Mortality Syndrome Research Articles

Human leukocyte antigen mismatch on lung transplantation outcomes.

Human leucocyte antigen (HLA) mismatch is a known risk factor for renal transplantation; however, there are conflicting and limited data on its ramifications within lung transplantation (LTx). Therefore, our study evaluated the effects of total HLA, HLA-A, -B and -DR mismatches on LTx outcomes. We retrospectively examined the United Network for Organ Sharing database for adult patients who had undergone LTx for the first time between January 2005 and July 2021. Total HLA mismatch (0-3, 4, 5 and 6) and HLA locus mismatch (0-1 and 2) were analysed, with the end points of interest being mortality and bronchiolitis obliterans syndrome (BOS) development. Kaplan-Meier curve analysis found a significant difference in both overall survival (n = 27 651; 11 830 events) and BOS development (n = 25 444; 8901 events) for the total number of HLA (P < 0.001, P < 0.001), HLA-A (P < 0.001, P = 0.006) and HLA-DR (P < 0.001, P < 0.001) mismatches. With reference to 0-3 total HLA mismatches, multivariable Cox regression model found that 6 mismatches had an increased risk of mortality (P = 0.002) while 4 (P = 0.010), 5 (P = 0.007) and 6 (P < 0.001) mismatches had an increased risk of BOS. HLA-B mismatch was not associated with an increased mortality (P = 0.975) or BOS risk (P = 0.512). This study demonstrates a significant relationship between increased HLA mismatches and BOS development, with decreased overall survival only apparent with 6 mismatches. HLA-A and -DR mismatches were associated with an increased risk of mortality and BOS development compared to groups with at least 1 locus match.

Seaweeds influence oyster microbiota and disease susceptibility.

A growing awareness of role that microbiota can play in mediating the effects of pathogens on hosts has given rise to the concept of the pathobiome. Recently, we demonstrated that the Pacific oyster mortality syndrome affecting Crassostrea gigas oysters is caused by infection with the Ostreid herpesvirus type 1 (OsHV-1) followed by infection with multiple bacterial taxa. Here we extend the concept of this pathobiome beyond the host species and its bacterial microbiota by investigating how seaweed living in association with oysters influences their response to the disease. We hypothesized that by their mere presence in the environment, different species of seaweeds can positively or negatively influence the risk of disease in oysters by shaping their bacterial microbiota and their immune response. Although seaweed and oysters do not have direct ecological interactions, they are connected by seawater and likely share microbes. To test our hypothesis, oysters were acclimated with green, brown or red algae for 2weeks and then challenged with OsHV-1. We monitored host survival and pathogen proliferation and performed bacterial microbiota and transcriptome analyses. We found that seaweeds can alter the bacterial microbiota of the host and its response to the disease. More particularly, green algae belonging to the genus Ulva spp. induced bacterial microbiota dysbiosis in oyster and modification of its transcriptional immune response leading to increased susceptibility to the disease. This work provides a better understanding of a marine disease and highlights the importance of considering both macrobiotic and microbiotic interactions for conservation, management and exploitation of marine ecosystems and resources.

Procedure-Specific Relationships Between Postoperative Troponin T and a Composite of Mortality and Low Cardiac Output Syndrome: A Retrospective Cohort Analysis.

