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Lifestyle interventions are an important and viable approach for preventing cognitive deficits. However, the results of studies on alcohol, coffee and tea consumption in relation to cognitive decline have been divergent, likely due to confounds from dose–response effects. This meta-analysis aimed to find the dose–response relationship between alcohol, coffee or tea consumption and cognitive deficits.
Prospective cohort studies or nested case-control studies in a cohort investigating the risk factors of cognitive deficits were searched in PubMed, Embase, the Cochrane and Web of Science up to 4th June 2020. Two authors searched the databases and extracted the data independently. We also assessed the quality of the studies with the Newcastle-Ottawa scale. Stata 15.0 software was used to perform model estimation and plot the linear or nonlinear dose–response relationship graphs.
The search identified 29 prospective studies from America, Japan, China and some European countries. The dose–response relationships showed that compared to non-drinkers, low consumption (<11 g/day) of alcohol could reduce the risk of cognitive deficits or only dementias, but there was no significant effect of heavier drinking (>11 g/day). Low consumption of coffee reduced the risk of any cognitive deficit (<2.8 cups/day) or dementia (<2.3 cups/day). Green tea consumption was a significant protective factor for cognitive health (relative risk, 0.94; 95% confidence intervals, 0.92–0.97), with one cup of tea per day brings a 6% reduction in risk of cognitive deficits.
Light consumption of alcohol (<11 g/day) and coffee (<2.8 cups/day) was associated with reduced risk of cognitive deficits. Cognitive benefits of green tea consumption increased with the daily consumption.
Previous studies have revealed associations of meteorological factors with tuberculosis (TB) cases. However, few studies have examined their lag effects on TB cases. This study was aimed to analyse nonlinear lag effects of meteorological factors on the number of TB notifications in Hong Kong. Using a 22-year consecutive surveillance data in Hong Kong, we examined the association of monthly average temperature and relative humidity with temporal dynamics of the monthly number of TB notifications using a distributed lag nonlinear models combined with a Poisson regression. The relative risks (RRs) of TB notifications were >1.15 as monthly average temperatures were between 16.3 and 17.3 °C at lagged 13–15 months, reaching the peak risk of 1.18 (95% confidence interval (CI) 1.02–1.35) when it was 16.8 °C at lagged 14 months. The RRs of TB notifications were >1.05 as relative humidities of 60.0–63.6% at lagged 9–11 months expanded to 68.0–71.0% at lagged 12–17 months, reaching the highest risk of 1.06 (95% CI 1.01–1.11) when it was 69.0% at lagged 13 months. The nonlinear and delayed effects of average temperature and relative humidity on TB epidemic were identified, which may provide a practical reference for improving the TB warning system.
We study the evolution of unidirectional water waves from a randomly forced input condition with uncorrelated Fourier components. We examine the kurtosis of the linearised free surface as a convenient proxy for the probability of a rogue wave. We repeat the laboratory experiments of Onorato et al. (Phys. Rev. E, vol. 70, 2004, 067302), both experimentally and numerically, and extend the parameter space in our numerical simulations. We consider numerical simulations based on the modified nonlinear Schrödinger equation and the fully nonlinear water wave equations, which are in good agreement. For low steepness, existing analytical models based on the nonlinear Schrödinger equation (NLS) are found to be accurate. For cases which are steep or have very narrow bandwidths, these analytical models over-predict the rate at which excess kurtosis develops. In these steep cases, the kurtosis in both our experiments and numerical simulations peaks before returning to an equilibrium level. Such transient maxima are not predicted by NLS-based analytical models. Above a certain threshold of steepness, the steady-state value of kurtosis is primarily dependent on the spectral bandwidth. We also examine how the average shape of extreme events is modified by nonlinearity over the evolution distance, showing significant asymmetry during the initial evolution, which is greatly reduced once the spectrum has reached equilibrium. The locations of the maxima in asymmetry coincide approximately with the locations of the maxima in kurtosis.
