tbuckley/cabot-search huggingface dataset:
Involvement of purine metabolites in dsRNA-induced IL-33 expression in human bronchial smooth muscle cells
Authors: Jenny Calvén, Hamid Akbarshahi, Mandy Menzel, Marco Idzko, Lena Uller
Journal: European Respiratory Journal (2014)

Rationale: Rhinovirus (RV) infections are main triggers of asthma exacerbations and along with tissue damage cause release of exogenous and endogenous danger signals. Considered such an alarmin, IL-33 has emerged as a potent inducer of Th2-type immunity and is implicated in asthma pathogenesis. Bronchial smooth muscle cells (BSMC) from severe asthmatics have previously been shown to overexpress IL-33. Here, we aimed to explore the effect of viral stimuli and purine metabolites on IL-33 in BSMC.

Methods: Primary human BSMC from three healthy donors were infected with RV1B (0.1-0.5MOI) or stimulated with the RV replication intermediate dsRNA (0.1-10μg/ml), ATP-γ-S or adenosine (10-500μM) for 3 or 24h. The NF-κB inhibitor PS1145 (1-10μM) or the purinergic receptor antagonist suramin (10-100μM) were added 1h prior to stimulation. Samples were analyzed by RT-qPCR, western blot and ELISA.

Results: IL-33 expression was dose-dependently increased in BSMC after 24h RV1B infection (p<0.01) and secreted IL-33 was detected in supernatants from RV-infected cells. dsRNA upregulated both mRNA and protein levels of IL-33 at 24h (p<0.001), but did not cause IL-33 release. IL-33 mRNA was also increased at 3 and 24h by ATP-γ-S and adenosine (p<0.01). Suramin, but not PS1145, abolished IL-33 expression induced by both purine metabolites and dsRNA (p<0.01).

Conclusions: Viral stimuli and purine metabolites triggered human BSMC expression of IL-33, implicating airway smooth muscle as a potential source of IL-33 in virus-infected or inflamed airways. The inhibitory effect of suramin on IL-33 responses also suggests a role for purine metabolites in mediating dsRNA-inducible IL-33 expression.
YAP promotes proliferation, chemoresistance, and angiogenesis in human cholangiocarcinoma through TEAD transcription factors
Authors: Patricia Marti, Claudia Stein, Tanja Blumer, Yann Abraham, Michael T. Dill, Monika Pikiolek, Vanessa Orsini, Giorgia Jurisic, Philippe Megel, Zuzanna Makowska, Claudia Agarinis, Luigi Tornillo, Tewis Bouwmeester, Heinz Ruffner, Andreas Bauer, Christian N. Parker, Tobias Schmelzle, Luigi M. Terracciano, Markus H. Heim, Jan S. Tchorz
Journal: Hepatology (2015)

The Yes‐associated protein (YAP)/Hippo pathway has been implicated in tissue development, regeneration, and tumorigenesis. However, its role in cholangiocarcinoma (CC) is not established. We show that YAP activation is a common feature in CC patient biopsies and human CC cell lines. Using microarray expression profiling of CC cells with overexpressed or down‐regulated YAP, we show that YAP regulates genes involved in proliferation, apoptosis, and angiogenesis. YAP activity promotes CC growth in vitro and in vivo by functionally interacting with TEAD transcription factors (TEADs). YAP activity together with TEADs prevents apoptosis induced by cytotoxic drugs, whereas YAP knockdown sensitizes CC cells to drug‐induced apoptosis. We further show that the proangiogenic microfibrillar‐associated protein 5 (MFAP5) is a direct transcriptional target of YAP/TEAD in CC cells and that secreted MFAP5 promotes tube formation of human microvascular endothelial cells. High YAP activity in human CC xenografts and clinical samples correlates with increased MFAP5 expression and CD31 + vasculature. Conclusions: These findings establish YAP as a key regulator of proliferation and antiapoptotic mechanisms in CC and provide first evidence that YAP promotes angiogenesis by regulating the expression of secreted proangiogenic proteins. (H epatology 2015;62:1497–1510)
The kinase GLK controls autoimmunity and NF-κB signaling by activating the kinase PKC-θ in T cells
Authors: Huai Chia Chuang, Joung Liang Lan, Der Yuan Chen, Chia Yu Yang, Yi Ming Chen, Ju Pi Li, Ching Yu Huang, Pao En Liu, Xiaohong Wang, Tse Hua Tan
Journal: Nature Immunology (2011)
Femoral Neck Fracture Fixation: Rigidity of Five Techniques Compared
Authors: A C Mackechnie-Jarvis
Journal: Journal of the Royal Society of Medicine (1983)

