Combined Blood Flow Restriction Training and Betaine Supplementation Impacts on Serum Betaine and Homocysteine Concentrations

Homocysteine (HCY) is a clinically implicated in inflammation and cardiovascular impairments. Although both betaine supplementation and acute resistance (both high-load [HL] and low-load blood flow restriction [LL-BFR]) training notably attenuate HCY concentrations, it is hitherto unknown if these independent modalities synergistically interact. PURPOSE: to determine whether a combination of betaine supplementation, as well as acute HL and/or LL-BFR training can attenuate post-exercise HCY more effectively than either isolated modality. METHODS: Eighteen recreationally trained males (25±5y) were randomized in double-blind fashion to supplement 6g/day of either betaine anhydrous (BET) or identically dosed cellulose placebo for 14-days. Subsequently, all subjects performed four standardized sets of one-leg press and two additional sets to muscular failure on both legs in a counter-balanced and crossover design. Specifically, one leg performed standard high-load (HL; 70%1RM) exercise and contralateral limb underwent BFR (LL-BFR; 20%1RM) training at 80% arterial occlusion pressure. Serum homocysteine (HCY) and betaine (BET) concentrations were analyzed before and 30-minutes post-exercise prior to quantification via ELISA and liquid chromatography-mass spectrometry, respectively. The changes in all aforementioned variables from baseline (∆HCY and ∆BET) were assessed via separate two-way mixed model ANOVA with repeated measures at a significance level of pRESULTS: Analyses failed to reveal any significant main nor interaction effects for serum ∆BET. Although no apparent main supplement nor interaction effects were observed, ∆HCY demonstrated a significant main exercise condition effect (p=.045; ηp2=.228), whereby the LL-BFR group displayed significantly greater concentrations versus HL (p=.045). CONCLUSION: While these findings ultimately do not support a betaine-resistance training synergy-mediated reduction in serum HCY, our data otherwise suggest BFR training may preferentially result in lower post-training concentrations relative to a commonly employed, high-load approach. Future research should elucidate the credence of this interpretation via additional longitudinal investigations amidst hyperhomocysteinemia-predisposed clinical populations

Random attractors for degenerate stochastic partial differential equations

We prove the existence of random attractors for a large class of degenerate stochastic partial differential equations (SPDE) perturbed by joint additive Wiener noise and real, linear multiplicative Brownian noise, assuming only the standard assumptions of the variational approach to SPDE with compact embeddings in the associated Gelfand triple. This allows spatially much rougher noise than in known results. The approach is based on a construction of strictly stationary solutions to related strongly monotone SPDE. Applications include stochastic generalized porous media equations, stochastic generalized degenerate p-Laplace equations and stochastic reaction diffusion equations. For perturbed, degenerate p-Laplace equations we prove that the deterministic, infinite dimensional attractor collapses to a single random point if enough noise is added.Comment: 34 pages; The final publication is available at http://link.springer.com/article/10.1007%2Fs10884-013-9294-

Safety, tolerability, and impact on allergic inflammation of autologous E.coli autovaccine in the treatment of house dust mite asthma - a prospective open clinical trial

Background: Asthma is increasing worldwide and results from a complex immunological interaction between genetic susceptibility and environmental factors. Autovaccination with E. coli induces a strong TH-1 immune response, thus offering an option for the treatment of allergic diseases. Methods: Prospective open trial on safety, tolerability, and impact on allergic inflammation of an autologous E.coli autovaccine in intermittent or mild persistent house dust mite asthma. Determination of exhaled nitric monoxide (eNO) before and after bronchial mite challenge initially and after nine months of autovaccination. Results: Median eNO increase after autovaccination was significantly smaller (from 27.3 to 33.8 ppb; p=0.334) compared to initial values (from 32.6 to 42.2 ppb; p=0.046) (p=0.034). In nine subjects and a total of 306 injections, we observed 101 episodes of local erythema (33.3%; median of maximal diameter 2.5 cm), 95 episodes of local swelling (31.1%; median of maximal diameter 3 cm), and 27 episodes of local pain (8.8%). Four subjects reported itching at the injection site with a total of 30 episodes (9.8%). We observed no serious adverse events. All organ functions (inclusive electrocardiogramm) and laboratory testing of the blood (clinical chemistry, hematology) and the urine (screening test, B-microglobuline) were within normal limits. Vital signs undulated within the physiological variability. Conclusion: The administration of autologous autovacine for the treatment of house dust mite asthma resulted in a reduction of the eNO increase upon bronchial mite challenge. In nine subjects and 306 injections, only a few mild local reactions and no systemic severe adverse events were observed. EudraCT Nr. 2005-005534-12 ClinicalTrials.gov ID NCT0067720

Effect of continuous positive airway pressure therapy on a large hemangioma complicated with obstructive sleep apnea syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Hemangiomas involving the upper airway can be an uncommon cause of obstructive sleep apnea syndrome.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man with a known history of a large hemangioma of his head and neck presented with sleep-disordered breathing to the sleep unit of our hospital. Severe obstructive sleep apnea syndrome was revealed on polysomnography. Nasal continuous positive airway pressure was implemented effectively, reducing daytime hypersomnolence and significantly improving sleep parameters. After three years of adherent use, the patient remains in a good condition and the hemangioma is stable.</p> <p>Conclusion</p> <p>Application of continuous positive airway pressure can be an effective treatment for patients with obstructive sleep apnea syndrome complicated with vascular tumors. Periodic follow-up of these patients is necessary, as little is known about the long-term effects of continuous positive airway pressure therapy.</p

