tbuckley/cabot-search huggingface dataset:
Intracellular pH and Tyrosine Phosphorylation but Not Calcium Determine Shear Stress–Induced Nitric Oxide Production in Native Endothelial Cells
Authors: Kazuhide Ayajiki, Markus Kindermann, Markus Hecker, Ingrid Fleming, Rudi Busse
Journal: Circulation Research (1996)

Abstract Signaling pathways determining the shear stress–induced production of NO from endothelial cells in situ were investigated using a bioassay system in which shear stress was increased by inducing vasoconstriction in an endothelium-intact donor segment (rabbit iliac artery) while maintaining a constant luminal perfusion rate. Shear stress–induced NO production, as assessed by changes in the tone of a preconstricted endothelium-denuded detector ring, was biphasic and consisted of an initial transient (20- to 25-minute) Ca 2+ -dependent phase followed by a Ca 2+ -independent plateau phase, which was maintained as long as the donor segment remained constricted. Stretching the donor segments to their in vivo length abolished the initial phase without affecting the plateau phase of NO release. Inhibition of the Na + -H + exchanger using HOE 694 elicited an intracellular acidification, which attenuated shear stress–induced NO production. The specific protein kinase C inhibitor, Ro 31-8220, was without effect, whereas the unspecific inhibitors, staurosporine and calphostin C, abolished the shear stress–induced production of NO. Erbstatin A, a tyrosine kinase inhibitor, attenuated the shear stress–induced tyrosine phosphorylation of specific cellular proteins and abrogated the associated NO production. In summary, these data indicate that shear stress activates the NO synthase at basal levels of [Ca 2+ ] i via a mechanotransduction cascade that involves tyrosine phosphorylation and can be modulated by changes in pH i . The apparent fundamental alteration of the endothelial NO synthase under shear stress that renders its maintained activation independent of an increase in [Ca 2+ ] i is probably the consequence of a change in the enzyme microenvironment.
Screening and Behavioral Counseling Interventions in Primary Care to Reduce Alcohol Misuse: U.S. Preventive Services Task Force Recommendation Statement
Authors: Virginia A Moyer
Journal: Annals of Internal Medicine (2013)

Description: Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation statement on screening and behavioral counseling interventions in primary care to reduce alcohol misuse. Methods: The USPSTF reviewed new evidence on the effectiveness of screening for alcohol misuse for improving health outcomes, the accuracy of various screening approaches, the effectiveness of various behavioral counseling interventions for improving intermediate or long-term health outcomes, the harms of screening and behavioral counseling interventions, and influences from the health care system that promote or detract from effective screening and counseling interventions for alcohol misuse. Population: These recommendations apply to adolescents aged 12 to 17 years and adults aged 18 years or older. These recommendations do not apply to persons who are actively seeking evaluation or treatment of alcohol misuse. Recommendation: The USPSTF recommends that clinicians screen adults aged 18 years or older for alcohol misuse and provide persons engaged in risky or hazardous drinking with brief behavioral counseling interventions to reduce alcohol misuse. (Grade B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening and behavioral counseling interventions in primary care settings to reduce alcohol misuse in adolescents. (I statement) Chinese translation
Corticosteroids in Heart Disease
Authors: J. V. Z. Maempel
Journal: BMJ (1966)

