a lesser extent, fasting plasma glucose. No clear pattern of associations was observed between red meat or poultry consumption and the components of the Mets. The current findings add weight to the evidence that the Mets may be positively associated with red meat consumption, inversely associated with fish consumption and neutrally associated with poultry consumption.
Self-efficacy is a pivotal factor in the etiology and prognosis of major depression. However, longitudinal studies on the relationship between self-efficacy and major depressive disorder (MDD) are scarce. The objectives were to investigate: (1) the associations between self-efficacy and the 1-year and 2-year risks of first onset of MDD and (2) the associations between self-efficacy and the 1-year and 2-year risks of the persistence/recurrence of MDD, in a sample of first-year university students.
We followed 8079 first-year university students for 2 years from April 2018 to October 2020. MDD was ascertained by the Chinese version of the Composite International Diagnostic Interview (CIDI-3.0) based on self-report. Self-efficacy was measured by the 10-item General Self-efficacy (GSE) scale. Random effect logistic regression modeling was used to estimate the associations.
Among participants without a lifetime MDD, the data showed that participants with high baseline GSE scores were associated with a higher risk of first onset of MDD over 2 years [odds ratio (OR) 1.04, 95% confidence interval (CI) 1.01–1.08]. Among those with a lifetime MDD, participants with high baseline GSE scores were less likely to have had a MDD over 2 years (OR 0.93, 95% CI 0.88–0.99) compared to others.
A high level of GSE may be protective of the risk of persistent or recurrent MDD. More longitudinal studies in university students are needed to further investigate the impact of GSE on the first onset of MDD.
The coffee white stem borer, Xylotrechus quadripes Chevrolat (Coleoptera: Cerambycidae), is a major destructive pest of Coffea arabica L. (Gentianales: Rubiaceae), widely planted in many Asian countries, including China. Quantitative real-time polymerase chain reaction (qRT-PCR) is a common method for quantitative analysis of gene transcription levels. To obtain accurate and reliable qRT-PCR results, it is necessary to select suitable reference genes to different experimental conditions for normalizing the target gene expression. However, the stability of the expression of reference genes in X. quadripes has rarely been studied. In this study, the expression stability of nine candidate reference genes were investigated under biotic and abiotic conditions for use in qRT-PCR's normalization. By integrating the results of four algorithms of NormFinder, BestKeeper, geNorm, and RefFinder, the optimal reference gene combinations in different experimental conditions were performed as follows: RPL10a and EIF3D were the optimal reference genes for developmental stage samples, EIF4E, RPL10a, and RPS27a for tissue samples, V-ATP and EF1α for the sex samples, EIF3D and V-ATP for temperature treatment, RPS27a and RPL10a for insecticide stress, and RPL10a, RPS27a, and EF1α for all the samples. This study will help to obtain the stable internal reference genes under biotic and abiotic conditions and lay the foundation for in-depth functional research of target genes or genomics on olfactory molecular mechanisms, temperature adaptability, and insecticide resistance in X. quadripes.
A 1178 J near diffraction limited 527 nm laser is realized in a complete closed-loop adaptive optics (AO) controlled off-axis multi-pass amplification laser system. Generated from a fiber laser and amplified by the pre-amplifier and the main amplifier, a 1053 nm laser beam with the energy of 1900 J is obtained and converted into a 527 nm laser beam by a KDP crystal with 62% conversion efficiency, 1178 J and beam quality of 7.93 times the diffraction limit (DL). By using a complete closed-loop AO configuration, the static and dynamic wavefront distortions of the laser system are measured and compensated. After correction, the diameter of the circle enclosing 80% energy is improved remarkably from 7.93DL to 1.29DL. The focal spot is highly concentrated and the 1178 J, 527 nm near diffraction limited laser is achieved.
This paper establishes a new version of integration by parts formula of Markov chains for sensitivity computation, under much lower restrictions than the existing researches. Our approach is more fundamental and applicable without using Girsanov theorem or Malliavin calculus as did by past papers. Numerically, we apply this formula to compute sensitivity regarding the transition rate matrix and compare with a recent research by an IPA (infinitesimal perturbation analysis) method and other approaches.
It is essential to investigate the experiences behind why adolescents start and continue to self-harm in order to develop targeted treatment and prevent future self-harming behaviours.
The aims of this study are to understand the motivations for initiating and repeating nonfatal self-harm, the different methods used between first-time and repeated self-harm and the reasons that adolescents do not seek help from health services.
Adolescents with repeated nonfatal self-harm experiences were recruited to participate in individual, semi-structured qualitative interviews. The interviews were analysed with interpretative phenomenological analysis.
