tbuckley/cabot-search huggingface dataset:
Central obesity induces a greater risk of hepatocellular carcinoma than general obesity
Authors: Qing Pang, Jing Yao Zhang, Kai Qu, Si Dong Song, Su Shun Liu, Chang Liu
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. To the Editor: We read with great interest the recent Hepatology article by El‐Serag et al.,1 in which they comprehensively reviewed the etiologies of hepatocellular carcinoma (HCC) and considered general obesity (elevated body mass index [BMI]) as a main risk. Indeed, numerous epidemiological studies and several meta‐analyses have confirmed the impact of general obesity on the incidence of HCC. However, we thought they neglected the significance of central obesity, which is mainly indicated by a high level of waist circumference (WC), waist‐hip ratio (WHR), or visceral abdominal fat, in the formation of HCC. El‐Serag et al.1 hinted that nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome (MetS), might be a crucial bridge that links obesity with HCC. However, in individuals with normal BMI, the prevalence of NAFLD is still high, especially in patients with central obesity.2 Additionally, in the definition of MetS,2 central obesity, rather than general obesity, is generally viewed to be an indispensable component. Recently, we3 performed a meta‐analysis and demonstrated that central obesity induces more risk of NAFLD than general obesity. Given that the majority of research only focused on investigating the link between BMI and risk of HCC, few data were available to assess the significance of central obesity on HCC occurrence. In a prospective, multicenter, cohort study conducted in Europe, central obesity showed a stronger association with HCC risk than general obesity.4 In addition, central obesity has been found to be a more significant predictor for the development of other digestive system cancers, such as colorectal carcinoma,5 than general obesity. In conclusion, although there is little direct evidence supporting the influence of central obesity on risk of HCC, the indirect evidence that central obesity causes more risk of NAFLD and other gastrointestinal cancers indicates a greater risk of developing HCC in patients with central obesity, compared with general obesity. In view that NAFLD affects approximately one third of the U.S. population,1 but few data assessed the impact of elevated WC/WHR in HCC risk worldwide, future studies should place a greater emphasis on central obesity.
Converging Evidence for the Association of Functional Genetic Variation in the Serotonin Receptor 2a Gene With Prefrontal Function and Olanzapine Treatment
Authors: Giuseppe Blasi, Caterina De Virgilio, Apostolos Papazacharias, Paolo Taurisano, Barbara Gelao, Leonardo Fazio, Gianluca Ursini, Lorenzo Sinibaldi, Ileana Andriola, Rita Masellis, Raffaella Romano, Antonio Rampino, Annabella Di Giorgio, Luciana Lo Bianco, Grazia Caforio, Francesco Piva, Teresa Popolizio, Cesario Bellantuono, Orlando Todarello, Joel E. Kleinman, Gemma Gadaleta, Daniel R. Weinberger, Alessandro Bertolino
Journal: JAMA Psychiatry (2013)

