Dietary Mg2+ Intake and the Na+/Mg2+ Exchanger SLC41A1 Influence Components of Mitochondrial Energetics in Murine Cardiomyocytes

Cardiomyocytes are among the most energy-intensive cell types. Interplay between the components of cellular magnesium (Mg) homeostasis and energy metabolism in cardiomyocytes is poorly understood. We have investigated the effects of dietary Mg content and presence/functionality of the Na+/Mg2+ exchanger SLC41A1 on enzymatic functions of selected constituents of the Krebs cycle and complexes of the electron transport chain (ETC). The activities of aconitate hydratase (ACON), isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (KGDH), and ETC complexes CI–CV have been determined in vitro in mitochondria isolated from hearts of wild-type (WT) and Slc41a1−/− mice fed a diet with either normal or low Mg content. Our data demonstrate that both, the type of Mg diet and the Slc41a1 genotype largely impact on the activities of enzymes of the Krebs cycle and ETC. Moreover, a compensatory effect of Slc41a1−/− genotype on the effect of low Mg diet on activities of the tested Krebs cycle enzymes has been identified. A machine-learning analysis identified activities of ICDH, CI, CIV, and CV as common predictors of the type of Mg diet and of CII as suitable predictor of Slc41a1 genotype. Thus, our data delineate the effect of dietary Mg content and of SLC41A1 functionality on the energy-production in cardiac mitochondria

CP Violation in Hyperon Nonleptonic Decays within the Standard Model

We calculate the CP-violating asymmetries A(Lambda_-^0) and A(Xi_-^-) in nonleptonic hyperon decay within the Standard Model using the framework of heavy-baryon chiral perturbation theory (chiPT). We identify those terms that correspond to previous calculations and discover several errors in the existing literature. We present a new result for the lowest-order (in chiPT) contribution of the penguin operator to these asymmetries, as well as an estimate for the uncertainty of our result that is based on the calculation of the leading nonanalytic corrections.Comment: 21 pages, 2 figures; discussion clarified, results & conclusions unchanged, to appear in Phys. Rev.

New Physics and CP Violation in Hyperon Nonleptonic Decays

The sum of the CP-violating asymmetries A(Lambda_-^0) and A(Xi_-^-) in hyperon nonleptonic decays is presently being measured by the E871 experiment. We evaluate contributions to the asymmetries induced by chromomagnetic-penguin operators, whose coefficients can be enhanced in certain models of new physics. Incorporating recent information on the strong phases in Xi->Lambda pi decay, we show that new-physics contributions to the two asymmetries can be comparable. We explore how the upcoming results of E871 may constrain the coefficients of the operators. We find that its preliminary measurement is already better than the epsilon parameter of K-Kbar mixing in bounding the parity-conserving contributions.Comment: 12 pages, 2 figure

Invasive meningococcal disease epidemiology and control measures: a framework for evaluation

