Long‐term oral administration of melatonin improves spatial learning and memory and protects against cholinergic degeneration in middle‐aged Ts65Dn mice,a model of Down syndrome

Ts65Dn mice (TS), the most commonly used model of Down syndrome (DS), exhibit phenotypic characteristics of this condition. Both TS mice and DS individuals present cognitive disturbances, age‐related cholinergic degeneration, and increased brain expression of β‐amyloid precursor protein (AβPP). These neurodegenerative processes may contribute to the progressive cognitive decline observed in DS. Melatonin is a pineal indoleamine that has been reported to reduce neurodegenerative processes and improve cognitive deficits in various animal models. In this study, we evaluated the potentially beneficial effects of long‐term melatonin treatment on the cognitive deficits, cholinergic degeneration, and enhanced AβPP and β‐amyloid levels of TS mice. Melatonin was administered for 5 months to 5‐ to 6‐month‐old TS and control (CO) mice. Melatonin treatment improved spatial learning and memory and increased the number of choline acetyltransferase (ChAT)‐positive cells in the medial septum of both TS and CO mice. However, melatonin treatment did not significantly reduce AβPP or β‐amyloid levels in the cortex or the hippocampus of TS mice. Melatonin administration did reduce anxiety in TS mice without inducing sensorimotor alterations, indicating that prolonged treatment with this indoleamine is devoid of noncognitive behavioral side effects (e.g., motor coordination, sensorimotor abilities, or spontaneous activity). Our results suggest that melatonin administration might improve the cognitive abilities of both TS and CO mice, at least partially, by reducing the age‐related degeneration of basal forebrain cholinergic neurons. Thus, chronic melatonin supplementation may be an effective treatment for delaying the age‐related progression of cognitive deterioration found in DS.     

Insights in Public Health: Developing the Ho‘ouna Pono Substance Use Prevention Curriculum: Collaborating with Hawaiian Youth and Communities

This article briefly outlines a collaboration among communities on Hawai‘i Island and a university-based research team to develop, implement, and evaluate a school-based substance use prevention curriculum called Ho‘ouna Pono. In addition to providing a rationale for the project, the goal of this paper is fourfold. First, an overview of the Ho‘ouna Pono research results to date (2007–2013) is provided. Second, within this overview, the ways in which selected results informed program development are highlighted. Third, the curriculum is briefly described, and finally, the role of the students and community in the video production is described.     

miR-326 associates with biochemical markers of bone turnover in lung cancer bone metastasis

Recent evidence suggests that miRNAs could be used as serum markers in a variety of normal and pathological conditions. In this study, we aimed to identify novel miRNAs associated with skeletal metastatic disease in a preclinical model of lung cancer bone metastasis. We assessed the validity of these miRNAs as reliable serum biochemical markers to monitor the extent of disease and response to treatment in comparison to imaging techniques and standard biochemical markers of bone turnover. Using a murine model of human lung cancer bone metastasis after zoledronic acid (ZA) treatment, PINP (procollagen I amino-terminal propeptide) was the only marker that exhibited a strong correlation with osteolytic lesions and tumor burden at early and late stages of bone colonization. In contrast, BGP (osteocalcin) and CTX (carboxyterminal telopeptide) demonstrated a strong correlation only at late stages. We performed qPCR based screening of a panel of 380 human miRNAs and quantified bone metastatic burden using micro-CT scans, X-rays and bioluminescence imaging. Interestingly, levels of miR-326 strongly associated with tumor burden and PINP in vehicle-treated animals, whereas no association was found in ZA-treated animals. Only miR-193 was associated with biochemical markers PINP, BGP and CTX in ZA-treated animals. Consistently, miR-326 and PINP demonstrated a strong correlation with tumor burden. Our findings, taken together, indicate that miR-326 could potentially serve as a novel biochemical marker for monitoring bone metastatic progression.     

