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Samuel H Sigal,1 Zachary Sherman,2 Arun Jesudian2 1Department of Medicine, Montefiore Medical Center, Bronx, NY, USA; 2Department of Medicine, Weill Cornell Medical Center, New York, NY, USACorrespondence: Samuel H SigalMontefiore Medical Center, Bronx, NY 10467 Tel +1 718 920-6240Fax +1917 398-8466Email ssigal@montefiore.orgAbstract: Thrombocytopenia is a frequent complication in patients with cirrhosis. As many as 84% of patients with cirrhosis have thrombocytopenia, and it is an independent variable indicative of advanced disease and poor prognosis. Although there is great concern that it may aggravate bleeding during surgical procedures, there is limited evidence to inform decisions regarding the treatment of cirrhotic patients with thrombocytopenia undergoing invasive procedures. Finally, there is evidence that platelets play a significant role in liver regeneration. In this report, the clinical implications of thrombocytopenia in cirrhotic patients are reviewed. The utility of platelet counts in the prognosis of cirrhosis and relationship to complications of advanced liver disease, including portal hypertension, esophageal varices, and hepatocellular carcinoma. The impact of low platelet counts on bleeding complications during invasive procedures is outlined. Finally, the role of platelets and potential adverse impact in liver regeneration is reviewed.Keywords: thrombocytopenia, prognosis, invasive procedures, liver regeneration

Oscar Mitchell,1 David M Feldman,1,2 Marla Diakow,1 Samuel H Sigal3 1Department of Medicine, 2Division of Gastroenterology and Liver Diseases, New York University School of Medicine, Langone Medical Center, New York, 3Division of Gastroenterology and Liver Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA Abstract: Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CLD). In addition to being an indicator of advanced disease and poor prognosis, it frequently prevents crucial interventions. Historically, thrombocytopenia has been attributed to hypersplenism, which is the increased pooling of platelets in a spleen enlarged by congestive splenomegaly secondary to portal hypertension. Over the past decade, however, there have been significant advances in the understanding of thrombopoiesis, which, in turn, has led to an improved understanding of thrombocytopenia in cirrhosis. Multiple factors contribute to the development of thrombocytopenia and these can broadly be divided into those that cause decreased production, splenic sequestration, and increased destruction. Depressed thrombopoietin levels in CLD, together with direct bone marrow suppression, result in a reduced rate of platelet production. Thrombopoietin regulates both platelet production and maturation and is impaired in CLD. Bone marrow suppression can be caused by viruses, alcohol, iron overload, and medications. Splenic sequestration results from hypersplenism. The increased rate of platelet destruction in cirrhosis also occurs through a number of pathways: increased shear stress, increased fibrinolysis, bacterial translocation, and infection result in an increased rate of platelet aggregation, while autoimmune disease and raised titers of antiplatelet immunoglobulin result in the immunologic destruction of platelets. An in-depth understanding of the complex pathophysiology of the thrombocytopenia of CLD is crucial when considering treatment strategies. This review outlines the recent advances in our understanding of thrombocytopenia in cirrhosis and CLD. Keywords: cirrhosis, thrombocytopenia, thrombopoietin

Deborah Lim Chua, Thomas Hahambis, Samuel H SigalDivision of Gastroenterology, Department of Medicine, New York University School of Medicine, New York, NY, USABackground: Chronic hepatitis C is the most common cause of cirrhosis in industrialized countries. Successful treatment of chronic hepatitis C in patients with advanced fibrosis or cirrhosis has significant benefits, including improvements in inflammation, fibrosis, and portal hypertension, with prevention of esophageal varices and clinical decompensation.Case: In this report, we present two patients with well-compensated hepatitis C cirrhosis who achieved an end-of-treatment response on a direct-acting antiviral therapy-based triple regimen for hepatitis C virus, but subsequently presented with new-onset ascites associated with virologic relapse.Conclusion: We propose that the development of ascites in this setting is due to the adverse impact of inflammation of the virologic relapse on portal hypertension. Our observation that ascites formation can be a manifestation of virologic relapse has potentially important clinical implications, as it highlights not only the importance of close monitoring of cirrhotic patients after achieving end-of-treatment response but also the impact of active inflammation on the severity of portal hypertension.Keywords: chronic hepatitis C, cirrhosis, virologic relapse, portal hypertension, ascites