<p>Abstract</p> <p>Background</p> <p>Meningococcal disease can have devastating consequences. As new vaccines emerge, it is necessary to assess their impact on public health. In the absence of long-term real world data, modeling the effects of different vaccination strategies is required. Discrete event simulation provides a flexible platform with which to conduct such evaluations.</p> <p>Methods</p> <p>A discrete event simulation of the epidemiology of invasive meningococcal disease was developed to quantify the potential impact of implementing routine vaccination of adolescents in the United States with a quadrivalent conjugate vaccine protecting against serogroups A, C, Y, and W-135. The impact of vaccination is assessed including both the direct effects on individuals vaccinated and the indirect effects resulting from herd immunity. The simulation integrates a variety of epidemiologic and demographic data, with core information on the incidence of invasive meningococcal disease and outbreak frequency derived from data available through the Centers for Disease Control and Prevention. Simulation of the potential indirect benefits of vaccination resulting from herd immunity draw on data from the United Kingdom, where routine vaccination with a conjugate vaccine has been in place for a number of years. Cases of disease are modeled along with their health consequences, as are the occurrence of disease outbreaks.</p> <p>Results</p> <p>When run without a strategy of routine immunization, the simulation accurately predicts the age-specific incidence of invasive meningococcal disease and the site-specific frequency of outbreaks in the Unite States. 2,807 cases are predicted annually, resulting in over 14,000 potential life years lost due to invasive disease. In base case analyses of routine vaccination, life years lost due to infection are reduced by over 45% (to 7,600) when routinely vaccinating adolescents 12 years of age at 70% coverage. Sensitivity analyses indicate that herd immunity plays an important role when this population is targeted for vaccination. While 1,100 cases are avoided annually when herd immunity effects are included, in the absence of any herd immunity, the number of cases avoided with routine vaccination falls to 380 annually. The duration of vaccine protection also strongly influences results.</p> <p>Conclusion</p> <p>In the absence of appropriate real world data on outcomes associated with large-scale vaccination programs, decisions on optimal immunization strategies can be aided by discrete events simulations such as the one described here. Given the importance of herd immunity on outcomes associated with routine vaccination, published estimates of the economic efficiency of routine vaccination with a quadrivalent conjugate vaccine in the United States may have considerably underestimated the benefits associated with a policy of routine immunization of adolescents.</p

Disorders of Transepidermal Elimination

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65203/1/j.1365-4362.1985.tb05799.x.pd

Topical antibiotics for preventing surgical site infection in wounds healing by primary intention

