211 research outputs found

    Sherwood Anderson : an experiment in journalism

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    James Schevill in his Sherwood Anderson His Life and Work describes Anderson\u27s plunge into journalism as an episode unique in American newspaper history, the first time a mature writer of important stature had been completely responsible for the contents of two country papers. Although it ha s bee n generally acknowledged that Anderson\u27s journalistic experiments are unique and make a significant contribution to the history of American journalism, these areas have never been analyzed in any detail by students of his work. This thesis will explore in depth the nature of Anderson\u27s journalistic experiments and evaluate his achievement in the history of American journalism in the 1920\u27s

    Late gestation modulation of fetal glucocorticoid effects requires the receptor for leukemia inhibitory factor: an observational study

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    BACKGROUND: Ablation of the low-affinity receptor subunit for leukemia inhibitory factor (LIFR) causes multi-systemic defects in the late gestation fetus. Because corticosterone is known to have a broad range of effects and LIF function has been associated with the hypothalamo-pituitary-adrenal axis, this study was designed to determine the role for LIFR in the fetus when exposed to the elevated maternal glucocorticoid levels of late gestation. Uncovering a requirement for LIFR in appropriate glucocorticoid response will further understanding of control of glucocorticoid function. METHODS: Maternal adrenalectomy or RU486 administration were used to determine the impact of the maternal glucocorticoid surge on fetal development in the absence of LIFR. The mice were analyzed by a variety of histological techniques including immunolabeling and staining techniques (hematoxylin and eosin, Alizarin red S and alcian blue). Plasma corticosterone was assayed using radioimmunoassay. RESULTS: Maternal adrenalectomy does not improve the prognosis for LIFR null pups and exacerbates the effects of LIFR loss. RU486 noticeably improves many of the tissues affected by LIFR loss: bone density, skeletal muscle integrity and glial cell formation. LIFR null pups exposed during late gestation to RU486 in utero survive natural delivery, unlike LIFR null pups from untreated litters. But RU486 treated LIFR null pups succumb within the first day after birth, presumably due to neural deficit resulting in an inability to suckle. CONCLUSION: LIFR plays an integral role in modulating the fetal response to elevated maternal glucocorticoids during late gestation. This role is likely to be mediated through the glucocorticoid receptor and has implications for adult homeostasis as a direct tie between immune, neural and hormone function

    Loneliness, social relations and health and wellbeing in deprived communities

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    There is growing policy concern about the extent of loneliness in advanced societies, and its prevalence among various social groups. This study looks at loneliness among people living in deprived communities, where there may be additional barriers to social engagement including low incomes, fear of crime, poor services and transient populations. The aim was to examine the prevalence of loneliness, and also its associations with different types of social contacts and forms of social support, and its links to self-reported health and wellbeing in the population group. The method involved a cross-sectional survey of 4,302 adults across 15 communities, with the data analysed using multinomial logistic regression controlling for sociodemographics, then for all other predictors within each domain of interest. Frequent feelings of loneliness were more common among those who: had contact with family monthly or less; had contact with neighbours weekly or less; rarely talked to people in the neighbourhood; and who had no available sources of practical or emotional support. Feelings of loneliness were most strongly associated with poor mental health, but were also associated with long-term problems of stress, anxiety and depression, and with low mental wellbeing, though to a lesser degree. The findings are consistent with a view that situational loneliness may be the product of residential structures and resources in deprived areas. The findings also show that neighbourly behaviours of different kinds are important for protecting against loneliness in deprived communities. Familiarity within the neighbourhood, as active acquaintance rather than merely recognition, is also important. The findings are indicative of several mechanisms that may link loneliness to health and wellbeing in our study group: loneliness itself as a stressor; lonely people not responding well to the many other stressors in deprived areas; and loneliness as the product of weak social buffering to protect against stressors

    Perceptions and experiences of frailty interventions:quantitative and qualitative results from a survey of partners within the European Innovation Partnership on Active and Healthy Ageing (EIP-AHA)

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    The European Innovation Partnership on Active and Healthy Ageing (EIP-AHA) was launched by the European Commission in 2011 to promote innovation in ageing research. This paper explores the experiences of partners delivering frailty interventions within Europe, registering their programmes with the EIP-AHA. Data were collected using an online survey from 21 partners in seven countries. A mixed-method approach was used with inductive thematic analysis of free-text responses to improve data richness. Responses indicated that there was a lack of consistency between EIP-AHA partners in methods of defining, screening and measuring for frailty and pre-frailty. Open responses to survey questions about intervention facilitators, moderators and barriers were coded into two themes: working with stakeholders and project management. We concluded that EIP-AHA partners are providing interventions addressing physical, cognitive and wellbeing elements of frailty. However, there needs to be an increase in the proportion of interventions that consistently apply valid methods of screening and/or measuring frailty and pre-frailty. Most, but not all projects are targeting pre-frail older adults, suggesting an appropriate balance of prevention in a useful ‘intervention window’ but also a growing understanding that frailty at later stages is amenable to intervention. Findings suggest design manipulations to improve outcomes and adherence to interventions, specifically inclusion of a perceived benefit/reward for older adults, e.g. a social aspect or health-care promotion

