Hepatocellular carcinoma after direct-acting antivirals for hepatitis C is associated with KIR-HLA types predicting weak NK cell-mediated immunity.

Background And Aims: Second-generation direct-acting antivirals (2G DAA) to cure HCV have led to dramatic clinical improvements. HCV-associated hepatocellular carcinoma (HCC), however, remains common. Impaired immune tumor surveillance may play a role in HCC development.

Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study.

Objectives: SARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.

Surgical Site Complications in Open Pronation-Abduction Ankle Fracture-Dislocations With Medial Tension Failure Wounds.

Objectives: To examine the incidence of surgical site complications associated with pronation-abduction ankle fracture-dislocations with an open medial tension wound.

Design: Retrospective case series.

Setting: Accredited Level-1 trauma center.

Skin closure with surgical staples in ankle fractures: a safe and reliable method.

Purpose: The purpose of this study is to examine the rates of surgical site complications of staple closure versus suture closure following open reduction and internal fixation of closed unstable ankle fractures.

Methods: Between 2014 and 2016, a total of 545 patients with closed ankle fractures were treated at our level-1 trauma centre by means of open reduction and internal fixation. A total of 360 patients matched the inclusion criteria and were included in the final analysis of this study.

Fate of the Uninsured Ankle Fracture: Significant Delays in Treatment Result in an Increased Risk of Surgical Site Infection.

Objective: To examine the impact of insurance status on access to orthopaedic care and incidence of surgical site complications in patients with closed unstable ankle fractures.

Design: Retrospective chart review.

Setting: Certified Level-1 urban trauma center and county facility.

SHIP1 Deficiency in Inflammatory Bowel Disease Is Associated With Severe Crohn's Disease and Peripheral T Cell Reduction.

In our previous study, we observed a severe reduction in the Src homology 2-containing-inositol-phosphatase-1 (SHIP1) protein in a subpopulation of subjects from a small adult Crohn's Disease (CD) cohort. This pilot study had been undertaken since we had previously demonstrated that engineered deficiency of SHIP1 in mice results in a spontaneous and severe CD-like ileitis. Here, we extend our analysis of SHIP1 expression in peripheral blood mononuclear cells in a second much larger adult Inflammatory Bowel Disease (IBD) cohort, comprised of both CD and Ulcerative Colitis patients, to assess contribution of SHIP1 to the pathogenesis of human IBD.

Identification of MHC Class Ib Ligands for Stimulatory and Inhibitory Ly49 Receptors and Induction of Potent NK Cell Alloresponses in Rats.

Early studies indicate that rats may have a repertoire of MHC class Ib-reactive Ly49 stimulatory receptors capable of mounting memory-like NK cell alloresponses. In this article, we provide molecular and functional evidence for this assumption. Pairs of Ly49 receptors with sequence similarities in the lectin-like domains, but with opposing signaling functions, showed specificity for ligands with class Ia-like structural features encoded from the first telomeric MHC class Ib gene cluster, , which is syntenic with the cluster in mice.

Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success.

The contribution of the host immune system to the efficacy of new anti-hepatitis C virus (HCV) drugs is unclear. We undertook a longitudinal prospective study of 33 individuals with chronic HCV treated with combination pegylated IFN-α, ribavirin, and telaprevir/boceprevir. We characterized innate and adaptive immune cells to determine whether kinetics of the host response could predict sustained virologic response (SVR).

NKG2D ligand expression in Crohn's disease and NKG2D-dependent stimulation of CD8 T cell migration.

Interaction between the activating NKG2D receptor on lymphocytes and its ligands MICA, MICB, and ULBP1-6 modulate T and NK cell activity and may contribute to the pathogenesis of Crohn's disease (CD). NKG2D ligands are generally not expressed on the cell surface of normal, non-stressed cells, but expression of MICA and MICB in CD intestine has been reported. In this exploratory study, we further characterize the expression of NKG2D and its ligands, including the less well-described ULBP4-6, in CD, and test if NKG2D ligand interactions are involved in the migration of activated T cells into the affected mucosal compartments.

