A before-school physical activity intervention to improve cognitive parameters in children: The Active-Start study

The aim of the study was threefold: (a) to test a before-school physical activity intervention (Active-Start) on academic performance, selective attention, and concentration capacity; (b) to test the effect of the Active-Start intervention on anthropometry, body composition, and physical fitness parameters; and (c) whether the physical fitness components are moderators of the effect of the Active-Start program on academic performance, selective attention, and concentration capacity in Chilean children. The Active-Start intervention was a RCT which comprised 170 children (8-10 years old) from three public schools with low socioeconomic status from the city of Santiago (Chile). The exercise intervention was delivered daily, before starting the first school-class (8:00-8:30 am ) for 8 weeks. Changes in academic performance, selective attention and concentration capacity, anthropometric, body composition, and physical fitness parameters were measured. The analyses used were mixed regression models for repeated measures over time. No statistically significant changes in attention and concentration capacity were found. However, significant changes were seen in language (0.63; 95% CI 0.49-0.77) and mathematics (0.49; 95% CI 0.32-0.66) performance (P < .001). Also, improvements were seen in fat mass, fat-free mass, muscular, and cardiorespiratory fitness (all P < .05). The Johnson-Neyman technique revealed a significant relationship between the effect of intervention and attention and concentration when change in cardiorespiratory fitness was above, but not below, 3.05 and 0.70 mL/kg/min, respectively. Implementing before-school physical activity programs such as the Active-Start to enhance the cardiorespiratory fitness may benefit attention capacity and academic success among schoolchildren.     

Perceived Cognitive Impairment among African American elders: health and functional impairments in daily life

Objectives: The Center for Disease Control began to assess Perceived Cognitive Impairment in 2009, yet there has been no in-depth study of how perceived decline in thinking or memory skills may be associated to the health and lifestyle of an independent community-dwelling older person. Among urban-dwelling older African Americans who are at elevated risk for cognitive impairment and dementia, we know even less regarding the interaction of these risk factors.Method: Five hundred and one African American elders (n = 501) between the ages of 55 and 95 with an average age of 70.73 years (SD = 8.6 years) participated in telephone interviews.Results: Approximately one-third of the elders reported that their memory, thinking skills, or ability to reason was worse than a year ago (n = 150; 29.9%) and 25% of this group (n = 38) reported that this Perceived Cognitive Impairment impacted their daily activities and/or warranted a consultation with their doctor. Bivariate analyses indicated that Perceived Cognitive Impairment was associated with increased health problems, mobility limitations, depressed mood, and lower social functioning.Conclusion: Elders who reported that cognitive problems impacted their daily functioning reported the greatest health and mental health problems. Perceived Cognitive Impairment is an important health variable with implications for an older adult's overall health, mobility, and mental health.     

The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their permeability in vitro. All the nanoparticles presented a size of approximately 200 nm. The nanoparticles' interaction with the mucus and the intestinal cells were enhanced after coating with chitosan (CS). PSi nanosystems presented the best association efficiency (AE) and loading degree (LD), even though a high AE was also observed for PLGA nanoparticles and SLN. Among all the nanosystems, PLGA and PSi were the only nanoparticles able to sustain the release of GLP-1 in biological fluids when coated with CS. This characteristic was also maintained when the nanosystems were in contact with the intestinal Caco-2 and HT29-MTX cell monolayers. The CS-coated PSi nanoparticles showed the highest GLP-1 permeation across the intestinal in vitro models. In conclusion, PLGA + CS and PSi + CS are promising nanocarriers for the oral delivery of GLP-1.     

Growth hormone releasing peptide (ghrelin) is synthesized and secreted by cardiomyocytes

OBJECTIVE: Ghrelin, the endogenous ligand of growth hormone secretagogue receptor (GHS-R), acts on the pituitary and the hypothalamus to stimulate the release of growth hormone (GH) and promotes appetite and adiposity. It has also been reported to increase myocardial contractility, induce vasodilation, and protect against myocardial-infarction-induced heart failure. Though principally gastric in origin, it is also produced by other tissues. This work investigated whether cardiomyocytes synthesize and secrete ghrelin, and how its production in these cells responds to stress and exogenous apoptotic agents. METHODS: Ghrelin and its receptor expression was studied by RT-PCR, immunohistochemistry, and competitive binding studies in mouse adult cardiomyocyte cell line HL-1, and primary cultured human cardiomyocytes. Ghrelin accumulation in cardiomyocyte culture medium was measured by radioimmunoassay. Viability and apoptosis assays were carried on by MTT and Hoechst dye vital staining, respectively. RESULTS: RT-PCR showed that HL-1 cells produce mRNAs for both ghrelin and GHS-R, and that GHS-R1a is expressed in human cardiomyocytes; and competitive binding studies using (125)I-labelled ghrelin showed efficient constitutive expression of GHS-R at the surface of HL-1 cells. Immunohistochemistry confirmed the presence of ghrelin in the cytoplasm of HL-1 cells and of isolated human cardiomyocytes in primary culture. Radioimmunoassay showed that ghrelin was secreted by HL-1 cells and human cardiomyocytes into the culture medium. Ghrelin did not modify the viability of HL-1 cells subjected to 12-h starvation, but did protect against the apoptosis inducer cytosine arabinoside (AraC). Finally, production of ghrelin mRNA in HL-1 cardiomyocytes was reduced by AraC but increased if exposure to AraC was preceded by GH treatment. CONCLUSIONS: Ghrelin is synthesized and secreted by isolated murine and human cardiomyocytes, probably with paracrine/autocrine effects, and may be involved in protecting these cells from apoptosis.     