BACKGROUND: Surgical site infections (SSI) can delay wound healing, impair cosmetic outcome and increase healthcare costs. Topical antibiotics are sometimes used to reduce microbial contaminant exposure following surgical procedures, with the aim of reducing SSIs.OBJECTIVES: The primary objective of this review was to determine whether the application of topical antibiotics to surgical wounds that are healing by primary intention reduces the incidence of SSI and whether it increases the incidence of adverse outcomes (allergic contact dermatitis, infections with patterns of antibiotic resistance and anaphylaxis).SEARCH METHODS: In May 2015 we searched: the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL; the Cochrane Library); Ovid MEDLINE; Ovid MEDLINE (In-Process &amp; Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL. We also searched clinical trial registries for ongoing studies, and bibliographies of relevant publications to identify further eligible trials. There was no restriction of language, date of study or setting. The search was repeated in May 2016 to ensure currency of included studies.SELECTION CRITERIA: All randomized controlled trials (RCTs) and quasi-randomised trials that assessed the effects of topical antibiotics (any formulation, including impregnated dressings) in people with surgical wounds healing by primary intention were eligible for inclusion.DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and independently extracted data. Two authors then assessed the studies for risk of bias. Risk ratios were calculated for dichotomous variables, and when a sufficient number of comparable trials were available, trials were pooled in a meta-analysis.MAIN RESULTS: A total of 10 RCTs and four quasi-randomised trials with 6466 participants met the inclusion criteria. Six studies involved minor procedures conducted in an outpatient or emergency department setting; eight studies involved major surgery conducted in theatre. Nine different topical antibiotics were included. We included two three-arm trials, two four-arm trials and 10 two-arm trials. The control groups comprised; an alternative topical antibiotic (two studies), topical antiseptic (six studies) and no topical antibiotic (10 studies), which comprised inert ointment (five studies) no treatment (four studies) and one study with one arm of each.The risk of bias of the 14 studies varied. Seven studies were at high risk of bias, five at unclear risk of bias and two at low risk of bias. Most risk of bias concerned risk of selection bias.Twelve of the studies (6259 participants) reported infection rates, although we could not extract the data for this outcome from one study. Four studies (3334 participants) measured allergic contact dermatitis as an outcome. Four studies measured positive wound swabs for patterns of antimicrobial resistance, for which there were no outcomes reported. No episodes of anaphylaxis were reported. Topical antibiotic versus no topical antibioticWe pooled the results of eight trials (5427 participants) for the outcome of SSI. Topical antibiotics probably reduce the risk of SSI in people with surgical wounds healing by primary intention compared with no topical antibiotic (RR 0.61, 95% CI 0.42 to 0.87; moderate-quality evidence downgraded once for risk of bias). This equates to 20 fewer SSIs per 1000 patients treated with topical antibiotics (95% CI 7 to 29) and a number needed to treat for one additional beneficial outcome (NNTB) (i.e. prevention of one SSI) of 50.We pooled the results of three trials (3012 participants) for the outcome of allergic contact dermatitis, however this comparison was underpowered, and it is unclear whether topical antibiotics affect the risk of allergic contact dermatitis (RR 3.94, 95% CI 0.46 to 34.00; very low-quality evidence, downgraded twice for risk of bias, once for imprecision). Topical antibiotic versus antiseptic We pooled the results of five trials (1299 participants) for the outcome of SSI. Topical antibiotics probably reduce the risk of SSI in people with surgical wounds healing by primary intention compared with using topical antiseptics (RR 0.49, 95% CI 0.30 to 0.80; moderate-quality evidence downgraded once for risk of bias). This equates to 43 fewer SSIs per 1000 patients treated with topical antibiotics instead of antiseptics (95% CI 17 to 59) and an NNTB of 24.We pooled the results of two trials (541 participants) for the outcome of allergic contact dermatitis; there was no clear difference in the risk of dermatitis between topical antibiotics and antiseptics, however this comparison was underpowered and a difference cannot be ruled out (RR 0.97, 95% CI 0.52 to 1.82; very low-quality evidence, downgraded twice for risk of bias and once for imprecision). Topical antibiotic versus topical antibioticOne study (99 participants) compared mupirocin ointment with a combination ointment of neomycin/polymyxin B/bacitracin zinc for the outcome of SSI. There was no clear difference in the risk of SSI, however this comparison was underpowered (very low-quality evidence downgraded twice for risk of bias, once for imprecision).A four-arm trial involved two antibiotic arms (neomycin sulfate/bacitracin zinc/polymyxin B sulphate combination ointment versus bacitracin zinc, 219 participants). There was no clear difference in risk of SSI between the combination ointment and the bacitracin zinc ointment. The quality of evidence for this outcome was low, downgraded once for risk of bias, and once for imprecision.AUTHORS' CONCLUSIONS: Topical antibiotics applied to surgical wounds healing by primary intention probably reduce the risk of SSI relative to no antibiotic, and relative to topical antiseptics (moderate quality evidence). We are unable to draw conclusions regarding the effects of topical antibiotics on adverse outcomes such as allergic contact dermatitis due to lack of statistical power (small sample sizes). We are also unable to draw conclusions regarding the impact of increasing topical antibiotic use on antibiotic resistance. The relative effects of different topical antibiotics are unclear.</p

Cost-Effectiveness of Adolescent Pertussis Vaccination for The Netherlands: Using an Individual-Based Dynamic Model

BACKGROUND: Despite widespread immunization programs, a clear increase in pertussis incidence is apparent in many developed countries during the last decades. Consequently, additional immunization strategies are considered to reduce the burden of disease. The aim of this study is to design an individual-based stochastic dynamic framework to model pertussis transmission in the population in order to predict the epidemiologic and economic consequences of the implementation of universal booster vaccination programs. Using this framework, we estimate the cost-effectiveness of universal adolescent pertussis booster vaccination at the age of 12 years in the Netherlands. METHODS/PRINCIPAL FINDINGS: We designed a discrete event simulation (DES) model to predict the epidemiological and economic consequences of implementing universal adolescent booster vaccination. We used national age-specific notification data over the period 1996-2000--corrected for underreporting--to calibrate the model assuming a steady state situation. Subsequently, booster vaccination was introduced. Input parameters of the model were derived from literature, national data sources (e.g. costing data, incidence and hospitalization data) and expert opinions. As there is no consensus on the duration of immunity acquired by natural infection, we considered two scenarios for this duration of protection (i.e. 8 and 15 years). In both scenarios, total pertussis incidence decreased as a result of adolescent vaccination. From a societal perspective, the cost-effectiveness was estimated at €4418/QALY (range: 3205-6364 € per QALY) and €6371/QALY (range: 4139-9549 € per QALY) for the 8- and 15-year protection scenarios, respectively. Sensitivity analyses revealed that the outcomes are most sensitive to the quality of life weights used for pertussis disease. CONCLUSIONS/SIGNIFICANCE: To our knowledge we designed the first individual-based dynamic framework to model pertussis transmission in the population. This study indicates that adolescent pertussis vaccination is likely to be a cost-effective intervention for The Netherlands. The model is suited to investigate further pertussis booster vaccination strategies