Myocardial injury after coronary artery bypass grafting (CABG) is defined as troponin concentrations >10 times 99th percentile upper reference limit (URL) according to the Fourth Universal Definition. However, troponin concentrations after non-CABG cardiac surgery which indicate greater-than-expected myocardial injury and increased risk for complications remain unclear. Our goal was to assess procedure-specific relationships between troponin T and a composite outcome of low cardiac output syndrome and in-hospital mortality in cardiac surgical patients. Patients having cardiac surgery between January 2010 and December 2017 were categorized into 4 groups by procedure: (1) CABG; (2) mitral valve repair; (3) aortic valve repair/replacement (AVR); (4) mitral valve replacement (MVR) or CABG + valve surgeries. Exclusion criteria were elevated preoperative troponin T, preoperative kidney failure, circulatory arrest, or preoperative/planned mechanical circulatory support. Logistic regression was used to assess the association between troponin T and composite outcome, both overall and by procedure, including assessment of the interaction between procedure and troponin T on outcome. Among 10,253 patients, 37 (0.4%) died and 393 (3.8%) developed the primary outcome. Troponin T concentrations differed by procedure (P < .001). Compared to CABG, AVR had 0.53 (99.2% confidence interval [CI], 0.50-0.56; unadjusted P < .001) times lower troponin T concentrations, while MVR/CABG + valve were 1.54 (99.2% CI, 1.45-1.62, unadjusted P < .001) times higher. There were linear relationships between log2 troponin T concentration and log odds mortality/low cardiac output syndrome. The (unadjusted) relationships were parallel for various types of surgery (interaction P = .59), but at different levels of the outcome. The relative increase in odds for mortality/low cardiac output syndrome per a similar increase in troponin T concentrations did not differ among cardiac surgical procedures, but the absolute troponin T concentrations did. Troponin concentrations should thus be interpreted in context of surgical procedure.

CRISPR/Cas12a Based Rapid Molecular Detection of Acute Hepatopancreatic Necrosis Disease in Shrimp.

Acute hepatopancreatic necrosis disease (AHPND), formerly called early mortality syndrome (EMS), causes high mortality in cultured penaeid shrimp, particularly Penaeus vannamei and Penaeus monodon. AHPND is mainly caused by Vibrio species carrying the pVA1 plasmid encoding the virulence genes Photorhabdus insect-related (pir) pirVPA and pirVPB. We developed a new molecular assay that combines recombinase polymerase amplification (RPA) and CRISPR/Cas12a technology (RPA-CRISPR/Cas12a) to detect pirVPA and pirVPB, with a fluorescent signal result. The fluorescence RPA-CRISPR/Cas12a assay had a detection limit of 20 copies/μL for pirVPA and pirVPB. To improve usability and visualize RPA-CRISPR/Cas12a assay results, a lateral flow strip readout was added. With the lateral flow strip, the RPA-CRISPR/Cas12a assay had a lower limit of detection of 200 copies/μL (0.3 fmol/L). The lateral flow assay can be completed in 2 h and showed no cross-reactivity with pathogens causing other shrimp diseases. In a field test of 60 shrimp samples, the RPA-CRISPR/Cas12a lateral flow assay showed 92.5% positive predictive agreement and 100% negative predictive agreement. As the new RPA-CRISPR/Cas12a assay is rapid, specific, and does not require complicated experimental equipment, it may have important field applications for detecting AHPND in farmed shrimp.

Corticosteroids in the prevention and treatment of infants with bronchopulmonary dysplasia: Part I. systemic corticosteroids.

Bronchopulmonary dysplasia (BPD) is the most significant respiratory complication of prematurity, and its consequences last from birth into adulthood. Unfortunately, the dramatic improvements in the management of premature infants have not led to a decreased incidence of BPD, or to breakthroughs in treatments offered for this long-lasting chronic respiratory disorder. Over recent decades the pathological picture of BPD has changed from inflammation, interstitial fibrosis and emphysema attributed to volu-, barotrauma and oxygen toxicity to larger, simplified alveoli and dysmorphic vessels related to arrested alveolarization and vasculogenesis with inflammation maintaining a central role. Corticosteroids (CSs) play a key role in the development of respiratory epithelial cells and lung maturation. These potent anti-inflammatory agents have long been used for the prevention and treatment of BPD; however, the risk/benefit ratio of their use remains unresolved. CSs administered antenatally have contributed to reduce mortality and respiratory distress syndrome, no such effect on BPD reduction has been observed. Postnatal systemic CSs reduced the rate and severity of BPD, yet their long-term neurodevelopmental and respiratory consequences markedly limit routine administration. This is the first in a two-part State-of-the-Art series that reviews the latest relevant clinical trials investigating the short-term and long-term effects of CSs in the prevention and treatment of BPD.

