tbuckley/cabot-search huggingface dataset:
Travel-associated sexually transmitted infections: an observational cross-sectional study of the GeoSentinel surveillance database
Authors: Alberto Matteelli, Patricia Schlagenhauf, Anna CC Carvalho, Leisa Weld, Xiaohong M Davis, Annelies Wilder-Smith, Elizabeth D Barnett, Philippe Parola, Prativa Pandey, Pauline Han, Francesco Castelli
Journal: The Lancet Infectious Diseases (2012)
A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance
Authors: Masaki Terabe, Jeremy Swann, Elena Ambrosino, Pratima Sinha, Shun Takaku, Yoshihiro Hayakawa, Dale I. Godfrey, Suzanne Ostrand-Rosenberg, Mark J. Smyth, Jay A. Berzofsky
Journal: The Journal of Experimental Medicine (2005)

The importance of immunoregulatory T cells has become increasingly apparent. Both CD4+CD25+ T cells and CD1d-restricted NKT cells have been reported to down-regulate tumor immunity in mouse tumor models. However, the relative roles of both T cell populations have rarely been clearly distinguished in the same tumor models. In addition, CD1d-restricted NKT cells have been reported to play a critical role not only in the down-regulation of tumor immunity but also in the promotion of the immunity. However, the explanation for these apparently opposite roles in different tumor models remains unclear. We show that in four mouse tumor models in which CD1d-restricted NKT cells play a role in suppression of tumor immunity, depletion of CD4+CD25+ T cells did not induce enhancement of immunosurveillance. Surprisingly, among the two subpopulations of CD1d-restricted NKT cells, Vα14Jα18+ (type I) and Vα14Jα18− (type II) NKT cells, type I NKT cells were not necessary for the immune suppression. These unexpected results may now resolve the paradox in the role of CD1d-restricted NKT cells in the regulation of tumor immunity, in that type II NKT cells may be sufficient for negative regulation, whereas protection has been found to be mediated by α-galactosylceramide–responsive type I NKT cells.
Atrial fibrillation in endurance-trained athletes: Table 1
Authors: A V Sorokin, C G S Araujo, S Zweibel, P D Thompson
Journal: British Journal of Sports Medicine (2009)

Background Endurance exercise training produces multiple cardiac adaptations including changes in electrophysiological function that may make endurance-trained athletes more vulnerable to atrial fibrillation (AF). This possible association is not recognised by many practising cardiologists and sports physicians. Consequently, we performed a literature review to examine the relationship between atrial fibrillation and endurance exercise training among athletes. PubMed was searched from January 1960 through December 2008 to identify articles examining the relationship between endurance exercise training and AF. Results Evidence suggests that athletes are at increased risk for development of AF. Possible factors increasing AF in this population include increased parasympathetic tone, reduced sympathetic tone, increased atrial size and increased inflammation. Discussion Suggested management of AF in athletes should follow similar principles to those used to manage AF in the general population.
Simulated Physician Learning Program Improves Glucose Control in Adults With Diabetes
Authors: JoAnn M. Sperl-Hillen, Patrick J. O'Connor, William A. Rush, Paul E. Johnson, Todd Gilmer, George Biltz, Stephen E. Asche, Heidi L. Ekstrom
Journal: Diabetes Care (2010)

Inexpensive and standardized methods to deliver medical education to primary care physicians (PCPs) are desirable. Our objective was to assess the impact of an individualized simulated learning intervention on diabetes care provided by PCPs.Eleven clinics with 41 consenting PCPs in a Minnesota medical group were randomized to receive or not receive the learning intervention. Each intervention PCP was assigned 12 simulated type 2 diabetes cases that took about 15 min each to complete. Cases were designed to remedy specific physician deficits found in their electronic medical record observed practice patterns. General linear mixed models that accommodated the cluster randomized study design were used to assess patient-level change from preintervention to 12-month postintervention of A1C, blood pressure, and LDL cholesterol. The relationship between the study arm and the total of intervention and patient health care costs was also analyzed.Intervention clinic patients with baseline A1C >or=7% significantly improved glycemic control at the last postintervention A1C measurement, intervention effect of -0.19% mean A1C (P = 0.034) and +6.7% in A1C <7% goal achievement (P = 0.0099). Costs trended lower, with the cost per patient -$71 (SE = 142, P = 0.63) relative to nonintervention clinic patients. The intervention did not significantly improve blood pressure or LDL control. Models adjusting for age, sex, and comorbidity showed similar results. PCPs reported high satisfaction.A brief individualized case-based simulated learning intervention for PCPs led to modest but significant glucose control improvement in adults with type 2 diabetes without increasing costs.
Relation of Cumulative Low-Level Lead Exposure to Depressive and Phobic Anxiety Symptom Scores in Middle-Age and Elderly Women
Authors: Ki-Do Eum, Susan A. Korrick, Jennifer Weuve, Olivia Okereke, Laura D. Kubzansky, Howard Hu, Marc G. Weisskopf
Journal: Environmental Health Perspectives (2012)

