tbuckley/cabot-search huggingface dataset:
Managing the care of adults with Down's syndrome
Authors: K. M. Jensen, P. D. Bulova
Journal: BMJ (2014)

#### Summary points

#### Sources and selection criteria

We based this narrative review on articles found by searching PubMed and the Cochrane Database of Systematic Reviews. We then applied snowball techniques to sources for the articles identified from both databases. Search terms first included “Down syndrome”, “preventive health care”, “epidemiology”, and “adults with Down syndrome”. We then searched specifically for articles dealing with comorbidities identified within that search. To date, few randomized controlled trials have involved adults with Down’s syndrome, and many studies that do exist used small sample sizes. We referenced many of these studies to ensure that our review was thorough and accurate. The information contained in this review results primarily from literature arising from observational studies and expert consensus, unless noted otherwise.

Down’s syndrome results from increased genetic material on all or a portion of chromosome 21 and is characterized by intellectual disability and risk for comorbidities involving multiple organ systems.1 2 3 The survival of people with Down’s …
Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27Kip1
Authors: Keiju Hiromura, Jeffrey W. Pippin, Matthew L. Fero, James M. Roberts, Stuart J. Shankland
Journal: Journal of Clinical Investigation (1999)

Proliferation and apoptosis are increased in many types of inflammatory diseases. A role for the cyclin kinase inhibitor p27Kip1 (p27) in limiting proliferation has been shown. In this study, we show that p27–/– mesangial cells and fibroblasts have strikingly elevated rates of apoptosis, not proliferation, when deprived of growth factors. Apoptosis was rescued by restoration of p27 expression. Cyclin A–cyclin-dependent kinase 2 (CDK2) activity, but not cyclin E–CDK2 activity, was increased in serum-starved p27–/– cells, and decreasing CDK2 activity, either pharmacologically (Roscovitine) or by a dominant–negative mutant, inhibited apoptosis. Our results show that a new biological function for the CDK inhibitor p27 is protection of cells from apoptosis by constraining CDK2 activity. These results suggest that CDK inhibitors are necessary for coordinating the cell cycle and cell-death programs so that cell viability is maintained during exit from the cell cycle.
Poor Cognitive Function and Risk of Severe Hypoglycemia in Type 2 Diabetes
Authors: Zubin Punthakee, Michael E. Miller, Lenore J. Launer, Jeff D. Williamson, Ronald M. Lazar, Tali Cukierman-Yaffee, Elizabeth R. Seaquist, Faramarz Ismail-Beigi, Mark D. Sullivan, Laura C. Lovato, Richard M. Bergenstal, Hertzel C. Gerstein
Journal: Diabetes Care (2012)

Self-management of type 2 diabetes including avoidance of hypoglycemia is complex, but the impact of cognition on safe self-management is not well understood. This study aimed to assess the effect of baseline cognitive function and cognitive decline on subsequent risk of severe hypoglycemia and to assess the effect of different glycemic strategies on these relationships.Prospective cohort analysis of data from the ACCORD trial included 2,956 adults aged ≥55 years with type 2 diabetes and additional cardiovascular risk factors. Cognitive tests (Digit Symbol Substitution Test [DSST], Rey Auditory Verbal Learning Test, Stroop Test, and Mini Mental Status Examination) were conducted at baseline and 20 months. Study outcomes were incident confirmed severe hypoglycemia requiring medical assistance (HMA) and hypoglycemia requiring any assistance (HAA).After a median 3.25-year follow-up, a 5-point-poorer baseline score on the DSST was predictive of a first episode of HMA (hazard ratio 1.13 [95% CI 1.08-1.18]). Analyses of the other cognitive tests and of HAA were consistent with the DSST results. Cognitive decline over 20 months increased the risk of subsequent hypoglycemia to a greater extent in those with lower baseline cognitive function (P(interaction) = 0.037). Randomization to an intensive versus standard glycemic strategy had no impact on the relationship between cognitive function and the risk of severe hypoglycemia.Poor cognitive function increases the risk of severe hypoglycemia in patients with type 2 diabetes. Clinicians should consider cognitive function in assessing and guiding their patients regarding safe diabetes self-management regardless of their glycemic targets.
Peer review system needs thorough evaluation, MPs hear
Authors: A. O'Dowd
Journal: BMJ (2011)

The peer review system used by many medical journals before they publish new research needs to be thoroughly evaluated to confirm its value, MPs have been told.

Several medical and scientific journal editors appearing before the parliamentary science and technology select committee on 11 May spoke of the many merits of peer review, but they raised some concerns about the variability of its quality and a lack of adequate evaluation of the system.