Yolk sac fry mortality syndrome

This datasheet on yolk sac fry mortality syndrome covers Identity, Distribution, Hosts/Species Affected.

Nervous mortality syndrome

This datasheet on nervous mortality syndrome covers Identity, Hosts/Species Affected.

Antenatal Corticosteroid Use and Perinatal Mortality According to Gestational Age among Preterm Singletons Born at 27 to 34 Weeks of Gestation in Hospitals in Tanzania

Background: Antenatal corticosteroid (ACS) treatment has been proven to decrease rates of adverse perinatal outcomes when administered to pregnant women at risk for preterm delivery. Given the uncertainty about the benefit of ACS according to gestational age, we aimed to examine whether there was any benefit of ACS on perinatal mortality and respiratory distress syndrome (RDS) according to different gestational ages at birth. Methods: Secondary analysis of data from an observational prospective chart review study was conducted in four hospitals located in the Mwanza region, Tanzania. The study population consisted of singleton infants delivered between 27 and 34 weeks of gestation between July 2019 and February 2020. Sociodemographic and medical data were recorded from participants’ medical records. Results: Over an eight-month period, 838 preterm singletons were delivered between 27 and 34 weeks of gestation. Three hundred and twelve (37.2%) pregnant women received at least one dose of ACS. Among infants exposed to ACS, perinatal mortality rates were significantly lower than those without exposure at the 27th week (27.8% vs 94.4%, P Conclusion: Our findings add to the literature about the benefits of ACS for preterm infants of various gestational ages in low-resource settings. Compared to unexposed infants, those exposed to ACS and born at 27th and 34th weeks of gestation experienced lower rates of perinatal mortality. Future research, especially among infants born before the 27th week of pregnancy, is a priority.

Physiological and antioxidant response of Litopenaeus vannamei against Vibrio parahaemolyticus infection after feeding supplemented diets containing Dunaliella sp. flour and β-glucans

The presence of pathogen agents in shrimp farming is the main obstacle for successful aquaculture. Vibrio species are naturally part of water because they play an important role as opportunistic bacteria. Vibrio parahaemolyticus was identified as the causative agent of the Early Mortality Syndrome in 2009, causing the loss of shrimp farming worldwide. Dunaliella sp. flour has been tested against Vibrio infection proving to be an effective prophylactic method that decreases mortality and improves physiological and immune response in Litopenaeus vannamei. Juvenile shrimp were exposed to 2% Dunaliella sp. flour and commercial 1.1% β -glucan diet provided every other day for 15 days and a posterior infection with V. parahaemolyticus (1 × 106 CFU/mL). To evaluate shrimp stress status, some parameters as glucose, lactate, cholesterol, triglycerides, relative superoxide dismutase (SOD) gene expression and circulating hemocytes were analyzed in hemolymph at zero and seven days before infection and at 0, 24, and 48 h post-infection. L. vannamei fed with Dunaliella sp. showed 93% and β -glucan 87% survival, compared with 79% in the infected control group. Additionally, Dunaliella sp. improved hemocyte and lipid concentrations compared to β -glucan while both immunostimulants showed an increase in SOD response against bacteria. The addition of 2% Dunaliella sp. every other day in L. vannamei diet enhanced stress response against V. parahaemolyticus infection.

