tbuckley/cabot-search huggingface dataset:
EXPECTANCY EFFECTS ON COMPETITIVE 5 KM TIME-TRIAL PERFORMANCE
Authors: P Hurst, L Board, J Roberts
Journal: British Journal of Sports Medicine (2013)

Manipulating athletes’ beliefs and expectations through deception has been shown to improve sport performance in artificial environments, but this has not been demonstrated systematically in real life competition where the effects could easily be masked. This study investigated the placebo effect of belief in a new performance-enhancing supplement on 5 km competitive time-trial performance. Fifteen competitive male endurance runners (mean± s : Age=33±5; Height=175±8.1 cm; Weight=71.0±7.2 kg, 5 km personal best: 19:13±1:13 minutes) volunteered to participate in four 5 km competitive time trials over a three week period (two experimental and two baseline). In experimental trials, participants ingested a placebo drink that was informed to improve 5 km endurance performance. Conditions were randomised between baseline and experimental. Magnitude inferences and 95% confidence intervals were used to determine if a positive expectancy could have a smallest worthwhile effect on 5 km endurance performance of 0.5%. Mean 5 km performance time-trial for the expectation of receiving a beneficial supplement was different from that of baseline (1195±79 s; 95% confidence interval 1152 to 1239 vs. 1216±81 s ; 1171 to 1261 s , P &lt;0.001). Relative to baseline, a very likely beneficial main effect of receiving a positive expectation (1.72±1.03, 95% CI 1.00±2.44%) was demonstrated. The results suggest that the placebo effect could be used in a real life competitive environment to improve 5 km running performance.
Parathyroid Hormone Regulation of Na+,K+-ATPase Requires the PDZ 1 Domain of Sodium Hydrogen Exchanger Regulatory Factor-1 in Opossum Kidney Cells
Authors: Syed Jalal Khundmiri, Edward J. Weinman, Deborah Steplock, Judith Cole, Aamir Ahmad, Patrick D. Baumann, Michelle Barati, Madhavi J. Rane, Eleanor Lederer
Journal: Journal of the American Society of Nephrology (2005)

It was demonstrated that expression of murine sodium hydrogen exchanger regulatory factor (NHERF-1) lacking the ezrin-binding domain blocks parathyroid hormone (PTH) regulation of Na<sup>+</sup>,K<sup>+</sup>-ATPase in opossum kidney (OK) cells. The hypothesis that the NHERF-1 PDZ domains contribute to PTH regulation of Na<sup>+</sup>,K<sup>+</sup>-ATPase was tested by comparison of PTH regulation of Na<sup>+</sup>,K<sup>+</sup>-ATPase in wild-type OK (OK-WT) cells, NHERF-deficient OKH cells, OK-WT transfected with siRNA for NHERF (NHERF siRNA OK-WT), and OKH cells that were stably transfected with full-length NHERF-1 or constructs with mutated PDZ domains. OKH cells and NHERF siRNA OK-WT showed decreased expression of NHERF-1 but equivalent expression of ezrin and Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>1</sub> subunit when compared with OK-WT cells. PTH decreased Na<sup>+</sup>,K<sup>+</sup>-ATPase activity and stimulated phosphorylation of the Na<sup>+</sup>,K<sup>+</sup>-ATPase α<sub>1</sub> in OK-WT cells but not in NHERF-deficient cells. Rubidium (<sup>86</sup>Rb) uptake was equivalent in OK-WT, OKH, and OKH cells that were transfected with all but the double PDZ domain mutants. PTH decreased <sup>86</sup>Rb uptake significantly in OK-WT but not in OKH cells. PTH also significantly inhibited <sup>86</sup>Rb uptake in OKH cells that were transfected with full-length NHERF-1 or NHERF-1 with mutated PDZ 2 but not in OKH cells that were transfected with mutated PDZ 1. Transfection with NHERF expressing both mutated PDZ domains resulted in diminished basal <sup>86</sup>Rb uptake that was not inhibited further by PTH. PTH stimulated protein kinase Cα activity and α<sub>1</sub> subunit phosphorylation in OK-WT but not in NHERF-deficient cells. Transfection of OKH cells with NHERF constructs that contained an intact PDZ1 domain restored PTH-stimulated protein kinase Cα activity and α<sub>1</sub> subunit phosphorylation. These results demonstrate that NHERF-1 is necessary for PTH-mediated inhibition of Na<sup>+</sup>,K<sup>+</sup>-ATPase activity and that the inhibition is mediated through the PDZ1, not PDZ2, domain.
ACUTE EXPERIMENTAL GLOMERULAR NEPHRITIS IN RABBITS: A CORRELATION OF MORPHOLOGICAL AND FUNCTIONAL CHANGES
Authors: William E. Ehrich, Richard E. Wolf, George M. Bartol
Journal: The Journal of Experimental Medicine (1938)