Degradation, Bioactivity, and Osteogenic Potential of Composites Made of PLGA and Two Different Sol–Gel Bioactive Glasses

We have developed poly(l-lactide-co-glycolide) (PLGA) based composites using sol–gel derived bioactive glasses (S-BG), previously described by our group, as composite components. Two different composite types were manufactured that contained either S2—high content silica S-BG, or A2—high content lime S-BG. The composites were evaluated in the form of sheets and 3D scaffolds. Sheets containing 12, 21, and 33 vol.% of each bioactive glass were characterized for mechanical properties, wettability, hydrolytic degradation, and surface bioactivity. Sheets containing A2 S-BG rapidly formed a hydroxyapatite surface layer after incubation in simulated body fluid. The incorporation of either S-BG increased the tensile strength and Young’s modulus of the composites and tailored their degradation rates compared to starting compounds. Sheets and 3D scaffolds were evaluated for their ability to support growth of human bone marrow cells (BMC) and MG-63 cells, respectively. Cells were grown in non-differentiating, osteogenic or osteoclast-inducing conditions. Osteogenesis was induced with either recombinant human BMP-2 or dexamethasone, and osteoclast formation with M-CSF. BMC viability was lower at higher S-BG content, though specific ALP/cell was significantly higher on PLGA/A2-33 composites. Composites containing S2 S-BG enhanced calcification of extracellular matrix by BMC, whereas incorporation of A2 S-BG in the composites promoted osteoclast formation from BMC. MG-63 osteoblast-like cells seeded in porous scaffolds containing S2 maintained viability and secreted collagen and calcium throughout the scaffolds. Overall, the presented data show functional versatility of the composites studied and indicate their potential to design a wide variety of implant materials differing in physico-chemical properties and biological applications. We propose these sol–gel derived bioactive glass–PLGA composites may prove excellent potential orthopedic and dental biomaterials supporting bone formation and remodeling

Combined inhibition of MEK and Plk1 has synergistic anti-tumor activity in NRAS mutant melanoma

About one third of cancers harbor activating mutations in rat sarcoma viral oncogene homolog (RAS) oncogenes. In melanoma, aberrant neuroblastoma-RAS (NRAS) signaling fuels tumor progression in about 20% of patients. Current therapeutics for NRAS driven malignancies barely impact overall survival. To date, pathway interference downstream of mutant NRAS seems to be the most promising approach. In this study, data revealed that mutant NRAS induced Plk1 expression, and pharmacologic inhibition of Plk1 stabilized the size of NRAS mutant melanoma xenografts. The combination of MEK and Plk1 inhibitors resulted in a significant growth reduction of NRAS mutant melanoma cells in vitro, and regression of xenografted NRAS mutant melanoma in vivo. Independent cell cycle arrest and increased induction of apoptosis underlies the synergistic effect of this combination. Data further suggest that the p53 signaling pathway is of key importance to the observed therapeutic efficacy. This study provides in vitro, in vivo and first mechanistic data, that a MEK/Plk1 inhibitor combination might be a promising treatment approach for patients with NRAS driven melanoma. Since mutant NRAS signaling is similar across different malignancies, this inhibitor combination could also offer a previously unreported treatment modality for NRAS mutant tumors of other cell origins

Porphyrin Homeostasis Maintained by ABCG2 Regulates Self-Renewal of Embryonic Stem Cells

Under appropriate culture conditions, undifferentiated embryonic stem (ES) cells can undergo multiple self-renewal cycles without loss of pluripotency suggesting they must be equipped with specific defense mechanisms to ensure sufficient genetic stability during self-renewal expansion. The ATP binding cassette transporter ABCG2 is expressed in a wide variety of somatic and embryonic stem cells. However, whether it plays an important role in stem cell maintenance remains to be defined.Here we provide evidence to show that an increase in the level of ABCG2 was observed accompanied by ES colony expansion and then were followed by decreases in the level of protoporphyrin IX (PPIX) indicating that ABCG2 plays a role in maintaining porphyrin homoeostasis. RNA-interference mediated inhibition of ABCG2 as well as functional blockage of ABCG2 transporter with fumitremorgin C (FTC), a specific and potent inhibitor of ABCG2, not only elevated the cellular level of PPIX, but also arrest the cell cycle and reduced expression of the pluripotent gene Nanog. Overexpression of ABCG2 in ES cells was able to counteract the increase of endogenous PPIX induced by treatment with 5-Aminolevulinic acid suggesting ABCG2 played a direct role in removal of PPIX from ES cells. We also found that excess PPIX in ES cells led to elevated levels of reactive oxygen species which in turn triggered DNA damage signals as indicated by increased levels of gammaH2AX and phosphorylated p53. The increased level of p53 reduced Nanog expression because RNA- interference mediated inhibition of p53 was able to prevent the downregulation of Nanog induced by FTC treatment.The present work demonstrated that ABCG2 protects ES cells from PPIX accumulation during colony expansion, and that p53 and gammaH2AX acts as a downstream checkpoint of ABCG2-dependent defense machinery in order to maintain the self-renewal of ES cells

Modelling opinion formation by means of kinetic equations

In this chapter, we review some mechanisms of opinion dynamics that can be modelled by kinetic equations. Beside the sociological phenomenon of compromise, naturally linked to collisional operators of Boltzmann kind, many other aspects, already mentioned in the sociophysical literature or no, can enter in this framework. While describing some contributions appeared in the literature, we enlighten some mathematical tools of kinetic theory that can be useful in the context of sociophysics