Vitamin D as Supplemental Therapy for Pneumocystis Pneumonia

The combination of all-trans retinoic acid (ATRA) and primaquine (PMQ) has been shown to be effective for therapy of Pneumocystis pneumonia (PCP). Since a high concentration of ATRA has significant adverse effects, the possibility that vitamin D can be used to replace ATRA for PCP therapy was investigated. C57BL/6 mice were immunosuppressed by depleting CD4+ cells and infected with Pneumocystis murina 1 week after initiation of immunosuppression. Three weeks after infection, the mice were treated orally for 3 weeks with vitamin D3 (VitD3) alone, PMQ alone, a combination of VitD3 and PMQ (VitD3-PMQ), or a combination of trimethoprim and sulfamethoxazole (TMP-SMX). Results showed that VitD3 (300 IU/kg/day) had a synergistic effect with PMQ (5 mg/kg/day) for therapy of PCP. Flow cytometric studies showed that this VitD3-PMQ combination recovered the CD11blow CD11chigh alveolar macrophage population in mice with PCP as effectively as TMP-SMX. The VitD3-PMQ combination also reduced the massive infiltration of inflammatory cells into the lungs and the severity of lung damage. VitD3 was also shown to reduce the dose of TMP-SMX required for effective treatment of PCP. Taken together, results of this study suggest that a VitD3-PMQ combination can be used as an alternative therapy for PCP

Androgen action via testicular arteriole smooth muscle cells is important for leydig cell function, vasomotion and testicular fluid dynamics

Regulation of blood flow through the testicular microvasculature by vasomotion is thought to be important for normal testis function as it regulates interstitial fluid (IF) dynamics which is an important intra-testicular transport medium. Androgens control vasomotion, but how they exert these effects remains unclear. One possibility is by signalling via androgen receptors (AR) expressed in testicular arteriole smooth muscle cells. To investigate this and determine the overall importance of this mechanism in testis function, we generated a blood vessel smooth muscle cell-specific AR knockout mouse (SMARKO). Gross reproductive development was normal in SMARKO mice but testis weight was reduced in adulthood compared to control littermates; this reduction was not due to any changes in germ cell volume or to deficits in testosterone, LH or FSH concentrations and did not cause infertility. However, seminiferous tubule lumen volume was reduced in adult SMARKO males while interstitial volume was increased, perhaps indicating altered fluid dynamics; this was associated with compensated Leydig cell failure. Vasomotion was impaired in adult SMARKO males, though overall testis blood flow was normal and there was an increase in the overall blood vessel volume per testis in adult SMARKOs. In conclusion, these results indicate that ablating arteriole smooth muscle AR does not grossly alter spermatogenesis or affect male fertility but does subtly impair Leydig cell function and testicular fluid exchange, possibly by locally regulating microvascular blood flow within the testis

RAFT-based polystyrene and polyacrylate melts under thermal and mechanical stress