<h3>Importance</h3> Serotonin (5-hydroxytryptamine) receptor 2a (5-HT2AR) signaling is important for modulation of corticostriatal pathways and prefrontal activity during cognition. Furthermore, newer antipsychotic drugs target 5-HT2AR. A single-nucleotide polymorphism in the 5-HT2AR gene (<i>HTR2A</i>rs6314, C&gt;T; OMIM 182135) has been weakly associated with differential 5-HT2AR signaling and with physiologic as well as behavioral effects. <h3>Objective</h3> To use a hierarchical approach to determine the functional effects of this single-nucleotide polymorphism on 5-HT2AR messenger RNA and protein expression, on prefrontal phenotypes linked with genetic risk for schizophrenia, and on treatment with olanzapine. <h3>Design</h3> In silico predictions, in vitro, and case-control investigations. <h3>Setting</h3> Academic and clinical facilities. <h3>Participants</h3> The postmortem study included 112 brains from healthy individuals; the in vivo investigation included a total sample of 371 healthy individuals and patients with schizophrenia. <h3>Exposures</h3> Patients received olanzapine monotherapy for 8 weeks. <h3>Main Outcomes and Measures</h3> In silico predictions, messenger RNA, and protein expression in postmortem human prefrontal cortex and HeLa cells, functional magnetic resonance imaging prefrontal activity and behavior during working memory and attention in healthy individuals, and response to an 8-week trial of olanzapine treatment in patients with schizophrenia. <h3>Results</h3> Bioinformatic analysis predicted that rs6314 alters patterns of splicing, with possible effects on<i>HTR2A</i>expression. Moreover, the T allele was associated with reduced prefrontal messenger RNA expression in postmortem prefrontal cortex, with reduced protein expression in vitro, inefficient prefrontal blood oxygen level–dependent functional magnetic resonance imaging response during working memory and attentional control processing, and impaired working memory and attention behavior, as well as with attenuated improvement in negative symptoms after olanzapine treatment. <h3>Conclusions and Relevance</h3> Our results suggest that<i>HTR2A</i>rs6314 affects 5-HT2AR expression and functionally contributes to genetic modulation of known endophenotypes of schizophrenia-like higher-level cognitive behaviors and related prefrontal activity, as well as response to treatment with olanzapine.
Expansion of cancer care and control in countries of low and middle income: a call to action
Authors: Paul Farmer, Julio Frenk, Felicia M Knaul, Lawrence N Shulman, George Alleyne, Lance Armstrong, Rifat Atun, Douglas Blayney, Lincoln Chen, Richard Feachem, Mary Gospodarowicz, Julie Gralow, Sanjay Gupta, Ana Langer, Julian Lob-Levyt, Claire Neal, Anthony Mbewu, Dina Mired, Peter Piot, K Srinath Reddy, Jeffrey D Sachs, Mahmoud Sarhan, John R Seffrin
Journal: The Lancet (2010)
Impact of Overweight on Chronic Microvascular Complications in Type 1 Diabetic Patients
Authors: Christophe E.M. De Block, Ivo H. De Leeuw, Luc F. Van Gaal
Journal: Diabetes Care (2005)

To investigate a possible association of BMI with retinopathy and neuropathy in type 1 diabetes. Retinopathy and neuropathy may not only be related to glycemic control and diabetes duration but also to blood pressure and BMI.A total of 592 type 1 diabetic patients without nephropathy were studied (M/F: 324/268; age: 41 +/- 12 years; duration: 19 +/- 11 years; HbA(1c) [A1C]: 7.9 +/- 1.1%). Patients were subdivided according to BMI: 168 men and 146 women with BMI <25 kg/m(2), and 156 men and 122 women with BMI > or =25 kg/m(2). Retinopathy was examined by fundoscopy and neuropathy by electromyography.Hypertension (>130/85 mmHg) was present in 40%, retinopathy in 53%, and neuropathy in 43% of patients. Overweight subjects had more retinopathy (63 vs. 45%, P < 0.0001, odds ratio [OR] = 2.1) and neuropathy (49 vs. 38%, P = 0.008, OR = 1.6) than normal-weight patients. Patients with retinopathy were older (45 +/- 12 vs. 37 +/- 11 years, P < 0.0001) and had a longer diabetes duration (25 +/- 10 vs. 12 +/- 8 years, P < 0.0001), a higher A1C (8.0 +/- 1.1 vs. 7.7 +/- 1.1%, P = 0.001), and a higher BMI (25.8 +/- 4.1 vs. 24.7 +/- 4.2 kg/m(2), P = 0.001) than individuals without retinopathy. The same results are found in neuropathy. Logistic regression analysis showed that diabetes duration (beta = 0.15, P < 0.0001), blood pressure (beta = 0.22, P = 0.0047), and A1C (beta = 0.24, P = 0.01), but not BMI, lipid levels, sex, or age, were independent risk factors for retinopathy. Likewise, duration (beta = 0.05, P < 0.0001), age (beta = 0.04, P = 0.0001), A1C (beta = 0.35, P < 0.0001), and sex (beta = 0.74, P = 0.0001) but not BMI, lipid levels, or hypertension were independently associated with neuropathy. Men had more neuropathy than women (50 vs. 34%, P < 0.0001, OR = 1.9). Leptin and adiponectin levels did not differ between individuals with or without microvascular complications.Retinopathy and neuropathy are more prevalent in overweight (BMI > or =25 kg/m(2)) type 1 diabetic subjects. However, logistic regression analysis showed that diabetes duration and A1C remain the main determinants for retinopathy and neuropathy.
Late-breaking abstract: Lung recruitment in normal and emphysematous rats during methacholine challenge
Authors: Zoltán Hantos, Margit Szabari, Jόzsef Tolnai, Béla Suki
Journal: European Respiratory Journal (2011)

