Virogenomics BioDevelopment (United States)

This manuscript reports the rare case of a pediatric patient with a nasal venous malformation (VM) with intracranial communication and bilateral internal jugular vein (IJV) occlusion. Due to the IJV occlusion, the nasal VM provided collateral circulation for blood drainage from the patient's brain. Spontaneous recanalization of the IJVs was reported in the patient, potentially allowing for new treatment modalities, as the nasal VM would be responsible for less collateral venous outflow. A literature review was conducted to identify the incidence of spontaneous recanalization of the jugular venous system. Through 3 databases, 413 peer-reviewed journal articles were obtained for the systematic review. After eliminating duplicate articles and screening titles, abstracts, and full texts, 4 articles were included in the final literature review. The level of evidence from the literature review was relatively low. All 4 articles identified in the literature review were case reports of spontaneous recanalization of thrombotic events. In our patient, spontaneous recanalization of IJV occlusion allowed for consideration of treatment options (ie, surgical excision) of a nasal VM, which otherwise provided critical venous drainage for the patient's brain. If flow through the IJVs is not sufficient, balloon angioplasty, patch angioplasty, or possible reconstruction of the IJVs may be necessary to allow for treatment of the nasal VM. If these surgical interventions prove to be too high-risk for the patient, conservative therapy may be the best option.

IntroductionCurrently, there are no FDA-approved medications to treat methamphetamine addiction, including the inflammatory, neurotoxic, and adverse neuropsychiatric effects. We have shown that partial (p)MHC class II constructs (i.e., Recombinant T-cell receptor Ligand – RTL1000), comprised of the extracellular α1 and β1 domains of MHC class II molecules linked covalently to myelin oligodendrocyte glycoprotein (MOG)-35-55 peptide, can address the neuroimmune effects of methamphetamine addiction through its ability to bind to and down-regulate CD74 expression, block macrophage migration inhibitory factor (MIF) signaling, and reduce levels of pro-inflammatory chemokine ligand 2 (CCL2). The present study evaluated the effects of our third-generation pMHC II construct, DRmQ, on cognitive function and concentration of inflammatory cytokines in the frontal cortex, a region critical for cognitive functions such as memory, impulse control, and problem solving.MethodsFemale and male C57BL/6J mice were exposed to methamphetamine (or saline) via subcutaneous (s.c.) injections administered four times per day every other day for 14 days. Following methamphetamine exposure, mice received immunotherapy (DRmQ or ibudilast) or vehicle s.c. injections daily for five days. Cognitive function was assessed using the novel object recognition test (NORT). To evaluate the effects of immunotherapy on inflammation in the frontal cortex, multiplex immunoassays were conducted. ANOVA was used to compare exploration times on the NORT and immune factor concentrations.ResultsPost hoc analysis revealed increased novel object exploration time in MA-DRmQ treated mice, as compared to MA-VEH treated mice (non-significant trend). One-way ANOVA detected a significant difference across the groups in the concentration of macrophage inflammatory protein-2 (MIP-2) (p = 0.03). Post hoc tests indicated that mice treated with methamphetamine and DRmQ or ibudilast had significantly lower levels of MIP-2 in frontal cortex, as compared to mice treated with methamphetamine and vehicle (p > 0.05).DiscussionBy specifically targeting CD74, our DRQ constructs can block the signaling of MIF, inhibiting the downstream signaling and pro-inflammatory effects that contribute to and perpetuate methamphetamine addiction.

Serious games (SGs) are interactive and entertaining software designed primarily with an educational purpose. This systematic review synthesizes evidence from experimental studies regarding the efficacy of SGs for supporting engagement and improving learning outcomes in healthcare professions education. Randomized controlled trials (RCTs) published between January 2005 and April 2019 were included. Reference selection and data extraction were performed in duplicate, independently. Thirty-seven RCTs were found and 29 were included in random-effect meta-analyses. Compared with other educational interventions, SGs did not lead to more time spent with the intervention {mean difference 23.21 minutes [95% confidence interval (CI) = -1.25 to 47.66]}, higher knowledge acquisition [standardized mean difference (SMD) = 0.16 (95% CI = -0.20 to 0.52)], cognitive [SMD 0.08 (95% CI = -0.73 to 0.89)], and procedural skills development [SMD 0.05 (95% CI = -0.78 to 0.87)], attitude change [SMD = -0.09 (95% CI = -0.38 to 0.20)], nor behavior change [SMD = 0.2 (95% CI = -0.11 to 0.51)]. Only a small SMD of 0.27 (95% CI = 0.01 to 0.53) was found in favor of SGs for improving confidence in skills.

The receptor-like tyrosine phosphatase CD45 regulates antigen receptor signaling by dephosphorylating the C-terminal inhibitory tyrosine of the src family kinases. However, despite its abundance, the function of the large, alternatively spliced extracellular domain of CD45 has remained elusive. We used normally spliced CD45 transgenes either incorporating a phosphatase-inactivating point mutation or lacking the cytoplasmic domain to uncouple the enzymatic and noncatalytic functions of CD45 in lymphocytes. Although these transgenes did not alter T-cell signaling or development irrespective of endogenous CD45 expression, both partially rescued the phenotype of CD45-deficient B cells. We identify a noncatalytic role for CD45 in regulating tonic, but not antigen-mediated, B-cell antigen receptor (BCR) signaling through modulation of the function of the inhibitory coreceptor CD22. This finding has important implications for understanding how naïve B cells maintain tonic BCR signaling while restraining inappropriate antigen-dependent activation to preserve clonal "ignorance."