Although controlled/living radical polymerization processes have significantly facilitated the synthesis of well-defined low polydispersity polymers with specific functionalities, a detailed and systematic knowledge of the thermal stability of the products-highly important for most industrial processes-is not available. Linear polystyrene (PS) carrying a trithiocarbonate mid-chain functionality (thus emulating the structure of the Z-group approach via reversible addition-fragmentation chain transfer (RAFT) based macromolecular architectures) with various chain lengths (20 kDa ≤ Mn,SEC ≤ 150 kDa, 1.27 ≤ Crossed D sign = Mw/Mn ≤ 1.72) and chain-end functionality were synthesized via RAFT polymerization. The thermal stability behavior of the polymers was studied at temperatures ranging from 100 to 200 C for up to 504 h (3 weeks). The thermally treated polymers were analyzed via size exclusion chromatography (SEC) to obtain the dependence of the polymer molecular weight distribution on time at a specific temperature under air or inert atmospheres. Cleavage rate coefficients of the mid-chain functional polymers in inert atmosphere were deduced as a function of temperature, resulting in activation parameters for two disparate Mn starting materials (Ea = 115 ± 4 kJ·mol-1, A = 0.85 × 109 ± 1 × 109 s-1, M n,SEC = 21 kDa and Ea = 116 ± 4 kJ·mol -1, A = 6.24 × 109 ± 1 × 109 s-1, Mn,SEC = 102 kDa). Interestingly, the degradation proceeds significantly faster with increasing chain length, an observation possibly associated with entropic effects. The degradation mechanism was explored in detail via SEC-ESI-MS for acrylate based polymers and theoretical calculations suggesting a Chugaev-type cleavage process. Processing of the RAFT polymers via small scale extrusion as well as a rheological assessment at variable temperatures allowed a correlation of the processing conditions with the thermal degradation properties of the polystyrenes and polyacrylates in the melt. © 2013 American Chemical Society.C.B.-K and M.W. gratefully acknowledge financial support from the German Research Council (DFG). M.L.C gratefully acknowledges generous allocations of supercomputing time from the Australian National Computing Facility, financial support from the Australian Research Council (ARC) Centre of Excellence for Free-radical Chemistry and Biotechnology and an ARC Future Fellowship. C.B.-K. acknowledges additional funding from the Karlsruhe Institute of Technology (KIT) in the context of the Helmholtz programs

Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus.

High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides. We used the microarrays to analyze serum samples from SLE patients and found individuals with high chemokine scores had significantly greater reactivity to 13 autoantigens than individuals with low chemokine scores. Our findings demonstrate that multiple autoantibodies, including antibodies to U1-70K and modified histone H2B tails, are associated with IFN dysregulation in SLE. Further, they show the microarrays are capable of identifying autoantibodies associated with relevant clinical manifestations of SLE, with potential for use as biomarkers in clinical practice

Artificial Intelligence and Big Data Innovations: Navigating the Technology World of the near Future

The following is a transcript of a 2018 Federalist Society panel entitled Technology, Social Media, and Professional Ethics. The panel originally occurred on November 15, 2018 during the National Lawyers Convention in Washington, D.C. The panelists were: Hon. Andrei lancu, Under Secretary of Commerce for Intellectual Property and Director of the U.S. Patent Trademark Office; Ognian Oggie Shentov, Of Counsel, Jones Day; Hon. Michelle K. Lee, Former Under Secretary of Commerce for Intellectual Property and Director of the U.S. Patent and Trademark Office; Shawn D. Hamacher, Assistant General Counsel, Steelcase; and James C. Cooper, Deputy Director for Economic Analysis, Bureau of Consumer Protection, Federal Trade Commission. The moderator was the Honorable David J. Porter of the United States Court of Appeals for the Third Circuit

Characterization of Biochars Produced From Peanut Hulls and Pine Wood with Different Pyrolysis Conditions

Background Application of modern biomass pyrolysis methods for production of biofuels and biochar is potentially a significant approach to enable global carbon capture and sequestration. To realize this potential, it is essential to develop methods that produce biochar with the characteristics needed for effective soil amendment. Methods Biochar materials were produced from peanut hulls and pine wood with different pyrolysis conditions, then characterized by cation exchange (CEC) capacity assays, nitrogen adsorption–desorption isotherm measurements, micro/nanostructural imaging, infrared spectra and elemental analyses. Results Under a standard assay condition of pH 8.5, the CEC values of the peanut hull-derived biochar materials, ranging from 6.22 to 66.56 cmol kg−1, are significantly higher than those of the southern yellow pine-derived biochar, which are near zero or negative. The biochar produced from peanut hulls with a steam activation process yielded the highest CEC value of 66.56 cmol kg−1, which is about 5 times higher than the cation exchange capacity (12.51 cmol kg−1) of a reference soil sample. Notably, biochar produced from peanut hulls with batch barrel retort pyrolysis also has a much higher CEC value (60.12 cmol kg−1) than that (12.45 cmol kg−1) from Eprida’s H2-producing continuous steam injection process. The CEC values were shown to correlate well with the ratios of oxygen atoms to carbon atoms (O:C ratios) in the biochar materials. The higher O:C ratio in a biochar material may indicate the presence of more hydroxyl, carboxylate, and carbonyl groups that contribute to a higher CEC value for the biochar product. In addition, the increase in surface area can also play a role in increasing the CEC value of biochar, as in the case of the steam activation char. Conclusion Comparison of characterization results indicated that CEC value is determined not only by the type of the source biomass materials but also by the pyrolysis conditions. Biochar with the desirable characteristics of extremely high surface area (700 m2/g) and cation exchange capacity (\u3e 60 cmol kg) was created through steam activation

