tbuckley/cabot-search huggingface dataset:
Advanced Dementia: State of the Art and Priorities for the Next Decade
Authors: Susan L. Mitchell, Betty S. Black, Mary Ersek, Laura C. Hanson, Susan C. Miller, Greg A. Sachs, Joan M. Teno, R. Sean Morrison
Journal: Annals of Internal Medicine (2012)

Dementia is a leading cause of death in the United States. This article outlines the current understanding of advanced dementia and identifies research priorities for the next decade. Research over the past 25 years has largely focused on describing the experience of patients with advanced dementia. This work has delineated abundant opportunities for improvement, including greater recognition of advanced dementia as a terminal illness, better treatment of distressing symptoms, increased access to hospice and palliative care services, and less use of costly and aggressive treatments that may be of limited clinical benefit. Addressing those opportunities must be the overarching objective for the field in the coming decade. Priority areas include designing and testing interventions that promote high-quality, goal-directed care; health policy research to identify strategies that incentivize cost-effective and evidence-based care; implementation studies of promising interventions and policies; and further development of disease-specific outcome measures. There is great need and opportunity to improve outcomes, contain expenditures, reduce disparities, and better coordinate care for the millions of persons in the United States who have advanced dementia.
Myeloid‐Related Proteins 8 and 14 Contribute to Monosodium Urate Monohydrate Crystal–Induced Inflammation in Gout
Authors: Dirk Holzinger, Nadine Nippe, Thomas Vogl, Kristina Marketon, Vijayashree Mysore, Toni Weinhage, Nicola Dalbeth, Bregina Pool, Tony Merriman, Dominique Baeten, Annette Ives, Nathalie Busso, Dirk Foell, Sylvette Bas, Cem Gabay, Johannes Roth
Journal: Arthritis & Rheumatology (2014)

Objective Monosodium urate monohydrate (MSU) crystal–induced interleukin‐1β (IL‐1β) secretion is a critical factor in the pathogenesis of gout. However, without costimulation by a proIL‐1β–inducing factor, MSU crystals alone are insufficient to induce IL‐1β secretion. The responsible costimulatory factors that act as a priming endogenous signal in vivo are not yet known. We undertook this study to analyze the costimulatory properties of myeloid‐related protein 8 (MRP‐8) and MRP‐14 (endogenous Toll‐like receptor 4 [TLR‐4] agonists) in MSU crystal–induced IL‐1β secretion and their relevance in gout. Methods MRP‐8/MRP‐14 was measured in paired serum and synovial fluid samples by enzyme‐linked immunosorbent assay (ELISA) and localized in synovial tissue from gout patients by immunohistochemistry. Serum levels were correlated with disease activity, and MSU crystal–induced release of MRPs from human phagocytes was measured. Costimulatory effects of MRP‐8 and MRP‐14 on MSU crystal–induced IL‐1β secretion from phagocytes were analyzed in vitro by ELISA, Western blotting, and polymerase chain reaction. The impact of MRP was tested in vivo in a murine MSU crystal–induced peritonitis model. Results MRP‐8/MRP‐14 levels were elevated in the synovium, tophi, and serum of patients with gout and correlated with disease activity. MRP‐8/MRP‐14 was released by MSU crystal–activated phagocytes and increased MSU crystal–induced IL‐1β secretion in a TLR‐4–dependent manner. Targeted deletion of MRP‐14 in mice led to a moderately reduced response of MSU crystal–induced inflammation in vivo. Conclusion MRP‐8 and MRP‐14, which are highly expressed in gout, are enhancers of MSU crystal–induced IL‐1β secretion in vitro and in vivo. These endogenous TLR‐4 ligands released by activated phagocytes contribute to the maintenance of inflammation in gout.
Man's Best Friend Equally Adapted to High Altitudes of Tibet
Authors: J. Caspermeyer
Journal: Molecular Biology and Evolution (2014)

