tbuckley/cabot-search huggingface dataset:
Should Burden of Disease Estimates Include Cannabis Use as a Risk Factor for Psychosis?
Authors: Louisa Degenhardt, Wayne D. Hall, Michael Lynskey, John McGrath, Jennifer McLaren, Bianca Calabria, Harvey Whiteford, Theo Vos
Journal: PLoS Medicine (2009)

N Comparative risk assessments estimate the proportion of a disease that can be attributed to a particular risk exposure and are important guides for health planning.N In observational studies, there has been consistent evidence that cannabis use is associated with an increased risk of schizophrenia and more generally, psychosis.N There is debate about whether such observational evidence is sufficient to infer that cannabis use is a contributory cause of psychosis.N Given the controversy, should the comparative risk assessment in the current revision of the Global Burden of Disease (GBD) include an attribution of psychosis to cannabis use?N We argue that the risk assessment should be included because the evidence is as good as that for many other risk factors included in the GBD, psychotic disorders are associated with substantial unavertable disability, and cannabis use is a potentially preventable exposure.
Electrical and Mechanical Characteristics of Vascular Smooth Muscle Response to Norepinephrine and Isoproterenol
Authors: BöJRE JOHANSSON, OLOF JOHSSON, JOHANN AXELSSON, BO WAHLSTRöm
Journal: Circulation Research (1967)

Effects of norepinephrine (NE) and isoproterenol on simultaneously recorded electrical and contractile activity in rat portal vein were studied using a sucrose-gaps technique. This vascular smooth muscle shows spontaneous phasic contractions correlated with bursts of action potentials. Norepinephrine (10 -9 9 to 10 -7 w/v) increases the duration of the bursts and shortens the interval between after an initial period of continuous spike discharge. The tension response is greater than can be accounted for by the increase in electrical activity. High NE concentrations (10-5) produce depolarization, decrease of spike amplitude, or even abolition of spikes and maintained contractions. Norepinephrine increases contracture tension of K + -depolarized portal vein without changing membrane potential. Electrical and mechanical activity is reinitiated in preparations inactivated by elimination of Ca 2+ this may be due to release of bound calcium. Phenoxybenzamine abolishes the above NE responses. The typical response to isoproterenol (10 9 to 10 7 ) in a normal ionic environment consists of moderate depolarization, decreased burst duration, but increased frequency of bursts and inhibition of tension development which is not simply correlated with the change in electrical activity. This pattern resembles that produced by lowering [Ca 2+ ] o . Contracture tension in high [K + ] o is reduced by isoproterenol without changes in membrane potential. These responses to isoproterenol are abolished by propranolol. At high concentrations of isoproterenol (10 -5 ) the inhibitory responses are not sustained, but revert to a pattern of activity resembling that induced by NE.
Familial Pathways to Early-Onset Suicide Attempt
Authors: David A. Brent, Nadine M. Melhem, Maria Oquendo, Ainsley Burke, Boris Birmaher, Barbara Stanley, Candice Biernesser, John Keilp, David Kolko, Steve Ellis, Giovanna Porta, Jamie Zelazny, Satish Iyengar, J. John Mann
Journal: JAMA Psychiatry (2014)

