tbuckley/cabot-search huggingface dataset:
Abstract P357: Omega-3 Fatty Acid Biomarkers and Coronary Heart Disease: a Pooling Project of 17 Cohort Studies
Authors: Liana C Del Gobbo, Stella Aslibekyan, Pascale Barberger-Gateau, Hannia Campos, Stephanie E Chiuve, Luc Djoussé, Paul Franks, Eliseo Guallar, Fumiaki Imamura, Jan-Håkan Jansson, Kay-Tee Khaw, Rozenn N Lemaitre, Robert Luben, Matti Marklund, Chisa Matsumoto, Eric B Rimm, Ulf Risérus, Cecilia Samieri, David Siscovick, Jyrki K Virtanen, Sari Voutilaninen, Maria Wennberg, Mohammad Yawar Yakoob, Dariush Mozaffarian
Journal: Circulation (2014)

Background: Recent trials have raised questions about the role of seafood-derived long-chain omega-3 fatty acids for prevention of CHD; and evidence linking intermediate-chain omega-3 fatty acids to CHD remains weak. Methods: We developed a global consortium of 17 prospective (cohort or nested case-control) and retrospective studies having circulating or tissue biomarker measures of eicosapentaenoic (EPA; 20:5n-3), docosapentaenoic (DPA; 22:5n-3), docosahexaenoic acid (DHA; 22:6n-3), and α-linolenic acid (ALA; 18:3n-3). Each study ascertained CHD risk, including total CHD, nonfatal MI, and/or fatal CHD. Associations of each omega-3 fatty acid biomarker with CHD were evaluated within each cohort using standardized models, exposures, outcomes, and covariates across studies. Omega-3 fatty acid levels were analyzed continuously (per SD) and categorically (quintiles), and study-specific estimates were centrally pooled using fixed effects meta-analysis. Results: Current findings (Oct 2013) were based on 13 of 17 participating studies, including 7105 total CHD, 4926 nonfatal MI, and 2466 fatal CHD events. In both continuous and categorical multivariable-adjusted analyses, each omega-3 biomarker was inversely associated with fatal CHD. For each 1 SD unit increment, ALA was associated with 9% lower risk [HR 0.91 (95% CI 0.84-0.99)]; EPA, with 8% lower risk [HR 0.92 (95% CI 0.85-1.00)]; DPA, with 8% lower risk [HR: 0.92 (0.87-0.98)]; and DHA, with 9% lower risk [HR: 0.91 (0.86-0.96)] (Figure). Associations with total CHD and nonfatal MI were generally weaker and non-significant, except for EPA and nonfatal MI [HR: 0.93 (0.89-0.98)] and DHA and nonfatal MI [HR: 0.95 (0.91-0.99)]. Conclusions: Based on all available studies from around the world, both long and intermediate-chain omega-3 fatty acids, measured using objective biomarkers, are associated with lower risk of fatal CHD. These findings support potential benefit of omega-3 fatty acids for reducing CHD death.
Trouble on two fronts for Home Secretary
Authors: W. Russell
Journal: BMJ (1983)

Troubles for politicians never come singly, and for Mr William Whitelaw, Home Secretary, they seem to keep on coming.Even his legislation in this parliament is trouble prone.He has two Bills currently in difficulties, both arousing strong opposition.The controversial Police and Criminal Evidence Bill, now finishing its committee stage in the Commons, has had the bishops added to the lengthy list of professions against it.I suspect that the government will not respond to the clerics meddling in politics, but some of the other critics may find their objections having effect, including the BMA.If amendments may be made to that Bill, however, there is no sign that the government intends to budge over the Data Protection Bill, Mr Whitelaw's other contentious measure.That has just finished its report stage in the Lords, where Labour peers have put up a tough fight against the provisions to permit disclosure of information on certain grounds without any judicial consent having to be sought, as is required by the Police and Criminal Evidence Bill.The battle that started during the committee stage was resumed last week over clause 28, which permits disclosure of personal data without the person doing so being liable to the penalties set out elsewhere in the Bill for wrongful disclosure.The clause permits disclosure for the prevention and detection of crime, the apprehension or prosecution of offenders, the assessment or collection of any tax or duty, and the control of immigration.The argument is that such blanket exemption may not require disclosure, but it will make it difficult for those asked, such as doctors, not to do so.The damage inherent to relations between doctors and patients is obvious.
Sex and gender issues in competitive sports: investigation of a historical case leads to a new viewpoint: Figure 1
Authors: Kaye N Ballantyne, Manfred Kayser, J Anton Grootegoed
Journal: British Journal of Sports Medicine (2011)