IL-33 promotes growth and liver metastasis of colorectal cancer in mice by remodeling the tumor microenvironment and inducing angiogenesis.

Liver metastasis is the major cause of death from colorectal cancer (CRC). Understanding its mechanisms is necessary for timely diagnosis and development of effective therapies. Interleukin-33 (IL-33) is an IL-1 cytokine family member that uniquely functions as a cytokine and nuclear factor.

Improved Survival Among all Interferon-α-Treated Patients in HCV-002, a Veterans Affairs Hepatitis C Cohort of 2211 Patients, Despite Increased Cirrhosis Among Nonresponders.

Background: As the era of interferon-alpha (IFN)-based therapy for hepatitis C ends, long-term treatment outcomes are now being evaluated.

Aim: To more fully understand the natural history of hepatitis C infection by following a multisite cohort of patients.

Methods: Patients with chronic HCV were prospectively enrolled in 1999-2000 from 11 VA medical centers and followed through retrospective medical record review.

Protective association of colonoscopy against proximal and distal colon cancer and patterns in interval cancer.

Background: The protective effect of colonoscopy against proximal colorectal cancer is variable and depends on the detection and complete removal of precancerous polyps.

Objective: To estimate the efficacy of colonoscopy in a medical center with open-access screening colonoscopy since 1998.

Design: Nested case-control study with incidence density sampling.

Transcriptomic signatures in whole blood of patients who acquire a chronic inflammatory response syndrome (CIRS) following an exposure to the marine toxin ciguatoxin.

Background: Ciguatoxins (CTXs) are polyether marine neurotoxins found in multiple reef-fish species and are potent activators of voltage-gated sodium channels. It is estimated that up to 500,000 people annually experience acute ciguatera poisoning from consuming toxic fish and a small percentage of these victims will develop a chronic, multisymptom, multisystem illness, which can last years, termed a Chronic Inflammatory Response Syndrome (CIRS). Symptoms of ciguatera CIRS include fatigue, cognitive deficits, neurologic deficits, pain and sensitivity to light.

Microarray applications to understand the impact of exposure to environmental contaminants in wild dolphins (Tursiops truncatus).

It is increasingly common to monitor the marine environment and establish geographic trends of environmental contamination by measuring contaminant levels in animals from higher trophic levels. The health of an ecosystem is largely reflected in the health of its inhabitants. As an apex predator, the common bottlenose dolphin (Tursiops truncatus) can reflect the health of near shore marine ecosystems, and reflect coastal threats that pose risk to human health, such as legacy contaminants or marine toxins, e.

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system.

Machine learning approaches to investigate the impact of PCBs on the transcriptome of the common bottlenose dolphin (Tursiops truncatus).

As top-level predators, common bottlenose dolphins (Tursiops truncatus) are particularly sensitive to chemical and biological contaminants that accumulate and biomagnify in the marine food chain. This work investigates the potential use of microarray technology and gene expression profile analysis to screen common bottlenose dolphins for exposure to environmental contaminants through the immunological and/or endocrine perturbations associated with these agents. A dolphin microarray representing 24,418 unigene sequences was used to analyze blood samples collected from 47 dolphins during capture-release health assessments from five different US coastal locations (Beaufort, NC, Sarasota Bay, FL, Saint Joseph Bay, FL, Sapelo Island, GA and Brunswick, GA).

Expanded use of aggressive therapies improves survival in early and intermediate hepatocellular carcinoma.

Background: Despite the increasing annual incidence of hepatocellular carcinoma (HCC) in the USA, now estimated at 2.7 cases per 100 000 population, only a small proportion of patients receive treatment and 5-year survival rates range from 9% to 17%.

Objectives: The present study examines the effects of multimodal treatment on survival in a mixed-stage HCC cohort, focusing on the impact of radical therapy in patients with Barcelona Clinic Liver Cancer (BCLC) stage B disease.

Monocyte activation by interferon α is associated with failure to achieve a sustained virologic response after treatment for hepatitis C virus infection.

Background: Interferon α (IFN-α) and ribavirin can induce a sustained virologic response (SVR) in some but not all hepatitis C virus (HCV)-infected patients. The mechanism of effective treatment is unclear. One possibility is that IFN-α differentially improves the functional capacity of classic myeloid dendritic cells (mDCs) by altering expression of surface molecules or cytokines.