Suicide attempts are strong predictors of suicide, a leading cause of adolescent mortality. Suicide attempts are highly familial, although the mechanisms of familial transmission are not understood. Better delineation of these mechanisms could help frame potential targets for prevention.To examine the mechanisms and pathways by which suicidal behavior is transmitted from parent to child.In this prospective study conducted from July 15, 1997, through June 21, 2012, a total of 701 offspring aged 10 to 50 years (mean age, 17.7 years) of 334 clinically referred probands with mood disorders, 191 (57.2%) of whom had also made a suicide attempt, were followed up for a mean of 5.6 years.The primary outcome was a suicide attempt. Variables were examined at baseline, intermediate time points, and the time point proximal to the attempt. Participants were assessed by structured psychiatric assessments and self-report and by interview measures of domains hypothesized to be related to familial transmission (eg, mood disorder and impulsive aggression).Among the 701 offspring, 44 (6.3%) had made a suicide attempt before participating in the study, and 29 (4.1%) made an attempt during study follow-up. Multivariate logistic regression revealed that proband suicide attempt was a predictor of offspring suicide attempt (odds ratio [OR], 4.79; 95% CI, 1.75-13.07), even controlling for other salient offspring variables: baseline history of mood disorder (OR, 4.20; 95% CI, 1.37-12.86), baseline history of suicide attempt (OR, 5.69; 95% CI, 1.94-16.74), and mood disorder at the time point before the attempt (OR, 11.32; 95% CI, 2.29-56.00). Path analyses were consistent with these findings, revealing a direct effect of proband attempt on offspring suicide attempt, a strong effect of offspring mood disorder at each time point, and impulsive aggression as a precursor of mood disorder.Parental history of a suicide attempt conveys a nearly 5-fold increased odds of suicide attempt in offspring at risk for mood disorder, even after adjusting for the familial transmission of mood disorder. Interventions that target mood disorder and impulsive aggression in high-risk offspring may attenuate the familial transmission of suicidal behavior.
Benchmarking Is Associated With Improved Quality of Care in Type 2 Diabetes
Authors: Michel P. Hermans, Moses Elisaf, Georges Michel, Erik Muls, Frank Nobels, Hans Vandenberghe, Carlos Brotons
Journal: Diabetes Care (2013)

To assess prospectively the effect of benchmarking on quality of primary care for patients with type 2 diabetes by using three major modifiable cardiovascular risk factors as critical quality indicators.Primary care physicians treating patients with type 2 diabetes in six European countries were randomized to give standard care (control group) or standard care with feedback benchmarked against other centers in each country (benchmarking group). In both groups, laboratory tests were performed every 4 months. The primary end point was the percentage of patients achieving preset targets of the critical quality indicators HbA1c, LDL cholesterol, and systolic blood pressure (SBP) after 12 months of follow-up.Of 4,027 patients enrolled, 3,996 patients were evaluable and 3,487 completed 12 months of follow-up. Primary end point of HbA1c target was achieved in the benchmarking group by 58.9 vs. 62.1% in the control group (P = 0.398) after 12 months; 40.0 vs. 30.1% patients met the SBP target (P < 0.001); 54.3 vs. 49.7% met the LDL cholesterol target (P = 0.006). Percentages of patients meeting all three targets increased during the study in both groups, with a statistically significant increase observed in the benchmarking group. The percentage of patients achieving all three targets at month 12 was significantly larger in the benchmarking group than in the control group (12.5 vs. 8.1%; P < 0.001).In this prospective, randomized, controlled study, benchmarking was shown to be an effective tool for increasing achievement of critical quality indicators and potentially reducing patient cardiovascular residual risk profile.
413 AGE AND THE INACTIVE HBsAg CARRIER STATE ARE PREDICTIVE OF HBsAg LOSS IN A “REAL-LIFE” COHORT OF PATIENTS WITH CHRONIC HBV INFECTION
Authors: F. Habersetzer, R. Moenne-Loccoz, N. Meyer, E. Schvoerer, P. Simo-Noumbissie, S. Dritsas, F. Stoll-Keller, S. Fafi-Kremer, T.F. Baumert, M. Doffo el
Journal: Journal of Hepatology (2013)
<i>CYP1A1/2</i> Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification
Authors: Melinda C. Aldrich, Steve Selvin, Helen M. Hansen, Lisa F. Barcellos, Margaret R. Wrensch, Jennette D. Sison, Karl T. Kelsey, Patricia A. Buffler, Charles P. Quesenberry, Michael F. Seldin, John K. Wiencke
Journal: Cancer Research (2009)

Abstract Prior studies of lung cancer and CYP1A1/2 in African-American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of CYP1A1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998–2003). African-Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28–3.19 and OR, 0.55; 95% CI, 0.36–0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos. [Cancer Res 2009;69(6):2340–8]
Prevention of Abdominal Aortic Aneurysm Progression by Targeted Inhibition of Matrix Metalloproteinase Activity With Batimastat-Loaded Nanoparticles
Authors: Nasim Nosoudi, Pranjal Nahar-Gohad, Aditi Sinha, Aniqa Chowdhury, Patrick Gerard, Christopher G. Carsten, Bruce H. Gray, Naren R. Vyavahare
Journal: Circulation Research (2015)

