Evaluation of antibacterial, antifungal and modulatory activity of methanol and ethanol extracts of Padina sanctae-crucis

Background: Multi-resistant microorganisms such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida tropicalis e Candida krusei are the main causes of microbial infections. Padina sanctae-crucis is a seaweed often used to check the contamination of ecosystems by materials such as heavy metals, but studies of the antimicrobial activity of the same seaweed were not found.Methods: The tests for the minimum inhibitory concentration and   modulation of microbial resistance, with the use of ethanolic and  methanolic extracts of Padina Sanctae-cruces combined with drugs of the class of aminoglycosides and antifungal were used to evaluate the activity against the cited microorganisms.Results: Was observed a modulation of antibiotic activity between the natural products and the E. coli and S. aureus strains, indicating a synergism and antagonism respectively.Conclusions: The results showed a moderate modulatory effect against some microorganisms studied.Keywords: multi-resistant microorganisms, modulation, Padina Sanctae-crucis, antimicrobial activity

Safety and Efficacy of Ombitasvir, Paritaprevir With Ritonavir ± Dasabuvir With or Without Ribavirin in Patients With Human Immunodeficiency Virus-1 and Hepatitis C Virus Genotype 1 or Genotype 4 Coinfection: TURQUOISE-I Part 2.

BACKGROUND: Ombitasvir, paritaprevir with ritonavir, and dasabuvir (OBV/PTV/r ± DSV) ±ribavirin (RBV) are approved to treat hepatitis C virus (HCV) genotype 1 and 4 infection. Here, we investigate the safety and efficacy of OBV/PTV/r + DSV ±RBV for HCV genotype 1, and OBV/PTV/r + RBV for HCV genotype 4, in human immunodeficiency virus (HIV)-1 coinfected patients with or without compensated cirrhosis. METHODS: TURQUOISE-I, Part 2 is a phase 3 multicenter study. Patients with or without cirrhosis were HCV treatment-naive or -experienced, on an HIV-1 antiretroviral regimen containing atazanavir, raltegravir, dolutegravir, or darunavir (for genotype 4 only), and had plasma HIV-1 ribonucleic acid <40 copies/mL at screening. Patients received OBV/PTV/r ± DSV ±RBV for 12 or 24 weeks. RESULTS: In total, 228 patients were treated according to guidelines. Sustained virologic response at posttreatment week 12 (SVR12) was achieved by 194 of 200 (97%) and 27 of 28 (96%) patients with HCV genotype 1 and genotype 4 infection, respectively. There were 2 virologic failures: 1 breakthrough and 1 relapse in a cirrhotic and a noncirrhotic patient with genotype 1b and 1a infection, respectively. One reinfection occurred at posttreatment week 12 in a genotype 1a-infected patient. Excluding nonvirologic failures, the SVR12 rates were 98% (genotype 1) and 100% (genotype 4). Adverse events were mostly mild in severity and did not lead to discontinuation. Laboratory abnormalities were rare. CONCLUSIONS: The OBV/PTV/r ±DSV was well tolerated and yielded high SVR12 rates in patients with HCV genotype 1 or genotype 4/HIV-1 coinfection. The OBV/PTV/r ± DSV ±RBV is a potent HCV treatment option for patients with HIV-1 coinfection, regardless of treatment experience

Anomalous Dimensions and Non-Gaussianity

We analyze the signatures of inflationary models that are coupled to strongly interacting field theories, a basic class of multifield models also motivated by their role in providing dynamically small scales. Near the squeezed limit of the bispectrum, we find a simple scaling behavior determined by operator dimensions, which are constrained by the appropriate unitarity bounds. Specifically, we analyze two simple and calculable classes of examples: conformal field theories (CFTs), and large-N CFTs deformed by relevant time-dependent double-trace operators. Together these two classes of examples exhibit a wide range of scalings and shapes of the bispectrum, including nearly equilateral, orthogonal and local non-Gaussianity in different regimes. Along the way, we compare and contrast the shape and amplitude with previous results on weakly coupled fields coupled to inflation. This signature provides a precision test for strongly coupled sectors coupled to inflation via irrelevant operators suppressed by a high mass scale up to 1000 times the inflationary Hubble scale.Comment: 40 pages, 10 figure

