tbuckley/cabot-search huggingface dataset:
PTU-141 Bile acid malabsorption: an evaluation of current practice
Authors: A Hashim, E Paulon, M Ahmed
Journal: Gut (2012)

<h3>Introduction</h3> Primary or idiopathic bile acid malabsorption (BAM) is increasingly recognised as a cause of chronic diarrhoea. Nevertheless, it remains underestimated by many gastroenterologists partly because of the limited use of the gold standard SeHCAT test. We aimed to determine the prevalence of primary bile acid malabsorption and the duration of diarrhoea in this category of patients. We also compared our current practice of BAM detection using SeHCAT with the British Society of Gastroenterology (BSG) guidelines for the investigation of chronic diarrhoea. <h3>Methods</h3> This is a retrospective evaluative study of chronic diarrhoea patients who underwent a SeHCAT test between January and October 2011. The study was undertaken at the BHRU Hospitals in Greater London, UK. A total coverage sample was obtained and data were retrieved from the local patient electronic records. <h3>Results</h3> The total number of patients who received SeHCAT was 47, of which 5 had to be excluded because of unavailability of the patients notes. Of the remaining 42 patients, 60% (25) had a positive SeHCAT test indicating significant bile acid malabsorption. To facilitate further analysis the study population was subcategorised into patients who had Crohn9s disease (24%), cholecystectomy (33%), gastric bypass (2%), IBS (10%) and unexplained diarrhoea (31%). Idiopathic bile acid malabsorption was detected in 19% (8) of the general study population, 25% of IBS patients and in 54% of those with unexplained diarrhoea. The mean duration of diarrhoea was 5.1 years in the total population with similar figures (4.6 years) among the subcategory of patients with idiopathic bile acid malabsorption. On comparison with the BSG, we found that only 76% and 71% had their haematenics and coeliac screening checked respectively. The latter is specifically relevant to the subject as coeliac disease may interfere with bile acid metabolism. The study also revealed that 90% (38) of our study population had colonoscopy. Twelve out of 14 patients aged &lt;45 years with no other indication for colonoscopy, received full colonoscopy. Although this is considered safe, it carries cost implications as the BSG suggests flexi-sigmoidoscopy alone for this group of patients, <h3>Conclusion</h3> The study revealed a high prevalence of idiopathic BAM in the study population and even higher among those who had IBS/unexplained diarrhoea. The results also showed a long average duration of diarhoea before a solid diagnosis of primary BAM was established. We therefore, recommend early consideration of BAM in all patients with unexplained chronic diarrhoea. The SeHCAT test is a safe, non-invasive, and cheap investigation and should be more widely used by gastroenterologists. However, initial basic diarrhoea investigations must be offered to all patients to avoid under-diagnosing other common conditions. <h3>Competing interests</h3> None declared.
Arsenic exposure from drinking water, and all-cause and chronic-disease mortalities in Bangladesh (HEALS): a prospective cohort study
Authors: Maria Argos, Tara Kalra, Paul J Rathouz, Yu Chen, Brandon Pierce, Faruque Parvez, Tariqul Islam, Alauddin Ahmed, Muhammad Rakibuz-Zaman, Rabiul Hasan, Golam Sarwar, Vesna Slavkovich, Alexander van Geen, Joseph Graziano, Habibul Ahsan
Journal: The Lancet (2010)
Bile salt export pump is dysregulated with altered farnesoid X receptor isoform expression in patients with hepatocellular carcinoma
Authors: Yuan Chen, Xiulong Song, Leila Valanejad, Alexander Vasilenko, Vijay More, Xi Qiu, Weikang Chen, Yurong Lai, Angela Slitt, Matthew Stoner, Bingfang Yan, Ruitang Deng
Journal: Hepatology (2012)