Rationale: Matrix metalloproteinases (MMPs)–mediated extracellular matrix destruction is the major cause of development and progression of abdominal aortic aneurysms. Systemic treatments of MMP inhibitors have shown effectiveness in animal models, but it did not translate to clinical success either because of low doses used or systemic side effects of MMP inhibitors. We propose a targeted nanoparticle (NP)–based delivery of MMP inhibitor at low doses to the abdominal aortic aneurysms site. Such therapy will be an attractive option for preventing expansion of aneurysms in patients without systemic side effects. Objective: Our previous study showed that poly( d , l -lactide) NPs conjugated with an antielastin antibody could be targeted to the site of an aneurysm in a rat model of abdominal aortic aneurysms. In the study reported here, we tested whether such targeted NPs could deliver the MMP inhibitor batimastat (BB-94) to the site of an aneurysm and prevent aneurysmal growth. Methods and Results: Poly( d , l -lactide) NPs were loaded with BB-94 and conjugated with an elastin antibody. Intravenous injections of elastin antibody–conjugated BB-94-loaded NPs targeted the site of aneurysms and delivered BB-94 in a calcium chloride injury-induced abdominal aortic aneurysms in rats. Such targeted delivery inhibited MMP activity, elastin degradation, calcification, and aneurysmal development in the aorta (269% expansion in control versus 40% elastin antibody–conjugated BB-94-loaded NPs) at a low dose of BB-94. The systemic administration of BB-94 alone at the same dose was ineffective in producing MMP inhibition. Conclusions: Targeted delivery of MMP inhibitors using NPs may be an attractive strategy to inhibit aneurysmal progression.
My personal mountain
Authors: M. E. Black
Journal: BMJ (2011)

I have finally submitted my doctoral thesis, a mixed methods case study of the first household survey of children and women in Bosnia-Hercegovina since the conflict.

The naive idea that this was merely a spare time project led me a tortuous dance through the bowels of analytical frameworks and the deep dark nights of numbers that never add up, my path dimly lit by the wisdom of an adviser who has seen it all before. I have drunk deeply from the cup of creative prevarication, been humbled by the simplest …
Dual angiotensin receptor and neprilysin inhibition as an alternative to angiotensin‐converting enzyme inhibition in patients with chronic systolic heart failure: rationale for and design of the Prospective comparison of ARNI with ACEI to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM‐HF)
Authors: John J. V. McMurray, Milton Packer, Akshay S. Desai, Jim Gong, Martin P. Lefkowitz, Adel R. Rizkala, Jean Rouleau, Victor C. Shi, Scott D. Solomon, Karl Swedberg, Michael R. Zile
Journal: European Journal of Heart Failure (2013)

Although the focus of therapeutic intervention has been on neurohormonal pathways thought to be harmful in heart failure (HF), such as the renin-angiotensin-aldosterone system (RAAS), potentially beneficial counter-regulatory systems are also active in HF. These promote vasodilatation and natriuresis, inhibit abnormal growth, suppress the RAAS and sympathetic nervous system, and augment parasympathetic activity. The best understood of these mediators are the natriuretic peptides which are metabolized by the enzyme neprilysin. LCZ696 belongs to a new class of drugs, the angiotensin receptor neprilysin inhibitors (ARNIs), which both block the RAAS and augment natriuretic peptides.
Assessment Of The Quality Of Life and Health Resource Utilization Burden Among Patients With Primary Immunodeficiency Disorder (PIDD) Prior To Treatment
Authors: John M. Routes, Beatriz Tavares Costa-Carvalho, Bodo Grimbacher, Kenneth Paris, Hans D. Ochs, Diane Ito, Yan Xiong, Josephine Li-McLeod, Richard I. Schiff
Journal: Journal of Allergy and Clinical Immunology (2014)
Shift in sleep apnoea type in heart failure patients in the CANPAP trial
Authors: C. M. Ryan, J. S. Floras, A. G. Logan, R. J. Kimoff, F. Series, D. Morrison, K. A. Ferguson, I. Belenkie, M. Pfeifer, J. Fleetham, P. J. Hanly, M. Smilovitch, M. Arzt, T. D. Bradley
Journal: European Respiratory Journal (2010)

