tbuckley/cabot-search huggingface dataset:
Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span
Authors: Emrush Rexhaj, Ariane Paoloni-Giacobino, Stefano F. Rimoldi, Daniel G. Fuster, Manuel Anderegg, Emmanuel Somm, Elisa Bouillet, Yves Allemann, Claudio Sartori, Urs Scherrer
Journal: Journal of Clinical Investigation (2013)

Children conceived by assisted reproductive technologies (ART) display a level of vascular dysfunction similar to that seen in children of mothers with preeclamspia. The long-term consequences of ART-associated vascular disorders are unknown and difficult to investigate in healthy children. Here, we found that vasculature from mice generated by ART display endothelial dysfunction and increased stiffness, which translated into arterial hypertension in vivo. Progeny of male ART mice also exhibited vascular dysfunction, suggesting underlying epigenetic modifications. ART mice had altered methylation at the promoter of the gene encoding eNOS in the aorta, which correlated with decreased vascular eNOS expression and NO synthesis. Administration of a deacetylase inhibitor to ART mice normalized vascular gene methylation and function and resulted in progeny without vascular dysfunction. The induction of ART-associated vascular and epigenetic alterations appeared to be related to the embryo environment; these alterations were possibly facilitated by the hormonally stimulated ovulation accompanying ART. Finally, ART mice challenged with a high-fat diet had roughly a 25% shorter life span compared with control animals. This study highlights the potential of ART to induce vascular dysfunction and shorten life span and suggests that epigenetic alterations contribute to these problems.
Biomarkers of oxidative stress following continuous positive airway pressure withdrawal: data from two randomised trials
Authors: John R. Stradling, Esther I. Schwarz, Christian Schlatzer, Ari R. Manuel, Regent Lee, Charalambos Antoniades, Malcolm Kohler
Journal: European Respiratory Journal (2015)

There is conflicting evidence whether intermittent hypoxia in obstructive sleep apnoea (OSA) influences oxidative stress. We hypothesised that withdrawal of continuous positive airway pressure (CPAP) from patients with OSA would raise markers of oxidative stress. 59 patients with CPAP-treated moderate-to-severe OSA (oxygen desaturation index (ODI) &gt;20 events·h −1 ) were randomised 1:1 to either stay on CPAP (n=30) or change to sham CPAP (n=29) for 2 weeks. Using samples from two similar studies at two sites, we measured early morning blood malondialdehyde (MDA, a primary outcome in one study and a secondary outcome in the other), lipid hydroperoxides, total antioxidant capacity, superoxide generation from mononuclear cells and urinary F2-isoprostane. We also measured superoxide dismutase as a marker of hypoxic preconditioning. “Treatment” effects (sham CPAP versus CPAP) were calculated via linear regression. Sham CPAP provoked moderate-to-severe OSA (mean ODI 46 events·h −1 ), but blood markers of oxidative stress did not change significantly (MDA “treatment” effect (95% CI) −0.02 (−0.23 to +0.19) μmol·L −1 ). Urinary F2-isoprostane fell significantly by ∼30% (−0.26 (−0.42 to −0.10) ng·mL −1 ) and superoxide dismutase increased similarly (+0.17 (+0.02 to +0.30) ng·mL −1 ). We found no direct evidence of increased oxidative stress in patients experiencing a return of their moderate-to-severe OSA. The fall in urinary F2-isoprostane and rise in superoxide dismutase implies that hypoxic preconditioning may have reduced oxidative stress.
Horner's syndrome caused by an intercostal chest drain.
Authors: P Campbell, T Neil, P N Wake
Journal: Thorax (1989)

Horner9s syndrome occurred in a young woman as a complication of the treatment of a traumatic pneumothorax with an intercostal drain. The nerve damage probably occurred when the lung had fully re-expanded, pressing the tip of the intercostal drain, lying at the apex of the pleural cavity, on to the sympathetic chain.
Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group.
Authors: M Karvonen, M Viik-Kajander, E Moltchanova, I Libman, R LaPorte, J Tuomilehto
Journal: Diabetes Care (2000)

