Lower Cumulative Mortality Research Articles

P2678Performance of the European society cardiology 0/1-hour algorithm in the diagnosis of myocardial infarction with high-sensitivity cardiac troponin T: meta-analysis

Abstract Introduction A rapid rule-out or rule-in protocol based on the 0-hour/1-hour algorithm using high-sensitivity cardiac troponin T (hs-cTnT) is recommended by the European Society of Cardiology (ESC), and recently multiple studies have validated it in their settings. We conducted a systematic review and meta-analysis with the aim of assess the diagnostic accuracy of the 2015 ESC guidelines for management of acute coronary syndrome (ACS) in patients without ST-segment elevation's 0-/1-hour algorithm using hs-cTnT for the early rule-out and rule-in of acute myocardial infarction (AMI) on presentation. For the secondary analysis we evaluate cumulative mortality at 30 days. Methods We carried out a systematic review and meta-analysis of prospective studies involving adults presenting to the emergency department with possible ACS in which hs-cTnT measurements were obtained according to the ESC algorithm and AMI outcomes were adjudicated during the initial hospitalization. We searched MEDLINE, EMBASE, Cochrane database and LILACS, and unpublished abstracts presented in international congresses from 2015 to November 2018.To obtain estimates of sensitivity and specificity, with corresponding 95% confidence intervals (CI), we used a bivariable random-effects model. Summary receiver operating characteristic curves were drawn, plotting individual studies as well as the summary estimate. Results Seven studies involving 9251 patients were identified. The summary sensitivity of these tests in diagnosing acute MI at presentation to the emergency department was estimated to be 99.1% (95% CI 97.2–99.7%) and the summary specificity was 92.5% (95% CI 86.6–95.9%). With a false positive rate of 0.075 (95% CI 0.041–0.134), diagnostic odds ratio (DOR) of 1293.1 (95% CI −52.48 to 2638.5), and Likelihood Ratio (LR) +13.193 (95% CI 5.3–21, and LR −0.010 (95% CI −0.001 to 0.021). Cumulative mortality at 30 days in the rule-out group was 0,08% (4 studies; n=3715). Conclusion The European Society Cardiology 0-Hour/1-Hour Algorithm using High-Sensitivity Cardiac Troponin T has high diagnostic accuracy, it allows safe rule-out as well as accurate rule-in of acute myocardial infarction. With low cumulative 30-day mortality in patients assigned the rule-out zone.

Effect of cooled perches on performance, plumage condition, and foot health of caged White Leghorn hens exposed to cyclic heat

We examined the effects of water-chilled perches as cooling devices on hen performance during 2 summers using daily cyclic heat. White Leghorns, 17 wk of age, were assigned to 36 cages arranged into 6 banks. The banks were assigned to cooled perches, air perches, and no perches resulting in 2 replicate banks and 12 cages per treatment. Chilled water (10°C) was circulated through the cooled perches during heat episodes. Daily cyclic heat of 35°C was applied from 0600 to1800 h with a lowering of temperature to 28°C from 1800 to 0600 h during the 2014 and 2015 summers when hens were 21 to 35 and 73 to 80 wk of age, respectively. Mortality and egg production were recorded daily. Feed utilization, egg weight, and shell quality traits were measured at 4-wk intervals during the heat episodes and at 8-wk intervals during thermoneutrality. Body weight was determined at 17, 35, 72, and 80 wk of age and physical condition at 80 wk of age. At several ages during the heat episodes, cooled perch hens had increased egg production (P < 0.0001) and feed usage (P < 0.04) as compared to both air perch and control hens. The cooled perch hens had higher BW at 35 and 72 wk of age (Ptreatment*age = 0.03) and lower cumulative mortality (P = 0.02) than control hens but not air perch hens. Eggs from cooled perch hens had overall heavier weights (P < 0.0001) and higher breaking force (P < 0.0001) than eggs from the other two group hens. Greater eggshell percentage (Ptreatment*age = 0.03) and eggshell thickness (Ptreatment*age = 0.01) occurred at some ages during the 2 heat episodes as compared to the other 2 treatments. Nail length, feet hyperkeratosis, and overall feather score were similar among treatments. These results indicate that cooled perch ameliorates the negative effects of heat stress on egg traits and performance without influencing the physical condition of hens.