In patients with heart failure (HF), the predominant type of sleep apnoea can change over time in association with alterations in circulation time. The aim of this study was to determine whether, in some patients with HF, a spontaneous shift from mainly central (&gt;50% central events) to mainly obstructive (&gt;50% obstructive events) sleep apnoea (CSA and OSA, respectively) over time coincides with improvement in left ventricular ejection fraction (LVEF). Therefore, sleep studies and LVEFs of HF patients with CSA from the control arm of the Canadian Continuous Positive Airway Pressure for Patients with Central Sleep Apnea and Heart Failure (CANPAP) trial were examined to determine whether some converted to mainly OSA and, if so, whether this was associated with an increase in LVEF. Of 98 patients with follow-up sleep studies and LVEFs, 18 converted spontaneously to predominantly OSA. Compared with those in the nonconversion group, those in the conversion group had a significantly greater increase in the LVEF (2.8% versus -0.07%) and a significantly greater fall in the lung-to-ear circulation time (-7.6 s versus 0.6 s). In patients with HF, spontaneous conversion from predominantly CSA to OSA is associated with an improvement in left ventricular systolic function. Future studies will be necessary to further examine this relationship.
Mesothelin-MUC16 binding is a high affinity, N-glycan dependent interaction that facilitates peritoneal metastasis of ovarian tumors
Authors: Jennifer AA Gubbels, Jennifer Belisle, Masanori Onda, Claudine Rancourt, Martine Migneault, Mitchell Ho, Tapan K Bera, Joseph Connor, Bangalore K Sathyanarayana, Byungkook Lee, Ira Pastan, Manish S Patankar
Journal: Molecular Cancer (2006)

Abstract Background The mucin MUC16 and the glycosylphosphatidylinositol anchored glycoprotein mesothelin likely facilitate the peritoneal metastasis of ovarian tumors. The biochemical basis and the kinetics of the binding between these two glycoproteins are not clearly understood. Here we have addressed this deficit and provide further evidence supporting the role of the MUC16-mesothelin interaction in facilitating cell-cell binding under conditions that mimic the peritoneal environment. Results In this study we utilize recombinant-Fc tagged human mesothelin to measure the binding kinetics of this glycoprotein to MUC16 expressed on the ovarian tumor cell line OVCAR-3. OVCAR-3 derived sublines that did not express MUC16 showed no affinity for mesothelin. In a flow cytometry-based assay mesothelin binds with very high affinity to the MUC16 on the OVCAR-3 cells with an apparent K d of 5–10 nM. Maximum interaction occurs within 5 mins of incubation of the recombinant mesothelin with the OVCAR-3 cells and significant binding is observed even after 10 sec. A five-fold molar excess of soluble MUC16 was unable to completely inhibit the binding of mesothelin to the OVCAR-3 cells. Oxidation of the MUC16 glycans, removal of its N-linked oligosaccharides, and treatment of the mucin with wheat germ agglutinin and erythroagglutinating phytohemagglutinin abrogates its binding to mesothelin. These observations suggest that at least a subset of the MUC16-asscociated N-glycans is required for binding to mesothelin. We also demonstrate that MUC16 positive ovarian tumor cells exhibit increased adherence to A431 cells transfected with mesothelin (A431-Meso + ). Only minimal adhesion is observed between MUC16 knockdown cells and A431-Meso + cells. The binding between the MUC16 expressing ovarian tumor cells and the A431-Meso + cells occurs even in the presence of ascites from patients with ovarian cancer. Conclusion The strong binding kinetics of the mesothelin-MUC16 interaction and the cell adhesion between ovarian tumor cells and A431-Meso+ even in the presence of peritoneal fluid strongly support the importance of these two glycoproteins in the peritoneal metastasis of ovarian tumors. The demonstration that N-linked glycans are essential for mediating mesothlein-MUC16 binding may lead to novel therapeutic targets to control the spread of ovarian carcinoma.
Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia
Authors: Alisdair J. MacDonald, Neil Johns, Nathan Stephens, Carolyn Greig, James A. Ross, Alexandra C. Small, Holger Husi, Kenneth C. H. Fearon, Tom Preston
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls. Experimental design: An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography–pyrolysis–isotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown. Results: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (≥5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weight-losing patients had higher synthetic rates than controls (P = 0.03). Conclusion: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting. Clin Cancer Res; 21(7); 1734–40. ©2014 AACR.
Allopurinol and glutamine attenuate bacterial translocation in chronic portal hypertensive and common bile duct ligated growing rats.
Authors: G Schimpl, P Pesendorfer, G Steinwender, G Feierl, M Ratschek, M E Hollwarth
Journal: Gut (1996)