In a striking case of pathogen transfer involving the bacterium responsible for human acne, Propionibacterium acnes, Campisano et al. (2014) report on a new type of P. acnes that exploits grapevines, dubbing it P. acnes-type Zappae. They named the bacterium after the Italian term “zappa,” meaning hoe, as well as a tribute to eclectic composer Frank Zappa, who once wrote of “sand-blasted zits” in one of his most famous satirical songs “Jewish Princess” from his controversial 1979 “Sheik Yerbouti” album. “This bacteria is so unconventional in its behavior, and its new habitat is so unexpected that we thought of Frank Zappa. Indeed, at the time we were discovering it, we were both playing a Zappa album in our cars,” say authors Andrea Campisano and Omar Rota-Stabelli. The bacterium was first discovered by the research team via a 16S rDNA gene-based microbiome analysis gathered from the stems of plants sampled from multiple sites throughout northeast Italy. The bacterium colonizes bark tissues and the pith, where the bacterium can localize intracellularly. Thus, compared with being a bane to millions of teenage faces, P. Zappae has adapted to an entirely new intracellular ecological niche in grapevines. The research team also investigated the evolutionary history of P. Zappae by using two marker genes, recA and tly. Remarkably, their results support a human origin for the P. Zappae bacterium. Their data also suggest a loss of function of recA, a protein essential for the repair of DNA, which means that P. Zappae must rely on its grapevine host for survival. Finally, they estimate the emergence of P. Zappae around 7,000 years ago, an age highly compatible with the first domestication of the grapevine and a time when human-intensive practices, such as the grafting and pruning of vines, may have led to the transfer to its new host. This is the first evidence ever of human to plant obligate transfer and gives new perspective of bacteria host transfer between humans and domesticated plants. The significance of P. Zappae and its influence on plant growth and health will be continued in future studies.
Autonomic symptoms are common and are associated with overall symptom burden and disease activity in primary Sjögren's syndrome
Authors: Julia L Newton, James Frith, Danielle Powell, Kate Hackett, Katharine Wilton, Simon Bowman, Elizabeth Price, Colin Pease, Jacqueline Andrews, Paul Emery, John Hunter, Monica Gupta, Saravanan Vadivelu, Ian Giles, David Isenberg, Peter Lanyon, Adrian Jones, Marian Regan, Annie Cooper, Robert Moots, Nurhan Sutcliffe, Michele Bombardieri, Costantino Pitzalis, John McLaren, Steven Young-Min, Bhaskar Dasgupta, Bridget Griffiths, Dennis Lendrem, Sheryl Mitchell
Journal: Annals of the Rheumatic Diseases (2012)

To determine the prevalence of autonomic dysfunction (dysautonomia) among patients with primary Sjögren's syndrome (PSS) and the relationships between dysautonomia and other clinical features of PSS.Multicentre, prospective, cross-sectional study of a UK cohort of 317 patients with clinically well-characterised PSS. Symptoms of autonomic dysfunction were assessed using a validated instrument, the Composite Autonomic Symptom Scale (COMPASS). The data were compared with an age- and sex-matched cohort of 317 community controls. The relationships between symptoms of dysautonomia and various clinical features of PSS were analysed using regression analysis.COMPASS scores were significantly higher in patients with PSS than in age- and sex-matched community controls (median (IQR) 35.5 (20.9-46.0) vs 14.8 (4.4-30.2), p<0.0001). Nearly 55% of patients (vs 20% of community controls, p<0.0001) had a COMPASS score >32.5, a cut-off value indicative of autonomic dysfunction. Furthermore, the COMPASS total score correlated independently with EULAR Sjögren's Syndrome Patient Reported Index (a composite measure of the overall burden of symptoms experienced by patients with PSS) (β=0.38, p<0.001) and disease activity measured using the EULAR Sjögren's Syndrome Disease Activity Index (β=0.13, p<0.009).Autonomic symptoms are common among patients with PSS and may contribute to the overall burden of symptoms and link with systemic disease activity.
Skin conditions are the commonest new reason people present to general practitioners in England and Wales
Authors: J.K. Schofield, D. Fleming, D. Grindlay, H. Williams
Journal: British Journal of Dermatology (2011)