Based on DNA analysis of a historical case, the authors describe how a female athlete can be unknowingly confronted with the consequences of a disorder of sex development resulting in hyperandrogenism emerging early in her sports career. In such a situation, it is harmful and confusing to question sex and gender. Exposure to either a low or high level of endogenous testosterone from puberty is a decisive factor with respect to sexual dimorphism of physical performance. Yet, measurement of testosterone is not the means by which questions of an athlete's eligibility to compete with either women or men are resolved. The authors discuss that it might be justifiable to use the circulating testosterone level as an endocrinological parameter, to try to arrive at an objective criterion in evaluating what separates women and men in sports competitions, which could prevent the initiation of complicated, lengthy and damaging sex and gender verification procedures.
Introduction to therapy of hepatitis C
Authors: Karen L. Lindsay
Journal: Hepatology (2002)

Since the 1997 National Institutes of Health Consensus Development Conference on management of hepatitis C there have been several important advances that significantly impact its therapy; notably the availability of sensitive, specific, and standardized assays for identifying hepatitis C virus (HCV) RNA in the serum, the addition of ribavirin to alpha interferon, the pegylation of alpha interferon, and the demonstration that sustained virological response (SVR) is the optimal surrogate endpoint of treatment. Using pegylated interferon and ribavirin, virological response with relapse and nonresponse are less common, but remain poorly understood. Current studies are evaluating nonvirological endpoints of treatment, namely biochemical response and histological response. To date, definitive treatment trials have primarily been conducted in adult patients with elevated aminotransferase levels, clinically compensated chronic liver disease, and no other significant medical disorder. Limited data are available from studies of other patient populations, and the safety of interferon-based treatment has not yet been established in several patient groups. Future research is needed to elucidate the mechanisms of viral response and clearance, to develop effective therapies for interferon nonresponse or intolerance, to define the role of complementary and alternative medicine and other nonspecific therapies, and to develop strategies for the optimal management and treatment of special patient populations who probably represent the majority of persons with chronic hepatitis C in the United States.
A painful experience
Authors: L. Farrell
Journal: BMJ (2002)

I was on an Airtours flight from Florida recently when medical assistance was called for. The patient had benign prostatic hyperplasia and was in retention. Since we had another seven hours to fly, holding on was not an option. He needed a catheter, so I was reassured that the plane's inventory of medical equipment included catheters and collecting bags. But I then found that there was no lignocaine gel, no lubricating jelly, and no gloves.

Performing a catheterisation without …
THE IMPACT OF THE TACKLE: SHOULDER INJURIES IN A RUGBY UNION TEAM
Authors: RDJ Whitham
Journal: British Journal of Sports Medicine (2013)

Background Rugby Union (rugby) is the third most popular contact sport in the world and has one of the highest reported incidences of injuries amongst all sports. Thoroughly characterising these injuries may help develop preventative methods to reduce absence from rugby at professional and amateur levels. Although the tackle event is most commonly associated with concussion and cervical nerve root injuries, shoulder injuries are responsible for up to 46% of days lost to participation at a professional level. Aims This study sought to evaluate the circumstances, severity, and type of shoulder injuries over the course of one season at a professional rugby team. Method All shoulder injuries from matches and training during the 2010–11 season at a Welsh regional rugby team were identified retrospectively using the SportsCode video analysis programme. Data recorded for circumstances included direction and height of a tackle, and player movement and the nature of a tackle (e.g. stopping tackle). Severity was measured by number of days lost from competition and/or training. Type of shoulder injury was classified using the Orchard Sports Injury Classification System (OSICS) version 10.1. Results There were 24 injuries (3 training injuries and 21 match-related) during the 2010–2011 season. The tackle event caused 92% of injuries (n=22) and resulted in 99% (399 of 405 days) of time lost to shoulder injuries. Cumulatively, players who were tackled remained injured for longer than those tackling (266 days vs. 133 days). Of the 19 videos available for analysis of injury circumstance, injuries most frequently occurred when tackles were high (74%), front-on (53%) and when players were moving with speed (68%). The commonest injuries sustained were acromioclavicular joint sprains (n=9), yet per injury the most severe were dislocation injuries (mean severity, 51.5 days). Discussion The tackle event causes the majority of shoulder injuries in professional rugby and is the commonest cause of days lost due to shoulder injuries. Therefore, potential methods of “prehabilitation” such as strengthening muscles around the joint to stabilise the shoulder and coaching correct tackle techniques are essential in minimising time lost. A larger study across a greater number of professional rugby teams, using immediate post-injury video analysis, is needed before evidence-based recommendations for shoulder injury prevention can be made.
Enhancement of acute lung injury related to bacterial endotoxin by components of diesel exhaust particles
Authors: R Yanagisawa
Journal: Thorax (2003)