A magnetic field configuration of an island divertor for a quasi-axisymmetric stellarator (CFQS) is proposed. The configuration incorporates large islands surrounding the core confinement region. The interface between the core region and the peripheral region of the island divertor is a clear magnetic separatrix similar to a tokamak divertor. The structure of divertor magnetic field lines is very regular without stochasticity and the connection length is sufficiently long for good divertor performance. Such a divertor configuration is produced in the magnetic field configuration for the CFQS device, which is now under construction in China.
Developing alternatives to antibiotics is an urgent need in livestock production. Antimicrobial peptides (AMPs) are regarded as powerful antibiotic substitutes (ASs) because AMPs have broad-spectrum antimicrobial activities and growth-promoting ability. Here, we aimed to comprehensively assess the effects of AMPs on the growth performance, diarrhea rate, intestinal morphology and immunity of healthy or challenged piglets, compared with an antibiotics group or negative control group. We performed a set of meta-analyses of feeding trials from database inception to 27 May 2019. Among the 1379 identified studies, 20 were included in our meta-analyses (56 arms and 4067 piglets). The meta-analyses revealed that (1) compared with the negative control group, AMPs significantly improved the healthy piglets’ average daily gain (ADG), average daily feed intake (ADFI), gain : feed ratio (G/F), levels of immune globulin (Ig) IgM and IgG, and intestinal villus height : crypt depth ratio (V/C) (P < 0.05). Meanwhile, AMPs significantly increased the challenged piglets’ ADG, ADFI, G/F and V/C of the jejunum and ileum, and notably deceased the diarrhea rate (P < 0.05); (2) compared with antibiotics group, the effects of AMPs were slightly weaker than those of antibiotics in the healthy piglets, but AMPs have similar effects to those of antibiotics in challenged piglets. In a higher purity, the optimal dose of AMPs may be approximately 0.01%. Our findings indicate that AMPs can improve piglet growth performance, enhance immunity, benefit intestinal morphology and decrease the diarrheal rate. AMPs could be great ASs especially under infection conditions.
A new developed spatially targeted mollusciciding technology for snail control was utilised in a research site. This study aims to analyse whether this technology can achieve rational effectiveness compared with the routine method. Snail density was monitored every spring and autumn from 2010 to 2017 at the research site and routine mollusciciding for snail control was then performed. After snail density monitoring in spring 2018, spatially targeted mollusciciding technology was adopted. Log-linear regression and nonlinear regression models were used for snail density prediction in autumn 2018 and the predicted value was compared with the actual snail density in autumn 2018 to verify the effectiveness of the spatially targeted mollusciciding. Monitoring results showed that overall snail density in the research site decreased from 2010 to 2018. The monitored snail density in autumn 2018 was 0.014/0.1 m2. Predicted by the log-linear regression model, the snail density in autumn 2018 would be 0.028 (95% CI 0.11–0.072)/0.1 m2. Predicted by the nonlinear regression model, the snail density growth in autumn 2018 in contrast to spring 2018 would be 79.79% (95% CI 54.81%–104.77%) and the actual value was 55.56%. Therefore, the effectiveness of the first application of spatially targeted mollusciciding was acceptable. However, the validation of its sustainable effectiveness still needs a replicated study comparing areas where targeted and untargeted methods are applied simultaneously and both snail abundance and human infection are monitored.
This paper presents a novel dual-band (DB) dual-polarized (DP) shared aperture antenna with high isolation by using a combination of microstrip dipoles and dielectric resonator antennas (DRAs) for S and C bands, respectively. In the S band, two sets of proximity coupled stacked microstrip dipoles which crossed at the center are employed to achieve dual-linear polarization (DLP) and obtain desired bandwidth (BW), isolation, and pure polarization. The rectangle DRA with hybrid feed is selected as the C band element for its advantages of small base area and high isolation, and a 2 × 2 array is presented with the “pair-wise” anti-phase feed technique to achieve a low cross-polarized level. Moreover, benefited from the back feed scheme, the proposed antenna has a symmetrical structure and has the potential of expanding into a larger aperture. The proposed antenna has been manufactured and measured, and the results agree well with simulations, which prove the validity of the proposed design.