Knowledge of the prevalence and incidence of skin conditions is a prerequisite for designing clinical services and providing appropriate training for primary health care professionals. In the U.K. the general practitioner and practice nurse are the first point of medical contact for persons with skin conditions.We aimed to obtain contemporary data in age-, gender- and diagnosis-specific detail on persons presenting to primary care with skin problems. Comparisons were made with similar data for other major disease groups and with similar data from other recent years.We used surveillance data collected in the Weekly Returns Service (WRS) of the Royal College of General Practitioners during 2006 and trend data for subsequent years. The WRS sentinel practices monitor all consultations by clinical diagnosis in a representative population of 950,000 in England and Wales.For conditions included in chapter XII of the International Classification of Diseases Ninth Revision (ICD9), 15% of the population consulted; a further 9% presented with skin problems classified elsewhere in the ICD9, making a total of 24%. There was no evidence of increasing or decreasing trend since 2006. Skin infections were the commonest diagnostic group, while 20% of children < 12 months were diagnosed with atopic eczema. Considered collectively, the incidence of new episodes of skin disorders (including diagnoses outside chapter XII) exceeded incidences for all other major disease groupings.Compared with other major disease groups, skin conditions are the most frequent reason for consultation in general practice. This result emphasizes the need for appropriate education and training for all medical students and particularly for continuing education in dermatology for all primary health care professionals.
What is the role for bisphosphonates in IBD?
Authors: Charles N Bernstein, Laura E Targownik, William D Leslie
Journal: Gut (2013)

IBD has been associated with an increased risk of osteoporosis and fracture.1 Current guidelines suggest using dual energy x-ray absorptiometry (DXA) to identify IBD patients with osteoporosis as candidates for possible therapy, but focus on IBD patients with established risk factors (ie, postmenopausal women, hypogonadal men or long term (≥3 month) users of glucocorticoids). While the exact role and timing for DXA in IBD is not fully defined, it is even more controversial to consider when therapeutic intervention is indicated. Among the possible choices, bisphosphonates remain the most commonly prescribed pharmacological osteoporosis intervention. While there is little debate when postmenopausal women have osteoporosis-related fractures or osteoporotic bone mineral density (BMD) (ie, T-scores −2.5 or lower),2 ,3 the use of bisphosphonates when patients with IBD are initiating a limited course of glucocorticoids, when T-scores are not in the osteoporotic range, in men or in premenopausal women, requires greater consideration.

The literature evaluating bisphosphonate therapy in IBD, on balance, suggests a benefit for bisphosphonates for increasing BMD and reducing the risk of vertebral fractures.4 However, the studies of bisphosphonate therapy in IBD are quite heterogeneous. Since the use of bisphosphonates in postmenopausal women is not controversial2 ,3 for postmenopausal women who have IBD, there is an added incentive for the healthcare provider to consider a test (DXA) and treat approach. The use of bisphosphonates in the postmenopausal woman and an older man who is a chronic glucocorticoid user is also not controversial.5 One group investigated the feasibility of using bisphosphonates for short term glucocorticoids and found a benefit over calcium and vitamin D plus placebo.6 However, it is uncertain whether short …
Promotion Criteria for Clinician-Educators in the United States and Canada
Authors: Brent W. Beasley
Journal: JAMA (1997)

Clinician-educators have concerns about their ability to be promoted and the criteria used by medical school promotion committees.To discover the criteria and methods that medical school promotion committees use to make decisions about the promotion of clinician-educators.In June 1996 we mailed a questionnaire to chairpersons of all medical school promotion committees in the United States and Canada.Of 142 schools surveyed, 115 (81%) responded; 45% of respondents had a clinician-educator promotion track. On a scale from 1 (minimally important) to 7 (extremely important), the mean importance ratings of aspects of clinician-educators' performance were the following: teaching skills (6.3), clinical skills (5.8), mentoring (5.7), academic administration (5.3), developing educational programs (5.3), nonresearch scholarship (5.1), clinical research (4.8), service coordination (4.7), and education research (4.5). Methods to evaluate each aspect of performance were rated by respondents for importance and frequency of use. The 4 most important methods for evaluating teaching were awards, peer evaluation, learner evaluation, and teaching portfolio; 70% or more of schools used these frequently or always. The 4 most important methods of evaluating clinical skills were peer evaluation, awards, trainee evaluation, and objective measures, which were used frequently or always by 78%, 65%, 58%, and 29% of schools, respectively. Clinician-educators were expected to have fewer peer-reviewed publications to be promoted than investigators (5.7 vs 10.6, P<.001). Schools with separate clinician-educator tracks differed little in survey responses from schools without such tracks.Most, but not all, promotion committees now assign high importance to the special contributions of clinician-educators and use a variety of methods to assess these, regardless of whether they have a separate clinician-educator promotion track.
Air pollution and asthma in Athens.
Authors: N Papageorgiou, M Gaga
Journal: Thorax (1995)

