N-acetylcysteine improves the hemodynamics and oxidative stress in hypoxic newborn pigs reoxygenated with 100% oxygen

Neonatal asphyxia may lead to cardiac and renal complications perhaps mediated by oxygen free radicals. Using a model of neonatal hypoxia-reoxygenation, we tested the hypothesis that N-acetylcysteine (NAC) would improve cardiac function and renal blood flow. Eighteen piglets (aged 1-4 days old, weighing 1.4-2.2 kg) were anesthetized and acutely instrumented for continuous monitoring of pulmonary and renal artery flow (cardiac index [CI] and renal artery flow index [RAFI], respectively) and mean blood pressure. Alveolar hypoxia was induced for 2 h, followed by resuscitation with 100% oxygen for 1 h and 21% oxygen for 3 h. Animals were randomized to sham-operated, hypoxic control, and NAC treatment (i.v. bolus of 150 mg/kg given at 10 min of reoxygenation followed by 100 mg/kg per h infusion) groups. Myocardial and renal tissue glutathione content and lipid hydroperoxide levels were assayed, and histology was examined. After 2 h of hypoxia, all animals were acidotic (pH 6.96 +/- 0.04) and in cardiogenic shock with depressed renal blood flow. Upon reoxygenation, CI and RAFI increased but gradually deteriorated later. The NAC treatment prevented the decreased CI, stroke volume, mean blood pressure, systemic oxygen delivery, RAFI, and renal oxygen delivery at 2 to 4 h of reoxygenation observed in hypoxic controls (versus shams, all P < 0.05). The myocardial and renal tissue glutathione content was significantly higher in the NAC treatment group (versus controls). The CI and RAFI at 4 h of reoxygenation correlated with the tissue glutathione redox ratio (r = 0.5 and 0.6, respectively, P < 0.05). There were no significant differences in heart rate, pulmonary artery pressure, systemic oxygen uptake, and tissue lipid hydroperoxide levels between groups. No histologic injury was found in the heart or kidney. In this porcine model of neonatal hypoxia and 100% reoxygenation, NAC improved cardiac function and renal perfusion, with improved tissue glutathione content.     

Waiting for a Pediatric Chronic Pain Clinic Evaluation: A Prospective Study Characterizing Waiting Times and Symptom Trajectories

Chronic pain during childhood is prevalent and costly, but the access to interdisciplinary pain care is limited. Studies investigating adults waiting for pain clinic evaluation found that symptoms and quality of life deteriorate over the waiting period, but little is known about the experience of adolescents. Therefore, we aimed to determine wait list times and the longitudinal trends of pain and physical, mental, and social health over a 12-week period. In total, 97 adolescents, aged 10 to 18 years (M?=?14.7 years, 82% female), waiting for evaluation at an interdisciplinary pediatric pain clinic completed assessments at enrollment and at 4-, 8-, and 12-week follow-up. We performed a review of the medical record of attendance patterns 12 months later. Twelve adolescents and their parents also completed qualitative interviews, describing their experience of waiting for evaluation. Wait times averaged 197.5 days (range?=?69–758 days) from the time of referral to the first-attended appointment, and 86.6% of youths completed appointments. Longitudinal repeated measures analyses demonstrated little improvement in pain or other domains of functioning over the 12-week period. In qualitative interviews, families described anxious anticipation for the upcoming appointment, combined with frustration in waiting. Findings highlight the need to consider approaches to reduce wait times and provide early intervention for youths awaiting pain clinic evaluation.Perspective: This study extends the literature on the characteristics and symptom trajectories of adolescents during the wait period for interdisciplinary pain clinic evaluation, described previously only in adults with chronic pain. Findings demonstrated an average wait time of 6.5 months, during which youths’ pain and physical and social health remained impaired.     

Air pollution exposure estimation using dispersion modelling and continuous monitoring data in a prospective birth cohort study in the Netherlands

Background

High temperature and humidity conditions are associated with short-term elevations in the mortality rate in many United States cities. Previous research has quantified this relationship in an aggregate manner over large metropolitan areas, but within these areas the response may differ based on local-scale variability in climate, population characteristics, and socio-economic factors.

Methods

We compared the mortality response for 48 Zip Code Tabulation Areas (ZCTAs) comprising Philadelphia County, PA to determine if certain areas are associated with elevated risk during high heat stress conditions. A randomization test was used to identify mortality exceedances for various apparent temperature thresholds at both the city and local scale. We then sought to identify the environmental, demographic, and social factors associated with high-risk areas via principal components regression.

Results

Citywide mortality increases by 9.3% on days following those with apparent temperatures over 34°C observed at 7:00 p.m. local time. During these conditions, elevated mortality rates were found for 10 of the 48 ZCTAs concentrated in the west-central portion of the County. Factors related to high heat mortality risk included proximity to locally high surface temperatures, low socioeconomic status, high density residential zoning, and age.

