Craig Technologies (United States)

Background:Predicting recovery following pediatric mild traumatic brain injury (mTBI) remains challenging. The identification of objective biomarkers for prognostic purposes could improve clinical outcomes. Telomere length (TL) has previously been used as a prognostic marker of cellular health in the context of mTBI and other neurobiological conditions. While psychosocial and environmental factors are associated with recovery outcomes following pediatric mTBI, the relationship between these factors and TL has not been investigated. This study sought to examine the relationships between TL and psychosocial and environmental factors, in a cohort of Canadian children with mTBI or orthopedic injury (OI).Methods:Saliva was collected at a postacute (median 7 days) timepoint following injury to assess TL from a prospective longitudinal cohort of children aged 8 to 17 years with either mTBI (n = 202) or OI (n = 90), recruited from 3 Canadian sites. Questionnaires regarding psychosocial and environmental factors were obtained at a postacute follow-up visit and injury outcomes were assessed at a 3-month visit. Univariable associations between TL and psychosocial, environmental, and outcome variables were assessed using Spearman’s correlation. Further adjusted analyses of these associations were performed by including injury group, age, sex, and site as covariates in multivariable generalized linear models with a Poisson family, log link function, and robust variance estimates.Results:After adjusting for age, sex, and site, TL in participants with OI was 7% shorter than those with mTBI (adjusted mean ratio = 0.93; 95% confidence interval, 0.89-0.98; P = .003). As expected, increasing age was negatively associated with TL (Spearman’s r = −0.14, P = .016). Sleep hygiene at 3 months was positively associated with TL (adjusted mean ratio = 1.010; 95% confidence interval, 1.001-1.020; P = .039).Conclusion:The relationships between TL and psychosocial and environmental factors in pediatric mTBI and OI are complex. TL may provide information regarding sleep quality in children recovering from mTBI or OI; however, further investigation into TL biomarker validity should employ a noninjured comparison group.

Au cours des dix dernieres annees, le probleme du trafic illicite des especes sauvages est devenu tres grave, mais, face a cette menace, les autorites ont repondu a l’appel, redoublant d’efforts pour corriger la situation. Pour mener a bien leur action, elles doivent souvent saisir et confisquer des especes sauvages, qu’il s’agisse de plantes, d’animaux ou de champignons. Bien que ces confiscations concernent parfois des specimens non vivants faisant partie d’objets, de produits alimentaires ou de produits medicamenteux, elles touchent souvent des especes vivantes. Sachant que les confiscations se font de plus en plus frequentes et portent souvent sur un grand nombre d’individus, il est important d’adopter des approches fondees sur les bonnes pratiques pour prioriser la conservation et assurer la sauvegarde de ces plantes et animaux. Ces lignes directrices sont destine a fournir une orientation en la matiere.

cardiovascular disease cholesterol, LDL-cholesterol diabetes mellitus drug therapy hydroxymethylglutaryl-CoA reductase inhibitors/statins hypercholesterolemia lipids patient compliance primary prevention risk assessment risk reduction discussion risk treatment discussion, secondary prevention ezetimibe proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9) inhibitors

Objective: Angiotensinogen (AGT) is the only substrate of the renin-angiotensin system to generate angiotensin peptides, including angiotensin II (AngII), a critical contributor to atherosclerosis. AGT interacts with megalin in proximal convoluted tubules of kidney. The purpose of this study was to determine effects of megalin on AGT, AngII, and atherosclerosis in mice. Methods and Results: Male C57BL/6 mice were injected subcutaneously with vehicle (PBS) or megalin second generation antisense oligonucleotides (ASO) for 5 weeks. Inhibition of megalin was confirmed by more than 80% reduction of megalin mRNA in kidney. Urine was collected using metabolic cages after 5 weeks of vehicle or ASO injections. At termination, blood was collected with EDTA and protease inhibitor cocktail to measure plasma concentrations of renin and AngII, respectively. Urine AGT and renin concentrations were profoundly increased, accompanied by reduction of renal, but not plasma, AngII production. To determine whether megalin inhibition influences atherosclerosis, male LDL receptor -/- mice were injected with vehicle, control ASO, or megalin ASO for 13 weeks. Western diet was started 1 week after the first injection and continued for 12 weeks. Atherosclerosis was quantified by en face analysis of the aortic intimal surface from the ascending aorta to 3 mm proximal to the left subclavian artery branch. Megalin ASO administration led to more than 70% reductions of megalin mRNA in kidney. Consistent with the effects in C57BL/6 mice, AGT concentrations were significantly higher in urine (Vehicle, control ASO and megalin ASO groups: 85 ± 10, 109 ± 71, and 4616 ± 637 ng/ml, respectively; P<0.001 by one way ANOVA with Holm-Sidak method). Plasma total cholesterol concentrations did not differ among groups. Megalin inhibition reduced atherosclerotic lesion area compared to the other two groups (Percent lesion area in Vehicle, control ASO and megalin ASO groups: 23 ± 2, 20 ± 2, 12 ± 1 %, respectively; P < 0.001 by one way ANOVA with Holm-Sidak method). Conclusions: Inhibition of megalin increased urine AGT and renin, reduced renal AngII concentrations, and diminished hypercholesterolemia-induced atherosclerosis in mice.

