Prophylactic anti-cytomegalovirus hyperimmunoglobulin in critically ill liver transplant patients: impact on early immunology and survival

Background: Anti-cytomegalovirus hyperimmunoglobulin (CMVIg) was shown to provide beneficial immunodulatory properties beyond antiviral efficacies. The aim of this retrospective study was to assess the impact of prophylactic CMVIg treatment on early outcome following liver transplantation (LT) in critically ill patients. Methods: Forty-three cirrhotic patients requiring pre-LT intensive care due to multiorgan failure were analyzed. Twenty-eight patients with enhanced CMV risk (D+/R+; D+/R−; D−/R+) received prophylactic CMVIg for a minimum of 7 days, while 15 patients (D−/R−) did not. Results: Post-transplantation rates of intra-abdominal infections (28% vs. 61.1%; p = 0.03), Epstein–Barr virus infections (0% vs. 33.3%; p = 0.034), allograft rejections (0% vs. 22.2%; p = 0.013) and sepsis-related mortality (4% vs. 27.8%; p = 0.026) were significantly lower, whereas incidence of CMV infections (4% vs. 22.2%; p = 0.066) tended to be lower in the CMVIg subset. In multivariate analysis, only pretransplant elevated serum lactate level (hazard ratio = 34.63; p = 0.009) and absence of CMVIg therapy (hazard ratio = 21.76; p = 0.023) were identified as independent promoters of 3-month mortality. Conclusion: Prophylactic treatment with CMVIg reduces predisposition for severe immunological and septic events and, thereby, early mortality in critically ill liver recipients

Hin-mediated DNA knotting and recombining promote replicon dysfunction and mutation

<p>Abstract</p> <p>Background</p> <p>The genetic code imposes a dilemma for cells. The DNA must be long enough to encode for the complexity of an organism, yet thin and flexible enough to fit within the cell. The combination of these properties greatly favors DNA collisions, which can knot and drive recombination of the DNA. Despite the well-accepted propensity of cellular DNA to collide and react with itself, it has not been established what the physiological consequences are.</p> <p>Results</p> <p>Here we analyze the effects of recombined and knotted plasmids in <it>E. coli </it>using the Hin site-specific recombination system. We show that Hin-mediated DNA knotting and recombination (i) promote replicon loss by blocking DNA replication; (ii) block gene transcription; and (iii) cause genetic rearrangements at a rate three to four orders of magnitude higher than the rate for an unknotted, unrecombined plasmid.</p> <p>Conclusion</p> <p>These results show that DNA reactivity leading to recombined and knotted DNA is potentially toxic and may help drive genetic evolution.</p

Olfactory Behavioral Testing in the Adult Mouse

The rodent olfactory system is of increasing interest to scientists, studied, in part, in systems biology because of its stereotyped, yet accessible circuitry. In addition, this area's unique ability to generate new neurons throughout an organism's lifetime makes it an attractive system for developmental and regenerative biologists alike. Such interest necessitates a means for a quick, yet reliable assessment of olfactory function. Many tests of olfactory ability are complex, variable or not specifically designed for mice. Also, some tests are sensitive to memory deficits as well as defects in olfactory abilities, confounding obtained results

Animal Agriculture in a Changing Climate Online Course: An Effective Tool for Creating Extension Competency

There is a need to create competency among Extension professionals on the topic of climate change adaptation and mitigation in animal agriculture. The Animal Agriculture in a Changing Climate online course provides an easily accessible, user-friendly, free, and interactive experience for learning science-based information on a national and regional level. The web-based curriculum is proving to be a useful tool and valuable resource for Extension educators in gaining knowledge and being better equipped to inform and influence livestock and poultry producers regarding climate issues

Sex Hormone-Binding Globulin Levels Are Inversely Associated With Nonalcoholic Fatty Liver Disease in HIV-Infected and -Uninfected Men.

BackgroundNonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease worldwide. Elevated sex hormone-binding globulin (SHBG) levels have been observed in the setting of HIV and may protect against some metabolic disorders. We aimed to investigate whether higher SHBG levels may protect against NAFLD in men with/without HIV.MethodsNAFLD was assessed using noncontrast computed tomography in 530 men in the Multicenter AIDS Cohort Study (MACS) who drank &lt;3 alcoholic drinks/d and were uninfected with chronic hepatitis C or B (340HIV+, 190HIV-). Morning serum samples were tested for SHBG, total testosterone (TT), and adiponectin. Multivariable logistic regression was used to assess associations between HIV, SHBG, TT, adiponectin, and NAFLD.ResultsMedian SHBG was highest among HIV+/NAFLD- men and lowest among HIV-/NAFLD+ men. Adjusted for demographics, HIV, visceral adiposity, HOMA-IR, TT, and PNPLA3 genotype, higher SHBG was associated with lower odds of NAFLD (odds ratio [OR], 0.52 per doubling; 95% confidence interval [CI], 0.34-0.80). In separate multivariable models without SHBG, HIV (OR, 0.46; 95% CI, 0.26-0.79) and higher adiponectin (OR, 0.66 per doubling; 95% CI, 0.49-0.89) were associated with lower NAFLD odds, whereas TT was not significantly associated (OR, 0.74 per doubling; 95% CI, 0.53-1.04). Adjusting for SHBG attenuated the associations of HIV (OR, 0.61; 95% CI, 0.34-1.08) and adiponectin (OR, 0.74; 95% CI, 0.54-1.02) with NAFLD.ConclusionsSHBG levels were higher among HIV+ men, were independently associated with lower NAFLD, and could partially explain the associations of HIV and higher adiponectin with lower NAFLD in our cohort. These findings suggest that SHBG may protect against NAFLD, supporting further prospective and mechanistic studies

Combining F-18-FDG positron emission tomography with Up-to-seven criteria for selecting suitable liver transplant patients with advanced hepatocellular carcinoma

The Up-to-seven (UTS) criteria (sum of tumor size and number not exceeding 7) for indicating liver transplantation (LT) in hepatocellular carcinoma (HCC) were originally based on explant pathology features and absence of microvascular invasion (MVI). F-18-fludeoxyglucose (F-18-FDG) positron emission tomography (PET) was shown to indicate the risk of MVI and tumor recurrence. The aim of this study was to analyze the prognostic significance of the clinical UTS criteria when being combined with PET-status of the tumor. Data of 116 liver transplant patients were subject to retrospective analysis. Five-year recurrence-free survival (RFS) rates in patients meeting (n = 85) and exceeding (n = 21) the radiographic UTS criteria were 81% and 55.1%, respectively (p = 0.014). In the UTS In subset, RFS was significantly better in PET-negative (94.9%) than in PET-positive patients (48.3%;p < 0.001). In the UTS Out subset, 5-year RFS rates were 87.1% and 19% in patients with non-F-18-FDG-avid and F-18-FDG-avid tumors (p < 0.001), respectively. Positive PET-status was identified as the only independent clinical predictor of tumor recurrence in beyond UTS patients (Hazard ratio [HR] 19.25;p < 0.001). Combining radiographic UTS criteria with FDG-PET may safely expand the HCC selection criteria for LT

Trehalose Uptake through P2X7 Purinergic Channels Provides Dehydration Protection

The tetra-anionic form of ATP (ATP4-) is known to induce monovalent and divalent ion fluxes in cells that express purinergic P2X7 receptors (Steinberg et al., 1987; Sung et al., 1985), and with sustained application of ATP it has been shown that dyes as large as 831 daltons can permeate the cell membrane (Steinberg et al, 1987). The current study explores the kinetics of loading α,α-trehalose (342 daltons) into ATP stimulated J774.A1 cells, which are known to express the purinergic P2X7 receptor (Steinberg et al., 1987). Cells that were incubated at 37 ̊C in a 50 mM phosphate buffer (pH 7.0) contailing 225 mM trehalose and 5 mM ATP, were shown to load trehalose linearly over time. Concentrations of ~50 mM were reached within 90 min of incubation. Cells incubated in the same solution at 4 ̊C loaded minimally, consistent with the inactivity of the receptor at low temperatures. However, extended incubation at 37 oC (\u3e60 min) resulted in zero next-day survival, with adverse effects appearing even with incubation periods as short as 30 min. By using a two-step protocol with a short time period at 37 oC to allow pore formation, followed by an extended loading period on ice, cells could be loaded with up to 50 mM trehalose while maintaining good next day recovery (49% ± 12 % by Trypan Blue exclusion, 56 ± 20% by Alamar BlueTM assay). Cells porated by this method and allowed an overnight recovery period exhibited improved dehydration tolerance suggesting a role for ATP poration in the anhydrous preservation of cells

Cancer testis antigen and interleukin expression correlates with survival in small bowel neuroendocrine tumors

View full abstracthttps://openworks.mdanderson.org/leading-edge/1042/thumbnail.jp