Cardiovascular diseases (CVDs) are the prevalent cause of mortality worldwide and account for the most common noncommunicable disease. CVDs describe a wide spectrum of disorders affecting the proper function, physiology and morphogenesis of the heart and blood vessels. The risk of developing cardiovascular diseases is modulated by a combination of environmental and genetic effectors. Thus, it’s highly important to identify candidate genes and elucidate their role in the manifestation of the disease. Large-scale human studies have revealed the implication of Craniofacial Development Protein 1 (<i>CFDP1)</i> in coronary artery disease (CAD). <i>CFDP1</i> belongs to the evolutionary conserved Bucentaur (BCNT) family and up to date, its function and mechanism of action in Cardiovascular Development is still unclear. In this study, we utilize zebrafish to investigate the role of <i>cfdp1</i> in the developing heart due to the high genomic homology, similarity in heart physiology and the ease of experimentally manipulation. We showed that <i>cfdp1</i> is expressed during development and at 120 hours post fertilization its expression is restricted to the region of the heart and the head. We then generated a <i>cfdp1</i>-null zebrafish line using CRISPR-Cas9 system which led to a lethal phenotype since <i>knockout</i> embryos do not reach adulthood. <i>cfdp1</i><sup>−/−</sup> embryos develop arrhythmic hearts and defective cardiac performance exhibiting statistically significant differences in heart features including End Diastolic Volume, Cardiac Output, Ejection Fraction and Stroke Volume. Myocardial trabeculation is also impaired in <i>cfdp1</i><sup>−/−</sup> embryonic hearts, implying its regulatory role also in this developmental process. Findings from both <i>knockdown</i> and <i>knockout</i> experiments showed that abrogation of <i>cfdp1</i> leads to downregulation of Wnt signaling in embryonic hearts during valve development but without affecting Notch activation in this process.
Histone H2AX stabilizes broken DNA strands to suppress chromosome breaks and translocations during V(D)J recombination
Authors: Bu Yin, Velibor Savic, Marisa M. Juntilla, Andrea L. Bredemeyer, Katherine S. Yang-Iott, Beth A. Helmink, Gary A. Koretzky, Barry P. Sleckman, Craig H. Bassing
Journal: The Journal of Experimental Medicine (2009)

The H2AX core histone variant is phosphorylated in chromatin around DNA double strand breaks (DSBs) and functions through unknown mechanisms to suppress antigen receptor locus translocations during V(D)J recombination. Formation of chromosomal coding joins and suppression of translocations involves the ataxia telangiectasia mutated and DNA-dependent protein kinase catalytic subunit serine/threonine kinases, each of which phosphorylates H2AX along cleaved antigen receptor loci. Using Abelson transformed pre–B cell lines, we find that H2AX is not required for coding join formation within chromosomal V(D)J recombination substrates. Yet we show that H2AX is phosphorylated along cleaved Igκ DNA strands and prevents their separation in G1 phase cells and their progression into chromosome breaks and translocations after cellular proliferation. We also show that H2AX prevents chromosome breaks emanating from unrepaired RAG endonuclease-generated TCR-α/δ locus coding ends in primary thymocytes. Our data indicate that histone H2AX suppresses translocations during V(D)J recombination by creating chromatin modifications that stabilize disrupted antigen receptor locus DNA strands to prevent their irreversible dissociation. We propose that such H2AX-dependent mechanisms could function at additional chromosomal locations to facilitate the joining of DNA ends generated by other types of DSBs.
Persistence of Peptide-induced CD4+ T cell Anergy In Vitro
Authors: Kelli R. Ryan, Brian D. Evavold
Journal: The Journal of Experimental Medicine (1998)