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USAAbstract: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity

Abstract Background Violence against nurses is common. Previous research has recommended further development of the measurement of violence against nurses and integration of the individual and ward-related factors that contribute to violence against hospital nurses. This study was designed to address these issues by investigating the associations between violence, the listening climate of hospital wards, professional burnout, and perceived quality of care. For this purpose, we used a new operationalization of the violence concept. Methods We sought nurses to participate in the study through social media which yielded 765 nurses working in various healthcare systems across Israel who volunteered to complete a self-administered online questionnaire. 80% of the sample were hospital nurses, and 84.7% were female. The questionnaire included validated measures of burnout, listening climate, and quality of care. Instead of using the traditional binary measure of exposure to violence to capture the occurrence and comprehensive impact of violence, this study measured the incremental load of violence to which nurses are subjected. Results There were significant correlations between violence load and perceived quality of care and between constructive and destructive listening climates and quality of care. Violence load contributed 14% to the variance of burnout and 13% to the variance of perceived quality of care. The ward listening climate moderated the relationship between burnout and quality of care. Conclusions The results of this study highlight the impact of violence load among nurses and the ward listening climate on the development of burnout and on providing quality care. The findings call upon policymakers to monitor violence load and allocate resources to foster supportive work environments to enhance nurse well-being and improve patient care outcomes.

Accumulating data on the increasing degradation of coral reefs worldwide has led to a focus on the unique mesophotic coral ecosystem (MCE) as a potential refuge for threatened shallow-water species (i.e., the deep reef refugia hypothesis: DRRH). Sponges play a crucial role in coral-reef functioning but are often overlooked in benthic surveys. This knowledge gap is especially true for the Red Sea, where data on sponge abundance, coverage and species composition are scarce. Furthermore, to date, no study has examined mesophotic sponges in the Red Sea. Here we compared sponge abundance and diversity metrics between shallow and mesophotic reefs at two sites in the Gulf of Aqaba, northern Red Sea. We also examined the role of biotic and abiotic parameters in determining sponge variability between sites and depths. Sponge diversity metrics significantly varied with increasing depth and between sites. Sponge species composition also differed significantly between depth and sites. However, parameters measured in the water column, that is, Total Organic Carbon (TOC), Particulate Organic Carbon (POC), NOx, etc., did not differ between depths and sites, except for Synechococcus and Prochlorococcus concentration, which did. The findings indicated that site characteristics and biotic interactions may play an essential role in determining sponge diversity and community composition. Between-site differences in sponge fauna revealed in the study highlight the importance of considering the variability in the benthic communities and the factors controlling it when designing management tools for coral reefs, particularly for the northern Red Sea.

Climate change is predicted to have detrimental impacts on sessile invertebrates, including sponges. Mesophotic ecosystems have been suggested to play a major role as refugia for coral reef sponge species, however knowledge regarding the ability of mesophotic sponges to cope with thermal stress is scarce. In this study we compared the response of the sponge Diacarnus erythraeanus, a widespread Red Sea sponge, from the shallow and mesophotic reef, to moderate and acute temperature elevation (2°C and 6°C, respectively) for short and long term periods (two and 35 days, respectively) by measuring physiological parameters (respiration, oxygen removal, pumping rates, and photosynthetic efficiency), and the microbiome composition change. The results indicated that mesophotic and shallow populations of D. erythraeanus are highly tolerant to both moderate and acute heat stress, demonstrating a high survival rate (100%) across the experimental treatments, with no visible signs of bleaching or necrosis. Exposure to heat stress resulted in significant alterations in the physiological parameters of sponges, including higher respiration rate and lower photosynthetic efficiency. These alterations were accompanied by correspondingly significant microbial adjustments, thus emphasizing the essential role of the microbiome in the host’s ability to persist when facing essential environmental stress. Moreover, while shallow and mesophotic sponges showed similar physiological tolerance to heat stress, their microbial response differed: while the microbiome diversity of the mesophotic sponges remained stable throughout the experiment, the shallow one significantly changed. This result suggests that their underlying coping mechanisms might differ between mesophotic and shallow populations. Since the associated-microbiome is largely regulated by the sponge-host genetics, difference in microbial adjustments to stress between populations, could indicate genetic variability between hosts. Therefore, while the results of this study support the hypothesis that mesophotic coral reefs could serve as thermal refugia for some sponge species, it raises the question regarding the validity of MCEs as a refuge for shallow populations. Finally, it emphasizes the crucial need to elucidate the underlying mechanisms governing the sponge-microbiome interactions, specifically in the context of the anticipated climate change scenarios.