Supersymmetric constraints from Bs -> mu+mu- and B -> K* mu+mu- observables

We study the implications of the recent LHCb limit and results on Bs -> mu+mu- and B -> K* mu+mu- observables in the constrained SUSY scenarios. After discussing the Standard Model predictions and carefully estimating the theoretical errors, we show the constraining power of these observables in CMSSM and NUHM. The latest limit on BR(Bs -> mu+mu-), being very close to the SM prediction, constrains strongly the large tan(beta) regime and we show that the various angular observables from B -> K* mu+mu- decay can provide complementary information in particular for moderate tan(beta) values.Comment: 30 pages, 14 figure

Animal Ca2+ release-activated Ca2+ (CRAC) channels appear to be homologous to and derived from the ubiquitous cation diffusion facilitators

<p>Abstract</p> <p>Background</p> <p>Antigen stimulation of immune cells triggers Ca²⁺entry through Ca²⁺release-activated Ca²⁺(CRAC) channels, promoting an immune response to pathogens. Defects in a CRAC (Orai) channel in humans gives rise to the hereditary Severe Combined Immune Deficiency (SCID) syndrome. We here report results that define the evolutionary relationship of the CRAC channel proteins of animals, and the ubiquitous Cation Diffusion Facilitator (CDF) carrier proteins.</p> <p>Findings</p> <p>CDF antiporters derived from a primordial 2 transmembrane spanner (TMS) hairpin structure by intragenic triplication to yield 6 TMS proteins. Four programs (IC/GAP, GGSEARCH, HMMER and SAM) were evaluated for identifying sequence similarity and establishing homology using statistical means. Overall, the order of sensitivity (similarity detection) was IC/GAP = GGSEARCH > HMMER > SAM, but the use of all four programs was superior to the use of any two or three of them. Members of the CDF family appeared to be homologous to members of the 4 TMS Orai channel proteins.</p> <p>Conclusions</p> <p>CRAC channels derived from CDF carriers by loss of the first two TMSs of the latter. Based on statistical analyses with multiple programs, TMSs 3-6 in CDF carriers are homologous to TMSs 1-4 in CRAC channels, and the former was the precursor of the latter. This is an unusual example of how a functionally and structurally more complex protein may have predated a simpler one.</p

The receptor tyrosine kinase EphB4 is overexpressed in ovarian cancer, provides survival signals and predicts poor outcome

EphB4 is a member of the largest family of transmembrane receptor tyrosine kinases and plays critical roles in axonal pathfinding and blood vessel maturation. We wanted to determine the biological role of EphB4 in ovarian cancer. We studied the expression of EphB4 in seven normal ovarian specimens and 85 invasive ovarian carcinomas by immunohistochemistry. EphB4 expression was largely absent in normal ovarian surface epithelium, but was expressed in 86% of ovarian cancers. EphB4 expression was significantly associated with advanced stage of disease and the presence of ascites. Overexpression of EphB4 predicted poor survival in both univariate and multivariate analyses. We also studied the biological significance of EphB4 expression in ovarian tumour cells lines in vitro and in vivo. All five malignant ovarian tumour cell lines tested expressed higher levels of EphB4 compared with the two benign cell lines. Treatment of malignant, but not benign, ovarian tumour cell lines with progesterone, but not oestrogen, led to a 90% reduction in EphB4 levels that was associated with 50% reduction in cell survival. Inhibition of EphB4 expression by specific siRNA or antisense oligonucleotides significantly inhibited tumour cell viability by inducing apoptosis via activation of caspase-8, and also inhibited tumour cell invasion and migration. Furthermore, EphB4 antisense significantly inhibited growth of ovarian tumour xenografts and tumour microvasculature in vivo. Inhibition of EphB4 may hence have prognostic and therapeutic utility in ovarian carcinoma

The effects of progressive resistance training combined with a whey-protein drink and vitamin D supplementation on glycaemic control, body composition and cardiometabolic risk factors in older adults with type 2 diabetes: study protocol for a randomized controlled trial