Clonal T cell unresponsiveness, or anergy, has been proposed as a mechanism of peripheral tolerance in vivo, and as a potential means of curbing unwanted T cell responses. In this study, anergy was induced in a T helper cell (Th) clone reactive to hemoglobin (Hb) peptide 64–76 by coculture of the T cells with live antigen-presenting cells (APCs) and 74L, a peptide analog of Hb(64–76) that contains a single amino acid substitution of leucine for glycine at position 74, or with a low concentration of the agonist ligand. The anergic state was characterized by blunted proliferation and interleukin (IL) 2 production upon restimulation with Hb(64–76), and was not the result of impaired TCR/CD3 downmodulation. The addition of exogenous IL-12 transiently restored proliferation of the anergic lines, but removal of IL-12 from culture returned the T cells to their nonproliferative state. Interestingly, persistence of the anergic phenotype was observed despite biweekly restimulation with antigen, APCs, and IL-2. Thus, T cell unresponsiveness induced by a peptide produced a stable, persistent anergic state in a Th0 clone that was not reversible by stimulation with IL-2 or -12.
Consultation with Police on Human Relations Training
Authors: LAWRENCE E. NEWMAN, J. LEONARD STEINBERG
Journal: American Journal of Psychiatry (1970)

As consultants to the Los Angeles Police Department, the authors designed and developed a human relations training program for new recruits and officers returning to the police academy for further in-service training. Special emphasis is given to relations between the police and minority groups. family crisis intervention, and dealing with personal stress. The most effective training modalities have been those in which individual participation is greatest, especially small group discussions led by an outstanding fellow officer of the same rank as the participants.
Lung Function Reference Values in Chinese Children and Adolescents in Hong Kong
Authors: MARY S. M. IP, EVA M. KARLBERG, JOHAN P. E. KARLBERG, KEITH D. K. LUK, JOHN C. Y. LEONG
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

As part of a comprehensive evaluation of lung function in Hong Kong-born Chinese children and adolescents, this study was conducted to determine updated prediction equations for spirometry, to evaluate the secular changes of lung function during the past decade, and to compare these results with other data sets. The results are based on 852 (392 male, 460 female) healthy students, age 7 to 19 yr, recruited from seven schools in Hong Kong. All were born and lived in Hong Kong, nonsmokers, free from past or present symptoms or diseases affecting the respiratory tract. A body plethysmograph was used to record lung function measurements. Natural logarithmic values of lung volumes and body height were used in the final regression model. Prediction equations for FVC, FEV(1), and maximal expiratory flow at 50% of the FVC (MEF(50)) for both sexes are presented, with standing height as the dependent variable. Compared with Hong Kong data from 1985, the results show a significant increase in height-corrected FVC and FEV(1) in both boys and girls, over the whole height range. Compared with recent data of whites, FVC in boys were 8 to 10% lower in the study population, and the difference increased to 12% above the 165 cm height ranges, while FVC in Chinese girls had similar or only slightly lower predicted values. FEV(1) values showed a similar pattern with lesser difference between the two ethnic groups. Compared with recent data from Chinese children in Singapore, a similar pattern with overall lesser difference of the two populations was present in boys, whereas there was no significant difference between girls in the two places. Our findings support the conclusion that exogenous factors may contribute significantly to the differences in lung function values among ethnic groups and that it is important to examine normative values of various populations for secular trends.
Seronegative pauciarticular arthritis and HLA B27.
Authors: C J Eastmond, S M Rajah, D Tovey, V Wright
Journal: Annals of the Rheumatic Diseases (1980)

Twenty-six patients with a pauciarticular arthritis have been studied clinically, radiologically and with histocompatibility typing. An increased frequency of HLA B27 was found (p = 1.87 x 10(-12)). Low back and buttock pain, Achilles tendinitis and dactylitis of the toes were more frequent in HLA-B27 positive patients. It is suggested that histocompatibility testing may be of some value in diagnosis and in the investigation of the possible 9reactive9 nature of this type of arthritis.
Analysis of national register of Down's syndrome in England and Wales: trends in prenatal diagnosis, 1989-91.
Authors: D E Mutton, R Ide, E Alberman, M Bobrow
Journal: BMJ (1993)

Clinical data on allpatients according to whether they had cysts and renal disease.Results are means (and SD) All patients Non-renal patients Renal patients Without cysts With cysts Without cysts With cysts Without cysts With cysts No of cases 1263
74 CANCER-ASSOCIATED FIBROBLASTS RECRUITMENT IS MEDIATED BY PLATELET-DERIVED GROWTH FACTOR (PDGF) SIGNALING IN CHOLANGIOCARCINOMA
Authors: L. Fabris, M. Cadamuro, L. Moserle, G. Nardo, L. Dall'Olmo, M. Colledan, I. Franceschet, S. Indraccolo, L. Okolicsanyi, M. Strazzabosco
Journal: Journal of Hepatology (2010)