Elastase-induced emphysema in rodents is characterized by enlarged alveoli and decreased lung elastance but generally no change in airway resistance. We studied airway and tissue mechanics and recruitment in rats before and during constrictor challenge.  Sprague-Dawley rats were treated by intratracheal instillation of 50 U porcine pancreatic elastase (PPE, n=6). Three weeks later, these animals and 6 controls (C) were anesthetized, tracheotomized and mechanically ventilated. From low-frequency impedance (Zrs), Newtonian resistance (RN), tissue damping (G), elastance (H) and hysteresivity (η=G/H) were estimated. The lungs were degassed in vivo with oxygen breathing (10 min) and tracheal occlusion (10 s), and then reinflated to 35 hPa, while the pressure-volume (PV) relationship and intratracheal crackle sound (Cra) were recorded. Measurements of Zrs, PV and Cra were repeated during i.v. infusion of methacholine (Mch) at 64 μg/kg/min.  RN was not different between groups PPE and C at baseline (44±4 vs 46±10 hPa.s/l) and during challenge (165±41 vs 176±37 hPa.s/l). G and H, respectively, were significantly lower in the PPE group compared to the controls (613±57 vs 839±165 hPa/l, and 2273±301 vs 3033±385 hPa/l), although their elevations due to Mch were similar (71±43% vs 79±34% for G, and 24±13% vs 25±20% for H). Whereas cumulative crackle intensity reached 80% at similar P levels in both groups, the recruited volume was more reduced during challenge (-39 vs -16%) in the PPE group.  In summary, while airway resistance and recruitment remained unaffected, the tissue damage was associated with an enhanced tissue constrictor response following elastase treatment.  Supported by grants OTKA 66700 and NIH HL090757.
Myofibroblasts in hollow visceral myopathy: the origin of gastrointestinal fibrosis?
Authors: J E Martin, M Benson, M Swash, V Salih, A Gray
Journal: Gut (1993)

A patient with hollow visceral myopathy is reported in whom light microscopical studies of the small and large intestine showed typical features of degeneration, thinning, and fibrous replacement of smooth muscle of the gastrointestinal tract. Electron microscopy showed a striking increase in collagen with minimal fibroblast proliferation. Smooth muscle fibres had a range of ultrastructural abnormalities including myofilament disarray, electron lucency of the cytoplasm, and proliferation of the endoplasmic reticulum. Some fibres seemed to have typical ultrastructural characteristics of myofibroblasts, and others to be transition forms between typical smooth muscle cells and typical myofibroblasts. It seems likely that the fibrosis typical of this disorder has its origin in the transformation of smooth muscle fibres from a purely contractile to a myofibroblast collagen synthetic phenotype.
New drug introduction 1973-1974
Authors: P. de Haen
Journal: JAMA (1975)

A review of the number of newly synthesized drugs introduced in the United States during the years 1973 and 1974 reveals that there has been an encouraging improvement in comparison with the previous two-year period. The number for 1971 to 1972 was 25, and for 1973 to 1974, thirty-seven. These drugs can be grouped into nine major therapeutic classifications. Some represent real advances in therapy; others enable the physician to vary his therapeutic regimen. In 1974, of all new and refill prescriptions, 68% were filled with 200 drugs. Of these, 126 contain one active ingredient, and 76 products contain more than one. The number of prescriptions written for each group is in close relationship to the number of drug products in each class. (<i>JAMA</i>234:728-733, 1975)
Double-blind randomised clinical trial of a pepsin-inhibitory pentapeptide (pepstatin) in the treatment of duodenal ulcer.
Authors: O Bonnevie, L B Svendsen, J Holst-Christensen, T S Johansen, J Soltoft, P M Christiansen
Journal: Gut (1979)

In a double-blind randomised clinical trial a specific inhibition of peptic activity with a pentapeptide, pepstatin, had no significant advantage over placebo in the ulcer healing and symptomatology of duodenal ulcer. Thus, the inhibition of pepsin in human gastric juice does not appear to have a major influence on the healing of duodenal ulcer.
Meeting Report: Toxicology Testing Requirements and the U.S.-Japan Collaborative Study on In Vitro Tests for Chromosomal Aberrations
Authors: M. D. Shelby, T. Sofuni
Journal: Environmental Health Perspectives (1991)

