3,706 research outputs found
COVID-19 and the Radiology Match: A Residency Program\u27s Survival Guide to the Virtual Interview Season
Incommensurable worldviews? Is public use of complementary and alternative medicines incompatible with support for science and conventional medicine?
Proponents of controversial Complementary and Alternative Medicines, such as homeopathy, argue that these treatments can be used with great effect in addition to, and sometimes instead of, ?conventional? medicine. In doing so, they accept the idea that the scientific approach to the evaluation of treatment does not undermine use of and support for some of the more controversial CAM treatments. For those adhering to the scientific canon, however, such efficacy claims lack the requisite evidential basis from randomised controlled trials. It is not clear, however, whether such opposition characterises the views of the general public. In this paper we use data from the 2009 Wellcome Monitor survey to investigate public use of and beliefs about the efficacy of a prominent and controversial CAM within the United Kingdom, homeopathy. We proceed by using Latent Class Analysis to assess whether it is possible to identify a sub-group of the population who are at ease in combining support for science and conventional medicine with use of CAM treatments, and belief in the efficacy of homeopathy. Our results suggest that over 40% of the British public maintain positive evaluations of both homeopathy and conventional medicine simultaneously. Explanatory analyses reveal that simultaneous support for a controversial CAM treatment and conventional medicine is, in part, explained by a lack of scientific knowledge as well as concerns about the regulation of medical research
Src-mediated morphology transition of lung cancer cells in three-dimensional organotypic culture
A fribotic tumor microenvironment promotes progression of cancer. In this study, we utilize a reconstituted basement membrane mimics Matrigel based three-dimensional organotypic culture (rBM 3-D) to investigate the mechanisms that mediate the tumor promoting effects of the fibrogenic mediators TGF-β1 and type I collagen (Col-1) on lung adenocarcinoma cells. Similar to normal alveolar epithelial cells, the well-differentiated lung adenocarcinoma cells in rBM 3-D culture undergo acinar morphogeneis that features polarized epithelial cell spheres with a single central lumen. Either TGF-β1 or Col-1 modestly distorts acinar morphogenesis. On the other hand, TGF-β1 and Col-1 synergistically induce a transition from acinar morphology into stellate morphology that is characteristic of invasive and metastatic cancer cells. Inhibition of the Src kinase activity abrogates induction of stellate morphology, activation of Akt and mTOR, and the expression of tumor promoting genes by TGF-β1 and Col-1. To a similar extent, pharmacological inhibition of mTOR abrogates the cellular responses to TGF-β1 and Col-1. In summary, we demonstrate that TGF-β1 and Col-1 promote stellate morphogenesis of lung cancer cells. Our findings further suggest that the Src-Akt-mTOR axis mediates stellate morphogenesis. These findings also indicate that rBM 3-D culture can serve as an ideal platform for swift and cost-effective screening of therapeutic candidates at the interface of the tumor and its microenvironment. © 2013 Nguyen et al.; licensee BioMed Central Ltd
Bone turnover in elderly men: relationships to change in bone mineral density
BACKGROUND: It is not clear whether bone turnover markers can be used to make inference regarding changes in bone mineral density (BMD) in untreated healthy elderly men. The present study was designed to address three specific questions: (i) is there a relationship between bone turnover markers and femoral neck BMD within an individual; (ii) is there a relationship between baseline measurements of bone turnover markers and subsequent change in BMD; and (iii) is there a relationship between changes in bone turnover markers and changes in femoral neck BMD? METHODS: The present study was part of the on-going Dubbo Osteoporosis Epidemiology Study, which was designed as a prospective investigation. Men who had had at least 3 sequential visits with serum samples available during follow-up were selected from the study population. Serum C-terminal telopeptide of type I collagen (sICTP), N-terminal propeptide of type I collagen (sPINP) and femoral neck BMD were measured by competitive radioimmunoassays. Femoral neck bone mineral density (BMD) was measured by a densitometer (GE Lunar Corp, Madison, WI). Various mixed-effects models were used to assess the association between the markers and changes in BMD. RESULTS: One hundred and one men aged 70 ± 4.1 years (mean ± SD) met the criteria of selection for analysis. On average, sPINP decreased by 0.7% per year (p = 0.026), sICTP increased by 1.7% per year (p = 0.0002), and femoral neck BMD decreased by 0.4% per year (p < 0.01). Within-subject analysis indicated that changes in BMD were significantly associated with changes in sPINP (p = 0.022), but not with changes in sICTP (p = 0.84). However, neither baseline sPINP (p = 0.50) nor baseline sICTP (p = 0.63) was associated with subsequent changes in BMD. Moreover, changes in BMD were not significantly associated with previous changes in sPINP (p = 0.13) or sICTP (p = 0.95). CONCLUSION: These results suggest that in elderly men of Caucasian background, changes in sPINP were inversely related to changes in BMD within an individual. However, neither sPINP nor sICTP was sufficiently sensitive to predict the rate of change in BMD for a group of individuals or for an individual
Acute kidney injury in patients hospitalized with COVID-19 from the ISARIC WHO CCP-UK Study: a prospective, multicentre cohort study.