The committee was holding the second oral evidence session as part of its inquiry into the peer review process in science ( BMJ 2011;342:d2858 doi:10.1136/bmj.d2858).

MPs asked about the BMJ ’s written evidence to the committee, which mentioned a study that had concluded that little empirical evidence was available to support the use of editorial peer review as a mechanism to ensure the quality of biomedical research.

Fiona Godlee, editor in chief …
Homeostatic proliferation generates long-lived natural killer cells that respond against viral infection
Authors: Joseph C. Sun, Joshua N. Beilke, Natalie A. Bezman, Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2011)

Cells of the immune system undergo homeostatic proliferation during times of lymphopenia induced by certain viral infections or caused by chemotherapy and radiation treatment. Natural killer (NK) cells are no exception and can rapidly expand in number when placed into an environment devoid of these cells. We explored the lifespan and function of mouse NK cells that have undergone homeostatic proliferation in various settings of immunodeficiency. Adoptive transfer of mature NK cells into lymphopenic mice resulted in the generation of a long-lived population of NK cells. These homeostasis-driven NK cells reside in both lymphoid and nonlymphoid organs for &amp;gt;6 mo and, similar to memory T cells, self-renew and slowly turn over at steady state. Furthermore, homeostatically expanded NK cells retained their functionality many months after initial transfer and responded robustly to viral infection. These findings highlight the ability of mature NK cells to self-renew and possibly persist in the host for months or years and might be of clinical importance during NK cell adoptive immunotherapy for the treatment of certain cancers.
Rheumatological manifestations of haematological diseases.
Authors: S Menon, D A Isenberg
Journal: Annals of the Rheumatic Diseases (1995)

In a review published in 1983, an attempt was made to highlight the rheumatological aspects of diseases generally regarded as haemato- logical in origin.'Since then, a variety of reports have served to strengthen the links between these two areas of medicine.In this review, we consider these more recent reports and focus on patient presentation, advances in treatment, and knowledge of underlying mech- anisms.Epidemiological data are reviewed and, in particular, we speculate on the pos- sible immunological mechanisms common to lymphoproliferative malignancy and auto- immune disease.
Out-of-Pocket Costs for Accessing Adjuvant Radiotherapy Among Canadian Women With Breast Cancer
Authors: Sophie Lauzier, Pascale Levesque, Mélanie Drolet, Douglas Coyle, Jacques Brisson, Benoît Mâsse, André Robidoux, Jean Robert, Elizabeth Maunsell
Journal: Journal of Clinical Oncology (2011)

Patients with breast cancer incur out-of-pocket costs when they receive adjuvant radiation. These treatments are administered in dedicated centers on a daily basis over 4 to 5 weeks. We assessed the extent of out-of-pocket costs to access radiotherapy and identified women at risk of experiencing higher costs.This prospective study was conducted among 800 women from eight Quebec hospitals (participation, 86%), of whom 693 women received adjuvant radiotherapy. Costs to access treatment (transportation, parking, lodging, and meals) were estimated on the basis of information collected by telephone interviews. Generalized linear models were used to identify women at risk of having higher costs.Mean and median total costs (including financial aid received) to access radiotherapy were 445 Canadian dollars (Can$; standard deviation, Can$407) and Can$311, respectively. Women who lived at home but far from the radiotherapy center had the highest risk of experiencing weekly costs of at least Can$122 (highest quartile; prevalence ratio [PR], 5.8; 95% CI, 4.7 to 7.1) followed by women who lived away from home and farther from the center (PR, 4.5; 95% CI, 3.4 to 6.0) and by women who lived away from home and closer to the center (PR, 2.14; 95% CI, 1.3 to 3.5). When women stayed at a cancer lodge during treatment, costs were reduced by 80%.Considered in and of themselves, out-of-pocket costs for access to radiotherapy appeared relatively modest. Financial assistance initiatives for women who lived away from home during treatments contributed to a substantial reduction of access costs. These efforts should be maintained, but financial assistance should also target patients with cancer who live at home during treatments but have to travel relatively long distances on a daily basis.
Prediction of potential for organ donation after cardiac death in patients in neurocritical state: a prospective observational study
Authors: Alejandro A Rabinstein, Alan H Yee, Jay Mandrekar, Jennifer E Fugate, Yorick J de Groot, Erwin JO Kompanje, Lori A Shutter, W David Freeman, Michael A Rubin, Eelco FM Wijdicks
Journal: The Lancet Neurology (2012)
Effect of fasudil on the bleomycin-induced pulmonary fibrosis and hypertension in mice
Authors: Yihua Bei, Sy Duong-Quy, Thong Hua-Huy, Nhat-Nam Le-Dong, Weihua Chen, Carole Nicco, Frédéric Batteux, Anh Tuan Dinh-Xuan
Journal: European Respiratory Journal (2012)