Conclusions

Within the larger Philadelphia metropolitan area, there exists statistically significant fine-scale spatial variability in the mortality response to high apparent temperatures. Future heat warning systems and mitigation and intervention measures could target these high risk areas to reduce the burden of extreme weather on summertime morbidity and mortality.     

Systematic Review of Intervention Practices for Depression in the Workplace

Design Systematic Review. Objective To determine which intervention approaches to manage depression in the workplace have been successful and yielded value for employers in developed economies. Data Sources We searched MEDLINE, EMBASE, CINAHL, Central, PsycINFO, and Business Source Premier up to June 2010 using search terms in four broad areas: work setting, depression, intervention, and work outcomes. Study Selection Two independent reviewers selected potential articles that met the following criteria: working age individuals with mild or moderate depression; interventions or programs that were workplace-based or could be implemented and/or facilitated by the employer; inclusion of a comparator group in the analysis; outcomes of prevention, management, and recurrences of work disability or sickness absence, and work functioning. Methods Two reviewers independently reviewed each article for quality and extracted data using standardised forms. Following guidelines from the GRADE Working Group, the quality of evidence addressing each outcome was graded as high, moderate, low, or very low on the basis of six criteria: study design, risk of bias, consistency, generalisability, data precision, and economic benefit. Using this information and following Cochrane Collaboration guidelines, the findings for each intervention were summarised and key messages were developed. Results We identified ten randomised trials and two non-randomised studies from various countries and jurisdictions that evaluated a wide range of intervention practices. The evidence was graded as ??very low?? for all outcomes identified. Therefore, no intervention could be recommended. Conclusions To date, there is insufficient quality of evidence to determine which interventions are effective and yield value to manage depression in the workplace.     

Biases and errors on allele frequency estimation and disease association tests of next-generation sequencing of pooled samples

Next-generation sequencing is widely used to study complex diseases because of its ability to identify both common and rare variants without prior single nucleotide polymorphism (SNP) information. Pooled sequencing of implicated target regions can lower costs and allow more samples to be analyzed, thus improving statistical power for disease-associated variant detection. Several methods for disease association tests of pooled data and for optimal pooling designs have been developed under certain assumptions of the pooling process, for example, equal/unequal contributions to the pool, sequencing depth variation, and error rate. However, these simplified assumptions may not portray the many factors affecting pooled sequencing data quality, such as PCR amplification during target capture and sequencing, reference allele preferential bias, and others. As a result, the properties of the observed data may differ substantially from those expected under the simplified assumptions. Here, we use real datasets from targeted sequencing of pooled samples, together with microarray SNP genotypes of the same subjects, to identify and quantify factors (biases and errors) affecting the observed sequencing data. Through simulations, we find that these factors have a significant impact on the accuracy of allele frequency estimation and the power of association tests. Furthermore, we develop a workflow protocol to incorporate these factors in data analysis to reduce the potential biases and errors in pooled sequencing data and to gain better estimation of allele frequencies. The workflow, Psafe, is available at http://bioinformatics.med.yale.edu/group/.     

Balloon angioplasty with stenting to correct a functionally interrupted aorta: A case report with three‐year follow‐up

A 16‐year‐old male presenting with upper extremity hypertension was found to have a severe form of discrete coarctation with complete luminal obliteration, causing a functional interruption of the thoracic aorta. Fluoroscopically guided perforation of the obstruction and creation of a neo‐aortic lumen was performed. This was followed by balloon angioplasty and stent placement, successfully relieving the coarctation. The procedural method, acute and late follow‐up results, and a discussion of the potential risks and benefits are presented. © 2008 Wiley‐Liss, Inc.     

Embolus in transit.

Since the advent of echocardiography, embolus in transit, historically found during surgical exploration or on postmortem examination, has been found with increasing frequency on antemortem examination. There is an inherent high mortality rate with this condition and awareness of the association between deep venous thrombosis and embolus in transit is paramount. On echocardiography the embolus is typically seen as a pleomorphic mass moving in a tumbling fashion. The most frequent symptoms are dyspnea and near syncopal episodes. The most common signs are diastolic "tumor plop" and a systolic ejection murmur heard on auscultation. Despite the success of some medical interventions, surgery should be strongly considered in patients with embolus in transit.     

Transcatheter coil closure of a right pulmonary artery to left atrial fistula in an ill neonate.

Although rare, a congenital direct fistula connection between the proximal right pulmonary artery and the left atrium can present as cyanosis in the newborn. We report the first case in which catheter-based coil closure of such a fistula in a neonate resulted in rapid clinical improvement, obviating the need for surgical repair.