Association of periodontal and cardiovascular diseases: South-Asian studies 2001-2012

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Anterior segment optical coherence tomography changes with introduction and discontinuation of tamsulosin

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A Novel Class of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors That Contains the Octahydro-2H-chromen-4-ol Scaffold.

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that mends topoisomerase 1-mediated DNA damage. Tdp1 is a current inhibition target for the development of improved anticancer treatments, as its inhibition may enhance the therapeutic effect of topoisomerase 1 poisons. Here, we report a study on the development of a novel class of Tdp1 inhibitors that is based on the octahydro-2H-chromene scaffold. Inhibition and binding assays revealed that these compounds are potent inhibitors of Tdp1, with IC50 and KD values in the low micromolar concentration range. Molecular modelling predicted plausible conformations of the active ligands, blocking access to the enzymatic machinery of Tdp1. Our results thus help establish a structural-activity relationship for octahydro-2H-chromene-based Tdp1 inhibitors, which will be useful for future Tdp1 inhibitor development work

Effect of dose and duration of reduction in dietary sodium on blood pressure levels: systematic review and meta-analysis of randomised trials.

OBJECTIVE: To examine the dose-response relation between reduction in dietary sodium and blood pressure change and to explore the impact of intervention duration. DESIGN: Systematic review and meta-analysis following PRISMA guidelines. DATA SOURCES: Ovid MEDLINE(R), EMBASE, and Cochrane Central Register of Controlled Trials (Wiley) and reference lists of relevant articles up to 21 January 2019. INCLUSION CRITERIA: Randomised trials comparing different levels of sodium intake undertaken among adult populations with estimates of intake made using 24 hour urinary sodium excretion. DATA EXTRACTION AND ANALYSIS: Two of three reviewers screened the records independently for eligibility. One reviewer extracted all data and the other two reviewed the data for accuracy. Reviewers performed random effects meta-analyses, subgroup analyses, and meta-regression. RESULTS: 133 studies with 12 197 participants were included. The mean reductions (reduced sodium v usual sodium) of 24 hour urinary sodium, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were 130 mmol (95% confidence interval 115 to 145, P<0.001), 4.26 mm Hg (3.62 to 4.89, P<0.001), and 2.07 mm Hg (1.67 to 2.48, P<0.001), respectively. Each 50 mmol reduction in 24 hour sodium excretion was associated with a 1.10 mm Hg (0.66 to 1.54; P<0.001) reduction in SBP and a 0.33 mm Hg (0.04 to 0.63; P=0.03) reduction in DBP. Reductions in blood pressure were observed in diverse population subsets examined, including hypertensive and non-hypertensive individuals. For the same reduction in 24 hour urinary sodium there was greater SBP reduction in older people, non-white populations, and those with higher baseline SBP levels. In trials of less than 15 days' duration, each 50 mmol reduction in 24 hour urinary sodium excretion was associated with a 1.05 mm Hg (0.40 to 1.70; P=0.002) SBP fall, less than half the effect observed in studies of longer duration (2.13 mm Hg; 0.85 to 3.40; P=0.002). Otherwise, there was no association between trial duration and SBP reduction. CONCLUSIONS: The magnitude of blood pressure lowering achieved with sodium reduction showed a dose-response relation and was greater for older populations, non-white populations, and those with higher blood pressure. Short term studies underestimate the effect of sodium reduction on blood pressure. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019140812

The Omega Deformation From String and M-Theory

We present a string theory construction of Omega-deformed four-dimensional gauge theories with generic values of \epsilon_1 and \epsilon_2. Our solution gives an explicit description of the geometry in the core of Nekrasov and Witten's realization of the instanton partition function, far from the asymptotic region of their background. This construction lifts naturally to M-theory and corresponds to an M5-brane wrapped on a Riemann surface with a selfdual flux. Via a 9-11 flip, we finally reinterpret the Omega deformation in terms of non-commutative geometry. Our solution generates all modified couplings of the \Omega-deformed gauge theory, and also yields a geometric origin for the quantum spectral curve of the associated quantum integrable system.Comment: LaTeX, 35 pages, 1 figure. Appendix on couplings of hypermultiplets in N=4 SYM adde

Potential vegetable sources for biodiesel production:Cashew, coconut and cotton

This work presents a study on crude oil and biodiesel obtained from the seeds of the tropical plants Anacardium occidentale L (cashew), Cocos nucifera (coconut palm) and Gossypium hirsutum (upland cotton). The following crude oil and biodiesel physical-chemical properties were determined: acid number, iodine value, copper corrosivity, density and viscosity at different temperatures. Also, the chemical composition of the fatty acid methyl esters was measured using gas chromatography and a comparison was made with biodiesel from other sources reported in the literature. The analysis pointed out that cashew, coconut palm and upland cotton are potential sources for biodiesel production. Among the biodiesel types tested, cashew showed the highest oxidation stability