Background - While physical activity, energy restriction and weight loss are the cornerstone of type 2 diabetes management, less emphasis is placed on optimizing skeletal muscle mass. As muscle is the largest mass of insulin-sensitive tissue and the predominant reservoir for glucose disposal, there is a need to develop safe and effective evidence-based, lifestyle management strategies that optimize muscle mass as well as improve glycaemic control and cardiometabolic risk factors in people with this disease, particularly older adults who experience accelerated muscle loss. Methods/Design - Using a two-arm randomized controlled trial, this 6-month study builds upon the community-based progressive resistance training (PRT) programme Lift for Life® to evaluate whether ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, body composition and cardiometabolic health in older adults with type 2 diabetes. Approximately 200 adults aged 50 to 75 years with type 2 diabetes, treated with either diet alone or oral hypoglycaemic agents (not insulin), will be recruited. All participants will be asked to participate in a structured, supervised PRT programme based on the Lift for Life® programme structure, and randomly allocated to receive a whey-protein drink (20 g daily of whey-protein plus 20 g after each PRT session) plus vitamin D supplements (2000 IU/day), or no additional powder and supplements. The primary outcome measures to be collected at baseline, 3 and 6 months will be glycated haemoglobin (HbA1c) and insulin sensitivity (homeostatic model assessment). Secondary outcomes will include changes in: muscle mass, size and intramuscular fat; fat mass; muscle strength and function; blood pressure; levels of lipids, adipokines and inflammatory markers, serum insulin-like growth factor-1 and 25-hydroxyvitamin D; renal function; diabetes medication; health-related quality of life, and cognitive function. Discussion - The findings from this study will provide new evidence on whether increased dietary protein achieved through the ingestion of a whey-protein drink combined with vitamin D supplementation can enhance the effects of PRT on glycaemic control, muscle mass and size, and cardiometabolic risk factors in older adults with type 2 diabetes

Association and Linkage Analysis of Aluminum Tolerance Genes in Maize

Aluminum (Al) toxicity is a major worldwide constraint to crop productivity on acidic soils. Al becomes soluble at low pH, inhibiting root growth and severely reducing yields. Maize is an important staple food and commodity crop in acidic soil regions, especially in South America and Africa where these soils are very common. Al exclusion and intracellular tolerance have been suggested as two important mechanisms for Al tolerance in maize, but little is known about the underlying genetics. linkage populations with approximately 200 individuals each were used to study genetic variation in this complex trait. Al tolerance was measured as net root growth in nutrient solution under Al stress, which exhibited a wide range of variation between lines. Comparative and physiological genomics-based approaches were used to select 21 candidate genes for evaluation by association analysis.). These four candidate genes are high priority subjects for follow-up biochemical and physiological studies on the mechanisms of Al tolerance in maize. Immediately, elite haplotype-specific molecular markers can be developed for these four genes and used for efficient marker-assisted selection of superior alleles in Al tolerance maize breeding programs

Triple antiplatelet therapy for preventing vascular events: a systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Dual antiplatelet therapy is usually superior to mono therapy in preventing recurrent vascular events (VEs). This systematic review assesses the safety and efficacy of triple antiplatelet therapy in comparison with dual therapy in reducing recurrent vascular events.</p> <p>Methods</p> <p>Completed randomized controlled trials investigating the effect of triple versus dual antiplatelet therapy in patients with ischaemic heart disease (IHD), cerebrovascular disease or peripheral vascular disease were identified using electronic bibliographic searches. Data were extracted on composite VEs, myocardial infarction (MI), stroke, death and bleeding and analysed with Cochrane Review Manager software. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using random effects models.</p> <p>Results</p> <p>Twenty-five completed randomized trials (17,383 patients with IHD) were included which involving the use of intravenous (iv) GP IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban), aspirin, clopidogrel and/or cilostazol. In comparison with aspirin-based therapy, triple therapy using an intravenous GP IIb/IIIa inhibitor significantly reduced composite VEs and MI in patients with non-ST elevation acute coronary syndromes (NSTE-ACS) (VE: OR 0.69, 95% CI 0.55-0.86; MI: OR 0.70, 95% CI 0.56-0.88) and ST elevation myocardial infarction (STEMI) (VE: OR 0.39, 95% CI 0.30-0.51; MI: OR 0.26, 95% CI 0.17-0.38). A significant reduction in death was also noted in STEMI patients treated with GP IIb/IIIa based triple therapy (OR 0.69, 95% CI 0.49-0.99). Increased minor bleeding was noted in STEMI and elective percutaneous coronary intervention (PCI) patients treated with GP IIb/IIIa based triple therapy. Stroke events were too infrequent for us to be able to identify meaningful trends and no data were available for patients recruited into trials on the basis of stroke or peripheral vascular disease.</p> <p>Conclusions</p> <p>Triple antiplatelet therapy based on iv GPIIb/IIIa inhibitors was more effective than aspirin-based dual therapy in reducing VEs in patients with acute coronary syndromes (STEMI and NSTEMI). Minor bleeding was increased among STEMI and elective PCI patients treated with a GP IIb/IIIa based triple therapy. In patients undergoing elective PCI, triple therapy had no beneficial effect and was associated with an 80% increase in transfusions and an eightfold increase in thrombocytopenia. Insufficient data exist for patients with prior ischaemic stroke and peripheral vascular disease and further research is needed in these groups of patients.</p