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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.
This paper provides a solution to the active vibration control of a microsatellite with two solar panels. At first, the microsatellite is processed as a finite element model containing a rigid body and two flexible bodies, according to the principles of mechanics, and that the dynamic characteristics are solved by modal analysis. Secondly, the equation involving vibration control is established according to the finite element calculation results. There are several actuators composed of macro fibre composite on the two solar panels for outputting control force. Furthermore, the control voltage for driving actuator is calculated by using fuzzy algorithm. It is clear that the smart structure consists of the flexible bodies and actuators. Finally, the closed-loop control simulation for suppressing harmful vibration is established. The simulation results illustrate that the responses to the external excitation are decreased significantly after adopting fuzzy control.
Prolactin (PRL) data from adolescents treated with olanzapine are presented.
Data from 454 adolescents (13-18, mean=15.9 yrs) with schizophrenia or bipolar mania were pooled from 4 olanzapine (2.5-20.0mg/day) studies (4-32 weeks; 2 double-blind, placebo-controlled studies [combined for acute phase endpoint PRL levels] with open-label extensions; 2 open-label studies). Age- and sex-specific Covance reference ranges defined normal PRL; categorical increases were based on multiples of the upper limit of normal (ULN). Baseline-to-endpoint PRL changes in adolescents were compared with data pooled from 84 olanzapine clinical trials in adults with schizophrenia or bipolar disorder.
Olanzapine-treated adolescents had mean PRL increases at both the acute (11.4μg/L) and open-label endpoints (4.7μg/L). Of those patients with normal PRL levels at baseline (N=311), high PRL occurred in 54.7% at anytime; 32.2% at endpoint. The percentage of patients in which PRL levels shifted from normal-to-abnormal was smaller at endpoint than at anytime during treatment; 26.7% shifted to a higher category. Among patients with normal baseline PRL, 32.7% remained <=1X ULN; 32.3% increased to 1¬<=2X; 6.0%, >2-<=3X; and 1.2%, >3X at anytime; 4.6% had at >=1 potentially PRL-related adverse event. Adolescents had significantly higher mean changes at endpoint (p=.004), and a greater incidence of high PRL levels at anytime during olanzapine treatment (p<.001) versus adults.
Incidence of high PRL was significantly higher, and mean increases in PRL were significantly greater in adolescents versus adults. Mean increases and high PRL incidence were lower at the open-label compared with the acute phase endpoint.
It is to estimate the trend of suicide rate changes during the past three decades in China and try to identify its social and economic correlates.
Official data of suicide rates and economic indexes during 1982–2005 from Shandong Province of China were analyzed. The suicide data were categorized for the rural / urban location and gender, and the economic indexes include GDP, GDP per capita, rural income, and urban income, all adjusted for inflation.
We found a significant increase of economic development and decrease of suicide rates over the past decades under study. The suicide rate decrease is correlated with the tremendous growth of economy.
The unusual decrease of Chinese suicide rates in the past decades is accounted for within the Chinese cultural contexts and maybe by the Strain Theory of Suicide.
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.
The changes in metabolic parameters in olanzapine-treated adolescents were examined.
Data from 454 adolescents (13–18, mean=15.9 years) with schizophrenia or bipolar I disorder were pooled from 4 olanzapine (2.5–20.0mg/day) studies (4–32 weeks). Changes in metabolic parameters in adolescents were compared with those of olanzapine-treated adults (pooled from 84 clinical trials); changes in weight and BMI were compared with US age- and sex-adjusted standardized growth curves.
