tbuckley/cabot-search huggingface dataset:
Transjugular liver biopsy: how good is it for accurate histological interpretation?
Authors: E Cholongitas, A Quaglia, D Samonakis, M Senzolo, C Triantos, D Patch, G Leandro, A P Dhillon, A K Burroughs
Journal: Gut (2006)

<b>Background:</b> A transjugular liver biopsy (TJLB) specimen is often smaller or more fragmented than a percutaneous liver biopsy (PLB) specimen. Recently, for PLB, the minimum requirements to evaluate chronic hepatitis have been set at 20–25 mm length and ⩾11 complete portal tracts. <b>Aim:</b> To evaluate and compare length of TJLB and PLB specimens, portal tract number, fragmentation and adequacy for histopathological diagnosis and staging. <b>Patients and methods:</b> 326 consecutive TJLB specimens in 274 patients (109 who had undergone a transplantation), always using three passes (19-G Tru-cut) and 40 consecutive PLB specimens (15-G Menghini). <b>Results:</b> No technical failures occurred with the TJLB, and histological diagnosis was possible in 98.5%. The median (range) number of fragments was 5 (1–13) and the median total length was 22 (3–46) mm, with 65% of specimens ⩾20 mm and 36% ⩾25 mm; 60% of TJLB specimens were ⩾28 mm long had ⩾11 complete portal tracts. No difference in complete portal tract number or biopsy length was found between PLB and TJLB specimens. <b>Conclusion:</b> A TJLB specimen with three passes is adequate for histological diagnosis, with 89% of specimens being either ⩾15 mm or having ⩾6 complete portal tracts. Although adequate sampling remains a limitation for staging and grading of chronic hepatitis, TJLB is comparable to PLB in this respect.
Genetic biomarkers and exercise-related injuries: current clinical applications?
Authors: M P Schwellnus
Journal: British Journal of Sports Medicine (2013)

<h3>Background</h3> Currently Ceylon tea is a major foreign exchange earner in Sri Lanka, only second to the foreign exchange earned by the garment industry. Tea industry has a large work force since it utilize manual labor for the major steps of its production. Estate population in Sri Lanka is relatively less educated and belongs to the lower socio-economic status compared to the general public. Most of the workers in tea factories are females and it has been reported that these females are commonly complaining musculoskeletal pain in multiple sites of the body. This was found to increase the work disability [1]. However this problem and its impact on quality of life have not been studied systematically. <h3>Objectives</h3> This research was carried out to study the multi-site pain and its impact on quality of life among the female tea factory workers in southern Sri Lanka. <h3>Methods</h3> This study was carried out among a random sample of female workers, working in tea factories in Akuressa division in southern Sri Lanka. Pain in two or more sites of the body for a minimum period of three months during the last 12 months was considered as chronic multi-site pain. Translated and validated WHO Quality of Life- Brief questionnaire was used to assess the quality of life of workers. Data was collected by medically qualified research assistants using a structured questionnaire. <h3>Results</h3> Four hundred female workers participated in the study. Mean age of workers was 38.25 years with the range of 19 years to 57 years. Most (61.5%) had an education only up to grade 5. Mean duration of work in tea factories is 15.55. 35.25% of workers were found to have multi-site pain. Only 25.50% rated their overall quality of life as very good or good, and 22.25% were satisfied with their health. Workers with multi-site pain were had significantly (p&lt;0.05) lower scores (worse) relating to psychological and physiological domains compared to the workers without multi-site pain. <h3>Conclusions</h3> More than one third of Female tea factory workers in Sri Lanka report chronic multi-site pain and they had lower quality of life compared to the other workers. Long term follow up studies for identify the risk factors of developing multi-site pain of these workers is therefore warranted. <h3>References</h3> Neupane S, Miranda H, Virtanen P, Siukolal A, Nygard CH. Multi-site pain and work ability among an industrial population, Occupational Medicine 2011:61(8):563-569. <h3>Disclosure of Interest</h3> None Declared
Melan-A–specific Cytotoxic T Cells Are Associated with Tumor Regression and Autoimmunity Following Treatment with Anti-CTLA-4
Authors: Oliver Klein, Lisa M. Ebert, Theo Nicholaou, Judy Browning, Sarah E. Russell, Marina Zuber, Heather M. Jackson, Nektaria Dimopoulos, Bee Shin Tan, Axel Hoos, Immanuel F. Luescher, Ian D. Davis, Weisan Chen, Jonathan Cebon
Journal: Clinical Cancer Research (2009)

