Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative Stress

Sildenafil citrate revolutionized the practice of sexual medicine upon its federal regulatory agency approval approximately 15 years ago as the prototypical phosphodiesterase type 5 inhibitor indicated for the treatment of male erectile dysfunction. We now provide scientific support for its alternative use in the management of priapism, a clinical disorder of prolonged and uncontrolled penile erection. Sildenafil administered continuously to sickle cell mice, which show a priapism phenotype, reverses oxidative/nitrosative stress effects in the penis, mainly via reversion of uncoupled endothelial nitric oxide synthase to the functional coupled state of the enzyme, which in turn corrects aberrant signaling and function of the nitric oxide/cyclic GMP/protein kinase G/phosphodiesterase type 5 cascade. Priapism tendencies in these mice are reverted partially toward normal neurostimulated erection frequencies and durations after sildenafil treatment in association with normalized cyclic GMP concentration, protein kinase G activity and phosphodiesterase type 5 activity in the penis. Thus, sildenafil exerts pleiotropic effects in the penis that extend to diverse erection disorders. © 2013 Bivalacqua et al

Coarse-grained simulation of transmembrane peptides in the gel phase

We use Dissipative Particle Dynamics simulations, combined with parallel tempering and umbrella sampling, to investigate the potential of mean force between model transmembrane peptides in the various phases of a lipid bilayer, including the low-temperature gel phase. The observed oscillations in the effective interaction between peptides are consistent with the different structures of the surrounding lipid phases

Exchange Bias and Vertical Shift in CoFe2O4 nanoparticles

Magnetic properties of core-shell cobalt ferrite nanoparticles 15 to 48nm prepared by a sol-gel route have been studied. It is shown that the coercivity follows non-monotonic size dependence varying as 1/d above the maximum (d is the particle size). Field cooled magnetization exhibited both horizontal (exchange bias) and vertical shifts. The exchange bias is understood as originating at the interface between a surface region with structural and spin disorder and a core ferrimagnetic region. The dependence of the exchange bias and vertical shifts on the particle sizes and cooling fields are found to have significant differences and the differences are explained in the light of recent results which suggest that both weakly and strongly pinned spins are present at the interface. It is suggested that the exchange bias is dominated by the weakly pinned spins while the vertical shift is affected by the strongly pinned ones.Comment: 2

Lithium interactions with non-steroidal anti-inflammatory drugs and diuretics – A review

Background: Lithium is often used in bipolar disorder and occasionally in unipolar depression. Non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics are frequently prescribed and their interaction with lithium is based mainly in few small studies. Objectives: Conduct a review, identify different interaction patterns and discuss treatment options. Methods: Three searches were made in PubMed in January 2016: 1) using the keywords “lithium” [and] “non-steroidal anti-inflammatory”; 2) using the keywords “lithium” [and] “diuretics” and the filter “title/abstract”; 3) using the terms “lithium” [and] “toxicity” and the filters “title” [and] “review”. From the 293 remaining articles, 10 were selected. Another search in Scielo.org was made, using the term “lítio” and the filter “Psiquiatria”. Two articles were selected from the initial 53. Six textbooks were added to expand the evidence, achieving a total of 18 references. Results: The majority of NSAIDs and diuretics rises lithium levels, specially thiazides. However, some show great variability or no interaction at all, and others even decrease lithium levels. Discussion: Lower-doses, shorter durations, lithium adjustments and levels' follow-ups are recommended, especially in elderly and multiple co-morbid patients

A Standardised Procedure for Evaluating Creative Systems: Computational Creativity Evaluation Based on What it is to be Creative