As part of the U.S.-Japan Agreement on Cooperation in Research and Development in Science and Technology, Japanese and American scientists met in North Carolina to exchange information on toxicology testing requirements and guidelines in the two countries and to review progress in a collaborative study on detection of chemically induced chromosomal aberrations in cultured mammalian cells.
Triclosan: A Widespread Environmental Toxicant with Many Biological Effects
Authors: Mei-Fei Yueh, Robert H. Tukey
Journal: The Annual Review of Pharmacology and Toxicology (2016)

Triclosan (TCS) is a broad-spectrum antimicrobial agent that has been added to personal care products, including hand soaps and cosmetics, and impregnated in numerous different materials ranging from athletic clothing to food packaging. The constant disposal of TCS into the sewage system is creating a major environmental and public health hazard. Owing to its chemical properties of bioaccumulation and resistance to degradation, TCS is widely detected in various environmental compartments in concentrations ranging from nanograms to micrograms per liter. Epidemiology studies indicate that significant levels of TCS are detected in body fluids in all human age groups. We document here the emerging evidence—from in vitro and in vivo animal studies and environmental toxicology studies—demonstrating that TCS exerts adverse effects on different biological systems through various modes of action. Considering the fact that humans are simultaneously exposed to TCS and many TCS-like chemicals, we speculate that TCS-induced adverse effects may be relevant to human health.
Pyruvate Kinase M2 Regulates Hif-1α Activity and IL-1β Induction and Is a Critical Determinant of the Warburg Effect in LPS-Activated Macrophages
Authors: Eva M. Palsson-McDermott, Anne M. Curtis, Gautam Goel, Mario A.R. Lauterbach, Frederick J. Sheedy, Laura E. Gleeson, Mirjam W.M. van den Bosch, Susan R. Quinn, Raquel Domingo-Fernandez, Daniel G.W. Johnston, Jian-kang Jiang, William J. Israelsen, Joseph Keane, Craig Thomas, Clary Clish, Matthew Vander Heiden, Ramnik J. Xavier, Luke A.J. O’Neill
Journal: Cell Metabolism (2015)
METHODS FOR ANALYZING HEALTH CARE UTILIZATION AND COSTS
Authors: P. Diehr, D. Yanez, A. Ash, M. Hornbrook, D. Y. Lin
Journal: Annual Review of Public Health (1999)

▪ Abstract Important questions about health care are often addressed by studying health care utilization. Utilization data have several characteristics that make them a challenge to analyze. In this paper we discuss sources of information, the statistical properties of utilization data, common analytic methods including the two-part model, and some newly available statistical methods including the generalized linear model. We also address issues of study design and new methods for dealing with censored data. Examples are presented.
RheumaTutor. A case-based rheumatological training program. Stefan Schewe. ($50, DM 98, students $34.00, DM 68). Wiesbaden: Ullstein Medical Verlag, 1999. ISBN 3-86126-934-1.
Authors: H. J B. MOENS
Journal: Annals of the Rheumatic Diseases (2000)

Two interactive rheumatology tutors on CD-ROMThe widespread availability of information and communication technology oVers new possibilities for education of professionals and of patients.One of these possibilities is computer assisted learning. 1Ten years ago, research focused on the development of computer assisted diagnosis and text based help to rheumatologists and others. 2Despite the initial enthusiasm about artificial intelligence (AI), resulting in several diagnostic expert systems, in routine care a precise diagnosis is rarely an important issue and as a consequence these systems are hardly used.The experience with expert systems, however, evolved into systems intended for educational purposes."AI/Learn", based on the "AI/Rheum" expert system and exploiting a videodisk with an image library, proved to be an eVective means of teaching rheumatology. 3 The same image library was used to teach occupational and physical therapy students with the "HP-Rheum" system (HP: Health Professionals). 4 In recent years the introduction of sound, images, and movies on PCs, and the replacement of videodisks by CD-ROM facilitated production and access to these methods.The products resulting from the AI/Rheum project are not yet available on this medium, but two European rheumatologists have now completed educational systems on CD-ROM.They are to be honoured for their pioneering eVorts.The main characteristics of the systems are summarised in table 1, details are discussed below.
The Timing of Normal Puberty and the Age Limits of Sexual Precocity: Variations around the World, Secular Trends, and Changes after Migration
Authors: Anne-Simone Parent, Grete Teilmann, Anders Juul, Niels E. Skakkebaek, Jorma Toppari, Jean-Pierre Bourguignon
Journal: Endocrine Reviews (2003)

