tbuckley/cabot-search huggingface dataset:
Impaired intestinal molecular tightness in the mucosa of irritable bowel syndrome: what are the mediators?
Authors: M. Vicario, C. Alonso, J. Santos
Journal: Gut (2009)

Being the most prevalent gastrointestinal disorder, the irritable bowel syndrome (IBS) remains as major challenge for the biomedical community due to its unclear pathophysiology, the lack of effective therapeutic options, and its negative impact on a sufferer’s quality of life. Not yet identified as a cause or a consequence, abnormal intestinal permeability characterises chronic inflammatory disorders such as coeliac disease, inflammatory bowel disease, multiple sclerosis or diabetes, in which this phenomenon has been connected to the disappearance of key structural proteins of the intestinal epithelial barrier.1 Oddly enough, although altered intestinal permeability has also been reported in patients with IBS, and the grade of barrier defect related to the onset of symptoms,2 the mechanism responsible and the mediators are ignored. It is therefore of great importance to perform studies to unravel the underlying events, and ultimately design and develop improved diagnostic and therapeutic tools. In this respect, the study by Piche and colleague3 in this issue of Gut ( see page 195 ) represents a significant contribution to this endeavour.

IBS is still quoted as an archetype for functional digestive disorders. The truth is that this time-honoured truism should be revised based on mounting evidence for a low-grade inflammatory process as a plausible contributor to IBS manifestations, at least in some subtypes.4 Mucosal inflammation has been described throughout the gut, from the jejunum to the rectum, and includes the proliferation of various lamina propria immune cells, mostly CD3+/CD8+/CD25+ lymphocytes, tryptase/CD117+ mast cells, and endocrine cells.5 This cellular infiltrate is commonly paralleled by the subtle increase of para-inflammatory molecules or their genes (interleukin 1β (IL1β), tumour necrosis factor α (TNFα), IL6, IL6r, transforming growth factor β (TGFβ), IL10, tryptase) in the mucosa, luminal content and peripheral circulation as well.6 7 Whether …
The Risk–Benefit Profile of Commonly Used Herbal Therapies: <i>Ginkgo</i>, St. John's Wort, Ginseng, Echinacea, Saw Palmetto, and Kava
Authors: Edzard Ernst
Journal: Annals of Internal Medicine (2002)

Because use of herbal remedies is increasing, a risk–benefit profile of commonly used herbs is needed. This article provides a clinically oriented overview of the efficacy and safety of ginkgo, St. John's wort, ginseng, echinacea, saw palmetto, and kava. Wherever possible, assessments are based on systematic reviews of randomized clinical trials. Encouraging data support the efficacy of some of these popular herbal medicinal products, and the potential for doing good seems greater than that for doing harm. The published evidence suggests that ginkgo is of questionable use for memory loss and tinnitus but has some effect on dementia and intermittent claudication. St. John's wort is efficacious for mild to moderate depression, but serious concerns exist about its interactions with several conventional drugs. Well-conducted clinical trials do not support the efficacy of ginseng to treat any condition. Echinacea may be helpful in the treatment or prevention of upper respiratory tract infections, but trial data are not fully convincing. Saw palmetto has been shown in short-term trials to be efficacious in reducing the symptoms of benign prostatic hyperplasia. Kava is an efficacious short-term treatment for anxiety. None of these herbal medicines is free of adverse effects. Because the evidence is incomplete, risk–benefit assessments are not completely reliable, and much knowledge is still lacking.
IL-2–induced CD4+ T-cell expansion in HIV-infected patients is associated with long-term decreases in T-cell proliferation
Authors: Irini Sereti, Kara B. Anthony, Hector Martinez-Wilson, Richard Lempicki, Joseph Adelsberger, Julia A. Metcalf, Claire W. Hallahan, Dean Follmann, Richard T. Davey, Joseph A. Kovacs, H. Clifford Lane
Journal: Blood (2004)
The script concordance test in paediatric rheumatology (SCT-PR): a novel tool to assess clinical reasoning competence
Authors: M J Cidon
Journal: Annals of the Rheumatic Diseases (2010)

ACGME competency based outcome standards mandate use of multiple assessment methods to evaluate resident progress. Currently, there are no validated tools to evaluate clinical reasoning in paediatric rheumatology.