It has been shown in this paper that structural and functional changes in acute glomerular nephritis in rabbits produced by nephrotoxins by the method of Masugi are the same as those found in human glomerular nephritis. The morbid anatomy is characterized by glomerular cell proliferation, and in some cases by deposition of fibrin and crescent formation of the glomeruli and by fatty changes of the tubules. The functional changes are: oliguria, proteinuria, hematuria, cylindruria, edema, rise in blood urea, and according to Masugi (1933, 1934) and Smadel (1936, 1937), rise in blood pressure, lipuria, and fall in urea clearance and plasma proteins. As we are unaware of any discrepancies between the experimentally induced disease and human nephritis, the conclusion follows that the two so closely resemble each other that they appear to be identical. As to the pathogenesis, it has been shown that the disease begins with a period of latency. This is characterizied anatomically by hyperemia of the glomeruli; and functionally, in at least a number of cases, by an increased diuresis. It follows, therefore, that the theory of Volhard, according to which glomerular nephritis is caused by arteriolar spasms, can no longer be maintained. It has further been demonstrated that proliferation of glomerular cells is the typical lesion, and that deposition of fibrin and crescent formation occur only in certain cases, and in these only in a widely varying number of glomeruli. As crescents are found as early as the proliferation itself, it follows that they should not be regarded as pathognomonic of the subacute phase, but that they represent a complication which probably aggravates the disease. As to correlation of morphological and functional changes, it has been demonstrated that oliguria, marked proteinuria and diminished excretion of cyanol appear at the time when the glomerular changes are at their peak. Evidence has been presented that the oliguria and the decrease in cyanol excretion in acute glomerular nephritis are chiefly the result of the glomerular damage. It has further been demonstrated that the excretion of azofuchsin was unchanged, except for a diminution in the rabbit which at autopsy showed a marked fatty change of the tubules. We regard these observations as evidence, that, in acute glomerular nephritis in rabbits, glomeruli and tubules may function independently of each other.
Long-term datasets in biodiversity research and monitoring: assessing change in ecological communities through time
Authors: Anne E. Magurran, Stephen R. Baillie, Stephen T. Buckland, Jan McP. Dick, David A. Elston, E. Marian Scott, Rognvald I. Smith, Paul J. Somerfield, Allan D. Watt
Journal: Trends in Ecology & Evolution (2010)
Pancreas-Targeted NIR Fluorophores for Dual-Channel Image-Guided Abdominal Surgery
Authors: Hideyuki Wada, Hoon Hyun, Christina Vargas, Julien Gravier, GwangLi Park, Sylvain Gioux, John V. Frangioni, Maged Henary, Hak Soo Choi
Journal: Theranostics (2014)

Objective: Pancreas-related complications are some of the most serious ones in abdominal surgery.The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury.Design: After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs.Dose ranging using 25 and 100 nmol, and 2.5 µmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species.Three different 800 nm NIR fluorophores were employed for dual-channel FLARE™ imaging in pigs: 2 μmol of ZW800-1 for vessels and kidney, 1 μmol of ZW800-3C for lymph nodes, and 2 μmol of ESNF31 for adrenal glands.Results: T700-F demonstrated the highest signal to background ratio (SBR), with peak SBR at 4 h postinjection in mice.In pigs, T700-F produced an SBR ≥ 2 against muscle, spleen, and lymph nodes for up to 8 h after a single intravenous injection.The combination of T700-F with each 800 nm NIR fluorophore provided simultaneous dual-channel intraoperative imaging of pancreas with surrounding organs in real time.Conclusion: Pancreas-targeted NIR fluorophores combined with the FLARE dual-channel imaging system enable the real-time intraoperative pancreas imaging which helps surgeons perform safer and more curative abdominal surgeries.
Targeting the RB-pathway in Cancer Therapy
Authors: Erik S. Knudsen, Jean Y. J. Wang
Journal: Clinical Cancer Research (2010)