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation.Objective: We assessed whether bone lead—a biomarker of cumulative lead exposure—is associated with depression and anxiety symptoms among middle-age and elderly women.Methods: Participants were 617 Nurses' Health Study participants with K-shell X-ray fluorescence bone lead measures and who had completed at last one Mental Health Index 5-item scale (MHI-5) and the phobic anxiety scale of the Crown-Crisp Index (CCI) assessment at mean ± SD age of 59 ± 9 years (range, 41–83 years). With exposure expressed as tertiles of bone lead, we analyzed MHI-5 scores as a continuous variable using linear regression and estimated the odds ratio (OR) of a CCI score ≥ 4 using generalized estimating equations.Results: There were no significant associations between lead and either outcome in the full sample, but associations were found among premenopausal women and women who consistently took hormone replacement therapy (HRT) between menopause and bone lead measurement (n = 142). Compared with women in the lowest tertile of tibia lead, those in the highest scored 7.78 points worse [95% confidence interval (CI): –11.73, –3.83] on the MHI-5 (p-trend = 0.0001). The corresponding OR for CCI ≥ 4 was 2.79 (95% CI: 1.02, 7.59; p-trend = 0.05). No consistent associations were found with patella lead.Conclusions: These results provide support for an association of low-level cumulative lead exposure with increased depressive and phobic anxiety symptoms among older women who are premenopausal or who consistently take postmenopausal HRT.
Design and implementation of a multi-part, flexible protocol to assess the tolerability and pharmacodynamic effects of PUR118 in healthy subjects and COPD patients
Authors: Lorna Patrick, Alyson Connor, Stuart Mair, Joanne Collier, Molly Rosano, John Hanrahan
Journal: European Respiratory Journal (2012)

Background   PUR118, an inhaled cationic airway lining modulator (iCALM), is a simple host-targeted therapy to prevent and control respiratory exacerbations. An innovative protocol was developed to establish single and multi-dose tolerability and early pharmacodynamic/efficacy data for this therapy.   Objective   To develop and conduct a flexible clinical protocol to obtain maximum data to support the further investigation of PUR118.   Methods   Data required to progress PUR118 development were identified and structured into a 4 part dose-ranging protocol in healthy subjects (HS) and COPD patients (COPD):  1. Crossover safety and tolerability of 3 single dose levels vs. placebo (12 HS)  2. 3 ascending dose 14-day safety and tolerability vs placebo (24 HS)  3. Parallel 3 dose level multi-dose safety and tolerability plus exploratory assessment of inflammatory biomarkers (sputum, serum, exhalation) in COPD  4. Impact of ascending of single dose vs. no treatment on mucociliary clearance velocity by gamma scintigraphy  The design was flexible to allow dose escalation or de-escalation. Selection of exploratory biomarkers was adaptive and not pre-determined in the protocol.   Results   A highly-flexible 4 part protocol was designed, submitted to and approved by the MHRA and EC in 27 days. Parts 1 and 2 in HS are complete, Parts 3 and 4 are ongoing. Preliminary results show PUR118 is well tolerated in HS and subjects with COPD.   Conclusions   This multi-part dose- ranging protocol, developed and implemented in the UK, demonstrates its regulatory framework embraces innovative, highly flexible, multi-part trials in early clinical development strategies.
A phase Ib, open-label study to assess the safety of continuous oral treatment with afatinib in combination with two chemotherapy regimens: cisplatin plus paclitaxel and cisplatin plus 5-fluorouracil, in patients with advanced solid tumors
Authors: J.B. Vermorken, S. Rottey, E. Ehrnrooth, K. Pelling, A. Lahogue, S. Wind, J.-P. Machiels
Journal: Annals of Oncology (2013)
Tailoring the Pharmacokinetics and Positron Emission Tomography Imaging Properties of Anti–Carcinoembryonic Antigen Single-Chain Fv-Fc Antibody Fragments
Authors: Vania Kenanova, Tove Olafsen, Desiree M. Crow, Gobalakrishnan Sundaresan, Murugesan Subbarayan, Nora H. Carter, David N. Ikle, Paul J. Yazaki, Arion F. Chatziioannou, Sanjiv S. Gambhir, Lawrence E. Williams, John E. Shively, David Colcher, Andrew A. Raubitschek, Anna M. Wu
Journal: Cancer Research (2005)