<h3>Objective</h3> To examine the impact of a disabling non-traumatic shoulder lesion on work participation and working life expectancy. <h3>Methods</h3> From a 70% random sample of the Finnish population, we selected 30–59-year-old wage earners with prolonged sickness absence due to a shoulder lesion (n=7644). We followed the persons from 2006 to 2014 and calculated the proportion of time a person spent in different work participation statuses. The associations of potential determinants with a preterm exit from paid employment were tested using Cox regression. Years expected to be spent in different work participation statuses were estimated applying the Sullivan method for healthy life expectancy. <h3>Results</h3> During 9 years of follow-up time spent at work was reduced from 77.7% to 46.7%, and 15.8% of the persons were granted disability retirement, mostly due to shoulder and other musculoskeletal diseases. Compared with the general population persons with a disabling shoulder disease are expected to lose from 1.8 to 8.1 years of working life, depending on their age. Age, gender, education, duration of initial sickness absence due to the shoulder lesion, not being able to return to work sustainably and participation in vocational rehabilitation predicted preterm exit from work. Heavy lifting increased the risk of preterm exit marginally. <h3>Conclusions</h3> Working life expectancy is markedly reduced in persons with a disabling shoulder lesion, mainly because of disability retirement due to musculoskeletal problems. Clinicians should consider interventions targeted at improving musculoskeletal functioning and necessary work modifications before shoulder problems become chronic or the persons develop disabling comorbid musculoskeletal conditions.
Renal effects of molecular targeted therapies in oncology: a review by the Cancer and the Kidney International Network (C-KIN)
Authors: V. Launay-Vacher, M. Aapro, G. De Castro, E. Cohen, G. Deray, M. Dooley, B. Humphreys, S. Lichtman, J. Rey, F. Scotté, H. Wildiers, B. Sprangers
Journal: Annals of Oncology (2015)
Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial
Authors: James W Denham, Allison Steigler, David S Lamb, David Joseph, Hedy Mameghan, Sandra Turner, John Matthews, Ian Franklin, Chris Atkinson, John North, Michael Poulsen, David Christie, Nigel A Spry, Keen-Hun Tai, Chris Wynne, Gillian Duchesne, Olga Kovacev, Catherine D'Este
Journal: The Lancet Oncology (2005)
In vivo nitrogen metabolism in ornithine transcarbamylase deficiency.
Authors: M Yudkoff, Y Daikhin, I Nissim, A Jawad, J Wilson, M Batshaw
Journal: Journal of Clinical Investigation (1996)

We developed a new technique that monitors metabolic competency in female heterozygotes for ornithine transcarbamylase deficiency (OTCD). The method uses mass spectrometry to measure conversion of (15)NH4Cl to [15N]urea and [5-(15)N]glutamine following an oral load of (15)NH4Cl. We found that heterozygotes converted significantly less NH3 nitrogen to urea, with this difference being particularly obvious for symptomatic carriers, in whom the blood [15N]urea concentration (mM) was significantly less than control values at most time points. The blood concentration of [5-(15)N]-glutamine (microM) was significantly higher in both asymptomatic and symptomatic heterozygotes than it was in the control subjects. The administration of a test dose of sodium phenylbutyrate to the control group did not affect the rate of [15N]urea formation. We conclude: (a) This test effectively monitors in vivo N metabolism and might obviate the need for liver biopsy to measure enzyme activity in OTCD; (b) Asymptomatic OTCD carriers form urea at a normal rate, indicating that ureagenesis can be competent even though enzyme activity is below normal; (c) Although ostensibly asymptomatic OTCD carriers form urea at a normal rate, their nitrogen metabolism is still abnormal, as reflected in their increased production of [5-(15)N]glutamine; and (d) This new test may be important for monitoring the efficacy of novel treatments for OTCD, e.g., liver transplantation and gene therapy.
DNA Methylation-Mediated Repression of miR-886-3p Predicts Poor Outcome of Human Small Cell Lung Cancer
Authors: Jianzhong Cao, Yongmei Song, Nan Bi, Jie Shen, Wenyang Liu, Jing Fan, Guogui Sun, Tong Tong, Jie He, Yuankai Shi, Xun Zhang, Ning Lu, Yinghua He, Hongyu Zhang, Kelong Ma, Xiaoying Luo, Lei Lv, Hui Deng, Jing Cheng, Jingde Zhu, Luhua Wang, Qimin Zhan
Journal: Cancer Research (2013)