Diesel exhaust particles (DEP) synergistically aggravate acute lung injury related to lipopolysaccharide (LPS) in mice, but the components in DEP responsible for this have not been identified. A study was undertaken to examine the effects of the organic chemicals (DEP-OC) and residual carbonaceous nuclei (washed DEP) derived from DEP on LPS related lung injury.ICR mice were divided into experimental groups and vehicle, LPS, washed DEP, DEP-OC, washed DEP+LPS, and DEP-OC+LPS were administered intratracheally. The cellular profile of the bronchoalveolar lavage (BAL) fluid, pulmonary oedema, lung histology, and expression of proinflammatory molecules and Toll-like receptors in the lung were evaluated.Both DEP-OC and washed DEP enhanced the infiltration of neutrophils into BAL fluid in the presence of LPS. Washed DEP combined with LPS synergistically exacerbated pulmonary oedema and induced alveolar haemorrhage, which was concomitant with the enhanced lung expression of interleukin-1beta, macrophage inflammatory protein-1alpha, macrophage chemoattractant protein-1, and keratinocyte chemoattractant, whereas DEP-OC combined with LPS did not. Gene expression of Toll-like receptors 2 and 4 was increased by combined treatment with washed DEP and LPS. The enhancement effects of washed DEP on LPS related changes were comparable to those of whole DEP.These results suggest that the residual carbonaceous nuclei of DEP rather than the extracted organic chemicals predominantly contribute to the aggravation of LPS related lung injury. This may be mediated through the expression of proinflammatory cytokines, chemokines, and Toll-like receptors.
Hospital outbreak caused by a carbapenem-resistant strain of Acinetobacter baumannii: patient prognosis and risk-factors for colonisation and infection
Authors: M. del Mar Tomas, M. Cartelle, S. Pertega, A. Beceiro, P. Llinares, D. Canle, F. Molina, R. Villanueva, J.M. Cisneros, G. Bou
Journal: Clinical Microbiology and Infection (2005)
Is the New Mayo Clinic Quadratic Equation Useful for the Estimation of Glomerular Filtration Rate in Type 2 Diabetic Patients?
Authors: Néstor Fontseré, Jordi Bonal, Isabel Salinas, Manel Ramírez de Arellano, Jose Rios, Ferran Torres, Anna Sanmartí, Ramón Romero
Journal: Diabetes Care (2008)

OBJECTIVE—To test the Mayo Clinic Quadratic (MCQ) equation against isotopic glomerular filtration rate, compared with the Modification of Diet in Renal Disease (MDRD) and the Cockcroft-Gault formulas, in type 2 diabetes. RESEARCH DESIGN AND METHODS—Based on values obtained with iothalamate, 118 type 2 diabetic patients were divided into three groups according to renal function: hyperfiltration (26), normal function (56), or chronic kidney disease (CKD) stages 3–4 (36). ANOVA, the Bland-Altman procedure, and Lins coefficient (Rc) were performed to study accuracy. RESULTS—In the hyperfiltration and normal function groups, all prediction equations significantly underestimated the value obtained with isotopic glomerular filtration rate (P &amp;lt; 0.05). In the CKD group, all equations also presented significant differences with the isotopic method. However, MDRD had a bias of −5.3 (Rc 0.452), Cockcroft-Gault formula −0.2 (Rc 0.471), and the MCQ −4.5 (Rc 0.526). CONCLUSIONS—The MCQ and prediction equations proved inaccurate (excessive underestimation) in type 2 diabetic patients with hyperfiltration or normal renal function. With regard to CKD, the results obtained provided no evidence of superiority of the MCQ over the MDRD or the Cockcroft-Gault formula.
Hyperglycemia Potentiates the Slowing of Gastric Emptying Induced by Exogenous GLP-1
Authors: Mark P. Plummer, Karen L. Jones, Caroline E. Cousins, Laurence G. Trahair, Juris J. Meier, Marianne J. Chapman, Michael Horowitz, Adam M. Deane
Journal: Diabetes Care (2015)

