Explore the vast range of titles available.

INTRODUCTION:Drug-induced liver injury (DILI) is a leading cause of acute liver injury in the US, most commonly caused by antibiotics and NSAIDS. The clinical history and biochemical pattern are often the most important clues to the diagnosis and a classic pattern can save the patient an invasive procedure such as liver biopsy. It becomes diagnostically challenging when the biochemical presentation is inconsistent with the drug reported, such as in this case.CASE DESCRIPTION/METHODS:A 34-year old Caucasian man presented to the hospital with progressive jaundice, vomiting and malaise. Medical history is remarkable for Ankylosing Spondylitis (AS) for which he is on Secukinumab, and for acute sinusitis diagnosed 23 days prior in clinic for which he completed a 10-day course Amoxicillin-Clavulanate (AC). Liver tests from 15 months prior were normal. Liver tests on presentation were remarkable for total bilirubin of 4.5 mg/dL, AST of 163 U/L, ALT of 449 U/L, and ALP of 132 U/L and peaked at total bilirubin of 12.5mg/dL, AST of 702 U/L, ALT of 1,292 U/L and ALP of 184 U/L. Viral hepatitis panel was notable for Hepatitis A and B immunity and Hepatitis C IgG positive but with undetectable viral load. Autoimmune hepatitis markers were also normal. In view of the progressive uptrend in transaminases despite medication discontinuation, hepatocellular biochemical pattern, and history of autoimmune disease (i.e., AS), autoimmune hepatitis was suspected and a liver biopsy was done. Liver biopsy was notable for mild mixed portal inflammation and bile duct distortion. The overall impression was DILI. He resumed Secukinumab but not AC. Upon follow up one month later, his liver tests completely normalized.DISCUSSION:AC-DILI presents most frequently among elderly men with a cholestatic biochemical pattern and self-limited course. AC-DILI of hepatocellular pattern is rare in adult patients, although more common among pediatric patients. Our report, interestingly, describes a distinct hepatocellular biochemical pattern of AC-DILI in an adult male patient with an underlying autoimmune disease. HLA B-27 allele (class I) is a strong genetic risk factor for the development of AS. Studies have shown that predisposition to AC-DILI is influenced by certain HLA haplotypes perhaps suggesting an involvement of the adaptive immune system. However, further studies are needed to determine whether this association might increase risk for organ injury as in DILI or if it alters the pattern of presentation and expected clinical course.

Biliary complications are a major cause of morbidity following orthotopic liver transplantation with an overall incidence between 11% and 25%. The most common complications are biliary leaks, strictures, and stones. These complications have an impact on graft survival, length of hospital stay, recovery, and overall cost of care. Therefore, knowledge of these complications and their management is important to the practicing gastroenterologist. Historically, biliary complications after liver transplantation have been managed surgically. However, with the growth of therapeutic endoscopic and percutaneous radiologic methods, most of these complications can now be managed less invasively. This article focuses on the incidence, timing, mechanism, and endoscopic management of biliary leak, strictures, stones, sludge, casts, and sphincter of Oddi dysfunction following liver transplantation.

Erythritol, a non-nutritive polyol, is the main component of the artificial sweetener Truvia®. Recent research has indicated that erythritol may have potential as an organic insecticide, given its harmful effects on several insects but apparent safety for mammals. However, for erythritol to have practical use as an insecticide in agricultural settings, it must have neutral to positive effects on crop plants and other non-target organisms. We examined the dose-dependent effects of erythritol (0, 5, 50, 500, 1000, and 2000 mM) on corn (Zea mays) and tomato (Solanum lycopersicum) seedling growth and seed germination. Erythritol caused significant reductions in both belowground (root) and aboveground (shoot) dry weight at and above the typical minimum insecticidal dose (500 mM erythritol) in tomato plants, but not in corn plants. Both corn and tomato seed germination was inhibited by erythritol but the tomato seeds appeared to be more sensitive, responding at concentrations as low as 50 mM erythritol (in contrast to a minimum damaging dose of 1000 mM erythritol for corn seeds). Our results suggest erythritol may have damaging non-target effects on certain plant crops when used daily at the typical doses needed to kill insect pests. Furthermore, if erythritol's damaging effects extend to certain weed species, it also may have potential as an organic herbicide.