Artificial cadaveric femoral neck fractures were internally fixed with five different devices and subjected to cyclical loading of 0–1.0 kilonewtons (approximately one body weight) whilst in an anatomical position. Displacement of the proximal fragment was detected by a transducer and charted. Bone strength was assessed by a preliminary control loading phase on the intact bone. Efficiency of each fracture fixator could then be directly compared by the relative movement in each case. Five specimens each were tested with Moore's Pins, Trifin Nail, Garden Screws and a sliding screw-plate (OEC Ltd). By the criteria of the experiment, which put a severe shearing load on the implant, none of these devices reliably bore the representative body weight. An extended barrel-plate, which supported the sliding screw almost up to the fracture line, was then made. This device, employing some of Charnley's concepts, tolerated body weight in four cases out of five.
Murine Colon Adenocarcinoma: Syngeneic Orthotopic Transplantation and Subsequent Hepatic Metastases2
Authors: M. H. Tan, E. D. Holyoke, M. H. Goldrosen
Journal: JNCI Journal of the National Cancer Institute (1977)

Syngeneic murine colon adenocarcinoma (MCA-38) cells were transplanted in the submucosa of distal colon, proximal colon, cecum, ileum, jejunum, and duodenum of male C57BL/6 mice, with local lymphoid follicles used as points of entry. The tumor grew best at the cecum and led to liver and mesenteric lymph node metastases in 8 and 9 weeks, respectively, after transplantation. Histologically, a local inflammatory reaction involving polymorphonuclear leukocytes was observed within 48–72 hours following transplantation; after this time, the microscopic tumor foci began to grow progressively. Mononuclear lymphoid cells of the gut-associated lymphoid tissue did not infiltrate the progressively growing tumor; however, polymor-phonuclear leukocytes were constantly observed at the tumor periphery in the lamina propria. The studies indicated that orthotopic transplantation as a model system can provide a means of examining the role of the local immune response as a focus of host resistance and as a factor in metastatic tumor spread. The findings also suggested the usefulness of this model in immunotherapeutic and chemotherapeutic studies of secondary hepatic disease.
Paying for the NHS
Authors: E. Mossialos
Journal: BMJ (2000)

News p 205

Criticisms last week of government policy on the NHS by someone who is not only a senior doctor but also a Labour peer and media personality inevitably attracted widespread attention. In a week in which the apparent failure of the NHS to cope with an influenza epidemic had barely been out of the headlines, Lord Robert Winston, a fertility specialist, argued that the NHS is in a worse state than under the previous government and that a new system of health—care financing is needed if it is to perform at a level comparable to that seen in the rest of western Europe.1 Although media coverage of his interview soon moved to whether his retraction of the comments the following day had been entirely voluntary,2 his call for a review of NHS funding echoes that of many others.3 So how does the NHS compare with the rest of Europe and, more importantly, what should it be spending?

Turning first to inputs, the United Kingdom spends 6.7% of its gross domestic product on health care. This is less than any other member of the European Union except Ireland and well behind Germany (10.7%), France (9.6%), and Sweden (8.6%). …
Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese Nationwide Colorectal Cancer Screening Program
Authors: Sherry Yueh-Hsia Chiu, Shu-Ling Chuang, Sam Li-Sheng Chen, Amy Ming-Fang Yen, Jean Ching-Yuan Fann, Dun-Cheng Chang, Yi-Chia Lee, Ming-Shiang Wu, Chu-Kuang Chou, Wen-Feng Hsu, Shu-Ti Chiou, Han-Mo Chiu
Journal: Gut (2015)