We found that nonfatal self-harm among adolescents occurred comparatively early and was often triggered by specific reasons. However, the subsequent nonfatal self-harm could be causeless, with repeated self-harm becoming a maladaptive coping strategy to handle daily pressure and negative emotions. The choice of tools used was related to the ease of accessibility, the life-threatening risk and the size of the scars. Adolescents often concealed their scars on purpose, which made early identification insufficient. Peer influence, such as online chat groups encouraging self-harm by discussing and sharing self-harm pictures, could also lead to increased self-harm. The results also included participants’ opinions on how to stop nonfatal self-harm and their dissatisfaction with the current healthcare services.
The current study provides important implications both for early identification and interventions for adolescents who engage in repeated nonfatal self-harm, and for individualising treatment planning that benefits them. It is also worthwhile to further investigate how peer influence and social media may affect self-harm in adolescents.
A recently developed pneumonia caused by SARS-CoV-2 has quickly spread across the world. Unfortunately, a simplified risk score that could easily be used in primary care or general practice settings has not been developed. The objective of this study is to identify a simplified risk score that could easily be used to quickly triage severe COVID-19 patients. All severe and critical adult patients with laboratory-confirmed COVID-19 on the West campus of Union Hospital, Wuhan, China, from 28 January 2020 to 29 February 2020 were included in this study. Clinical data and laboratory results were obtained. CURB-65 pneumonia score was calculated. Univariate logistic regressions were applied to explore risk factors associated with in-hospital death. We used the receiver operating characteristic curve and multivariate COX-PH model to analyse risk factors for in-hospital death. A total of 74 patients (31 died, 43 survived) were finally included in the study. We observed that compared with survivors, non-survivors were older and illustrated higher respiratory rate, neutrophil-to-lymphocyte ratio, D-dimer and lactate dehydrogenase (LDH), but lower SpO2 as well as impaired liver function, especially synthesis function. CURB-65 showed good performance for predicting in-hospital death (area under curve 0.81, 95% confidence interval (CI) 0.71–0.91). CURB-65 ⩾ 2 may serve as a cut-off value for prediction of in-hospital death in severe patients with COVID-19 (sensitivity 68%, specificity 81%, F1 score 0.7). CURB-65 (hazard ratio (HR) 1.61; 95% CI 1.05–2.46), LDH (HR 1.003; 95% CI 1.001–1.004) and albumin (HR 0.9; 95% CI 0.81–1) were risk factors for in-hospital death in severe patients with COVID-19. Our study indicates CURB-65 may serve as a useful prognostic marker in COVID-19 patients, which could be used to quickly triage severe patients in primary care or general practice settings.
Predictors of compliance with aspirin in children following cardiac catheterisation have not been identified. The aim of this study is to identify the caregivers’ knowledge, compliance with aspirin medication, and predictors of compliance with aspirin in children with Congenital Heart Disease (CHD) post-percutaneous transcatheter occlusion.
A cross-sectional explorative design was adopted using a self-administered questionnaire and conducted between May 2017 and May 2018. Recruited were 220 caregivers of children with CHD post-percutaneous transcatheter occlusion. Questionnaires included child and caregivers’ characteristics, a self-designed and tested knowledge about aspirin scale (scoring scale 0–2), and the 8-item Morisky Medication Adherence Scale (scoring scale 0–8). Data were analysed using multivariate binary logistic regression analysis to identify predictors of compliance with aspirin.
Of the 220 eligible children and caregivers, 210 (95.5%) responded and 209 surveys were included in the analysis. The mean score of knowledge was 7.25 (standard deviation 2.27). The mean score of compliance was 5.65 (standard deviation 1.36). Child’s age, length of aspirin use, health insurance policies, relationship to child, monthly income, and knowledge about aspirin of caregivers were independent predictors of compliance with aspirin (p < 0.05).
Caregivers of children with CHD had an adequate level of knowledge about aspirin. Compliance to aspirin medication reported by caregivers was low. Predictors of medium to high compliance with aspirin were related to the child’s age and socio-economic reasons. Further studies are needed to identify effective strategies to improve knowledge, compliance with medication, and long-term outcomes of children with CHD.
