Less-structured time in children's daily lives predicts self-directed executive functioning.

Executive functions (EFs) in childhood predict important life outcomes. Thus, there is great interest in attempts to improve EFs early in life. Many interventions are led by trained adults, including structured training activities in the lab, and less-structured activities implemented in schools. Such programs have yielded gains in children's externally-driven executive functioning, where they are instructed on what goal-directed actions to carry out and when. However, it is less clear how children's experiences relate to their development of self-directed executive functioning, where they must determine on their own what goal-directed actions to carry out and when. We hypothesized that time spent in less-structured activities would give children opportunities to practice self-directed executive functioning, and lead to benefits. To investigate this possibility, we collected information from parents about their 6-7 year-old children's daily, annual, and typical schedules. We categorized children's activities as "structured" or "less-structured" based on categorization schemes from prior studies on child leisure time use. We assessed children's self-directed executive functioning using a well-established verbal fluency task, in which children generate members of a category and can decide on their own when to switch from one subcategory to another. The more time that children spent in less-structured activities, the better their self-directed executive functioning. The opposite was true of structured activities, which predicted poorer self-directed executive functioning. These relationships were robust (holding across increasingly strict classifications of structured and less-structured time) and specific (time use did not predict externally-driven executive functioning). We discuss implications, caveats, and ways in which potential interpretations can be distinguished in future work, to advance an understanding of this fundamental aspect of growing up

Dissection of Melanogenesis with Small Molecules Identifies Prohibitin as a Regulator

SummaryBioactive compounds can be used to selectively modulate gene function. We utilized a chemical genetic approach to dissect the mammalian pigmentation pathway and identify protein regulators. We screened a tagged library of 1170 small molecules in a cell-based assay and discovered a class of pigment-enhancing chemicals. From this class we characterized the small molecule melanogenin. Using melanogenin bound to an affinity matrix and amino acid sequencing, we identified the mitochondrial protein, prohibitin, as an intracellular binding target. Studies employing siRNA demonstrate that prohibitin is required for melanogenin to exert its propigmentary effects and reveal an unsuspected functional role for this protein in melanin induction. This represents a mechanism by which propigmentary signals are transduced and ultimately provides a potential target for the treatment of pigmentary disorders

Sensitivity of Yeast Strains with Long G-Tails to Levels of Telomere-Bound Telomerase

The Saccharomyces cerevisiae Pif1p helicase is a negative regulator of telomere length that acts by removing telomerase from chromosome ends. The catalytic subunit of yeast telomerase, Est2p, is telomere associated throughout most of the cell cycle, with peaks of association in both G1 phase (when telomerase is not active) and late S/G2 phase (when telomerase is active). The G1 association of Est2p requires a specific interaction between Ku and telomerase RNA. In mutants lacking this interaction, telomeres were longer in the absence of Pif1p than in the presence of wild-type PIF1, indicating that endogenous Pif1p inhibits the active S/G2 form of telomerase. Pif1p abundance was cell cycle regulated, low in G1 and early S phase and peaking late in the cell cycle. Low Pif1p abundance in G1 phase was anaphase-promoting complex dependent. Thus, endogenous Pif1p is unlikely to act on G1 bound Est2p. Overexpression of Pif1p from a non-cell cycle-regulated promoter dramatically reduced viability in five strains with impaired end protection (cdc13–1, yku80Δ, yku70Δ, yku80–1, and yku80–4), all of which have longer single-strand G-tails than wild-type cells. This reduced viability was suppressed by deleting the EXO1 gene, which encodes a nuclease that acts at compromised telomeres, suggesting that the removal of telomerase by Pif1p exposed telomeres to further C-strand degradation. Consistent with this interpretation, depletion of Pif1p, which increases the amount of telomere-bound telomerase, suppressed the temperature sensitivity of yku70Δ and cdc13–1 cells. Furthermore, eliminating the pathway that recruits Est2p to telomeres in G1 phase in a cdc13–1 strain also reduced viability. These data suggest that wild-type levels of telomere-bound telomerase are critical for the viability of strains whose telomeres are already susceptible to degradation

Podocalyxin in the Diagnosis and Treatment of Cancer

Kelly M. McNagny, Michael R. Hughes, Marcia L. Graves, Erin J. DeBruin, Kimberly Snyder, Jane Cipollone, Michelle Turvey, Poh C. Tan, Shaun McColl and Calvin D. Roskelle

Identification and Characterization of Cell Type–Specific and Ubiquitous Chromatin Regulatory Structures in the Human Genome