As a canalicular bile acid effluxer, the bile salt export pump (BSEP) plays a vital role in maintaining bile acid homeostasis. BSEP deficiency leads to severe cholestasis and hepatocellular carcinoma (HCC) in young children. Regardless of the etiology, chronic inflammation is the common pathological process for HCC development. Clinical studies have shown that bile acid homeostasis is disrupted in HCC patients with elevated serum bile acid level as a proposed marker for HCC. However, the underlying mechanisms remain largely unknown. In this study, we found that BSEP expression was severely diminished in HCC tissues and markedly reduced in adjacent nontumor tissues. In contrast to mice, human BSEP was regulated by farnesoid X receptor (FXR) in an isoform-dependent manner. FXR-α2 exhibited a much more potent activity than FXR-α1 in transactivating human BSEP in vitro and in vivo. The decreased BSEP expression in HCC was associated with altered relative expression of FXR-α1 and FXR-α2. FXR-α1/FXR-α2 ratios were significantly increased, with undetectable FXR-α2 expression in one third of the HCC tumor samples. A similar correlation between BSEP and FXR isoform expression was confirmed in hepatoma Huh7 and HepG2 cells. Further studies showed that intrahepatic proinflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α), were significantly elevated in HCC tissues. Treatment of Huh7 cells with IL-6 and TNF-α resulted in a marked increase in FXR-α1/FXR-α2 ratio, concurrent with a significant decrease in BSEP expression.BSEP expression is severely diminished in HCC patients associated with alteration of FXR isoform expression induced by inflammation. Restoration of BSEP expression through suppressing inflammation in the liver may reestablish bile acid homeostasis.
ERADICATION OF VACCINE-PREVENTABLE DISEASES
Authors: A. Hinman
Journal: Annual Review of Public Health (1999)

▪ Abstract Eradication is the permanent reduction to zero of the worldwide incidence of infection caused by a specific agent as a result of deliberate efforts; intervention measures are no longer needed. To date, the only infectious disease that has been eradicated is smallpox. Poliomyelitis is targeted for eradication by the year 2000, and the eradication initiative is well under way, with the Western Hemisphere certified as being polio-free and more than one year having passed since polio cases occurred in the Western Pacific Region of the World Health Organization. A review of the technical feasibility of eradicating other diseases preventable by vaccines currently licensed for civilian use in the United States indicates that measles, hepatitis B, mumps, rubella, and possibly disease caused by Haemophilus influenzae type b are potential candidates. From a practical point of view, measles seems most likely to be the next target. Global capacity to undertake eradication is limited, and care must be taken to ensure that a potential measles eradication effort does not impede achievement of polio eradication. Even in the absence of eradication, major improvements in control are both feasible and necessary with existing vaccines. New and improved vaccines may give further possibilities of eradication in the future. Eradication represents the ultimate in sustainability and social justice.
PRIMARY PREVENTION OF DIABETES: What Can Be Done and How Much Can Be Prevented?
Authors: Matthias B. Schulze, Frank B. Hu
Journal: Annual Review of Public Health (2004)

▪ Abstract Although it is widely believed that type 2 diabetes mellitus is the result of a complex interplay between genetic and environmental factors, compelling evidence from epidemiologic studies indicates that the current worldwide diabetes epidemic is largely due to changes in diet and lifestyle. Prospective cohort studies and randomized clinical trials have demonstrated that type 2 diabetes can be prevented largely through moderate diet and lifestyle modifications. Excess adiposity is the most important risk factor for diabetes, and thus, maintaining a healthy body weight and avoiding weight gain during adulthood is the cornerstone of diabetes prevention. Increasing physical activity and reducing sedentary behaviors such as prolonged TV watching are important both for maintaining body weight and improving insulin sensitivity. There is increasing evidence that the quality of fat and carbohydrate plays a more important role than does the quantity, and thus, public health strategies should emphasize replacing saturated and trans fats with unsaturated fats and replacing refined grain products with whole grains. Recent studies have also suggested a potential role for coffee, dairy, nuts, magnesium, and calcium in preventing diabetes. Overall, a healthy diet, together with regular physical activity, maintenance of a healthy weight, moderate alcohol consumption, and avoidance of sedentary behaviors and smoking, could nearly eliminate type 2 diabetes. However, there is still a wide gap between what we know and what we practice in the field of public health; how to narrow that gap remains a major public health challenge.
Outbreak of human listeriosis associated with tomme cheese in northwest Switzerland, 2005
Authors: J Bille, D S Blanc, H Schmid, K Boubaker, A Baumgartner, H H Siegrist, M L Tritten, R Lienhard, D Berner, R Anderau, M Treboux, J M Ducommun, R Malinverni, D Genné, P Erard, U Waespi
Journal: Eurosurveillance (2006)

