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Studies revealed that prenatal stress (PS) may increase the vulnerability to depression in their offspring, and ERK-CREB signal system might play a role in its mechanism.
Objectives and aims
The present study investigated the effect of MK-801 on depressive-like behavior and its impacts on ERK2, CREB, Bcl-2 mRNA expression in PS female rat offspring.
The pregnant rats were randomly divided into three groups, the control group (Con) was left undisturbed, the PS-saline group (PS-saline) and the PS-MK-801 group (PS-MK-801) were subjected to restraint stress on days 14–20 of pregnancy three times daily for 45 min, and received an i.p. administration of saline or MK-801(sigma, 0.2 mg/kg) 30 min before the first stress respectively. Forced swimming test was undertaken to assess depressive-like behavior in one month female offspring. ERK2, CREB, Bcl-2 mRNA in the hippocampus, frontal cortex, and striatum were detected by RT-PCR.
PS-saline spent significantly more immobile time compared to Con and PS-MK-801 (P < 0.05). ERK2 and CREB mRNA expression in hippocampus and frontal cortex was significantly decreased in PS-saline compared to Con and PS-MK-801 (P < 0.05), while in striatum CREB mRNA expression in PS-saline was lower than Con (P < 0.05). Bcl-2 mRNA expression in hippocampus and striatum was significantly decreased in PS-saline (P < 0.05), and in frontal cortex, its expression was significantly lower in PS-saline and PS-MK-801 (P < 0.05).
PS may suppress ERK-CREB signal pathway in female offspring rats, which could be partly prevented by MK- 801. (Supported by National Natural Science Foundation of China, No: 30970952).
Emerging research evidence suggested that attributional style is one of the main predictors of schizophrenia symptoms.
This study aimed to develop and validate Attribution Questionnaire on Symptom for Schizophrenia (AQSS) in response to the deficiencies in current scales.
The AQSS was developed based on subscales relating to several psychopathological domains included in diagnostic categories in the Diagnostic and Statistical Manual of Mental Disorders IV version. The test items were checked by experienced clinicians for face validity and were tested through a pilot study. The final questionnaire included nine events reflecting four dimensions in each: controllability, internality, stability and globality. Attributional Style Questionnaire (ASQ) was used to assess the concurrent validity of the AQSS.
A four factor structure was extracted from the data using exploratory factor analysis: controllability, internality, stability and globality. Internal consistency of Cronbach’s alphas ranges from 0.84, 0.89, 0.90 and 0.91 respectively, with a total Cronbach’s alpha level is 0.92. The test-retest reliability ranged from 0.72 to 0.82. Three dimensions of AQSS (i.e.internality, stability and globality) significantly correlated with the same dimensions of the Attributation Style Questionnaire, with correlation coefficients of 0.33, 0.65 amd 0.61 for internality, stability and globality respectively. Confirmatory factor analysis confirmed the excellent level of model fit in the four factor structure.
The AQSS has high level of reliability and validity. It is a satisfactory instrument to assess attributional style in patients with schizophrenia.
In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.
The present study evaluates the use of multiple correspondence analysis (MCA), a type of exploratory factor analysis designed to reduce the dimensionality of large categorical data sets, in identifying behaviours associated with measures of overweight/obesity in Vanuatu, a rapidly modernizing Pacific Island country.
Starting with seventy-three true/false questions regarding a variety of behaviours, MCA identified twelve most significantly associated with modernization status and transformed the aggregate binary responses of participants to these twelve questions into a linear scale. Using this scale, individuals were separated into three modernization groups (tertiles) among which measures of body fat were compared and OR for overweight/obesity were computed.
Ni-Vanuatu adults (n 810) aged 20–85 years.
Among individuals in the tertile characterized by positive responses to most of or all the twelve modernization questions, weight and measures of body fat and the likelihood that measures of body fat were above the US 75th percentile were significantly greater compared with individuals in the tertiles characterized by mostly or partly negative responses.
The study indicates that MCA can be used to identify individuals or groups at risk for overweight/obesity, based on answers to simply-put questions. MCA therefore may be useful in areas where obtaining detailed information about modernization status is constrained by time, money or manpower.
