tbuckley/cabot-search huggingface dataset:
Effect of a Nutrition Supplement and Physical Activity Program on Pneumonia and Walking Capacity in Chilean Older People: A Factorial Cluster Randomized Trial
Authors: Alan D. Dangour, Cecilia Albala, Elizabeth Allen, Emily Grundy, Damian G. Walker, Cristian Aedo, Hugo Sanchez, Olivia Fletcher, Diana Elbourne, Ricardo Uauy
Journal: PLoS Medicine (2011)

Ageing is associated with increased risk of poor health and functional decline. Uncertainties about the health-related benefits of nutrition and physical activity for older people have precluded their widespread implementation. We investigated the effectiveness and cost-effectiveness of a national nutritional supplementation program and/or a physical activity intervention among older people in Chile.We conducted a cluster randomized factorial trial among low to middle socioeconomic status adults aged 65-67.9 years living in Santiago, Chile. We randomized 28 clusters (health centers) into the study and recruited 2,799 individuals in 2005 (~100 per cluster). The interventions were a daily micronutrient-rich nutritional supplement, or two 1-hour physical activity classes per week, or both interventions, or neither, for 24 months. The primary outcomes, assessed blind to allocation, were incidence of pneumonia over 24 months, and physical function assessed by walking capacity 24 months after enrollment. Adherence was good for the nutritional supplement (~75%), and moderate for the physical activity intervention (~43%). Over 24 months the incidence rate of pneumonia did not differ between intervention and control clusters (32.5 versus 32.6 per 1,000 person years respectively; risk ratio = 1.00; 95% confidence interval 0.61-1.63; p = 0.99). In intention-to-treat analysis, after 24 months there was a significant difference in walking capacity between the intervention and control clusters (mean difference 33.8 meters; 95% confidence interval 13.9-53.8; p = 0.001). The overall cost of the physical activity intervention over 24 months was US$164/participant; equivalent to US$4.84/extra meter walked. The number of falls and fractures was balanced across physical activity intervention arms and no serious adverse events were reported for either intervention.Chile's nutritional supplementation program for older people is not effective in reducing the incidence of pneumonia. This trial suggests that the provision of locally accessible physical activity classes in a transition economy population can be a cost-effective means of enhancing physical function in later life.Current Controlled Trials ISRCTN 48153354.
Strategies to Reduce Cancer-Care Costs
Authors: Merrill Goozner
Journal: JNCI Journal of the National Cancer Institute (2013)

Payment for cancer care will change radically over the next decade as the nation struggles to hold down health care costs, experts told an early October Institute of Medicine forum, Delivering Affordable Cancer Care in the 21st Century. Traditional fee-for-service medicine, in which oncology reimbursement relies disproportionately on profits from expensive chemotherapy drugs, will give way to a variety of alternative payment mechanisms that Medicare and insurance companies are now testing. These systems include bundled payments for episodes of care, value-based insurance design, and shared savings models linked with pay-for-performance programs that reward physicians who adhere to standardized treatment protocols. “If you think it’s been a tough reimbursement environment up to now, just wait. It’s going to be much, much tougher in a year or two,” said Mark McClellan, M.D., Ph.D., former administrator of the Centers
MICROBIAL PERSISTENCE
Authors: Robert M. McCune, Floyd M. Feldmann, Harold P. Lambert, Walsh McDermott
Journal: The Journal of Experimental Medicine (1966)

A previously reported form of microbial persistence whereby large populations of tubercle bacilli can be made to "vanish" uniformly from the tissues of mice has been shown to occur generally throughout each group of animals subjected to the experimental procedure; it does not reflect the eradication of the bacilli in the majority of animals with their persistence and ultimate revival in only a minority. The one demonstrable alteration of the tubercle bacilli while "vanished" is that they are sterile. Thus, they are undetectable by cell-free culture, tissue culture, and blind animal passage, i.e. by any method based on microbial multiplication. Whether they have also undergone alteration in morphology and persist in some unconventional form cannot be stated. Acid-fast forms similar to tubercle bacilli can be detected in small numbers by intensified microscopic search of tissue homogenates but the relationship of these forms to the sterile bacilli that ultimately revive is unclear. Thus, the persisting tubercle bacilli are more correctly designated as being in a "sterile state" than one of true latency. The uniform induction of the sterile state is a specific phenomenon requiring the participation of both the nicotinamide derivative, pyrazinamide, and isoniazid. Once assumed, this sterile state is relatively stable and the time required for revival of the tubercle bacilli in the spleens in one-half the animals is seven months. This process can be speeded up by the administration of large doses of cortisone in the third or fourth month after sterilization but revival is not significantly affected by the administration of cortisone earlier.
Rapid-growth pneumatocele mimics massive pneumothorax in a HIV-positive patient
Authors: Min-Shiau Hsieh, Chun-Ku Chen, Wing-Wai Wong, Chien-Sheng Huang
Journal: Thorax (2012)

We present a rare fast-growing giant pneumatocele in a patient presenting with suspected pneumocystis pneumonia (PCP) infection and bilateral pneumothoraces as a primary manifestation of AIDS (HIV viral loading test: 628 000 copies/ml). Tube thoracostomies were performed and complicated with enduring air leakage and subcutaneous …
High sensitivity of five colorectal screening programmes with faecal immunochemical test in the Veneto Region, Italy
Authors: M. Zorzi, C. Fedato, G. Grazzini, F. C. Stocco, F. Banovich, A. Bortoli, L. Cazzola, A. Montaguti, T. Moretto, M. Zappa, M. Vettorazzi
Journal: Gut (2010)

Although guaiac-based faecal occult blood test screening has been shown to be effective in reducing colorectal cancer (CRC) mortality, it has been criticised mostly for its low sensitivity. Italian CRC screening programmes are based on immunochemical tests (iFOBT). We collected and analysed the interval cancers (ICs) found by five screening programmes to estimate their sensitivity.ICs were identified in subjects who had a negative result in a screening examination from 2002 to 2007 (N=267,789); data were linked with 2002-2008 hospital discharge records. Analysis was based on the follow up of 468,306 person-years. The proportional incidence-based sensitivity was estimated overall and by sex, age class, time since last negative iFOBT result, anatomical site, and history of screening (first or subsequent test).Overall, 126 ICs were identified, compared to 572 expected cancers. The proportional incidences were 15.3% and 31.0% in the first and the second interval-years, respectively, with an overall episode sensitivity of 78.0% (95% CI: 73.8 to 81.6). Sensitivity was higher for males than females (80.1% vs 74.8%); no differences were observed by age, anatomical site or between programmes. The test sensitivity of iFOBT was 82.1% (95% CI 78.1% to 85.3%).iFOBT-based screening programmes showed a high performance in terms of sensitivity as estimated through the IC rates. The screening schedule utilised in our programmes (single iFOBT, positivity threshold of 100 ng Hb/ml of sample solution, inter-screening interval of 2 years) shows low rates of missed cancers that are diagnosed during the interval. HDR are a convenient and reliable source of data for IC studies.
Large-Scale Allelotype of Pancreaticobiliary Carcinoma Provides Quantitative Estimates of Genome-Wide Allelic Loss
Authors: Christine A. Iacobuzio-Donahue, Michiel S. van der Heijden, Mark R. Baumgartner, William J. Troup, Jane M. Romm, Kimberly Doheny, Elizabeth Pugh, Charles J. Yeo, Michael G. Goggins, Ralph H. Hruban, Scott E. Kern
Journal: Cancer Research (2004)

Abstract Studies of the allelotype of human cancers have provided valuable insights into those chromosomes targeted for genetic inactivation during tumorigenesis. We present the comprehensive allelotype of 82 xenografted pancreatic or biliary cancers using 386 microsatellite markers and spanning the entire genome at an average coverage of 10 cM. Allelic losses were nonrandomly distributed across the genome and most prevalent for chromosome arms 9p, 17p, and 18q (&amp;gt;60%), sites of the known tumor suppressor genes CDKN2A, TP53, and MADH4. Moderate rates of loss (at any one locus) were noted for chromosome arms 3p, 6q, 8p, 17q, 18p, 21q, and 22q (40–60%). A mapping of individual loci of allelic loss revealed 11 “hot spots” of loss of heterozygosity (&amp;gt;30%) in addition to loci near known tumor suppressor genes, corresponding to 3p, 4q, 5q, 6q, 8p, 12q, 14q, 21q, 22q, and the X chromosome. The average genomic fractional allelic loss was 15.3% of all tested markers for the 82 xenografted cancers, with allelic loss affecting as little as 1.5% to as much as 32.1% of tested loci, a remarkable 20-fold range. We determined the chromosome location (in cM) of each of the 386 markers used based on mapping data available from the National Center for Biotechnology Information, and we provide the first distance-based estimates of chromosome material lost in a human epithelial cancer. Specifically, we found that the cumulative size of allelic losses ranged from 58 to 1160 cM, with an average loss of 561.32 cM/tumor. We compared the genomic fractional allelic loss of each xenografted cancer with known clinicopathological features for each patient and found a significant correlation with smoking status (P &amp;lt; 0.01). These findings offer new loci for investigation of the genetic alterations common to pancreaticobiliary cancers and aid the understanding of mechanisms of allelic loss in human carcinogenesis.
Immunodeficiency and the Risk of Death in HIV Infection
Authors: A N Phillips, J Elford, C Sabin, M Bofill, G Janossy, C A Lee
Journal: JAMA (1992)

<h3>Objective.</h3> —To describe the rate of development of immunodeficiency in human immunodeficiency virus (HIV) infection and to relate this to the risk of death. <h3>Design.</h3> —Inception cohort followed up for up to 12 years from HIV seroconversion until January 1, 1992. <h3>Setting.</h3> —A regional hemophilia center based in a major teaching hospital. <h3>Patients.</h3> —All 111 patients with hemophilia who seroconverted to HIV-1 between 1979 and 1985 were registered at the center. Patients have been closely followed up clinically and immunologically. <h3>Outcome Measures.</h3> —Development of immunodeficiency, defined by a CD4 lymphocyte count falling beneath 0.20 and 0.05 ×10<sup>9</sup>/L, and death. <h3>Results.</h3> —Kaplan-Meier estimates suggest that almost half (46%; 95% confidence interval [CI], 26% to 66%) of patients alive 12 years after seroconversion will have a CD4 lymphocyte count that has remained above 0.05 ×10<sup>9</sup>/L. Thirty-five percent (95% CI, 22% to 48%) remain above 0.20 ×10<sup>9</sup>/L. Thirty-seven patients died of HIV-related causes, and there was a 52% probability (95% CI, 35% to 69%) of HIV-related mortality by 12 years from seroconversion. Mortality risk was closely associated with severe immunodeficiency. There was only a 15% chance (95% CI, 6% to 25%) of HIV-related death occurring before a CD4 count of below 0.05 × 10<sup>9</sup>/L had been reached. There was an average of one HIV-related death per 96.7 patient-years of observation before the CD4 count had fallen below 0.05 ×10<sup>9</sup>/L, as compared with one death per 2.5 patient-years of observation after the CD4 count had fallen below this level (<i>P</i>&lt;.0001). <h3>Conclusions.</h3> —In patients with HIV infection who are closely followed up, the risk of death is low before the CD4 lymphocyte count has fallen to 0.05 × 10<sup>9</sup>/L, a count many patients remain above up to 12 years after seroconversion. (<i>JAMA</i>. 1992;268:2662-2666)
Confocal Fluorescence Imaging Enables Noninvasive Quantitative Assessment of Host Cell Populations In Vivo Following Photodynamic Therapy
Authors: Soumya Mitra, Oleg Mironov, Thomas H. Foster
Journal: Theranostics (2012)

We report the use of optical imaging strategies to noninvasively examine photosensitizer distribution and physiological and host responses to 2-[1-hexyloxyethyl]-2 devinyl pyropheophorbide-a (HPPH)-mediated photodynamic therapy (PDT) of EMT6 tumors established in the ears of BALB/c mice.24 h following intravenous (IV) administration of 1 mol kg -1 HPPH, wide-field fluorescence imaging reveals tumor selectivity with an approximately 2-3-fold differential between tumor and adjacent normal tissue.Confocal microscopy demonstrates a relatively homogeneous intratumor HPPH distribution.Labeling of host cells using fluorophore-conjugated antibodies allowed the visualization of Gr1 + /CD11b + leukocytes and major histocompatibility complex class II (MHC-II) + cells in vivo.Imaging of the treated site at different time-points following irradiation shows significant and rapid increases in Gr1 + cells in response to therapy.The maximum accumulation of Gr1 + cells is found at 24 h post-irradiation, followed by a decrease at the 48 h time-point.Using IV-injected FITC-conjugated dextran as a fluorescent perfusion marker, we imaged tissue perfusion at different times post-irradiation and found that the reduced Gr1 + cell density at 48 h correlated strongly with functional damage to the vasculature as reported via decreased perfusion status.Dual color confocal imaging experiments demonstrates that about 90% of the anti-Gr1 cell population co-localized with anti-CD11b labeling, thus indicating that majority of the Gr1-labeled cells were neutrophils.At 24 h post-PDT, an approximately 2-fold increase in MHC-II+ cells relative to untreated control is also observed.Co-localization analysis reveals an increase in the fraction of Gr1 + cells expressing MHC-II, suggesting that HPPH-PDT is stimulating neutrophils to express an antigen-presenting phenotype.
An en masse phenotype and function prediction system for Mus musculus
Authors: Murat Taşan, Weidong Tian, David P Hill, Francis D Gibbons, Judith A Blake, Frederick P Roth
Journal: Genome biology (2008)

Individual researchers are struggling to keep up with the accelerating emergence of high-throughput biological data, and to extract information that relates to their specific questions. Integration of accumulated evidence should permit researchers to form fewer - and more accurate - hypotheses for further study through experimentation. Here a method previously used to predict Gene Ontology (GO) terms for Saccharomyces cerevisiae (Tian et al.: Combining guilt-by-association and guilt-by-profiling to predict Saccharomyces cerevisiae gene function. Genome Biol 2008, 9(Suppl 1):S7) is applied to predict GO terms and phenotypes for 21,603 Mus musculus genes, using a diverse collection of integrated data sources (including expression, interaction, and sequence-based data). This combined 'guilt-by-profiling' and 'guilt-by-association' approach optimizes the combination of two inference methodologies. Predictions at all levels of confidence are evaluated by examining genes not used in training, and top predictions are examined manually using available literature and knowledge base resources. We assigned a confidence score to each gene/term combination. The results provided high prediction performance, with nearly every GO term achieving greater than 40% precision at 1% recall. Among the 36 novel predictions for GO terms and 40 for phenotypes that were studied manually, >80% and >40%, respectively, were identified as accurate. We also illustrate that a combination of 'guilt-by-profiling' and 'guilt-by-association' outperforms either approach alone in their application to M. musculus.
Health information for patients: time to look beyond patient information leaflets
Authors: Anthea Colledge, Josip Car, Ailsa Donnelly, Azeem Majeed
Journal: Journal of the Royal Society of Medicine (2008)

The 2004 United Kingdom white paper ‘Better information, better choices, better health’ sets out an ambitious strategy for the provision of health information. Everyone should have improved access to high quality information, health professionals should communicate more effectively with patients, and there should be a nationally coordinated process to produce and deliver information. There has been some progress towards these goals (e.g. NHS Direct now provides consumer health information by telephone, internet and digital television), but many patients and consumers still do not have access to the information they need or want, in a format they can understand. A lack of appropriate health information can have serious or even fatal consequences. As the target date for implementing the strategy is 2008, we discuss health information provision and what can be done to improve health communication.
Vitamin C prevents zidovudine-induced NAD(P)H oxidase activation and hypertension in the rat
Authors: I PAPPARELLA, G CEOLOTTO, L BERTO, M CAVALLI, S BOVA, G CARGNELLI, E RUGA, O MILANESI, L FRANCO, M MAZZONI
Journal: Cardiovascular Research (2006)

Cardiovascular risk is increased among HIV-infected patients receiving antiretroviral therapy due to the development of hypertension and metabolic abnormalities. In this study, we investigated the effects of long-term treatment with zidovudine (AZT) and vitamin C, alone and in combination, on blood pressure and on the chain of events linking oxidative stress to cardiac damage in the rat.Six adult Wistar Kyoto rats received AZT (1 mg/ml) in the drinking water for 8 months, six vitamin C (10 g/kg of food) and AZT, six vitamin C alone, and six served as controls.AZT increased systolic blood pressure, expression of gp91(phox) and p47(phox) subunits of NAD(P)H oxidase, and protein kinase C (PKC) delta activation and reduced antioxidant power of plasma and cardiac homogenates. AZT also caused morphological alterations in cardiac myocyte mitochondria, indicative of functional damage. All of these effects were prevented by vitamin C.Chronic AZT administration increases blood pressure and promotes cardiovascular damage through a NAD(P)H oxidase-dependent mechanism that involves PKC delta. Vitamin C antagonizes these adverse effects of AZT in the cardiovascular system.
Attitudes Toward Direct Predictive Testing for the Huntington Disease Gene
Authors: R Babul, S Adam, B Kremer, S Dufrasne, S Wiggins, M Huggins, J Theilmann, M Bloch, M R Hayden
Journal: JAMA (1993)