Transcriptomic responses of juvenile Pacific whiteleg shrimp, Litopenaeus vannamei, to hypoxia and hypercapnic hypoxia.

Estuarine crustaceans are often exposed to low dissolved O2 (hypoxia) accompanied by elevated CO2 (hypercapnia), which lowers water pH. Acclimatory responses to hypoxia have been widely characterized; responses to hypercapnia in combination with hypoxia (hypercapnic hypoxia) are less well known. Here we used oligonucleotide microarrays to characterize changes in global gene expression in the hepatopancreas of Pacific whiteleg shrimp, Litopenaeus vannamei, exposed to hypoxia or hypercapnic hypoxia for 4 or 24 h, compared with time-matched animals held in air-saturated water (normoxia).

Nonresponse to interferon-α based treatment for chronic hepatitis C infection is associated with increased hazard of cirrhosis.

Background: The long-term consequences of unsuccessful interferon-α based hepatitis C treatment on liver disease progression and survival have not been fully explored.

Methods And Findings: We performed retrospective analyses to assess long-term clinical outcomes among treated and untreated patients with hepatitis C virus in two independent cohorts from a United States Veterans Affairs Medical Center and a University Teaching Hospital. Eligible patients underwent liver biopsy during consideration for interferon-α based treatment between 1992 and 2007.

Impaired lymphocyte reactivity measured by immune function testing in untransplanted patients with cirrhosis.

The immune function test is an integrated measure of total mitogen-inducible CD4(+) T cell metabolic activity in the peripheral blood, and it is used to guide the dosing of immunosuppressive medications after solid organ transplantation. Recently, low CD4(+) T cell metabolic activity due to pharmacologic immunosuppression has been linked to rapidly progressive cirrhosis in hepatitis C virus (HCV)-infected liver transplant recipients. We speculate that either cirrhosis or HCV might adversely affect the CD4(+) T cell reactivity even in the absence of immunosuppressive medications.

Transcriptome remodeling associated with chronological aging in the dinoflagellate, Karenia brevis.

The toxic dinoflagellate, Karenia brevis, forms dense blooms in the Gulf of Mexico that persist for many months in coastal waters, where they can cause extensive marine animal mortalities and human health impacts. The mechanisms that enable cell survival in high density, low growth blooms, and the mechanisms leading to often rapid bloom demise are not well understood. To gain an understanding of processes that underlie chronological aging in this dinoflagellate, a microarray study was carried out to identify changes in the global transcriptome that accompany the entry and maintenance of stationary phase up to the onset of cell death.

Health status, infection and disease in California sea lions (Zalophus californianus) studied using a canine microarray platform and machine-learning approaches.

Conservation biologists face many challenges in assessing health, immune status and infectious diseases in protected species. These challenges include unpredictable sample populations, diverse genetic and environmental backgrounds of the animals, as well as the practical, legal and ethical issues involved in experimentation. The use of whole genome scale transcriptomics with animal samples obtained in a minimally invasive manner is an approach that shows promise for health assessment.

Development of a measure of work motivation for a meta-theory of motivation.

This study presents a measure of work motivation designed to assess the motivational concepts of the meta-theory of motivation. These concepts include intrinsic process motivation, goal internalization motivation, instrumental motivation, external self-concept motivation, and internal self-concept motivation. Following a process of statement development and identification, six statements for each concept were presented to a sample of working professionals (N = 330) via a paper-and-pencil questionnaire.

The rat NK cell receptors Ly49s4 and Ly49i4 recognize nonclassical MHC-I molecules on Listeria monocytogenes-infected macrophages.

Ly49 receptors in rodents, like KIRs in humans, regulate NK cell activity. Although inhibitory Ly49 receptors clearly recognize MHC-I molecules, ligands for the activating Ly49 receptors are less well defined. Here, we show that the activating Ly49s4 and the inhibitory Ly49i4 receptors recognize nonclassical MHC-I molecules on the rat macrophage cell line R2 (RT1(d)).