tbuckley/cabot-search huggingface dataset:
Exhaled nitric oxide measurements with dynamic flow restriction in children aged 4-8 yrs
Authors: M.W.H. Pijnenburg, E.T. Lissenberg, W. Hofhuis, L. Ghiro, W.C.J. Hop, W.P. Holland, J.C. de Jongste
Journal: European Respiratory Journal (2002)

Fractional exhaled nitric oxide concentration (FENO) depends on exhalation flow; however, children often are unable to perform controlled flow procedures. Therefore, a device was developed for off-line FENO sampling, with dynamic flow restriction (DFR). The authors compared off-line with on-line FENO, assessed feasibility, and obtained normal values for FENO in children aged 4-8 yrs. Subjects inhaled nitric oxide (NO)-free air and exhaled into the device, where DFR kept exhalation flow constant at 50 mL x s(-1). Dead space air was discarded. Exhaled air was collected in a 150 mL mylar balloon. On-line measurements were performed and values compared with off-line FENO in 19 adult volunteers. Seventy-nine children performed off-line sampling. All samples were analysed with a chemiluminescence NO-analyser. Normal values were obtained in 34 healthy children. There was an excellent correlation between on- and off-line values. Bland and Altman plots showed good agreement between on- and off-line FENO. Seventy-four out of 79 children were able to perform a correct off-line procedure. Geometric mean+/-SEM FENO in healthy children was 4.9+/-1.2 parts per billion (ppb) for male children and 7.6+/-1.1 ppb for female children. It can be concluded that off-line fraction of exhaled nitric oxide measurements with dynamic flow restriction are feasible in young children and correspond to on-line values.
Low diversity and biased substitution patterns in the mitochondrial DNA control region of sperm whales: implications for estimates of time since common ancestry
Authors: T. Lyrholm, O. Leimar, U. Gyllensten
Journal: Molecular Biology and Evolution (1996)

The mitochondrial DNA (mtDNA) control region was sequenced in 37 sperm whales from a large part of the global range of the species. Nucleotide diversity was several-fold lower than that reported for control regions of abundant and outbred mammals, but similar to that for populations known to have experienced bottlenecks. Relative neck tests did not suggest that the low diversity is due to a lower substitution rate in sperm whale mtDNA. Rather, it is more likely that demographic factors have reduced diversity. The pattern of nucleotide substitutions was examined by cladistic methods, facilitated by the apparent monophyly of lineages from the Southern Hemisphere, as defined by a single base pair deletion. Substitutions were nonrandom in nature, confined to a few "hot spots," and parallel substitutions constituted a majority of the inferred changes. The substitution pattern fitted a negative binomial distribution better than a Poisson distribution, and the bias in number of substitutions among sites was considerably higher than previously reported for the mtDNA control region of any species. A novel method of estimating time since common ancestry was developed, which utilizes the transition/transversion ratio R and the number of substitutions inferred from a parsimony analysis. Using this method, we estimated the age of sperm whale mtDNA diversity to be about 6,000-25,000 years, and when the uncertainty of R was accounted for, a range of about 1,000-100,000 years was obtained.
We are getting there!
Authors: Lars Engebretsen, Kathrin Steffen
Journal: British Journal of Sports Medicine (2010)

Warm upWhile fi nishing our paper on injuries and illnesses during the Olympic Games in Vancouver, we were contemplating our achievements in research on protection of the athlete's health.Granted, 15 years ago, very little had been done except for the occasional epidemiological study, oftentimes with defi cient methodology.National and international sports federations were reluctant to even mention injury problems in their sport and not willing to allocate research money.How much this fi eld has changed over the years!The fi nal proof of the merit of this fi eld came with the International Olympic Committee (IOC) President Jacques Rogge's editorial in the British Journal of Sports Medicine 2009, in which he highlighted the new IOC initiatives in the protection of athletes. 1he most recent news comes from the American Orthopedic Society for Sports Medicine (AOSSM) and their Stop Sports Injuries campaign. 2Their background is the following: injury rates are rising.In a recent report from the Center for Disease Control, high school athletes accounted for an estimated 2 million injuries.More than 5 million sports-related injuries requiring medical treatment occur in children under 18 years old; 50% of the injuries are due to overuse and are therefore preventable; and the combined healthcare cost in the USA for treatment of youth injuries is more than US$2.5 billion.Both of these initiatives cater for the young athlete, and they both emphasise the importance of increasing physical activity levels of our adolescent population.
Patient‐centered care: A new paradigm for chronic liver disease
Authors: Manisha Verma, Victor Navarro
Journal: Hepatology (2015)