Substitution effect of the combined fouling macroalgae Ulva australis and Sargassum horneri for Undaria pinnatifida in formulated diets on growth and body composition of juvenile abalone (Haliotis discus, Reeve 1846) subjected to air exposure stressor

The effect of substituting the combined macroalgae Ulva australis and Sargassum horneri for Undaria pinnatifida in formulated diets on growth and body composition of abalone subjected to air exposure stressor was investigated. A total of 1260 juvenile abalone were distributed into 21 cages. Six formulated diets were prepared. The control (CUS0) diet contained 20% U. pinnatifida. Twenty, 40, 60, 80, and 100% of U. pinnatifida were substituted with an equal amount of the combined U. australis and S. horneri, referred to as the CUS20, CUS40, CUS60, CUS80, and CUS100 diets, respectively. Finally, dry U. pinnatifida was prepared to compare the growth performance of abalone. Abalone were fed with one of the experimental diets once a day for 16 weeks and then subjected to air stressor for 24 h. The cumulative mortality of abalone was monitored for the following 4 days after 24 h of air exposure. Abalone fed all formulated diets attained higher survival, weight gain, and specific growth rate (SGR) than U. pinnatifida. Abalone fed the CUS100 diet achieved greatest weight gain and SGR, followed by the CUS80 and CUS60 diets. The greatest shell growth and heaviest soft-body weight were obtained in abalone fed the CUS100 diet. Proximate composition of the soft body of abalone, except for moisture content, was not affected by the experimental diets. The cumulative mortality of abalone fed the U. pinnatifida was higher than that of abalone fed all formulated diets at 84 h until the end of the 4-day post observation. The lowest cumulative mortality was obtained in abalone fed the CUS80 diet at the end of the 4-day post observation. Therefore, U. pinnatifida could be completely replaced with the combined U. australis and S. horneri in abalone (H. discus) feed.

Long-term demography and stem productivity of Everglades mangrove forests (Florida, USA): Resistance to hurricane disturbance

Mangrove wetlands along coastal regions in neotropical northern latitudes are exposed to frequent hurricanes and therefore depend on resistant and resilient attributes to persist after these extreme events. However, few long-term studies have documented mangrove forest dynamics following hurricane disturbance to determine how species-specific phenotypic plasticity, species range shifts, and environmental stress interact to determine recovery trajectories. We present here a comprehensive analysis of Hurricane Wilma’s (hereafter, “Wilma”) impact (category 3, October 2005) on mangrove forest demography and aboveground net productivity in the Everglades, Florida (USA). We determined spatiotemporal patterns over a 15-year period (5 pre- and 10 post-Wilma) in three impacted sites on a productivity gradient along the Shark River Estuary. Hurricane resistance was evident in the low cumulative tree mortality and long-term recovery from defoliation (∼10 years). Aboveground standing carbon stocks were not significantly reduced, as mortality ranged only from 3 to 10%. A negative linear relationship between Leaf Net Primary Productivity (NPPL) and foliar residence time along the estuary shows that an increase in foliar production results in shorter residence time, which is defined by the interannual variation in NPPL rates and recovery periods across sites. We propose this relationship as a proxy of canopy recovery in latitudinal comparative studies across mangrove ecotypes and coastal settings. This work advances ecological disturbance theory and ecological modeling of mangrove forests; specifically, we provide quantitative relationships among structural properties and dynamic processes to validate agent-based demographic and biogeochemical models to forecast the impact of natural and human disturbances on mangrove wetlands under climate change.