Abstract Antibody fragments are recognized as promising vehicles for delivery of imaging and therapeutic agents to tumor sites in vivo. The serum persistence of IgG1 and fragments with intact Fc region is controlled by the protective neonatal Fc receptor (FcRn) receptor. To modulate the half-life of engineered antibodies, we have mutated the Fc-FcRn binding site of chimeric anti–carcinoembryonic antigen (CEA) antibodies produced in a single-chain Fv-Fc format. The anti-CEA T84.66 single-chain Fv-Fc format wild-type and five mutants (I253A, H310A, H435Q, H435R, and H310A/H435Q, Kabat numbering system) expressed well in mammalian cell culture. After purification and characterization, effective in vitro antigen binding was shown by competition ELISA. Biodistribution studies in BALB/c mice using 125I- and 131I-labeled fragments revealed blood clearance rates from slowest to fastest as follows: wild-type &amp;gt; H435R &amp;gt; H435Q &amp;gt; I253A &amp;gt; H310A &amp;gt; H310A/H435Q. The terminal half-lives of the mutants ranged from 83.4 to 7.96 hours, whereas that of the wild-type was ∼12 days. Additionally, 124I-labeled wild-type, H435Q, I253A, H310A, and H310A/H435Q variants were evaluated in LS174T xenografted athymic mice by small animal positron emission tomography imaging, revealing localization to the CEA-positive xenografts. The slow clearing wild-type and H435Q constructs required longer to localize to the tumor and clear from the circulation. The I253A and H310A fragments showed intermediate behavior, whereas the H310A/H435Q variant quickly localized to the tumor site, rapidly cleared from the animal circulation and produced clear images. Thus, attenuating the Fc-FcRn interaction provides a way of controlling the antibody fragment serum half-life without compromising expression and tumor targeting.
Carnosic Acid and Promotion of Monocytic Differentiation of HL60-G Cells Initiated by Other Agents
Authors: M. Danilenko, X. Wang, G. P. Studzinski
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Carnosic acid is a plant-derived polyphenol food preservative with chemoprotective effects against carcinogens when tested in animals. Recently, we showed that carnosic acid potentiates the effects of 1α,25-dihydroxyvitamin D3 (1α,25[OH]2D3) and of all-trans-retinoic acid (ATRA) on differentiation of human leukemia cells. We now examine the mechanisms associated with carnosic acid-induced enhancement of cell differentiation (in subline HL60-G) initiated by 1α,25(OH)2D3, ATRA, or 12-O-tetradecanoylphorbol-13-acetate (TPA). Methods: We evaluated monocytic differentiation markers (CD11b, CD14, and monocytic serine esterase), cell cycle parameters, and cell proliferation rates after treatment of cells with different agents with or without carnosic acid. We also assessed the abundance of the vitamin D receptor (VDR), retinoid X receptor (RXR)-α, retinoic acid receptor (RAR)-α, and cell cycle-associated proteins by immunoblot analysis (p27, early growth response gene [EGR]-1, and p35Nck5a), the expression of corresponding genes by reverse transcription–polymerase chain reaction (RT–PCR), and the activity of VDR by electrophoretic mobility shift analysis. The two-sided nonparametric Kruskal–Wallis one-way analysis-of-variance test with Dunn's adjustment was used for statistical analyses. Results: Monocytic differentiation induced by low (1 nM) concentrations of 1α,25(OH)2D3, ATRA, or TPA was enhanced by carnosic acid (10 μM), as shown by the increased expression of monocytic serine esterase (P<.001, P<.001, and P = .043, respectively) and of CD11b (P = .008, P = .046, and P = .041, respectively). Increased expression of CD14 was seen only for 1α,25(OH)2D3 and ATRA (P = .009 and P = .048, respectively) and also for several cell cycle-associated proteins. Carnosic acid in combination with 1α,25(OH)2D3 and ATRA resulted in decreased cell proliferation and blocked the cell cycle transition from G1 to S phase (P<.05). Carnosic acid alone increased the expression of VDR and RXR-α, but the expression was greatly enhanced in the presence of 1α,25(OH)2D3 and ATRA. In combination with TPA, carnosic acid potentiated the expression of VDR and RAR-α. Conclusion: Carnosic acid enhances a program of gene expression consistent with 1α,25(OH)2D3-, ATRA-, or TPA-induced monocytic differentiation of HL60-G cells.
VIP for PT, or very important PEDro for physiotherapy
Authors: Mario Bizzini
Journal: British Journal of Sports Medicine (2013)