The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type–specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifying the location of functional regulatory elements. We used a high throughput method called DNase-chip to identify 3,904 DNaseI HS sites from six cell types across 1% of the human genome. A significant number (22%) of DNaseI HS sites from each cell type are ubiquitously present among all cell types studied. Surprisingly, nearly all of these ubiquitous DNaseI HS sites correspond to either promoters or insulator elements: 86% of them are located near annotated transcription start sites and 10% are bound by CTCF, a protein with known enhancer-blocking insulator activity. We also identified a large number of DNaseI HS sites that are cell type specific (only present in one cell type); these regions are enriched for enhancer elements and correlate with cell type–specific gene expression as well as cell type–specific histone modifications. Finally, we found that approximately 8% of the genome overlaps a DNaseI HS site in at least one the six cell lines studied, indicating that a significant percentage of the genome is potentially functional

Lower numbers of natural killer T cells in HIV-1 and Mycobacterium leprae co-infected patients

Natural killer T (NKT) cells are a heterogeneous population of lymphocytes that recognize antigens presented by CD1d and have attracted attention because of their potential role linking innate and adaptive immune responses. Peripheral NKT cells display a memory-activated phenotype and can rapidly secrete large amounts of pro-inflammatory cytokines upon antigenic activation. In this study, we evaluated NKT cells in the context of patients co-infected with HIV-1 and Mycobacterium leprae. The volunteers were enrolled into four groups: 22 healthy controls, 23 HIV-1-infected patients, 20 patients with leprosy and 17 patients with leprosy and HIV-1-infection. Flow cytometry and ELISPOT assays were performed on peripheral blood mononuclear cells. We demonstrated that patients co-infected with HIV-1 and M.leprae have significantly lower NKT cell frequencies [median 0.022%, interquartile range (IQR): 0.0070.051] in the peripheral blood when compared with healthy subjects (median 0.077%, IQR: 0.0320.405, P < 0.01) or HIV-1 mono-infected patients (median 0.072%, IQR: 0.0300.160, P < 0.05). Also, more NKT cells from co-infected patients secreted interferon-? after stimulation with DimerX, when compared with leprosy mono-infected patients (P = 0.05). These results suggest that NKT cells are decreased in frequency in HIV-1 and M.leprae co-infected patients compared with HIV-1 mono-infected patients alone, but are at a more activated state. Innate immunity in human subjects is strongly influenced by their spectrum of chronic infections, and in HIV-1-infected subjects, a concurrent mycobacterial infection probably hyper-activates and lowers circulating NKT cell numbers.National Institutes of Health [R01-AI52731, AI060379]Fogarty International Center [D43 TW00003]Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [04/15856-9/Kallas, 2010/05845-0/Kallas]Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Brazilian Ministry of Science and Technology [484230/2011-5]New York Community Trus

Biomarkers and Noncalcified Coronary Artery Plaque Progression in Older Men Treated With Testosterone.

ObjectiveRecent results from the Cardiovascular Trial of the Testosterone Trials showed that testosterone treatment of older men with low testosterone was associated with greater progression of noncalcified plaque (NCP). We evaluated the effect of anthropometric measures and cardiovascular biomarkers on plaque progression in individuals in the Testosterone Trial.MethodsThe Cardiovascular part of the trial included 170 men aged 65 years or older with low testosterone. Participants received testosterone gel or placebo gel for 12 months. The primary outcome was change in NCP volume from baseline to 12 months, as determined by coronary computed tomography angiography (CCTA). We assayed several markers of cardiovascular risk and analyzed each marker individually in a model as predictive variables and change in NCP as the dependent variable.ResultsOf 170 enrollees, 138 (73 testosterone, 65 placebo) completed the study and were available for the primary analysis. Of 10 markers evaluated, none showed a significant association with the change in NCP volume, but a significant interaction between treatment assignment and waist-hip ratio (WHR) (P = 0.0014) indicated that this variable impacted the testosterone effect on NCP volume. The statistical model indicated that for every 0.1 change in the WHR, the testosterone-induced 12-month change in NCP volume increased by 26.96 mm3 (95% confidence interval, 7.72-46.20).ConclusionAmong older men with low testosterone treated for 1 year, greater WHR was associated with greater NCP progression, as measured by CCTA. Other biomarkers and anthropometric measures did not show statistically significant association with plaque progression