During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European countries. These observations are raising the issues of current differences and secular trends in timing of puberty in relation to ethnic, geographical, and socioeconomic background. None of these factors provide an unequivocal explanation for the earlier onset of puberty seen in the United States. In the formerly deprived migrating children, refeeding and catch-up growth may prime maturation. However, precocious puberty is seen also in some nondeprived migrating children. Attention has been paid to the changing milieu after migration, and recently, the possible role of endocrine- disrupting chemicals from the environment has been considered. These observations urge further study of the onset of puberty as a possible sensitive and early marker of the interactions between environmental conditions and genetic susceptibility that can influence physiological and pathological processes.
Response to Kennedy and Farthing
Authors: Iain Chalmers
Journal: Journal of the Royal Society of Medicine (2010)

The most serious allegations about the CNEP trial were that consent forms had been forged. Four years ago, Edmund Hey and I wrote1: ‘It is high time that the public received an authoritative statement about whether the allegations are true or false’. At a meeting of COPE, Michael Farthing stated that UKRIO would not be able to test these allegations forensically. Are Kennedy, Farthing and UKRIO really now able to deliver this?
Gait mechanics after ACL reconstruction: implications for the early onset of knee osteoarthritis
Authors: R J Butler, K I Minick, R Ferber, F Underwood
Journal: British Journal of Sports Medicine (2008)

Individuals who sustain a rupture of the anterior cruciate ligament (ACL) are at an increased risk for developing early-onset knee osteoarthritis (OA). The mechanism behind the early onset of the disease is still unknown. Knee OA progression has been previously examined by calculating the internal knee-abduction moment during gait. However, knee-joint moments have not been examined in individuals after ACL reconstruction as a potential mechanism for disease progression in early knee OA.To determine if individuals who have undergone ACL reconstruction exhibit altered gait mechanics that may be associated with knee OA progression.In total, 17 people who had previously undergone ACL reconstruction were enrolled in the study. A matched control group was recruited for comparison. All participants underwent gait analysis at an intentional walking speed to examine variables previously associated with knee OA progression, primarily the internal peak knee-abduction moment, during gait. One way ANOVAs were performed to examine differences in gait mechanics between the two groups. All joint moments were calculated as internal moments.The peak knee-abduction moment was increased by 21% in the ACL compared with the control group (p = 0.04). No other differences were seen in frontal plane knee or hip mechanics.It seems that individuals who have undergone ACL reconstruction exhibit an increased peak knee-abduction moment that may establish a potential mechanism of the earlier onset of knee OA in this population.
WITHDRAWN: Sense and stretchability: The role of titin and titin-associated proteins in myocardial stress-sensing and mechanical dysfunction
Authors: W LINKE
Journal: Cardiovascular Research (2007)

Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes, which respond with changes in contractile performance and gene expression. External forces play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced stress-sensing machinery causes mechanical dysregulation, cardiac remodelling, and heart failure. Nodal points of mechanosensing in the cardiomyocytes may reside in the Z-disk, I-band, and M-band regions of the sarcomeres. Longitudinal linkage of these regions is provided by the titin filament, and several 'hot spots' along this giant protein, in complex with some of its >20 ligands, may be pivotal to the myofibrillar stress or stretch response. This review outlines the known interaction partners of titin, highlights the putative stress/stretch-sensor complexes at titin's NH2 and COOH termini and their role in myopathies, and summarizes the known disease-associated mutations in those titin regions. Another focus is the elastic I-band titin section, which interacts with a diverse number of proteins and whose main function is as a determinant of diastolic distensibility and passive stiffness. The discussion centers on recent insights into the plasticity, mechanical role, and regulation of the elastic titin springs during cardiac development and in human heart disease. Titin and titin-based protein complexes are now recognized as integral parts of the mechanosensitive protein network and as critical components in cardiomyocyte stress/stretch signalling.