BACKGROUND: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). This study investigated adults hospitalized with COVID-19 and hypothesized that risk factors for AKI would include comorbidities and non-White race. METHODS: A prospective multicentre cohort study was performed using patients admitted to 254 UK hospitals with COVID-19 between 17 January 2020 and 5 December 2020. RESULTS: Of 85 687 patients, 2198 (2.6%) received acute kidney replacement therapy (KRT). Of 41 294 patients with biochemistry data, 13 000 (31.5%) had biochemical AKI: 8562 stage 1 (65.9%), 2609 stage 2 (20.1%) and 1829 stage 3 (14.1%). The main risk factors for KRT were chronic kidney disease (CKD) [adjusted odds ratio (aOR) 3.41: 95% confidence interval 3.06-3.81], male sex (aOR 2.43: 2.18-2.71) and Black race (aOR 2.17: 1.79-2.63). The main risk factors for biochemical AKI were admission respiratory rate >30 breaths per minute (aOR 1.68: 1.56-1.81), CKD (aOR 1.66: 1.57-1.76) and Black race (aOR 1.44: 1.28-1.61). There was a gradated rise in the risk of 28-day mortality by increasing severity of AKI: stage 1 aOR 1.58 (1.49-1.67), stage 2 aOR 2.41 (2.20-2.64), stage 3 aOR 3.50 (3.14-3.91) and KRT aOR 3.06 (2.75-3.39). AKI rates peaked in April 2020 and the subsequent fall in rates could not be explained by the use of dexamethasone or remdesivir. CONCLUSIONS: AKI is common in adults hospitalized with COVID-19 and it is associated with a heightened risk of mortality. Although the rates of AKI have fallen from the early months of the pandemic, high-risk patients should have their kidney function and fluid status monitored closely
Population genomics of domestic and wild yeasts
The natural genetics of an organism is determined by the distribution of sequences of its genome. Here we present one- to four-fold, with some deeper, coverage of the genome sequences of over seventy isolates of the domesticated baker's yeast, _Saccharomyces cerevisiae_, and its closest relative, the wild _S. paradoxus_, which has never been associated with human activity. These were collected from numerous geographic locations and sources (including wild, clinical, baking, wine, laboratory and food spoilage). These sequences provide an unprecedented view of the population structure, natural (and artificial) selection and genome evolution in these species. Variation in gene content, SNPs, indels, copy numbers and transposable elements provide insights into the evolution of different lineages. Phenotypic variation broadly correlates with global genome-wide phylogenetic relationships however there is no correlation with source. _S. paradoxus_ populations are well delineated along geographic boundaries while the variation among worldwide _S. cerevisiae_ isolates show less differentiation and is comparable to a single _S. paradoxus_ population. Rather than one or two domestication events leading to the extant baker's yeasts, the population structure of _S. cerevisiae_ shows a few well defined geographically isolated lineages and many different mosaics of these lineages, supporting the notion that human influence provided the opportunity for outbreeding and production of new combinations of pre-existing variation
Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: A phase one open-label study
Background: Patients with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA) are vitamin D deficient and in vitro treatment with 1,25 (OH) vitamin D of CD4+ cells from CF patients with ABPA decreases Aspergillus fumigatus(Af)-induced Th2 responses. This Phase I clinical trial investigated the safety and effectiveness of daily vitamin D supplementation in CF patients with ABPA to reduce allergic responses and ABPA symptoms, and increase serum vitamin D levels. Methods: Seven patients ages 12 years and older with a clinical diagnosis of CF and ABPA with current evidence of Af sensitization received 4000 IU vitamin D (cholecalciferol) daily for 24 weeks. The primary outcome of the study was safety followed by the Aspergillus induced IL-13 response in CD4+ T cells to test the hypothesis that vitamin D supplementation is safe and