Background: Viral infection is associated with a significant rewire of the host metabolic pathways, presenting attractive metabolic targets for intervention. Methods: We chart the metabolic response of lung epithelial cells to SARS-CoV-2 infection in primary cultures and COVID-19 patient samples and perform in vitro metabolism-focused drug screen on primary lung epithelial cells infected with different strains of the virus. We perform observational analysis of Israeli patients hospitalized due to COVID-19 and comparative epidemiological analysis from cohorts in Italy and the Veteran’s Health Administration in the United States. In addition, we perform a prospective non-randomized interventional open-label study in which 15 patients hospitalized with severe COVID-19 were given 145 mg/day of nanocrystallized fenofibrate added to the standard of care. Results: SARS-CoV-2 infection produced transcriptional changes associated with increased glycolysis and lipid accumulation. Metabolism-focused drug screen showed that fenofibrate reversed lipid accumulation and blocked SARS-CoV-2 replication through a PPARα-dependent mechanism in both alpha and delta variants. Analysis of 3233 Israeli patients hospitalized due to COVID-19 supported in vitro findings. Patients taking fibrates showed significantly lower markers of immunoinflammation and faster recovery. Additional corroboration was received by comparative epidemiological analysis from cohorts in Europe and the United States. A subsequent prospective non-randomized interventional open-label study was carried out on 15 patients hospitalized with severe COVID-19. The patients were treated with 145 mg/day of nanocrystallized fenofibrate in addition to standard-of-care. Patients receiving fenofibrate demonstrated a rapid reduction in inflammation and a significantly faster recovery compared to patients admitted during the same period. Conclusions: Taken together, our data suggest that pharmacological modulation of PPARα should be strongly considered as a potential therapeutic approach for SARS-CoV-2 infection and emphasizes the need to complete the study of fenofibrate in large randomized controlled clinical trials. Funding: Funding was provided by European Research Council Consolidator Grants OCLD (project no. 681870) and generous gifts from the Nikoh Foundation and the Sam and Rina Frankel Foundation (YN). The interventional study was supported by Abbott (project FENOC0003). Clinical trial number: NCT04661930.

Summary: The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013–2018), Phase 2 of the program (ERCC2, 2019–2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2’s current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Summary: Patients with SARS-CoV-2 infection (COVID-19) risk developing long-term neurologic symptoms after infection. Here, we identify biomarkers associated with neurologic sequelae one year after hospitalization for SARS-CoV-2 infection. SARS-CoV-2-positive patients were followed using post-SARS-CoV-2 online questionnaires and virtual visits. Hospitalized adults from the pre-SARS-CoV-2 era served as historical controls. 40% of hospitalized patients develop neurological sequelae in the year after recovery from acute COVID-19 infection. Age, disease severity, and COVID-19 infection itself was associated with additional risk for neurological sequelae in our cohorts. Glial fibrillary astrocytic protein (GFAP) and neurofilament light chain (NF-L) were significantly elevated in SARS-CoV-2 infection. After adjusting for age, sex, and disease severity, GFAP and NF-L remained significantly associated with longer term neurological symptoms in patients with SARS-CoV-2 infection. GFAP and NF-L warrant exploration as biomarkers for long-term neurologic complications after SARS-CoV-2 infection.