1Einstein Healthcare Network, Division of HepatologyPhiladelphiaPA *Address reprint requests to: Victor Navarro, M.D., Division of Hepatology, Einstein Healthcare Network, 5401 Old York Road, Klein 505, Philadelphia PA 19141. E‐mail: [email protected]; fax: +1‐215‐456‐8058.
Interleukin-1 receptor-associated kinase-1 plays an essential role for Toll-like receptor (TLR)7- and TLR9-mediated interferon-α induction
Authors: Satoshi Uematsu, Shintaro Sato, Masahiro Yamamoto, Tomonori Hirotani, Hiroki Kato, Fumihiko Takeshita, Michiyuki Matsuda, Cevayir Coban, Ken J. Ishii, Taro Kawai, Osamu Takeuchi, Shizuo Akira
Journal: The Journal of Experimental Medicine (2005)

Toll-like receptors (TLRs) recognize microbial pathogens and trigger innate immune responses. Among TLR family members, TLR7, TLR8, and TLR9 induce interferon (IFN)-α in plasmacytoid dendritic cells (pDCs). This induction requires the formation of a complex consisting of the adaptor MyD88, tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and IFN regulatory factor (IRF) 7. Here we show an essential role of IL-1 receptor-associated kinase (IRAK)-1 in TLR7- and TLR9-mediated IRF7 signaling pathway. IRAK-1 directly bound and phosphorylated IRF7 in vitro. The kinase activity of IRAK-1 was necessary for transcriptional activation of IRF7. TLR7- and TLR9-mediated IFN-α production was abolished in Irak-1–deficient mice, whereas inflammatory cytokine production was not impaired. Despite normal activation of NF-κB and mitogen-activated protein kinases, IRF7 was not activated by a TLR9 ligand in Irak-1–deficient pDCs. These results indicated that IRAK-1 is a specific regulator for TLR7- and TLR9-mediated IFN-α induction in pDCs.
Strategies for Improving Long-Term Survival in Patients with ESRD
Authors: Charles R. Nolan
Journal: Journal of the American Society of Nephrology (2005)

In 2003, more than 320,000 people in the United States were receiving dialysis for ESRD, with predicted increases to 650,000 by 2010 and 2 million by 2030. Mortality from cardiovascular disease (CVD) in patients with ESRD is 10 to 30 times higher than in the general population. The exact mechanism of accelerated CVD in patients with kidney disease is unknown. Treatment costs for ESRD are in excess of $14 billion annually (6.4% of Medicare budget). Strategies to improve long-term outcomes include aggressive risk factor modification, minimization of dialysis complications, and kidney transplantation. Because abnormalities of mineral metabolism contribute to mortality risk, phosphate binder therapy is fundamental. More expensive non-calcium-containing phosphate binders such as sevelamer have been recommended to reduce cardiovascular calcification. However, the lack of outcome data and the $2 to $3 billion annual cost make it difficult to justify widespread utilization of newer binders as first-line therapy. Conversely, kidney transplantation is known to improve survival in ESRD. Progression of atherosclerosis and CVD in patients with renal failure is largely due to loss of renal function per se, and provision of a functioning kidney through renal transplantation halts the progression of CVD and dramatically reduces mortality. Despite this fact, many patients lose Medicare funding for immunosuppressive therapy 3 yr posttransplantation. To achieve the goal of prevention of cardiovascular mortality in patients with ESRD, it clearly would be more prudent, efficacious, and cost-effective to use Medicare prescription drug dollars to provide full coverage for life-long immunosuppressive drug therapy after renal transplantation.
Effects of octreotide on responses to colorectal distension in the rat
Authors: X Su, M B Burton, G F Gebhart
Journal: Gut (2001)