We present a long-term seasonal tree ring cellulose oxygen isotope (δ18Oc) time series created by analyzing four segments (S1, S2, S3, and S4) per year during the period of 1951–2009 from southeastern Tibetan Plateau. This intraseasonal δ18Oc reveals the onset and mature phase of the summer monsoon precipitation in this region. Analysis indicates that the δ18Oc of S1 has the strongest correlation with precipitation during the regional monsoon onset (29–33 pentads, May 21–June 10, r = −0.69), and the δ18Oc values for S2, S3, and S4 correlate strongly with June, July, and August precipitation, respectively. Combined δ18Oc of S2, S3, and S4 shows the most robust correlation (r = −0.82) with the mature-phase monsoon precipitation (June-July-August, JJA), passing rigorous statistical tests for calibration and verification in dendroclimatology. These results demonstrate the feasibility in using long-term intraseasonal δ18Oc to reconstruct the Asian summer monsoon's intraseasonal variations.
Many studies showed the differences in subjective response to sexual stimuli between heterosexual and homosexual men. However, the underlying neurobiological factors of sexual orientation are largely unknown. We addressed the question what is the major attribution of the expected differences in brain activation, i.e. neural circuits or different cognitive process. Twenty-eight healthy male volunteers, 14 heterosexuals and 14 homosexuals, were scanned by functional Magnetic Resonance Imaging while subjects were viewing different types of stimuli, i.e. heterosexual couple stimuli (HCS), gay couple stimuli (GCS), lesbian couple stimuli (LCS) and neutral stimuli (NS). SPM02 was used for data analysis. Rating of sexual attractiveness was assessed. Subjective sexual arousal was induced by HCS and GCS in heterosexual and homosexual men, respectively. And sexual disgust was induced by GCS and LCS in heterosexual and homosexual men, respectively. As compared to viewing NS, viewing sexual stimuli induced significant different brain activations most of which had characteristic for cognitive process. These observations suggested that different cognitive pattern was major attribution of different subjective response to sexual stimuli between heterosexual and homosexual men.
Genetic variation of the catechol-O-methyltransferase (COMT) gene has long been thought to confer susceptibility to schizophrenia because of its catalytic activity for dopamine degradation. The negative symptom is a severe form of the illness related to prefrontal hypodopaminergia. In the present study, we attempted to perform a quantitative trait test for genetic association between the COMT gene and the negative symptoms in a Chinese population.
A total of 160 unrelated schizophrenic individuals were recruited for genetic analysis and their symptoms were assessed and scored by Positive and Negative Syndrome Scale (PANSS). The quantitative trait test was performed by the UNPHASED program to see the correlation between scored negative symptoms and some single nucleotide polymorphisms (SNPs) present in the COMT gene.
rs362204 (Del/Ins SNP) showed allelic association with four negative symptoms, including blunted affect (p=0.00008), poor rapport (p=0.00006), passive/apathetic social withdrawal (p=0.0003) and lack of spontaneity and flow of conversation (p=0.001). The rs165656(C)-rs6267(G)-rs4680 (G)-rs362204 (Del) haplotype was strongly associated with both blunted affect (p=0.0245) and poor rapport (p=0.0186).
The present study suggests that COMT may etiologically contribute to the severity of negative symptoms of schizophrenia but its precise mechanism needs further investigating.