<h3>Objectives</h3> Interval colorectal cancer (CRC) after colonoscopy may affect effectiveness and cost-effectiveness of screening programmes. We aimed to investigate whether and how faecal haemoglobin concentration (FHbC) of faecal immunochemical testing (FIT) affected the risk prediction of interval cancer (IC) caused by inadequate colonoscopy quality in a FIT-based population screening programme. <h3>Design</h3> From 2004 to 2009, 29 969 subjects underwent complete colonoscopy after positive FIT in the Taiwanese Nationwide CRC Screening Program. The IC rate was traced until the end of 2012. The incidence of IC was calculated in relation to patient characteristics, endoscopy-related factors (such adenoma detection rate (ADR)) and FHbC. Poisson regression analysis was performed to assess the potential risk factors for colonoscopy IC. <h3>Results</h3> One hundred and sixty-two ICs developed after an index colonoscopy and the estimated incidence was 1.14 per 1000 person-years of observation for the entire cohort. Increased risk of IC was most remarkable in the uptake of colonoscopy in settings with ADR lower than 15% (adjusted relative risk (aRR)=3.09, 95% CI 1.55 to 6.18) and then higher FHbC (μg Hb/g faeces) (100–149: aRR=2.55, 95% CI 1.52 to 4.29, ≥150: aRR=2.74, 95% CI 1.84 to 4.09) with adjustment for older age and colorectal neoplasm detected at baseline colonoscopy. Similar findings were observed for subjects with negative index colonoscopy. <h3>Conclusions</h3> Colonoscopy ICs arising from FIT-based population screening programmes were mainly influenced by inadequate colonoscopy quality and independently predicted by FHbC that is associated with a priori chance of advanced neoplasm. This finding is helpful for future modification of screening logistics based on FHbC.
Pediatric Venous Thromboembolism—Like Adult Clots, Only Smaller
Authors: Matthew J. Martin
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Poor correlation with Jarman index may be due to changes in deprivation since 1981
Authors: R S James
Journal: BMJ (1995)

To validate the index the authors correlate it with the level of prescribing of certain drugs, hormone replacement therapy, and tamoxifen, which they regard as indicators of the social class composition of the practice population.This procedure involves unsupported assumptions, particularly in relation to hormone replacement therapy.An underlying problem with the authors' use of PACT data is the implicit assumption that prescribing is a standardised procedure in which general practitioners diagnose and treat disease systematically.The literature does not support this assumption; indeed, it shows great variation among doctors, much of which can be explained only by personal idiosyncrasy.2It seems dangerous to base an objective measure of deprivation on such subjective behaviour.Although the correlation between exempted precriptions and deprivation at health authority level is high, the measure proposed by Lloyd and colleagues is intended for practice based research rather than epidemiological research on larger populations.For example, the authors suggest that it would be useful in researching topics such as prescribing.Given that PACT data are Britain's main source of prescribing data and also provide the data for the authors' deprivation index, however, this suggestion seems tautologous.Further efforts are needed to develop a reliable and valid measure of deprivation at the practice level.
Relationships of body size with breast cancer.
Authors: L A Kalish
Journal: Journal of Clinical Oncology (1984)

Three measures of body size (weight, height, and obesity) were compared with other patient characteristics in 852 operable node-positive breast cancer patients (age, 25-74 years) newly diagnosed in the United States. Weight and obesity were significantly associated with number of positive nodes. In postmenopausal women, weight and obesity were weakly associated with estrogen receptors. Observed weight and height distributions were compared with national averages and found to be highly aberrant in older women. There was an excess of tall woman (greater than or equal to 66 inches) among the study group in all age groups. An excess of heavy women (greater than or equal to 140 pounds) among the study group was observed only in the 55-74 years age group.
Deformation-Induced Injury of Alveolar Epithelial Cells
Authors: DANIEL J. TSCHUMPERLIN, JANE OSWARI, AND SUSAN S. MARGULIES
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

The onset of ventilator-induced lung injury (VILI) is linked to a number of possible mechanisms. To isolate the possible role of alveolar epithelial deformation in the development of VILI, we have developed an in vitro system in which changes in alveolar epithelial cell viability can be measured after exposure to tightly controlled and physiologically relevant deformations. We report here a study of the relative effect of deformation frequency, duration, and amplitude on cell viability. We exposed rat primary alveolar epithelial cells to a variety of biaxial stretch protocols, and assessed deformation-induced cell injury quantitatively, using a fluorescent cell viability assay. Deformation-induced injury was found to depend on repetitive stretching, with cyclic deformations significantly more damaging than tonically held deformations. In cyclically deformed cells, injury occurred rapidly, with the majority of cell death occurring during the first 5 min of deformation. Deformation-induced injury was increased with the frequency of sustained cyclic deformations, but was not dependent on the deformation rate during a single stretch. Reducing the amplitude of cell deformations by superimposing small cyclic deformations on a tonic deformation significantly reduced cell death as compared with large-amplitude deformations with the same peak deformation.
Impact of p16 status on the results of the phase III cetuximab (cet)/radiotherapy (RT).
Authors: David Ira Rosenthal, Paul M. Harari, Jordi Giralt, Diana Bell, David Raben, Joyce Liu, Jeltje Schulten, K. Kian Ang, James A. Bonner
Journal: Journal of Clinical Oncology (2014)