Designing effective control for complex three-dimensional flow fields proves to be non-trivial. Often, intuitive control strategies lead to suboptimal control. To navigate the control space, we use a linear parabolized stability analysis to guide the design of a control scheme for a trailing vortex flow field aft of a NACA0012 half-wing at an angle of attack
and a chord-based Reynolds number
. The stability results show that the unstable mode with the smallest growth rate (fifth wake mode) provides a pathway to excite a vortex instability, whereas the principal unstable mode does not. Inspired by this finding, we perform direct numerical simulations that excite each mode with body forces matching the shape function from the stability analysis. Relative to the uncontrolled case, the controlled flows show increased attenuation of circulation and peak streamwise vorticity, with the fifth-mode-based control set-up outperforming the principal-mode-based set-up. From these results, we conclude that a rudimentary linear stability analysis can provide key insights into the underlying physics and help engineers design effective physics-based flow control strategies.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
Extensive insecticide use has led to the resistance of mosquitoes to these insecticides, posing a major barrier to mosquito control. Previous Solexa high-throughput sequencing of Culex pipiens pallens in the laboratory has revealed that the abundance of a novel microRNA (miRNA), miR-13664, was higher in a deltamethrin-sensitive (DS) strain than a deltamethrin-resistant (DR) strain. Real-time quantitative PCR revealed that the miR-13664 transcript level was lower in the DR strain than in the DS strain. MiR-13664 oversupply in the DR strain increased the susceptibility of these mosquitoes to deltamethrin, whereas inhibition of miR-13664 made the DS strain more resistant to deltamethrin. Results of bioinformatic analysis, quantitative reverse-transcriptase polymerase chain reaction, luciferase assay and miR mimic/inhibitor microinjection revealed CpCYP314A1 to be a target of miR-13664. In addition, downregulation of CpCYP314A1 expression in the DR strain reduced the resistance of mosquitoes to deltamethrin. Taken together, our results indicate that miR-13664 could regulate deltamethrin resistance by interacting with CpCYP314A1, providing new insights into mosquito resistance mechanisms.
Background: EMBRACE (NCT02462759) Part 1 is a randomized, double-blind, sham-procedure controlled study assessing safety/tolerability of intrathecal nusinersen (12-mg equivalent dose) in symptomatic infants/children with SMA who were not eligible to participate in ENDEAR or CHERISH. Methods: Eligible participants had onset of SMA symptoms at ≤6 months with 3 SMN2 copies; onset at ≤6 months, age >7 months and 2 copies; or onset at >6 months, age ≤18 months, and 2/3 copies. Safety/tolerability was the primary endpoint. Exploratory endpoints included Hammersmith Infant Neurological Examination Section 2 (HINE-2) motor milestone attainment, change in ventilator use, and growth. Results: EMBRACE Part 1 was terminated early based on positive results from ENDEAR. Safety/tolerability was similar to previous trials. More nusinersen-treated (11/14;79%) vs. sham–treated individuals (2/7;29%) were HINE-2 motor milestone responders. Between Day 183 and 302, mean (SD) hours of ventilator use changed by +1.236 (3.712) hours in nusinersen-treated (n=12) and +2.123 (3.023) hours in sham–treated individuals (n=7). Similar increases in weight and body length were observed in nusinersen-treated and sham–treated individuals by Day 183. Conclusions: In EMBRACE Part 1, nusinersen demonstrated a favorable benefit-risk profile. These results add to the aggregated efficacy, safety/tolerability data of nusinersen in SMA.