Clinical outcomes of hemodialysis patients in a public-private partnership care framework in Italy: a retrospective cohort study

BackgroundInnovative care models such as public-private partnerships (PPPs) may help meet the challenge of providing cost-effective high-quality care for the steadily growing and complex chronic kidney disease population since they combine the expertise and efficiency of a specialized dialysis provider with the population care approach of a public entity. We report the five-years main clinical outcomes of a population of patients treated on hemodialysis within a PPP-care model in Italy.MethodsThis descriptive retrospective cohort study consisted of all consecutive hemodialysis patients treated in the NephroCare-operated Nephrology and Dialysis unit of the Seriate Hospital in 2012–2016, which exercises a PPP-care model. Clinical and treatment information was obtained from the European Clinical Database. Hospitalization outcomes and cumulative all-cause mortality incidences that accounted for competing risks were calculated.ResultsWe included 401 hemodialysis patients (197 prevalent and 204 incident patients) in our study. The mean cohort age and age-adjusted Charlson Comorbidity Index were 67.0 years and 6.7, respectively. Patients were treated with online high-volume hemodiafiltration or high-flux hemodialysis. Parameters of treatment efficiency were above the recommended targets throughout the study period. Patients in the PPP experienced benefits in terms of hospitalization (average number of hospital admissions/patient-year: 0.79 and 1.13 for prevalent and incident patients, respectively; average length of hospitalization: 8.9 days for both groups) and had low cumulative all-cause mortality rates (12 months: 10.6 and 7.8%, 5 years: 42.0 and 35.9%, for prevalent and incident patients, respectively).ConclusionsResults of our descriptive study suggest that hemodialysis patients treated within a PPP-care model framework received care complying with recommended treatment targets and may benefit in terms of hospitalization and mortality outcomes.

How long does it take until the effects of endoscopic screening on colorectal cancer mortality are fully disclosed?: a Markov model study.

A recent randomized trial has suggested persisting protection from colorectal cancer (CRC) incidence and mortality of a single flexible sigmoidoscopy for up to 17 years and possibly beyond. We performed a simulation study to explore the time course and magnitude of protection provided by screening colonoscopy against CRC death over 25 years. Using data from the German national screening colonoscopy registry, a multistate Markov model was set up based on the adenoma-carcinoma pathway to estimate cumulative CRC mortality when different proportions of the population have a single screening colonoscopy at age 55, or two screening colonoscopies at ages 55 and 65. Cumulative CRC mortality continuously increased with age and reached 2.6 and 1.7% at age 80 in the absence of screening for men and women, respectively. A single colonoscopy at age 55, even with limited uptake, would lead to much lower cumulative mortality (0.7% for men and 0.5% for women at age 80 under 100% uptake). Relative mortality reduction continued to increase over more than 10 years and reached the maximum around 12-13 years after screening. Absolute risk reduction steadily increased throughout follow-up and more than half of the total risk reduction would occur between 15-25 years. A repeat colonoscopy 10 years later further enhanced the effects and cumulative mortality remained at 0.1-0.2% under 100% uptake. Even a single (once-only) screening colonoscopy has the potential to prevent most of CRC mortalities. Protective effects are expected to be long-lasting and to become fully manifest after more than two decades from screening.

Effect of evidence-based cardiac drug therapy on mortality in patients with acute coronary syndrome: Findings from the Gulf COAST registry.

To evaluate the prevalence and impact of the prescribing of an evidence-based cardiac medication (EBM) combination on 1-month, 6-months, and 12-months all-cause mortality in patients with acute coronary syndrome (ACS). Data were analyzed from 3681 consecutive patients diagnosed with ACS admitted to 29 hospitals in 4 Middle Eastern countries from January 2012 to January 2013. The EBM combination consisted of concurrent prescribing of an antiplatelet therapy, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), β-blocker, and a statin, at hospital discharge. Analyses were performed using univariate and multivariate statistical techniques. The overall mean age of the cohort was 60±13years, 66% (n=2436) were males. In all, 69% (n=2542) of the patients received the quadruple EBM combination at discharge. Two-way interactions between EBM and age (P=0.824), EBM and GRACE risk score (P=0.873) and between EBM and discharge diagnosis (P=0.836) were all not statistically significant. Adjusting for demographic and clinical characteristics, the prescribing of EBM combination was associated with significantly lower cumulative all-cause mortality at 1-month (adjusted OR (aOR), 0.43; 95% confidence interval (CI): 0.24-0.79; P=0.007), which persisted at 6-months (aOR, 0.52; 95% CI: 0.38-0.72; P<0.001) and at 12-months of follow-up (aOR, 0.58; 95% CI: 0.44-0.75; P<0.001) posthospital discharge. Among patients discharged after an ACS event, concurrent EBM prescribing was associated with lower all-cause mortality that persists for up to 12-months posthospital discharge. The relative benefits of EBMs were also consistent across age, GRACE risk score, and discharge diagnosis.