Objective: Recent data point to an important immunomodulatory role for neural guidance molecules, including semaphorin 3a (Sema-3A), in inflammatory diseases. Sema-3A is a secreted member of the Sema family and is produced by several immune cells including macrophages. We found that Sema-3A receptors are expressed in macrophages and in atherosclerotic plaques. Approach and results: To investigate the role of Sema-3A in atherosclerosis, ApoE-/- mice were administered with a Sema-3A overexpressing or a control plasmid and were fed a high fat diet for 9 weeks. Sema-3A receptors were expressed in macrophages and atherosclerotic plaques. Our results show that Sema-3A overexpressing mice had significantly smaller atherosclerotic plaques than control mice in the aortic sinus (0.3±0.02 vs. 0.4±0.03 mm 2 ), the brachiocephalic artery (0.04±0.01 vs. 0.1±0.01 mm 2 ) and the aorta (9.5±1.4 vs 15.3±2.9%), assessed by oil red O staining. No differences were observed in plaque stability, measured by collagen and smooth muscle cell alpha-actin staining. However, there was significantly less (2-fold) macrophage content in the plaques of Sema-3A compared to control mice, associated with decreased circulating monocytes determined by flow cytometry as cd11b positive and Gr-1 negative cells (4.97±0.74 vs. 7.2±0.62%). To better define the involved mechanisms, we investigated macrophage function In vitro and found that recombinant Sema-3A increased by 4 fold migration of M2 but not M1 macrophages. In addition, active beta-1 integrin expression was significantly enhanced (2-fold) by Sema-3A in human M2 macrophages. Importantly, Sema-3A induced a significant increase (by 50%) of focal adhesion kinase phosphorylation. Conclusions: Our data show that Sema-3A prevents atherosclerotic plaque formation in ApoE -/- mice. This may be due in part to enhanced motility and function of M2 macrophages through regulation of beta-1 integrin.

Environmental and genetic influences cause individuals of a species to differ in size. As they do so, organ size and shape are scaled to available resources whilst maintaining function. The scaling of entire organs has been investigated extensively but scaling within organs remains poorly understood. By making use of the structure of the insect compound eye, we show that different regions of an organ can respond differentially to changes in body size. Wood ant (Formica rufa) compound eyes contain facets of different diameters in different regions. When the animal body size changes, lens diameters from different regions can increase or decrease in size either at the same rate (a ‘grade’ shift) or at different rates (a ‘slope’ shift). These options are not mutually exclusive, and we demonstrate that both types of scaling apply to different regions of the same eye. This demonstrates that different regions within a single organ can use different rules to govern their scaling, responding differently to their developmental environment. Thus, the control of scaling is more nuanced than previously appreciated, diverse responses occurring even among homologous cells within a single organ. Such fine control provides a rich substrate for the diversification of organ morphology.

Recently, NASA Headquarters invited the pacific international space center for exploration systems (PISCES) to become a strategic partner in a new project called “additive construction with mobile emplacement (ACME)”. The goal of this project is to investigate technologies and methodologies for constructing facilities and surface systems infrastructure on the Moon and Mars using planetary basalt and other in situ materials. The first phase of this project was to robotically-build a 20 meter (66-ft) diameter vertical takeoff, vertical landing (VTVL) prototype pad out of local basalt material on the Big Island of Hawaii. This VTVL pad is a technology “proof of concept” demonstration project to show how a robotic precursor mission could viably construct a VTVL pad on a planetary surface. Such VTVL pads can mitigate the effects of a lander rocket engine exhaust plume impinging on the regolith surface, which can cause cratering and high speed ejecta. In March 2015 a “lunar sidewalk” construction was first completed in Hilo, Hawaii, which proved that raw crushed Hawaiian basalt could be sintered into modular paver elements. The Hawaiian basalt is very similar to granular materials found on Mars and the Moon. Subsequently, PISCES and the NASA Kennedy space center (KSC) Swamp Works team completed the basalt construction of a tele-operated, robotically-built basalt VTVL pad. Construction was started in October 2015 and successfully completed by the end of December 2015. PISCES and NASA KSC assessed various in situ construction methodologies for the 2015 VTVL pad deployment demonstration using additive construction with Hawaiian basalt regolith. Using the PISCES robotic rover (named “Helelani”) as the central platform for construction, the team evaluated a variety of technologies for stabilizing the basalt surface, and then selected a sintered inter-locking paver system to meet the requirements. New methods for sintered basalt regolith paver production were developed and a tele-operated paver deployment mechanism (PDM) was developed and installed on the PISCES rover to simulate VTVL pad construction operations during an actual space mission. The rover was tele-operated locally in Hilo, Hawaii, and also from NASA KSC in Florida, which created valuable lessons learned for future space missions requiring a VTVL pad capability.