Abstract Small cell lung cancer (SCLC) is one of the most aggressive types of cancer, yet the pathologic mechanisms underlying its devastating clinical outcome remain elusive. In this report, we surveyed 924 miRNA (miR) for their expressions in the formalin-fixed paraffin-embedded specimens from 42 patients with SCLC, and found that the downregulated miR-886-3p is closely correlated with the shorter survival of SCLC. This correlation was validated with another 40 cases. It was further discovered that loss of miR-886-3p expression was mediated by DNA hypermethylation of its promoter in both cultured SCLC cells and tumor samples. Moreover, miR-886-3p potently repressed cell proliferation, migration, and invasion of NCI-H446 cell in cell culture via suppression of the expression of its target genes: PLK1 and TGF-β1 at posttranscription levels. Forced upregulation of miR-886-3p greatly inhibited in vivo tumor growth, bone/muscle invasion, and lung metastasis of NCI-H446 cells. This newly identified miR-886-3p-PLK1/TGF-β1 nexus that modulates SCLC aggression suggests that both loss of miR-886-3p expression and hypermethylation of the miR-886 promoter are the promising indicators for poor outcome of as well as new therapeutic targets for SCLC. Cancer Res; 73(11); 3326–35. ©2013 AACR.
Long‐term effect of HCV eradication in patients with mixed cryoglobulinemia: A prospective, controlled, open‐label, cohort study
Authors: Laura Gragnani, Elisa Fognani, Alessia Piluso, Barbara Boldrini, Teresa Urraro, Alessio Fabbrizzi, Cristina Stasi, Jessica Ranieri, Monica Monti, Umberto Arena, Claudio Iannacone, Giacomo Laffi, Anna Linda Zignego
Journal: Hepatology (2014)

Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)–associated mixed cryoglobulinemia (MC), especially concerning the long‐term effects of HCV eradication. The aim of this study was to evaluate the influence of MC on the virological response and the long‐term effects of viral eradication on MC. We prospectively enrolled 424 HCV + patients belonging to the following groups: MC syndrome (MCS)‐HCV (121 patients with symptomatic MC), MC‐HCV (132 patients with asymptomatic MC), and HCV (158 patients without MC). Pegylated interferon plus ribavirin treatment was administered according to standard protocols. Posttreatment follow‐up ranged from 35 to 124 months (mean 92.5 months). A significant difference was observed in the rate of sustained virological response between the HCV group and both the MC‐HCV ( P = 0.009) and MC‐HCV+MCS‐HCV ( P = 0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of nonresponse. The clinical–immunological response in MCS‐HCV correlated with the virological one. All patients with sustained virological response also experienced a sustained clinical response, either complete or partial. In the majority of sustained virological response patients all MCS symptoms persistently disappeared (36 patients, 57%); in only two (3%) did definite MCS persist. All virological nonresponders were also clinical nonresponders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of interferon‐based therapy on HCV patients with and without MC and with and without symptoms, as well as the long‐term effects of viral eradication on MC. Conclusion : MC is a negative prognostic factor of virological response. Clearance of HCV led to persistent resolution or improvement of MCS, strongly suggesting the need for a next generation of highly effective antiviral drugs. (H epatology 2015;61:1145‐1153)
Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after surgery, with or without radiation therapy
Authors: Shang-Ming Chiou, L. Dade Lunsford, Ajay Niranjan, Douglas Kondziolka, John C. Flickinger
Journal: Neuro-Oncology (2001)

This study evaluated the role of stereotactic radiosurgery in the multimodality management of craniopharyngioma patients whose prior therapies failed. Ten consecutive patients (3 males and 7 females) had radiosurgery for craniopharyngioma during a 10-year interval. Their ages ranged from 9 to 64 years (median, 14.5 years). The median interval between diagnosis and radiosurgery was 46.5 months. In total, 12 stereotactic radiosurgical procedures were performed to control the solid component of the tumor (2 intrasellar and 10 suprasellar tumors). The median tumor volume was 1.35 cm3. One to 9 isocenters with different beam diameters were used; the median marginal dose was 16.4 Gy; and the dose to the optic apparatus was limited to less than 8 Gy. Clinical and imaging follow-up data were obtained at a median of 63 months (range, 13-150 months) from radiosurgery. Overall, 7 of 12 tumors became smaller or vanished within a median of 8.5 months. Prior visual defects objectively improved in 6 patients. One patient with prior visual defect deteriorated further and lost vision 9 months after radiosurgery. Multimodality therapy is often necessary for patients with refractory solid and cystic craniopharyngiomas. Stereotactic radiosurgery is a reasonable option in select patients with small recurrent or residual craniopharyngioma.
Functional FGFR4 Gly388Arg Polymorphism Predicts Prognosis in Lung Adenocarcinoma Patients
Authors: Monica Spinola, Vera Leoni, Carmen Pignatiello, Barbara Conti, Fernando Ravagnani, Ugo Pastorino, Tommaso A. Dragani
Journal: Journal of Clinical Oncology (2005)