Mitochondrial-derived peptide humanin as therapeutic target in cancer and degenerative diseases

Introduction: Mitochondrial-derived peptides (MDPs) are encoded within the mitochondrial genome. They signal within the cell or are released to act as autocrine/paracrine/endocrine cytoprotective factors playing a key role in the cellular stress response. The first reported and better characterized MDP is humanin (HN), which exerts robust protective effects against a myriad of cytotoxic stimuli in many cell types. These effects have led to the evaluation of HN and its analogs as therapeutic targets for several chronic diseases.

Areas covered: We describe the latest findings on the mechanism of action of HN and discuss the role of HN as therapeutic target for neurodegenerative and cardiovascular diseases, diabetes, male infertility, and cancer. Since HN can be detected in circulation, we also depict its value as a biomarker for these diseases.

Expert opinion: HN analogs and peptide mimetics have been developed over the last decade and show promising results in preclinical models of degenerative diseases. Local administration of gene therapy vectors that overexpress or silence endogenous HN could also hold therapeutic potential. Controversy on the role of HN in cancer progression and chemoresistance should be addressed before the translation of these therapeutic approaches.     

Evaluación formativa mediante el portafolio de 4 promociones de residentes de medicina de familia y comunitaria de la Unidad Docente de Murcia

ObjectiveTo evaluate the performance and quality of the 10 groups of training tasks envisaged in the portfolio training model undertaken by all residents of the Primary Care Teaching Unit in Murcia.DesignA cross-sectional study was conducted on the portfolios provided and completed by all residents in May 2011.ParticipantsAll residents who were in training at that time (131).MethodTen groups of training tasks were established from those recommended by the National Commission for the specialty. The performance of each one in each of the portfolios was evaluated, and the compliance for each training task was calculated. The quality of the performance of each of the tasks was given a score, 0 points (very poor) to 10 points (excellent).ResultsAs regards compliance, the tasks that were most performed were: filling in the Resident book correctly and using the resident skills guide, both with 99.24%, followed by reflection reports on the training visits. All tasks had a compliance rate higher than 67%. The mean percentage of compliance was 86.49%. All tasks obtained an average score greater than 7 (outstanding). The overall mean score was 7,8 points.ConclusionsThe level of perfomance of the tasks set out in the portfolio by the residents was very satisfying. It is necessary to continue working on improving the performance of the portfolio.     

Prognostic Value of Subdivisions of Nighttime Blood Pressure Fall in Hypertensives Followed Up for 8.2 Years. Does Nondipping Classification Need to Be Redefined?

J Clin Hypertens(Greenwich). 2010;12:508–515. © 2010 Wiley Periodicals, Inc. To evaluate the long-term prognostic significance of different ranges of the percentage fall in nighttime blood pressure (BP) of the nondipping pattern, 1200 hypertensive patients (645 women, age 51±12 years) underwent ambulatory BP monitoring under stabilized therapy. The occurrence of cardiovascular (CV) events was followed for 9833 patient-years and analyzed by the Cox hazard model. There were 152 CV fatal/nonfatal events (79 strokes, 51 coronary events, 22 others) during the 15.2 years of follow-up. According to nighttime BP fall (%) the authors noted: <0% (reverse-dippers [RD], n=83); 0%–4.9% (nondippers 1 [ND1], n=207); 5%–9.9% (nondippers 2 [ND2], n=311), 10%–19.9% (dippers [D], n=523); and ≥20% (extreme dippers [ED], n=76). After adjustment for confounding variables, hazard ratios (95% confidence interval) of CV event and stroke in RD vs D were 2.29 (1.31–3.99) and 2.46 (1.11–5.49); of ND1 vs D were 1.42 (1.12–1.79) and 1.62 (1.17–2.23); and of ND1 vs ND2 were 2.24 (1.33–3.75) and 2.30 (1.15–4.58). No differences were found in RD vs ND1 and ND2 vs D. Nondippers have a higher CV risk than dippers but only for a nighttime BP fall <5% suggesting that the limits for nondipping should be redefined for a stratification of CV risk.