The treatment of refractory schizophrenia has been a clinical challenge for most psychiatrists. The possible mechanism of the refractory schizophrenia included diagnostic errors, medical conditions and brain dysgensis. Here, we described a patient with childhood-onset schizophrenia who had severe psychiatric symptoms such as auditory hallucination and persecutory delusion and so on. We reexamined all his possible medical conditions and found the patient had an abnormal enlarged Cavus Septum Pellucidum (CSP) combined with Cavum Vergae (CV) (maximum length>30 mm). Some reports suggested that abnormal CSP(length>6 mm) has an significant association with schizophrenia. However, abnormally large CSP or CSP/CV and related prognosis were reported rarely. This case suggested that abnormally enlarged CSP or CSP/CV may lead to schizophrenia and worse prognosis.
The present study was designed to detect three single nucleotide polymorphisms (SNPs) located on 22q11 that was thought as being of particularly importance for genetic research into schizophrenia. We recruited a total of 176 Chinese family trios of Han descent, consisting of mothers, fathers and affected offspring with schizophrenia for the genetic analysis. The transmission disequilibrium test (TDT) showed that of three SNPs, rs10314 in the 3′-untranslated region of the CLDN5 locus was associated with schizophrenia (χ2 = 4.75, P = 0.029). The other two SNPs, rs1548359 present in the CDC45L locus centromeric of rs10314 and rs739371 in the 5′-flanking region of the CLDN5 locus, did not show such an association. The global chi-square (χ2) test showed that the 3-SNP haplotype system was not associated with schizophrenia although the 1-df test for individual haplotypes showed that the rs1548359(C)-rs10314(G)-rs739371(C) haplotype was excessively non-transmitted (χ2 = 5.32, P = 0.02). Because the claudin proteins are a major component for barrier-forming tight junctions that could play a crucial role in response to changing natural, physiological and pathological conditions, the CLDN5 association with schizophrenia may be an important clue leading to look into a meeting point of genetic and environmental factors.
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.
To evaluate the efficacy of lurasidone for schizophrenia using an established five-factor model of the Positive and Negative Syndrome Scale (PANSS).
Patient-level data were pooled from five randomized, double-blind, placebo-controlled, 6-week studies of lurasidone (fixed doses, 40–160 mg/d) for patients with an acute exacerbation of schizophrenia. Changes in five established PANSS factors were assessed using mixed-model repeated measures analysis.
Compared with placebo (n = 496), lurasidone (n = 1029, dose groups pooled) significantly improved the PANSS total score at Week 6 (−22.6 vs. −12.8; P < 0.001; effect size, 0.45), as well as all factor scores (P < 0.001 for each): positive symptoms (−8.4 vs. −6.0; effect size, 0.43), negative symptoms (−5.2 vs. −3.3; effect size, 0.33), disorganized thought (−4.9 vs. −2.8; effect size, 0.42), hostility/excitement (−2.7 vs. −1.6; effect size, 0.31), and depression/anxiety (−3.2 vs. −2.3; effect size, 0.31). Separation from placebo occurred at Week 1 for the positive symptoms, disorganized thought, and hostility/excitement factors and at Week 2 for the other factors.
In this pooled analysis of short-term studies in patients with acute schizophrenia, lurasidone demonstrated significant improvement for each of the five PANSS factor scores, indicating effectiveness across the spectrum of schizophrenia symptoms.
Metabolic syndrome induced by atypical antipsychotics is more prevalence in schizophrenic patients. Much less is known regarding paliperidone ER. The objective of this study was to compare matched paliperidone-ER- and olanzapine-treated schizophrenic patients on measures of glucose and lipid metabolism. Eighty hospitalized patients with schizophrenia (DSM-) were randomly assigned to treatment with paliperidone ER or olanzapine for 12 weeks. At baseline and every 4 weeks, we assessed weight, subcutaneous fat, waist and hip circumferences, fasting glucose, insulin, glycohemoglobin A1, cholesterol, triglycerides, high density level (HDL) cholesterol, low density level (LDL) cholesterol and prolactin. And we also evaluate the body mass index (BMI), homeostasis insulin resistance (HOMA-IR) and homeostasis β-cell function (HOMA-B). 33 patients randomly assigned to paliperidone ER and 23 patients randomly assigned to olanzapine completed the entire 12-week treatment. Within-group overall analysis showed that the fasting measures were increased in weight, BMI, waist circumferences, hip circumferences, subcutaneous fat, cholesterol, triglyceride and prolactin for two groups, and fasting glucose, LDL and HOMA-B were increased for olanzapine group. There was significantly difference in serum prolactin between paliperidone ER and olanzapine group. And there was a trend for HOMA-B to increase in olanzapine group over 12 weeks compared to paliperidone ER group. However, there were no overall differential drug effects over 12 weeks on the fasting measures of BMI, glucose, glycohemoglobin A1, insulin, HDL, LDL, cholesterol, triglyceride and HOMA-IR. The study further reinforces the necessity of regular monitoring the metabolic parameters in schizophrenic patients with atypical antipsychotics including paliperidone ER.