Protective efficacy of Shilajit enriched diet on growth performance and immune resistance against Aeromonas hydrophila in Oreochromis mossambicus

We investigated the effects of dietary enriched with Shilajit in three dose levels: 2.0, 4.0, and 6.0 g kg−1 in the basal diet on growth rate, non-specific immune response, and disease resistance for 60 days in Oreochromis mossambicus against an opportunist pathogen, Aeromonas hydrophila. The results showed that the Shilajit enriched diets at 4.0 and 6.0 g kg−1 diets significantly (p < 0.05) enhance survival rate, weight gain (WG), protein efficiency ratio (PER), specific growth rate (SGR), and feed efficiency (FE), whereas it significantly decrease the feed conversion ratio (FCR) from weeks 1–4 when compared with control. The innate immune parameters, such as the phagocytic, complement, respiratory burst, and lysosome activities in infected fish fed with all Shilajit enriched diet were significantly (p < 0.05) enhances on weeks 2–4. A very low cumulative mortality, 8.0% and 12.0% were observed in the infected fish fed with 4.0 and 6.0 g kg−1 Shilajit enriched diets, whereas 18% mortality was found with 2 g kg−1 diet. In conclusion, 4.0 and 6.0 g kg−1 Shilajit enriched diets significantly increased the growth performance, innate immune response, and disease resistance in O. mossambicus against A. hydrophila infection.

Evaluation of the Impacts of Long-Term Enriched Artemia with Bacillus subtilis on Growth Performance, Reproduction, Intestinal Microflora, and Resistance to Aeromonas hydrophila of Ornamental Fish Poecilia latipinna.

The present study investigated the effect of enriched Artemia with Bacillus subtilis on growth performance, reproductive factors, proximate composition, intestinal microflora, and resistance to Aeromonas hydrophila of ornamental fish, Poecilia latipinna. Using a completely randomized design, the experiment included three groups. The first group was fed with commercial food without any probiotic. The second group was fed with unenriched Artemia, and the last group consumed long-time enriched Artemia with Bacillus subtilis. The bacteria B. subtilis with a density of 1 × 105CFUmL-1 was added daily to Artemia culture medium. The total microflora and Bacillus subtilis counts were significantly increased in enriched Artemia compared to the unenriched group (P < 0.05). In fish fed groups, growth factors did not show any significant difference (P > 0.05). The maximum relative fecundity (28.65 ± 2.52egg numberg-1), fry production (62.93 ± 4.6 individual per female), and fry survival (70.97 ± 1.56%) obtained in the third group were found to be significantly more than those in the first and the second groups. Moreover, intestinal bacterial count for Bacillus revealed that the higher concentration of bacteria was significantly related to the third group (6.24 ± 0.11logCFUg-1) (P < 0.05). Maximum protein and fat contents were observed in fish fed with Bacillus-enriched Artemia; however, no significant difference was found between control and unenriched Artemia groups (P > 0.05). The highest amount of ash was observed in fish fed with commercial food without any probiotic (P < 0.05). At the end of the feeding period, each of the three groups along with positive group (oxytetracycline 100mgkg-1 of commercial food) was exposed to A. hydrophila (BCCM5/LMG3770) bacteria intraperitoneally. Based on the results, the lowest cumulative mortality was significantly found in group three (68.75 ± 3.6%) and positive group (62.5 ± 7.0%) compared to control and unenriched Artemia groups (P < 0.05). Hence, B. subtilis with a concentration of 1 × 105CFUmL-1 during the period of Artemia culturing can improve the reproductive parameters, intestinal microflora, and resistance to pathogenic bacteria of Poecilia latipinna.

