Noninvasive Cerebral Cooling in a Swine Model of Cardiac Arrest

Objective: Mild cerebral hypothermia improves neurologic outcome in animals resuscitated from cardiac arrest. This study examined whether one practical external cooling method, i.e., local application of ice to the heads and necks of swine, during resuscitation induces cerebral cooling.
Methods: Local external cerebral cooling was examined in a prospective laboratory investigation using 24 female swine in a model of cardiac arrest. The swine were randomized into hypothermia and normothermia groups. Intracerebral temperature was measured in the parietal cortex. Eight minutes after induction of ventricular fibrillation, chest compressions and mechanical ventilation were initiated. The hypothermia group was treated with 1,500 mL of ice in plastic bags applied to the head and neck, while the normothermia group received no extra interventions. Data were analyzed using repeated-measures ANOVA.
Results: In the normothermia group, there was no significant change in nasopharyngeal (-0.8 ± 0.6°C), intracerebral (-0.6 ± 0.8°C), or esophageal (-0.2 ± 0.6°C) temperatures during 20 minutes of resuscitation. However, in the hypothermia group, application of ice during resuscitation significantly reduced nasopharyngeal (-2.9 ± 1.4°C), intracerebral (-2.1 ± 0.6°C), and esophageal (-1.4 ± 0.8°C) temperatures.
Conclusions: External application of ice packs during resuscitation effectively reduced intracerebral temperatures in swine by an amount that improved neurologic outcomes in previous large animal studies. These data suggest that clinically significant cerebral cooling could be accomplished with a noninvasive, inexpensive, and universally available intervention. Further studies are required to assess the clinical feasibility and therapeutic efficacy of this intervention.     

Voluntary Cough Airflow Differentiates Safe Versus Unsafe Swallowing in Amyotrophic Lateral Sclerosis

Dysphagia and aspiration are prevalent in amyotrophic lateral sclerosis (ALS) and contribute to malnutrition, aspiration pneumonia, and death. Early detection of at risk individuals is critical to ensure maintenance of safe oral intake and optimal pulmonary function. We therefore aimed to determine the discriminant ability of voluntary cough airflow measures in detecting penetration/aspiration status in ALS patients. Seventy individuals with ALS (El-Escorial criteria) completed voluntary cough spirometry testing and underwent a standardized videofluoroscopic swallowing evaluation (VFSE). A rater blinded to aspiration status derived six objective measures of voluntary cough airflow and evaluated airway safety using the penetration–aspiration scale (PAS). A between groups ANOVA (safe vs. unsafe swallowers) was conducted and sensitivity, specificity, area under the curve (AUC) and likelihood ratios were calculated. VFSE analysis revealed 24 penetrator/aspirators (PAS ≥3) and 46 non-penetrator/aspirators (PAS ≤2). Cough volume acceleration (CVA), peak expiratory flow rise time (PEFRT), and peak expiratory flow rate (PEFR) were significantly different between airway safety groups (p < 0.05) and demonstrated significant discriminant ability to detect the presence of penetration/aspiration with AUC values of: 0.85, 0.81, and 0.78, respectively. CVA <45.28 L/s/s, PEFR <3.97 L/s, and PEFRT >76 ms had sensitivities of 91.3, 82.6, and 73.9 %, respectively, and specificities of 82.2, 73.9, and 78.3 % for identifying ALS penetrator/aspirators. Voluntary cough airflow measures identified ALS patients at risk for penetration/aspiration and may be a valuable screening tool with high clinical utility.     

Effects of vitamin D in skeletal muscle: falls,strength, athletic performance and insulin sensitivity

Accompanying the high rates of vitamin D deficiency observed in many countries, there is increasing interest in the physiological functions of vitamin D. Vitamin D is recognized to exert extra‐skeletal actions in addition to its classic roles in bone and mineral homeostasis. Here, we review the evidence for vitamin D's actions in muscle on the basis of observational studies, clinical trials and basic research. Numerous observational studies link vitamin D deficiency with muscle weakness and sarcopaenia. Randomized trials predominantly support an effect of vitamin D supplementation and the prevention of falls in older or institutionalized patients. Studies have also examined the effect of vitamin D in athletic performance, both inferentially by UV radiation and directly by vitamin D supplementation. Effects of vitamin D in muscle metabolic function, specifically insulin sensitivity, are also addressed in this review. At a mechanistic level, animal studies have evaluated the roles of vitamin D and associated minerals, calcium and phosphate, in muscle function. In vitro studies have identified molecular pathways by which vitamin D regulates muscle cell signalling and gene expression. This review evaluates evidence for the various roles of vitamin D in skeletal muscle and discusses controversies that have made this a dynamic field of research.     