The RB-pathway, consisting of inhibitors and activators of cyclin-dependent kinases, the retinoblastoma tumor suppressor (RB), and the E2F-family of transcription factors, plays critical roles in the regulation of cell cycle progression and cell death. Components of this pathway, particularly p16Ink4a, cyclin D1, and RB, are frequently altered in sporadic human cancers to promote deregulated cellular proliferation. The consistent disruption of the RB-pathway in human cancers raises the possibility of exploiting tumor-specific RB-pathway defects to improve the efficacy of current therapies and to develop new therapeutic strategies. This article discusses how the RB-pathway status impacts the cellular responses to cytotoxic, cytostatic, and hormone therapies, and how the components of the RB-pathway may be directly targeted to treat cancer.
Retinoic Acid Induces Neuroblastoma Cell Death by Inhibiting Proteasomal Degradation of Retinoic Acid Receptor α
Authors: Jun-ichi Nagai, Takuya Yazawa, Koji Okudela, Hisato Kigasawa, Hitoshi Kitamura, Hitoshi Osaka
Journal: Cancer Research (2004)

To seek a novel therapeutic approach to neuroblastoma (NBL), we used three NBL cell lines (SK-N-DZ, NH12, and SK-N-SH) to examine the underlining molecular mechanisms of cellular reactions and sensitivity to all-trans-retinoic acid (ATRA). SK-N-DZ cells expressed relatively high levels of retinoic acid receptor alpha (RAR-alpha) and underwent ATRA-induced cell death that was blocked by an RAR-alpha antagonist. By contrast, RAR-alpha expression gradually decreased in NH12 and SK-N-SH cells, which did not experience increased cell death in response to ATRA. We report here the ubiquitin-dependent down-regulation of RAR-alpha expression during ATRA treatment. Our data suggest that SK-N-DZ cells have a defect in RAR-alpha down-regulation, resulting in sustained high expression of RAR-alpha that confers high sensitivity to ATRA. Accordingly, treatment with a proteasome inhibitor dramatically increased ATRA-induced cell death in NH12 and SK-N-SH cell lines. Our results reveal the crucial involvement of the RAR-alpha signaling pathway in NBL cell death and show that three NBL cell lines are differentially sensitive to ATRA. These data suggest a potential novel therapy for NBL involving retinoic acid treatment combined with the inhibition of RAR-alpha degradation.
Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data
Authors: S. S. Jick, R. K. Hernandez
Journal: BMJ (2011)

To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel.Nested case-control and cohort study.The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans.The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time.Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives.186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100,000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100,000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8).The risk of non-fatal venous thromboembolism among users of oral contraceptives containing drospirenone seems to be around twice that of users of oral contraceptives containing levonorgestrel, after the effects of potential confounders and prescribing biases have been taken into account.
Nitric Oxide–Mediated Zinc Release Contributes to Hypoxic Regulation of Pulmonary Vascular Tone
Authors: Paula J. Bernal, Karanee Leelavanichkul, Eileen Bauer, Rong Cao, Annette Wilson, Karla J. Wasserloos, Simon C. Watkins, Bruce R. Pitt, Claudette M. St. Croix
Journal: Circulation Research (2008)