Efficacy of dietary fermented vegetable product on immune response, up-regulation of immune-related genes and protection of kuruma shrimp (Marsupenaeus japonicus) against Vibrio parahaemolyticus

The present study was carried out to investigate the effects of dietary fermented vegetable product (FVP) on the innate immune response, immune-related genes expression and resistance of kuruma shrimp Marsupenaeus japonicus against Vibrio parahaemolyticus. Four hundred and eighty healthy kuruma shrimp (15.3 ± 1.15 g) were distributed into four treatment groups and fed with diets containing 0 (control), 0.55, 5.5, and 55 g FVP (kg diet)−1 for 11 days. The results revealed that administration of FVP significantly elevated the innate immune parameters of kuruma shrimp including total hemocyte count (THC), phagocytosis, phenoloxidase activity, reactive oxygen species (ROS) production and bactericidal activity (P < 0.05). Furthermore, dietary supplementation of 5.5, and 55 g FVP (kg diet)−1 remarkably up-regulated the expression of antimicrobial peptides (AMPs) and toll-like receptors (TLR) in various tissues, particularly in the intestine. Shrimp groups supplemented with FVP diets showed significantly lower cumulative mortality percentage after being challenged with Vibrio parahaemolyticus (P < 0.05). The results suggest that FVP can be recommended as a feed supplement to elevate innate immune response, upregulate immune related genes expression and increase disease resistance in kuruma shrimp.

How long does it take until the effects of endoscopic screening on colorectal cancer mortality are fully disclosed? A Markov Model study

Introduction Colorectal cancer (CRC) is one of the leading causes of cancer morbidity and mortality worldwide. A recent randomized trial has suggested persisting protection from CRC incidence and mortality of a single flexible sigmoidoscopy for up to 17 years and possibly beyond. We performed a simulation study to explore the time course and magnitude of protection provided by screening colonoscopy against CRC death over 25 years. Methods Using data from the German national screening colonoscopy registry, a multi-state Markov model was set up based on the adenoma-carcinoma pathway to estimate the cumulative CRC mortality when different proportions of the population have a single screening colonoscopy at age 55, or two screening colonoscopies at ages 55 and 65. Ratio and difference of the expected cumulative CRC mortalities among screened and unscreened populations were calculated over follow-up to reflect the impact of screening colonoscopy. Results Cumulative CRC mortality continuously increased with age, and in the absence of screening reached 2.6% and 1.7% at age 80 for men and women, respectively. A single colonoscopy at age 55, even with limited uptake, was predicted to lead to much lower cumulative mortality (0.7% and 0.5% for men and women, respectively at age 80 when uptake was 100%). Relative mortality reduction continued to increase over more than 10 years and reached the maximum around 12–13 years after screening. Although relative risk reduction became attenuated for even longer periods of follow-up, absolute risk reduction steadily increased throughout follow-up and more than 70% of the total risk reduction was observed between 13–25 years. A repeat colonoscopy 10 year later further enhanced the effects and the cumulative mortality remained at 0.1% to 0.2% throughout follow-up when uptake was 100%. Conclusions Even a single (once only) screening colonoscopy has the potential to prevent most of CRC mortalities. Protective effects are expected to be long lasting and to become fully manifest after more than two decades from screening.

Organic acids blend as dietary antibiotic replacer in marine fish olive flounder,Paralichthys olivaceus

The present study was conducted to evaluate the efficacy of organic acid blends as dietary antibiotic replacer in marine fish olive flounder, Paralichthys olivaceus. Fish averaging 3.5 ± 0.05 g (mean ± SD) were fed one of the four experimental diets: (1) without antibiotic or organic acid (Control/CON); (2) with antibiotic—50 mg oxytetracycline per kg body weight per day (OTC); (3) with organic acid blend A—4 g/kg diet (OAA); and (4) with organic acid blend B—4 g/kg diet (OAB), for 10 weeks. At the end of the experiment, total intestinal bacterial counts in fish-fed OAA, OAB and OTC were significantly lower than that of fish-fed CON diet (p < 0.05). Further, the group of fish-fed organic acid blends (OAA, OAB) or antibiotic (OTC)-supplemented diets exhibited lower intestinal Vibrio sp. counts compared with fish-fed CON diet. Disease challenge test with bacteria Edwardsiella tarda showed significantly lower cumulative mortality rates for the group of fish-fed OAA, OAB or OTC than that of fish-fed CON diet (p < 0.05). There were no negative effects on the growth, serological characteristics and proximate composition among the group of fish-fed different experimental diets. Therefore, the present experiment demonstrates that blends of organic acid could be a promising alternative to dietary antibiotics for the preventive and/or curative health management in marine fish olive flounder aquaculture.