OBJECTIVE Acute hyperglycemia markedly slows gastric emptying. Exogenous GLP-1 also slows gastric emptying, leading to diminished glycemic excursions. The primary objective was to determine whether hyperglycemia potentiates the slowing of gastric emptying induced by GLP-1 administration. RESEARCH DESIGN AND METHODS Ten healthy participants were studied on 4 separate days. Blood glucose was clamped at hyperglycemia using an intravenous infusion of 25% dextrose (∼12 mmol/L; hyper) on 2 days, or maintained at euglycemia (∼6 mmol/L; eu) on 2 days, between t = −15 and 240 min. During hyperglycemic and euglycemic days, participants received intravenous GLP-1 (1.2 pmol/kg/min) and placebo in a randomized double-blind fashion. At t = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq technetium-99m–sulfur colloid and 3 g 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from t = 0 to 240 min and serum 3-OMG taken at regular intervals from t = 15 to 240 min. The areas under the curve for gastric emptying and 3-OMG were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. RESULTS Hyperglycemia slowed gastric emptying (eu/placebo vs. hyper/placebo; P &amp;lt; 0.001) as did GLP-1 (eu/placebo vs. eu/GLP-1; P &amp;lt; 0.001). There was an additive effect of GLP-1 and hyperglycemia, such that gastric emptying was markedly slower compared with GLP-1 administration during euglycemia (eu/GLP-1 vs. hyper/GLP-1; P &amp;lt; 0.01). CONCLUSIONS Acute administration of exogenous GLP-1 profoundly slows gastric emptying during hyperglycemia in excess of the slowing induced by GLP-1 during euglycemia. Studies are required to determine the effects of hyperglycemia on gastric emptying with the subcutaneously administered commercially available GLP-1 agonists in patients with type 2 diabetes.
p65 Activity and ZAP-70 Status Predict the Sensitivity of Chronic Lymphocytic Leukemia Cells to the Selective IκB Kinase Inhibitor BMS-345541
Authors: Mónica López-Guerra, Gaël Roué, Patricia Pérez-Galán, Roberto Alonso, Neus Villamor, Emili Montserrat, Elias Campo, Dolors Colomer
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Constitutive nuclear factor-κB (NF-κB) activation has been implicated in the pathogenesis of chronic lymphocytic leukemia (CLL). Our purpose was to characterize the molecular mechanisms underlying for the selective IκB kinase inhibitor BMS-345541 in CLL cells together with the analysis of its combination with several antineoplasic drugs. Experimental Design: Primary cells from 34 CLL patients were incubated with different doses of BMS-345541. NF-κB DNA-binding activity was analyzed by ELISA-based kits and the characterization of the apoptotic pathway was done by flow cytometry, immunoblotting, quantitative reverse transcription-PCR, and immunofluorescence techniques. Results: BMS-345541 selectively induced apoptosis in CLL cells in the low micromolar range irrespective of p53 status. Noteworthy, the high ZAP-70 group was significantly more sensitive to BMS-345541 than the low ZAP-70 group, in correlation with high levels of p65 phosphorylation and DNA-binding activity. Following NF-κB inhibition, BMS-345541 led to induction of the mitochondrial apoptotic pathway and activation of both caspase-dependent and caspase-independent factors. Moreover, BMS-345541-induced apoptosis was accompanied by down-regulation of several antiapoptotic NF-κB-target genes, including both BCL2 family members and apoptotic endogenous inhibitors. In addition, we showed a strong synergism between BMS-345541 and conventional chemotherapeutics such as mitoxantrone and dexamethasone as well as with new promising drugs such as the BH3-mimetic GX15-070/Obatoclax or the anti-TRAIL-R1 monoclonal antibody mapatumumab. Conclusions: These data confirm that NF-κB is a relevant target in CLL and indicate that inhibitors of IκB kinase, alone or in combination, represent a novel therapeutic strategy for the treatment of CLL patients, especially for the group with high ZAP-70.
Ubiquitin, a novel paracrine messenger of cardiac cell survival
Authors: D. Li, C. Depre
Journal: Cardiovascular Research (2010)