Background and aims – Plants display a variety of resistance and tolerance responses to herbivory. Compensation, or changes in growth, allocation, and/or physiology, after damage is one way that plants tolerate herbivory, but geographic patterns in intraspecific plant compensatory responses are understudied. We aimed to study geographic variation in tolerance to herbivory to help explain geographic patterns in the distribution of resistance traits and the relationship between tolerance and resistance traits in common milkweed, Asclepias syriaca . Material and methods – We grew milkweed from 14 different populations in the greenhouse, mechanically applied 25% leaf damage to an experimental group, and compared the control and experimental groups to measure compensatory responses in final biomass, root:shoot ratios, stem investment, and relative growth rate. We compared compensatory responses across populations grouped by latitude and by temperature. Key results – Compared to controls, milkweed plants that were damaged lost mass and expressed reduced root:shoot ratios. However, the effect of damage on total mass, stem investment, and relative growth rate varied among genetic families. In regional contrasts, plants from colder climates grew larger and invested less in stems and roots than plants from warmer climates under control conditions, but they were less able to compensate for damage in terms of biomass. Plants from cold regions also showed a tendency to reduce growth rate and stem investment after damage; whereas, plants from warmer climates tended to increase their growth rate and stem investment in response to damage. Conclusion – While plants from high latitudes and colder climates were less able to compensate for damage than those from lower latitudes, we are not confident that these differences are caused by geographic differences in growth rate, or that they explain differences in resistance to herbivory. Instead, we suspect that differences in the phenology of development in plants from regions with different climates affect the impact of damage and the potential for compensatory growth. Milkweed plants from colder regions with short growing seasons grew larger during our measurement period, while those from regions with longer growing seasons invested more in stems and roots, traits which may have facilitated greater long-term growth, as well as the greater compensatory ability observed in our study. Future studies should explicitly manipulate the timing of damage applied to plants from different regions to test the relationship between phenology and compensation.

Tuberculosis (TB) is a major cause of morbidity and mortality worldwide despite widespread intradermal (ID) BCG vaccination in newborns. We previously demonstrated that changing the route and dose of BCG vaccination from 5×10 CFU ID to 5×10 CFU intravenous (IV) resulted in prevention of infection and disease in a rigorous, highly susceptible non-human primate model of TB. Identifying the immune mechanisms of protection for IV BCG will facilitate development of more effective vaccines against TB. Here, we depleted select lymphocyte subsets in IV BCG vaccinated macaques prior to Mtb challenge to determine the cell types necessary for that protection. Depletion of CD4 T cells or all CD8α expressing lymphoycytes (both innate and adaptive) resulted in loss of protection in most macaques, concomitant with increased bacterial burdens (~4-5 log thoracic CFU) and dissemination of infection. In contrast, depletion of only adaptive CD8αβ+ T cells did not significantly reduce protection against disease. Our results demonstrate that CD4 T cells and innate CD8α+ lymphocytes are critical for IV BCG-induced protection, supporting investigation of how eliciting these cells and their functions can improve future TB vaccines.

Immunological memory elicited either through previous or ongoing (Mtb) infection provides a critical mechanism by which hosts protect against re-infection and disease progression upon Mtb re-exposure. Conversely, the uneven competition between distinct Mtb strains suggest certain bacterial clades have enhanced ability to spread across communities and circulate globally, potentially by evading memory responses gained by prior infection with genomically different strains. To address whether memory responses induced by one strain can protect against a genetically distinct strain, we conducted a heterologous reinfection study in cynomolgus macaques involving primary infection by a Lineage 4 Erdman Mtb strain and subsequent re-challenge by a Lineage 2 strain, HT-L2. Recent epidemiologic studies have shown that the clade to which HT-L2 belongs has been spreading successfully over the last decade in Lima, Peru. Here, through microbiologic, PET-CT imaging and sequencing of Mtb genomic barcodes, we show that reinfected animals developed fewer lung lesions and controlled both pulmonary and disseminated forms of infection better than naïve animals without prior exposure to Mtb. Our data support that protection against reinfection is not limited by Mtb lineage, providing optimism that vaccines can be effective across populations and geographic locations.