Introduction: Serum levels of B-type natriuretic peptide (BNP), C-reactive protein (CRP), interleukin-6 (IL-6) and IL-10 are predictors of poor prognosis in patients with heart failure (HF). These biomarkers are detectable in saliva after myocardial infarction; however, they have not been evaluated in patients with HF. Purpose: To describe correlations and agreement between salivary and serum BNP, CRP, IL-6 and IL-10, and determine whether they predict worse NYHA functional class in patients with HF, after controlling for visible levels of oral inflammation. Methods: In this cross-sectional investigation, serum and whole saliva samples were collected from 75 hospitalized patients with HF [57 ± 12 years, 43% female, NYHA Class I (4%), II (43%), and III (53%)] and analyzed using Biosite Triage (BNP) and a Luminex IS100. Levels of oral inflammation were rated by trained research nurses as good, fair, or poor. Spearman’s rho and the Bland Altman method were used to determine salivary-serum correlations and agreement. Logistic regression was used to determine whether each biomarker was a predictor of worse NYHA functional class, controlling for age, gender, and oral inflammation. Results: Median biomarker concentrations were: BNP [serum 361 pg/mL (25th% = 151, 75th% = 777); saliva 9 (4, 29)], CRP [serum 13 ng/mL (6.9, 29.9); saliva 25.6 (5, 51)], IL-6 [serum 19.3 pg/mL (9.1, 38.6); saliva 10.5 (3.7, 28.2)] and IL-10 [serum 64.1 pg/mL (36.2, 135.5); saliva 4.7 (0.1, 20.3)]. There was a strong correlation for serum-salivary CRP (rs = 0.594, p < .001), moderate correlation for serum-salivary IL-6 (rs = 0.288, p = .037), and no correlations between serum-salivary BNP and IL-10. The Bland Altman test showed good serum-salivary agreement for all biomarkers, but as serum concentrations rose, salivary measures underestimated serum levels. In logistic regressions, none of the biomarkers predicted NYHA functional class, but oral inflammation was a predictor of worse functional class in 6 of 8 regression models. Conclusions: Salivary CRP and IL-6 correlated with serum measures; however, only oral inflammation- not biomarkers- predicted worse functional class. Prospective studies are needed to explore the relationship between oral health and outcomes in patients with HF.

Introduction: Our laboratory has shown that Axl, a receptor tyrosine kinase, is important in both vascular and immune functions during deoxycorticosterone acetate (DOCA)-salt hypertension. We hypothesized that Axl activity specifically in T lymphocytes could explain the dependence of hypertension on Axl. Methods and Results: We did adoptive transfers of either Axl+/+ or Axl-/- CD4+ T cells to RAG1-/- mice that lack mature T cells. Once CD4+ T cell repopulations were confirmed, we induced DOCA-salt hypertension for 6 weeks. Systolic blood pressure (BP, mmHg) increased by 20±5 in Axl+/+RAG-/- mice after DOCA-salt, but Axl-/- RAG-/- mice had increases in BP by only 6+3 after 6 weeks of DOCA-salt. We isolated naïve CD4+ T cells from both Axl+/+ and Axl-/- littermates and primed them under either Th1 or Th2 polarizing conditions in culture. Production of interferon gamma (IFN-γ ng/mL) was significantly decreased (-23%, p<0.05) in Axl-/- (396±23) compared to Axl+/+ (512±42) under Th1-priming. However, Axl had no effect on interleukin 4 (IL-4, ng/mL) production under Th2 polarizing conditions. Intracellular staining of the Th1/Th2 cells with IFN-γ and IL-4 antibodies by flow cytometry confirmed expression of cytokines in culture media. Complete blood counts showed that Axl-/- mice had significantly lower white blood cells due to decreased numbers of lymphocytes (4.5±0.7x10 9 ) compared to Axl+/+ mice (7.8±0.7x10 9 ). We found a higher population of AnnexinV (marker of early apoptosis)-positive peripheral leukocytes in Axl-/- mice (10±1%) compared to Axl+/+ (4±1%) by flow cytometry; while the percentages of dead cells (~10%) were similar between Axl+/+ and Axl-/- mice. Conclusions: Altogether we show that expression of Axl by T cells drives salt-induced hypertension. The mechanism of Axl-dependent effects on T cells occurs via T-cell-dependent expression of the pro-inflammatory cytokine IFN-γ. In addition, Axl plays a role in inhibiting lymphocyte apoptosis in the circulation. Future work will focus on how Axl expression in T cells affects T cell-dependent vascular remodeling during hypertension.