During an eight week period in spring 2005, 10 cases of listeriosis were reported in a small area of northwest Switzerland (150,000 inhabitants). Eight cases were in older immunocompromised patients who became ill with bacteraemia (three deaths), and two cases were in pregnant women who had septic abortion. All cases were due to a serotype 1/2a isolate with one of two pulsovars found by PFGE. Patient interviews quickly revealed that a locally made and distributed soft cheese (known as 'tomme') was the food source responsible for the outbreak. Samples of this cheese, and of butter made in the same factory, revealed Listeria monocytogenes sv 1/2a of the same pulsovar in amounts of 1000-10 000 and 10-100 cfu/g, respectively. The prompt suspension of production, the market recall of the product, and a public alert terminated the outbreak. However, two cases of febrile gastroenteritis due to the same strains were reported within 10 days of product recall. The restricted distribution area of the contaminated cheese and the collaboration of local physicians, medical microbiologists and food health services all contributed to a rapid and successful investigation. This small outbreak of listeriosis reinforces the need for a laboratory-based surveillance system with rapid typing, as well as collaboration between physicians and microbiologists.
Doxazosin blocks the angiotensin II-induced smooth muscle cell DNA synthesis in the media, but not in the neointima of the rat carotid artery after balloon injury
Authors: E Van Kleef
Journal: Cardiovascular Research (1996)

Infusion of angiotensin II (AngII) during the third and fourth week after balloon injury of the left common carotid artery of the rat induces smooth muscle cell (SMC) DNA synthesis. In this study we wanted to investigate whether alpha 1-adrenoreceptors are involved in AngII-induced SMC DNA synthesis in the neointima.Adult male Wistar Kyoto rats were subcutaneously infused for 2 weeks with AngII and the alpha 1-adrenoreceptor antagonist doxazosin during the 3rd and the 4th week after balloon injury of the left common carotid artery. Control groups received AngII, 0.9% NaCl, AngII + 50% dimethylsulfoxide (DMSO, the solvent of doxazosin), doxazosin or 50% dimethylsulfoxide. Each rat received 5-bromo-2'-deoxyuridine in a separate osmotic minipump to label DNA-synthesizing SMC. Systolic blood pressures were measured in all groups.Angiotensin II caused an increase in systolic blood pressure, whereas addition of doxazosin did not affect the increase in SBP caused by AngII. In the media of the non-injured carotid artery, AngII increased SMC DNA synthesis, as the BrdUrd labeling fraction increased from 0.2 +/- 0.1% (mean +/- s.e.m.) in the NaCl group towards 3.4 +/- 0.6% in the AngII group. Coinfusion with doxazosin reduced the AngII-induced increase in BrdUrd labeling fraction from 3.2 +/- 0.8% in the AngII + DMSO group towards 0.6 +/- 0.2% in the AngII+doxazosin group. A similar effect of doxazosin was found in the media of the injured left carotid artery, in which coinfusion with doxazosin also reduced the BrdUrd labeling fraction from 2.6 +/- 0.8% in the AngII+DMSO group towards 0.3 +/- 0.1% in the AngII+doxazosin group. In the neointima of the injured left carotid artery, AngII increased the BrdUrd labeling fraction from 11.7 +/- 1.6% in the NaCl group towards 28.0 +/- 3.4% in the AngII group. Coinfusion with doxazosin did not influence the AngII-induced SMC DNA synthesis, since the BrdUrd labeling fraction in the neointima of the AngII+doxazosin group was 22.5 +/- 2.9%, whereas the neointimal BrdUrd labeling fraction in the AngII+DMSO group was 22.9 +/- 2.3%. Little effect was found on the medial cross-sectional area. The neointimal cross-sectional area was increased as a result of infusion of AngII (0.12 +/- 0.01 mm2 vs. 0.18 +/- 0.01 mm2), and coinfusion of doxazosin did not reduce the AngII-induced increase in neointimal cross-sectional area (0.18 +/- 0.03 mm2).These data suggest that alpha 1-adrenoreceptors are not involved in AngII-induced neointimal SMC DNA synthesis and cross-sectional area, but only play a role in the media of the carotid artery.
SUICIDE IN ADOLESCENTS
Authors: BENJAMIN H. BALSER, JAMES F. MASTERSON
Journal: American Journal of Psychiatry (1959)

1. The prevalence of suicidal attempts in adolescents has been obscured by the paucity of completed suicides in that period. 2. In adults the relationship between affective disorders and suicide has been established. In adolescents it would seem that this relationship exists between schizophrenic reaction and suicidal attempt rather than affective disorder and suicidal attempts.
Private firm launches 16 point transformation plan for failing NHS hospital
Authors: A. O'Dowd
Journal: BMJ (2012)

A private company has unveiled an ambitious 16 point action plan to transform the NHS hospital that it has just taken over running.