The metal binding protein metallothionein (MT) is a target for nitric oxide (NO), causing release of bound zinc that affects myogenic reflex in systemic resistance vessels. Here, we investigate a role for NO-induced zinc release in pulmonary vasoregulation. We show that acute hypoxia causes reversible constriction of intraacinar arteries (<50 microm/L) in isolated perfused mouse lung (IPL). We further demonstrate that isolated pulmonary (but not aortic) endothelial cells constrict in hypoxia. Hypoxia also causes NO-dependent increases in labile zinc in mouse lung endothelial cells and endothelium of IPL. The latter observation is dependent on MT because it is not apparent in IPL of MT(-/-) mice. Data from NO-sensitive fluorescence resonance energy transfer-based reporters support hypoxia-induced NO production in pulmonary endothelium. Furthermore, hypoxic constriction is blunted in IPL of MT(-/-) mice and in wild-type mice, or rats, treated with the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylenediamine (TPEN), suggesting a role for chelatable zinc in modulating HPV. Finally, the NO donor DETAnonoate causes further vasoconstriction in hypoxic IPL in which NO vasodilatory pathways are inhibited. Collectively, these data suggest that zinc thiolate signaling is a component of the effects of acute hypoxia-mediated NO biosynthesis and that this pathway may contribute to constriction in the pulmonary vasculature.
A practical scoring system to determine whether to proceed with surgical resection in recurrent glioblastoma
Authors: C.-K. Park, J. H. Kim, D.-H. Nam, C.-Y. Kim, S.-B. Chung, Y.-H. Kim, H. J. Seol, T. M. Kim, S. H. Choi, S.-H. Lee, D. S. Heo, I. H. Kim, D. G. Kim, H.-W. Jung
Journal: Neuro-Oncology (2013)

To determine the benefit of surgical management in recurrent glioblastoma, we analyzed a series of patients with recurrent glioblastoma who had undergone surgery, and we devised a new scale to predict their survival. Clinical data from 55 consecutive patients with recurrent glioblastoma were evaluated after surgical management. Kaplan–Meier survival analysis and Cox proportional hazards regression modeling were used to identify prognostic variables for the development of a predictive scale. After the multivariate analysis, performance status (P = .078) and ependymal involvement (P = .025) were selected for inclusion in the new prognostic scale. The devised scale was validated with a separate set of 96 patients from 3 different institutes. A 3-tier scale (scoring range, 0–2 points) composed of additive scores for the Karnofsky performance status (KPS) (0 for KPS ≥ 70 and 1 for KPS < 70) and ependymal involvement (0 for no enhancement and 1 for enhancement of the ventricle wall in the magnetic resonance imaging) significantly distinguished groups with good (0 points; median survival, 18.0 months), intermediate (1 point; median survival, 10.0 months), and poor prognoses (2 points; median survival, 4.0 months). The new scale was successfully applied to the validation cohort of patients showing distinct prognosis among the groups (median survivals of 11.0, 9.0, and 4.0 months for the 0-, 1-, and 2-point groups, respectively). We developed a practical scale to facilitate deciding whether to proceed with surgical management in patients with recurrent glioblastoma. This scale was useful for the diagnosis of prognostic groups and can be used to develop guidelines for patient treatment.
Comparison of the Glycemic Effects of Rosiglitazone and Pioglitazone in Triple Oral Therapy in Type 2 Diabetes
Authors: Michael T. Tran, Maria D. Navar, Mayer B. Davidson
Journal: Diabetes Care (2006)

To date, there have been few comparison studies between rosiglitazone and pioglitazone (1,2) and none of the two thiazolidinediones (TZDs) as a third agent in triple oral therapy. In February 2003, pioglitazone replaced rosiglitazone as the TZD on the pharmacy formulary at our hospital. This gave us the opportunity to compare the effectiveness of rosiglitazone and pioglitazone added to type 2 diabetic patients already on maximum (tolerated) doses of metformin and a sulfonylurea agent whose HbA1c (A1C) levels did not meet the American Diabetes Association goal of <7.0%.

Our diabetes clinic treatment algorithm mandates starting small doses of either a sulfonylurea agent or metformin and increasing the dose every 2 weeks until either a fasting plasma glucose (FPG) concentration of  130 mg/dl, the alternate drug is added and also increased every 2 weeks. When the FPG goal is achieved, further therapeutic decisions are based on A1C levels measured 2–3 months later. Only when both agents are maximized and either the FPG concentration 2 weeks after the last increase remains >130 mg/dl or an A1C level is ≥7.0% 2–3 months after the FPG goal is reached, or at any time thereafter, is a maximal dose of a TZD added. The maximal dose is used because it can take up to …
PCR-based DNA test to confirm clinical diagnosis of autosomal recessive spinal muscular atrophy
Authors: G. van der Steege, P.M. Grootscholten, P. van der Vlies, T.G. Draaijers, J. Osinga, J.M. Cobben, H. Scheffer, C.H.C.M. Buys
Journal: The Lancet (1995)
Sputum induction in young cystic fibrosis patients
Authors: K. De Boeck, M. Alifier, S Vandeputte
Journal: European Respiratory Journal (2000)