Abstract Objectives To examine the association between listening and disruptive behaviors and the association between disruptive behavior and the wellbeing of the nurse. To test whether constructive and destructive listening has an incremental validity. Methods A structured questionnaire survey that measured the (constructive & destructive) listening climate at work, exposure to disruptive behaviors, well-being and feeling as a victim. We presented this survey using the Qualtrics software. Results Of the final sample of 567 respondents who reported that they were nurses, MAge = 38.41, 67% indicated that they were exposed to some form of disruptive behavior. Experiencing listening in the ward was associated with low levels of exposure to disruptive behaviors; exposure to disruptive behaviors, in turn, predicted reduction in the nurses’ wellbeing; the reduction in wellbeing was especially pronounced among nurses who felt like a victim. Each of the facets of the listening measure—constructive listening and destructive listening—had incremental validity in predicting exposure to disruptive behaviors. Finally, the effect of exposure to disruptive behavior on wellbeing was curvilinear. Conclusions Disruptive behavior is a major challenge to the workplace well-being for nurses. The victim mentality has an adverse impact on nurses. Preventive efforts aimed at reducing disruptive behaviors among nurses and decreasing their sense of victimization are crucial for the well-being of nurses.

Polychaetes are among the most common marine organisms, and in many habitats they dominate both in species richness and abundance. They are often found in association with other organisms. Specifically, sponges with their complex three-dimensional internal architecture, are known to host a great diversity of polychaetes. Due to the fact that a large number of sponge-associated polychaete species are known to be common on other substrates, most studies agree that they represent an opportunistic part of the sponge-inhabiting assemblage, without any selection of species tightly associated with sponges. The current study aimed to shed light on polychaetes affinity to sponges. We applied Clarke and Warwick’s taxonomic distinctness indices and test for random assembly, to a dataset compiled of 13 publications that provided polychaete species lists from massive-sponges across the Mediterranean Sea, and compared them with benthic-polychaete species lists from all of the Mediterranean and its zoogeographical regions. These indices are considered to be independent of sampling efforts and setting, and can be applied on presence/absence data, making it possible to compare data from multiple studies. We further compared the trophic structure of sponge-associated polychaetes between the Mediterranean’s zoogeographical regions. Our results show that the trophic structure of the sponge-associated polychaete community, was found to be stable across the entire Mediterranean Sea. Moreover, randomization tests showed that at almost all observational scales (e.g., study, region, Mediterranean) the phylogenetic diversity is not assembled at random, and that sponge-associated polychaete communities are composed of taxonomically related species. These results support the statement that polychaete assemblages inhabiting sponges are not a transient facultative assembly of species, but rather stable, diverse and specialized communities which are well adapted for life in this habitat.

Sponges have long been considered as “living hotels” due to the great diversity and abundance of other taxonomic groups often found in association with them. Sponges are the dominant components of benthic communities in the Levant Sea; and especially in the recently discovered mesophotic sponge grounds off the coast of Israel. However, almost no data exist regarding their associated macrofauna. The current study sought to identify the macrofauna associated with massive sponges along the Israeli Mediterranean coast; and to compare the role of sponges, as ecosystem engineers, or “living hotels,” in both the shallow-water and mesophotic habitats. Sixty-four massive sponge specimens, from 10 different species, were collected from shallow and mesophotic habitats by SCUBA diving and Remotely Operated Vehicle, respectively. Sponge volume was estimated, specimens were dissected, and the associated macrofauna were identified. Our results reveal that the sponges supported a diverse assemblage of associated macrofauna. A total of 61 associated taxa were found, including species reported for the first time in Israel. A clear, differentiation existed in the structure of the associated assemblage between the two habitats, which is mainly attributed to four species (two polychaetes, a crustacean, and a brittle star). The trophic composition remained stable across the two habitats. No correlation was found between sponge volume and the associated fauna community parameters. The highest richness of associated fauna was found in the mesophotic habitat, where sponge diversity is also higher. In contrast, a greater endobiont abundance and density were recorded in the shallow habitat, where massive sponges may be a limiting factor due to their lower richness and abundance. Our findings emphasize the importance of sponges as ecosystem engineers, and suggest that sponge diversity may be an important factor that contribute to benthic biodiversity in these regions.

We report the case of a 56-year-old male patient, who over two decades, sequentially presented with a combination of clinical manifestations. These included thrombotic thrombocytopenic purpura (TTP), right leg deep vein thrombosis (DVT), and eventually constitutional symptoms, arthralgia, diffuse lymphadenopathy, pancytopenia, skin rash, pericarditis, and glomerulonephritis. Serologic tests and renal pathology uncovered a diagnosis of systemic lupus erythematosus (SLE), and immunosuppressive therapy was initiated. Soon after, the patient developed striking cytomegalovirus (CMV) viremia, requiring prolonged antiviral therapy and reduction of immunosuppression. Finally, an acute embolic stroke complicated the disease course. Prompt interventions allowed an excellent clinical outcome.