reduces Aspergillus induced IL-13 responses in CD4+ T cells. Secondary outcomes included total IgE, Aspergillus- specific IgE, vitamin D levels, FEV , urinary calcium/creatinine ratio, and cytokine production by Aspergillus-stimulated peripheral blood T cells. Results: Six months of vitamin D supplementation resulted in significant increases in serum 25-(OH) vitamin D level, and the treatment was well tolerated without evidence of vitamin D toxicity or hypercalcemia. There were no serious adverse events. Daily vitamin D supplementation led to significantly decreased Aspergillus induced IL-13 responses between the baseline visit and that at 24 weeks (p = 0.04). Aspergillus-specific IgE level was also significantly decreased after 8 (p = 0.035) and 24 weeks of daily vitamin D supplementation (p = 0.04). Conclusions: 4000 IU vitamin D daily over a 24-week period is well tolerated in CF patients with a history ABPA and current evidence of Th2 immunity to Af. Daily vitamin D supplementation was associated with reduced Aspergillus induced IL-13 responses from peripheral. CD4+ T cells and Aspergillus-specific IgE levels, as well as increased serum vitamin D levels. This treatment was well tolerated and the study supports further investigation of the use of vitamin D supplementation in Th2 mediated diseases. 2 3 3 3 1 3
Case-based reported mortality associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection in the Netherlands: the 2009-2010 pandemic season versus the 2010-2011 influenza season
<p>Abstract</p> <p>Background</p> <p>In contrast to seasonal influenza epidemics, where the majority of deaths occur amongst elderly, a considerable part of the 2009 pandemic influenza related deaths concerned relatively young people. In the Netherlands, all deaths associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection had to be notified, both during the 2009-2010 pandemic season and the 2010-2011 influenza season. To assess whether and to what extent pandemic mortality patterns were reverting back to seasonal patterns, a retrospective analyses of all notified fatal cases associated with laboratory-confirmed influenza A(H1N1) 2009 virus infection was performed.</p> <p>Methods</p> <p>The notification database, including detailed information about the clinical characteristics of all notified deaths, was used to perform a comprehensive analysis of all deceased patients with a laboratory-confirmed influenza A(H1N1) 2009 virus infection. Characteristics of the fatalities with respect to age and underlying medical conditions were analysed, comparing the 2009-2010 pandemic and the 2010-2011 influenza season.</p> <p>Results</p> <p>A total of 65 fatalities with a laboratory-confirmed influenza A(H1N1) 2009 virus infection were notified in 2009-2010 and 38 in 2010-2011. During the pandemic season, the population mortality rates peaked in persons aged 0-15 and 55-64 years. In the 2010-2011 influenza season, peaks in mortality were seen in persons aged 0-15 and 75-84 years. During the 2010-2011 influenza season, the height of first peak was lower compared to that during the pandemic season. Underlying immunological disorders were more common in the pandemic season compared to the 2010-2011 season (p = 0.02), and cardiovascular disorders were more common in the 2010-2011 season (p = 0.005).</p> <p>Conclusions</p> <p>The mortality pattern in the 2010-2011 influenza season still resembled the 2009-2010 pandemic season with a peak in relatively young age groups, but concurrently a clear shift toward seasonal patterns was seen, with a peak in mortality in the elderly, i.e. ≥ 75 years of age.</p
Equity and Geography: The Case of Child Mortality in Papua New Guinea
Background: Recent assessments show continued decline in child mortality in Papua New Guinea (PNG), yet complete subnational analyses remain rare. This study aims to estimate under-five mortality in PNG at national and subnational levels to examine the importance of geographical inequities in health outcomes and track progress towards Millennium Development Goal (MDG) 4
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