6001 Background: This is a retrospective analysis of the phase III IMCL-9815 trial assessing the role of HPV status in LASCCHN patients (pts) receiving RT+cet or RT by measuring p16 status. Methods: The intent-to-treat (ITT) population (424 pts) was randomized to RT+cet or RT. p16INK4A status was determined by immunohistochemistry. Results: 312/424 (74%) of the ITT pts were p16 evaluable. Baseline characteristics in the ITT and p16 evaluable pts were similar. In both p16+ and p16- pts, the addition of cet to RT improved locoregional control (LRC), overall survival (OS), and progression-free survival (PFS) (Table). Univariate analyses showed a more pronounced treatment effect of RT+cet vs RT in p16+ pts across all endpoints in both the ITT and the oropharyngeal (OPC) populations; however, interaction tests for LRC, OS and PFS (ITT and OPC) did not demonstrate a significant interaction between p16 status and treatment effect. There were no new safety findings. Conclusions: p16 tumor status is strongly prognostic for pts with LASCCHN. Although the number of pts is small, these data showed that the pts benefit more from RT+cet compared with RT alone regardless of p16 status. HPV data are to be presented at the meeting. Observations in the OPC population are being evaluated in the RTOG 1016 trial. Clinical trial information: NCT00004227. Treatment effect. p16- p16+ RT+cet RT HR (95% CI) p value RT+cet RT HR (95% CI) p value Interaction test ITT No. pts 109 120 44 39 LRC median (mo) 12.9 11.3 0.78 (0.57–1.05) 0.101 NE NE 0.35 (0.13–0.90) 0.023 0.098 OS median (mo) 24.4 20.6 0.90 (0.66–1.22) 0.492 NE NE 0.45 (0.19–1.06) 0.062 0.134 PFS median (mo) 12.3 9.2 0.76 (0.57–1.03) 0.078 NE NE 0.47 (0.21–1.08) 0.070 0.252 OPC No. pts 44 63 41 34 LRC median (mo) 12.3 11.9 0.79 (0.50–1.26) 0.319 NE NE 0.31 (0.11–0.88) 0.020 0.087 OS median (mo) 26.8 20.6 0.92 (0.58–1.46) 0.717 NE NE 0.38 (0.15–0.94) 0.030 0.085 PFS median (mo) 11.7 10.1 0.77 (0.49–1.22) 0.260 NE NE 0.46 (0.19–1.10) 0.073 0.253 Abbreviations: mo: months; HR: hazard ratio; NE: median not reached.
Association Between ADHD and Obesity: A Systematic Review and Meta-Analysis
Authors: Samuele Cortese, Carlos Renato Moreira-Maia, Diane St. Fleur, Carmen Morcillo-Peñalver, Luis Augusto Rohde, Stephen V. Faraone
Journal: American Journal of Psychiatry (2015)

Objective: Impulsivity and inattention related to attention deficit hyperactivity disorder (ADHD) may increase food intake and, consequently, weight gain. However, findings on the association between obesity/overweight and ADHD are mixed. The authors conducted a meta-analysis to estimate this association. Method: A broad range of databases was searched through Aug. 31, 2014. Unpublished studies were also obtained. Study quality was rated with the Newcastle-Ottawa Scale. Random-effects models were used. Results: Forty-two studies that included a total of 728,136 individuals (48,161 ADHD subjects; 679,975 comparison subjects) were retained. A significant association between obesity and ADHD was found for both children (odds ratio=1.20, 95% CI=1.05–1.37) and adults (odds ratio=1.55, 95% CI=1.32–1.81). The pooled prevalence of obesity was increased by about 70% in adults with ADHD (28.2%, 95% CI=22.8–34.4) compared with those without ADHD (16.4%, 95% CI=13.4–19.9), and by about 40% in children with ADHD (10.3%, 95% CI=7.9–13.3) compared with those without ADHD (7.4%, 95% CI=5.4–10.1). The significant association between ADHD and obesity remained when limited to studies 1) reporting odds ratios adjusted for possible confounding factors; 2) diagnosing ADHD by direct interview; and 3) using directly measured height and weight. Gender, study setting, study country, and study quality did not moderate the association between obesity and ADHD. ADHD was also significantly associated with overweight. Individuals medicated for ADHD were not at higher risk of obesity. Conclusions: This study provides meta-analytic evidence for a significant association between ADHD and obesity/overweight. Further research should address possible underlying mechanisms and the long-term effects of ADHD treatments on weight in individuals with both ADHD and obesity.
Damage‐Associated Molecular Patterns Generated in Osteoarthritis Directly Excite Murine Nociceptive Neurons Through Toll‐like Receptor 4
Authors: Rachel E. Miller, Abdelhak Belmadani, Shingo Ishihara, Phuong B. Tran, Dongjun Ren, Richard J. Miller, Anne‐Marie Malfait
Journal: Arthritis & Rheumatology (2015)