Determining demosponge reproductive strategies is essential to understanding their ecology and life history, as well as for the management of benthic marine environments. This is especially important in mesophotic ecosystems, which have been suggested to serve as a refuge for shallow-water populations and for which knowledge is lacking. Here we compared the reproductive strategies of two common Mediterranean demosponges species: Chondrosia reniformis and Axinella polypoides, which can be found in both shallow and mesophotic habitats along the Israeli coast. Samples were collected over 2 years, via SCUBA diving from the shallow coast (2–32 m) and Remotely Operated Vehicle from the mesophotic sponge grounds (95–120 m). A. polypoides and C. renifornis differed in oocyte morphology and development, but both demonstrated reproductive plasticity with regard to temperature and depth: temperature appears to regulate their reproduction in the shallow water, as both species exhibited seasonality; whereas, in the mesophotic zone, where the temperature amplitude is much smaller, seasonality was not observed for either species. Furthermore, in the mesophotic zone, C. reniformis exhibited low fecundity and probably invests more in asexual reproduction by budding. Mesophotic A. polypoides, in contrast, exhibited enhanced and continuous asynchronous sexual reproduction year-round. Our findings suggest that reproduction plasticity may be a general rule for sponge species that inhabit different habitats; such plasticity could allow sponges to thrive in different environmental conditions. These findings further emphasize the importance of protecting the mesophotic sponge grounds, which can serve as a refuge in the face of the adverse impact of anthropogenic disturbances and rising seawater temperatures.

Sponges hold a key role in benthic environments, and specifically in the Mediterranean Sea. Past events of mass mortality in sponge communities have been linked to extended periods of high-temperature anomalies, yet it is unknown how a gradual change, such as the constant rise in global seawater temperatures, will affect biodiversity. Here we present a case study of Agelas oroides, a common massive sponge in the Mediterranean Sea, found at a wide depth range of 1–150 m. Last documented in the 1970s, A. oroides was considered lost from the Israeli coastal fauna. However, its recent rediscovery in mesophotic depths, where environmental conditions are stable, provided an opportunity to examine whether it can survive the present conditions in the shallow Israeli coast – where temperatures increased by 3°C during the past 60 years, while the nutrients concentration decreased following the damming of the Nile River. To test this hypothesis, A. oroides individuals were collected during winter from mesophotic sponge grounds (100–120 m) and transplanted to a shallow rocky habitat (10 m). Control individuals were transplanted back to the mesophotic habitat. Sponge survival, temperature, and nutrient concentrations were measured in both habitats. The shallow-transplanted sponges’ survival decreased only when the ambient temperature exceeded 28°C. In contrast, the control group at the mesophotic depth, where the temperature never rose above 20°C, survived the duration of the experiment. Our findings suggest that a prolonged period of high temperatures may constitute a major factor in A. oroides survival and disappearance from the Israeli shallow habitats.

