tbuckley/cabot-search huggingface dataset:
Modest alcohol consumption decreases the risk of non-alcoholic fatty liver disease: a meta-analysis of 43 175 individuals
Authors: Silvia Sookoian, Gustavo O Castaño, Carlos J Pirola
Journal: Gut (2013)

Epidemiological studies suggested that the prevalence and the disease severity of non-alcoholic fatty liver disease (NAFLD) are lower for people who drink modest amounts of alcohol than those who are abstainers. Nevertheless, the evidence is still inconclusive because some recently published studies1 showed that modest alcohol consumption (MAC) increases hepatic fat without increasing the risk of advanced fibrosis.

Remarkably, we found in our population that MAC has a beneficial effect in preventing not only NAFLD but the main features of the metabolic syndrome, including body mass index (BMI), blood pressure, homeostatic model assessment-insulin resistance and C-reactive protein levels. Accordingly, NAFLD and non-alcoholic steatohepatitis (NASH) prevalence, liver enzymes and inflammatory markers were lower in subjects who took modest amounts of alcohol than those who are abstainers (table 1).

View this table:

Table 1 
Clinical and biochemical characteristics of the Argentinean population according to drinking status: non-drinkers versus modest drinkers



Hence, we propose to take advantage of meta-analysis to estimate from published data …
Rho-ROCK-LIMK-Cofilin Pathway Regulates Shear Stress Activation of Sterol Regulatory Element Binding Proteins
Authors: Tong Lin, Lingfang Zeng, Yi Liu, Kathryn DeFea, Martin A. Schwartz, Shu Chien, John Y.-J. Shyy
Journal: Circulation Research (2003)

Previous studies have shown that integrin activation and fluid shear stress can modulate the activity of sterol regulatory element binding proteins (SREBPs) in vascular endothelial cells. We investigated the role of small GTPase Rho-mediated signal transduction pathway in this mode of SREBP activation. Fluid shear stress activates the Rho downstream effectors ROCK, LIM kinase (LIMK), and cofilin. The various negative mutants of RhoA, ROCK, LIMK, and cofilin can block the shear stress activation of SREBPs. The shear stress-activated SREBP depends on S2P proteases but not caspase-3. Mechanistically, the endoplasmic reticulum-to-Golgi transport of SREBP cleavage-activating protein requires the actin-based cytoskeleton and is enhanced by the Rho-ROCK-LIMK-cofilin pathway. By enhancing the SREBP-mediated cholesterol metabolism, this unique mechanism may contribute to endothelial cell functions under flow.
Novel Bone-Targeted Strategies in Oncology
Authors: Sonia Vallet, Matthew R. Smith, Noopur Raje
Journal: Clinical Cancer Research (2010)

Most patients with bone metastases experience skeletal complications, resulting in significant morbidity and increased risk of death. Although the use of bisphosphonates is a well-established form of supportive care treatment for bone metastasis, complications arising from long-term use require schedule optimization and a search for alternative strategies. Moreover, the scope of use of bone-targeted agents in oncology has widened to include therapy-induced bone loss and antitumor effects. Indeed, bone provides a permissive niche to tumor growth, and targeting the interactions within the bone microenvironment is a promising antitumor strategy. In addition, the pathogenesis of cancer-related bone disease has been partially unraveled with a focus on the anabolic bone compartment, and the rapid bench-to-bedside translation has resulted in the identification of novel therapeutically amenable targets. This review focuses on studies optimizing bisphosphonate use and recent clinical data on denosumab in the treatment of bone disease. We also provide data on trials that have evaluated the antitumor effects of bisphosphonates and summarize the most recent discoveries on the role of the bone niche in cancer development, with insights into the preclinical rationale and clinical assessment of novel antiresorptive and anabolic bone-targeted agents.
Age-dependent inaccuracy of asthma death certification in Northern England, 1991-1992
Authors: DW Reid, VJ Hendrick, TC Aitken, WT Berrill, SC Stenton, DJ Hendrick
Journal: European Respiratory Journal (1998)

