Exploiting PI3K/mTOR signaling to accelerate epithelial wound healing

The molecular circuitries controlling the process of skin wound healing have gained new significant insights in recent years. This knowledge is built on landmark studies on skin embryogenesis, maturation, and differentiation. Furthermore, the identification, characterization, and elucidation of the biological roles of adult skin epithelial stem cells and their influence in tissue homeostasis have provided the foundation for the overall understanding of the process of skin wound healing and tissue repair. Among numerous signaling pathways associated with epithelial functions, the PI3K/Akt/mTOR signaling route has gained substantial attention with the generation of animal models capable of dissecting individual components of the pathway, thereby providing a novel insight into the molecular framework underlying skin homeostasis and tissue regeneration. In this review, we focus on recent findings regarding the mechanisms involved in wound healing associated with the upregulation of the activity of the PI3K/Akt/mTOR circuitry. This review highlights critical findings on the molecular mechanisms controlling the activation of mTOR, a downstream component of the PI3K–PTEN pathway, which is directly involved in epithelial migration and proliferation. We discuss how this emerging information can be exploited for the development of novel pharmacological intervention strategies to accelerate the healing of critical size wounds.     

The development and validation of the hypertension evaluation of lifestyle and management knowledge scale

Hypertension knowledge is an integral component of the chronic care model. A valid scale to assess hypertension knowledge and self-management skills is needed. The hypertension evaluation of lifestyle and management (HELM) scale was developed as part of a community-based study designed to improve self-management of hypertension. Participants included 404 veterans with hypertension. Literature review and an expert panel were used to identify required skills. Items were generated and pilot tested in the target population. Validity was assessed through comparisons of performance with education, health numeracy, print numeracy, patient activation and self-efficacy, and hypertension control. The HELM knowledge scale had 14 items across 3 domains: general hypertension knowledge, lifestyle and medication management, and measurement and treatment goals. Scores were positively associated with education (0.28, P<.0001), print health literacy (0.21, P<.001), health numeracy (0.17, P<.001), and patient activation (0.12, P=.015) but no association was found with diastolic or systolic blood pressure. The HELM knowledge scores increased following the educational intervention from baseline (mean, 8.7; standard deviation, 2.2) to 12-month follow-up (mean, 9.2, standard deviation, 2.2; P<.001). We conclude that the HELM provides a valid measure of the knowledge required for patients to take an active role in the chronic disease management of hypertension.     

Therapeutic prospects for Parkinson disease

Dopaminergic therapies such as levodopa have provided benefit for millions of patients with Parkinson's disease (PD) and revolutionized the treatment of this disorder. However patients continue to experience disability despite the best of modern treatment. Dopaminergic and surgical therapies are associated with potentially serious side effects. Non‐motor and non‐dopaminergic features such as freezing, falling, and dementia are not adequately controlled with available medications and represent the major source of disability for advanced patients. And, the disease continues to relentlessly progress. Major therapeutic unmet needs include a dopaminergic therapy that is not associated with serious side effects, a therapy that addresses the non‐motor and non‐dopaminergic features of the disease, and a disease‐modifying therapy that slows or stops disease progression. This review will consider current attempts to address these issues and the obstacles that must be overcome in order to develop more effective therapies for PD. Ann Neurol 2013;74:337–347     

Protective effects of Mentha piperita Linn on benzo[a]pyrene-induced lung carcinogenicity and mutagenicity in Swiss albino mice

The Editor-in-Chief has retracted the published paper "ProtectiveEffects of     

Generation of normal human red cell volume, hemoglobin content, and membrane area distributions by "birth" or regulation?

Using flow cytometry and osmotic lysis measurements, we document here the means and coefficients of variation of the following red cell (RBC) properties: hemoglobin (Hb) content, volume, Hb concentration, and relative lytic tonicity distributions in populations of normal human RBCs, before and after density fractionation. The distributions showed a pattern characterized by much larger coefficients of variation of the Hb content and volume distributions than of the Hb concentration and relative lytic tonicity distributions. From analysis of the factors that determine those RBC properties, the patterns were interpreted as reflecting previously unrecognized statistical proportionalities between cell osmolyte content, Hb content, and membrane area. The possible origin of these statistical links was analyzed by considering alternative models with and without the participation of regulatory processes during cell maturation. A model was shown to be feasible in which mature RBC variability with proportional volume, area, and Hb content arises solely from cell size variability at the last erythroid cell division.