COH outcomes in breast cancer patients for fertility preservation: a comparison with the expected response by age

PurposeBreast cancer is the most common cancer diagnosed during childbearing age, and fertility preservation is becoming increasingly more essential. However, recent studies indicate a possible poorer response to controlled ovarian hyperstimulation (COH) in cancer patients than in non-cancer controls and a negative impact of BRCA mutations on female fertility. This study aims to evaluate ovarian response and the number of mature oocytes (MII) vitrified in women with breast cancer, with or without BRCA mutation, comparing them to the expected response according to an age-related nomogram.MethodsThis is a retrospective observational study involving sixty-one breast cancer patients who underwent COH for oocyte cryopreservation. The age-specific nomogram was built using 3871 patients who underwent COH due to oocyte donation, fertility preservation for non-medical reasons, or FIVET for male factor exclusively.ResultsThe mean number of oocytes retrieved was 13.03, whereas the mean number of MII oocytes was 10.00. After the application of the z-score, no statistically significant differences were found compared with the expected response in the general population, neither by dividing patients according to the presence or absence of BRCA mutation nor according to the phase in which they initiated stimulation.ConclusionThe results obtained do not support the notion of a negative impact of the BRCA mutation on the ovarian response of women with breast cancer. Women with breast cancer undergoing COH for fertility preservation can expect the ovarian response predicted for their age.     

An evidence‐based review of the impact of periprocedural myocardial infarction in carotid revascularization

Landmark trials comparing carotid endarterectomy (CEA) with medical therapy in patients with symptomatic or asymptomatic atherosclerotic stenosis of extracranial carotid arteries have favored carotid revascularization. Carotid artery stenting (CAS) has emerged as a minimally invasive option for revascularization of carotid artery stenoses and has been shown to be noninferior to CEA, regardless of patient symptom status. Debate continues regarding the importance of periprocedural myocardial infarction (PMI) as an endpoint in carotid revascularization trials. Recent randomized comparisons of CEA and CAS pre‐specify PMI as an endpoint. Understanding PMI in CEA and CAS, the need for routine biomarker assessment surrounding both revascularization strategies, the effect of PMI on long‐term morbidity and mortality, and the groups most at risk for PMI are of critical importance when choosing a carotid revascularization strategy for symptomatic and asymptomatic patients, since decreasing the incidence of PMI will make revascularization safer. This review examines available data regarding the relevance of PMI in vascular and carotid‐specific outcomes. © 2013 Wiley Periodicals, Inc.     

Endoplasmic reticulum stress is a target for therapy in Waldenstrom macroglobulinemia

Waldenstrom macroglobulinemia (WM) is an incurable low-grade lymphoma characterized by bone marrow (BM) involvement of IgM secreting lymphoplasmacytic cells. The induction of unfolded protein response (UPR) genes ("physiologic" UPR) enables cells to differentiate into professional secretory cells capable of production of high amounts of endoplasmic reticulum (ER)-processed proteins, such as immunoglobulins. Ultimately, the initially cytoprotective UPR triggers an apoptotic cascade if ER stress is not corrected, called proapoptotic/terminal UPR. We show that WM cells inherently express the physiologic UPR machinery compared with normal BM cells, and that increased ER stress leads to proapoptotic/terminal UPR in WM cells. We therefore examined tunicamycin, ER stress inducer, for potential antitumor effects in WM. Tunicamycin induced significant cytotoxicity, apoptosis and cell-cycle arrest, and inhibited DNA synthesis in WM cell lines and primary BM CD19(+) cells from patients with WM with an inhibitory concentration (IC(50)) of 0.5 microg/mL to 1 microg/mL, but not in healthy donor cells. Importantly, coculture of WM cells in the context of the BM microenvironment did not inhibit tunicamycin-induced cytotoxicity. Finally, we demonstrate that ER stress inducer synergizes with other agents used in the treatment of WM. These preclinical studies provide a framework for further evaluation of ER stress inducing agents as therapeutic agents in WM.