BACKGROUND: Spontaneous bacterial infections and septicaemia result in morbidity and mortality in patients with portal hypertension and obstructive jaundice. AIM: The aim of this study in rats was to investigate the incidence of bacterial translocation in portal hypertension and obstructive jaundice, and to evaluate the effects of allopurinol and glutamine. METHODS: Rats were subjected to sham laparotomy (SL), portal hypertension (PH) by calibrated stenosis of the portal vein, and common bile duct ligation (CBDL). Animals of each group were either treated with allopurinol (50 mg/kg twice a week), glutamine (1 g/kg/d), and allopurinol and glutamine. RESULTS: After four weeks, significant bacterial translocation in the untreated PH and CBDL rats occurred. Intestinal mucosal malondialdehyde concentrations (MDA), as an indicator for lipid peroxidation, and myeloperoxidase activity (MPO) released from activated neutrophils were also significantly increased (p &lt; 0.01). Allopurinol and glutamine in PH and CBDL rats improved bacterial translocation, and decreased MDA and MPO values (p &lt; 0.01). CONCLUSION: In PH and CBDL rats significant bacterial translocation, ileal mucosal lipid peroxidation, and neutrophil derived MPO activity occurred. Allopurinol and glutamine significantly reduced bacterial translocation, as well as ileal mucosal MDA and MPO activities.
High-frequency (20-50 MHz) ultrasonography of pseudoxanthoma elasticum skin lesions
Authors: M. Guérin-Moreau, G. Leftheriotis, Y. Le Corre, M. Etienne, R. Amode, J.F. Hamel, A. Croué, O. Le Saux, L. Machet, L. Martin
Journal: British Journal of Dermatology (2013)

In most patients pseudoxanthoma elasticum (PXE) manifests with yellowish cutaneous papules and dermal elastorrhexis on skin biopsy. In a small number of cases there are no skin manifestations on clinical examination, and establishing a diagnosis of PXE in such patients is challenging. High-frequency ultrasonography (HFUS) may be of use in predicting skin areas that would yield a biopsy specimen positive for elastorrhexis.To describe characteristics of clinically visible PXE skin using HFUS, and to evaluate its relevance for diagnosis.HFUS was performed in a cohort of patients with PXE and in controls at a referral centre. HFUS images of PXE skin were compared with those of other conditions. Five operators blind-scored multiple HFUS images of photoprotected or photoexposed skin from patients with PXE and controls. The diagnostic indices (sensitivity, specificity, likelihood ratios, interobserver agreement) were calculated.The HFUS changes considered as diagnostic for PXE were primarily oval homogeneous hypoechogenic areas in the mid-dermis. The size of these areas closely matched the extent of the histological changes. The sensitivity and specificity of the diagnostic items and interobserver agreement were high, particularly in photoprotected skin. Dermal hypoechogenicity in PXE could be related to high hydration of connective tissue due to the presence of glycosaminoglycans despite elastic fibre mineralization.HFUS provides suggestive images of PXE skin lesions. HFUS should now be studied to determine whether it is a potentially valuable technique for the noninvasive identification of elastorrhexis in patients with PXE in whom skin involvement is clinically minimal or absent.