Effects of dietary inulin and mannan oligosaccharide on immune related genes expression and disease resistance of Pacific white shrimp, Litopenaeus vannamei

The effects of inulin and mannan oligosaccharide (MOS) at different doses (2.5, 4 and 10 mg/g) in singular or combined diet on growth rate, immune related genes expression, and resistance to white spot syndrome virus (WSSV) and Vibrio alginolyticus in Pacific white shrimp (Litopenaeus vannamei) were investigated. At the end of 28-day singular feeding experiment, the highest values of specific growth rate (SGR) and the expression of toll-like receptor1, 2 and 3 (TLR1, 2, 3), signal transducer and activator of transcription (STAT), crustin, anti-lipopolysaccharide factor (ALF) as well as prophenoloxidase (proPO) were observed in shrimp individually fed with 5 mg/g dietary inulin or MOS, respectively. Compared with individual treatments, diet containing combined prebiotics (5 mg/g inulin and MOS) significantly improved the expression of TLRs, STAT, proPO, crustin and ALF in L. vannamei after four-week feeding. Additionally, Pacific white shrimp fed with combined dietary prebiotics showed significantly higher expression of immune related genes and lower cumulative mortality in WSSV and Vibrio alginolyticus challenges, compared to the singular feeding groups and control. These results in the present study demonstrated that the combined supplementation of inulin (5 mg/g) and MOS (5 mg/g) remarkably enhanced innate immune response and pathogen resistance of shrimp, and should be considered as a promising immunostimulatory additive for the culture of Pacific white shrimp.

Identification and functional characterization of unfolded protein response transcription factor ATF6 gene in kuruma shrimp Marsupenaeus japonicus

Activating transcription factor 6 (ATF6) pathway is the key branch of unfolded protein response (UPR). In this study, a homolog of ATFα from Marsupenaeus japonicus (MjATF6) was identified using genome sequencing and characterized, so as to investigate the role of ATF6 pathway in anti-viral immunity of M. japonicus. The cDNA of MjATF6 obtained was 1008 bp in length, with an open reading frame (ORF) of 849bp, which had encoded a putative of 283 amino acid proteins. Results of qRT-PCR showed that MjATF6 was distributed in all the six tested tissues, with the higher expression level being seen in hemocytes and hepatopancreas. Furthermore, MjATF6 expression would be up-regulated from 1 day to 7 day under white spot syndrome virus (WSSV) challenge. In comparison, RNA interference-induced MjATF6 knockdown had resulted in a lower 7-day cumulative mortality of M. japonicus in the presence of WSSV infection. Additionally, our results also revealed that less VP28 mRNA was extracted from hemocytes or hepatopancreas of MjATF6 knockdown shrimp than that from the control. Taken together, these results have confirmed that ATF6 pathway is vital for WSSV replication, and that UPR in M. japonicus may facilitate WSSV infection.

Bentonite clay supplemented diet on immunity in stinging catfish, Heteropneustes fossilis against Aeromonas hydrophila

The effect of Sodium Bentonite (SB) enriched diet on growth performance, innate immune response, and disease resistance in stinging catfish, Heteropneustes fossilis against Aeromonas hydrophila is reported. The infected fish fed with 5% SB had the maximum weight gain diet (PWG %) and specific growth rate (SGR %) were 26% and 29% when compared to 14% and 17% with 10% diet. Similarly the phagocytic activity increased significantly when infected fish were fed with 5% or 10% SB diets during the experimental period; the complement, respiratory burst and lysozyme activities were also significantly enhanced on weeks 2 and 4. The lower cumulative mortality (10% and 15%) was observed when the infected fish were fed with 5% and 10% SB diets for 30 days. The results suggest that the infected H. fossilis after administration of 5% and 10% SB enriched diets for 30 days had significantly improved growth performance, innate immunity, and disease resistance against A. hydrophilla. Hence, sodium bentonite can be used as a feed additive to stimulate immunity and for disease resistance in the effective production of economically valuable freshwater catfish, H. fossilis.