Olanzapine-treated adolescents had significant increases from baseline-to-endpoint in fasting glucose (p=.021); total cholesterol, LDL, and triglycerides (p<.001); and significant decreases in HDL (p<.001). Significantly more adolescents gained >=7% of their baseline weight versus adults (65.1% vs. 35.6%, p<.001); mean change from baseline-to-endpoint in weight was significantly greater in adolescents (7.0 vs. 3.3kg, p<.001). Adolescents had significantly lower mean changes from baseline-to-endpoint in fasting glucose (0.3 vs. 0.1mmol/L, p=.002) and triglycerides (0.3 vs. 0.2mmol/L, p=.007) versus adults. Significantly more adults experienced treatment-emergent normal-to-high changes at anytime in fasting glucose (4.8% vs. 1.2%, p=.033), total cholesterol (6.9% vs. 1.1%, p=.001), LDL (5.8% vs. 1.5%, p=.014), and triglycerides (25.7% vs. 17.4%, p=.030). Compared with standardized growth curves, olanzapine-treated adolescents had greater increases from baseline-to-endpoint in weight (1.0 vs. 7.1kg, p<.001), height (0.5 vs. 0.7cm, p<.001), and BMI (0.2 vs. 2.2kg/m2, p<.001).
Olanzapine-treated adolescents may gain significantly more weight compared with adults, but may have smaller changes in other metabolic parameters. Clinicians may want to consider both efficacy and changes in metabolic parameters when selecting treatment options for individual adolescent patients.
GABRB2, the gene for β2 subunit of the gamma-aminobutyric acid type A (GABAA) receptor, is known to display two splicing isoforms in the brain, namely β2L containing Exon 10 and β2S devoid of Exon 10. Previously, the expressions of these isoforms were correlated with both schizophrenia and various sequence polymorphisms of the gene. in the present study, a series of deletions made on Intron 9 of a minigene construct affected the expression of Exon 10, and generated additional splicing variations suggesting the existence of additional splicing variants of β2subunit. A search among brain cDNAs uncovered the two novel short forms: β2S1which is devoid of Exons 10 and 11 and bears an extended Exon 9, and β2S2 which is devoid of Exon 10 and bears a shortened Exon 11.Real-time quantitative polymerase chain reaction, performed with a cohort of 31 schizophrenics, 30 bipolar disorder and 31 controls of US population, showed that the level of β2S2 was significantly decreased in bipolar disorder, and marginally decreased in schizophrenia, while β2S1 was marginally increased in both of these psychotic disorders. Significant genotypic effects of rs1816071, rs1816072 and rs187269 on β2S2 level were observed in male schizophrenic and bipolar patients. These findings pointed to the neighborhood of Exon 10 as an alternate-splicing hot-spot, and underlined the relevance of β2 subunit isoforms to the etiology of psychotic disorders.
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.
Opiate drug psychological dependence is acknowledged as a difficult problem in the world. Several studies have shown the short-term efficacy of deep brain stimulation (DBS) in reducing opiate addiction. In this case report, we report on long-term results up to five years in an opiate addiction patient.
A 24-year-old man with three-year history of opiate addiction presented with several withdraw syndromes and more than three-time failures in detoxification.
The patient was treated with bilateral DBS of the nucleus accumbens (NAc) for opiate psychological dependence. No relapse was found during the follow-up periods.
This study suggests that DBS of the NAC could be an effective treatment of patients in reducing psychological dependence with a good recovery in psychological dysfunction.
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.
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.
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.
There is growing international interest in cross-cultural research of depressed patients to contribute to the aetiology discussion of the disorder and to find culture specific treatment strategies.
The aim of this study is to investigate the psychodynamic conflicts and structures of Chinese and German depressed patients and their influence on symptomatology.
A total of 111, SCID-I assessed depressed patients (57 Chinese and 64 German patients) were included in this study. the Beck Depression Inventory (BDI) and the conflict and the structure axes of the Operationalized Psychodynamic Diagnostics (OPD-2) were applied for evaluating the severity of the symptomatology and the psychodynamic profiles, respectively.