To describe the development of the first clinical reasoning tool in paediatric rheumatology for residents based on script concordance methodology.

Content domain of the SCT-PR is …
Investigation of gene expression correlating with centrosome amplification in development and progression of breast cancer
Authors: Wilma Lingle, Stephen Iturria, Patrick Roche, Fergus Couch, James Ingle, Youzhen Wang, Kathleen Steinmann, Yong Yao Xu, Maureen Mertens, Yueying Cao, James Lillie
Journal: Nature Genetics (2001)
Circulating Endothelial Progenitor Cells in Preterm Infants with Bronchopulmonary Dysplasia
Authors: Alessandro Borghesi, Margherita Massa, Rita Campanelli, Lina Bollani, Chryssoula Tzialla, Tiziana A Figar, Giovanna Ferrari, Elisa Bonetti, Gaia Chiesa, Annalisa de Silvestri, Arsenio Spinillo, Vittorio Rosti, Mauro Stronati
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

The new form of bronchopulmonary dysplasia (BPD) is characterized by lung immaturity with disrupted alveolar and capillary development after extremely premature birth, but the mechanism of impaired lung vascular formation is still not completely understood.We tested the hypothesis that reduced numbers of circulating endothelial progenitor cells at birth are associated with the development of BPD.We studied ninety-eight preterm infants with gestational age of less than 32 weeks or a birth weight less than 1,500 g. Endothelial colony-forming cells (ECFCs) were assessed by clonogenic analysis in infants for whom cord blood was available. The proportion of circulating endothelial and hematopoietic cells was measured by flow cytometry at birth, at 48 hours, and at 7 days of life.ECFCs in cord blood were lower in infants who later developed BPD (median [range]: 0.00 [0.00-0.48] vs. 2.00 [0.00-21.87]; P = 0.002). ECFCs decreased with decreasing gestational age (r = 0.41; P = 0.02), but even at extremely low gestational ages, infants with higher numbers of ECFCs were protected from BPD. The endothelial and hematopoietic cell subsets studied by flow cytometry were comparable in infants with and without BPD and rapidly decreased after birth.ECFCs are low at extremely low gestational ages and increase during gestation; extremely preterm infants who display lower numbers at birth have an increased risk of developing BPD. Our findings suggest that decreased ECFCs following extremely preterm birth may be associated with the risk for developing lung vascular immaturity characteristic of new BPD.
A systematic review of predictors and moderators of response to psychological therapies in OCD: Do we have enough empirical evidence to target treatment?
Authors: Jasmin Knopp, Sarah Knowles, Penny Bee, Karina Lovell, Peter Bower
Journal: Clinical Psychology Review (2013)

Obsessive-compulsive disorder (OCD) is a disabling mental health condition. Despite effective psychological treatments for OCD, a significant percentage of patients fail to experience lasting benefit. Factors underlying variable treatment response are poorly understood. Moderators of outcome can help understand "for whom" and "under what circumstances" an intervention works best and thus improve service effectiveness. This paper synthesizes the evidence on predictors and moderators and assesses the quality of reporting of related analyses in psychological therapies for adults with OCD. Trials were identified through electronic searches (CENTRAL, MEDLINE, PsycINFO, EMBASE), key author, and reference list searches of relevant systematic reviews. Fifty five percent (38/69) of relevant trials reported baseline factors associated with outcome; these encompassed clinical, demographic, interpersonal, OCD symptom-specific, psychological/psychosocial, and treatment-specific variables. Predictors were commonly assessed via a validated pre-randomization measure, though few trials adopted best practice by stating a priori hypotheses or conducting a test of interaction. Potential associations emerged between worse OCD treatment outcome and the following factors: hoarding pathology, increased anxiety and OCD symptom severity, certain OCD symptom subtypes, unemployment, and being single/not married. However, the applied utility of these analyses is currently limited by methodological weaknesses.
Altered expression of angiogenesis and lymphangiogenesis markers in the uninvolved skin of plaque-type psoriasis
Authors: A. Henno, S. Blacher, C. Lambert, A. Colige, L. Seidel, A. Noël, C. Lapière, M. de la Brassinne, B.V. Nusgens
Journal: British Journal of Dermatology (2009)