Enfermedades crónicas

Adherencia al tratamiento farmacol&oacute;gico y relaci&oacute;n con el control metab&oacute;lico en pacientes con DM2Aluminio en pacientes con terapia de reemplazo renal cr&oacute;nico con hemodi&aacute;lisis en Bogot&aacute;, ColombiaAmputaci&oacute;n de extremidades inferiores: &iquest;est&aacute;n aumentando las tasas?Consumo de edulcorantes artificiales en j&oacute;venes universitariosC&oacute;mo crecen ni&ntilde;os normales de 2 a&ntilde;os que son sobrepeso a los 7 a&ntilde;osDiagn&oacute;stico con enfoque territorial de salud cardiovascular en la Regi&oacute;n MetropolitanaEfecto a corto plazo de una intervenci&oacute;n con ejercicio f&iacute;sico, en ni&ntilde;os con sobrepesoEfectos de la cirug&iacute;a bari&aacute;trica en pacientes con s&iacute;ndrome metab&oacute;lico e IMC &lt; 35 KG/M2Encuesta mundial de tabaquismo en estudiantes de profesiones de saludEnfermedades cr&oacute;nicas no transmisibles: Consecuencias sociales-sanitarias de comunidades rurales en ChileEpidemiolog&iacute;a de las muertes hospitalarias por patolog&iacute;as relacionadas a muerte encef&aacute;lica, Chile 2003-2007Estado nutricional y conductas alimentarias en adolescentes de 4&ordm; medio de la Regi&oacute;n de CoquimboEstudio de calidad de vida en una muestra del plan piloto para hepatitis CEvaluaci&oacute;n del proceso asistencial y de resultados de salud del GES de diabetes mellitus 2Factores de riesgo cardiovascular en poblaci&oacute;n universitaria de la Facsal, universidad de Tarapac&aacute;Implicancias psicosociales en la g&eacute;nesis, evoluci&oacute;n y tratamiento de pacientes con hipertensi&oacute;n arterial esencialInfarto agudo al miocardio (IAM): Realidad en el Hospital de Puerto Natales, 2009-2010Introducci&oacute;n de nuevas TIC y mejor&iacute;a de la asistencia a un programa de saludNi&ntilde;os obesos atendidos en el Cesfam de Puerto Natales y su entorno familiarPerfil de la mortalidad por c&aacute;ncer de cuello uterino en R&iacute;o de JaneiroPerfil del paciente primo-consultante del Programa de Salud Cardiovascular, Consultorio Cordillera Andina, Los AndesPrevalencia de automedicaci&oacute;n en mujeres beneficiarias del Hospital Comunitario de Til-TiPrevalencia de caries en poblaci&oacute;n preescolar y su relaci&oacute;n con malnutrici&oacute;n por excesoPrevalencia de retinopat&iacute;a diab&eacute;tica en comunas dependientes del Servicio de Salud Metropolitano Occidente (SSMOC)Problemas de adherencia farmacol&oacute;gica antihipertensiva en poblaci&oacute;n mapuche: Un estudio cualitativoRol biol&oacute;gico de los antioxidantes innatos en pacientes portadores de VIH/SidaSobrepeso en empleados de un restaurante de una universidad p&uacute;blica del estado de S&atilde;o Paul

Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe