tbuckley/cabot-search huggingface dataset:
Patient Characteristics and Cell Source Determine the Number of Isolated Human Cardiac Progenitor Cells
Authors: Ayelet Itzhaki-Alfia, Jonathan Leor, Ehud Raanani, Leonid Sternik, Dan Spiegelstein, Shiri Netser, Radka Holbova, Meirav Pevsner-Fischer, Jacob Lavee, Israel M. Barbash
Journal: Circulation (2009)

Background— The identification and isolation of human cardiac progenitor cells (hCPCs) offer new approaches for myocardial regeneration and repair. Still, the optimal source of human cardiac progenitor cells and the influence of patient characteristics on their number remain unclear. Using a novel method to isolate human cardiac progenitor cells, we aimed to define the optimal source and association between their number and patient characteristics. Methods and Results— We developed a novel isolation method that produced viable cells (7×10 6 ±6.53×10 5 /g) from various tissue samples obtained during heart surgery or endomyocardial biopsies (113 samples from 94 patients 23 to 80 years of age). The isolated cardiac cells were grown in culture with a stem cell expansion medium. According to fluorescence-activated cell sorting analysis, cultured cells derived from the right atrium generated higher amounts of c-kit + (24±2.5%) and Islet-1 + cells (7%) in culture (mean of passages 1, 2, and 3) than did cultured cells from the left atrium (7.3±3.5%), right ventricle (4.1±1.6%), and left ventricle (9.7±3%; P =0.001). According to multivariable analysis, the right atrium as the cell source and female sex were associated with a higher number of c-kit + cells. There was no overlap between c-kit + and Islet-1 expression. In vitro assays of differentiation into osteoblasts, adipocytes, and myogenic lineage showed that the isolated human cardiac progenitor cells were multipotent. Finally, the cells were transplanted into infarcted myocardium of rats and generated myocardial grafts. Conclusion— Our results show that the right atrium is the best source for c-kit + and Islet-1 progenitors, with higher percentages of c-kit + cells being produced by women.
Decline in Invasive Pneumococcal Disease after the Introduction of Protein–Polysaccharide Conjugate Vaccine
Authors: Cynthia G. Whitney, Monica M. Farley, James Hadler, Lee H. Harrison, Nancy M. Bennett, Ruth Lynfield, Arthur Reingold, Paul R. Cieslak, Tamara Pilishvili, Delois Jackson, Richard R. Facklam, James H. Jorgensen, Anne Schuchat
Journal: New England Journal of Medicine (2003)

In early 2000, a protein-polysaccharide conjugate vaccine targeting seven pneumococcal serotypes was licensed in the United States for use in young children.We examined population-based data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention to evaluate changes in the burden of invasive disease, defined by isolation of Streptococcus pneumoniae from a normally sterile site. Serotyping and susceptibility testing of isolates were performed. We assessed trends using data from seven geographic areas with continuous participation from 1998 through 2001 (population, 16 million).The rate of invasive disease dropped from an average of 24.3 cases per 100,000 persons in 1998 and 1999 to 17.3 per 100,000 in 2001. The largest decline was in children under two years of age. In this group, the rate of disease was 69 percent lower in 2001 than the base-line rate (59.0 cases per 100,000 vs. 188.0 per 100,000, P<0.001); the rate of disease caused by vaccine and vaccine-related serotypes declined by 78 percent (P<0.001) and 50 percent (P<0.001), respectively. Disease rates also fell for adults; as compared with base line, the rate of disease in 2001 was 32 percent lower for adults 20 to 39 years of age (7.6 cases per 100,000 vs. 11.2 per 100,000, P<0.001), 8 percent lower for those 40 to 64 years of age (19.7 per 100,000 vs. 21.5 per 100,000, P=0.03), and 18 percent lower for those 65 years of age or more (49.5 per 100,000 vs. 60.1 per 100,000, P<0.001). The rate of disease caused by strains that were not susceptible to penicillin was 35 percent lower in 2001 than in 1999 (4.1 cases per 100,000 vs. 6.3 per 100,000, P<0.001).The use of the pneumococcal conjugate vaccine is preventing disease in young children, for whom the vaccine is indicated, and may be reducing the rate of disease in adults. The vaccine provides an effective new tool for reducing disease caused by drug-resistant strains.
Estrogen Receptor α Regulates Tripartite Motif–Containing Protein 21 Expression, Contributing to Dysregulated Cytokine Production in Systemic Lupus Erythematosus
Authors: Siobhán Smith, Joan Ní Gabhann, Eoghan McCarthy, Barbara Coffey, Rebecca Mahony, Jennifer C. Byrne, Kevin Stacey, Elizabeth Ball, Aubrey Bell, Gaye Cunnane, Michele F. Doran, Eamonn S. Molloy, Ruth Z. Lee, Brian Harvey, Grainne Kearns, Caroline A. Jefferies
Journal: Arthritis & Rheumatology (2013)

To examine the role of 17β-estradiol in the regulation of the autoantigen tripartite motif-containing protein 21 (TRIM-21) in patients with systemic lupus erythematosus (SLE).Monocytes isolated from healthy control subjects and patients with SLE were stimulated with 17β-estradiol and/or the estrogen receptor α (ERα) antagonist methyl-piperidino-pyrazole dihydrochloride. TRIM-21, ERα, and CREMα expression was determined by real-time polymerase chain reaction (PCR) analysis. MatInspector software was used to identify putative binding sites within the TRIM-21 promoter. ERα binding to the TRIM-21 gene promoter region in monocytes was analyzed by chromatin immunoprecipitation (ChIP) assay. TRIM-21 and interferon regulatory factor 3 protein levels were analyzed by Western blotting.Real-time PCR analysis demonstrated a role of estrogen in the regulation of TRIM-21 expression in monocytes, which correlated positively with ERα gene expression in patients with SLE. Investigations into the human TRIM-21 promoter revealed the presence of an estrogen response element, with ChIP assays confirming ERα binding to this site. Studies into estrogen-induced TRIM-21 expression revealed a hyperresponsiveness of SLE patients to 17β-estradiol, which led to the enhanced levels of TRIM-21 observed in these individuals.Our results demonstrate a role of estrogen in the regulation of TRIM-21 expression through an ERα-dependent mechanism, a pathway that we observed to be overactive in SLE patients. Treatment of monocytes with an ERα antagonist abrogated estrogen-induced TRIM-21 expression and, as a consequence, decreased the expression of interleukin-23. These findings identify TRIM-21 as a novel ERα-regulated gene and provide novel insights into the link between estrogen and the molecular pathogenesis of SLE.
Type 5 Adenylyl Cyclase Increases Oxidative Stress by Transcriptional Regulation of Manganese Superoxide Dismutase via the SIRT1/FoxO3a Pathway
Authors: Lo Lai, Lin Yan, Shumin Gao, Che-Lin Hu, Hui Ge, Amy Davidow, Misun Park, Claudio Bravo, Kousaku Iwatsubo, Yoshihiro Ishikawa, Johan Auwerx, David A. Sinclair, Stephen F. Vatner, Dorothy E. Vatner
Journal: Circulation (2013)

For reasons that remain unclear, whether type 5 adenylyl cyclase (AC5), 1 of 2 major AC isoforms in heart, is protective or deleterious in response to cardiac stress is controversial. To reconcile this controversy we examined the cardiomyopathy induced by chronic isoproterenol in AC5 transgenic (Tg) mice and the signaling mechanisms involved.Chronic isoproterenol increased oxidative stress and induced more severe cardiomyopathy in AC5 Tg, as left ventricular ejection fraction fell 1.9-fold more than wild type, along with greater left ventricular dilation and increased fibrosis, apoptosis, and hypertrophy. Oxidative stress induced by chronic isoproterenol, detected by 8-OhDG was 15% greater, P=0.007, in AC5 Tg hearts, whereas protein expression of manganese superoxide dismutase (MnSOD) was reduced by 38%, indicating that the susceptibility of AC5 Tg to cardiomyopathy may be attributable to decreased MnSOD expression. Consistent with this, susceptibility of the AC5 Tg to cardiomyopathy was suppressed by overexpression of MnSOD, whereas protection afforded by the AC5 knockout (KO) was lost in AC5 KO×MnSOD heterozyous KO mice. Elevation of MnSOD was eliminated by both sirtuin and MEK inhibitors, suggesting both the SIRT1/FoxO3a and MEK/ERK pathway are involved in MnSOD regulation by AC5.Overexpression of AC5 exacerbates the cardiomyopathy induced by chronic catecholamine stress by altering regulation of SIRT1/FoxO3a, MEK/ERK, and MnSOD, resulting in oxidative stress intolerance, thereby shedding light on new approaches for treatment of heart failure.
Association of bone scintigraphic abnormalities with knee malalignment and pain
Authors: V B Kraus, G McDaniel, T W Worrell, S Feng, T P Vail, G Varju, R E Coleman
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> The information content of knee bone scintigraphy was evaluated, including pattern, localisation and intensity of retention relative to radiographic features of knee osteoarthritis, knee alignment and knee symptoms. <h3>Methods:</h3> A total of 308 knees (159 subjects) with symptomatic and radiographic knee osteoarthritis of at least one knee was assessed by late-phase <sup>99m</sup>Technetium methylene disphosphonate bone scintigraph, fixed-flexion knee radiograph, full limb radiograph for knee alignment and for self-reported knee symptom severity. Generalised linear models were used to control for within-subject correlation of knee data. <h3>Results:</h3> The compartmental localisation (medial vs lateral) and intensity of knee bone scan retention were associated with the pattern (varus vs valgus) (p&lt;0.001) and severity (p&lt;0.001) of knee malalignment and localisation and severity of radiographic osteoarthritis (p&lt;0.001). Bone scan agent retention in the tibiofemoral, but not patellofemoral, compartment was associated with severity of knee symptoms (p&lt;0.001) and persisted after adjusting for radiographic osteoarthritis (p&lt;0.001). <h3>Conclusion:</h3> To the authors' knowledge, this is the first study describing a relationship between knee malalignment, joint symptom severity and compartment-specific abnormalities by bone scintigraphy. This work demonstrates that bone scintigraphy is a sensitive and quantitative indicator of symptomatic knee osteoarthritis. Used selectively, bone scintigraphy is a dynamic imaging modality that holds great promise as a clinical trial screening tool and outcome measure.
Medicine Residents' Understanding of the Biostatistics and Results in the Medical Literature
Authors: Donna M. Windish, Stephen J. Huot, Michael L. Green
Journal: JAMA (2007)

Physicians depend on the medical literature to keep current with clinical information. Little is known about residents' ability to understand statistical methods or how to appropriately interpret research outcomes.To evaluate residents' understanding of biostatistics and interpretation of research results.Multiprogram cross-sectional survey of internal medicine residents.Percentage of questions correct on a biostatistics/study design multiple-choice knowledge test.The survey was completed by 277 of 367 residents (75.5%) in 11 residency programs. The overall mean percentage correct on statistical knowledge and interpretation of results was 41.4% (95% confidence interval [CI], 39.7%-43.3%) vs 71.5% (95% CI, 57.5%-85.5%) for fellows and general medicine faculty with research training (P < .001). Higher scores in residents were associated with additional advanced degrees (50.0% [95% CI, 44.5%-55.5%] vs 40.1% [95% CI, 38.3%-42.0%]; P < .001); prior biostatistics training (45.2% [95% CI, 42.7%-47.8%] vs 37.9% [95% CI, 35.4%-40.3%]; P = .001); enrollment in a university-based training program (43.0% [95% CI, 41.0%-45.1%] vs 36.3% [95% CI, 32.6%-40.0%]; P = .002); and male sex (44.0% [95% CI, 41.4%-46.7%] vs 38.8% [95% CI, 36.4%-41.1%]; P = .004). On individual knowledge questions, 81.6% correctly interpreted a relative risk. Residents were less likely to know how to interpret an adjusted odds ratio from a multivariate regression analysis (37.4%) or the results of a Kaplan-Meier analysis (10.5%). Seventy-five percent indicated they did not understand all of the statistics they encountered in journal articles, but 95% felt it was important to understand these concepts to be an intelligent reader of the literature.Most residents in this study lacked the knowledge in biostatistics needed to interpret many of the results in published clinical research. Residency programs should include more effective biostatistics training in their curricula to successfully prepare residents for this important lifelong learning skill.
A Comprehensive Assessment of Parental Age and Psychiatric Disorders
Authors: John J. McGrath, Liselotte Petersen, Esben Agerbo, Ole Mors, Preben Bo Mortensen, Carsten Bøcker Pedersen
Journal: JAMA Psychiatry (2014)

There has been recent interest in the findings that the offspring of older fathers have an increased risk of both de novo mutations and neuropsychiatric disorders. However, the offspring of younger parents are also at risk for some adverse mental health outcomes.To determine the association between maternal and paternal age and a comprehensive range of mental health disorders.A comprehensive, population-based record linkage study using the Danish Psychiatric Central Research Register from January 1, 1995, through December 31, 2011. A total of 2 894 688 persons born in Denmark from January 1, 1955, through December 31, 2006, were followed up during the study period.Maternal and paternal age at the time of offspring's birth.We examined a broad range of International Classification of Diseases-defined mental disorders, including substance use; schizophrenia and related disorders; mood disorders; neurotic, stress-related, and somatoform disorders; eating disorders; specific personality disorders; and a range of developmental and childhood disorders. The incidence rate ratios for each mental disorder outcome were estimated by log linear Poisson regression with adjustments for the calendar period, age, sex, and age of the other parent.The cohort was observed for 42.7 million person-years, during which 218 441 members of the cohort had their first psychiatric contact for any psychiatric disorder. Based on the overall risk of psychiatric disorders, the offspring of younger and older parents were at increased risk compared with those of parents aged 25 to 29 years. When the offspring were examined for particular disorders, the nature of the relationship changed. For example, the offspring of older fathers were at an increased risk of schizophrenia and related disorders, mental retardation, and autism spectrum disorders. In contrast, the offspring of young mothers (and to a lesser extent young fathers) were at an increased risk for substance use disorders, hyperkinetic disorders, and mental retardation.The offspring of younger mothers and older fathers are at risk for different mental health disorders. These differences can provide clues to the complex risk architecture underpinning the association between parental age and the mental health of offspring.
Failure to detect an effect of prolactin on pulmonary surfactant and adrenal steroids in fetal sheep and rabbits.
Authors: P L Ballard, P D Gluckman, A Brehier, J A Kitterman, S L Kaplan, A M Rudolph, M M Grumbach
Journal: Journal of Clinical Investigation (1978)

Recent reports have indicated an association between low cord prolactin (PRL) and the occurrence of respiratory distress syndrome in premature infants, and it is reported that PRL administration increases the lecithin content of fetal rabbit lung. We administered 1 mg ovine PRL to 32 rabbit fetuses on day 24 of gestation and evaluated lung phospholipid synthesis and content on day 26. Compared with diluent-injected littermates, PRL had no effect on the rate of choline incorporation into lecithin, tissue content of phospholipid and disaturated lecithin, or plasma corticoids. However, both choline incorporation and corticoids were increased in all animals undergoing surgery compared with unoperated controls. We also infused PRL (1 mg/day, i.v.) into three fetal sheep continuously over five periods of 5-8 days. Although supraphysiologic concentrations of PRL were achieved in plasma and amniotic fluid, there was no effect of this treatment on the flux of tracheal fluid surfactant or on plasma concentrations of corticoids of dehydroepiandrosterone sulfate. Thus, in this study, we failed to detect either a stimulation of the surfactant system or an adreno-corticotropic effect by PRL as previously postulated. This suggests that the relationship between PRL and respiratory distress sundrome is an indirect association.
Epidemiological time series studies of PM<sub>2.5</sub>and daily mortality and hospital admissions: a systematic review and meta-analysis
Authors: R W Atkinson, S Kang, H R Anderson, I C Mills, H A Walton
Journal: Thorax (2014)

<h3>Background</h3> Short-term exposure to outdoor fine particulate matter (particles with a median aerodynamic diameter &lt;2.5 μm (PM<sub>2</sub>.<sub>5</sub>)) air pollution has been associated with adverse health effects. Existing literature reviews have been limited in size and scope. <h3>Methods</h3> We conducted a comprehensive, systematic review and meta-analysis of 110 peer-reviewed time series studies indexed in medical databases to May 2011 to assess the evidence for associations between PM<sub>2</sub>.<sub>5</sub> and daily mortality and hospital admissions for a range of diseases and ages. We stratified our analyses by geographical region to determine the consistency of the evidence worldwide and investigated small study bias. <h3>Results</h3> Based upon 23 estimates for all-cause mortality, a 10 µg/m<sup>3</sup> increment in PM<sub>2</sub>.<sub>5</sub> was associated with a 1.04% (95% CI 0.52%&nbsp;to 1.56%) increase in the risk of death. Worldwide, there was substantial regional variation (0.25% to 2.08%). Associations for respiratory causes of death were larger than for cardiovascular causes, 1.51% (1.01% to 2.01%) vs 0.84% (0.41% to 1.28%). Positive associations with mortality for most other causes of death and for cardiovascular and respiratory hospital admissions were also observed. We found evidence for small study bias in single-city mortality studies and in multicity studies of cardiovascular disease. <h3>Conclusions</h3> The consistency of the evidence for adverse health effects of short-term exposure to PM<sub>2</sub>.<sub>5</sub> across a range of important health outcomes and diseases supports policy measures to control PM<sub>2</sub>.<sub>5</sub> concentrations. However, reasons for heterogeneity in effect estimates in different regions of the world require further investigation. Small study bias should also be considered in assessing and quantifying health risks from PM<sub>2</sub>.<sub>5</sub>.
Detection of persistent measles virus infection in Crohn's disease: current status of experimental work
Authors: S GHOSH, E ARMITAGE, D WILSON, P D MINOR, M A AFZAL
Journal: Gut (2001)

The aetiology of Crohn's disease is unknown. Any hypothesis must take into account the continuing increase in incidence in some countries, including the UK. The increase affects the population from early teens, and specific comprehensive epidemiological studies in children and adolescents show a continuing rise in the rate of age and sex standardised incidence in Scotland.1 This suggests an environmental trigger, which may interact with underlying genetic susceptibility. A number of such environmental triggers have been proposed, including persistent infections, transient infections in a host with abnormal mucosal immunity, particulate materials, or dietary changes. Persistent infection with the measles virus after wild-type virus infections or immunisation with live attenuated measles vaccine have been proposed as important environmental triggers based on epidemiological observations.2 3 Measles is a single stranded RNA virus which can induce immune suppression. Measles infection is generally self limited and results in long term immunity, but rarely, persistent infection may occur after wild-type virus infection. The virus has special affinity for epithelial cells of the respiratory tract and cells of the immune system, such as lymphocytes and macrophages.4 A number of chronic diseases have been linked with persistent measles virus infection. These include multiple sclerosis, Paget's disease, a variety of autoimmune diseases, and autism, although definite evidence is lacking in each. Inflammatory bowel disease (IBD), especially Crohn's disease, has been linked to persistent measles virus infection. Ekbom et al proposed perinatal exposure to wild-type measles virus may lead to development of Crohn's disease later in life.2 3 Such case control epidemiological studies are of course prone to a variety of confounding factors, especially selection and recall biases. Epidemiologically robust data from a large controlled prospective study showed absence of a link between intrauterine exposure to measles and Crohn's disease.5 However, epidemiological studies linking …
Evolution of Tuberculosis Control and Prospects for Reducing Tuberculosis Incidence, Prevalence, and Deaths Globally
Authors: Christopher Dye
Journal: JAMA (2005)

The United Nations Millennium Development Goals (MDGs) are stimulating more rigorous evaluations of the impact of DOTS (the WHO-recommended approach to tuberculosis control based on 5 essential elements) and other possible strategies for tuberculosis (TB) control.To evaluate the prospects for detecting 70% of new sputum smear-positive cases and successfully treating 85% of these by the end of 2005, for reducing TB incidence, and for halving TB prevalence and deaths globally between 1990 and 2015, as specified by the MDGs.TB case notifications (1980-2003) from DOTS and non-DOTS programs and cohort treatment outcomes (1994-2002) reported annually to the World Health Organization (WHO) by up to 200 countries, TB death registrations, and prevalence surveys of infection and disease.Case notification series that reflect trends in incidence, treatment outcomes from DOTS cohorts, death statistics from countries with WHO-validated vital registration systems, and national prevalence surveys of infection and disease.Case reports, treatment outcomes, prevalence surveys, and death registrations from WHO's global TB database covering 1990-2003 to estimate TB incidence, prevalence, and death rates through 2015 for 9 epidemiologically different world regions.TB incidence increased globally in 2003, but incidence, prevalence, and death rates were approximately stable or decreased in 7 of 9 regions. The exceptions were regions of Africa with low (<4% in adults 15-49 years) and high rates (> or =4%) of HIV infection. The global detection rate of new smear-positive cases by DOTS programs increased from 11% in 1995 to 45% in 2003 (with the lowest case-detection rates in Eastern Europe and the highest rates in the Western Pacific) and could reach 60% by 2005. More than 17 million patients were treated in DOTS programs between 1994 and 2003, with overall treatment success rates more than 80% since 1998. In 2003, overall reported treatment success was 82%, with much variation among regions. The highest rates were reported in the Western Pacific region (89%) and lowest rates in African countries with high and low HIV infection rates (71% and 74%, respectively), in established market economies (77%), and in Eastern Europe (75%). To halve the prevalence rate by 2015, TB control programs must reach global targets for detection (70%) and treatment success (85%) and also reduce the incidence rate by at least 2% annually. To halve the death rate, incidence must decrease more steeply, by at least 5% to 6% annually.Reduction of TB incidence, prevalence, and deaths by 2015 could be achieved in most of the world, but the challenge will be greatest in Africa and Eastern Europe.