Summer Mortality Syndrome Affecting Cultured European Seabass at Kafrelsheikh Province, Egypt

The present work aimed to investigate the causes of summer mortality syndrome affecting cultured European seabass (Dicentrarchus labrax) by examining physiochemical farm water characteristics, isolation, and identification of recovered bacterial pathogens from diseased fish studying the effect of water temperature on stress biomarkers and disease severity. Studied water parameters were normal except ammonia and dissolved oxygen was higher and lower than the standard value. Sixty-two bacterial isolates were recovered from moribund fish and identified as 31 Vibrio fluvialis, 23 Pseudomonas aeruginosa and 8 Staphylococcus aureus isolates. The calculated LD50 of V. fluvialis, P. aeruginosa and S. aureus for D. labrax fingerlings were 4.67 × 107, 2.37 × 106 and 1.38 × 107, respectively. There was a direct correlation between water temperature and mortality rate of fish challenged with V. fluvialis as the mortality rate was 44.44, 50, 66.66, and 83.33% for fish maintained at 27, 30, 33, and 36°C. Plasma cortisol, superoxide dismutase, catalase and malondialdehyde significantly increased when the water temperature exceeded 30°C. The experimentally infected fish showed similar clinical signs and postmortem lesions of naturally diseased fish with no boundary between different pathogens. Antibiogram test indicated that florfenicol was the most effective antibiotic against all the recovered bacterial isolates while all isolates resisted sulfamethoxazole-trimethoprim. Massive degenerative changes observed in the hepatopancreas, posterior kidney and gill tissues of experimentally infected fish.

Pathogenicity of Field Marek's Disease Virus Serotype-1 and Vaccine Efficacy Test in Chicken in Eastern Shewa Ethiopia.

BackgroundMarek’s disease is a chicken lymphoproliferative viral illness. As new viruses emerge, vaccination immunity is being broken and hence pathogenecity assessment and vaccine evaluation related to the pathogen is critical for developing vaccine immunity in the field.MethodsAn experimental investigation was conducted to determine the pathogenicity of field isolates against Marek’s disease in antibody-free chicks and to assess the protective efficacy of the Marek’s disease vaccination. The viral isolates in question were discovered during an outbreak investigation for a previous study. The pathogenicity and effectiveness trial used a complete random design.ResultsIn the pathogenicity trial, chickens inoculated with Bishoftu and Mojo field isolate had lower body weight 77.7±3.757 and 78.15±1.95 g at 10 dpi, respectively, when compared to un-inoculated controls, 89.85±3.838 g at 10 dpi. Incidence of early mortality syndrome (35% and 25%), lymphoma (53.8% and 40%), and overall mortality (50% and 45%) between Bishoftu and Mojo isolates, respectively, was discovered. Vaccinations with Herpes virus of turkey challenged chickens were provided complete protection against Marek’s disease.ConclusionBased on the findings in pathogenecity assessment experimental trials, Bishoftu and Mojo isolates were designated as virulent Marek’s disease viruses. Regular vaccinations with Herpes virus of turkey vaccine and supported by biosecurity measures in poultry farms are important to prevent the disease.

P007 COMPLETE FASCIAL CLOSURE IN LARGE HERNIAS AFTER LIVER TRANSPLANT USING BOTOX

Abstract Aim Hernias after liver transplant (HaLT), being transverse, preclude mechanical muscle release for fascial advancement. However, even with large HaLT, complete fascial closure is possible following Botox muscle release. Material and Methods A retrospective review included 31 consecutive large primary HaLT repairs between 2017 and 2021. Patients were immunosuppressed, with BMI=33+/-5. Fascial defects were 13+/-5cm (range 7.5-28cm) transversely and 11+/-3cm (range 5-17cm) vertically. Botox was administered 29+/-3days preoperatively. After extensive myofascial mobilization, mesh was inserted intraperitoneally and covered with omental flap alone or with posterior components, followed by fascial closure, progressive tension sutures and drains. Results Operative time was 235+/-69min (range 111-418min), with no enterotomy or blood transfusion. Complete fascial closure was achieved in all. No mortality or abdominal compartment syndrome occurred. Two patients had long ICU stays (135 and 75days, aspiration and caecal necrosis), but were discharged with intact repairs, off dialysis and sound mentally. Other patients had a postoperative hospital stay of 5.8+/-2.2days (range 3-13days). Mean follow-up was 48+/-28.3 months (range 1-84 months). One patient with a mainly left sided repair developed a hernia on the right, beyond the mesh edge. No other recurrence or mesh infection occurred. One wound required open abscess drainage. Two seromas were aspirated. Conclusions Abdominal wall reconstruction with complete fascial closure is possible following abdominal muscle release with Botox, even in large HaLT. However, these immunosuppressed patients with multiple comorbidities may develop significant medical complications. One recurrence along the mesh edge suggests the need for complete incision mesh coverage, not just hernia coverage.