Vascular alterations are significant events in the pathomechanism of psoriasis. A disorder in the mechanisms regulating skin angiogenesis and lymphangiogenesis could participate in the pathogenesis of the disease.To quantify differences in the expression of angiogenesis and lymphangiogenesis growth factors, receptors, coreceptors as well as their antagonists in the uninvolved skin of patients with psoriasis compared with the skin of nonpsoriatic volunteers.Skin biopsies were collected from the involved skin of 13 patients with untreated plaque-type psoriasis, from their nonlesional skin at distance from the lesions and from the skin of 16 healthy volunteers. The mRNA steady-state level of keratins 10, 14 and 16, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), vimentin, collagen I and IV, proliferating cell nuclear antigen, the various splice variants of vascular endothelial growth factor, VEGF-A, VEGF-C and VEGF-D, their receptors VEGFR1, VEGFR2 and VEGFR3, neuropilin (NRP)-1 and its soluble forms, NRP-2, semaphorin 3A and prox-1, was measured by reverse transcription-polymerase chain reaction. Immunohistochemistry was performed for Ki-67, von Willebrand factor and D2-40. Blood and lymphatic vessel density, area and distance from epidermis were estimated by morphological analysis coupled to an original computer-assisted method of quantification.Skin from healthy volunteers and nonlesional skin from patients with psoriasis displayed similar histological, morphometric and proliferative features. However, a significant overexpression of VEGFR3, the VEGF-A isoform VEGF121, soluble 12 NRP-1 and GAPDH was observed in the nonlesional psoriatic skin as compared with that of normal volunteers.These data point to significant differences in the blood and lymphatic vascular transcriptome between the clinically normal-appearing skin of patients with psoriasis and the skin of volunteers without psoriasis.
Association of genetic variations in neurokinin-2 receptor with enhanced cough sensitivity to capsaicin in chronic cough
Authors: H-K Park, S-Y Oh, T-B Kim, J-W Bahn, E-S Shin, J-E Lee, H-B Oh, Y-K Kim, T Park, S-H Cho, K-U Min, Y-Y Kim
Journal: Thorax (2006)

<b>Background:</b> Chronic cough is associated with increased sensitivity to inhaled capsaicin, and both tachykinins and their receptors play important roles in the cough reflex. However, associations between polymorphisms of the tachykinin receptor genes and cough sensitivity in patients with non-productive chronic cough have not been reported. <b>Methods:</b> Direct sequencing was used to identify single nucleotide polymorphisms (SNPs) in the genes for the neurokinin-1 and neurokinin-2 receptors (NK-1R and NK-2R, respectively). Informative non-synonymous SNPs were scored using the single base extension method for 312 patients with chronic cough and for 100 age matched healthy controls. The cough response to capsaicin was recorded for 312 patients with chronic cough, and the potential genetic association between cough sensitivity to capsaicin and the NK-1R and NK-2R genotypes was evaluated. <b>Results:</b> Two informative SNPs were identified in <i>NK-2R</i> (Gly231Glu and Arg375His), whereas no informative SNP was found in <i>NK-1R</i>. After adjusting for atopy, sex, age, and smoking, the prevalence of enhanced cough sensitivity to capsaicin was higher in the chronic cough patients with the 231Glu allele (p = 0.004; OR 1.69 (95% CI 1.18 to 2.42)) and the 231Glu_375Arg haplotype (p = 0.003; OR 1.71 (95% CI 1.20 to 2.24)]. Moreover, the lowest capsaicin concentration to cause five consecutive coughs (C5) was significantly lower in patients with 231Glu (mean (SD) 44.1 (53.2) <i>v</i> 60.9 (55.8) μM/l, p = 0.04) and those with 231Glu_375Arg (43.2 (52.7) <i>v</i> 69.6 (52.0) μM/l, p = 0.03). <b>Conclusions:</b> The results of this study suggest that <i>NK-2R</i> gene polymorphisms are involved in the enhanced cough sensitivity to capsaicin of patients with chronic cough.
National institute offers NHS trusts £64m for collaborative research projects
Authors: Adrian O’Dowd
Journal: BMJ (2008)

The government has announced funding of £64m (€80m; $128m) for different research projects around England that may lead to the rapid introduction of new and effective treatments for a wide range of medical conditions.