To determine whether selected damage-associated molecular patterns (DAMPs) present in the osteoarthritic (OA) joints of mice excite nociceptors through Toll-like receptor 4 (TLR-4).The ability of S100A8 and α2 -macroglobulin to excite nociceptors was determined by measuring the release of monocyte chemoattractant protein 1 (MCP-1) by cultured dorsal root ganglion (DRG) cells as well as by measuring the intracellular calcium concentration ([Ca(2+) ]i ) in cultured DRG neurons from naive mice or from mice that had undergone surgical destabilization of the medial meniscus (DMM) 8 weeks previously. The role of TLR-4 was assessed using TLR-4(-/-) cells or a TLR-4 inhibitor. The [Ca(2+) ]i in neurons within ex vivo intact DRGs was measured in samples from Pirt-GCaMP3 mice. Neuronal expression of the Tlr4 gene was determined by in situ hybridization. DMM surgery was performed in wild-type and TLR-4(-/-) mice; mechanical allodynia was monitored, and joint damage was assessed histologically after 16 weeks.DRG neurons from both naive and DMM mice expressed Tlr4. Both S100A8 and α2 -macroglobulin stimulated release of the proalgesic chemokine MCP-1 in DRG cultures, and the neurons rapidly responded to S100A8 and α2 -macroglobulin with increased [Ca(2+) ]i . Blocking TLR-4 inhibited these effects. Neurons within intact DRGs responded to the TLR-4 agonist lipopolysaccharide. In both of the calcium-imaging assays, it was primarily the nociceptor population of neurons that responded to TLR-4 ligands. TLR-4(-/-) mice were not protected from mechanical allodynia or from joint damage associated with DMM.Our experiments suggest a role of TLR-4 signaling in the excitation of nociceptors by selected DAMPs. Further research is needed to delineate the importance of this pathway in relation to OA pain.
Adolescent parricide: a comparison with other adolescent murder
Authors: Billie F Corder, Brenda C. Ball, Thomas M. Haizlip, Robert Rollins, Ralph Beaumont
Journal: American Journal of Psychiatry (1976)

The authors examined the available data for 10 adolescents who had been charged with parricide and compared these with data for matched groups of 10 adolescents charged with murdering another relative or a close acquaintance and 10 charged with murdering a stranger. They found significant differences between parricidal adolescents and other homicidal adolescents on personality, family, social, and follow-up adjustment variables.
Changes in asthma remission or control in the last decade in Italy
Authors: Lucia Cazzoletti, Angelo Guido Corsico, Amelia Grosso, Elena Ansaldo, Vanessa Ronzoni, Bianca Tripon, Pietro Pirina, Massimiliano Bugiani, Roberto de Marco, Isa Cerveri
Journal: European Respiratory Journal (2011)

There are few information on longitudinal changes in asthma remission or control in the last decade. For this purpose, in the frame of the Italian Study on Asthma in the Young Adults, a random sample of 354 asthmatics identified between 1998 and 2000 in 6 Italian centres (Pavia, Torino, Verona, Pisa, Sassari and Sassuolo) was followed-up 10 years apart (response rate 61%). At follow-up, asthma was considered in remission if a subject did not report any asthma-like symptoms or drug use in the last 12 months. Either at baseline or follow-up, asthma was intermittent if a subject reported rare symptoms and did not use anti-inflammatory drugs in the last 3 months, persistent otherwise. Asthma was controlled if a subject on therapy reported rare symptoms in the last 3 months. Fifty-seven respondents (27%) were remittent; they were more likely to be intermittent at baseline (32/57, 56%) than non remittent subjects (53/152, 35%) (p=0.005). Among the 141 non remittent subjects with information on symptoms and drug use at both occasions, intermittent asthma increased from 33% at baseline to 46% at follow-up. Subjects with intermittent asthma at baseline were more likely to have intermittent asthma also at follow-up (29/46,63%) with respect to subjects with persistent asthma at baseline (36/95, 38%) (p=0.005). Controlled asthma increased from 37% at baseline to 42% at follow-up. In conclusion, both asthma severity and control seem to be improved over the last decade in Italy.  Supported, in part, by the Italian Medicines Agency (FARM5JYS5A).