30 Risk Factors for Stage III Necrotizing Enterocolitis in Very Low Birth Weight Neonates – A retrospective case-control study

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Stage III necrotizing enterocolitis (NEC-III) is a serious intestinal inflammatory disease in neonates, with high case fatality rate and significant morbidities including need for surgical intervention. Research focusing on risk factors for the development of NEC-III are lacking. Objectives To determine the risk factors for NEC-III and its outcomes among neonates born under 33 weeks gestational age (GA). Design/Methods This was a single-centre retrospective case-control study of preterm neonates born under 33 weeks GA who were admitted to Stollery Children’s Hospital neonatal intensive care unit (NICU), Edmonton, Alberta, between January 2015 and December 2018. NEC-III cases were compared with Stage II NEC (NEC-II) and matched with 2-4 non-NEC controls by GA ± 1 week and date of birth within 3 months. Univariate and multivariate analysis compared the risk factors for NEC-III, adjusting for GA, birth weight, and sex. Results Out of 1360 babies born &amp;lt;33weeks, 71(5.2%) had NEC-II and above during the study period (Figure 1). NEC-III constituted 46% of the total number of NEC cases. Average age of onset of NEC-III was 13.7 days versus 23.9 days for NEC-II (p=0.01). Neonates with NEC-III were of lower GA (25.4weeks) compared to NEC-II(27.3 weeks) and non-NEC (26 weeks), (p=0.0008), had higher severity of illness with Score for Neonatal Acute Physiology Perinatal Extension-II (SNAPPE-II score) of 47.5 versus 28.4 for NEC-II and 37 for non-NEC ( p=0.003), spent more days on vasoactive agents (3.7 days versus 1.1 days and 1.8 days for NEC-II and non-NEC respectively; p=0.05). There was a trend towards lower Apgar score &amp;lt;7 at 10 mintues in NEC-III versus non-NEC (AOR 2.59, 95% CI [0.88-7.67]; p=0.085). Death or short bowel syndrome was higher for NEC III (AOR 12.4, 95% CI [1.16-132.28]; p=0.037). Conclusion In this case-control study of neonates born under 33 weeks GA, after adjustment for known confounders, duration of UAC and prolonged rupture of membranes were significantly associated with increased incidence of NEC-III. Composite outcome of mortality or short bowel syndrome were higher in NEC-III.

A Direct Mass Spectrometry Method for the Rapid Analysis of Ubiquitous Tire-Derived Toxin N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine Quinone (6-PPDQ).

The oxidative transformation product of a common tire preservative, identified as N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ), has recently been found to contribute to "urban runoff mortality syndrome" in Coho salmon at nanogram per liter levels. Given the number of fish-bearing streams with multiple stormwater inputs, large-scale campaigns to identify 6-PPDQ sources and evaluate mitigation strategies will require sensitive, high-throughput analytical methods. We report the development and optimization of a direct sampling tandem mass spectrometry method for semiquantitative 6-PPDQ determinations using a thin polydimethylsiloxane membrane immersion probe. The method requires no sample cleanup steps or chromatographic separations, even in complex, heterogeneous samples. Quantitation is achieved by the method of standard additions, with a detection limit of 8 ng/L and a duty cycle of 15 min/sample. High-throughput screening provides semiquantitative concentrations with similar sensitivity and a full analytical duty cycle of 2.5 min/sample. Preliminary data and performance metrics are reported for 6-PPDQ present in representative environmental and stormwater samples. The method is readily adapted for real-time process monitoring, demonstrated by following the dissolution of 6-PPDQ from tire fragments and subsequent removal in response to added sorbents.