Antipsychotics and mortality in a nationwide cohort of 29,823 patients with schizophrenia

IntroductionIt has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration. MethodsWe linked prospectively gathered nationwide register-based data during 2006–2013 to study all-cause mortality among all patients aged 16–64years with schizophrenia in Sweden (N=29,823 in total; N=4603 in the incident cohort). Multivariate Cox regression models were adjusted for clinical and sociodemographic covariates. Sensitivity analyses with the incident cohort were conducted to control for survival bias. ResultsDuring the mean follow-up of 5.7years, 2515 patients (8.4%) died. During the maximum follow-up (7.5years), the lowest cumulative mortality was observed for second generation (SG) long-acting injection (LAI) use (7.5%). Adjusted hazard ratios (aHRs) compared to SG LAI use were 1.37 (95%CI 1.01–1.86) for first generation (FG) LAIs, 1.52 (1.13–2.05) for SG orals, 1.83 (1.33–2.50) for FG orals, and 3.39 (2.53–4.56) for nonuse of antipsychotics. Concerning specific agents, the lowest mortality was observed for once-monthly paliperidone LAI (0.11, 0.03–0.43), oral aripiprazole (0.22, 0.15–0.34), and risperidone LAI (0.31, 0.23–0.43). In pairwise comparison, LAIs were associated with 33% lower mortality than equivalent orals (0.67, 0.56–0.80). The results with incident cohort were consistent with the primary analyses. ConclusionsAmong patients with schizophrenia, LAI use is associated with an approximately 30% lower risk of death compared with oral agents. SG LAIs and oral aripiprazole are associated with the lowest mortality.

Display of GCRV vp7 protein on the surface of Escherichia coli and its immunoprotective effects in grass carp (Ctenopharyngodon idella)

Infection with Grass carp reovirus (GCRV) is becoming unprecedentedly widespread in grass carp (Ctenopharyngodon idella) aquaculture industry, yet the management of GCRV infection still remains a challenge. Therefore, it is of importance to develop effective means against GCRV. As a delivery system of viral antigens, surface displaying of heterologous proteins on bacteria using anchoring motifs has successfully been implemented in human and veterinary vaccines research. In this study, a novel vaccine (BL21/InpN/vp7) was developed based on surface displaying a major capsid protein (vp7) of GCRV using the anchoring motif of N-terminal unique domain of ice-nucleation protein (InpN) on Escherichia coli BL21 (DE3) vaccine. Then the grass carp were immunized by surface displaying BL21/InpN/vp7 vaccine against GCRV using both intraperitoneal injection and bath immunization and their immune responses were tested. The results revealed that some non-specific immune parameters (acid phosphatase (ACP), alkaline phosphatase (AKP) and total antioxidant capacity (T-AOC)) were strongly increased in grass carp post injection inoculation (vp7 dose ranged from 10 to 20 μg). The specific antibody levels against GCRV and the transcriptional of immune-related genes (TNF-α, IL-1β, MHCI and IgM) were also significantly enhanced in grass carp by injection inoculation (vp7 dose ranged from 5 to 20 μg). On the other hand, only the highest dose of bath vaccination significantly induced the production of specific antibody and up-regulated transcriptions of several immune-related genes (IgM and MHCI) in grass carp. The lower cumulative mortality of grass carp in vaccinated groups after GCRV challenge clearly demonstrated that surface displayed vp7 vaccine could protect fish against GCRV infection. The relative percentage survival (RPS) value in injection vaccinated group (88.89%) was much higher compared to bath group (18.89%), which was in consistent with the production of specific serum antibodies, non-specific immune response and immune related genes expression. To sum up, our results indicated the surface display of heterologous antigenic proteins on E. coli BL21 (DE3) using the anchoring motif of ice-nucleation protein may provide a promising approach to the vaccine development of aquatic animals and suggested its potential to be used as vaccine to fight against GCRV infection.

