Host-Adaptation of Francisella tularensis Alters the Bacterium's Surface-Carbohydrates to Hinder Effectors of Innate and Adaptive Immunity

The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase.SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice.F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development

Adenovirus respiratory infection: significant increase in diagnosis using PCR comparing with antigen detection and culture methods

Adenovirus (AdV) respiratory infections are usually described as being associated with high mortality rates. Laboratory diagnosis is essential for the establishment of the appropriate therapy, and for guiding the implementation of preventive measures in order to prevent the spread of the infection. Aiming to analyze the sensitivity and specificity of the laboratorial diagnosis methods available, we compared antigen detection by indirect immunofluorescence assay (IF), and a specific nested polymerase chain reaction (PCR), to detect AdV in respiratory samples collected from patients admitted to hospital with acute respiratory disease. Positive samples were inoculated into a cell culture to confirm the results. We analyzed 381 samples from the nasopharyngeal aspirates collected during the year 2008; of these, 2.6% tested were positive for adenovirus through IF and 10% through PCR; positive isolation was obtained in 40% and 26% of these cases, respectively. Most infected patients were children under six months of age, and despite of the fact that a significant number of patients required intensive care, the mortality rate was low (5%). In conclusion, molecular methods were found to be useful for rapid diagnosis of adenovirus infections with higher sensitivity than antigen detection; their introduction permitted a significant increase in diagnoses of adenovirus infections

Postpartum Care in the United States - New Policies for a New Paradigm

The article discusses postpartum care in the U.S. Topics discussed include the new paradigm called for postpartum care by the American College of Obstetricians and Gynecologists (ACOG) in 2018; improved care recommendations; and postpartum complications such as pain and bleeding, high blood pressure, and lactation difficulties

Use of contraception before and after a diabetes diagnosis: An observational matched cohort study

AimsTo determine how a diabetes diagnosis affects contraception use.MethodsThis retrospective cohort study used private insurance data from non-pregnant women aged 15-49 years, 2000-2014. We identified women with a new diabetes diagnosis and a control group without diabetes, matched on important potential confounders. We compared rates of prescription or procedural contraception use in the two groups before and after an index date (diabetes diagnosis and outpatient visit, respectively), yielding difference-in-differences estimates of the effect of a diabetes diagnosis on contraception use.ResultsWe identified 75,355 women with a new diabetes diagnosis and 7.5 million women without a diabetes diagnosis. Overall rates of contraception use did not increase in the year after diagnosis (absolute difference-in-difference: 0.4% [99.9% CI, -2.1% to 2.9%]; p < 0.001). In method-specific analyses, there was a decline in estrogen-containing and injectable contraceptives in the year after diagnosis (absolute difference-in-difference: -2.2% [-4.0% to -0.4%] and -0.8% [-1.5% to -0.1%], respectively; p < 0.001); no corresponding increase was noted for intrauterine contraception or subdermal implants.ConclusionsWomen with diabetes are less likely to use contraception after their diabetes diagnosis. Efforts are needed to ensure that women with diabetes receive the counseling and clinical services needed to carefully plan their pregnancies

Parathyroid Hormone-Related Protein for the Treatment of Postmenopausal Osteoporosis: Defining the Maximal Tolerable Dose

Context: PTH is the only approved skeletal anabolic agent for the treatment of human osteoporosis. Unlike PTH, which is a mixed anabolic and catabolic agent, PTHrP displays features suggesting that it may be a pure anabolic agent when intermittently administered. The full dose range of PTHrP is unknown