From 1 February, Circle took over management of Hinchingbrooke Health Care NHS Trust in Cambridgeshire—the first private firm to run a whole NHS trust—and has promised to turn around its fortunes.

The trust has debts of around £40m (€48m; $63m), which Circle says it is confident it can clear thanks to its transformation plan, which was drawn up with extensive contributions from staff and the local population.

Clinicians and staff can expect several changes to how the trust is run with plans for staff incentive schemes, devolved power to clinical …
No small matter: qualitatively distinct challenges of pediatric genomic studies
Authors: Isaac S Kohane
Journal: Genome Medicine (2011)

�ere are a number of compelling reasons why pediatric populations should be preferentially studied to understand the genomic basis of disease. First, many forms of adult disease have genetic etiologies that were discovered in pediatric studies (for example, cardiomyopathies, several causes of infertility and colorectal cancer) where the more penetrant or homozygous mutations, clinically presenting in early childhood, made the genetic pathogenesis much clearer than in adult disease. Second, being able to detect the genetic antecedents of adult disease best allows us to study how the disease develops on the way to adulthood and, just as importantly, gives the longest possible lead time for the implementation of the most cost-effective primary prevention (for example, use of angiotensin converting enzyme inhibitors to reduce the cardiac manifestations of Marfan syndrome if given in childhood). �ird, the individual variation due to environmental exposures, whether it be diet, drugs or other habits, is by definition relatively small compared with that of adults who have had an order of magnitude more exposure to the environment. Consequently, the case could be made that a greater fraction of pathophysiological variability in children can be attributable to inherited traits (although one could make several opposing arguments, including the increased suscepti bility of children to certain environmental insults). Last, and most importantly, children constitute a population with distinct physiology and disease risks and there is no substitute for pediatric genomics studies in order to better understand and ultimately manage or treat these risks and diseases. So why is it that pediatric genomic studies form only a small fraction of the entire collection of genomic studies formed to date? Challenges in pediatric genomics research �ere is more here than just the usual underfunding of pediatric projects relative to adult projects, although this certainly may be an important factor [1]. In many ways the barriers mirror some of those that cause underrepresentation of historically under-represented and underserved minorities in genetic studies as outlined by Francis Collins and colleagues [2]. One important consideration is that it is just much harder to perform genetic studies with children. To start with, there is the matter of consent and assent. Children are not children forever and therefore the parental consent most likely has to be eventually replaced by childhood assent and then full consent as they reach maturity [3]. �is already imposes significantly more in terms of overheads for consent management than those incurred by adult prospective studies.
US ophthalmologists plead with drug regulator not to restrict access to Avastin
Authors: D. Cohen
Journal: BMJ (2015)

Ophthalmologists in the United States have criticized the Food and Drug Administration for issuing guidance that would potentially restrict the use of bevacizumab (Avastin) for eye conditions. Some critics have suggested that the agency’s advisory committee has conflicts of interest.

Bevacizumab is approved for various cancers and is also repackaged into smaller doses in compounding pharmacies and used “off label” for eye conditions, the FDA said. However, after outbreaks of endophthalmitis from contaminated repackaged bevacizumab the FDA sought to regulate compounding pharmacies. In draft proposals it said that there would be a maximum limit of five days allowed between splitting up the drug in a pharmacy and it being used.