Fibroblast growth factor receptor 4 (FGFR4) is a member of a family of transmembrane receptors with ligand-induced tyrosine kinase activity. The Gly388Arg polymorphism in the FGFR4 gene was reported to modulate cancer cell migration in vitro and to be associated with breast, colon, and prostate cancer prognostic parameters. The purpose of this study was to investigate the involvement of the FGFR4 polymorphism in lung tumorigenesis.A case-control study was performed including 274 patients with histologically confirmed lung adenocarcinoma and 401 healthy control subjects from general population. mRNA expression analysis was carried out in healthy lung of cancer patients.Patients with the Arg/Arg or Gly/Arg genotype compared to those with a Gly/Gly genotype had an earlier age at cancer onset (median age, 60.2 v 63.4 years), higher proportion of poor clinical stage disease (hazard ratio [HR], 2.3; 95% CI, 1.4 to 3.9; P = .002), of nodal involvement (HR, 1.9; 95% CI, 1.1 to 3.2; P = .027), or of short-term survivors (HR, 1.6; 95% CI, 1.1 to 2.3; P = .008). In healthy lungs, FGFR4 did not show allele-specific expression and mRNA levels were not associated with genotype.This study suggests that FGFR4 Gly388Arg polymorphism may predict prognosis in lung adenocarcinoma.
Synaptic Plasticity and Memory: An Evaluation of the Hypothesis
Authors: S. J. Martin, P. D. Grimwood, R. G. M. Morris
Journal: Annual Review of Neuroscience (2000)

Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that “activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed.” We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency.
Impact of accelerometer wear time on physical activity data: a NHANES semisimulation data approach
Authors: Stephen D Herrmann, Tiago V Barreira, Minsoo Kang, Barbara E Ainsworth
Journal: British Journal of Sports Medicine (2012)

Background Current research practice employs wide-ranging accelerometer wear time criteria to identify a valid day of physical activity (PA) measurement. Objective To evaluate the effects of varying amounts of daily accelerometer wear time on PA data. Methods A total of 1000 days of accelerometer data from 1000 participants (age=38.7±14.3 years; body mass index=28.2±6.7 kg/m 2 ) were selected from the 2005–2006 National Health and Nutrition Examination Study data set. A reference data set was created using 200 random days with 14 h/day of wear time. Four additional samples of 200 days were randomly selected with a wear time of 10, 11, 12 and 13 h/day 1 . These data sets were used in day-to-day comparison to create four semisimulation data sets (10, 11, 12, 13 h/day) from the reference data set. Differences in step count and time spent in inactivity (&lt;100 cts/min), light (100–1951 cts/min), moderate (1952–5724 cts/min) and vigorous (≥5725 cts/min) intensity PA were assessed using repeated-measures analysis of variance and absolute percent error (APE). Results There were significant differences for moderate intensity PA between the reference data set and semisimulation data sets of 10 and 11 h/day. Differences were observed in 10–13 h/day 1 for inactivity and light intensity PA, and 10–12 h/day for steps (all p values &lt;0.05). APE increased with shorter wear time (13 h/day=3.9–14.1%; 12 h/day=9.9–15.2%, 11 h/day=17.1–35.5%; 10 h/day=24.6–40.3%). Discussion These data suggest that using accelerometer wear time criteria of 12 h/day or less may underestimate step count and time spent in various PA levels.
Extended Follow-Up of a Cohort of British Chemical Workers Exposed to Formaldehyde
Authors: David Coggon, E Clare Harris, Jason Poole, Keith T Palmer
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Formaldehyde is mutagenic and, when inhaled at high concentrations, carcinogenic in rats. Some epidemiologic studies have linked occupational exposure to formaldehyde with cancers of the nose, nasopharynx, and lung, but the evidence for human carcinogenicity has been inconsistent and requires clarification. Methods: We extended by 11 years the follow-up of an existing cohort of 14 014 men employed after 1937 at six British factories where formaldehyde was produced or used. Subjects had been identified from employment records, and their jobs had been classified for potential exposure to formaldehyde. Standardized mortality ratios (SMRs) were derived using the person-years method and were compared with the expected numbers of deaths for the national population. Results: During follow-up through December 31, 2000, 5185 deaths were recorded, including two from sino-nasal cancer (2.3 expected) and one from nasopharyngeal cancer (2.0 expected). Relative to the national population, mortality from lung cancer was increased among those who worked with formaldehyde, particularly in men in the highest of four estimated exposure categories (>2 ppm) (SMR = 1.58, 95% confidence interval = 1.40 to 1.78), and the increase persisted after adjustment for local geographic variations in mortality (SMR = 1.28, 95% confidence interval = 1.13 to 1.44). However, there was a statistically nonsignificant decrease in the risk of death from lung cancer with duration of high exposure (Ptrend = .18), and this risk showed no trend with time since first high exposure (Ptrend = .99). Conclusions: The evidence for human carcinogenicity of formaldehyde remains unconvincing. Although a small effect on sino-nasal or nasopharyngeal cancer cannot be ruled out, a possible increase in the risk of lung cancer is a greater concern.
Ethical Issues in Stopping Randomized Trials Early Because of Apparent Benefit
Authors: Paul S. Mueller, Victor M. Montori, Dirk Bassler, Barbara A. Koenig, Gordon H. Guyatt
Journal: Annals of Internal Medicine (2007)

