Lipopolysaccharide inhibits hypothalamic Agouti-related protein gene expression via activating mechanistic target of rapamycin signaling in chicks.

Lipopolysaccharide (LPS) induces profound anorexia in birds. However, the neuronal regulatory network underlying LPS-provoked anorexia is unclear. To determine whether any cross talk occurs among hypothalamic mechanistic target of rapamycin (mTOR) and LPS in the regulation of appetite, we performed an intracerebroventricular injection of rapamycin (an mTOR inhibitor) on LPS-treated chicks. The results indicate that peripheral administrations of LPS decreased the agouti-related protein (AgRP) mRNA level, but increased the phosphorylated mTOR and nuclear factor-кB (NF-кB) protein level. Blocking mTOR significantly attenuated LPS-induced anorexia, AgRP suppression, and p-NF-кB increase. Thus, the results suggest that LPS causes anorexia via the mTOR-AgRP signaling pathway, and mTOR signaling is also associated with the regulation of LPS in p-NF-кB.

Different effects of probiotics and antibiotics on the composition of microbiota, SCFAs concentrations and FFAR2/3 mRNA expression in broiler chickens.

AIMS: The aims of this study were to investigate the effects of probiotics and antibiotics on microbial composition, short chain fatty acids (SCFAs) concentration and free fatty acid receptor 2/3 (FFAR2/3) expression in boiler chickens. METHODS AND RESULTS: A total of 150 1-day-old male broilers were randomly allocated into three groups, control (CON) group, probiotics (PB) group and antibiotics (ATB) group. Results indicated that PB improved the average body weight from 1 to 21 days and feed intake from 21 to 42 days (P < 0·05), while ATB improved the feed efficiency from 1 to 42 days (P < 0·05). Based on 16s rRNA sequencing, PB treatment increased the amount of kingdom bacteria, and the relative abundance of the main bacteria including acetate and butyrate producing bacteria of phylum Firmicutes, family Ruminococcaceae and genus Faecalibacterium. ATB treatment also increased the relative abundance of phylum Firmicutes, family Ruminococcaceae and Lachnospiraceae, however, it introduced some pathogenic bacteria, such as bacteria of family Rikenellaceae and Enterobacteriaceae. Gas chromatography and mass spectrometry (GC-MS) assay revealed that PB increased acetate and butyrate concentrations at both 21 and 42 days, and propionate at 42 days in the colorectum. Moreover qRT-PCR analysis showed PB treatment significantly activated the FFAR2/3 mRNA expressions. On the contrast, ATB treatment lowered the colorectal propionate at 21 days, and decreased acetate, propionate and butyrate concentrations at 42 days, accompanied with decreased FFAR2/3 mRNA expressions. CONCLUSIONS: Compared to the CON birds, an enriched SCFAs producing bacteria with higher SCFAs contents and activated FFAR2/3 expressions are prominent features of PB birds. However, antibiotics treatment plays the reverse effect compared to PB treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: This study brings a significant idea that less SCFAs concentration may be another reason why the antibiotics inhibit the immune system development and immunity of the body.

[Comparison of severity classification of Chinese protocol, pneumonia severity index and CURB-65 in risk stratification and prognostic assessment of coronavirus disease 2019].