Social media for health promotion and weight management: A critical debate

© 2018 The Author(s). Background: In 2016 an estimated 1.9 billion adults world-wide were either overweight or obese. The health consequences of obesity are responsible for 2.8 million preventable deaths per year. The WHO now considers obesity as a global epidemic and recommends population-wide health promotion strategies to address this issue. Weight gain is caused by increased energy intake and physical inactivity, so treatment should focus on changes to behaviour regarding diet and physical activity. Discussion: The WHO has also recognised the importance of social resources as a valuable agent for behaviour change in health promotion. Social resources are translated at the community level as support provided by significant others such as family, partners and peers, in the form of information, material aid and encouragement. Social support has been shown to improve health and well-being, whereas social isolation has been shown to have a negative impact on health outcomes. Social support provided by peers has been shown to be a useful strategy to employ in weight management programmes. The documented increased use of ICT and social media has presented health promoters with a potentially useful medium to increase social support for weight management. Conclusion: While the use of social media for health promotion is an emerging field of investigation, preliminary research suggests that it increases participant engagement, and may provide a cost-effective tool to provide social support for individuals participating in weight management programmes. With stringent privacy protocols in place, social media may be a useful, cost-effective accompaniment to multifactorial weight management programmes. However more research is needed to identify how to make the best use of social media as health promotion tool

Alcohol marketing and drunkenness among students in the Philippines: findings from the nationally representative Global School-based Student Health Survey

BACKGROUND: A largely unaddressed issue in lower income countries and the Philippines, in particular, is the role of alcohol marketing and its potential link to early alcohol use among youth. This study examines the associations between exposures to alcohol marketing and Filipino youths’ drinking prevalence and drunkenness. METHODS: Cross-sectional analyses were used to examine the Global School-based Student Health Survey (GSHS) conducted in Philippines (2011). The self-administered questionnaires were completed by students primarily 13 to 16 years of age (N = 5290). Three statistical models were computed to test the associations between alcohol marketing and alcohol use, while controlling for possible confounding factors. RESULTS: Alcohol marketing, specifically through providing free alcohol through a company representative, was associated with drunkenness (AOR: 1.84; 95% CI = 1.06–3.21) among youths after controlling for demographic and psychosocial characteristics, peer environment, and risky behaviors. In addition, seeing alcohol ads in newspapers and magazines (AOR: 1.65, 95% CI = 1.05–2.58) and seeing ads at sports events, concerts or fairs (AOR: 1.50, 95% CI = 1.06–2.12) were significantly associated with increased reports of drunkenness. CONCLUSIONS: There are significant associations between alcohol marketing exposure and increased alcohol use and drunkenness among youth in the Philippines. These findings highlight the need to put policies into effect that restrict alcohol marketing practices as an important prevention strategy for reducing alcohol use and its dire consequences among vulnerable youth

Illness management and recovery (IMR) in Danish community mental health centres

<p>Abstract</p> <p>Background</p> <p>Schizophrenia and bipolar disorder are severe mental illnesses that can have a significant disabling impact on the lives of people. Psychosocial interventions that stress hope and recovery as a part of a multi-dimensional approach are possibly indicated to support people with severe mental illness in facilitating recovery. Illness Management and Recovery (IMR) is a curriculum-based psychosocial intervention designed as structured program with a recovery-oriented approach. The aim of IMR is to rehabilitate people with severe mental illnesses by helping them acquire knowledge and skills in managing their illness and achieve personal recovery goals. Previous randomised clinical trials indicate that IMR can be implemented with a good effect and a high fidelity though further trials are crucial to demonstrate the potential effectiveness of IMR.</p> <p>Methods/Design</p> <p>The trial design is a randomised, assessor-blinded, multi-centre, clinical trial of the IMR program compared with treatment as usual for 200 participants diagnosed with schizophrenia or bipolar disorder under the care of two community mental health centres in the Capital Region of Denmark. The primary outcome is level of functioning at the end of treatment. The secondary outcomes are disease symptoms; use of alcohol/drugs; individual meaning of recovery; hope; hospital admissions and out-patient psychiatric treatment at the end of treatment and the abovementioned and level of functioning at follow-up 21 months after baseline.</p> <p>Discussion</p> <p>If the results of this trial show IMR to be effective these positive results will strengthen the evidence of IMR as an effective comprehensive psychosocial intervention with a recovery-oriented approach for people with severe mental illness. This will have significant implications for the treatment and recovery of people with severe mental illness.</p> <p>Trial registration</p> <p>Registration number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01361698">NCT01361698</a>.</p