Recent advances in coaxial rotor design have shown benefits of this configuration. Nevertheless, issues related to rotor-head drag, aerodynamic performance, wake interference, and vibration should also be considered. Simulating the unsteady aerodynamic loads for a coaxial rotor, including the aerodynamic interactions between rotors and rotor blades, is an essential part of analysing their vibration characteristics. In this article, an unsteady aerodynamic analysis based on a vortex particle method is presented. In this method, a reversed-flow model for the retreating side of the coaxial rotor is proposed based on an unsteady panel technique. To account for reversed flow, shedding a vortex from the leading edge is used rather than from the trailing edge. Moreover, vortex-blade aerodynamic interactions are accounted for. The model considers the unsteady pressure term induced on a blade by tip vortices of other blades, and thus accounts for the aerodynamic interaction between the rotors and its contribution to the unsteady airloads. Coupling the reversed-flow model and the vortex-blade aerodynamic interaction model with the viscous vortex-particle method is used to simulate the complex wake of the coaxial rotor. The unsteady aerodynamic loads on the X2 coaxial rotor are simulated in forward flight, and compared with the results of PRASADUM (Parallelized Rotorcraft Analysis for Simulation And Design, developed at the University of Maryland) and CFD/CSD computations with the OVERFLOW and the CREATE-AV Helios tools. The results of the present method agree with the results of the CFD/CSD method, and compare to it better than the PRASADUM solutions. Furthermore, the influence of the aerodynamic interaction between the coaxial rotors on the unsteady airloads, frequency, wake structure, induced flow, and force distributions are analysed. Additionally, the results are also compared against computations for a single-rotor case, simulated at similar conditions as the coaxial rotor. It is shown that the effect of tip vortex interaction plays a significant role in unsteady airloads of coaxial rotors at low speeds, while the rotor blade passing effect is obviously strengthened at high-speed.
One of the goals of soft robotics is the ability to interface with the human body. Traditionally, silicone materials have dominated the field of soft robotics. In order to shift to materials that are more compatible with the body, developments will have to be made into biodegradable and biocompatible soft robots. This investigation focused on developing gummy actuators which are biodegradable, edible, and tasty. Creating biodegradable and edible actuators can be both sold as an interactive candy product and also inform the design of implantable soft robotic devices. First, commercially available gelatin-based candies were recast into pneumatic actuators utilizing molds. Edible robotic devices were pneumatically actuated repeatedly (up to n=8 actuations) using a 150 psi power inflator. To improve upon the properties of actuators formed from commercially available candy, a novel gelatin-based formulation, termed the “Fordmula” was also developed and used to create functional actuators. To investigate the mechanics and functionality of the recast gummy material and the Fordmula, compression testing and biodegradation studies were performed. Mechanical compression tests showed that recast gummy materials had similar properties to commercially available candies and at low strain had similar behavior to traditional silicone materials. Degradation studies showed that actuation was possible within 15 minutes in a biologically relevant solution followed by complete dissolution of the actuator afterwards. A taste test with elementary aged children demonstrated the fun, edible, and educational appeal of the candy actuators. Edible actuator development was an entry and winning submission in the High School Division of the Soft Robotics Toolkit Design Competition hosted by Harvard University. Demonstration of edible soft robotic actuators created by middle and high school aged students shows the applicability of the Soft Robotics Toolkit for K12 STEM education.
The discovery of the first electromagnetic counterpart to a gravitational wave signal has generated follow-up observations by over 50 facilities world-wide, ushering in the new era of multi-messenger astronomy. In this paper, we present follow-up observations of the gravitational wave event GW170817 and its electromagnetic counterpart SSS17a/DLT17ck (IAU label AT2017gfo) by 14 Australian telescopes and partner observatories as part of Australian-based and Australian-led research programs. We report early- to late-time multi-wavelength observations, including optical imaging and spectroscopy, mid-infrared imaging, radio imaging, and searches for fast radio bursts. Our optical spectra reveal that the transient source emission cooled from approximately 6 400 K to 2 100 K over a 7-d period and produced no significant optical emission lines. The spectral profiles, cooling rate, and photometric light curves are consistent with the expected outburst and subsequent processes of a binary neutron star merger. Star formation in the host galaxy probably ceased at least a Gyr ago, although there is evidence for a galaxy merger. Binary pulsars with short (100 Myr) decay times are therefore unlikely progenitors, but pulsars like PSR B1534+12 with its 2.7 Gyr coalescence time could produce such a merger. The displacement (~2.2 kpc) of the binary star system from the centre of the main galaxy is not unusual for stars in the host galaxy or stars originating in the merging galaxy, and therefore any constraints on the kick velocity imparted to the progenitor are poor.
We present techniques developed to calibrate and correct Murchison Widefield Array low-frequency (72–300 MHz) radio observations for polarimetry. The extremely wide field-of-view, excellent instantaneous (u, v)-coverage and sensitivity to degree-scale structure that the Murchison Widefield Array provides enable instrumental calibration, removal of instrumental artefacts, and correction for ionospheric Faraday rotation through imaging techniques. With the demonstrated polarimetric capabilities of the Murchison Widefield Array, we discuss future directions for polarimetric science at low frequencies to answer outstanding questions relating to polarised source counts, source depolarisation, pulsar science, low-mass stars, exoplanets, the nature of the interstellar and intergalactic media, and the solar environment.