Ipilimumab is a monoclonal antibody that blocks the immune-inhibitory interaction between CTL antigen 4 (CTLA-4) and its ligands on T cells. Clinical trials in cancer patients with ipilimumab have shown promising antitumor activity, particularly in patients with advanced melanoma. Often, tumor regressions in these patients are correlated with immune-related side effects such as dermatitis, enterocolitis, and hypophysitis. Although these reactions are believed to be immune-mediated, the antigenic targets for the cellular or humoral immune response are not known.We enrolled patients with advanced melanoma in a phase II study with ipilimumab. One of these patients experienced a complete remission of his tumor. The specificity and functional properties of CD8-positive T cells in his peripheral blood, in regressing tumor tissue, and at the site of an immune-mediated skin rash were investigated.Regressing tumor tissue was infiltrated with CD8-positive T cells, a high proportion of which were specific for Melan-A. The skin rash was similarly infiltrated with Melan-A-specific CD8-positive T cells, and a dramatic (>30-fold) increase in Melan-A-specific CD8-positive T cells was apparent in peripheral blood. These cells had an effector phenotype and lysed Melan-A-expressing tumor cells.Our results show that Melan-A may be a major target for both the autoimmune and antitumor reactions in patients treated with anti-CTLA-4, and describe for the first time the antigen specificity of CD8-positive T cells that mediate tumor rejection in a patient undergoing treatment with an anti-CTLA-4 antibody. These findings may allow a better integration of ipilimumab into other forms of immunotherapy.
Colon-Specific Deletion of Epithelial Sodium Channel Causes Sodium Loss and Aldosterone Resistance
Authors: Sumedha Malsure, Qing Wang, Roch-Philippe Charles, Chloe Sergi, Romain Perrier, Birgitte Mønster Christensen, Marc Maillard, Bernard C. Rossier, Edith Hummler
Journal: Journal of the American Society of Nephrology (2014)

Aldosterone promotes electrogenic sodium reabsorption through the amiloride-sensitive epithelial sodium channel (ENaC). Here, we investigated the importance of ENaC and its positive regulator channel-activating protease 1 (CAP1/Prss8) in colon. Mice lacking the αENaC subunit in colonic superficial cells (Scnn1a(KO)) were viable, without fetal or perinatal lethality. Control mice fed a regular or low-salt diet had a significantly higher amiloride-sensitive rectal potential difference (∆PDamil) than control mice fed a high-salt diet. In Scnn1a(KO) mice, however, this salt restriction-induced increase in ∆PDamil did not occur, and the circadian rhythm of ∆PDamil was blunted. Plasma and urinary sodium and potassium did not change with regular or high-salt diets or potassium loading in control or Scnn1a(KO) mice. However, Scnn1a(KO) mice fed a low-salt diet lost significant amounts of sodium in their feces and exhibited high plasma aldosterone and increased urinary sodium retention. Mice lacking the CAP1/Prss8 in colonic superficial cells (Prss8(KO)) were viable, without fetal or perinatal lethality. Compared with controls, Prss8(KO) mice fed regular or low-salt diets exhibited significantly reduced ∆PDamil in the afternoon, but the circadian rhythm was maintained. Prss8(KO) mice fed a low-salt diet also exhibited sodium loss through feces and higher plasma aldosterone levels. Thus, we identified CAP1/Prss8 as an in vivo regulator of ENaC in colon. We conclude that, under salt restriction, activation of the renin-angiotensin-aldosterone system in the kidney compensated for the absence of ENaC in colonic surface epithelium, leading to colon-specific pseudohypoaldosteronism type 1 with mineralocorticoid resistance without evidence of impaired potassium balance.
Parenting programme for parents of children at risk of developing conduct disorder: cost effectiveness analysis
Authors: Rhiannon T Edwards, Alan Céilleachair, Tracey Bywater, Dyfrig A Hughes, Judy Hutchings
Journal: BMJ (2007)