Stopping randomized trials early because of an apparent benefit is becoming more common. To protect and promote the interests of trial participants, investigators may feel obligated to stop a trial early because of the apparent benefit of a study treatment (compared with placebo or other treatment). There are, however, serious ethical problems with doing so. Truncated trials systematically overestimate treatment effects; in cases where the number of accrued outcome events is small, the overestimation may be very large. Generating seriously inflated estimates of treatment effect violates the ethical research requirement of scientific validity. Subsequent use of inflated estimates to inform clinical decision making and practice guidelines violates the ethical requirements of social value and a favorable risk-benefit ratio. Researchers should ensure that a large number of outcome events accrues before stopping a trial and then continue recruitment to assess whether positive trends continue. This can balance the need to protect research participants with the ethical requirements of scientific validity, social value, and a favorable risk-benefit ratio.
Doctors battle to contain cholera in Rwandan camps
Authors: L Byrne
Journal: BMJ (1994)

As cholera continues to rage through the refugee camps in and around the Zairean border town of Goma over 200 expatriate doctors and nurses are now working in the region for the medical aid agency Medecins Sans Frontieres. It is the largest contingent ever deployed by the agency in a disaster area at one time. Most of the volunteers are working in the Goma region. Further teams are active in refugee camps in Rwanda, Burundi, and Tanzania. As the death toll from cholera continues to rise, however, the agency is appealing for more volunteers.

The agency's clinics, which were originally opened in Goma and along its access roads to deal with all types of medical problems, are now working full time to stem the cholera epidemic. Other medical problems such …
Long-term efficacy of dietary weight loss in sleep apnoea/hypopnoea syndrome
Authors: G Sampol, X Munoz, MT Sagales, S Marti, A Roca, M Dolors de la Calzada, P Lloberes, F Morell
Journal: European Respiratory Journal (1998)

Weight loss is associated with clinical improvement in sleep apnoea/ hypopnoea syndrome (SAHS). The aim of this study was to ascertain whether the therapeutic efficacy of dietary weight loss is maintained in the long-term. From a total of 216 overweight SAHS patients treated by only a weight reduction programme, 24 cured by this method (apnoea/hypopnoea index (AHI) at diagnosis 443+/-27.8, after weight loss 3+/-3.1) were re-evaluated after a mean (+/-SD) period of 94.3+/-27.4 months post-cure. No correlation was found between changes in AHI and body mass index experienced by each patient in the two phases of the study (diagnosis to cure and cure to long-term follow-up), r=0.29, p=0.156, demonstrating a marked intra-individual variability. Six of the 13 patients who maintained their weight presented recurrence of SAHS (AHI 40.5+/-24.1) as did eight of the 11 who had regained weight (AHI 44.3+/-23.). Weight maintenance was more frequent among patients who had continued to attend periodic appointments, 10/11 versus 3/13 (p&lt;0.001). In conclusion, weight-loss efficacy is maintained in the long-term in some sleep apnoea/hypopnoea syndrome patients. This study indicates the need for periodic follow-up of these patients as a reinforcement for weight maintenance and for early detection of the reappearance of sleep apnoea/hypopnoea syndrome.