A Community-Based Obesity Prevention Program Decreased the Body Mass Index of University-Affiliated Participants

Obesity is a national health concern and the focus of many health promotion programs. The purpose of this study was to evaluate the behavioral impact of a 12-week obesity prevention program on a university campus. Participants were provided questionnaires with weights, heights, and body mass indices (BMIs) determined at the pre-phase weigh-in and post-phase weigh-out. At the weigh-in, participants received pedometers and information about upcoming educational sessions to assist them with reaching their health behavior goals. A total of 247 (38.2% of 646) individuals (79.4% women) completed the program. A mean weight loss of 1.8 kg caused a decrease in BMI from 29.3 at weigh-in to 28.7 at weigh-out (p = .002). Pre- and post-questionnaires indicated increases (p \u3c 0.001) in physical activity; using pedometers; and intakes of fruits, vegetables, and water at the end of the program. The 6-month follow-up questionnaire (33.2% response rate) indicated healthy habits were being maintained for fruit and vegetable consumption. Further intervention development to incorporate innovative strategies for promoting healthy behaviors among students and employees on university campuses could help decrease the prevalence of obesity

Agreement of self-reported physician diagnosis of migraine with international classification of headache disorders-II migraine diagnostic criteria in a cross-sectional study of pregnant women

Background: Migraine, a common chronic-intermittent disorder among reproductive age women, has emerged as a novel risk factor for adverse perinatal outcomes. Diagnostic reliability of self-report of physician-diagnosed migraine has not been investigated in pregnancy cohort studies. We investigated agreement of self-report of physician-diagnosed migraine with the diagnostic criteria promoted by the International Classification of Headache Disorders, 2nd edition (ICHD-II). Methods: The cross-sectional study was conducted among 500 women who provided information on a detailed migraine questionnaire that allowed us to apply all ICHD-II diagnostic criteria. Results: Approximately 92% of women reporting a diagnosis of migraine had the diagnosis between the ages of 11 and 40 years (40 years 1.0%). We confirmed self-reported migraine in 81.6% of women when applying the ICHD-II criteria for definitive migraine (63.1%) and probable migraine (18.5%). Conclusion: There is good agreement between self-reported migraine and ICHD-II-based migraine classification in this pregnancy cohort. We demonstrate the feasibility of using questionnaire-based migraine assessment according to full ICHD-II criteria in epidemiological studies of pregnant women

3D Symmetry Measure Invariant to Subject Pose During Image Acquisition

In this study we evaluate the influence of subject pose during image acquisition on quantitative analysis of breast morphology. Three (3D) and two-dimensional (2D) images of the torso of 12 female subjects in two different poses; (1) hands-on-hip (HH) and (2) hands-down (HD) were obtained. In order to quantify the effect of pose, we introduce a new measure; the 3D pBRA (Percentage Breast Retraction Assessment) index, and validate its use against the 2D pBRA index. Our data suggests that the 3D pBRA index is linearly correlated with the 2D counterpart for both of the poses, and is independent of the localization of fiducial points within a tolerance limit of 7 mm. The quantitative assessment of 3D asymmetry was found to be invariant of subject pose. This study further corroborates the advantages of 3D stereophotogrammetry over 2D photography. Problems with pose that are inherent in 2D photographs are avoided and fiducial point identification is made easier by being able to panoramically rotate the 3D surface enabling views from any desired angle