There are multiple possible causes of ascites in patients with end-stage renal disease on hemodialysis therapy. In this report, we describe a patient with chronic hepatitis C infection who presented with refractory inflammatory ascites, along with cachexia, hypoalbuminemia, and erythropoietin resistance associated with the chronic inflammatory state induced by a failed kidney transplant. Evaluation showed only mild hepatic fibrosis, absence of portal hypertension, and no other identifiable cause of the ascites. Furthermore, the inflammatory ascites did not respond to antibiotic therapy, but promptly resolved, along with the other manifestations of the chronic inflammatory state, after transplant nephrectomy. This report describes a novel cause for refractory inflammatory ascites in a patient with a failed kidney transplant and emphasizes the importance of transplant nephrectomy. Copyright © 2007 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Patients with cirrhosis can acquire pulmonary conditions that may or may not be related to their illness. Although posing a greater risk for complications, chest tubes are sometimes placed as treatment for hepatic hydrothorax and other pulmonary conditions. The aim of this study was to analyze the outcomes of chest tube placement in cirrhotic patients. METHODS: A retrospective analysis was performed of 59 adults with cirrhosis undergoing chest tube placement. Variables that were investigated included reason for chest tube placement, complications developing while having the tube in place, and outcome. RESULTS: The 59 subjects were classified as having Child-Turcotte-Pugh (CTP) class A cirrhosis (n = 3), CTP class B cirrhosis (n = 31), and CTP class C cirrhosis (n = 25). Indications for having a chest tube placed were hepatic hydrothorax (n = 24), pneumothorax (n = 9), empyema (n = 8), video-assisted thoracoscopy (VAT) [n = 7], non-VAT (n = 5), and hemothorax (n = 3). The CTP class A subjects had their chest tubes removed without further complications early in the course, and were excluded from further statistical analysis. Twenty-five subjects (42%) had significant pleural effusions requiring chest tube placement. Among the CTP class B and class C subjects, the median duration with chest tube in place was 5.0 days (range, 1 to 53 days). Serum total bilirubin levels, presence of portosystemic encephalopathy, and CTP C classification were predictors of mortality. Mortalities were seen in 5 of 31 CTP class B subjects (16%), and 10 of 25 CTP class C subjects (40%). The tubes were successfully removed in a total of 39 subjects (66%) with no further procedure. Forty-seven subjects (80%) acquired one or more of the following complications: renal dysfunction, electrolyte imbalances, and infection. CONCLUSIONS: When placed for all indications, chest tubes may be successfully removed in the majority of cirrhotic patients. However, a third of all patients still die with the chest tube still in place. Failure to remove the chest tube increases mortality in patients with increasing severity of liver disease. [ABSTRACT FROM AUTHOR]

Abstract Background Violence against medical personnel is unexpected in hospitals which are devoted to healing, and yet, it is frequent and of concern in the health system. Little is known about the factors that lead to hospital violence, and even less is known about the interactions among these factors. The aim of the study was to identify and describe the perceptions of staff and patients regarding the factors that lead to violence on the part of patients and those accompanying them. Methods A mixed-methods study in a large, general, university tertiary hospital. A self-administered survey yielding 678 completed questionnaires, comprising 34% nurses and 66% physicians (93% response rate). Eighteen in-depth interviews were conducted separately with both victims and perpetrators of violent episodes, and four focus-groups (N = 20) were undertaken separately with physicians, staff nurses, head-nurses, and security personnel. Results Violence erupts as a result of interacting factors encompassing staff behavior, patient behavior, hospital setting, professional roles, and waiting times. Patients and staff reported similar perceptions and emotions regarding the episodes of violence in which they were involved. Of 4,047 statements elicited in the staff survey regarding the eruption of violence, 39% referred to staff behavior; 26 % to patient/visitor behavior; 17% to organizational conditions, and 10% to waiting times. In addition, 35% of the staff respondents reported that their own behavior contributed to the creation of the most severe violent episode in which they were involved, and 48% stated that staff behavior contributed to violent episodes. Half of the reasons stated by physicians and nurses for violence eruption were related to patient dissatisfaction with the quality of service, the degree of staff professionalism, or an unacceptable comment of a staff member. In addition, data from the focus groups pointed to lack of understanding of the hospital system on the part of patients, together with poor communication between patients and providers and expectations gaps. Conclusions Our various and triangulated data sources show that staff and patients share conditions of overload, pressure, fatigue, and frustration. Staff also expressed lack of coping tools to prevent violence. Self-conscious awareness regarding potential interacting factors can be used to develop interventions aimed at prevention of and better coping with hospital violence for both health systems' users and providers.

Inhibition of endothelial nitric oxide synthase (eNOS) accelerates atherosclerosis in ApoE-null mice by impairing the balance between angiotensin II (AII) and NO. Our previous data suggested a role for PPARα in the deleterious effect of the renin-angiotensin system (RAS). We tested the hypothesis that ApoE-null mice lacking PPARα (DKO mice) would be resistant to the proatherogenic effect of NOS inhibition. DKO mice fed a Western diet were immune to the 23% worsening in aortic sinus plaque area seen in the ApoE-null animals under 12 weeks of NOS inhibition with a subpressor dose of L-NAME, P=0.002. This was accompanied by a doubling of reactive oxygen species (ROS-) generating aortic NADPH oxidase activity (a target of AII, which paralleled Nox1 expression) and by a 10-fold excess of the proatherogenic iNOS, P