Objective: To investigate the application of severity classification according to the protocol on the Diagnosis and Treatment of coronavirus disease 2019(COVID-19)by the National Health Commission of China, pneumonia severity index(PSI) and CURB-65　in risk stratification and prognostic assessment of COVID-19. Methods: Clinical data of 234 in-hospital patients with COVID-19 were collected and retrospectively reviewed in Wuhan Tongji Hospital. Patients were divided into 3 groups (common, severe, and critical type) at admission according to the sixth version of the protocol issued by the National Health Commission of China on Diagnosis and Treatment of COVID-19. At the same time, the severity of pneumonia was calculated by PSI and CURB-65, and the patients were stratified into 3 risk groups, namely mild, moderate, and severe groups. The hospital mortality rate was evaluated in each group. Sensitivity, specificity, positive predictive values, negative predictive values, and the area under the receiver operating characteristic(ROC) curve(AUC) for predicting hospital mortality in each rule were assessed. Results: According to the severity classification of Chinese protocol, the proportion of patients with common type, severe type, and the critical type was 15.8%, 75.6%, and 8.5%, respectively. No in-hospital death occurred in the common type. As for PSI and CURB-65, greater proportions of patients were classified as low risk(79.1% and 75.6%, respectively), while smaller proportions of patients were classified as moderate and high risk(16.2%, 15.0%; 4.7%, 9.4%, respectively). In-hospital death occurred in low and moderate risk patients identified by these 2 scoring systems. The mortality of the critical group of the Chinese protocol was 65%, and the sensitivity and specificity of predicting in-hospital mortality were 36.4% and 97.0%, respectively. The mortality in the high risk group of PSI and CURB-65 was 100% and 77.3%. The risk class V of PSI and CURB-65 score 3-5 had high specificity(100% and 97.4%, respectively)but low sensitivity(33.3% and 51.5%, respectively)in predicting in-hospital mortality. The AUC of the Chinese protocol severity classification, PSI, and CURB-65 was 0.735, 0.951, and 0.912. The optimal cut-off point of PSI was risk class Ⅳ, and the sensitivity and specificity for predicting mortality were 90.9% and 90.5%. The optimal cut-off point of CURB-65 was score 2, and the corresponding sensitivity and specificity were 84.8% and 85.6%. Conclusions: PSI and CURB-65 can be used for risk stratification and prognostic assessment in patients with COVID-19.

[Clinical effect of nebulized acetylcysteine inhalation combined with bronchoscopy in the treatment of elderly patients with severe ventilator-associated pneumonia].

Objective: To explore the clinical effect of nebulized acetylcysteine inhalation combined with bronchoscopy in treating elderly patients with severe ventilator-associated pneumonia (VAP). Methods: From January 2016 to December 2017, 80 elderly patients with severe VAP who were hospitalized in Zhejiang Hospital were divided into acetylcysteine+ bronchoscopy group [24 males and 16 females, aged (78±7) years] and bronchoscopy group [26 males and 14 females, aged (80±7) years]using random number table for a prospective cohort study. Patients in bronchoscopy group were treated with bronchoscopy in addition to conventional supportive care of symptoms. Patients in acetylcysteine+ bronchoscopy group received nebulized acetylcysteine inhalation therapy on the basis of the treatment given to patients in bronchoscopy group. Patients in both groups received treatment continuously for 7 days. The simplified clinical pulmonary infection score (CPIS) in both groups was assessed before and after treatment. Venous blood of 10 mL was collected before and after treatment to detect leukocyte count, serum C-reactive protein, and procalcitonin. Arterial blood of 1 mL was collected before and after treatment to detect partial arterial oxygen pressure (PaO(2)), partial arterial carbon dioxide pressure (PaCO(2)), oxygenation index. The inhalation platform pressure (Pplat), dynamic lung compliance (Cdyn), airway resistance, work of breathing, time of antibiotic use, and time of mechanical ventilation of patients in two groups were recorded before and after treatment. Data were statistically analyzed with chi-square test and t test. Results: (1) The simplified CPIS, leukocyte count, serum C-reactive protein, and procalcitonin of patients in acetylcysteine+ bronchoscopy group were significantly lower than those in bronchoscopy group after treatment (t=2.32, 2.15, 6.08, 7.12, P<0.05 or P<0.01). The simplified CPIS, leukocyte count, serum C-reactive protein, and procalcitonin of patients in acetylcysteine+ bronchoscopy group and bronchoscopy group after treatment were significantly lower than those before treatment (t=13.76, 13.60, 12.70, 8.32, 11.44, 14.28, 9.48, 9.50, P<0.01). (2) Compared with bronchoscopy group, patients in acetylcysteine+ bronchoscopy group had significantly higher PaO(2) and oxygenation index (t=4.14, 2.55, P<0.05 or P<0.01) but significantly lower PaCO(2) (t=4.36, P<0.01) after treatment. The PaO(2) and oxygenation index of patients in acetylcysteine+ bronchoscopy group after treatment were significantly higher than those before treatment (t=10.90, 43.72, P<0.01). The PaO(2) and oxygenation index of patients in bronchoscopy group after treatment were also significantly higher than those before treatment (t=6.55, 43.03, P<0.01). The PaCO(2) of patients in both groups after treatment were significantly lower than those before treatment (t=21.54, 21.92, P<0.01). (3) The Cdyn of patients in acetylcysteine+ bronchoscopy group after treatment was significantly higher than that in bronchoscopy group (t=5.41, P<0.01), and Pplat, airway resistance, and work of breathing were significantly lower than those in bronchoscopy group (t=2.18, 5.46, 2.49, P<0.05 or P<0.01). The Cdyn of patients in both groups after treatment were significantly higher than those before treatment (t=16.10, 10.90, P<0.01), and Pplat, airway resistance, and work of breathing were significantly lower than those before treatment (t=21.18, 11.13, 9.32, 15.50, 5.17, 5.97, P<0.01). (4)The time of mechanical ventilation and antibiotic usage of patients in acetylcysteine+ bronchoscopy group were (6.9±1.9)and (8.7±2.8) d, respectively, which were significantly shorter than (10.1±2.2) and (11.6±3.5) d in bronchoscopy group (t=6.85, 4.09, P<0.01). Conclusions: Nebulized acetylcysteine inhalation combined with bronchoscopy can significantly control the degree of lung infection in elderly patients with severe VAP, improve patients' respiratory mechanics parameter and blood gas analysis indicator, and shorten the time for mechanical ventilation and antibiotic usage.

Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China.

BACKGROUND: Cancer patients are regarded as a highly vulnerable group in the current Coronavirus Disease 2019 (COVID-19) pandemic. To date, the clinical characteristics of COVID-19-infected cancer patients remain largely unknown. PATIENTS AND METHODS: In this retrospective cohort study, we included cancer patients with laboratory-confirmed COVID-19 from three designated hospitals in Wuhan, China. Clinical data were collected from medical records from 13 January 2020 to 26 February 2020. Univariate and multivariate analyses were carried out to assess the risk factors associated with severe events defined as a condition requiring admission to an intensive care unit, the use of mechanical ventilation, or death. RESULTS: A total of 28 COVID-19-infected cancer patients were included; 17 (60.7%) patients were male. Median (interquartile range) age was 65.0 (56.0-70.0) years. Lung cancer was the most frequent cancer type (n = 7; 25.0%). Eight (28.6%) patients were suspected to have hospital-associated transmission. The following clinical features were shown in our cohort: fever (n = 23, 82.1%), dry cough (n = 22, 81%), and dyspnoea (n = 14, 50.0%), along with lymphopaenia (n = 23, 82.1%), high level of high-sensitivity C-reactive protein (n = 23, 82.1%), anaemia (n = 21, 75.0%), and hypoproteinaemia (n = 25, 89.3%). The common chest computed tomography (CT) findings were ground-glass opacity (n = 21, 75.0%) and patchy consolidation (n = 13, 46.3%). A total of 15 (53.6%) patients had severe events and the mortality rate was 28.6%. If the last antitumour treatment was within 14 days, it significantly increased the risk of developing severe events [hazard ratio (HR) = 4.079, 95% confidence interval (CI) 1.086-15.322, P = 0.037]. Furthermore, patchy consolidation on CT on admission was associated with a higher risk of developing severe events (HR = 5.438, 95% CI 1.498-19.748, P = 0.010). CONCLUSIONS: Cancer patients show deteriorating conditions and poor outcomes from the COVID-19 infection. It is recommended that cancer patients receiving antitumour treatments should have vigorous screening for COVID-19 infection and should avoid treatments causing immunosuppression or have their dosages decreased in case of COVID-19 coinfection.

[Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19].

