Blocked dihydropteridines as nitric oxide synthase activators

It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings

The ergogenic effect of beta-alanine combined with sodium bicarbonate on high-intensity swimming performance

We investigated the effect of beta-alanine (BA) alone (study A) and in combination with sodium bicarbonate (SB) (study B) on 100- and 200-m swimming performance. In study A, 16 swimmers were assigned to receive either BA (3.2 g·day−1 for 1 week and 6.4 g·day−1 for 4 weeks) or placebo (PL; dextrose). At baseline and after 5 weeks of supplementation, 100- and 200-m races were completed. In study B, 14 were assigned to receive either BA (3.2 g·day−1 for 1 week and 6.4 g·day−1 for 3 weeks) or PL. Time trials were performed once before and twice after supplementation (with PL and SB), in a crossover fashion, providing 4 conditions: PL-PL, PL-SB, BA-PL, and BA-SB. In study A, BA supplementation improved 100- and 200-m time-trial performance by 2.1% (p = 0.029) and 2.0% (p = 0.0008), respectively. In study B, 200-m time-trial performance improved in all conditions, compared with presupplementation, except the PL-PL condition (PL-SB, +2.3%; BA-PL, +1.5%; BA-SB, +2.13% (p < 0.05)). BA-SB was not different from BA-PL (p = 0.21), but the probability of a positive effect was 78.5%. In the 100-m time-trial, only a within-group effect for SB was observed in the PL-SB (p = 0.022) and BA-SB (p = 0.051) conditions. However, 6 of 7 athletes swam faster after BA supplementation. The probability of BA having a positive effect was 65.2%; when SB was added to BA, the probability was 71.8%. BA and SB supplementation improved 100- and 200-m swimming performance. The coingestion of BA and SB induced a further nonsignificant improvement in performance

The safety of paediatric surgery between COVID-19 surges:an observational study

Despite the ongoing coronavirus disease 2019 (COVID-19) pandemic, elective paediatric surgery must continue safely through the first, second and subsequent waves of disease. This study presents outcome data from a children's hospital in north-west England, the region with the highest prevalence of COVID-19 in England. Children and young people undergoing elective surgery isolated within their household for 14 days, then presented for real-time reverse transcriptase polymerase chain reaction testing for severe acute respiratory syndrome coronavirus disease-2 (SARS-CoV-2) within 72 h of their procedure (or rapid testing within 24 h in high-risk cases), and completed a screening questionnaire on admission. Planned surgery resumed on 26 May 2020; in the four subsequent weeks, there were 197 patients for emergency and 501 for elective procedures. A total of 488 out of 501 (97.4%) elective admissions proceeded, representing a 2.6% COVID-19-related cancellation rate. There was no difference in the incidence of SARS-CoV-2 among children and young people who had or had not isolated for 14 days (p > 0.99). One out of 685 (0.1%) children who had surgery re-presented to the hospital with symptoms potentially consistent with SARS-CoV-2 within 14 days of surgery. Outcomes were similar to those in the same time period in 2019 for length of stay (p = 1.0); unplanned critical care admissions (p = 0.59); and 14-day hospital re-admission (p = 0.17). However, the current cohort were younger (p = 0.037); of increased complexity (

Periodic solutions for a class of nonlinear partial differential equations in higher dimension

We prove the existence of periodic solutions in a class of nonlinear partial differential equations, including the nonlinear Schroedinger equation, the nonlinear wave equation, and the nonlinear beam equation, in higher dimension. Our result covers cases where the bifurcation equation is infinite-dimensional, such as the nonlinear Schroedinger equation with zero mass, for which solutions which at leading order are wave packets are shown to exist.Comment: 34 page

K\"{a}hler-Einstein metrics on strictly pseudoconvex domains

The metrics of S. Y. Cheng and S.-T. Yau are considered on a strictly pseudoconvex domains in a complex manifold. Such a manifold carries a complete K\"{a}hler-Einstein metric if and only if its canonical bundle is positive. We consider the restricted case in which the CR structure on $\partial M$ is normal. In this case M must be a domain in a resolution of the Sasaki cone over $\partial M$. We give a condition on a normal CR manifold which it cannot satisfy if it is a CR infinity of a K\"{a}hler-Einstein manifold. We are able to mostly determine those normal CR 3-manifolds which can be CR infinities. Many examples are given of K\"{a}hler-Einstein strictly pseudoconvex manifolds on bundles and resolutions.Comment: 30 pages, 1 figure, couple corrections, improved a couple example