BACKGROUND AND AIMS It has been suggested that the analgesic effect of the somatostatin analogue octreotide in visceral pain involves peripheral mechanisms. We evaluated the effect of octreotide on responses to noxious colorectal distension in rats. METHODS In a behavioural study, pressor and electromyographic responses to colorectal distension were evaluated before and after intravenous or intrathecal administration of octreotide. In pelvic nerve afferent fibre recordings, responses of mechanosensitive fibres innervating the colon to noxious colorectal distension (80 mm Hg, 30 seconds) were tested before and after octreotide. RESULTS Octreotide was ineffective in attenuating responses to colorectal distension in either normal or acetic acid inflamed colon when administered intravenously but attenuated responses when given intrathecally. Administration of octreotide over a broad dose range (0.5 μg/kg to 2.4 mg/kg) did not alter responses of afferent fibres to noxious colorectal distension in untreated, or acetic acid or zymosan treated colons. CONCLUSIONS In the rat, octreotide has no peripheral (pelvic nerve) modulatory action in visceral nociception. The antinociceptive effect of octreotide in this model of visceral nociception is mediated by an action at central sites.
Serum Zinc and Secretory IgA Levels Are Important Factors in Children with Food Allergy
Authors: Yosuke Baba, Reina Yokota, Hiromi Yagisawa, Susumu Yamazaki, Asuka Ishida, Eisuke Inage, Mari Mori, Yoshikazu Ohtsuka, Toshiaki Shimizu
Journal: Journal of Allergy and Clinical Immunology (2015)
UTX and MLL4 Coordinately Regulate Transcriptional Programs for Cell Proliferation and Invasiveness in Breast Cancer Cells
Authors: Jae-Hwan Kim, Amrish Sharma, Shilpa S. Dhar, Sung-Hun Lee, Bingnan Gu, Chia-Hsin Chan, Hui-Kuan Lin, Min Gyu Lee
Journal: Cancer Research (2014)

Histone methyltransferases and demethylases reversibly modulate histone lysine methylation, which is considered a key epigenetic mark associated with gene regulation. Recently, aberrant regulation of gene expression by histone methylation modifiers has emerged as an important mechanism for tumorigenesis. However, it remains largely unknown how histone methyltransferases and demethylases coregulate transcriptional profiles for cancer cell characteristics. Here, we show that in breast cancer cells, the histone H3 lysine 27 (H3K27) demethylase UTX (also known as KDM6A) positively regulates gene expression programs associated with cell proliferation and invasion. The majority of UTX-controlled genes, including a cohort of oncogenes and prometastatic genes, are coregulated by the H3K4 methyltransferase mixed lineage leukemia 4 (MLL4, also called ALR, KMT2D, and MLL2). UTX interacted with a C-terminal region of MLL4. UTX knockdown resulted in significant decreases in the proliferation and invasiveness of breast cancer cells in vitro and in a mouse xenograft model. Such defective cellular characteristics of UTX-depleted cells were phenocopied by MLL4 knockdown cells. UTX-catalyzed demethylation of trimethylated H3K27 and MLL4-mediated trimethylation at H3K4 occurred interdependently at cotarget genes of UTX and MLL4. Clinically, high levels of UTX or MLL4 were associated with poor prognosis in patients with breast cancer. Taken together, these findings uncover that coordinated regulation of gene expression programs by a histone methyltransferase and a histone demethylase is coupled to the proliferation and invasion of breast cancer cells.
A Local University for London
Authors: J. K. Fowler
Journal: BMJ (1897)

Fthat it would be very injurious if their voluntary system were turned into a municipal system.They believed mostly in persuasion.It had been said that there should be considerable funds at the disposal of the central body.He had always believed that it was necessary, and that there was no disgrace in the fact; it certainly smoothed difficulties, and those institutions which deserved it would receive help.The voluntary system answered splendidly in connection with polytechnics in London; why not in hospitals?They were not relying on an unknown method, and such a course was not without precedent.The Charity Organisation Society in this matter was not seeking power and control; it was sug- gesting, proposing, and advancing ideas, which would be evi- dent to anyone who consulted the original scheme.He believed there was a mean between what was called compulsion and what was the ordinary method of co-operation in voluntary work.He believed they were creating in the public mind by their voluntary and municipal work a spirit of co- operation and give-and-take, and good feeling, which would react upon their whole system, and it was to such a feeling he would prefer to trust to bring about that extremely-wanted reform in their medical charities.The resolution was then put from the chair and carried, only two voting against.
Oral Tolvaptan Is Safe and Effective in Chronic Hyponatremia
Authors: Tomas Berl, Friederike Quittnat-Pelletier, Joseph G. Verbalis, Robert W. Schrier, Daniel G. Bichet, John Ouyang, Frank S. Czerwiec
Journal: Journal of the American Society of Nephrology (2010)