After controlling socioeconomic factors (age, gender, familial status and employment) German patients compared with Chinese patients showed significantly lower BDI total scores (24.16 ± 8.67 vs. 28.66 ± 11.01, p < 0.05). in terms of the OPD-2 parameters, German patients suffered from more frequent conflicts like the “desire for care vs. self-sufficiency conflict” (1.84 ± 1.13 vs. 1.12 ± 1.07, p < 0.01) as well as the “guilt conflict” (1.02 ± 0.85 vs. 0.65 ± 0.95, p < 0.05). in contrast, we found more frequent “dependence vs. individuation” conflicts in the Chinese sample compared with German patients (1.21 ± 1.19 vs. 0.78 ± 0.98, p < 0.05). there was no relationship between the psychodynamic profiles and the symptoms’ severity.
The findings suggest more culture specific psychodynamic psychotherapy strategies for depressed patients coming from different countries and cultures.
We describe an analytical method of SH-SY5Y cell membrane chromatography (SH-SY5Y/CMC) for recognition, separation and identification of active components from traditional Chinese medicines (TCMs). SH-SY5Y cells by means of culture with SH-SY5Y cell lines were used for preparation of the stationary phase in the CMC model. Retention components by the SH- SY5Y/CMC model were collected and active components then analyzed by SH-SY5Y/CMC under the optimized conditions. After investigating the suitability and reliability of the SH-SY5Y /CMC method using risperidone, sertraline and clozapine as standard compounds, this method was applied in screening active components from the extracts of TCMs such as Radix Gentianae, Radix Bupleuri, stir-baked semen ziziphi spinosae, rehmannia dride rhizome, uncaria rhynchophylla. Retention components from the extracts in the SH-SY5Y/CMC model were gentiopicrin and rosmarinci acid identified by the GC/MS method. In vitro pharmacological trials indicated that gentiopicrin and rosmarinci acid could concentration dependently protect the SH-SY5Y pre-treated by H2O2 (P < 0.05). The SH-SY5Y/CMC method is an effective screening system that can rapidly detect target components from a complex sample for antipsychotic candidate drug.
The main aim of the present studies is to determine whether, or to some extent, specific cognitive domains could differentiate the main subtypes of mood disorder in the depressed and clinically remitted status respectively.
Three groups of bipolar I (n = 92), bipolar II (n = 131) and unipolar depression patients (n = 293) were tested with a battery of neuropsychological tests at baseline and after 6 weeks of treatment, contrasting with 202 healthy controls on cognitive performance.
At the acute depressive state, the three patients groups (bipolar I, bipolar II and unipolar depression) showed cognitive dysfunction in processing speed, memory, verbal fluency and executive function but not attention compared with controls. And post comparisons revealed that bipolar I patients performed significantly worse in these impaired cognitive domain than bipolar II and unipolar depression patients in verbal fluency and executive function. After treatment, clinically remitted bipolar I and bipolar II patients only displayed cognitive impairment in processing speed and visual memory in relative to controls, while remitted unipolar depression patients showed cognitive impairment in executive function in addition to processing speed and visual memory.
Bipolar I, bipolar II and unipolar depression patients have a similar pattern of cognitive impairment during the state of acute depressive episodes. At the clinically remission, still both bipolar disorder and unipolar depression patients showed cognitive deficits in processing speed and visual memory, and executive dysfunction might be a status-maker for bipolar disorder, but a trait-marker for unipolar depression
The association between gray matter and cognitive dysfunction in young major depression remains unclear.
To investigate the brain gray matter and the correlation with cognitive function in first-episode, treatment-naive patients with major depressive disorder (MDD).
To explore brain structural pathological mechanisms of cognitive impairment in MDD.
46 MDD aged 18-45 year and 46 controls were assessed by Wisconsin Card Sorting Test (WCST) and Trail making test (TMT). Then, 30 patients and 30 controls were obtained by MRI scan.