Women, men and coronary heart disease: a review of the qualitative literature

Aim. This paper presents a review of the qualitative literature which examines the experiences of patients with coronary heart disease. The paper also assesses whether the experiences of both female and male patients are reflected in the literature and summarizes key themes. Background. Understanding patients' experiences of their illness is important for coronary heart disease prevention and education. Qualitative methods are particularly suited to eliciting patients' detailed understandings and perceptions of illness. As much previous research has been 'gender neutral', this review pays particular attention to gender. Methods. Published papers from 60 qualitative studies were identified for the review through searches in MEDLINE, EMBASE, CINAHL, PREMEDLINE, PsychINFO, Social Sciences Citation Index and Web of Science using keywords related to coronary heart disease. Findings. Early qualitative studies of patients with coronary heart disease were conducted almost exclusively with men, and tended to generalize from 'male' experience to 'human' experience. By the late 1990s this pattern had changed, with the majority of studies including women and many being conducted with solely female samples. However, many studies that include both male and female coronary heart disease patients still do not have a specific gender focus. Key themes in the literature include interpreting symptoms and seeking help, belief about coronary 'candidates' and relationships with health professionals. The influence of social roles is important: many female patients have difficulties reconciling family responsibilities and medical advice, while male patients worry about being absent from work. Conclusions. There is a need for studies that compare the experiences of men and women. There is also an urgent need for work that takes masculinity and gender roles into account when exploring the experiences of men with coronary heart disease

An acute naproxen dose does not affect core temperature or Interleukin-6 during cycling in a hot environment

Non-steroidal anti-inflammatory drugs’ anti-pyretic and anti-inflammatory effects has led some individuals to theorize these medications may blunt core body temperature (Tc) increases during exercise. We utilized a double-blind, randomized, and counterbalanced cross-over design to examine the effects of a 24-h naproxen dose (3–220 ​mg naproxen pills) and placebo (0 ​mg naproxen) on Tc and plasma interleukin-6 (IL-6) concentrations during cycling in a hot or ambient environment. Participants (n ​= ​11; 6 male, 5 female; age ​= ​27.8 ​± ​6.5 years, weight ​= ​79.1 ​± ​17.9 ​kg, height ​= ​177 ​± ​9.5 ​cm) completed 4 conditions: 1) placebo and ambient (Control); 2) placebo and heat (Heat); 3) naproxen and ambient (Npx); and 4) naproxen and heat (NpxHeat). Dependent measures were taken before, during, and immediately after 90 ​min of cycling and then 3 ​h after cycling. Overall, Tc significantly increased pre- (37.1 ​± ​0.4 ​°C) to post-cycling (38.2 ​± ​0.3 ​°C, F1.7,67.3 ​= ​150.5, p ​< ​0.001) and decreased during rest (37.0 ​± ​0.3 ​°C, F2.0,81.5 ​= ​201.6, p ​< ​0.001). Rate of change or maximum Tc were not significantly different between conditions. IL-6 increased pre- (0.54 ​± ​0.06 ​pg/ml) to post-exercise (2.46 ​± ​0.28 ​pg/ml, p ​< ​0.001) and remained significantly higher than pre-at 3 ​h post- (1.17 ​± ​0.14 ​pg/ml, 95% CI ​= ​−1.01 to −0.23, p ​= ​0.001). No significant IL-6 differences occurred between conditions. A 24-h, over-the-counter naproxen dose did not significantly affect Tc or IL-6 among males and females cycling in hot or ambient environments

Amplitude measurements of Faraday waves

A light reflection technique is used to measure quantitatively the surface elevation of Faraday waves. The performed measurements cover a wide parameter range of driving frequencies and sample viscosities. In the capillary wave regime the bifurcation diagrams exhibit a frequency independent scaling proportional to the wavelength. We also provide numerical simulations of the full Navier-Stokes equations, which are in quantitative agreement up to supercritical drive amplitudes of 20%. The validity of an existing perturbation analysis is found to be limited to 2.5% overcriticaly.Comment: 7 figure

Holographic Discreteness of Inflationary Perturbations

The holographic entropy bound is used to estimate the quantum-gravitational discreteness of inflationary perturbations. In the context of scalar inflaton perturbations produced during standard slow-roll inflation, but assuming that horizon-scale perturbations ``freeze out'' in discrete steps separated by one bit of total observable entropy, it is shown that the Hilbert space of a typical horizon-scale inflaton perturbation is equivalent to that of about 10^5 binary spins-- approximately the inverse of the final scalar metric perturbation amplitude, independent of other parameters. Holography thus suggests that in a broad class of fundamental theories, inflationary perturbations carry a limited amount of information (about 10^5 bits per mode) and should therefore display discreteness not predicted by the standard field theory. Some manifestations of this discreteness may be observable in cosmic background anisotropy.Comment: 13 pages, Latex, 4 figures, to appear in Phys. Rev. D. New figures and references adde