6,412 research outputs found

    The Effect of Goal Setting, Motivation, and Fitness Trackers on Daily Step Counts

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    Purpose: Wearable devices for tracking health and fitness-related activities are thought to motivate individuals to participate in regular exercise. It has been suggested that personal activity trackers can empower individuals to create and keep fitness goals. Therefore, this research was conducted to examine whether using a fitness tracking device in combination with working towards a given goal, self-reporting daily steps, and receiving motivational emails would increase physical activity. Methods: 44 participants (13 males, 31 females) were recruited and randomized into either an experimental (goal setting) or control group (n=22 per group). Participants reported step counts every day for four weeks using an online form. After the first week of data collection, daily step count averages were calculated and goals were given to participants in the experimental group, by adding 500 steps to their daily average. Participants were notified of this goal and sent motivational emails each week, while participants in the control group were not given a specific goal or motivation. Results: Week one step count averages were similar between groups (8460.9 ± 3329.8 steps for the control group and 8783.6 ± 4317.6 steps for the experimental group). Step counts declined in both groups across the three-week period. The week three average was 7731.8 ± 4231.5 steps for the control group and 7642.1 ± 4208.9 steps for the experimental group. Despite email encouragement in the experimental group, only 40.9 percent met their given goal in week one. By the third week, only 27.3 percent of participants in the experimental group met their goal, missing this goal by an average of 1595.88 ± 3294 steps. Participants reported that the use of these devices encouraged them to participate in physical activity (44.8 percent of the control group and 63.7 percent of the experimental group) despite the declining step count trend observed. 69.6 percent of the control group and 72.7 percent of the experimental group reported that they would continue to wear a fitness tracking device outside of the study. Conclusion: There was no significant difference between experimental and control groups with their adherence to the program and step count levels throughout each week. Both groups on average did not reach the widely accepted recommendation of 10,000 steps per day. Interestingly, the majority of participants reported that they still plan to use a fitness tracking device in the future and consider them to be a piece of motivational technology

    Activation of Akt at T308 and S473 in alcohol, tobacco and HPV-induced HNSCC:is there evidence to support a prognostic or diagnostic role?

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    BACKGROUND: Tobacco, alcohol and HPV infection are associated with increased risk of HNSCC. However, little is known about the underlying signaling events influencing risk. We aimed to investigate the relationship between these risk factors and Akt phosphorylation, to determine prognostic value. METHOD: VEGF-positive HNSCC biopsies, with known HPV status, were analyzed by immunohistochemistry (IHC) for Akt, phosphorylated at residues S473 and T308. Comparisons between the tissues were carried out using a Mann–Whitney U test. Associations between the variables and continuous immunohistochemical parameters were evaluated with general linear models. Patient characteristics and pAkt IHC score were analyzed for possible association with overall survival by Cox proportional hazard models. RESULTS: Immunohistochemistry revealed that cancer patients had significantly higher levels of pAkt T308 than S473 (P < 0.001). Smoking and alcohol were found to be independent risk factors for Akt phosphorylation at T308 (P = 0.022 and 0.027, respectively). Patients with tumors positive for HPV or pAkt S473 had a poorer prognosis (P = 0.005, and 0.004, respectively). Patients who were heavy drinkers were 49 times more likely to die than non-drinkers (P = 0.003). Patients with low pAkt T308 were more likely to be HPV positive (P = 0.028). Non-drinkers were also found to have lower levels of pAkt T308 and were more likely to have tumors positive for HPV than heavy drinkers (P = 0.044 and 0.007, respectively). CONCLUSION: This study suggests different mechanisms of carcinogenesis are initiated by smoking, alcohol and HPV. Our data propose higher phosphorylation of Akt at T308 as a reliable biomarker for smoking and alcohol induced HNSCC progression and higher phosphorylation of Akt at S473 as a prognostic factor for HNSCC