Patellofemoral pain syndrome (PFPS) is one of the most frequent diagnoses in sports medicine,2 and probably one of the most difficult to treat. Successful management of patients and athletes is dependent on updated evidence-based guidelines. Over the years, the Physiotherapy Evidence Database (PEDro) has developed to become the source for high-quality evidence for physiotherapy (including sports physiotherapy) interventions (bjsports-2012-091804). PEDro has reached VIP status among physiotherapists, and BJSM provides a great service to physiotherapists for regularly publishing PEDro systematic review updates.

A recent PEDro systematic review update (bjsports-2012-091986) showed how multimodal physiotherapy, especially exercises, can significantly …
Proceedings: Joint involvement in spondylo-epiphyseal dysplasias.
Authors: M F Kahn, M T Corvol, S De Seze
Journal: Annals of the Rheumatic Diseases (1974)

DR. ZAPHIROPOULOS The answer to the first question is no, we did not repeat them.We did measure the albumin level of all patients, both rheumatoid and nonrheumatoid, and they were very comparable.This is a criticism of the previous paper by Paulus and others where their patients with rheumatoid arthritis had lower levels of
<i>Die Epileptischen Erkrankungen. Ihre Anatomischen und Physiologischen Unterlagen sowie Ihre Chirurgische Behandlung.</i>By Prof. Fedor Krause und Dr. Heinrich Schum. (<i>Stuttgart: II Häfte. Neue Deutsche Chirurgie, von Ferdinand Enke, 1932.</i>)
Authors: J. Notkin
Journal: American Journal of Psychiatry (1932)
Toll-like receptors 2 and 4 are differentially involved in Fas dependent apoptosis in Peyer's patch and the liver at an early stage after bile duct ligation in mice
Authors: A Ogawa
Journal: Gut (2005)

Surgical management of extrahepatic cholestasis is frequently complicated by bacterial translocation and severe liver injury. The aim of this study was to clarify the involvement of Toll-like receptors (TLRs) in the pathogenesis of bacterial translocation and liver injury in obstructive cholestasis.TLR2 deficient (TLR2(-/-)), MyD88(-/-), Jalpha281(-/-), gld/gld, and lpr/lpr mice, all of which have a C57BL/6 background, and C3H/HeN and TLR4 mutated C3H/HeJ mice were subjected to bile duct ligation (BDL). Faecal IgA and serum alanine aminotransferase levels were determined after BDL. Apoptosis was examined by histological and flow cytometric analyses of cells from Peyer's patches and the liver.The size and number of B cells in Peyer's patches markedly decreased on day 3 after BDL. Increased apoptosis in Peyer's patch B cells was evident on day 1 after BDL in control mice but not in lpr/lpr, MyD88(-/-), or C3H/HeJ mice. On the other hand, TLR2 and Fas ligand expression on intrahepatic NK1.1(+) T cells increased on day 1 after BDL in C57BL/6 mice. Liver injury and apoptosis were evident on day 1 after BDL in control and C3H/HeJ mice but were significantly reduced in TLR2(-/-), Jalpha281(-/-), gld/gld, and lpr/lpr mice.TLR4 and TLR2 may play important roles in Fas dependent apoptosis in Peyer's patch B cells and hepatocytes, respectively, at an early stage after BDL in mice.
New uncertainties in prenatal screening for neural tube defect
Authors: M Super
Journal: BMJ (1981)

news programmes.Such meetings would not be for the airing of complaints, but for the free and frank exploration of difficulties in the relationship, and would provide an opportunity for newsmen to question doctors outside the context of particular news stories.Other, larger, meetings to tackle specific issues might occasionally be useful, not least in enabling a wider circle of doctors and reporters to meet each other.We also endorse the suggestion in your article about the development of a code of good practice, and hope that such a code might grow out of the experience of regular meetings between the professions.
If the magical number is 4, how does one account for operations within working memory?
Authors: Juan Pascual-Leone
Journal: Behavioral and Brain Sciences (2001)