Changes of Metabolic Biomarker Levels upon One-Year Anti-TNF-α Therapy in Rheumatoid Arthritis and Ankylosing Spondylitis: Associations with Vascular Pathophysiology.

Background: Cardiovascular (CV) morbidity, mortality, and metabolic syndrome are associated with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). Here, lipids and other metabolic markers in relation to vascular function and clinical markers were evaluated in RA and AS patients undergoing one-year anti-TNF therapy. Patients and methods: Fifty-three patients including 36 RA patients treated with either etanercept (ETN) or certolizumab pegol (CZP) and 17 AS patients treated with ETN were included in a 12-month follow-up study. Various lipids, paraoxonase (PON) and arylesterase (ARE) activities, myeloperoxidase (MPO) and adipokine levels were determined overtime. Ultrasonography was performed to determine flow-mediated vasodilation (FMD), common carotid intima-media thickness (ccIMT), and arterial pulse-wave velocity (PWV) in all patients. All assessments were performed at baseline and 6 and 12 months after treatment initiation. Results: Anti-TNF therapy decreased ARE activity, MPO, adiponectin, and chemerin levels after 12 months (p < 0.05). Lipids, PON activity, and leptin remained unchanged. Regression analyses suggested variable associations of IMT, PWV, and FMD with ARE, MPO, leptin, and lipids (p < 0.05). On the other hand, these metabolic parameters were significantly associated with disease duration, CV history, CRP, obesity, PWV, and IMT (p < 0.05). One-year anti-TNF treatment together with baseline leptin (p = 0.039) or CRP (p = 0.016) levels determined 12 months of lipid changes overtime. TNF inhibition together with baseline disease activity determined ARE activity changes (p = 0.046). Anti-TNF therapy and baseline chemerin levels determined IMT changes overtime (p = 0.003). Conclusions: Assessment of various metabolic parameters together with disease activity, CRP, and ultrasound-based techniques may exert additional value in determining CV burden and in monitoring the effects of biologics on preclinical vascular pathophysiology.

Hospital-based delays to revascularization increase risk of postoperative mortality and short bowel syndrome in acute mesenteric ischemia

ObjectiveAcute mesenteric ischemia (AMI) is a surgical emergency for which delays in treatment have been closely associated with high morbidity and mortality. Although the duration of ischemia as a determinant of outcomes for AMI is well known, the objective of this study was to identify hospital-based determinants of delayed revascularization and their effects on postoperative morbidity and mortality in AMI. MethodsAll patients who underwent any surgery for AMI from a multi-center hospital system between 2010 and 2020 were divided into two groups based on timeliness of mesenteric revascularization after presentation. Early revascularization (ER) was defined as having both vascular consultation ≤12 hours of presentation and vascular surgery performed at the patient’s initial operation. Delayed revascularization (DR) was defined as having either delays to vascular consultation or vascular surgery. A retrospective review of demographic and postoperative data was performed. The effect of DR on major postoperative outcomes, including 30-day and 2-year mortality, total length of bowel resection, and development of short bowel syndrome, were analyzed. Effects of delayed vascular consultation alone, delayed vascular surgery alone, no revascularization during admission, and admitting service on outcomes were also examined on subgroup analyses. ResultsA total of 212 patients were analyzed. Ninety-nine patients received ER, whereas the remaining 113 patients experienced a DR after hospital presentation. Among the DR group, 55 patients (25.9%) had delayed vascular consultation, whereas vascular surgery was deferred until after the initial operation in 37 patients (17.4%). Fifty-one patients (24.0%) were never revascularized during admission. DR was a significant predictor of 30-day (odds ratio [OR], 2.09; 95% confidence interval [CI], 1.4-4.9; P = .03) and 2-year mortality (hazard ratio, 1.55, 95% CI, 1.0-2.3; P = .04). DR was also independently associated with increased bowel resection length (OR, 7.47; P < .01) and postoperative short bowel syndrome (OR, 2.4; P = .03) on multivariate analyses. When examined separately on subgroup analysis, both delayed vascular consultation (OR, 3.38; P = .03) and vascular surgery (OR, 4.31; P < .01) independently increased risk of 30-day mortality. Hospital discharge after AMI without mesenteric revascularization was associated with increased risk of short bowel syndrome (OR, 2.94; P < .01) and late mortality (hazard ratio, 1.60; P = .04). ConclusionsDelayed vascular consultation and vascular surgery are both significant hospital-based determinants of postoperative mortality and short bowel syndrome in patients with AMI. Timing-based management protocols that emphasize routine evaluation by a vascular surgeon and early, definitive mesenteric revascularization should be established and widely adopted for all patients with clinically suspected AMI at presentation.