    DNA repair in the trinucleotide repeat disorders

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    Background Inherited diseases caused by unstable repeated DNA sequences are rare, but together represent a substantial cause of morbidity. Trinucleotide repeat disorders are severe, usually life-shortening, neurological disorders caused by nucleotide expansions, and most have no disease-modifying treatments. Longer repeat expansions are associated with genetic anticipation (ie, earlier disease onset in successive generations), although the differences in age at onset are not entirely accounted for by repeat length. Such phenotypic variation within disorders implies the existence of additional modifying factors in pathways that can potentially be modulated to treat disease. Recent developments A genome-wide association study detected genetic modifiers of age at onset in Huntington's disease. Similar findings were seen in the spinocerebellar ataxias, indicating an association between DNA damage-response and repair pathways and the age at onset of disease. These studies also suggest that a common genetic mechanism modulates age at onset across polyglutamine diseases and could extend to other repeat expansion disorders. Genetic defects in DNA repair underlie other neurodegenerative disorders (eg, ataxia-telangiectasia), and DNA double-strand breaks are crucial to the modulation of early gene expression, which provides a mechanistic link between DNA repair and neurodegeneration. Mismatch and base-excision repair are important in the somatic expansion of repeated sequences in mouse models of trinucleotide repeat disorders, and somatic expansion of the expanded CAG tract in HTT correlates with age at onset of Huntington's disease and other trinucleotide repeat disorders. Where next? To understand the common genetic architecture of trinucleotide repeat disorders and any further genetic susceptibilities in individual disorders, genetic analysis with increased numbers of variants and sample sizes is needed, followed by sequencing approaches to define the phenotype-modifying variants. The findings must then be translated into cell biology analyses to elucidate the mechanisms through which the genetic variants operate. Genes that have roles in the DNA damage response could underpin a common DNA repeat-based mechanism and provide new therapeutic targets (and hence therapeutics) in multiple trinucleotide repeat disorders

    Regional Differences in Presence of Shiga toxin-producing Escherichia coli Virulence-Associated Genes in the Environment in the North West and East Anglian regions of England

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    Shiga toxin-producing Escherichia coli is carried in the intestine of ruminant animals, and outbreaks have occurred after contact with ruminant animals or their environment. The presence of STEC virulence genes in the environment was investigated along recreational walking paths in the North West and East Anglia regions of England. In all, 720 boot sock samples from walkers’ shoes were collected between April 2013 and July 2014. Multiplex PCR was used to detect E. coli based on the amplification of the uidA gene and investigate STEC-associated virulence genes eaeA, stx1 and stx2. The eaeA virulence gene was detected in 45·5% of the samples, where stx1 and/or stx2 was detected in 12·4% of samples. There was a difference between the two regions sampled, with the North West exhibiting a higher proportion of positive boot socks for stx compared to East Anglia. In univariate analysis, ground conditions, river flow and temperature were associated with positive boot socks. The detection of stx genes in the soil samples suggests that STEC is present in the English countryside and individuals may be at risk for infection after outdoor activities even if there is no direct contact with animals. Significance and Impact of the Study: Several outbreaks within the UK have highlighted the danger of contracting Shiga toxin-producing Escherichia coli from contact with areas recently vacated by livestock. This is more likely to occur for STEC infections compared to other zoonotic bacteria given the low infectious dose required. While studies have determined the prevalence of STEC within farms and petting zoos, determining the risk to individuals enjoying recreational outdoor activities that occur near where livestock may be present is less researched. This study describes the prevalence with which stx genes, indicative of STEC bacteria, were found in the environment in the English countryside

    Perceived Differences in Knowledge About Interactive Technology Between Young Adults and Their Parents

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    This study was designed to investigate generational differences in knowledge about interactive technology (i.e., cell phones, social networking, email, video chat) between parents and their young adult children. Parents (n = 555) and young adults (n = 604) residing in the United States provided information about their knowledge in the use of interactive technology. Young adult children also reported their perceptions of their parents’ technological knowledge for the various technologies. Comparisons of young adult self-reported technological knowledge and their parents’ own reports of technological knowledge revealed that young adults were perceived to be much more knowledgeable than their parents (by both the young adults and their parents) regardless of the technology medium. The largest differences between parents and their young adult children were associated with newer interactive technologies, with the largest gap between parent and young adult knowledge in the area of social networking. Perceived differences between parents and their young adult children were smaller among the technologies that have been in use longer (such as such as e-mail), and larger among the newer modes of interactive technology (e.g., video chat)

    The alternate GNB3 splice variant, Gβ3s, exhibits an altered signalling response to EGF stimulation, which leads to enhanced cell migration