<b>Objective</b> To investigate the cost effectiveness of a parenting programme. <b>Design</b> An incremental cost effectiveness analysis alongside a pragmatic randomised controlled trial of the effectiveness of a group parenting programme delivered through Sure Start in the community. <b>Setting</b> Sure Start areas in north and mid Wales. <b>Participants</b> Parents of 116 children aged 36-59 months (87% of the clinical sample) at risk of developing conduct disorders defined by scoring over the clinical cut off on the Eyberg child behaviour inventory). Children were identified by health visitors and recruited by the research team. <b>Intervention</b> The Webster-Stratton Incredible Years basic parenting programme or a six month waiting list control. <b>Main outcome measure</b> Incremental cost per unit of improvement on the intensity score of the Eyberg child behaviour inventory. <b>Results</b> The bootstrapped incremental cost effectiveness ratio point estimate was £73 (€109, $142) per one point improvement on the intensity score (95% confidence interval £42 to £140). It would cost £5486 (€8190, $10 666) to bring the child with the highest intensity score to below the clinical cut-off point and £1344 (€2006, $2618) to bring the average child in the intervention group within the non-clinical limits on the intensity score (below 127). For a ceiling ratio of £100 (€149, $194) per point increase in intensity score, there is an 83.9% chance of the intervention being cost effective. The mean cost per child attending the parenting group was £1934 (€2887, $3760) for eight children and £1289 (€1924, $2506) for 12 children, including initial costs and materials for training group leaders. When we categorised the sample into relatively mild, moderate, and severe behaviour groups based on intensity scores at baseline the intervention seemed more cost effective in those with the highest risk of developing conduct disorder. <b>Conclusion</b> This parenting programme improves child behaviour as measured by the intensity score of the Eyberg child behaviour inventory at a relatively low cost and was cost effective compared with the waiting list control. This parenting programme involves modest costs and demonstrates strong clinical effect, suggesting it would represent good value for money for public spending.
Role of cognitive factors in symptom induction following high and low fat meals in patients with functional dyspepsia
Authors: C Feinle-Bisset
Journal: Gut (2003)

and aims: Dietary fat plays a role in the pathophysiology of symptoms in functional dyspepsia (FD). In healthy subjects, cognitive factors enhance postprandial fullness; in FD patients, attention increases gut perception. We hypothesised that the information given to patients about the fat content of a meal would affect dyspeptic symptoms.Fifteen FD patients were each studied on four occasions in a randomised double blind fashion. Over two days they ingested a high fat yoghurt (HF) and over the other two days a low fat yoghurt (LF). For each yoghurt, the patients received the correct information about its fat content on one day (HF-C, LF-C) and the opposite (wrong) information on the other day (HF-W, LF-W). Dyspeptic symptoms, plasma cholecystokinin (CCK) concentrations, and gastric volumes were evaluated.Both the fat content and information about the fat content affected fullness and bloating scores-both were higher after HF-C compared with LF-C, and LF-W compared with LF-C, with no differences between HF-C and HF-W. Nausea scores were higher after HF compared with LF, with no effect of the information about fat content. No differences between discomfort and pain scores were found between study conditions. Plasma CCK and gastric volumes were greater following HF compared with LF, with no effect of the information given to the patients. All differences are p<0.05.Cognitive factors contribute to symptom induction in FD. Low fat foods may also elicit symptoms if patients perceive foods as high in fat, while CCK and gastric volumes do not appear to be affected by cognitive factors.
Parallel Organization of Functionally Segregated Circuits Linking Basal Ganglia and Cortex
Authors: G E Alexander, M R DeLong, P L Strick
Journal: Annual Review of Neuroscience (1986)

Information about the basal ganglia has accumulated at a prodigious pace over the past decade, necessitating major revisions in our concepts of the structural and functional organization of these nuclei. From earlier data it had appeared that the basal ganglia served primarily to integrate diverse inputs from the entire cerebral cortex and to funnel these influences, via the ventrolateral thalamus, to the motor cortex (Allen & Tsukahara 1974, Evarts & Thach 1969, Kemp & Powell 1971). In particular, the basal
Sirolimus Therapy to Halt the Progression of ADPKD
Authors: Norberto Perico, Luca Antiga, Anna Caroli, Piero Ruggenenti, Giorgio Fasolini, Mariateresa Cafaro, Patrizia Ondei, Nadia Rubis, Olimpia Diadei, Giulia Gherardi, Silvia Prandini, Andrea Panozo, Rodolfo Flores Bravo, Sergio Carminati, Felipe Rodriguez De Leon, Flavio Gaspari, Monica Cortinovis, Nicola Motterlini, Bogdan Ene-Iordache, Andrea Remuzzi, Giuseppe Remuzzi
Journal: Journal of the American Society of Nephrology (2010)

Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not detect a difference between the two treatments (P=0.45). Cyst volume was stable on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.
Prevalence of Morphometric Vertebral Fractures in Patients With Type 1 Diabetes
Authors: Volha V. Zhukouskaya, Cristina Eller-Vainicher, Volha V. Vadzianava, Alla P. Shepelkevich, Irina V. Zhurava, Galina G. Korolenko, Olga B. Salko, Elisa Cairoli, Paolo Beck-Peccoz, Iacopo Chiodini
Journal: Diabetes Care (2013)

Several studies showed low bone mineral density (BMD) and elevated risk of symptomatic fractures in patients with type 1 diabetes (T1D). To our knowledge, there has been no investigation on the prevalence of asymptomatic vertebral fractures (VFx) in T1D. In the current study, we assessed BMD and the prevalence of VFx in T1D.We evaluated 82 T1D patients (26 males and 56 females, aged 31.1 ± 8.6 years, BMI 23.5 ± 3.3 kg/m(2), disease duration 12.8 ± 8.3 years) and 82 controls (22 females and 60 males, aged 32.9 ± 5.8 years, BMI 23.9 ± 4.8 kg/m(2)). Spinal and femoral BMD (as Z-score, Z-LS and Z-FN, respectively) and the prevalence of VFx were evaluated by dual X-ray absorptiometry.T1D patients had lower Z-LS and Z-FN than controls (-0.55 ± 1.3 vs. 0.35 ± 1.0, P < 0.0001, and -0.64 ± 1.1 vs. 0.29 ± 0.9, P < 0.0001, respectively) and a higher prevalence of VFx (24.4 vs. 6.1%, P = 0.002). Age, diabetes duration, age at diabetes manifestation, glycosylated hemoglobin, Z-LS, Z-FN, and the prevalence of chronic complications were similar for patients with and without VFx. In the logistic regression analysis, the presence of VFx was associated with the presence of T1D but not with lumbar spine BMD. Whereas moderate or severe VFx was associated with low lumbar spine BMD in the whole combined group of T1D patients and controls, there was no association between moderate or severe VFx and lumbar spine BMD in the T1D group.T1D patients have low BMD and elevated prevalence of asymptomatic VFx, which is associated with the presence of T1D independently of BMD.
PCSK9
Authors: Nabil G. Seidah, Zuhier Awan, Michel Chrétien, Majambu Mbikay
Journal: Circulation Research (2014)

Since the discovery of proprotein convertase subtilisin kexin 9 (PCSK9) in 2003, this PC has attracted a lot of attention from the scientific community and pharmaceutical companies. Secreted into the plasma by the liver, the proteinase K-like serine protease PCSK9 binds the low-density lipoprotein (LDL) receptor at the surface of hepatocytes, thereby preventing its recycling and enhancing its degradation in endosomes/lysosomes, resulting in reduced LDL-cholesterol clearance. Surprisingly, in a nonenzymatic fashion, PCSK9 enhances the intracellular degradation of all its target proteins. Rare gain-of-function PCSK9 variants lead to higher levels of LDL-cholesterol and increased risk of cardiovascular disease; more common loss-of-function PCSK9 variants are associated with reductions in both LDL-cholesterol and risk of cardiovascular disease. It took 9 years to elaborate powerful new PCSK9-based therapeutic approaches to reduce circulating levels of LDL-cholesterol. Presently, PCSK9 monoclonal antibodies that inhibit its function on the LDL receptor are evaluated in phase III clinical trials. This review will address the biochemical, genetic, and clinical aspects associated with PCSK9's biology and pathophysiology in cells, rodent and human, with emphasis on the clinical benefits of silencing the expression/activity of PCSK9 as a new modality in the treatment of hypercholesterolemia and associated pathologies.
Asbestos as a Public Health Risk: Disease and Policy
Authors: H Weill, J M Hughes
Journal: Annual Review of Public Health (1986)