OBJECTIVES/SPECIFIC AIMS: Peripheral neuropathy is the dose limiting toxicity of paclitaxel treatment. Paclitaxel pharmacokinetics (PK), specifically the Cmax and amount of time the concentration remains above 0.05 µM (Tc>0.05), have been associated with occurrence of severe, clinician-documented neuropathy. The objective of this study was to confirm that paclitaxel PK predicts progression of patient-reported neuropathy. METHODS/STUDY POPULATION: This observational trial enrolled breast cancer patients receiving weekly 1-hour paclitaxel infusions (80 mg/m2×12 cycles) at the University of Michigan Comprehensive Cancer Center. Paclitaxel concentration was measured via LC/MS in plasma samples collected at the end of (Cmax) and 16–24 hours after (Tc>0.05) first infusion. Patient-reported neuropathy was collected (EORTC CIPN20) at baseline and each cycle. The rate of neuropathy severity increase per treatment cycle is being modeled for each patient. Cmax and Tc>0.05 values will be introduced into the model to confirm that PK independently contributes to neuropathy progression. RESULTS/ANTICIPATED RESULTS: PK and neuropathy data have been collected from 60 patients for ongoing analysis. Our initial model will characterize the expected severity of neuropathy after each cycle of paclitaxel treatment. The PK-neuropathy model will include either PK parameter to validate their contribution to the progression of neuropathy severity during treatment. We anticipate, based on our preliminary analysis of the first 16 patients, that both PK parameters will significantly contribute to the model but Tc>0.05 will be more strongly associated with neuropathy progression. DISCUSSION/SIGNIFICANCE OF IMPACT: This project will generate a model that can be used to predict a patient’s neuropathy severity throughout treatment using a single, conveniently collected and easily measured PK sample during their first cycle. The next steps of this project include identifying genetic and metabolomic biomarkers that predict which patients experienced more severe neuropathy than would be anticipated based on their paclitaxel PK, and a planned interventional trial of personalized paclitaxel dosing to enhance efficacy and/or prevent neuropathy.
The stability characteristics of compressible spanwise-periodic open-cavity flows are investigated with direct numerical simulation (DNS) and biglobal stability analysis for rectangular cavities with aspect ratios of
and 6. This study examines the behaviour of instabilities with respect to stable and unstable steady states in the laminar regime for subsonic as well as transonic conditions where compressibility plays an important role. It is observed that an increase in Mach number destabilizes the flow in the subsonic regime and stabilizes the flow in the transonic regime. Biglobal stability analysis for spanwise-periodic flows over rectangular cavities with large aspect ratio is closely examined in this study due to its importance in aerodynamic applications. Moreover, biglobal stability analysis is conducted to extract two-dimensional (2-D) and 3-D eigenmodes for prescribed spanwise wavelengths
about the 2-D steady state. The properties of 2-D eigenmodes agree well with those observed in the 2-D nonlinear simulations. In the analysis of 3-D eigenmodes, it is found that an increase of Mach number stabilizes dominant 3-D eigenmodes. For a short cavity with
, the 3-D eigenmodes primarily stem from centrifugal instabilities. For a long cavity with
, other types of eigenmodes appear whose structures extend from the aft-region to the mid-region of the cavity, in addition to the centrifugal instability mode located in the rear part of the cavity. A selected number of 3-D DNS are performed at
for cavities with
and 6. For
, the properties of 3-D structures present in the 3-D nonlinear flow correspond closely to those obtained from linear stability analysis. However, for
, the 3-D eigenmodes cannot be clearly observed in the 3-D DNS due to the strong nonlinearity that develops over the length of the cavity. In addition, it is noted that three-dimensionality in the flow helps alleviate violent oscillations for the long cavity. The analysis performed in this paper can provide valuable insights for designing effective flow control strategies to suppress undesirable aerodynamic and pressure fluctuations in compressible open-cavity flows.
Worldwide 350 million people suffer from major depression, with the majority of cases occurring in low- and middle-income countries. We examined the patterns, correlates and care-seeking behaviour of adults suffering from major depressive episode (MDE) in China.