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    It has recently been reported that the duplication of the GNB3 gene has been shown to be directly linked to an obesity phenotype, both in humans and also in a humanised mouse model. Moreover, the common human GNB3 c.825C&gt;T polymorphism (rs5443) causes this ubiquitously expressed gene to be aberrantly spliced approximately 50% of the time leading to the production of both a normal Gβ3 protein and a truncated, possibly less stable subunit, known as Gβ3s. The presence of the GNB3 825T allele has previously been shown to be associated with predisposition to hypertension, obesity, various cancers, Alzheimers, age related cognitive function, erectile dysfunction as well as a marker for pharmacogenetic drug action. Great controversy, however, currently exists as to whether these phenotypes associated with the 825T allele are a) mainly due to the presence of the smaller, possibly more active, Gβ3s subunit or b) merely down to the haploinsufficiency of the normal GNB3 transcript, due to its frequent aberrant splicing. In order to try and address these two conflicting hypothesis, we report on the identification and characterisation of signalling alterations unique to the presence of Gβ3s protein subunit. Moreover we also show the physiological consequences associated with altered signalling, directly induced by the Gβ3s subunit. For this, we used both an EBV transformed lymphoblast cell line homozygote for GNB3 825T/825T (TT) and a stable Gβ3s expressing recombinant COS-7 clone. In both of these cell lines that express the Gβ3s subunit, we found enhanced cytosolic calcium influx upon stimulation with EGF, TGFα and VEGF ligands, as compared to “normal” GNB3 controls with the 825C/825C (CC) genotype. This aberrant calcium influx also led to an increase in ERK, but not AKT1, phosphorylation. Despite the lack of AKT1 activation, we paradoxically observed a significant increase in phosphorylation of its downstream substrates, namely mTOR and p70S6k (KS6B2). Moreover we observed a decrease in phospho FoxO3a only in Gβ3s expressing cells, but not in the “normal” GNB3 (CC) control cell line. The presence of the Gβ3s subunit also appeared to alter the distinct localisation patterns of both Foxo3a and AKT1, while also increasing the colocalisation of mTOR and p70S6K. Subsequent growth factor stimulation studies revealed that EGF treatment, of Gβ3s expressing cells, appeared to cause a significant decrease in cAMP levels, which, in turn resulted in both enhanced caveolin-1a phosphorylation, and an increase in actin stress fibre formation. The identification of these distinct Gβ3s specific signalling alterations were indicative of a more aggressive migratory phenotype. This led us to further investigate and confirm that the presence of the Gβ3s subunit also appears to cause significantly enhanced migration and robust scratch wound healing kinetics, as compared to cells harbouring only the normal copy of the gene. These data therefore present convincing evidence that the Gβ3s subunit is stable, functional and its presence can significantly alter signalling pathways, in different cell types

    Association between insulin monotherapy versus insulin plus metformin and the risk of all-cause mortality and other serious outcomes: a retrospective cohort study

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    Aims To determine if concomitant metformin reduced the risk of death, major adverse cardiac events (MACE), and cancer in people with type 2 diabetes treated with insulin. Methods For this retrospective cohort study, people with type 2 diabetes who progressed to insulin with or without metformin from 2000 onwards were identified from the UK Clinical Practice Research Datalink (≈7% sample of the UK population). The risks of all-cause mortality, MACE and incident cancer were evaluated using multivariable Cox models comparing insulin monotherapy with insulin plus metformin. We accounted for insulin dose. Results 12,020 subjects treated with insulin were identified, including 6,484 treated with monotherapy. There were 1,486 deaths, 579 MACE (excluding those with a history of large vessel disease), and 680 cancer events (excluding those in patients with a history of cancer). Corresponding event rates were 41.5 (95% CI 39.4–43.6) deaths, 20.8 (19.2–22.5) MACE, and 21.6 (20.0–23.3) cancer events per 1,000 person-years. The adjusted hazard ratios (aHRs) for people prescribed insulin plus metformin versus insulin monotherapy were 0.60 (95% CI 0.52–0.68) for all-cause mortality, 0.75 (0.62–0.91) for MACE, and 0.96 (0.80–1.15) for cancer. For patients who were propensity-score matched, the corresponding aHRs for all-cause mortality and cancer were 0.62 (0.52–0.75) and 0.99 (0.78–1.26), respectively. For MACE, the aHR was 1.06 (0.75–1.49) prior to 1,275 days and 1.87 (1.22–2.86) after 1,275 days post-index. Conclusions People with type 2 diabetes treated with insulin plus concomitant metformin had a reduced risk of death and MACE compared with people treated with insulin monotherapy. There was no statistically significant difference in the risk of cancer between people treated with insulin as monotherapy or in combination with metformin

    Identifying the Coping Strategies of Nonoffending Pedophilic and Hebephilic Individuals From Their Online Forum Posts

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    Individuals who identify as pedophilic or hebephilic, and who do not offend, are increasingly visible in online discourse and as a focus of research. Developing knowledge about this population will offer insights into their psychological needs and, potentially, into the mechanisms and strategies individuals use to live offense-free lives. This study examined coping strategies among members of an online forum supporting pedohebephilic individuals who do not wish to offend. Forum users’ posts were analyzed using thematic analysis. Eleven themes emerged which were classifiable into three superordinate themes around (1) the acceptance of pedophilia, (2) strategies to stay safe, and (3) dealing with sexual arousal. These themes offer insight into the varying strategies used by these individuals to cope with stress and/or to remain offense free. Understanding whether these strategies are adaptive or maladaptive may help develop better support services for those who have not offended and may inform prevention efforts
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