The total number of errors, number of preservative errors, random errors of WSCT in MDD were significantly more than that in controls, and the completion time in the TMT-A and TMT-B was longer than that in controls. MDD showed significant less gray matter volumns than controls in frontal lobe (right precentral gyrus, bilateral superior frontal gyrus and right middle frontal gyrus), parietal lobe (left postcentral gyrus, left paracentral lobule, and bilateral precuneus), temporal lobe (right superior temporal gyrus), and occipital lobe (left superior occipital gyrus). There was a significant negative correlation between left postcentral gyrus and left superior occipital gyrus gray matter density and the TMT-B completion time (r=-0.462, P=0.017; r=-0.448, P=0.022).
The first-episode MDD patient exhibiteded cognitive impairment and showed significant lower gray matter density than controls in frontal lobe, parietal lobe, temporal lobe, occipital lobe. Decreased gray matter density in left postcentral gyrus and left superior occipital gyrus may be involved in the executive dysfunction.
Patients with schizophrenia are at high risk for diabetes, dyslipidemia, hypertension, and obesity, which can be exacerbated by some atypical antipsychotics.
To evaluate the effect of lurasidone on weight and metabolic parameters.
To establish the cardiometabolic safety of lurasidone.
Short-term data were pooled from seven, double-blind, 6-week studies of subjects with acute exacerbation of schizophrenia treated with lurasidone 20-160 mg/day (N=1508); haloperidol 10 mg/day (N=72); olanzapine 15 mg/day (N=122); risperidone 4 mg/day (N=65); quetiapine XR 600 mg/day (N=119) or placebo (N=708). Long-term data (6-22 months) were pooled from patients treated with lurasidone 40-120 mg/day (flexibly dosed).
Proportions of patients experiencing ≥7% weight gain during short-term treatment were: lurasidone 4.8%, haloperidol 4.2%, olanzapine 34.4%, risperidone 6.2%, quetiapine XR 15.3%, and placebo 3.3%. Median lipid changes were: triglycerides (mg/dL), lurasidone -4.0, haloperidol -3.0, olanzapine +25.0, risperidone +4.0, quetiapine XR +9.5, and placebo -6.0; total cholesterol (mg/dL), lurasidone -5.0, haloperidol -8.0, olanzapine +9.0, risperidone +6.5, quetiapine XR +6.0, and placebo -5.0; trends were similar for LDL. Median changes in glucose (mg/dL) were similar for lurasidone (0.0) and placebo (0.0), and higher for haloperidol (+2.0), olanzapine (+4.0), risperidone (+3.0), and quetiapine XR (+3.0). Minimal-to-no changes in HbA1c were observed. With long-term lurasidone treatment, mean weight change after 12-month exposure was -0.73 kg and median metabolic changes were: -2.0 mg/dL for total cholesterol and -5.0 mg/dL for triglycerides.
Short- and long-term treatment with lurasidone showed minimal changes in weight and decrease in mean total and LDL cholesterol and triglycerides.
In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation.
Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group.
11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1.
The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.
Cigarette smoking is strongly associated with major depressive disorder (MDD). However, any genetic etiology of such comorbidity and causal relations is poorly understood, especially at the genome-wide level.
In the present in silico research, we analyzed summary data from the genome-wide association study of the Psychiatric Genetic Consortium for MDD (n = 191 005) and UK Biobank for smoking (n = 337 030) by using various biostatistical methods including Bayesian colocalization analysis, LD score regression, variant effect size correlation analysis, and Mendelian randomization (MR).
By adopting a gene prioritization approach, we identified 43 genes shared by MDD and smoking, which were significantly enriched in membrane potential, gamma-aminobutyric acid receptor activity, and retrograde endocannabinoid signaling pathways, indicating that the comorbid mechanisms are involved in the neurotransmitter system. According to linkage disequilibrium score regression, we found a strong positive correlation between MDD and current smoking (rg = 0.365; p = 7.23 × 10−25) and a negative correlation between MDD and former smoking (rg = −0.298; p = 1.59 × 10−24). MR analysis suggested that genetic liability for depression increased smoking.
These findings inform the concomitant conditions of MDD and smoking and support the use of self-medication with smoking to counteract depression.