This double-blind (DB), relapse prevention, phase-3 study was designed to evaluate the efficacy and safety of paliperidone palmitate long-acting 3-monthly formulation (PP3M) versus placebo in delaying time-to-relapse of schizophrenia symptoms.
Adults (18-70 years old) with schizophrenia (DSM-IV-TR) were treated with PP (17-week, open-label [OL] transition phase: 50, 75, 100, or 150 mg eq, once-monthly, [PP1M]; 12-week OL maintenance phase: 3.5-fold PP1M stabilized dose, single injection), and then randomized (1:1) to PP3M fixed doses (175, 263, 350 or 525 mg eq.) or placebo.
305/506 patients enrolled were randomized (PP3M: n=160; placebo: n=145); majority were men (75%), white (59%), mean age 38.4 years. Interim analysis results favored PP3M vs. placebo (p = 0.0002, two-sided log-rank test; HR: 3.45, 95% CI: 1.73; 6.88); median time-to-relapse was 274 days in placebo and not estimable in PP3M group. Final results were consistent with interim analysis. Both PANSS total score and CGI-S score showed a significant effect over time in PP3M- vs. placebo-treated patients (p>0.001). 330/506 (65.2%) patients in OL phase and 183/305 (60.0%) in DB phase (PP3M: 61.9% vs. placebo: 57.9%) had ≥1 treatment-emergent adverse event (TEAE). The TEAEs noted more frequently in PP3M-vs. placebo (DB phase) were nasopharyngitis (5.6% vs. 1.4%), weight gain (8.8% vs. 3.4%), headache (8.8% vs.4.1%) and akathisia (4.4% vs. 0.7%).
Compared with placebo, PP3M significantly delayed time to first relapse in patients with schizophrenia, previously treated for 4 months with PP1M. PP3M was tolerable with a safety profile generally consistent with other marketed formulations of paliperidone.
The majority of neuroimaging studies reported smaller hippocampal volumes in patients with posttraumatic stress disorder (PTSD). Our previous study found that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields However, the causality of smaller hippocampal volumes and PTSD cannot be determined in these studies because of the cross-sectional nature of them. The purpose of this longitudinal study was to determine if PTSD caused hippocampal subfields volume loss following traffic accidents. Volumes of hippocampal subfields in thirty seven traffic accident survivors were measured using 3T MRI in one week after accident, and twenty five of them completed one year follow-up MRI scan. Fourteen participants met the PTSD diagnosis in one year follow-up while other eleven did not met PTSD diagnosis criteria. PTSD was significantly associated with volumes reduction of CA3/dentate gyrus subfield (β=0.244 p=0.017) while other subfields were spared. It also shown volume loses of Entorhinal Cortex (ERC) of both side in one year follow-up for the whole sample (mean volume reduction: right 19.25mm3, left 22.04 mm3). But no association has been found between PTSD and ERC volume alteration. The findings indicate for the first time in humans that selective volume loss of the CA3/dentate gyrus subfields is the results but not the risk factor of PTSD. It also suggested that ERC may also be a stress sensitive region.