Culture medium from a marine endophytic fungus protects shrimp against acute hepatopancreatic necrosis disease (AHPND)

Because endophytic fungi are widely known for producing secondary metabolites and bioactive compounds, they are of interest to pharmaceutical and biotechnology industries. Many species are found in mangrove forests that are habitats for marine animals, especially in their early life stages. In this research, we screened 42 endophytic fungi originating from Thai mangrove forests for inhibitors of biofilm and planktonic cell growth of 7 Vibrio isolates. Some of these isolates were collected from shrimp ponds exhibiting early mortality syndrome (EMS) and diagnosed as outbreaks of acute hepatopancreatic necrosis disease (AHPND) that is caused by specific isolates of Vibrio parahaemolyticus (VPAHPND). Cell-free supernatants (CFS) of two fungal isolates (MCR433 and MCR 440) that inhibited biofilm growth for at least 5 out of the 7 Vibrio isolates were chosen for further study in shrimp feeding trials. One (MCR433) had strong biofilm inhibition and the other (MCR 440) weak biofilm inhibition for VPAHPND. Feed supplementation with CFS of MCR 433 protected shrimp against AHPND (72% mean survival) when compared to control shrimp given un-supplemented feed (20% mean survival) or given feed supplemented with CFS of MCR 440 (0% survival). Histological analysis of the hepatopancreas confirmed that shrimp given feed supplemented with MCR 433 showed little or no signs of AHPND pathology while shrimp in the other two groups showed histopathology typical AHPND. Using a multigene molecular typing approach, both MCR 433 and MCR 440 were identified as distinct members of the order Muyocopronales, class Dothideomycetes and phylum Ascomycota with differing biological activities. Further research is needed on the lead compounds generated by these strains. Those from MCR 433 have potential for use as feed additives against VPAHPND as an alternative to antibiotics.

A Novel Glutathione S-Transferase Gtt2 Class (VpGSTT2) Is Found in the Genome of the AHPND/EMS Vibrio parahaemolyticus Shrimp Pathogen.

Glutathione S-transferases are a family of detoxifying enzymes that catalyze the conjugation of reduced glutathione (GSH) with different xenobiotic compounds using either Ser, Tyr, or Cys as a primary catalytic residue. We identified a novel GST in the genome of the shrimp pathogen V. parahaemolyticus FIM- S1708+, a bacterial strain associated with Acute Hepatopancreatic Necrosis Disease (AHPND)/Early Mortality Syndrome (EMS) in cultured shrimp. This new GST class was named Gtt2. It has an atypical catalytic mechanism in which a water molecule instead of Ser, Tyr, or Cys activates the sulfhydryl group of GSH. The biochemical properties of Gtt2 from Vibrio parahaemolyticus (VpGSTT2) were characterized using kinetic and crystallographic methods. Recombinant VpGSTT2 was enzymatically active using GSH and CDNB as substrates, with a specific activity of 5.7 units/mg. Low affinity for substrates was demonstrated using both Michaelis–Menten kinetics and isothermal titration calorimetry. The crystal structure showed a canonical two-domain structure comprising a glutathione binding G-domain and a hydrophobic ligand H domain. A water molecule was hydrogen-bonded to residues Thr9 and Ser 11, as reported for the yeast Gtt2, suggesting a primary role in the reaction. Molecular docking showed that GSH could bind at the G-site in the vicinity of Ser11. G-site mutationsT9A and S11A were analyzed. S11A retained 30% activity, while T9A/S11A showed no detectable activity. VpGSTT2 was the first bacterial Gtt2 characterized, in which residues Ser11 and Thr9 coordinated a water molecule as part of a catalytic mechanism that was characteristic of yeast GTT2. The GTT2 family has been shown to provide protection against metal toxicity; in some cases, excess heavy metals appear in shrimp ponds presenting AHPND/EMS. Further studies may address whether GTT2 in V. parahaemolyticus pathogenic strains may provide a competitive advantage as a novel detoxification mechanism.