Computational creativity is a flourishing research area, with a variety of creative systems being produced and developed. Creativity evaluation has not kept pace with system development with an evident lack of systematic evaluation of the creativity of these systems in the literature. This is partially due to difficulties in defining what it means for a computer to be creative; indeed, there is no consensus on this for human creativity, let alone its computational equivalent. This paper proposes a Standardised Procedure for Evaluating Creative Systems (SPECS). SPECS is a three-step process: stating what it means for a particular computational system to be creative, deriving and performing tests based on these statements. To assist this process, the paper offers a collection of key components of creativity, identified empirically from discussions of human and computational creativity. Using this approach, the SPECS methodology is demonstrated through a comparative case study evaluating computational creativity systems that improvise music

Approximate Solutions to Fractional Subdiffusion Equations: The heat-balance integral method

The work presents integral solutions of the fractional subdiffusion equation by an integral method, as an alternative approach to the solutions employing hypergeometric functions. The integral solution suggests a preliminary defined profile with unknown coefficients and the concept of penetration (boundary layer). The prescribed profile satisfies the boundary conditions imposed by the boundary layer that allows its coefficients to be expressed through its depth as unique parameter. The integral approach to the fractional subdiffusion equation suggests a replacement of the real distribution function by the approximate profile. The solution was performed with Riemann -Liouville time-fractional derivative since the integral approach avoids the definition of the initial value of the time-derivative required by the Laplace transformed equations and leading to a transition to Caputo derivatives. The method is demonstrated by solutions to two simple fractional subdiffusion equations (Dirichlet problems): 1) Time-Fractional Diffusion Equation, and 2) Time-Fractional Drift Equation, both of them having fundamental solutions expressed through the M-Write function. The solutions demonstrate some basic issues of the suggested integral approach, among them: a) Choice of the profile, b) Integration problem emerging when the distribution (profile) is replaced by a prescribed one with unknown coefficients; c) Optimization of the profile in view to minimize the average error of approximations; d) Numerical results allowing comparisons to the known solutions expressed to the M-Write function and error estimations.Comment: 15 pages, 7 figures, 3 table

Early childhood caries in preschool children of Kosovo - a serious public health problem

<p>Abstract</p> <p>Background</p> <p>Even though it has been widely studied, early childhood caries (ECC) remains a serious public health problem, especially in countries where there is no national program of oral health assessment and no genuine primary oral health care, such as in Kosovo. The purpose of this study was to assess the prevalence of ECC and analyze caries risk factors.</p> <p>Methods</p> <p>The subjects were 1,008 preschool children, selected by stratified random cluster sampling, in the municipality of Prishtina, capital of Kosovo. Data were collected through clinical examination and interviews. Dmft data were recorded according to WHO criteria. Bacterial examination (CRT bacteria test) and plaque test of Greene-Vermillion were used.</p> <p>Results</p> <p>The mean dmft of preschool children was found to be 5.8. The prevalence of ECC was 17.36%, with a mean dmft of 11 ± 3.6. Streptococcus mutans prevalence in ECC children was 98%. A significant correlation between dmft and S mutans counts (≥10⁵CFU/mL saliva) was demonstrated. A correlation was also found between daily sweets consumption and dmft in children with ECC (<it>P </it>< 0.001). Comparing the dmft of ECC children and duration of bottle feeding showed a statistical correlation (<it>P </it>< 0.001). The mean plaque test was 1.52. None of the examined children had ever used fluoride.</p> <p>Conclusion</p> <p>The prevalence of ECC was high among preschool children in the municipality of Kosovo. We recommend increasing parents' knowledge of proper feeding habits and oral health practices, and increasing preschool children's accessibility to dental services.</p

Early Childhood Caries among a Bedouin community residing in the eastern outskirts of Jerusalem