From the Cover: Field-evolved resistance by western corn rootworm to multiple Bacillus thuringiensis toxins in transgenic maize

The widespread planting of crops genetically engineered to produce insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt) places intense selective pressure on pest populations to evolve resistance. Western corn rootworm is a key pest of maize, and in continuous maize fields it is often managed through planting of Bt maize. During 2009 and 2010, fields were identified in Iowa in which western corn rootworm imposed severe injury to maize producing Bt toxin Cry3Bb1. Subsequent bioassays revealed Cry3Bb1 resistance in these populations. Here, we report that, during 2011, injury to Bt maize in the field expanded to include mCry3A maize in addition to Cry3Bb1 maize and that laboratory analysis of western corn rootworm from these fields found resistance to Cry3Bb1 and mCry3A and cross-resistance between these toxins. Resistance to Bt maize has persisted in Iowa, with both the number of Bt fields identified with severe root injury and the ability western corn rootworm populations to survive on Cry3Bb1 maize increasing between 2009 and 2011. Additionally, Bt maize targeting western corn rootworm does not produce a high dose of Bt toxin, and the magnitude of resistance associated with feeding injury was less than that seen in a high-dose Bt crop. These first cases of resistance by western corn rootworm highlight the vulnerability of Bt maize to further evolution of resistance from this pest and, more broadly, point to the potential of insects to develop resistance rapidly when Bt crops do not achieve a high dose of Bt toxin.The global area devoted to transgenic crops producing insecticidal toxins derived from the bacterium Bacillus thuringiensis (Bt) has increased rapidly over the past 15 y, with Bt crops covering more than 69 million hectares in 2012 (1). Most of this area was planted in Bt cotton and Bt maize (1). Benefits of Bt crops include effective management of target pests, decreased use of conventional insecticides, and reduced harm to nontarget organisms (2–5). However, the evolution of resistance could diminish these benefits. The western corn rootworm, Diabrotica virgifera virgifera LeConte (Coleoptera: Chrysomelidae), is a major pest of maize, with larval feeding on maize roots and associated management costs causing economic losses in excess of $1 billion per year (6). Through 2013, three Bt toxins have been used in transgenic maize for management of western corn rootworm: Cry3Bb1, mCry3A, and Cry34/35Ab1 (7).In the United States and elsewhere, commercial registration of a Bt crop is accompanied by a resistance-management plan to delay the onset of pest resistance. Resistance management for Bt crops has focused on the refuge strategy, in which refuges of non-Bt crops allow the survival of Bt-susceptible insects, which may mate with resistant insects that survive on the Bt crop (8). To the extent that the heterozygous progeny from these matings have lower fitness on a Bt crop than their Bt-resistant parent, delays in resistance may be achieved, and these delays in resistance increase with the quantity of refuge (9). Additionally, refuges are far more effective in delaying resistance when Bt crops achieve a high dose of toxin against a target pest. High-dose Bt crops kill more than 99.99% of susceptible insects and render resistance a functionally recessive trait (9, 10). None of the currently commercialized Bt maize targeting the western corn rootworm is high dose, so the risk of resistance is increased (11, 12).In 2003, Cry3Bb1 maize was registered by the United States Environmental Protection Agency (US EPA) for management of western corn rootworm larvae (7). In 2009, farmers in Iowa observed severe injury to Cry3Bb1 maize by larval western corn rootworm in the field, and subsequent laboratory assays revealed that this injury was associated with Cry3Bb1 resistance (13). More fields with Cry3Bb1 resistance were identified in 2010 (14), and research in fields identified in 2009 as harboring Cry3Bb1-resistant western corn rootworm found no difference in survival for this pest between non-Bt maize and Cry3Bb1 maize (11). Current threats to Bt maize include the spread of Bt-resistant western corn rootworm and the loss of additional Bt toxins through the presence of cross-resistance. In this paper we report that injury to Cry3Bb1 maize in the field has persisted through 2011 and expanded to include mCry3A maize. Analysis of western corn rootworm collected in 2011 revealed that (i) severe injury to Cry3Bb1 maize and mCry3A maize in the field was associated with resistance, and (ii) cross-resistance between Cry3Bb1 and mCry3A was present. These results demonstrate that insects can evolve resistance rapidly to Bt crops that are not high dose and raise concerns about the adequacy of current resistance-management strategies.     

Quality of life issues in women with vertebral fractures due to osteoporosis

Objective. To learn about the physical, emotional, and social limitations experienced by postmenopausal women who have back pain due to vertebral fractures resulting from osteoporosis. Methods. We conducted a cross-sectional survey of female patients with persistent pain due to vertebral fractures. Results. Respondents had a mean (±SD) bone density of 0.87 ± 0.13 gm/cm² and a mean (±SD) of 2.48 ± 2.18 fractures. Disability was identified in pain, movement, activities of daily living, and emotion. There was a poor correlation between quality of life and findings on radiography or densitometry. Conclusion. To evaluate the effects of osteoporosis on a patient's functional status, direct questioning is required.