Cowan fails to obtain a magical number of 7 because his analysis is faulty. This is revealed by an alternative analysis of Cowan's own tasks. The analysis assumes a number 7 for adults, and neoPiagetian mental- capacity values for children. Data patterns and proportions of success (reported in Cowan's Figs. 2 and 3) are thus quantitatively explained in detail for the first time.
Degradation of tungsten coils implanted into the subclavian artery of New Zealand white rabbits is not associated with local or systemic toxicity
Authors: Matthias Peuster, Christoph Fink, Peter Wohlsein, Michael Bruegmann, Alexander Günther, Volker Kaese, Matthias Niemeyer, Heinz Haferkamp, Christian v Schnakenburg
Journal: Biomaterials (2002)
Drug-induced liver injury: present and future
Authors: Ki Tae Suk, Dong Joon Kim
Journal: Clinical and Molecular Hepatology (2012)

Liver injury due to prescription and nonprescription medications is a growing medical, scientific, and public health problem. Worldwide, the estimated annual incidence rate of drug-induced liver injury (DILI) is 13.9-24.0 per 100,000 inhabitants. DILI is one of the leading causes of acute liver failure in the US. In Korea, the annual extrapolated incidence of cases hospitalized at university hospital is 12/100,000 persons/year. Most cases of DILI are the result of idiosyncratic metabolic responses or unexpected reactions to medication. There is marked geographic variation in relevant agents; antibiotics, anticonvulsants, and psychotropic drugs are the most common offending agents in the West, whereas in Asia, 'herbs' and 'health foods or dietary supplements' are more common. Different medical circumstances also cause discrepancy in definition and classification of DILI between West and Asia. In the concern of causality assessment, the application of the Roussel Uclaf Causality Assessment Method (RUCAM) scale frequently undercounts the cases caused by 'herbs' due to a lack of previous information and incompatible time criteria. Therefore, a more objective and reproducible tool that could be used for the diagnosis of DILI caused by 'herbs' is needed in Asia. In addition, a reporting system similar to the Drug-Induced Liver Injury Network (DILIN) in the US should be established as soon as possible in Asia. Keywords: Drug-Induced Liver Injury; Asia; Herbal Medicine
Survival and disease progression in UK patients with lymphangioleiomyomatosis
Authors: S R Johnson
Journal: Thorax (2004)

<b>Background:</b> Lymphangioleiomyomatosis (LAM) is a rare and progressive disease of young women with no effective treatment. Previous estimates of 10 year survival, based mostly on case series or patients from tertiary centres, have ranged from 40% to 79%; no data are available on the progression of respiratory disability. In order to provide data for patients and for planning intervention studies, we have looked at the time course of LAM using a national cohort. <b>Methods:</b> Time to death, time to MRC dyspnoea grades 2–5, and need for oxygen in patients on the UK LAM database were analysed using Kaplan-Meier analysis and Cox regression. <b>Results:</b> Fifty seven of 72 patients responded with a median duration of follow up of 12.6 years (range 2.3–37) from the onset of symptoms. Ten year survival was 91% from onset of symptoms but varied widely with 11 patients alive after 20 years. Median time to MRC grade 3 dyspnoea (breathless walking on the flat) was 9.3 years (95% CI 5.1 to 13.4) from onset of symptoms. <b>Conclusions:</b> Survival from LAM appears to be better than that reported in early studies. These data should be helpful for patients and for planning clinical trials.
Effect of bismuth subcitrate and sucralfate on rat duodenal and human gastric bicarbonate secretion in vivo.
Authors: C J Shorrock, A Garner, A H Hunter, J R Crampton, W D Rees
Journal: Gut (1990)

Acid and alkali secretion have been examined together with prostaglandin E2 production in response to two mucosal protective drugs, colloidal bismuth subcitrate and sucralfate. Doses of colloidal bismuth subcitrate in the therapeutic range (120 and 1200 mg) had no effect on alkali secretion or luminal PGE2 output when perfused into the stomach of human volunteers. Similarly, in the anaesthetised rat, neither gastric acid nor duodenal alkali secretions were influenced by iv (12 mg/kg) or topical (120 mg/ml) administration of colloidal bismuth subcitrate. In contrast, perfusion of the human stomach with 1 g sucralfate stimulated bicarbonate output by 50%, a response which was unaffected by indomethacin (25 mg/h). A rise of 64% in gastric PGE2 output after sucralfate was, however, prevented by indomethacin pretreatment. Alkali secretion by rat duodenum was also increased by sucralfate but the response depended on the basal secretory rate. Low basal secretors (less than 3 mumol) showed a 75% stimulation whereas rats with high basal secretory rates (greater than 3 mumol) showed no significant response. All duodenal preparations regardless of basal secretory rate showed a stimulation of bicarbonate output with topical PGE2. The results suggest that enhancement of gastroduodenal bicarbonate secretion may play a role in the protective action of sucralfate but is unlikely to explain mucosal protection by colloidal bismuth subcitrate.