Asthma mortality appeared to increase two-fold in the UK from the mid- 1970s to the early 1990s, but there is evidence of inaccuracy in asthma death certification and so a region-wide investigation was undertaken to assess whether this recorded statistical trend might have been partly or wholly artefactual. A total of 35 respiratory physicians, distributed in panels of three, systemically reviewed the hospital and general practice records of 210 subjects with physician-diagnosed asthma who died in 1991 and 1992. The death certificates indicated that asthma was considered to be the primary cause of death in 103 (group 1), a contributory cause in 70 (group 2) and not relevant in 37 (group 3). There was agreement within the panels that 43% of the subjects had probably never suffered from asthma. Discordance between the panels and the certifying physicians over the correct death certification category was high for group 1 (45% for those aged <65 yrs, 75% for those aged > or =65 yrs and 64% overall) and group 2 (67%), but much less for group 3 (22%). This study concludes that asthma death certification provides a markedly inaccurate picture of asthma mortality, particularly in elderly subjects. Thus, it is speculated that if the magnitude of this source of inaccuracy has increased over the last two decades, the apparent recent increase in asthma mortality may be largely artefactual.
Public Health Certification
Authors: Kristine M. Gebbie
Journal: Annual Review of Public Health (2009)

In 2003, the Institute of Medicine (IOM) recommended voluntary certification of graduates achieving the Master of Public Health degree. The Association of Schools of Public Health (ASPH), the American Public Health Association, the Association of State and Territorial Health Officials, the National Association of County and City Health Officials, and the Association for Prevention Teaching and Research joined together to establish the National Board of Public Health Examiners (5). This new body will certify graduates of accredited schools and programs of public health who successfully pass their examination. If this certification becomes common, the debate will move to other questions such as (a) can those who lack a degree from a school of public health be certified through the same examination, or a similar one; (b) how will this general certificate relate to specialized areas of public health practice which are also learned elsewhere; and (c) how will we assess the public health competence of public health workers who do not have a professional education?
α <sub>1</sub> -Adrenergic Receptors Activate AKT via a Pyk2/PDK-1 Pathway That Is Tonically Inhibited by Novel Protein Kinase C Isoforms in Cardiomyocytes
Authors: Jianfen Guo, Abdelkarim Sabri, Hasnae Elouardighi, Vitalyi Rybin, Susan F. Steinberg
Journal: Circulation Research (2006)

AKT is a potent antiapoptotic kinase, but its role in the cardioprotective actions of alpha(1)-adrenergic receptors (ARs) remains uncertain, because alpha(1)-ARs typically induce little-to-no AKT activation in most cardiomyocyte models. This study identifies a prominent alpha(1)-AR-dependent AKT activation pathway that is under tonic inhibitory control by novel protein kinase Cs (nPKCs) in neonatal rat cardiomyocyte cultures. We also implicate Pyk2, Pyk2 complex formation with PDK-1 and paxillin, and increased PDK-1-Y373/376 phosphorylation as the mechanism that links alpha(1)-AR activation to increased AKT phosphorylation. nPKCs (which are prominent alpha(1)-AR effectors) interfere with this alpha(1)-AR-dependent AKT activation by blocking Pyk2/PDK-1/paxillin complex formation and PDK-1-Y373/376 phosphorylation. Additional studies used an adenoviral-mediated overexpression strategy to show that Pyk2 exerts dual controls on antiapoptotic PDK-1/AKT and proapoptotic c-Jun N-terminal kinase (JNK) pathways. Although the high nPKC activity of most cardiomyocyte models favors Pyk2 signaling to JNK (and cardiac apoptosis), the cardioprotective actions of Pyk2 through the PDK-1/AKT pathway are exposed when PKC or JNK activation is prevented. Collectively, these studies identify JNK and AKT as functionally distinct downstream components of the alpha(1)-AR/Pyk2 signaling pathway. We also implicate nPKCs as molecular switches that control the balance of signaling via proapoptotic JNK and antiapoptotic PDK-1/AKT pathways, exposing a novel mechanism for nPKC-dependent regulation of cardiac hypertrophy and failure.
Physician Characteristics Are Associated with Quality of Cancer Care
Authors: Liz Savage, Andrea Widener
Journal: JNCI Journal of the National Cancer Institute (2008)

Whether a woman receives radiation after breast cancer surgery may be associated with certain characteristics of her surgeon, including sex and medical training, according to a study published online January 29 in the Journal of the National Cancer Institute.Many breast cancer patients do not receive radiation after undergoing breast conservation surgery, despite the fact that this treatment is considered a standard of quality cancer care and has been shown to reduce breast cancer recurrence.Previous studies have shown that certain patient characteristics, such as a patient ' s race and distance from a radiation therapy facility, are associated with receiving post-surgical radiation.But it has been unclear whether physician characteristics also play a role in the quality of breast cancer care.Dawn Hershman, M.D., of Herbert Irving Comprehensive Cancer Center at Columbia University in New York and colleagues investigated whether surgeon characteristics were associated with a patient receiving radiation after breast cancer surgery.They identifi ed and analyzed data on nearly 30,000 women aged 65 and older with breast cancer who were diagnosed between 1991 and 2002 and who received breast-conserving surgery.They also collected information on the 4,453 surgeons who operated on these women -including their sex, year of graduation, medical school location, patient volume, and type of medical degree.About 75 percent of the women received radiation after surgery.Each year from 1991 to 2002, the proportion of women receiving radiation increased.Nonetheless, older women, black women, unmarried women, and those living outside urban areas were less likely to receive radiation.After adjusting for patient and tumor characteristics, the researchers found that women who received radiation were more likely to have a surgeon who was female, had an M.D. degree (compared to a D.O. degree), or was trained in the United States."Our study is one of the fi rst to demonstrate associations between certain surgeon characteristics and quality of breast cancer care … If confi rmed, more research is needed on whether they refl ect surgeon behavior, patient response, or physician-patient interactions," the authors write.
Roles of prostaglandin E receptors in mesangial cells under high-glucose conditions
Authors: Rieko Ishibashi, Issei Tanaka, Masato Kotani, Seiji Muro, Masahisa Goto, Akira Sugawara, Masashi Mukoyama, Yukihiko Sugimoto, Atsushi Ichikawa, Shuh Narumiya, Kazuwa Nakao
Journal: Kidney International (1999)
Modeling lexical effects on phonetic categorization and semantic effects on word recognition
Authors: M. Gareth Gaskell
Journal: Behavioral and Brain Sciences (2000)

I respond to Norris et al.'s criticism of Gaskell and Marslen- Wilson (1997). When the latter's network is tested in circumstances comparable to the Merge simulations in the target article, it produces the desired pattern of results. In another area of potential feedback in spoken word processing, aspects of lexical content influence word recognition and our network provides a simple explanation of why such effects emerge. It is unclear how such effects would be accommodated by Merge.
The opsonic fragment of the third component of human complement (C3).
Authors: T P Stossel, R J Field, J D Gitlin, C A Alper, F S Rosen
Journal: The Journal of Experimental Medicine (1975)

Human peripheral blood phagocytes ingest Escherichia coli 026:B6 lipopolysaccharide (LPS)-coated paraffin oil droplets containing Oil red O only if fresh serum deposits C3 on the surfaces of the particles (opsonizes them), by reactions involving the properdin system. The rate of binding of purified [125-I]C3 in serum to LPS-coated particles correlated precisely with the rate of acquisition of ingestibility assayed spectrophotometrically. Once opsonized, LPS-coated particles remained fully ingestible and retained fixed [125-I]C3 radioactivity even after exposure to extremes of temperature, pH, ionic strength, phospholipases, urea or guanidine, some nonionic and ionic detergents, and organic solvents. Trypsin, human conglutinogen-activating factor, another heat-stable activity found in human serum, and sodium dodecyl sulfate removed radioactivity and diminished ingestibility of the opsonized particles. Alkylation, reduction plus alkylation and F(ab')2 from anti-C3 blocked ingestibility but did not alter particle-bound radioactivitymelectrophoretic and tryptic peptide autoradiographic analysis of dodecyl sulfate eluates of opsonized particles, cleansed of many contaminating proteins by boiling with 2 M NaCl (yet still opsonized), revealed that the polypeptide with C3-derived radioactivity had a mol wt of approximately 140,000 and was composed of 70,000 mol wt subunits linked by disulfide bonds. Immunochemical analysis and comparison of the peptide structure of the eluate with that of C3 indicated that the opsonic fragment is not the fragment defined as C3b but a smaller derivative of C3.
Basic helix-loop-helix proteins E2A and HEB induce immature T-cell receptor rearrangements in nonlymphoid cells
Authors: Anton W. Langerak, Ingrid L. M. Wolvers-Tettero, Ellen J. van Gastel-Mol, Monique E. C. M. Oud, Jacques J. M. van Dongen
Journal: Blood (2001)
Prescribing injectable and oral methadone to opiate addicts: results from the 1995 national postal survey of community pharmacies in England and Wales
Authors: J. Strang, J. Sheridan, N. Barber
Journal: BMJ (1996)