Vasopressin antagonists increase the serum sodium concentration in patients who have euvolemia and hypervolemia with hyponatremia in the short term (</=30 days), but their safety and efficacy with longer term administration is unknown. SALTWATER was a multicenter, open-label extension of the Study of Ascending Levels of Tolvaptan in Hyponatremia (SALT-1 and SALT-2). In total, 111 patients with hyponatremia received oral tolvaptan for a mean follow-up of 701 days, providing 77,369 patient-days of exposure. All patients had hyponatremia at randomization in SALT-1 and SALT-2, and 85% continued to have hyponatremia at entry in SALTWATER. The most common adverse effects attributed to tolvaptan were pollakiuria, thirst, fatigue, dry mouth, polydipsia, and polyuria. Six drug-related adverse effects led to study discontinuation. The increase in serum sodium exceeded the desired 1 mmol/L per h at initiation in five patients. Hypernatremia (>145 mmol/L) led to discontinuation in one patient. Mean serum sodium increased from 130.8 mmol/L at baseline to >135 mmol/L throughout the observation period (P < 0.001 versus baseline at most points). Responses were comparable between patients with euvolemia and those with heart failure but more modest in patients with cirrhosis. In conclusion, prolonged administration of tolvaptan maintains an increased serum sodium with an acceptable margin of safety.
Inhibition of Cell Adhesion by Antibodies to Arg-Gly-Asp (RGD) in Normal Immunoglobulin for Therapeutic Use (Intravenous Immunoglobulin, IVIg)
Authors: Tchavdar L. Vassilev, Michel D. Kazatchkine, Jean-Paul Duong Van Huyen, Medina Mekrache, Emmanuelle Bonnin, Jean Claude Mani, Chantal Lecroubier, Dirk Korinth, Dominique Baruch, Folke Schriever, Srini V. Kaveri
Journal: Blood (1999)
Comparison of Two Methods to Detect Publication Bias in Meta-analysis
Authors: Jaime L. Peters
Journal: JAMA (2006)

Egger's regression test is often used to help detect publication bias in meta-analyses. However, the performance of this test and the usual funnel plot have been challenged particularly when the summary estimate is the natural log of the odds ratio (lnOR).To compare the performance of Egger's regression test with a regression test based on sample size (a modification of Macaskill's test) with lnOR as the summary estimate.Simulation of meta-analyses under a number of scenarios in the presence and absence of publication bias and between-study heterogeneity.Type I error rates (the proportion of false-positive results) for each regression test and their power to detect publication bias when it is present (the proportion of true-positive results).Type I error rates for Egger's regression test are higher than those for the alternative regression test. The alternative regression test has the appropriate type I error rates regardless of the size of the underlying OR, the number of primary studies in the meta-analysis, and the level of between-study heterogeneity. The alternative regression test has comparable power to Egger's regression test to detect publication bias under conditions of low between-study heterogeneity.Because of appropriate type I error rates and reduction in the correlation between the lnOR and its variance, the alternative regression test can be used in place of Egger's regression test when the summary estimates are lnORs.
Protective role of macrophage-derived ceruloplasmin in inflammatory bowel disease
Authors: Bakytzhan Bakhautdin, Maria Febbraio, Esen Goksoy, Carol A de la Motte, Muhammet F Gulen, Erin Patricia Childers, Stanley L Hazen, Xiaoxia Li, Paul L Fox
Journal: Gut (2012)