Background:    RhoA/Rho kinase (ROCK) pathway is important in regulating vascular tone and vascular remodelling in pulmonary hypertension (PH). It has been shown to be altered in the bleomycin-induced pulmonary fibrosis (PF) and PH in mice. However, the exact mechanism by which it leads to PF and PH remains to be clarified.    Objectives:    The present study aimed to assess whether fasudil, a ROCK inhibitor, is able to inhibit PF and PH induced by bleomycin in mice.    Methods:    Male C57BL/6 mice were randomized into 3 groups: G1 (saline), G2 (bleomycin) and G3 (bleomycin + fasudil). Bleomycin (3.3U/kg) was given intratracheally (day 0) and fasudil (30mg/kg/d) intraperitoneally from day -1 during 21 days. Right ventricular systolic pressure (RVSP) was measured by RV puncture at 7, 14, and 21 days, followed by sacrifice and lung and heart samplings for collagen analysis.    Results:    Pulmonary fibrosis was present at 7 days, and became more apparent at 14 days. RVSP increased at 14 days, accompanied by right ventricular hypertrophy. Fasudil improved survival, reversed PF and attenuated PH.    Conclusions:  The efficacy of the ROCK inhibitor, Fasudil, suggests that RhoA/ROCK is involved in causing PF and PH induced by bleomycin in mice.
Body Mass Index
Authors: Robert Wolk, Peter Berger, Ryan J. Lennon, Emmanouil S. Brilakis, Virend K. Somers
Journal: Circulation (2003)

In patients with coronary artery disease (CAD), acute thrombosis frequently occurs in coronary arteries with only mild or moderate stenoses. Obesity increases the risk of atherosclerosis, but it is not known whether it also increases the risk of coronary thrombosis. We hypothesized that body mass index (BMI) might be an independent predictor of an acute coronary syndrome in patients with established coronary atherosclerosis.Of 504 patients undergoing coronary angiography, those with evidence of >10% coronary artery stenoses were divided into 2 groups, with either stable (n=226) or unstable CAD (unstable angina or myocardial infarction; n=156). After adjusting for other risk factors (age, gender, blood pressure, lipid levels, insulin resistance, leptin, fibrinogen, C-reactive protein (CRP), CAD severity on angiography, smoking status, and a history of myocardial infarction or hypertension), BMI had a significant independent association with an acute coronary syndrome, with an odds ratio of 1.49 (P=0.014). This positive relation between BMI and the risk of acute coronary events was evident for even mildly elevated BMI values. Multivariate analysis also showed that CRP and the number of coronary lesions were independent predictors of risk of an acute coronary event.In patients with established coronary atherosclerosis, BMI, as well as CRP and number of coronary lesions, are independently associated with acute coronary syndromes. There is evidence of increased risk even at mildly elevated BMI levels.
CXCL9 is a prognostic marker in patients with liver cirrhosis receiving transjugular intrahepatic portosystemic shunt
Authors: Marie-Luise Berres, Sonja Asmacher, Jennifer Lehmann, Christian Jansen, Jan Görtzen, Sabine Klein, Carsten Meyer, Holger M. Strunk, Rolf Fimmers, Frank Tacke, Christian P. Strassburg, Christian Trautwein, Tilman Sauerbruch, Hermann Elard Wasmuth, Jonel Trebicka
Journal: Journal of Hepatology (2014)
Efficacy of indoor residual spraying with dichlorodiphenyltrichloroethane against malaria in Gambian communities with high usage of long-lasting insecticidal mosquito nets: a cluster-randomised controlled trial
Authors: Margaret Pinder, Musa Jawara, Lamin B S Jarju, Kolawole Salami, David Jeffries, Majidah Adiamoh, Kalifa Bojang, Simon Correa, Balla Kandeh, Harparkash Kaur, David J Conway, Umberto D'Alessandro, Steve W Lindsay
Journal: The Lancet (2014)
Air Pollution and Atherosclerosis: A Cross-Sectional Analysis of FourEuropean Cohort Studies in the ESCAPE Study
Authors: Laura Perez, Kathrin Wolf, Frauke Hennig, Johanna Penell, Xavier Basagaña, Maria Foraster, Inmaculada Aguilera, David Agis, Rob Beelen, Bert Brunekreef, Josef Cyrys, Kateryna B. Fuks, Martin Adam, Damiano Baldassarre, Marta Cirach, Roberto Elosua, Julia Dratva, Regina Hampel, Wolfgang Koenig, Jaume Marrugat, Ulf de Faire, Göran Pershagen, Nicole M. Probst-Hensch, Audrey de Nazelle, Mark J. Nieuwenhuijsen, Wolfgang Rathmann, Marcela Rivera, Jochen Seissler, Christian Schindler, Joachim Thiery, Barbara Hoffmann, Annette Peters, Nino Künzli
Journal: Environmental Health Perspectives (2015)