George Williams, secretary for federal affairs at the American Academy of Ophthalmologists and professor of ophthalmology at Associated Retinal Consultants in Michigan, told The BMJ , “If this BUD [beyond use date] is implemented the logistical implications will greatly impede the use of Avastin …
COMIT: identification of noncoding motifs under selection in coding sequences
Authors: Deniz Kural, Yang Ding, Jiantao Wu, Alicia M Korpi, Jeffrey H Chuang
Journal: Genome biology (2009)

Abstract Coding nucleotide sequences contain myriad functions independent of their encoded protein sequences. We present the COMIT algorithm to detect functional noncoding motifs in coding regions using sequence conservation, explicitly separating nucleotide from amino acid effects. COMIT concurs with diverse experimental datasets, including splicing enhancers, silencers, replication motifs, and microRNA targets, and predicts many novel functional motifs. Intriguingly, COMIT scores are well-correlated to scores uncalibrated for amino acids, suggesting that nucleotide motifs often override peptide-level constraints.
Variability of human immunodeficiency virus-1 in the female genital reservoir during genital reactivation of herpes simplex virus type 2
Authors: J. LeGoff, P. Roques, M.-A. Jenabian, C. Charpentier, C. Brochier, H. Bouhlal, G. Gresenguet, E. Frost, J. Pepin, P. Mayaud, L. Belec
Journal: Clinical Microbiology and Infection (2015)
Preventing Cancer by Disrupting Progression of Precancerous Lesions
Authors: W. J. Blot
Journal: JNCI Journal of the National Cancer Institute (2000)

In this issue of the Journal, Correa et al. (1) provide results from the first reported randomized intervention trial of the effects of anti-Helicobacter pylori treatment and of vitamin supplementation on precancerous lesions of the stomach.The findings are encouraging, with evidence that therapy for H. pylori and supplementation with ␤-carotene or vitamin C may help limit progression and enhance regression of conditions believed to be in the pathway of gastric cancer.Randomized clinical trials provide one of the most scientifically rigorous approaches to evaluate potential inhibitors of cancer.Trials directly evaluating cancer as an outcome require large numbers of persons to be followed, often for many years.In some circumstances, an effective alternative is a smaller, shorter term trial focusing on the carcinogenic process leading to the onset of clinically detectable cancer.Correa et al. followed this strategy in Colombia in an area where gastric cancer rates are high and precancerous lesions of the stomach are fairly common.By studying the effects of interventions on the progression/ regression of these common lesions, information can be obtained on whether intervening may inhibit the early changes leading to cancer.The inherent assumption in such a study is that the carcinogenic process does, in fact, involve a transition from normal epithelium through advancing precancerous lesions.Such a process may exist for a number of cancers, although evidence for most forms of cancer is scanty.For stomach cancer (especially the common intestinal type), however, epidemiologic and pathologic studies have documented that a series of transitions typically are involved (2).In most cases, particularly in high-risk areas, a sequence of events occurs whereby normal gastric mu-
Increased Endothelin-1 in Bleomycin-induced Pulmonary Fibrosis and the Effect of an Endothelin Receptor Antagonist
Authors: SUNG-HAE PARK, DINA SALEH, ADEL GIAID, RENÉ P. MICHEL
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Idiopathic pulmonary fibrosis (IPF) is characterized by an alveolitis with epithelial and endothelial damage progressing to fibrosis. Numerous mediators have been implicated in this complex process. Studies in humans have shown that endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide, is a mediator in IPF. To determine the role of ET-1 and endothelin-converting enzyme (ECE)-1 and the effect of bosentan, an ET receptor antagonist, in an animal model of IPF, we studied three groups of rats (n = 6 each): Group 1, control, received saline; Group 2, fibrosis, received 1.5 U bleomycin intratracheally; Group 3, fibrosis-bosentan treated, received bleomycin and bosentan daily by gavage. After 28 d, right upper lobes were fixed for immunohistochemistry (IHC) and sections were stained with antisera to ET-1 and ECE-1 and graded semiquantitatively. Sections from left lungs were embedded in paraffin and stained for light microscopic morphometry to quantitate the fibrosis. By IHC, we found increased ET-1 immunoreactivity (ir) in airway epithelium and inflammatory cells, and ECE-1-ir in airway epithelium, type II pneumocytes and endothelial cells (p < 0.05). By morphometry, the volume fraction (Vv) of connective tissue (CT) increased and the Vv of air decreased in the fibrosis group compared with that in the control group. Bosentan reduced the Vv of CT and increased the Vv of air compared with that in the fibrosis group (p < 0.05). These results indicate that ET-1 is involved in the pathogenesis of pulmonary fibrosis in the rodent model and that blockage of its receptors reduces the fibrosis.