Objective: To evaluate the cardiovascular damage of patients with COVID-19, and determine the correlation of serum N-terminal pro B-type natriuretic peptide (NT-proBNP） and cardiac troponin-I (cTnI） with the severity of COVID-19, and the impact of concomitant cardiovascular disease on severity of COVID-19 was also evaluated. Methods: A cross-sectional study was designed on 150 consecutive patients with COVID-19 in the fever clinic of Tongji Hospital in Wuhan from January 19 to February 13 in 2020, including 126 mild cases and 24 cases in critical care. Both univariate and multivariate logistic regression were used to analyze the correlation of past medical history including hypertension, diabetes and coronary heart disease (CHD）, as well as the levels of serum NT-proBNP and cTnI to the disease severity of COVID-19 patients. Results: Age, hypersensitive C-reactive protein(hs-CRP) and serum creatinine levels of the patients were higher in critical care cases than in mild cases(all P<0.05). Prevalence of male, elevated NT-proBNP and cTnI, hypertension and coronary heart disease were significantly higher in critical cases care patients than in the mild cases(all P<0.05). Univariate logistic regression analysis showed that age, male, elevated NT-proBNP, elevated cTnI, elevated hs-CRP, elevated serum creatinine, hypertension, and CHD were significantly correlated with critical disease status(all P<0.05). Multivariate logistic regression analysis showed that elevated cTnI(OR=26.909，95%CI 4.086-177.226，P=0.001) and CHD (OR=16.609，95%CI 2.288-120.577，P=0.005) were the independent risk factors of critical disease status. Conclusions: COVID-19 can significantly affect the heart function and lead to myocardial injury. The past medical history of CHD and increased level of cTnI are 2 independent determinants of clinical disease status in patients with COVID-19.

Fibroblast growth factor 23 mRNA expression profile in chickens and its response to dietary phosphorus.

In mammals, fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis in kidney by binding α-Klotho, a coreceptor of FGF23. FGF23 mRNA is highly expressed in bone and slightly expressed in liver, and is regulated by dietary phosphorus. Little is known about distribution and regulation of FGF23 mRNA in avian lineage. The expression of FGF23 and its coreceptor α-Klotho in chicken and embryo were investigated by real-time quantitative PCR. The effect of dietary phosphorus on FGF23 expression was measured. 36 laying hens at 25 wk were randomly assigned to three dietary available phosphorus (AP) treatments for 11 days: 0.15% AP (LP), 0.40% AP (MP), and 0.80% AP (HP). We first cloned the full coding sequence of FGF23 by the reverse transcription PCR from chicken liver and calvaria. Bioinformatics analysis indicated that the deduced amino acid sequence was 57-87% identical to FGF23 of other species. In adult chicken FGF23 mRNA was expressed at unexpected higher level in liver than other tissues evaluated, including calvaria, femur, tibia, medullary bone, brain, spleen, duodenum, jejunum, ileum, heart and kidney (P < 0.0001), and α-Klotho was expressed at highest level in kidney. However, in 18-d chicken embryos, FGF23 mRNA level was much higher in tibia than in liver, heart and jejunum (P < 0.0001). Chickens at 2, 25, 50 and 80 wk had higher FGF23 expression in liver than 18-d chicken embryos, whereas chickens at 25 wk had lower FGF23 expression in tibia than 18-d chicken embryos and 2-wk-old chickens. HP diets significantly increased serum inorganic phosphorus level (P < 0.001) and FGF23 expression (P < 0.05) in bone tissue compared with LP diets, however, FGF23 mRNA abundance in liver was not changed significantly (P > 0.05) by dietary phosphorus treatments. In conclusion, FGF23 mRNA expression pattern in chicken was clearly different from that in mammals and dietary phosphorus regulated the expression of FGF23 in a tissue-specific way.

Leucine alters immunoglobulin a secretion and inflammatory cytokine expression induced by lipopolysaccharide via the nuclear factor-κB pathway in intestine of chicken embryos.

The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.

Depression and cancer risk: a systematic review and meta-analysis.