In four European cohorts, we investigated the cross-sectional association between long-term exposure to air pollution and intima-media thickness of the common carotid artery (CIMT), a preclinical marker of atherosclerosis.Individually assigned levels of nitrogen dioxide, nitrogen oxides, particulate matter ≤ 2.5 μm (PM2.5), absorbance of PM2.5 (PM2.5abs), PM10, PMcoarse, and two indicators of residential proximity to highly trafficked roads were obtained under a standard exposure protocol (European Study of Cohorts for Air Pollution Effects-ESCAPE study) in the Stockholm area (Sweden), the Ausburg and Ruhr area (Germany), and the Girona area (Spain). We used linear regression and meta-analyses to examine the association between long-term exposure to air pollution and CIMT.The meta-analysis with 9,183 individuals resulted in an estimated increase in CIMT (geometric mean) of 0.72% (95% CI: -0.65%, 2.10%) per 5-μg/m3 increase in PM2.5 and 0.42% (95% CI: -0.46%, 1.30%) per 10-5/m increase in PM2.5abs. Living in proximity to high traffic was also positively but not significantly associated with CIMT. Meta-analytic estimates for other pollutants were inconsistent. Results were similar across different adjustment sets and sensitivity analyses. In an extended meta-analysis for PM2.5 with three other previously published studies, a 0.78% (95% CI: -0.18%, 1.75%) increase in CIMT was estimated for a 5-μg/m3 contrast in PM2.5.Using a standardized exposure and analytical protocol in four European cohorts, we found that cross-sectional associations between CIMT and the eight ESCAPE markers of long-term residential air pollution exposure did not reach statistical significance. The additional meta-analysis of CIMT and PM2.5 across all published studies also was positive but not significant.
A single germline VH gene segment of normal A/J mice encodes autoantibodies characteristic of systemic lupus erythematosus.
Authors: Y Naparstek, J André-Schwartz, T Manser, L J Wysocki, L Breitman, B D Stollar, M Gefter, R S Schwartz
Journal: The Journal of Experimental Medicine (1986)

These experiments tested the hypothesis that unmutated germline genes from normal mice can encode autoantibodies. We found that the unmutated VHIdCR gene segment, which encodes a large proportion of antiarsonate antibodies in A/J mice, also encodes antibodies with the ability to bind to DNA and cytoskeletal proteins. After Ars immunization, at a time when the VHIdCR gene segment mutates and antibody affinity for the hapten increases, reactivity with the autoantigens was lost. Six antibodies obtained after immunization with Ars bound both the Ars and DNA. Results of competitive inhibition assays suggested that the same variable region site in the antibodies bound to both Ars and DNA. The properties of the individual germline-encoded antibodies, which include reactivity to both DNA and cytoskeletal proteins, suggest that autoantibodies characteristic of SLE might be a subset of antibodies encoded by unmutated germline V genes.
Zoledronic acid and risedronate in the prevention and treatment of glucocorticoid-induced osteoporosis (HORIZON): a multicentre, double-blind, double-dummy, randomised controlled trial
Authors: David M Reid, Jean-Pierre Devogelaer, Kenneth Saag, Christian Roux, Chak-Sing Lau, Jean-Yves Reginster, Philemon Papanastasiou, Alberto Ferreira, Florian Hartl, Taiwo Fashola, Peter Mesenbrink, Philip N Sambrook
Journal: The Lancet (2009)
Preischaemic bradykinin and ischaemic preconditioning in functional recovery of the globally ischaemic rat heart
Authors: J Starkopf
Journal: Cardiovascular Research (1997)

