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

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

Serum 25-hydroxyvitamin D concentrations and risk for hip fractures

BACKGROUND: The relationship between serum 25-hydroxyvitamin D [25(OH) vitamin D] concentration and hip fractures is unclear. OBJECTIVE: To see whether low serum 25(OH) vitamin D concentrations are associated with hip fractures in community-dwelling women. DESIGN: Nested case-control study. SETTING: 40 clinical centers in the United States. PARTICIPANTS: 400 case-patients with incident hip fracture and 400 control participants matched on the basis of age, race or ethnicity, and date of blood draw. Both groups were selected from 39 795 postmenopausal women who were not using estrogens or other bone-active therapies and who had not had a previous hip fracture. MEASUREMENTS: Serum 25(OH) vitamin D was measured and patients were followed for a median of 7.1 years (range, 0.7 to 9.3 years) to assess fractures. RESULTS: Mean serum 25(OH) vitamin D concentrations were lower in case-patients than in control participants (55.95 nmol/L [SD, 20.28] vs. 59.60 nmol/L [SD, 18.05]; P = 0.007), and lower serum 25(OH) vitamin D concentrations increased hip fracture risk (adjusted odds ratio for each 25-nmol/L decrease, 1.33 [95% CI, 1.06 to 1.68]). Women with the lowest 25(OH) vitamin D concentrations (\u3c or =47.5 nmol/L) had a higher fracture risk than did those with the highest concentrations (\u3e or =70.7 nmol/L) (adjusted odds ratio, 1.71 [CI, 1.05 to 2.79]), and the risk increased statistically significantly across quartiles of serum 25(OH) vitamin D concentration (P for trend = 0.016). This association was independent of number of falls, physical function, frailty, renal function, and sex-steroid hormone levels and seemed to be partially mediated by bone resorption. LIMITATIONS: Few case-patients were nonwhite women. Bone mineral density and parathyroid hormone levels were not accounted for in the analysis. CONCLUSION: Low serum 25(OH) vitamin D concentrations are associated with a higher risk for hip fracture

Algoritmo evolucionário para otimização do plano de tratamento em radioterapia conformal 3D

O planejamento do tratamento por radioterapia tem por objetivo atingir um volume alvo com altas doses de radiação tomando cuidado para não expor órgãos sadios a doses elevadas. É, portanto, muito importante que se encontre um balanço ideal entre esses objetivos conflitantes. O presente trabalho relata um modelo de programação matemática multiobjetivo e introduz um Algoritmo Transgenético para o problema de seleção do direcionamento dos feixes de radiação no planejamento em radioterapia conformal 3D. A seleção das direções dos feixes é feita através de uma técnica denominada de isocentros variáveis. Com a finalidade de testar o potencial do algoritmo desenvolvido, realiza-se um experimento comparativo com um Algoritmo Genético Multiobjetivo. O experimento computacional obtém dados quantitativos e qualitativos que são analisados no trabalho.<br>The radiotherapy treatment planning aims to achieve a target volume with high doses of radiation taking care not to expose healthy organs to high doses. It is therefore very important to find an optimal balance between these conflicting goals. This paper reports a mathematical model of multiobjective programming and presents a Transgenetic Algorithm for the problem of selecting the direction of radiation beams in 3D conformal radiotherapy planning. The selection of beams directions is done with a technique called variable isocenters. In order to test the potential of the developed algorithm, a comparative experiment with a multiobjective genetic algorithm was done. The computational experiment obtains quantitative and qualitative data that are analyzed in this paper