OBJECTIVE: To assess the associations between depression and incident cancer risk. STUDY DESIGN: Systematic review and meta-analysis. METHODS: The Cochrane Library, Web of Science, MEDLINE, and PubMed databases were searched to identify studies. The quality of included studies was assessed using the Newcastle Ottawa Scale. Risk ratios (RRs) were used to measure effect size. A random-effects model was applied to synthesize the associations between depression and cancer risk. A forest plot was produced to visually assess RRs and 95% confidence intervals (CIs). Heterogeneity across studies was assessed using the I-squared statistic. A funnel plot was generated to assess potential publication bias, and Egger's regression was applied to test the symmetry of the funnel plot. RESULTS: In total, 1,469,179 participants and 89,716 incident cases of cancer from 25 studies were included. Depression was significantly associated with overall cancer risk (RR = 1.15, 95% CI: 1.09-1.22) and with liver cancer (RR = 1.20, 95% CI: 1.01-1.43) and lung cancer (RR = 1.33, 95% CI: 1.04-1.72). Subgroup analysis of studies in North America resulted in a significant summary relative risk (RR = 1.30, 95% CI: 1.15-1.48). No significant associations were found for breast, prostate, or colorectal/colon cancer. The average Newcastle Ottawa score was 7.56 for all included studies. CONCLUSION: Our findings showed a small and positive association between depression and the overall occurrence risk of cancer, as well as liver cancer and lung cancer risks. However, multinational and larger sample studies are required to further research and support these associations. Moreover, confounding factors such as cigarette smoking and alcohol use/abuse should be considered in future studies.

[Correlation between expression of long non-coding RNA ZXF1 and prognosis of lung adenocarcinoma and its potential molecular mechanism].

Objective: To investigate the correlation between expression of long non-coding RNA (lncRNA) ZXF1 and clinicopathological characteristics, as well as prognosis of lung adenocarcinoma; and to explore its potential molecular mechanism. Methods: A total of 83 lung adenocarcinoma tissue samples and 83 paracancerous lung tissue samples from lung adenocarcinoma patients were collected. The mRNA expression of ZXF1 in the tumors and the corresponding adjacent non-tumor tissues were determined by real-time fluorescence quantitative PCR. The correlation between ZXF1 level and clinicopathological characteristics such as age, gender, smoking history, tumor size, tumor differentiation and lymph node metastasis was evaluated. Survival analysis was performed using Kaplan-Meier and Cox multivariate regression, based on the data of a 12-56 months follow-up after surgery. In vitro ZXF1 was over-expressed in lung adenocarcinoma A549 cells, and then the proteins functionally related to ZXF1 were identified by protein array analysis. Results: Of the 83 cases of lung adenocarcinoma, the ZXF1 mRNA levels in the tumor and adjacent non-tumor tissues were 8.32±3.05 and 1.05±0.47, respectively (P<0.05), and a high-level the high expression of ZXF1 in the tumor tissues was detected in 56 cases. The expression status of ZXF1 was closely correlated with the tumor differentiation and lymph node metastasis (P<0.05), but was not significantly related to age, gender and tumor size. Based on a 12-56 months follow-up, the patients with high level ZXF1 expression had a shorter disease free survival (DFS) and overall survival (OS) than that of the group with low level ZXF1 (all P<0.05). Multivariate analysis showed that ZXF1 expression, tumor size and lymph node metastasis were independent risk factors to DFS; and ZXF1 expression, tumor size, lymph node metastasis and tumor differentiation were independent risk factors to OS. The protein array data revealed that expressions of bone morphogenetic protein 5 (BMP-5)and stem cell factor receptor (SCFR)were upregulated upon overexpression of the ZXF1 in A549 cells. Conclusions: lncRNA ZXF1 is overexpressed in lung adenocarcinoma, and is closely correlated with tumor differentiation and lymph node metastasis. As an independent risk factor, a high expression of ZXF1 indicates a poor prognosis for the patients. ZXF1 may influence the biological behavior of lung adenocarcinoma by enhancing the protein expression of BMP-5 and SCFR.

Live performance, carcass characteristic and blood metabolite responses of broilers to two distinct corn types with different extent of grinding.

