Immune Modulation as Adjunctive Therapy for Pneumocystis pneumonia

Pneumocystis is an opportunistic fungal respiratory pathogen that causes life-threatening pneumonia (Pcp) in patients suffering from defects in cell-mediated immunity, including those with acquired immunodeficiency syndrome (AIDS) and immunosuppression secondary to chemotherapy or organ transplantation. Despite major advances in health care, the mortality associated with Pcp has changed little over the past 25  years. Pcp remains a leading cause of death among HIV infected patients, with mortality rates of 50% or higher for patients developing severe Pcp. In addition, as more potent immunosuppressive therapies are developed for chronic inflammatory diseases, more cases of Pcp are occurring in non-HIV patients and in previously unreported clinical settings. These features highlight the importance of developing a better understanding of the pathogenesis of this disease, and the need to search for new therapeutic strategies to improve the outcome of Pcp patients. Immune-mediated inflammatory responses play an important role in the pathogenesis of Pcp, and may be even more significant in determining the outcome of Pcp than direct damage due to the organism itself. In this review we will summarize the immunopathogenic mechanisms that contribute to Pcp-associated lung injury, and discuss the potential to target these pathways for adjunctive immune modulation therapy for Pcp

Understanding Soybean Plant Population Recommendations for Iowa

Concerns over rapidly escalating seed prices have caused farmers, agronomists, and seed suppliers to revisit soybean planting rates. This publication discusses optimum soybean planting rates in Iowa and surrounding states. This is a must read for those who want to reduce their seed input costshttps://lib.dr.iastate.edu/extension_ag_pubs/1179/thumbnail.jp

What treatments relieve arthritis and fatigue associated with systemic lupus erythematosus?

Q: What treatments relieve arthritis and fatigue associated with systemic lupus erythematosus? A: Hydroxychloroquine and chloroquine improve the arthritis associated with mild systemic lupus erythematosus (SLE)--producing a 50% reduction in arthritis flares and articular involvement--and have few adverse effects (strength of recommendation [SOR]: a, systematic review of randomized controlled trials [RCTs]). Methotrexate reduces arthralgias by as much as 79%, but produces adverse effects in up to 70% of patients (SOR: b, systematic review of RCTs with limited patient-oriented evidence). Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are often used for SLE joint pain (SOR: c, expert opinion). Omega-3 fatty acids may reduce arthritis symptoms by about 35% (SOR: b, RCTs with inconsistent evidence). Abatacept and dehydroepiandrosterone don't produce clinically meaningful improvements in fatigue associated with SLE, and abatacept causes significant adverse effects (SOR: b, posthoc analysis of a single RCT). Aerobic exercise may help fatigue (SOR: b, systematic review with inconsistent evidence)

Alamo Lumber and Texas Usury Law: Playing with Fire in the Usury Forest.

The effect of Alamo Lumber Co. v. Gold, and later cases interpreting third party assumption of debt as interest can be perilous to lenders. Lenders are in the business of offering loans to make money. Lenders achieve profit maximization by charging as much interest as possible in the market. Although economic and market factors are always considerations in a lender’s business, in Texas, lenders must also consider harsh usury laws that restrain the maximum amount of chargeable loan interest. Texas defines interest broadly. Statutes define interest as the receipt of compensation for the detention, forbearance or use of money. The expansive definition of interest often results in usury problems when lenders charge separate fees, other than and in addition to interest, and a court considers these fees to be interest. Additionally, facts surrounding the issuance of loans may result in a courting finding usurious interest, even if interest amounts are not excessive. The Texas Supreme court held in Alamo Lumber that when a lender requires a borrower to accept a third party debt to secure a loan, the debt obligation of the third party is a portion of the borrower’s interest making the loan usurious. While the scenario appears to be straight forward, there are several situations where a court could potentially apply Alamo Lumber in holding a loan usurious. Party’s relationship to the debt, financial analysis, independent consideration, defining debt of another, collateral pledge, contingent obligations, savings clauses, and federal regulations may all affect a courts final ruling interpreting loan conditions as interest. Usury penalties in Texas are severe. Penalty may include three times the usurious interest in addition to potentially forfeiting principal. Lenders must be diligent in reviewing the conditions of their loans to ensure avoidance of usurious claims