<h3>Abstract</h3> <b>Objective</b>: To establish the extent of prescribing injectable and oral methadone to opiate addicts and the practice characteristics and dispensing arrangements attached to these prescriptions. <b>Design</b>: National survey of 25% random sample of community (high street) pharmacies through postal questionnaire, with four mailings. <b>Setting</b>: England and Wales. <b>Subjects</b>: 1 in 4 sample of all 10 616 community pharmacies, stratified by family health services authority. <b>Main outcome measures</b>: Data were collected on each prescription for controlled drugs currently being dispensed by pharmacies to misusers, describing the drug, form, dose, source (general practice or hospital; and NHS or private), and numbers of dispensing pick ups a week. <b>Results</b>: Methadone was the opiate most commonly dispensed to misusers (96.0% of 3846 opiate prescriptions). 79.6% of methadone prescriptions were for the oral liquid form, 11.0% for tablet, and 9.3% for injectable ampoules. More than one third of all methadone prescriptions were for weekly or fortnightly pick up, with a further third being for daily pick up. Tablets and ampoules were even less likely to be dispensed on a daily basis. Private prescriptions were significantly more likely than NHS ones to be for tablets or ampoules, to be for substantially higher daily doses, and to be collected on a weekly or fortnightly basis. <b>Conclusions</b>: The distinctively British practice of prescribing injectable methadone was found to be widespread and, contrary to guidance, to be as prevalent in non-specialist as specialist settings. In view of the frequent crushing and injecting of methadone tablets, clearer more authoritative guidance is needed on the contexts in which injectable methadone (tablets as well as ampoules) should be prescribed and on the responsibilities for monitoring and supervision which should be attached. <h3>Key messages</h3> Tablets and ampoules make up one fifth of methadone prescriptions Arrangements already exist for daily dispensing of methadone to patients, but many prescribers (particularly general practitioners and private doctors) prescribe large amounts with long intervals between pick ups As well as ampoules, methadone tablets (when crushed) may be injected; clearer guidance is needed on the clinical criteria for prescribing injectable methadone Daily dispensing arrangements are insufficiently used, and guidelines for pre- scribers on dispensing arrangements need to be reviewed
Carbamazepine, Seizure Disorders, and Pregnancy
Authors: C. David Butler
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Dr Stenchever's answer to the questions about seizure disorders and pregnancy<sup>1</sup>nicely touches almost all aspects that must be considered. However, the inclusive statement about all anticonvulsive agents offering potential danger to the fetus seems a bit misleading. The discussion is directed toward birth defects. Of course, any drug offers the potential for danger to the fetus; however, carbamazepine has not been known to be associated with fetal defects.<sup>2,3</sup>While one study showed a correlation between carbamazepine use and lower—birth weight infants, no deformities have been noted.<sup>4</sup> This is not to suggest that the patient be changed from therapy with one drug to use of another, because, as Dr Stenchever suggests, it is imprudent to alter therapy in a patient whose condition has been controlled by current therapy for an unproved, even questionable, advantage. Yet, carbamazepine has been shown to be as effective as
Myocardial contractile function and myofibrillar adenosine triphosphatase activity in chemically sympathectomized rats.
Authors: R T Dowell
Journal: Circulation Research (1976)