<h3>Objective</h3> Intestinal microflora and inflammatory cell infiltrates play critical roles in the pathogenesis of acute colitis. Ceruloplasmin is an acute-phase plasma protein produced by hepatocytes and activated macrophages, and has ferroxidase with bactericidal activities. The goal is to understand the role of ceruloplasmin in colitis progression in a genetically modified murine model. <h3>Design</h3> Experimental colitis was induced in ceruloplasmin null (Cp<sup>−/−</sup>) and wild-type (WT) mice by dextran sulphate sodium administration. The role of ceruloplasmin was further evaluated by transplantation of WT macrophages into Cp<sup>−/−</sup> mice. <h3>Results</h3> Cp<sup>−/−</sup> mice rapidly lost weight and were moribund by day 14, while WT mice survived at least 30 days. Colon culture supernatants from Cp<sup>−/−</sup> mice exhibited elevated levels of TNFα, KC and MCP-1, indicative of increased inflammation and neutrophil and macrophage infiltration. Elevated leucocytes and severe histopathology were observed in Cp<sup>−/−</sup> mice. Elevated protein carbonyl content was detected in colons from Cp<sup>−/−</sup> mice suggesting ceruloplasmin antioxidant activity might contribute to its protective function. Unexpectedly, intraperitoneal administration of human ceruloplasmin into Cp<sup>−/−</sup> mice did not afford protection. Bone marrow transplantation from WT mice or injection of isolated peripheral blood monocytes markedly reduced severity of colitis and morbidity in Cp<sup>−/−</sup> mice. <h3>Conclusion</h3> Macrophage-derived ceruloplasmin contributes importantly to protection against inflammation and tissue injury in acute and chronic experimental colitis. The findings suggest that defects in ceruloplasmin expression or processing may influence the onset or progression of inflammatory bowel disease in patients.
Authors’ response: what determines which 6MWT is conventional?
Authors: Emmylou Beekman, Ilse Mesters, Rik Gosselink, Onno C P van Schayck, Rob A de Bie
Journal: Thorax (2014)

We thank the co-chairs of the joint American Thoracic Society (ATS) and the European Respiratory Society (ERS) task force for their comments on our paper and interest in our article on reference values for the 6-min walk test (6MWT) performed over a 10m course. In their correspondence, the shorter course length is considered as one specific protocol deviation from the ATS statement1 that does not represent a conventional 6MWT. What is the ‘conventional’ 6MWT? Fourteen years ago, the ATS guidelines were published with the advice to test on a 30m course. However, at that time some studies used other course lengths, as was mentioned in the statement.1 Since then, more studies2–4 and healthcare providers have used a shorter course length due to space limitations. Moreover, …
Impact of supplementing newborn infants with vitamin A on early infant mortality: community based randomised trial in southern India
Authors: Lakshmi Rahmathullah, James M Tielsch, R D Thulasiraj, Joanne Katz, Christian Coles, Sheela Devi, Rajeesh John, Karthik Prakash, A V Sadanand, N Edwin, C Kamaraj
Journal: BMJ (2003)

To assess the impact of supplementing newborn infants with vitamin A on mortality at age 6 months.Community based, randomised, double blind, placebo controlled trial.Two rural districts of Tamil Nadu, southern India.11 619 newborn infants allocated 24 000 IU oral vitamin A or placebo on days 1 and 2 after delivery.Primary outcome measure was mortality at age 6 months.Infants in the vitamin A group had a 22% reduction in total mortality (95% confidence interval 4% to 37%) compared with those in the placebo group. Vitamin A had an impact on mortality between two weeks and three months after treatment, with no additional impact after three months.Supplementing newborn infants with vitamin A can significantly reduce early infant mortality.
Frequency by Decades of Unicuspid, Bicuspid, and Tricuspid Aortic Valves in Adults Having Isolated Aortic Valve Replacement for Aortic Stenosis, With or Without Associated Aortic Regurgitation
Authors: William C. Roberts, Jong M. Ko
Journal: Circulation (2005)

Background— Aortic valve stenosis (with or without aortic regurgitation and without associated mitral stenosis) in adults in the Western world has been considered in recent years to most commonly be the result of degenerative or atherosclerotic disease. Methods and Results— We examined operatively excised, stenotic aortic valves from 932 patients aged 26 to 91 years (mean±SD, 70±12), and none had associated mitral valve replacement or evidence of mitral stenosis: A total of 504 (54%) had congenitally malformed valves (unicuspid in 46 [unicommissural in 42; acommissural in 4] and bicuspid in 458); 417 (45%) had tricuspid valves (either absent or minimal commissural fusion); and 11 (1%) had valves of undetermined type. It is likely that the latter 11 valves also had been congenitally malformed. Of the 584 men, 343 (59%) had either a unicuspid or a bicuspid valve; of the 348 women, 161 (46%) had either a unicuspid or a bicuspid aortic valve. Conclusions— The data from this large study of adults having isolated aortic valve replacement for aortic stenosis (with or without associated aortic regurgitation) and without associated mitral stenosis or mitral valve replacement strongly suggest that an underlying congenitally malformed valve, at least in men, is more common than a tricuspid aortic valve.