Ubiquitin is a highly conserved and ubiquitously expressed protein that covalently binds other peptides by a lysine (K) residue. Traditionally, the role of ubiquitin is associated with the proteolytic function of the proteasome in what is known as the ubiquitin-proteasome system (UPS), responsible for the degradation of about 70–90% of intracellular proteins.1,2 In the UPS, ubiquitin binds the proteins to be degraded in a process known as ubiquitination and transfers them to the proteasome for proteolysis. Ubiquitination results from the formation of a peptide bond between the C-terminal carboxyl group of ubiquitin and the e-amino group of a lysine residue of the target protein, and this is followed by the synthesis of a multi-ubiquitin chain in which the e-amino group of the lysine-48 residue of the conjugated ubiquitin (UbK48) is bound to the C-terminal carboxyl group of the incoming ubiquitin moiety.3 Ubiquitination of a target protein largely depends on the identity of specific members of the large family of E3 ubiquitin ligases, which catalyze the formation of the peptide bond between ubiquitin and the client.4 Poly-ubiquitination of the client protein signals its targeting to the proteasome for degradation by several proteolytic enzymes, which is accompanied by the recycling of the ubiquitin units.5 Proper function of the UPS is critical for cellular homeostasis, and its dysfunction participates in multiple forms of disease, including in the cardiovascular system, as reviewed recently in a Spotlight issue of the Journal .6

Beside this ‘canonical’ function of ubiquitin in the UPS, an emerging literature relates to ‘non-canonical’, proteasome-independent, and non-proteolytic activities of ubiquitin related to cellular functions … 

*Corresponding author. Tel: +1 973 972 3926; fax: +1 973 9727489, Email: deprech{at}umdnj.edu
Asthma affects time to pregnancy and fertility: a register-based twin study
Authors: Elisabeth J. Gade, Simon F. Thomsen, Svend Lindenberg, Kirsten O. Kyvik, Sofie Lieberoth, Vibeke Backer
Journal: European Respiratory Journal (2013)

Coexistence of infertility and asthma has been observed clinically. Therefore, we investigated the association between asthma and delayed pregnancy in a nationwide population-based cohort of twins. A cohort of 15 250 twins living in Denmark (aged 12–41 years) participated in a questionnaire study including questions about the presence of asthma and fertility. Differences in time to pregnancy and pregnancy outcome were analysed in subjects with asthma, allergy and in healthy individuals using multiple regression analysis. Asthma was associated with an increased time to pregnancy, the percentage of asthmatics with a time to pregnancy &gt;1 year was 27% versus 21.6% for non-asthmatics (OR (95% CI) 1.31 (1.1–1.6); p=0.009). The association remained significant after adjustment for age, age at menarche, body mass index and socioeconomic status (OR (95% CI) 1.25 (1.0–1.6); p=0.05), and was more pronounced in those &gt;30 years of age (32.2% versus 24.9%, OR (95% CI) 1.44 (1.1–1.9); p=0.04). Untreated asthmatics had a significant increased risk of prolonged time to pregnancy compared to healthy individuals (OR (95% CI) 1.79 (1.20–2.66); p=0.004), while asthmatics receiving any kind of treatment for asthma tended to have a shorter time to pregnancy than untreated asthmatics (OR 1.40; p=0.134). Asthma prolongs time to pregnancy. The negative effect of asthma on fertility increases with age and with disease intensity, indicating that a systemic disease characterised by systemic inflammation also can involve reproductive processes.
Lymphadenopathies in homosexual men. Relationships with the acquired immune deficiency syndrome
Authors: H. L. Ioachim
Journal: JAMA (1983)

Generalized, persistent lymphadenopathies were observed in homosexual men and considered a possible prodrome of acquired immune deficiency syndrome (AIDS). To evaluate these lymphadenopathies, 25 lymph node biopsy specimens from homosexual men with lymphadenopathy (18), lymphadenopathy associated with AIDS (five), and lymphadenopathy associated with non-Hodgkin's lymphoma (two) were reviewed and correlated with the clinical symptoms. In the absence of opportunistic infections, the lymph node lesions were essentially uniform and represented acute inflammatory processes resembling those commonly seen in viral lymphadenitides. This suggests that a lymphotropic agent, probably a virus, causes AIDS as a result of its destructive effects on certain populations of lymphoid cells.