Objectives: Substantial release of bradykinin has been demonstrated to occur during short periods of myocardial ischaemia in various species. The aim of the present study was to investigate the protective effect of bradykinin in ischaemia and whether bradykinin could be involved in ischaemic preconditioning in the rat heart. Methods: Isolated, buffer-perfused hearts were subjected to 30 min of global ischaemia, followed by 30 min of reperfusion. Postischaemic functional recovery was recorded in the following groups: (1) control; (2) treatment with 0.1 μM bradykinin for 10 min before ischaemia (BK); (3) bradykinin treatment combined with pretreatment with the specific bradykinin B2-receptor antagonist, HOE 140; (4) ischaemic preconditioning by 5 min ischaemia + 5 min reperfusion prior to sustained ischaemia (IP); and (5) ischaemic preconditioning combined with HOE 140 administration. Results: Postischaemic myocardial function was significantly improved in both BK and IP groups (developed pressure 66.9 ± 6.8 and 67.6 ± 7.1 mmHg, respectively, vs. 43.1 ± 5.9 mmHg in controls, P < 0.05). Pretreatment with 1 μM HOE 140 completely abolished the effect of bradykinin, while protection achieved by IP was unaltered by this drug. None of the protective interventions was associated with any significant improvement in myocardial adenosine triphosphate, creatine phosphate, glycogen, lactate or glucose tissue levels, detected either at the end of ischaemia or after 30 min of reperfusion. Conclusions: Bradykinin, acting via B2-receptors, can protect against postischaemic contractile dysfunction to a similar extent as IP. An involvement of B2-receptors in the ischaemic preconditioning phenomenon could, however, not be demonstrated.
Hemagglutination by purified type I Escherichia coli pili.
Authors: I E Salit, E C Gotschlich
Journal: The Journal of Experimental Medicine (1977)

Many enterobacteria can cause agglutination of erythrocytes, but previous investigations have not proven which components of the bacteria are responsible. We used a strain of Escherichia coli K12 which causes mannose-sensitive hemagglutination (HA) of guinea pig cells. Common pili were purified from these bacteria by shearing them from the bacteria followed by selective precipitation in acid and ammonium sulfate. Isopycnic centrifugation in cesium chloride removed the remaining outer membrane protein contaminants. These pili are pure by electron microscopy and gel electrophoresis. By amino acid analysis, they have a mol wt of 17,099 and consist of 45% nonpolar residues. These purified pili agglutinate guinea pig erythrocytes, a reaction that is inhibited by anti-pili antibodies and by saccharides related in structure to D-mannose. Proteolytic treatment of erythrocytes does not diminish HA but rather increases the pili-induced HA of human cells. Neuraminidase enhances HA and mannosidase slightly diminishes it. It is concluded that purified pili alone cause HA of erythrocytes by binding to mannose-like molecules on the erythrocyte surface. Thus HA by bacterial pili serves as a useful model system for the mechanism of bacterial pili attachment ot cell membranes.
Neutrophil to lymphocyte ratio (NLR) of five predicts 30-day morbidity in ruptured abdominal aortic aneurysms (rAAA): A retrospective cohort study
Authors: Ali Kordzadeh, George Malietzis, Tom Browne, Ioannis Prionidis, Yiannis P. Panayiotopoulos
Journal: International Journal of Surgery (2015)
PROTEIN METABOLISM AND EXCHANGE AS INFLUENCED BY CONSTRICTION OF THE VENA CAVA
Authors: Frank W. McKee, Robert E. Hyatt, William G. Wilt, Garson H. Tishkoff, George H. Whipple
Journal: The Journal of Experimental Medicine (1949)

Further studies of ascitic fluid production and related factors in dogs with constriction of the vena cava above the diaphragm are reported. Whole dog plasma given intravenously to such animals produces a rise in circulating plasma protein to normal levels, but increases the output of ascitic fluid with a loss of protein via the ascites equivalent to 72, 76, and 65 per cent respectively, of the injected protein. Forced ingestion of water in excess of the test animal's normal needs and desires produces no significant changes in the circulating plasma protein level or in ascitic fluid production. Amino acid growth mixtures given intravenously in distilled water cause weight loss, elevation of circulating plasma proteins, a slightly negative nitrogen balance, but no ascitic fluid production. Amino acid growth mixtures given intravenously in normal saline cause depression of the circulating plasma proteins, negative nitrogen balance, and significant ascitic fluid production. Ascitic fluid given intravenously to the test animals causes a marked depression of circulating plasma proteins, a marked increase in ascitic fluid production containing the equivalent of 116 and 98 per cent of the injected protein, and a negative nitrogen balance. Ascitic fluid given orally produces a marked depression of circulating plasma proteins, and a marked increase in ascitic fluid secretion, containing the equivalent of 66, 66, and 54 per cent respectively, of the ingested protein. Sodium chloride is a dominant factor in some of these experiments where abundant ascites production is recorded. Protein levels and intake are important, but take second place to sodium. Ascitic fluids show electrophoretic patterns which are almost identical to the plasma patterns. The A/G ratios are often equal in ascitic fluid and plasma, sometimes even lower in the ascitic fluid. This emphasizes the ease with which globulins pass cell or other membrane barriers in these experiments.