The association of medical resource utilization with physical morbidity and premature mortality among patients with schizophrenia: An historical prospective population cohort study

BackgroundSchizophrenia patients have shorter life expectancy often owing to preventable physical illnesses and sub-optimal utilization of medical services. However, the association between service-utilization and mortality has not been explored. AimTo assess whether medical service-utilization moderates the association between physical morbidity and premature mortality in a nation-wide cohort. MethodsA population representative database of the largest health provider in Israel was analyzed. All electronic health records of patients with schizophrenia diagnosis (ICD code F.20) (n = 24,679) were followed-up between 2012 and 2015, and compared to the general population (n = 2,232,804), in terms of metabolic and cardiovascular morbidity, all-cause mortality, primary medical and specialist health service-utilization and general hospitalizations. ResultsSchizophrenia was associated with increased mortality risk (adjusted hazard ratio (aHR) = 3.52, 95%CI 3.35–3.72). Most deaths were related to physical illnesses. Metabolic syndrome components, except chronic hypertension, were more prevalent among patients. They were referred more frequently to primary and less to secondary services (aHR = 1.05, 95%CI 1.04–1.06, aHR = 0.95, 95%CI 0.94–0.97, respectively), with higher hospitalization rates (0.23 ± 0.90 vs 0.10 ± 0.50 per year), and longer mean duration of hospitalization (2.02 ± 10.24 vs 0.68 ± 5.51 days, P < 0.001). More contacts with primary care physicians or specialists positively moderated the association between mortality and metabolic disturbances in patients with schizophrenia; more contacts were associated with better outcomes. ConclusionsAn association between premature mortality and metabolic syndrome was found among schizophrenia patients while utilization of primary/secondary medical services moderated the lethal effects of metabolic dysregulation. Increased integrative primary care and a national monitoring system are warranted to reduce mortality rate in this population.

Treading Water: Tire Wear Particle Leachate Recreates an Urban Runoff Mortality Syndrome in Coho but Not Chum Salmon.

Tire tread wear particles (TWP) are increasingly recognized as a global pollutant of surface waters, but their impact on biota in receiving waters is rarely addressed. In the developed U.S. Pacific Northwest, acute mortality of adult coho salmon (Oncorhynchus kisutch) follows rain events and is correlated with roadway density. Roadway runoff experimentally triggers behavioral symptoms and associated changes in blood indicative of cardiorespiratory distress prior to death. Closely related chum salmon (O. keta) lack an equivalent response. Acute mortality of juvenile coho was recently experimentally linked to a transformation product of a tire-derived chemical. We evaluated whether TWP leachate is sufficient to trigger the acute mortality syndrome in adult coho salmon. We characterized the acute response of adult coho and chum salmon to TWP leachate (survival, behavior, blood physiology) and compared it with that caused by roadway runoff. TWP leachate was acutely lethal to coho at concentrations similar to roadway runoff, with the same behaviors and blood parameters impacted. As with runoff, chum salmon appeared insensitive to TWP leachate at concentrations lethal to coho. Our results confirm that environmentally relevant TWP exposures cause acute mortalities of a keystone aquatic species.