Predicting Changes in Bee Assemblages Following State Transitions at North American Dryland Ecotones

Drylands worldwide are experiencing ecosystem state transitions: the expansion of some ecosystem types at the expense of others. Bees in drylands are particularly abundant and diverse, with potential for large compositional differences and seasonal turnover across ecotones. To better understand how future ecosystem state transitions may influence bees, we compared bee assemblages and their seasonality among sites at the Sevilleta National Wildlife Refuge (NM, USA) that represent three dryland ecosystem types (and two ecotones) of the southwestern U.S. (Plains grassland, Chihuahuan Desert grassland, and Chihuahuan Desert shrubland). Using passive traps, we caught bees during two-week intervals from March–October, 2002–2014. The resulting dataset included 302 bee species and 56 genera. Bee abundance, composition, and diversity differed among ecosystems, indicating that future state transitions could alter bee assemblage composition in our system. We found strong seasonal bee species turnover, suggesting that bee phenological shifts may accompany state transitions. Common species drove the observed trends, and both specialist and generalist bee species were indicators of ecosystem types or months; these species could be sentinels of community-wide responses to future shifts. Our work suggests that predicting the consequences of global change for bee assemblages requires accounting for both within-year and among-ecosystem variation

Intrinsic Programming of Alveolar Macrophages for Protective Antifungal Innate Immunity Against Pneumocystis Infection

Invasive fungal infections, including Pneumocystis Pneumonia (PcP), remain frequent life-threatening conditions of patients with adaptive immune defects. While innate immunity helps control pathogen growth early during infection, it is typically not sufficient for complete protection against Pneumocystis and other human fungal pathogens. Alveolar macrophages (AM) possess pattern recognition molecules capable of recognizing antigenic and structural determinants of Pneumocystis. However, this pathogen effectively evades innate immunity to infect both immunocompetent and immunosuppressed hosts, albeit with differing outcomes. During our studies of mouse models of PcP, the FVB/N strain was identified as unique because of its ability to mount a protective innate immune response against Pneumocystis infection. In contrast to other immunocompetent strains, which become transiently infected prior to the onset of adaptive immunity, FVB/N mice rapidly eradicated Pneumocystis before an adaptive immune response was triggered. Furthermore, FVB/N mice remained highly resistant to infection even in the absence of functional T cells. The effector mechanism of innate protection required the action of functional alveolar macrophages, and the adoptive transfer of resistant FVB/N AMs, but not susceptible CB.17 AMs, conferred protection to immunodeficient mice. Macrophage IFNγ receptor signaling was not required for innate resistance, and FVB/N macrophages were found to display markers of alternative activation. IFNγ reprogrammed resistant FVB/N macrophages to a permissive M1 biased phenotype through a mechanism that required direct activation of the macrophage IFNγR. These results demonstrate that appropriately programmed macrophages provide protective innate immunity against this opportunistic fungal pathogen, and suggest that modulating macrophage function may represent a feasible therapeutic strategy to enhance antifungal host defense. The identification of resistant and susceptible macrophages provides a novel platform to study not only the mechanisms of macrophage-mediated antifungal defense, but also the mechanisms by which Pneumocystis evades innate immunity

Enhancing permanganate chemiluminescence detection for the determination of glutathione and glutathione disulfide in biological matrices

Acidic potassium permanganate chemiluminescence enables direct post-column detection of glutathione, but its application to assess the redox state of a wider range of biological fluids and tissues is limited by its sensitivity. Herein we show that the simple on-line addition of an aqueous formaldehyde solution not only enhances the sensitivity of the procedure by two orders of magnitude, but also provides a remarkable improvement in the selectivity of the reagent towards thiols such as glutathione (compared to phenols and amino acids that do not possess a thiol group). This enhanced mode of detection was applied to the determination of glutathione and its corresponding disulfide species in homogenised striatum samples taken from both wild type mice and the R6/1 transgenic mouse model of Huntington\u27s disease, at both 8 and 12 weeks of age. No significant difference was observed between the GSH/GSSG ratios of wild type mice and R6/1 mice at either age group, suggesting that the early disease progression had not significantly altered the intracellular redox environment