Seven collaborations between NHS trusts and universities are to receive the funds from the National Institute for Health Research (NIHR) over five years.

The minister for public health, Dawn Primarolo, announced the seven successful bids for the research money this week, awarded under the name of NIHR Collaborations for Health Research and Care. Each collaboration has to match that central funding with its …
Trauma on the Isle of Man.
Authors: R G Hackney, G Varley, D Stevens, A Green
Journal: British Journal of Sports Medicine (1993)

The Isle of Man Tourist Trophy motorcycle races remain one of the most popular venues for motorcycle races. This is despite the reduced status of the event. The reason for the loss of world championship and formula one status is the nature of the road racing circuit itself. The twisting narrow roads are only closed to the public at certain times during the practice and race weeks. Motorcycling visitors to the event attempt to emulate their heroes on machines capable of high speeds. Casualties from both visitors and racers are dealt with efficiently by an expanded medical service. This includes the use of an aeromedical evacuation helicopter. Casualties from the visitors exceeded those from the racers themselves during the period reported.
Surface antigens of Leishmania donovani promastigotes.
Authors: D A Lepay, N Nogueira, Z Cohn
Journal: The Journal of Experimental Medicine (1983)

Surface antigen profiles of Leishmania donovani promastigote isolates have been studied. Surface patterns of Brazilian and African isolates display remarkable similarities and are extremely simple, consisting of three major peptides of 65,000, 25,000, and 23,000 mol wt. Surface iodination and biosynthetic labeling coupled to immunoprecipitation techniques revealed that a single major determinant of 65,000 mol wt is recognized in all strains by sera from kala-azar patients from both Brazil and Africa. This major determinant is not brought down by sera from normal individuals and shows no significant cross-reactivity with sera from Chagas' disease, leprosy, or syphilis patients. Binding to concanavalin A suggests a glycoprotein nature for this antigen. Sera from patients with cutaneous leishmaniasis (L. braziliensis) also recognized the same 65,000-mol wt determinant, although to a lesser extent. The possibility that this major surface antigen is shared, with minor differences, not only by L. donovani strains but between Leishmania species in general is suggested.
Aromatase inhibition alters the mechanical properties of non small-cell lung cancer cells affecting cell movement
Authors: E. Giannopoulou, I. Kritikou, D. Metsiou, G. Athanassiou, H.P. Kalofonos
Journal: European Respiratory Journal (2013)

Introduction  A critical step during invasion and metastasis is the ability of cancer cells to move. Cell stiffness is important in their transmigration through a basement membrane [1]. The correlation between cancer cell mechanical properties and movement has not been determined. Estrogen signaling is critical in the progression of malignancies expressing estrogen receptors and may also be involved in the pathogenesis of NSCLC [2]. Aromatase catalyses the final step in estrogen synthesis locally in tissues. Exemestane (EXE) is an aromatase inhibitor.  Methods  NSCLC cell lines H23 and A549 were used. Cell movement was determined with boyden chamber assay. With a micropipette method we applied negative pressure on individual cells through the pipette and we measured the cell stiffness and the elastic shear modulus (ESM) prior and after their treatment with EXE [3].  Results  ESM of the untreated A549 and H23 was 480.0 ± 237.23Pa and 159.10 ± 62.10Pa, respectively. 24 hours after cell treatment with EXE, ESM was 269.87 ± 43.0Pa and 125.0 ± 65.05Pa, respectively. Cell treatment with EXE reduced H23 (36.7% ± 12.4) but did not affect A549 movement.  Discussion  Both cell lines had different ESM and reduced their stiffness after treatment with EXE. The cells with the higher ESM were resistant to EXE regarding movement implying that lower stiffness might render cells more sensitive to movement inhibition. However, the reduced ESM by EXE in A549 was not associated with alterations in cell movement. The project is ongoing.  References  1.V.Swaminathan et al,CancerRes71,1-6,2011.  2.L.P.Stabile et al,CancerRes 65,1459-70,2005  3.C.T.Lim et al, J Biomech, 39:195-216, 2006.
High-Density Lipoprotein-Cholesterol in Survivors of Myocardial Infarction
Authors: D. Willem Erkelens
Journal: JAMA (1979)