The major objective of this research was to establish the main and interactive effects of corn type and extent of grinding on broiler performance including carcass characteristics. A completely randomized experimental design with a 2 (corn type) × 2 (fine and coarse) factorial arrangement, each with six replicates of 45 male Ross chicks, was applied. Experimental diets, containing dent or hard corn, were formulated with two extents of grinding (3.00 or 6.00 mm screens) for three growing phases. In comparison with dent corn, the hard corn increased body weight (BW) gain and thigh muscle yield (p < 0.05), while decreasing feed conversion ratio (p < 0.01) and abdominal fat deposition (p < 0.05), some aspects of which were age-dependent and appeared to vary with extent of grinding. Coarser grinding increased the weight of proventriculus (p < 0.01), gizzard (p < 0.05) and small + large intestine (p < 0.10) relative to BW, particularly towards market size. These results suggest that feeding hard corn or large-particle-size corn have some favourable effects on growth performance or gastrointestinal development for finishing broilers.

Phylogenetic analysis of the pathogenic genus Aeromonas spp. isolated from diseased eels in China.

Analyses of 16S rRNA and housekeeping genes (HKGs) were valuated as identification markers for pathogenic Aeromonas isolated from diseased eels. The interrelationships of 32 Aeromonas strains which had been verified as pathogens to eels were studied using phylogenetic analysis with 16S rRNA and HKG sequences (cpn60, gyrB, rpoB and dnaJ) and identified by Biolog automatic microbiology analysis system (gene III). From the analysis of 5 genes, the mean gene divergences of 16S rRNA, cpn60, gyrB, rpoB and dnaJ in 32 isolates were 1.4 ± 0.2%, 7.1 ± 0.7%, 5.2 ± 0.5%, 2.2 ± 0.4% and 6.8 ± 0.5%, respectively. The results of comparative phylogeny between nucleotide based analyses (excluding the third codon position) of four HKGs with the sequences from 55 strains of Aeromonas (including 23 referenced strains of Aeromonas) showed cpn60 and dnaJ have higher discriminate power than gyrB and rpoB comparing with the taxonomical identification by Biolog system. In addition, amino acid sequences of concatenated cpn60-rpoB-gyrB is a good method for Aeromonas pathogens identification. This study showed analysis of HKG sequences can be used as an alternative method for sound identification of bacterial pathogens isolated from diseased eels in China.

Impaired glucose tolerance in first-episode drug-naïve patients with schizophrenia: relationships with clinical phenotypes and cognitive deficits.

BACKGROUND: Schizophrenia patients have a higher prevalence of type 2 diabetes mellitus with impaired glucose tolerance (IGT) than normals. We examined the relationship between IGT and clinical phenotypes or cognitive deficits in first-episode, drug-naïve (FEDN) Han Chinese patients with schizophrenia. METHOD: A total of 175 in-patients were compared with 31 healthy controls on anthropometric measures and fasting plasma levels of glucose, insulin and lipids. They were also compared using a 75 g oral glucose tolerance test and the homeostasis model assessment of insulin resistance (HOMA-IR). Neurocognitive functioning was assessed using the MATRICS Consensus Cognitive Battery (MCCB). Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Of the patients, 24.5% had IGT compared with none of the controls, and they also had significantly higher levels of fasting blood glucose and 2-h glucose after an oral glucose load, and were more insulin resistant. Compared with those patients with normal glucose tolerance, the IGT patients were older, had a later age of onset, higher waist or hip circumference and body mass index, higher levels of low-density lipoprotein and triglycerides and higher insulin resistance. Furthermore, IGT patients had higher PANSS total and negative symptom subscale scores, but no greater cognitive impairment except on the emotional intelligence index of the MCCB. CONCLUSIONS: IGT occurs with greater frequency in FEDN schizophrenia, and shows association with demographic and anthropometric parameters, as well as with clinical symptoms but minimally with cognitive impairment during the early course of the disorder.

Ovalbumin expression in the oviduct magnum of hens is related to the rate of egg laying and shows distinct stress-type-specific responses.