In the present work, the ankle rehabilitation robot (ARR) dynamic model that implements a new series of connection control strategies is introduced. The dynamic models are presented in this regard. This model analyzes the robot LuGre friction model and the nonlinear disturbance model. To improve the ARR system’s rapidity and robustness, a composite 2-degree of freedom (2-DOF) internal model control (IMC) controller is presented. The control performance of the compound 2-DOF IMC controller is simulated and analyzed in the present work. The simulation shows that the composite 2-DOF IMC controller has high following performance. For practical testing purposes, 1-DOF passive training and predetermined trajectory following have been completed for different swing amplitudes and frequencies. Moreover, the thrust and tension torque of the robotic dynamic and static loading characteristics are studied in active control mode. The experimental results show the effectiveness of passive training of the given trajectory and impedance training active control strategy. This paper gives the specific functions of ARR.
Effects of dietary supplemental stachyose on caecal skatole concentration, hepatic cytochrome P450 (CYP450, CYP) mRNA expressions and enzymatic activities in broilers were evaluated. Arbor Acre commercial mixed male and female chicks were assigned randomly into six treatments. The positive control (PC) diet was based on maize–soyabean meal, and the negative control (NC) diet was based on maize–non-soyabean meal. The NC diet was then supplemented with 4, 5, 6 and 7 g/kg stachyose to create experimental diets, named S-4, S-5, S-6 and S-7, respectively. Each diet was fed to six replicates of ten birds from days 1 to 49. On day 49, the caecal skatole concentrations in the PC, S-4, S-5, S-6 and S-7 groups were lower than those in the NC group by 42·28, 23·68, 46·09, 15·31 and 45·14 % (P < 0·01), respectively. The lowest pH value was observed in the S-5 group (P < 0·05). The stachyose-fed groups of broilers had higher caecal acetate and propionate levels compared with control groups, and propionate levels in the S-6 and S-7 groups were higher than those in the S-4 and S-5 groups (P < 0·001). The highest CYP3A4 expression was found in the S-7 group (P < 0·05), but this was not different from PC, S-4, S-5 and S-6 treatments. There was no significant difference in CYP450 (1A2, 2D6 and 3A4) enzymatic activities among the groups (P > 0·05). In conclusion, caecal skatole levels can be influenced by dietary stachyose levels, and 5 g/kg of stachyose in the diet was suggested.
Previous studies have shown conflicting findings regarding the relationship between maternal vitamin D deficiency (VDD) and fetal growth restriction (FGR). We hypothesised that parathyroid hormone (PTH) may be an underlying factor relevant to this potential association. In a prospective birth cohort study, descriptive statistics were evaluated for the demographic characteristics of 3407 pregnancies in the second trimester from three antenatal clinics in Hefei, China. The association of the combined status of vitamin D and PTH with birth weight and the risk of small for gestational age (SGA) was assessed by a multivariate linear and binary logistic regression. We found that declined status of 25-hydroxyvitamin D is associated with lower birth weight (for moderate VDD: adjusted β = −49·4 g, 95 % CI −91·1, −7·8, P < 0·05; for severe VDD: adjusted β = −79·8 g, 95 % CI −127·2, −32·5, P < 0·01), as well as ascended levels of PTH (for elevated PTH: adjusted β = −44·5 g, 95 % CI −82·6, −6·4, P < 0·05). Compared with the non-VDD group with non-elevated PTH, pregnancies with severe VDD and elevated PTH had the lowest neonatal birth weight (adjusted β = −124·7 g, 95 % CI −194·6, −54·8, P < 0·001) and the highest risk of SGA (adjusted risk ratio (RR) = 3·36, 95 % CI 1·41, 8·03, P < 0·01). Notably, the highest risk of less Ca supplementation was founded in severe VDD group with elevated PTH (adjusted RR = 4·67, 95 % CI 2·78, 7·85, P < 0·001). In conclusion, elevated PTH induced by less Ca supplementation would further aggravate the risk of FGR in pregnancies with severe VDD through impaired maternal Ca metabolism homoeostasis.
Aiming at the influence of coupling coefficient variation on the output voltage of a high-power LCC-S topology inductively coupled power transfer (ICPT) system, a synchronous three-phase triple-parallel Buck converter is used as the voltage adjustment unit. The control method for the three-phase current sharing of synchronous three-phase triple-parallel Buck converter and the constant voltage output ICPT system under the coupling coefficient variation is studied. Firstly, the hybrid model consisting of the circuit averaging model of the three-phase triple-parallel Buck converter and the generalized state-space average model for the LCC-S type ICPT system is established. Then, the control methods for three-phase current sharing of the synchronous three-phase triple-parallel Buck converter and constant voltage output of ICPT system are studied to achieve the multi-objective integrated control of the system. Finally, a 3.3 kW wireless charging system platform is built, the experimental results have verified the effectiveness of the proposed modeling and control method, and demonstrated the stability of the ICPT system.