A nationwide study recruited 512 891 adults aged 30–79 years from 10 provinces across China during 2004–2008. The 12-month prevalence of MDE was assessed by the Modified Composite International Diagnostic Interview-short form. Logistic regression yielded adjusted odds ratios (ORs) of MDE associated with socio-economic, lifestyle and health-related factors and major stressful life events.
Overall, 0.7% of participants had MDE and a further 2.4% had major depressive symptoms. Stressful life events were strongly associated with MDE [adjusted OR 14.7, 95% confidence interval (CI) 13.7–15.7], with a dose–response relationship with the number of such events experienced. Family conflict had the highest OR for MDE (18.9, 95% CI 16.8–21.2) among the 10 stressful life events. The risk of MDE was also positively associated with rural residency (OR 1.5, 95% CI 1.4–1.7), low income (OR 2.3, 95% CI 2.1–2.4), living alone (OR 2.6, 95% CI 2.3–3.0), smoking (OR 1.4, 95% CI 1.3–1.6) and certain other mental disorders (e.g. anxiety, phobia). Similar, albeit weaker, associations were observed with depressive symptoms. Among those with MDE, about 15% sought medical help or took psychiatric medication, 15% reported having suicidal ideation and 6% reported attempting suicide.
Among Chinese adults, the patterns and correlates of MDE were generally consistent with those observed in the West. The low rates of seeking professional help and treatment highlight the great gap in mental health services in China.
Association mapping based on linkage disequilibrium is an effective approach for dissecting the inheritance of complex multi-gene traits. In the present study, association mapping was performed for yield traits based on 172 popular Upland cotton (Gossypium hirsutum L.) cultivars in China and 331 polymorphic simple sequence repeat (SSR) markers. The gene diversity index of 331 markers ranged from 0·0387 to 0·7799 with an average of 0·4002, and the polymorphism information content ranged from 0·0379 to 0·7473 with an average of 0·3375. A total of 93 significantly associated markers for seven yield traits were identified across more than one environment, among which 11 were for seed cotton yield, 12 for lint yield, 11 for boll number per plant, 13 for boll weight, 21 for lint percentage, 14 for lint index and 11 for seed index. The corresponding ranges in phenotypic variation explained by markers across four environments for these seven traits were 1·75–10·49, 1·75–9·34, 2·84–11·80, 2·59–9·89, 2·38–13·97, 2·73–14·82 and 2·50–11·88%, respectively. Some of the yield-associated markers detected were found to be linked to or associated with the same traits identified in previous studies. Furthermore, elite alleles for yield traits were also mined. The present study can provide useful information for further understanding the genetic basis of yield traits, and facilitate high-yield breeding by molecular design in Upland cotton.
The contribution of mixed infection in recurrent Clostridium difficile infection (CDI) episodes is not known. Among paired isolates from 52 patients, mixed infection due to >1 toxigenic strain of C. difficile was identified in 8% of first episodes. Among recurrences, relapse from 1 or both co-infecting strains was uncommon; it was detected in a single case each.
An outbreak of acute hepatitis recently occurred in a nursing home in Zhejiang Province, China. The objectives of this study were to confirm the outbreak and identify the aetiology, source and transmission patterns. All residents and staff in or near the nursing home during the period from 1 October 2014 to 21 May 2015 were investigated regarding hygiene and for epidemiological information including water and food (eating meat especially pork products). Serum and stool specimens were collected for detection of hepatitis E virus (HEV) antibodies using ELISA and RNA using RT–PCR. Samples that were RNA positive were genotyped. Of 185 senior residents and 24 staff in the nursing home, there were 37 laboratory-confirmed cases during the outbreak. Of these cases, 12 patients (three deaths) were symptomatic with jaundice, a common clinical symptom for hepatitis E infection. HEV strains were isolated from three cases and they formed a single cluster within genotype 4d. A case-control study was conducted to investigate potential risk factors for the outbreak and the results revealed that cases more often washed their dishes and rinsed their mouths using tap water than the controls (P < 0·05). Based on hygiene investigation and meteorological information, it is likely that HEV-infected sewage and faeces contaminated the water network on rainy days. Collectively, these results suggest that the outbreak of HEV genotype 4 infection was most likely caused by contaminated tap water rather than food.