High-density lipoprotein-cholesterol (HDL-Chol) levels were higher in a group of 83 myocardial infarction survivors who participated in a moderate, graded exercise program (47 +/- 13 mg/dL) than in 103 nonexercising coronary heart disease patients (40 +/- 11 mg/dL, P less than .001), reaching levels undistinguishable from those of 181 population controls (44 +/- 12 mg/dL). The level of exercise and concentration of HDL-Chol were correlated (r = .24, P less than .05). In 18 patients studied longitudinally, HDL-Chol levels increased from 35 +/- 8 mg/dL before participation to 40 mg/dL (P less than .001) after one week, and remained at that level for six months. Concurrently, functional aerobic impairment decreased from 31% +/- 29% to 11% (P less than .01). These observations suggest that participation in a moderate exercise program increases HDL-Chol levels in myocardial infarction survivors and may contribute to lowering the risk for subsequent infarction.
T cell receptor-mediated selection of functional rat CD8 T cells from defined immature thymocyte precursors in short-term suspension culture.
Authors: T Hünig, R Mitnacht
Journal: The Journal of Experimental Medicine (1991)

Recent results have indicated that positive and negative repertoire selection act on the major population of CD4,8 double-positive (DP) thymocytes that express 5-10-fold less T cell receptor (TCR) than mature T cells (i.e., they are TCRlow). Since DP cells obtained ex vivo are heterogeneous with regard to their stage within thymic selection, a homogeneous population of virgin DP cells suitable for selection studies was generated in vitro from their immediate precursors, the CD8 single-positive (SP) immature blast cells. To mimic TCR-mediated selection signals, these virgin DP cells were then cultured for another 2 d in the presence of immobilized anti-TCR monoclonal antibodies with or without interleukin 2 (IL-2). Daily monitoring of recovery and phenotype showed that without TCR stimulation, the cells remained DP and became small, TCRlow cells that were lost with a half-life of 1 d, regardless of the presence of IL-2. TCR stimulation resulted in rapid downregulation of CD4 and CD8, maintenance of a larger cell size, and induction of the CD53 antigen that marks mature and CD4,8 double-negative rat thymocytes. In the absence of IL-2, viability decreased as rapidly as without TCR stimulation. Addition of IL-2 rescued TCR-stimulated virgin DP cells and prevented CD8 downregulation, so that 50-80% of input DP cells were recovered after 2 d as CD4-8+53+ cells. After release from modulation, these in vitro generated CD8 SP cells quantitatively upregulated the TCR to the TCRhigh phenotype and were readily induced to proliferate and exhibit cytotoxic T lymphocyte (CTL) activity in a polyclonal readout. Evidence is presented implicating an IL-2 receptor (IL-2R) not containing the p55 chain (i.e., most likely the p70 intermediate affinity IL-2R) in the TCR plus IL-2-driven in vitro differentiation of virgin DP cells towards the mature CD8 SP phenotype.
Single-channel endoscopic closure of large endoscopy-related perforations
Authors: Chun-Yan Zeng, Guo-Hua Li, Yin Zhu, Xiao-Jiang Zhou, Nong-Hua Lv, You-Xiang Chen
Journal: Endoscopy (2015)

Gastrointestinal endoscopy procedures, such as endoscopic retrograde cholangiopancreatography (ERCP), endoscopic submucosal dissection (ESD), and colonoscopy are widely used for the diagnosis or treatment of digestive diseases. Perforation is a rare but potentially lethal complication. Large perforations usually require immediate endoscopic or surgical repair. Endoscopic closure using a nylon loop pouch suture is usually performed with a double-channel endoscope. This paper describes the endoscopic closure of large procedure-related perforations using a single-channel endoscope.A total of 10 patients with large perforations (2.5 - 4.0 cm), which occurred during ERCP, ESD, or colonoscopy, were treated using the single-channel endoscope technique.All perforations were successfully closed using a nylon loop pouch suture through the single-channel endoscope. No surgery or further endoscopic intervention was required.Nylon loop pouch suture through a single-channel endoscope was easy to perform and was feasible for the closure of large gastrointestinal perforations.