<h3>Objective.</h3> —To assess attitudes toward, and projected utilization of, direct mutation testing by individuals at risk for Huntington disease (HD). <h3>Design.</h3> —Prior to the cloning of the gene for HD, a questionnaire concerning the use of a definitive test was constructed and mailed to 354 participants in the Canadian Collaborative Study for HD. Completed questionnaires were received from 250 participants (response rate, 71%). Persons were asked to indicate whether they would participate in a new predictive test that was either 100% accurate (the definitive test, requiring blood only from the proband) or only 99% accurate. <h3>Results.</h3> —Most (72%) of the persons who had previously received a result in a predictive testing program said they would request testing in either situation. Significantly more persons would request the definitive test than the 99% accurate test (72% vs 58%;<i>P</i>&lt;.02). Respondents for whom testing was uninformative in the linkage test program or who had previously received an increased-risk result were more likely to indicate they would use the test than those who received a decreased-risk result or chose not to have the original test (<i>P</i>=.0003). Less than half (46%) of the participants who initially chose not to have the linkage test said they would return for the new direct test. The major factor that has limited acceptance of predictive testing for this group is the concern about receiving an increased-risk result in the absence of any therapy to alter progression of the disease. <h3>Conclusions.</h3> —A direct mutation test for HD will most readily be accepted by persons who wanted but could not previously receive a result in the linkage test program and those who previously received an increased-risk result. In the absence of therapy, the majority of persons who previously chose not to have predictive testing are unlikely to participate in a new test despite improved accuracy. This has implications for the expected demands for testing services for other adult-onset genetic disorders. (<i>JAMA</i>. 1993;270:2321-2325)
COPD and death: what exactly is the relationship?
Authors: M. Rudolf
Journal: Thorax (2007)

It’s time to take stock of what we do and do not know about what patients with COPD actually die from

The categorisation of different causes of death in patients with chronic obstructive pulmonary disease (COPD) has not usually been regarded as an important topic, but with all-cause mortality and cause-specific mortality now being used as outcome measures in large multicentre clinical trials,1,2 it is perhaps time to take stock of what we do and do not know about what patients with COPD actually die from. A number of studies that have addressed this issue over the years have, not surprisingly, found varying proportions of deaths ascribed to respiratory causes, lung cancer and cardiovascular disease (the three principal categories), with the results of any one study being highly dependent on both the source (and accuracy) of patient information and on the severity of underlying disease.3–7

The past year has witnessed a flurry of papers and editorials covering a number of widely different aspects of mortality in COPD, with topics ranging from the confidence we can have in interpreting mortality data,8 the possible …
LRP1 plays a major role in the amyloid-β clearance in microglia
Authors: Aurelie N’Songo, Takahisa Kanekiyo, Guojun Bu
Journal: Molecular Neurodegeneration (2013)

Background Alzheimer’s disease (AD), a progressive neurodegenerative disorder and the most prevalent type of dementia in the elderly, is characterized by the accumulation and deposition of amyloid-b (Ab) peptides and hyperphosphorylated tau in the brain. Impairment of Ab metabolism induces the formation of toxic Ab oligomers as well as the deposition of Ab in intraneuronal spaces and senile plaques, ultimately resulting in neuronal death. While familial AD is known to be caused by genetic mutations leading to an increase in Ab production, several lines of evidence suggest that sporadic AD is due to an impairment of Ab clearance. Ab is cleared from the central nervous system by elimination through the blood-brain barrier, extracellular proteolytic degradation or cellular uptake and subsequent lysosomal degradation. The low-density lipoprotein receptor-related protein 1 (LRP1) has been shown to play a major role in Ab metabolism in neurons, astrocytes and brain vessels. LRP1 is a large transmembrane receptor which mediates endocytosis of more than 30 ligands including apolipoprotein E and at2-macroglobulin. Microglia cells are the resident immune and phagocytic cells in the brain and are likely involved in the pathogenesis of AD by contributing to Ab clearance. Thus, we focused on roles of LRP1 in Ab clearance in microglia.