Developmental dosing with a MEK inhibitor (PD0325901) rescues myopathic features of the muscle-specific but not limb-specific Nf1 knockout mouse

Neurofibromatosis Type 1 (NF1) is a common autosomal dominant genetic disorder While NF1 is primarily associated with predisposition for tumor formation, muscle weakness has emerged as having a significant impact on quality of life. NF1 inactivation is linked with a canonical upregulation Ras-MEK-ERK signaling. This in this study we tested the capacity of the small molecule MEK inhibitor PD0325901 to influence the intramyocellular lipid accumulation associated with NF1 deficiency. Established murine models of tissue specific Nf1 deletion in skeletal muscle (Nf1_MyoD^?/?) and limb mesenchyme (Nf1_Prx1^?/?) were tested.Developmental PD0325901 dosing of dams pregnant with Nf1_MyoD^?/? progeny rescued the phenotype of day 3 pups including body weight and lipid accumulation by Oil Red O staining. In contrast, PD0325901 treatment of 4?week old Nf1_Prx1^?/? mice for 8?weeks had no impact on body weight, muscle wet weight, activity, or intramyocellular lipid. Examination of day 3 Nf1_Prx1^?/? pups showed differences between the two tissue-specific knockout strains, with lipid staining greatest in Nf1_MyoD^?/? mice, and fibrosis higher in Nf1_Prx1^?/? mice.These data show that a MEK/ERK dependent mechanism underlies NF1 muscle metabolism during development. However, crosstalk from Nf1-deficient non-muscle mesenchymal cells may impact upon muscle metabolism and fibrosis in neonatal and mature myofibers.     

Intrathyroidal thymic tissue in children: Avoiding unnecessary surgery

Background/Purpose

Intrathyroidal thymic tissue may be misinterpreted as a thyroid lesion in children, leading to invasive tests or resection. We sought to describe the characteristic imaging features of these lesions and to evaluate the safety of non-operative management.

The "New Look" approach to patient safety: a guide for clinical nurse specialist leadership

This article describes a complex system model based on human performance factors that is borrowed from other industries but can be used by clinical nurse specialists for making progress in patient safety. Traditional approaches to investigation and follow-up of errors in healthcare organizations have not resulted in improvement in patient safety. The New Look approach described in this article emphasizes the complexity in which healthcare workers make decisions about patient c are every day and how increased learning about the resiliency of healthcare workers in the face of multiple system gaps and discontinuities will lead to long-lasting improvements in safety. The article describes how the clinical nurse specialist can lead efforts using the New Look human performance-based approach in 4 areas: changing to a nonpunitive culture, learning about system complexity, learning about healthcare worker resiliency, and preparing for the complexity of introducing change.     

Treating Posttraumatic Stress Disorder in Diverse Settings: Recent Advances and Challenges for the Future

Racial and ethnic minorities are at high risk for developing posttraumatic stress disorder (PTSD) after experiencing a traumatic event and are less likely to receive evidence-based treatment for their symptoms. There is a growing body of literature showing that culturally appropriate interventions result in greater uptake, symptom reduction, and sustained treatment gains. This article review explores new findings in the cultural understanding of PTSD among racial and ethnic minorities. We first review recent advances in the understanding of PTSD symptomotology. Next, we provide overview of trials demonstrating efficacy and effectiveness of cognitive processing therapy (CPT), prolonged exposure (PE), and trauma-focused cognitive-behavioral therapy (TF-CBT) in diverse communities. Then, we discuss specific implementation strategies common across intervention trials used to increase feasibility, acceptability, adoption, and sustainability. Last, we discuss areas for future research and dissemination efforts.     

Impact of expiratory strength training in amyotrophic lateral sclerosis

Introduction: We evaluated the feasibility and impact of expiratory muscle strength training (EMST) on respiratory and bulbar function in persons with amyotrophic lateral sclerosis (ALS). Methods: Twenty‐five ALS patients participated in this delayed intervention open‐label clinical trial. Following a lead‐in period, patients completed a 5‐week EMST protocol. Outcome measures included: maximum expiratory pressure (MEP); physiologic measures of swallow and cough; and penetration–aspiration scale (PAS) scores. Results: Of participants who entered the active phase of the study (n = 15), EMST was well tolerated and led to significant increases in MEPs and maximum hyoid displacement during swallowing post‐EMST (P < 0.05). No significant differences were observed for PAS scores or cough spirometry measures. Conclusions: EMST was feasible and well tolerated in this small cohort of ALS patients and led to improvements in expiratory force‐generating pressures and swallow kinematics. Further investigation is warranted to confirm these preliminary findings. Muscle Nerve 54 : 48–53, 2016