Microsymposia C199 MScases causes problems during complementary SEM/EDS analyses when the sample is not transferred onto a different sample holder with regard to minimization of risk of its damage, loss or contamination.Therefore monocrystalline silicon plates with indicated conductivity of 5 Ω.cm -1 were tested in practice.This value is sufficient for SEM (based on measurements -carbon conductive strips specially intended for SEM have the conductivity of approx.500 kΩ and higher).The plates with thickness of 300µm (±15µm) can also be used for subsequent direct FTIR analysis even in transmission mode, without the need of plate exchange.A method employing the image analysis system was introduced for precise sample adjustment for microdiffraction and the choice of the area to be measured.The trace of the primary beam on a fluorescent disc was scanned for different angles 2theta and subsequently saved as binary overlay images.A camera reads the live image of the sample through the focusing microscope and the operator can choose a spot for the analysis in ergonomic conditions (the second monitor was placed directly into the diffractometer chamber).This procedure is very convenient for heterogeneous samples, various abrasions, etc.The system is further used for quantitative drug analysis.Both Rietveld method or method with the scale factor and the RIR (Reference Intensity Ratio) values (also called I/Ic values) are used.The results are cross-checked by standard methods of organic analysis (GCMS, FTIR), XRD analysis, in addition, enables precise phase analysis of inorganic components.

Este artigo apresenta um estudo do desempenho térmico dos edifícios do novo centro de pesquisas da Petrobras, CENPES II, no Rio de Janeiro, incluindo edifícios naturalmente ventilados e edifícios condicionados artificialmente. O projeto foi objeto de um concurso nacional em 2004, com um programa de 100.000m2 e dez edifícios. O edital propôs quatro edifícios naturalmente ventilados e outros seis artificialmente climatizados, pelas exigências do uso e especificidades da função. Nos edifícios com ventilação natural foi aplicado um modelo adaptativo de conforto térmico e as avaliações de desempenho foram realizadas com o suporte de ferramentas avançadas de simulação computacional. Na maioria dos ambientes com ventilação natural encontrou-se condições similares ao clima externo à sombra, comprovando a adequação da arquitetura ao clima. Nos ambientes de trabalho em que a climatização artificial foi colocada como premissa foi identificado, inicialmente, um potencial de 30% de ventilação natural durante as horas de ocupação, justificando a verificação das possibilidades do modo-misto de climatização.

In post hoc analyses, to examine in low perceived social support (LPSS) patients enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial (n = 1503), the pattern of social support following myocardial infarction (MI), the impact of psychosocial intervention on perceived support, the relationship of perceived support at the time of MI to subsequent death and recurrent MI, and the relationship of change in perceived support 6 months after MI to subsequent mortality. Partner status (partner, no partner) and score (<12 = low support; >12 = moderate support) on the ENRICHD Social Support Instrument (ESSI) were used post hoc to define four levels of risk. The resulting 4 LPSS risk groups were compared on baseline characteristics, changes in social support, and medical outcomes to a group of concurrently enrolled acute myocardial infarction patients without depression or LPSS (MI comparison group, n = 408). Effects of treatment assignment on LPSS and death/recurrent MI were also examined. All 4 LPSS risk groups demonstrated improvement in perceived support, regardless of treatment assignment, with a significant treatment effect only seen in the LPSS risk group with no partner and moderate support at baseline. During an average 29-month follow-up, the combined end point of death/nonfatal MI was 10% in the MI comparison group and 23% in the ENRICHD LPSS patients; LPSS conferred a greater risk in unadjusted and adjusted models (HR = 1.74-2.39). Change in ESSI score and/or improvement in perceived social support were not found to predict subsequent mortality. Baseline LPSS predicted death/recurrent MI in the ENRICHD cohort, independent of treatment assignment. Intervention effects indicated a partner surrogacy role for the interventionist and the need for a moderate level of support at baseline for the intervention to be effective.

We evaluated the contribution of darkfield and epi-polarization microscopy to the detection of leukocyte cell surface antigens with immunogold-silver staining (IGSS). Lymphocyte cell surface differentiation antigens were labeled with monoclonal antibodies and IGSS as described for brightfield microscopy. In darkfield and epi-polarization microscopy the labeling appeared as bright spots on a dark background. The sensitivity of detection was much higher than that of brightfield microscopy. Sixteenfold higher dilutions of the monoclonal antibody could be used to detect all cells expressing the antigen in the cell suspension. However, non-specific staining was also better visualized. The latter could be reduced to a level comparable to that of brightfield microscopy only by use of weaker labeling conditions. A 25% reduction of the silver enhancement time was necessary for this purpose. However, these weaker labeling conditions also reduced the intensity of the specific staining. Therefore, the efficiency of IGSS, as detected with darkfield and epi-polarization microscopy, was only fourfold greater than that found with brightfield microscopy or that of an immunofluorescence procedure. Especially in combination with transmitted light, to improve cell identification, epi-polarization microscopy is a reliable and sensitive method for detection of immunogold-silver-labeled cell surface antigens for diagnostic and research purposes.