<p>Abstract</p> <p>Background</p> <p>ECC is commonly prevalent among underprivileged populations. The Jahalin Bedouin are a severely deprived, previously nomadic tribe, dwelling on the eastern outskirts of Jerusalem. The aim of this study was to assess ECC prevalence and potentially associated variables.</p> <p>Methods</p> <p>102 children aged 12–36 months were visually examined for caries, mothers' anterior dentition was visually subjectively appraised, demographic and health behavior data were collected by interview.</p> <p>Results</p> <p>Among children, 17.6% demonstrated ECC, among mothers, 37.3% revealed "fairly bad" anterior teeth. Among children drinking bottles there was about twice the level of ECC (20.3%) than those breast-fed (13.2%). ECC was found only among children aged more than one year (p < 0.001); more prevalent ECC (55.6%) was found among large (10–13 children) families than among smaller families (1–5 children: 13.5%, 6–9 children: 15.6%) (p = 0.009); ECC was more prevalent among children of less educated mothers (p = 0.037); ECC was more prevalent among mothers with "fairly poor" anterior dentition (p = 0.04). Oral hygiene practices were poor.</p> <p>Conclusion</p> <p>ECC levels in this community were not very high but neither low. This changing population might be on the verge of a wider dental disease "epidemic". Public health efforts clearly need to be invested towards the oral health and general welfare of this community.</p

Impact of risk factors on the timing of first postpartum venous thromboembolism: a population-based cohort study from England

For women with preeclampsia, BMI &gt;30 kg/m2, infection, or those having cesarean delivery, VTE risk remained elevated for 6 weeks postpartum.For women with postpartum hemorrhage or preterm birth, the relative rate of VTE was only increased for the first 3 weeks postpartum.Impact on the timing of first postpartum venous thromboembolism (VTE) for women with specific risk factors is of crucial importance when planning the duration of thromboprophylaxis regimen. We observed this using a large linked primary and secondary care database containing 222 334 pregnancies resulting in live and stillbirth births between 1997 and 2010. We assessed the impact of risk factors on the timing of postpartum VTE in term of absolute rates (ARs) and incidence rate ratios (IRRs) using a Poisson regression model. Women with preeclampsia/eclampsia and postpartum acute systemic infection had the highest risk of VTE during the first 3 weeks postpartum (ARs ≥2263/100 000 person-years; IRR ≥2.5) and at 4-6 weeks postpartum (AR ≥1360; IRR ≥3.5). Women with body mass index (BMI) &gt;30 kg/m2 or those having cesarean delivery also had elevated rates up to 6 weeks (AR ≥1425 at 1-3 weeks and ≥722 at 4-6 weeks). Women with postpartum hemorrhage or preterm birth, had significantly increased VTE rates only in the first 3 weeks (AR ≥1736; IRR ≥2). Our findings suggest that the duration of the increased VTE risk after childbirth varies based on the type of risk factors and can extend up to the first 3 to 6 weeks postpartum

Dexmedetomidine sedation in ICU

Dexmedetomidine (DEX), a highly selective α2-adrenergic receptor agonist, is the newest agent introduced for sedation in intensive care unit (ICU). The sedation strategy for critically ill patients has stressed light sedation with daily awakening and assessment for neurologic, cognitive, and respiratory functions, since Society of Critical Care Medicine (SCCM) guidelines were presented in 2002. The traditional GABAergic agents, including benzodiazepines and propofol, have some limitations for safe sedatives in this setting, due to an unfavorable pharmacokinetic profile and to detrimental adverse effects (such as lorazepam associated propylene glycol intoxication and propofol infusion syndrome). DEX produces it's sedative, analgesic and cardiovascular effects through α2 receptors on the locus ceruleus (LC). Activities of LC, the tuberomammillary nucleus (TMN) are depressed and activity of the ventrolateral preoptic nucleus (VLPO) is increased during DEX sedation, which is similar in features to normal non-REM (NREM) sleep. At the same time, perifornical orexinergic activity is maintained, which might be associated with attention. This mechanism of action produces a normal sleep-like, cooperative sedation. The characteristic feature of sedation, together with a concomitant opioid sparing effect, may decrease the length of time spent on a ventilator, length of stay in ICU, and prevalence and duration of delirium, as the evidence shown from several comparative studies. In addition, DEX has an excellent safety profile. In conclusion, DEX is considered as a promising agent optimized for sedation in ICU