    Lineage relationship of prostate cancer cell types based on gene expression

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    <p>Abstract</p> <p>Background</p> <p>Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells.</p> <p>Methods</p> <p>Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology) and pattern 4 (aglandular) sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype) and LuCaP 49 (neuroendocrine/small cell carcinoma) grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts.</p> <p>Results</p> <p>Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like) grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness.</p> <p>Conclusions</p> <p>Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.</p

    Green tea polyphenols supplementation and Tai Chi exercise for postmenopausal osteopenic women: safety and quality of life report

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    <p>Abstract</p> <p>Background</p> <p>Evidence suggests that both green tea polyphenols (GTP) and Tai Chi (TC) exercise may benefit bone health in osteopenic women. However, their safety in this population has never been systematically investigated. In particular, there have been hepatotoxicity concerns related to green tea extract. This study was to evaluate the safety of 24 weeks of GTP supplementation combined with TC exercise in postmenopausal osteopenic women, along with effects on quality of life in this population.</p> <p>Methods</p> <p>171 postmenopausal women with osteopenia were randomly assigned to 4 treatment arms for 24 weeks: (1) Placebo (500 mg starch/day), (2) GTP (500 mg GTP/day), (3) Placebo + TC (placebo plus TC training at 60 min/session, 3 sessions/week), and (4) GTP + TC (GTP plus TC training). Safety was examined by assessing liver enzymes (aspartate aminotransferase, alanine aminotransferase), alkaline phosphatase, and total bilirubin at baseline and every 4 weeks. Kidney function (urea nitrogen and creatinine), calcium, and inorganic phosphorus were also assessed at the same times. Qualify of life using SF-36 questionnaire was evaluated at baseline, 12, and 24 weeks. A mixed model of repeated measures ANOVA was applied for analysis.</p> <p>Results</p> <p>150 subjects completed the study (12% attrition rate). The compliance rates for study agents and TC exercise were 89% and 83%, respectively. Neither GTP supplementation nor TC exercise affected liver or kidney function parameters throughout the study. No adverse event due to study treatment was reported by the participants. TC exercise significantly improved the scores for role-emotional and mental health of subjects, while no effect on quality of life was observed due to GTP supplementation.</p> <p>Conclusions</p> <p>GTP at a dose of 500 mg/day and/or TC exercise at 3 hr/week for 24 weeks appear to be safe in postmenopausal osteopenic women, particularly in terms of liver and kidney functions. TC exercise for 24 weeks (3 hr/wk) significantly improved quality of life in terms of role-emotional and mental health in these subjects. ClinicalTrials.gov identifier: NCT00625391.</p

    Epiblastic Cited2 deficiency results in cardiac phenotypic heterogeneity and provides a mechanism for haploinsufficiency

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    AIMS: Deletion of the transcription factor Cited2 causes penetrant and phenotypically heterogenous cardiovascular and laterality defects and adrenal agenesis. Heterozygous human CITED2 mutation is associated with congenital heart disease, suggesting haploinsufficiency. Cited2 functions partly via a Nodal--&gt;Pitx2c pathway controlling left-right patterning. In this present study we investigated the primary site of Cited2 function and mechanisms of haploinsufficiency. METHODS AND RESULTS: A Cited2 conditional allele enabled its deletion in particular cell lineages in mouse development. A lacZ reporter cassette allowed indication of deletion. Congenic Cited2 heterozygous mice were used to investigate haploinsufficiency. Embryos were examined by magnetic resonance imaging, by sectioning and by quantitative real-time polymerase chain reaction (qRT-PCR). Epiblast-specific deletion of Cited2 using Sox2Cre recapitulated penetrant and phenotypically heterogenous cardiovascular and laterality defects. Neural crest-specific deletion using Wnt1Cre affected cranial ganglia but not cardiac development. Mesodermal deletion with Mesp1Cre resulted in low penetrance of septal defect. Mesodermal deletion with T-Cre resulted in adrenal agenesis, but infrequent cardiac septal and laterality defects. beta-Galatactosidase staining and qRT-PCR demonstrated the efficiency and location of Cited2 deletion. Murine Cited2 heterozygosity is itself associated with cardiac malformation, with three of 45 embryos showing ventricular septal defect. Cited2 gene expression in E13.5 hearts was reduced 2.13-fold in Cited2(+/-) compared with wild-type (P = 2.62 x 10(-6)). The Cited2 target gene Pitx2c was reduced 1.5-fold in Cited2(+/-) (P = 0.038) hearts compared with wild-type, and reduced 4.9-fold in Cited2(-/-) hearts (P = 0.00031). Pitx2c levels were reduced two-fold (P = 0.009) in Cited2(+/-) embryos, in comparison with wild-type. Cited2 and Pitx2c expression were strongly correlated in wild-type and Cited2(+/-) hearts (Pearson rank correlation = 0.68, P = 0.0009). Cited2 expression was reduced 7474-fold in Sox2Cre deleted hearts compared with controls (P = 0.00017) and Pitx2c was reduced 3.1-fold (P = 0.013). Deletion of Cited2 with Mesp1Cre resulted in a 130-fold reduction in cardiac Cited2 expression compared with control (P = 0.0002), but Pitx2c expression was not affected. CONCLUSION: These results indicate that phenotypically heterogenous and penetrant cardiac malformations in Cited2 deficiency arise from a primary requirement in epiblast derivatives for left-right patterning, with a secondary cell-autonomous role in the mesoderm. Cardiac malformation associated with Cited2 haploinsufficiency may occur by reducing expression of key Cited2 targets such as Pitx2c
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