Three trials were performed to evaluate the association of ovalbumin (OVA) abundance in the oviduct magnum with egg production and the underlying regulatory mechanism by glucocorticoids. In trial 1, twenty Hy-Line Brown layers (56-60 weeks of age) with different combinations (n = 5/combination) of laying rate (high or low) and egg weight (high or low) were selected from an initial group of 300. An upregulated expression of magnum OVA was observed (p < 0.05) in hens with higher laying rate, regardless of egg weight. In trial 2, eighty Hy-Line Brown layers (80-90 weeks of age) were subjected to the forced moulting (n = 8). The abundance of OVA transcript and protein in the magnum was significantly decreased during moulting (p < 0.01), and the same was true for laying rate (p < 0.01) and serum oestrogen (p < 0.05). In trial 3, forty-five 56-week-old Hy-Line Brown layers were kept individually (n = 15) in the following conditions for 10 days: constant optimal ambient temperature at 23 °C and ad libitum feeding, high ambient temperature at 32 °C for 6 h/day (10:00-16:00) and ad libitum feeding (32AL), and constant optimal ambient temperature at 23 °C and pair-fed to the 32AL hens. In spite of elevated corticosterone in circulation, OVA synthesis, blood oestrogen and laying rate were not affected by heat exposure (p > 0.05). These results allow concluding that OVA expression in the oviduct magnum of hens is related to the rate of egg laying and shows distinct stress-type-specific responses.

Metformin treatment of antipsychotic-induced dyslipidemia: an analysis of two randomized, placebo-controlled trials.

Dyslipidemia is one of the most common adverse effects in schizophrenia patients treated with antipsychotics. However, there are no established effective treatments. In this study, data were pooled from two randomized, placebo-controlled trials, which were originally designed to examine the efficacy of metformin in treating antipsychotic-induced weight gain and other metabolic abnormalities. In total, 201 schizophrenia patients with dyslipidemia after being treated with an antipsychotic were assigned to take 1000 mg day-1 metformin (n=103) or placebo (n=98) for 24 weeks, with evaluation at baseline, week 12 and week 24. The primary outcome was the low-density lipoprotein cholesterol (LDL-C) levels. After metformin treatment, the mean difference in the LDL-C value between metformin treatment and placebo was from 0.16 mmol l-1 at baseline to -0.86 mmol l-1 at the end of week 24, decreased by 1.02 mmol l-1 (P<0.0001); and 25.3% of patients in the metformin group had LDL-C ≥3.37 mmol l-1, which is significantly <64.8% in the placebo group (P<0.001) at week 24. Compared with the placebo, metformin treatment also have a significant effect on reducing weight, body mass index, insulin, insulin resistance index, total cholesterol and triglyceride, and increasing high-density lipoprotein cholesterol. The treatment effects on weight and insulin resistance appeared at week 12 and further improved at week 24, but the effects on improving dyslipidemia only significantly occurred at the end of week 24. We found that metformin treatment was effective in improving antipsychotic-induced dyslipidemia and insulin resistance, and the effects improving antipsychotic-induced insulin resistance appeared earlier than the reducing dyslipidemia.

Rapamycin, a specific inhibitor of the target of rapamycin complex 1, disrupts intestinal barrier integrity in broiler chicks.

To uncover the molecular mechanisms underlying the intestinal barrier integrity, this study determined whether the rapamycin (RAPA)-sensitive target of rapamycin complex 1 (TORC1) pathway was involved in this process. Three groups of 4-day-old male chicks were randomly subjected to one of the following treatments for 6 days: high-dose RAPA [a specific inhibitor of TORC1; an intraperitoneal injection of 1.0 mg/kg body weight (BW), once daily at 09:00 hours], low-dose RAPA (0.4 mg/kg BW) and RAPA vehicle (control). Results showed that the RAPA treatment increased mortality, while decreasing villus height (p < 0.01), claudin 1 expression, content of immunoglobulin A (IgA), extent of TORC1 phosphorylation (p < 0.05), ratio of villus height to crypt depth (p < 0.01), and population of IgA-positive B cells in intestinal mucosa, particularly for the jejunum. Some aspects of these responses were dose dependent and appeared to result from weight loss. Together, RAPA exerts the expected inhibition of small intestinal development and IgA production in birds, suggesting the important role of TORC1 in gut barrier integrity.