Dimension-Six Terms in the Standard Model Lagrangian

When the Standard Model is considered as an effective low-energy theory, higher dimensional interaction terms appear in the Lagrangian. Dimension-six terms have been enumerated in the classical article by Buchmueller and Wyler [3]. Although redundance of some of those operators has been already noted in the literature, no updated complete list has been published to date. Here we perform their classification once again from the outset. Assuming baryon number conservation, we find 15 + 19 + 25 = 59 independent operators (barring flavour structure and Hermitian conjugations), as compared to 16 + 35 + 29 = 80 in Ref.[3]. The three summed numbers refer to operators containing 0, 2 and 4 fermion fields. If the assumption of baryon number conservation is relaxed, 4 new operators arise in the four-fermion sector.Comment: 16 pages, no figures, v3: Redundant B-violating operator remove

The Omega Deformation, Branes, Integrability, and Liouville Theory

We reformulate the Omega-deformation of four-dimensional gauge theory in a way that is valid away from fixed points of the associated group action. We use this reformulation together with the theory of coisotropic A-branes to explain recent results linking the Omega-deformation to integrable Hamiltonian systems in one direction and Liouville theory of two-dimensional conformal field theory in another direction.Comment: 96 p

A relative value method for measuring and evaluating cardiac reserve

BACKGROUND: Although a very close relationship between the amplitude of the first heart sound (S1) and the cardiac contractility have been proven by previous studies, the absolute value of S1 can not be applied for evaluating cardiac contractility. However, we were able to devise some indicators with relative values for evaluating cardiac function. METHODS: Tests were carried out on a varied group of volunteers. Four indicators were devised: (1) the increase of the amplitude of the first heart sound after accomplishing different exercise workloads, with respect to the amplitude of the first heart sound (S1)recorded at rest was defined as cardiac contractility change trend (CCCT). When the subjects completed the entire designed exercise workload (7000 J), the resulting CCCT was defined as CCCT(1); when only 1/4 of the designed exercise workload was completed, the result was defined as CCCT(1/4). (2) The ratio of S1 amplitude to S2 amplitude (S1/S2). (3) The ratio of S1 amplitude at tricuspid valve auscultation area to that at mitral auscultation area T1/M1 (4) the ratio of diastolic to systolic duration (D/S). Data were expressed as mean ± SD. RESULTS: CCCT(1/4) was 6.36 ± 3.01 (n = 67), CCCT(1) was 10.36 ± 4.2 (n = 33), S1/S2 was1.89 ± 0.94 (n = 140), T1/M1 was 1.44 ± 0.99 (n = 144), and D/S was 1.68 ± 0.27 (n = 172). CONCLUSIONS: Using indicators CCCT(1/4) and CCCT(1) may be beneficial for evaluating cardiac contractility and cardiac reserve mobilization level, S1/S2 for considering the factor for hypotension, T1/M1 for evaluating the right heart load, and D/S for evaluating diastolic cardiac blood perfusion time

Simvastatin inhibits TLR8 signaling in primary human monocytes and spontaneous TNF production from rheumatoid synovial membrane cultures

Simvastatin has been shown to have anti-inflammatory effects that are independent of its serum cholesterol lowering action, but the mechanisms by which these anti-inflammatory effects are mediated have not been elucidated. To explore the mechanism involved, the effect of simvastatin on Toll-like receptor (TLR) signalling in primary human monocytes was investigated. A short pre-treatment with simvastatin dose-dependently inhibited the production of tumor necrosis factor-α (TNF) in response to TLR8 (but not TLRs 2, 4, or 5) activation. Statins are known inhibitors of the cholesterol biosynthetic pathway, but intriguingly TLR8 inhibition could not be reversed by addition of mevalonate or geranylgeranyl pyrophosphate; downstream products of cholesterol biosynthesis. TLR8 signalling was examined in HEK 293 cells stably expressing TLR8, where simvastatin inhibited IKKα/β phosphorylation and subsequent NF-κB activation without affecting the pathway to AP-1. Since simvastatin has been reported to have anti-inflammatory effects in RA patients and TLR8 signalling contributes to TNF production in human RA synovial tissue in culture, simvastatin was tested in these cultures. Simvastatin significantly inhibited the spontaneous release of TNF in this model which was not reversed by mevalonate. Together, these results demonstrate a hitherto unrecognized mechanism of simvastatin inhibition of TLR8 signalling that may in part explain its beneficial anti-inflammatory effects