Plasma 3-nitrotyrosine and outcome in neonates with severe bronchopulmonary dysplasia after inhaled nitric oxide

Plasma protein levels of 3-nitrotyrosine and 3-chlorotyrosine were measured by LC-MS/MS at 0 and 72 h after the initiation of inhaled nitric oxide (INO) at 20 ppm in 22 prematurely born infants with clinically documented bronchopulmonary dysplasia. Infants were classified at the time of hospital discharge as either "off mechanical ventilation," "on mechanical ventilation," or "expired/organ failure." These outcomes were tested for association with changes in plasma levels of 3-nitrotyrosine and 3-chlorotyrosine and selected clinical risk factors. Infants whose 3-nitrotyrosine levels decreased over the 72 h period were more likely to wean off of mechanical ventilation (p =.03). There was no significant association between changes in 3-chlorotyrosne levels and outcome. After controlling for other variables, an odds ratio of 8.3 (95% CI: 1.3-54.4) for improved outcomes was observed if the 3-nitrotyrosine levels decreased. These data suggest that nitrative and oxidative stress may be related to the severity of lung disease and, consequentially, the overall outcome in this select group of infants with severe bronchopulmonary dysplasia.     

The Association of Statin Use after Cancer Diagnosis with Survival in Pancreatic Cancer Patients: A SEER-Medicare Analysis

Background

Pancreatic cancer has poor prognosis and existing interventions provide a modest benefit. Statin has anti-cancer properties that might enhance survival in pancreatic cancer patients. We sought to determine whether statin treatment after cancer diagnosis is associated with longer survival in those with pancreatic ductal adenocarcinoma (PDAC).

Methods

We analyzed data on 7813 elderly patients with PDAC using the linked Surveillance, Epidemiology, and End Results (SEER) - Medicare claims files. Information on the type, intensity and duration of statin use after cancer diagnosis was extracted from Medicare Part D. We treated statin as a time-dependent variable in a Cox regression model to determine the association with overall survival adjusting for follow-up, age, sex, race, neighborhood income, stage, grade, tumor size, pancreatectomy, chemotherapy, radiation, obesity, dyslipidemia, diabetes, chronic pancreatitis and chronic obstructive pulmonary disease (COPD).

Results

Overall, statin use after cancer diagnosis was not significantly associated with survival when all PDAC patients were considered (HR = 0.94, 95%CI 0.89, 1.01). However, statin use after cancer diagnosis was associated with a 21% reduced hazard of death (Hazard ratio = 0.79, 95% confidence interval (CI) 0.67, 0.93) in those with grade I or II PDAC and to a similar extent in those who had undergone a pancreatectomy, in those with chronic pancreatitis and in those who had not been treated with statin prior to cancer diagnosis.

Conclusions

We found that statin treatment after cancer diagnosis is associated with enhanced survival in patients with low-grade, resectable PDAC.     

Selection against Heteroplasmy Explains the Evolution of Uniparental Inheritance of Mitochondria

Why are mitochondria almost always inherited from one parent during sexual reproduction? Current explanations for this evolutionary mystery include conflict avoidance between the nuclear and mitochondrial genomes, clearing of deleterious mutations, and optimization of mitochondrial-nuclear coadaptation. Mathematical models, however, fail to show that uniparental inheritance can replace biparental inheritance under any existing hypothesis. Recent empirical evidence indicates that mixing two different but normal mitochondrial haplotypes within a cell (heteroplasmy) can cause cell and organism dysfunction. Using a mathematical model, we test if selection against heteroplasmy can lead to the evolution of uniparental inheritance. When we assume selection against heteroplasmy and mutations are neither advantageous nor deleterious (neutral mutations), uniparental inheritance replaces biparental inheritance for all tested parameter values. When heteroplasmy involves mutations that are advantageous or deleterious (non-neutral mutations), uniparental inheritance can still replace biparental inheritance. We show that uniparental inheritance can evolve with or without pre-existing mating types. Finally, we show that selection against heteroplasmy can explain why some organisms deviate from strict uniparental inheritance. Thus, we suggest that selection against heteroplasmy explains the evolution of uniparental inheritance.     

The effect of helmets on the risk of head and neck injuries among skiers and snowboarders: a meta-analysis

Background

The prevention of head injuries in alpine activities has focused on helmets. However, no systematic review has examined the effect of helmets on head and neck injuries among skiers and snowboarders.

Methods

We searched electronic databases, conference proceedings and reference lists using a combination of the key words “head injury or head trauma,” “helmet” and “skiing or snowboarding.” We included studies that used a control group; compared skiers or snowboarders with and without helmets; and measured at least one objectively quantified outcome (e.g., head injury, and neck or cervical injury).

Results

We included 10 case–control, 1 case–control/case-crossover and 1 cohort study in our analysis. The pooled odds ratio (OR) indicated that skiers and snowboarders with a helmet were significantly less likely than those without a helmet to have a head injury (OR 0.65, 95% confidence interval [CI] 0.55–0.79). The result was similar for studies that used controls without an injury (OR 0.61, 95% CI 0.36–0.92), those that used controls with an injury other than a head or neck injury (OR 0.63, 95% CI 0.52–0.80) and studies that included children under the age of 13 years (OR 0.41, 95% CI 0.27–0.59). Helmets were not associated with an increased risk of neck injury (OR 0.89, 95% CI 0.72–1.09).

Interpretation

Our findings show that helmets reduce the risk of head injury among skiers and snowboarders with no evidence of an increased risk of neck injury.Skiing and snowboarding are popular winter activities.¹ Estimates from numerous countries indicate that head injuries account for 9% to 19%, and neck injuries for 1% to 4%, of all injuries reported by ski patrols and emergency departments.^2–11 Rates of head and neck injuries have been reported between 0.09 and 0.46 per 1000 outings.¹² Head and neck injuries are disproportionately represented in cases of severe trauma, and traumatic brain injury is the leading cause of death and serious injury among skiers and snow-boarders.¹³ As far back as 1983, Oh and Schmid recommended mandatory helmet use for children while skiing.¹⁴Many studies of the relation between helmet use and head injuries among skiers and snowboarders have found a protective effect.^15–24 It has been suggested that the use of helmets may increase the risk of neck injury in a crash or fall.²⁵ This may be more evident among children because they have a greater head:body ratio than adults, and the additional size and weight of the helmet may increase the risk of neck injury in an otherwise routine fall.²⁶ We conducted a systematic review of the effect of helmets on head and neck injuries among skiers and snowboarders.     

Subcellular localization and turnover of Arabidopsis phototropin 1

We reported recently that internalization of the plant blue light receptor phototropin 1 (phot1) from the plasma membrane in response to irradiation is reliant on receptor autophosphorylation. Pharmacological interference and co-immunoprecipitation analyses also indicated that light-induced internalization of phot1 involves clathrin-dependent processes. Here, we describe additional pharmacological studies that impact the subcellular localization and trafficking of Arabidopsis phot1. Alterations in the microtububle cytoskeleton led to dramatic differences in phot1 localization and function. Likewise, inhibition of phosphatidic acid (PA) signaling was found to impair phot1 localization and function. However, action of PA inhibition on phot1 function may be attributed to pleiotropic effects on cell growth. While phot1 kinase activation is necessary to stimulate its internalization, autophosphorylation is not required for phot1 turnover in response to prolonged blue light irradiation. The implications of these findings in regard to phot1 localization and function are discussed.Key words: phototropin 1 (phot1), phototropism, subcellular trafficking, autophosphorylation, protein turnover