The contractile properties and contractile protein enzymatic activity of skeletal muscle can be altered by neural influences. To determine whether similar influences apply to cardiac muscle, adult rats were chemically sympathectomized by intravenous injection of 6-hydroxydopamine (6-OHDA). After 2 weeks of treatment, rats were anesthetized and an index of myocardial contractility (max dP/dt) was measured in situ. Max dP/dt was depressed in 6-OHDA-treated rats [4560 +/- 420 (mean +/- SE) mm Hg/sec] when compared to controls (6710 +/- 580 mm Hg/sec). Sympathectomy was verified by reduced hemodynamic responsiveness to tyramine injections. After functional measurements had been completed, the heart was excised. Myofibrils were prepared from left ventricular tissue and analyzed for ATPase activity. Myofibrillar protein yield averaged 38 +/- 2 mg/g in controls and was not significantly different in 6-OHDA rats. Myofibrillar ATPase activity was 0.314 +/- 0.014 mumol P1/mg per min in controls. Enzyme activity was significantly reduced to 0.230 +/- 0.020 mumol P1/mg per min in 6-OHDA rats. The results demonstrate that a chronic reduction in sympathetic stimulation to the heart results in a depression of an index of myocardial contractile function which is accompanied by reduced myofibrillar ATPase activity. Acute (16-18 hours) chemical sympathectomy depressed the contractile function index without altering ATPase activity. Bilateral adrenalectomy produced no further decrement in myofibrillar ATPase activity in chronically (2 weeks) sympathectomized rats. Therefore, it appears that the changes in contractile protein enzymatic properties are mediated by sympathetic neural influences and may involve the synthesis of new contractile protein(s) with altered enzymatic properties.
Surgical stabilization of spondylolisthesis in a wrestler.
Authors: G L Garcés, J L Rasines
Journal: British Journal of Sports Medicine (1995)

Sporting activity in wrestlers operated on for spondylolisthesis is not well documented in the literature. We present the case of a wrestler with a grade I L5-S1 spondylolisthesis who was L4-S1 arthrodesed due to pain not relieved by conservative methods. One year after surgery he had returned to full wrestling activity, including competitions. Two years later, he continues to wrestle at the same level of competition.
Cellular and ventricular contractile dysfunction in experimental canine mitral regurgitation.
Authors: Y Urabe, D L Mann, R L Kent, K Nakano, R J Tomanek, B A Carabello, G Cooper
Journal: Circulation Research (1992)

This study was designed to answer two questions. First, does the left ventricular contractile dysfunction resulting from mitral regurgitation (MR) reflect a primary defect in the cardiac muscle cell? Second, what is the basis for any change in cellular contractile function that might be observed? Left ventricular volume overload was produced in 10 dogs by catheter transection of mitral chordae tendineae. Three months later in these and in seven control dogs, left ventricular contractile function was characterized by the end-ejection stress-volume relation (EESVR). Investigators who were blinded to these results then characterized the contractile performance of cardiac muscle cells, or cardiocytes, from these same left ventricles in terms of the viscosity (graded external load)-velocity relation. Finally, the tissue and cellular components of these same left ventricles were analyzed morphometrically. Both the left ventricles from the MR group and their constituent cardiocytes showed marked contractile abnormalities. By matching ventricles with cells from the same MR dogs, ventricular EESVR was correlated with cardiocyte peak sarcomere shortening velocity (SSV). The correlation coefficient between EESVR and SSV was 0.63, but between a size-independent measure of active ventricular stiffness and SSV, it was 0.88. No change in left ventricular interstitial volume fraction was found in MR dogs, but both ventricular and cellular contractile dysfunction strongly correlated with a decreased volume fraction of cardiocyte myofibrils. Last, in an attempt to relate the degree of contractile dysfunction to the hypertrophic response, left ventricular mass in the MR dogs was correlated with both cellular and ventricular contractile indexes; no significant correlation was found. Three conclusions are warranted by these studies. First, chronic left ventricular volume overload from mitral regurgitation leads to contractile defects at both the ventricular and cellular levels, the extent of which correlates well in individual animals. Second, no quantitative interstitial change resulted from MR. Taken together, these two findings strongly suggest that the contractile defect is intrinsic to the cardiocyte. Third, while the contractile abnormality in MR remains undefined, the most basic defects appear to be a combination of myofibrillar loss with the failure of compensatory hypertrophy to occur in response to progressive decrements in cellular and ventricular function.