Effects of dietary herbal formulae combined by Astragalus polysaccharides, chlorogenic acid and allicin in different combinations and proportions on growth performance, non-specific immunity, antioxidant status, vibriosis resistance and damage indexes of

In this study, a feeding trial followed by a challenge test was performed to evaluate effects of six herbal formulae which were different combinations of Astragalus polysaccharides (APS), chlorogenic acid (CGA) and allicin on growth performance, non-specific immune response, antioxidant capacity, disease resistance and biomolecule damage of white shrimp Litopenaeus vannamei. Shrimp were fed seven diets, control diet (basal diet with no herbal formulae) and six herbal formula diets (G1–G6, basal diet supplemented with 0.1% APS + 0.05% allicin, 0.1% APS + 0.1% allicin, 0.1% CGA + 0.05% allicin, 0.1% CGA + 0. 1% allicin, 0.1% APS + 0.1% CGA and 0.1% APS + 0.1% CGA + 0.05% allicin respectively), for 21 days. After that, shrimp were challenged with Vibrio harveyi and then the cumulative mortality of shrimp was recorded for 7 days post challenge. The results showed that there were no significant differences in growth performance among all groups, while the non-specific immune responses and antioxidant indexes were significantly improved (p < .05) in shrimp fed herbal formula diets when compared to the control. Meanwhile, the lowest cumulative mortality was observed in shrimp fed herbal formula diets with 0.1% APS, 0.1% CGA and 0.05% allicin supplementation after V. harveyi challenge. Additionally, herbal formulae could not cause biomolecule damage to the hepatopancreas of shrimp. In conclusion, these results indicated that synergistic effect of APS, CGA and allicin helped to boost immunity, antioxidant capacity and disease resistance of shrimp without biomolecule damage.

Dietary supplements of guanosine improve the growth, non-specific immunity of sea cucumber, Apostichopus japonicus Selenka, and its resistance against Vibrio splendidus

The growth response, non-specific immune activities and disease resistance were measured in sea cucumber, Apostichopus japonicus Selenka (initial average weight 6.80 ± 0.10 g), when fed diets supplemented with graded levels of guanosine from the guanosine-5’-monophosphate disodium (GMP) at 0 (control), 0.3, 0.6 and 1.2 g/kg for 8 weeks. The results showed that GMP supplemented at 0.6 and 1.2 g/kg significantly enhanced the growth of sea cucumber. Sea cucumber fed a diet with 0.6 g/kg of GMP had significantly higher intracellular superoxide anion production, nitric oxide synthase activity, lysozyme activity and the total superoxide dismutase (T-SOD) activity than those in control group (p < .05). Increased lysozyme activity and T-SOD activity were also found in sea cucumber fed GMP at 1.2 g/kg. Moreover, there was significantly lower cumulative mortality after the disease challenge in sea cucumber fed the diets with 0.6 and 1.2 g/kg GMP than that in control and 0.3 g/kg GMP groups (p < .05), and no significant difference was observed between 0.6 and 1.2 g/kg GMP groups. These results suggested that feeding GMP at a dose of 0.6 g/kg could enhance growth, non-specific immunity of sea cucumber as well as its resistance against Vibrio splendidus.

Effects of Seeding Date and Seed Size on Crassostrea gigas (Thunberg, 1793) Culture in a Subtropical Climate

Studies that carefully monitor and attempt to explain causes of massive oyster mortalities are urgently needed. The objective of the present study was to assess the effects of seeding dates on the mortality and reproductive cycle of the oyster Crassostrea gigas. Seeds of two sizes (3.5–4 mm and 1.5–2 mm) were planted during three seasons: early summer, early autumn, and late autumn. The experimental period was 6 mo. Mortalities of C. gigas at culture phase nursery lantern-nets, intermediate lantern-nets, and final lantern-nets were recorded. The reproductive cycle of the oysters grown from 3.5 to 4 mm seeds planted in each season was closely monitored (bimonthly) during the experimental period. In addition, seawater parameters [temperature (daily) and salinity (weekly)] were monitored throughout the experimental period. Results of this study demonstrated that the planting season affected C. gigas mortality after the nursery phase. Lower cumulative mortality was observed for 3.5–4 mm seeds than for 1.5–2 mm seeds when the seeds were planted in early (MarL: 0.29 ± 0.02) and late (JunL: 0.22 ± 0.10) autumn, after 6 mo of culture. The reproductive cycle of seeds planted in the summer exhibited an early maturation process, and those planted in the autumn exhibited late reproductive development.