Optimal societal benefit from public policy decision making concerning en­ vironmental and occupational health issues can be obtained only when these decisions are fully and appropriately based on existing scientific knowledge. Regarding asbestos and its use in our society, this important goal has been elusive for a number of reasons. First, scientists have been unwilling or unable to communicate technical issues to decision makers, in part due to their complexity, but also because the forum for this interaction has often been adversarial in nature. Second, the public and their policymakers have some­ times mistrusted science and technology; particularly recently, technological progress is often viewed as detrimental to society, particularly in environmental matters. And third, scientists' opinions have, at times, been based more on personal choice than on professional expertise. These, and possibly other factors, have made for an uneasy union between scientists and policymakers in areas in which communication is essential if society is to deal effectively with many of these complex expectations. Nevertheless, communication between these two sectors is improving. Sci­ entists, recognizing the importance of these concerns (and that decisions must often be made, with or without scientific input), are becoming increasingly willing to participate in dialogues concerning public policy issues. The public,
Pain, cortex, and consciousness
Authors: Marshall Devor
Journal: Behavioral and Brain Sciences (2007)

Painful stimuli evoke functional activations in the cortex, but electrical stimulation of these areas does not evoke pain sensation, nor does widespread epileptic discharge. Likewise, cortical lesions do not eliminate pain sensation. Although the cortex may contribute to pain modulation, the planning of escape responses, and learning, the network activity that constitutes the actual experience of pain probably occurs subcortically.
Pulmonary function of a paediatric cohort of patients with postinfectious bronchiolitis obliterans. A long term follow-up
Authors: Alejandro J Colom, Alberto Maffey, Facundo Garcia Bournissen, Alejandro Teper
Journal: Thorax (2014)

<h3>Background</h3> Postinfectious bronchiolitis obliterans (BO) is a chronic respiratory disease that usually follows a severe adenovirus infection. <h3>Objective</h3> To determine the evolution of pulmonary function and clinical outcome of children with postinfectious BO during childhood. <h3>Methods</h3> The study included patients diagnosed with postinfectious BO in whom at least two spirometries were performed within a minimum interval of 3 months. <h3>Results</h3> 46 met the inclusion criteria. The mean (±SD) follow-up period was 12.5 (±3.5) years. 197 spirometries and 41 plethysmographies were performed. Initial (9±3 years old) lung function was as follows (z score, mean±SD): forced vital capacity (FVC) −3.8±1; forced expiratory volume in 1 s (FEV<sub>1</sub>) −4.4±1; FEV<sub>1</sub>/FVC −2.2±1; forced expiratory flow (FEF)<sub>25–75</sub> −3.7±1; total lung capacity (TLC) 120±26%; residual volume (RV) 309±108%; and RV/TLC 55±13. During childhood, FVC and FEV<sub>1</sub> increased by a mean of 11%/year (95% CI 9.3% to 12.6%; p&lt;0.0001) and 9%/year (95% CI 7.7% to 10.2%; p&lt;0.0001), and the FEV<sub>1</sub>/FVC ratio decreased by 1.9%/year (95% CI 1% to 2.8; p&lt;0.001). The z score for FVC, FEV<sub>1</sub> and FEV<sub>1</sub>/FVC decreased by 0.07 z score/year (95% CI 0.1 to 0.01; p&lt;0.05), 0.09 z score/year (95% CI 0.1 to 0.05; p&lt;0.01) and 0.04 z score/year (95% CI 0.09 to 0.001; p&lt;0.02), respectively. During the follow-up period, 69% of patients required at least one hospital readmission and five required mechanical ventilation. Nine patients developed a thoracic deformity, and seven whose bronchiectasis did not respond to clinical treatment underwent a lobectomy. <h3>Conclusions</h3> After a 12 year follow-up period, pulmonary function remained severely impaired, showing an obstructive pattern with air trapping that slowly improved during childhood. An unequal growth of lung parenchyma over the airways suggests dysinaptic growth. Patients required frequent readmission due to recurrent respiratory infections, and hypoxaemia improved slowly over time.
Inter-assay variability in the degree of platelet inhibition following GPIIb/IIIa receptor blockade in patients undergoing coronary intervention: a comparison of three different point-of-care assays
Authors: Daniel Soffer, William W. O'Neill, Kishore J. Harjai, Simon R. Dixon, Judith Boura, Robert D. Safian, Cindy L. Grines, Issam Moussa, Gary S. Roubin, Jeffrey W. Moses
Journal: Journal of the American College of Cardiology (2002)