A culture from the lower airway secretions is the optimal sample to guide antibiotic therapy in cystic fibrosis (CF) lung disease. The authors therefore examined whether sputum induction is an efficient, safe and acceptable procedure in CF children without spontaneous expectorations. Nineteen patients were studied. Their mean age (range) was 8.6 yrs (4.3-15.2 yrs). Their mean forced expiratory volume in one second (FEV1) was 88% predicted (46-122%). NaCl solutions from 0.9-6% were inhaled, after baseline lung function tests before and after salbutamol. All patients did produce secretions. Alveolar macrophages were present in 16/19 induced samples. The procedure induced minor but significant bronchoconstriction: the mean change (range) in postsalbutamol FEV1 (% pred) was -7 (-24-16). Percutaneous oxygen saturation remained above 90% in all children. The test had to be discontinued in one child because of cough and wheeze. Acceptability of the procedure evaluated using a visual analogue scale from -7-7 showed a mean value (range) at the final concentration of -1.23 (-6.16-5.88). It is concluded that sputum induction is possible, safe and acceptable in cystic fibrosis children who do not expectorate spontaneously.
Antihypertensive Treatment With Metoprolol or Hydrochlorothiazide in Patients Aged 60 to 75 Years
Authors: John Wikstrand
Journal: JAMA (1986)

In a randomized double-blind study (N = 562), a traditional treatment schedule, starting antihypertensive treatment in elderly hypertensive patients (60 to 75 years old) with 25 mg of hydrochlorothiazide once daily and doubling the dose if a satisfactory response was not achieved, was compared with antihypertensive treatment of 100 mg of metoprolol once daily, adding 12.5 mg of hydrochlorothiazide for patients whose response was not satisfactorialy achieved with metoprolol alone. Systolic and diastolic blood pressure was significantly reduced with both regimens. The frequency rates of responders (diastolic blood pressure, less than or equal to 95 mm Hg) in the metoprolol group and the hydrochlorothiazide group were 50% and 47% after four weeks and 65% and 61% after eight weeks, respectively. There were no significant differences in total symptom score or single symptoms between the regimens, but significantly more patients had hypokalemia and hyperuricemia with the hydrochlorothiazide regimen. Thus, we conclude that beginning antihypertensive treatment with 100 mg of metoprolol once daily and adding a small dose of hydrochlorothiazide (12.5 mg) in patients whose response is not satisfactory with metoprolol alone appears to be effective and safe in elderly hypertensive patients.
CON: encouraging resistance to rule-based medicine is essential to improving outcomes
Authors: Mark Rosenthal
Journal: Thorax (2014)

Know the rules well, so you can break them effectively. – Dalai Lama XIV The golden rule is that there are no golden rules. – George Bernard Shaw

Of course my rules are necessary, proportionate and flexible, it is your rules that are the problem, being arbitrary in nature, excessive in force and of course far too numerous, all of which lead to unintended consequences.

Rules like so much else in medicine are a quantitative science and until the far off day of every fact being known allows reliable rules to be formulated, then like an elevator in a skyscraper, the trick is knowing on which floor to get off when the current known rules stop applying to a situation. Hence this article opposes at least in part the paper in this issue by Blakey et al .1

PubMed yields 18 962 results where ‘rule’ or rules’ are in the title and in our comparatively enlightened trust there are about 160 clinical guidelines varying from 2 to 274 pages and some 475 other trust policies and guidelines. Despite this, there are so many situations where there simply are no rules.

The first reference by Blakey et al concluding that algorithmic predictions are superior to clinical judgement2 is based on studies from 1944 to 1989 only and covers everything from the prediction of coupon utilisation from mail order catalogues via the risk of malingering to the ‘diagnosis’ of homosexuality! Of the few papers cited published between 1980 and 1989, clinicians predicted intensive care unit mortality and the diagnosis of abdominal pain better than algorithms but clinicians were worse on diagnosis of myocardial infarction and chest pain. The enthusiasm of Blakey et al for new technology and the papers they cite undoubtedly shows better capture of data nowadays but the outcomes …