OBJECTIVE: To investigate and monitor the patterns in incidence of childhood type 1 diabetes worldwide. RESEARCH DESIGN AND METHODS: The incidence of type 1 diabetes (per 100,000 per year) from 1990 to 1994 was determined in children &amp;lt; or =14 years of age from 100 centers in 50 countries. A total of 19,164 cases were diagnosed in study populations totaling 75.1 million children. The annual incidence rates were calculated per 100,000 population. RESULTS: The overall age-adjusted incidence of type 1 diabetes varied from 0.1/100,000 per year in China and Venezuela to 36.8/100,000 per year in Sardinia and 36.5/100,000 per year in Finland. This represents a &amp;gt;350-fold variation in the incidence among the 100 populations worldwide. The global pattern of variation in incidence was evaluated by arbitrarily grouping the populations with a very low (&amp;lt;1/100,000 per year), a low (1-4.99/100,000 per year), an intermediate (5-9.99/100,000 per year), a high (10-19.99/100,000 per year), and a very high (&amp;gt; or =20/100,000 per year) incidence. Of the European populations, 18 of 39 had an intermediate incidence, and the remainder had a high or very high incidence. A very high incidence (&amp;gt; or =20/ 100,000 per year) was found in Sardinia, Finland, Sweden, Norway Portugal, the U.K., Canada, and New Zealand. The lowest incidence (&amp;lt;1/100,000 per year) was found in the populations from China and South America. In most populations, the incidence increased with age and was the highest among children 10-14 years of age. CONCLUSIONS: The range of global variation in the incidence of childhood type 1 diabetes is even larger than previously described. The earlier reported polar-equatorial gradient in the incidence does not seem to be as strong as previously assumed, but the variation seems to follow ethnic and racial distribution in the world population.
Lung cancer * 9: Molecular biology of lung cancer: clinical implications
Authors: K M Fong
Journal: Thorax (2003)

It has been hypothesised that clinically evident lung cancers have accumulated many different genetic or epigenetic abnormalities in oncogenes and/or tumour suppressor genes. This notion has important clinical ramifications. Recent developments in our knowledge of the molecular biology of lung cancer are reviewed, with particular reference to genetic abnormalities in tumour suppressor gene inactivation and overactivity of growth promoting oncogenes. These changes lead to the "hallmarks of lung cancer". These hallmarks are the new rational targets for early detection, prevention, and treatment of lung cancer.
‘What's happening?’ A content analysis of concussion-related traffic on<i>Twitter</i>
Authors: S John Sullivan, Anthony G Schneiders, Choon-Wi Cheang, Emma Kitto, Hopin Lee, Jason Redhead, Sarah Ward, Osman H Ahmed, Paul R McCrory
Journal: British Journal of Sports Medicine (2011)

Background Twitter is a rapidly growing social networking site (SNS) with approximately 124 million users worldwide. Twitter allows users to post brief messages (‘tweets’) online, on a range of everyday topics including those dealing with health and wellbeing. Currently, little is known about how tweets are used to convey information relating to specific injuries, such as concussion, that commonly occur in youth sports. Objective The purpose of this study was to analyse the online content of concussion-related tweets on the SNS Twitter , to determine the concept and context of mild traumatic brain injury as it relates to an online population. Study design A prospective observational study using content analysis. Methods Twitter traffic was investigated over a 7-day period in July 2010, using eight concussion-related search terms. From the 3488 tweets identified, 1000 were randomly selected and independently analysed using a customised coding scheme to determine major content themes. Results The most frequent theme was ‘news’ (33%) followed by ‘sharing personal information/situation’ (27%) and ‘inferred management’ (13%). Demographic data were available for 60% of the sample, with the majority of tweets (82%) originating from the USA, followed by Asia (5%) and the UK (4.5%). Conclusion This study highlights the capacity of Twitter to serve as a powerful broadcast medium for sports concussion information and education.
Is asthma treatment affordable in developing countries?
Authors: J. P. Watson, R. A. Lewis
Journal: Thorax (1997)

BACKGROUND: A study was undertaken to assess whether the therapeutic aspects of published international asthma management guidelines are practically applicable in developing countries. METHODS: Questionnaires were sent to expatriate doctors working in developing countries. RESULTS: Forty one replies were received from 24 countries in Africa and Asia. Oral salbutamol was prescribed "usually" or "often" by 35 of the 41 respondents, theophyllines by 30, inhaled bronchodilators by 12, inhaled steroids by two, and cromoglycate by two. Theophyllines were locally available in all 41 cases, oral salbutamol in 40, inhaled bronchodilators in 34, and inhaled steroids (usually beclomethasone 50 micrograms) in only 15. Where they were available, the median (range) coat of a beclomethasone 50 micrograms inhaler was 20% (6.8-100%) of average local monthly income, salbutamol inhaler 13% (3.3-250%), 90 salbutamol 4 mg tablets 3.8% (0.8-75%), and 90 aminophylline 100 mg tablets 4.5% (0.5-70%). If they were available locally at a cheaper price, 34 (83%) respondents would prescribe more inhaled steroids and 37 (90%) would prescribe more inhaled bronchodilators. CONCLUSIONS: Many asthma patients in developing countries are not receiving adequate treatment because the required drugs are not available in their area or are prohibitively expensive.
Is Hyperglycemia a Causal Factor in Cardiovascular Disease?
Authors: Jaime A. Davidson, Christopher G. Parkin
Journal: Diabetes Care (2009)

Given that cardiovascular disease is a common complication of diabetes (1) and the leading cause of death among people with diabetes (2,3), it is important that we use the most effective therapies to manage lipids, blood pressure, and glycemia to reduce the risk, progression, and impact of macrovascular disease. Recent studies by Gaede et al. (4) clearly demonstrated that intensive management of all risk factors, including lipids, blood pressure, and glycemia, had significant beneficial effects on cardiovascular-related deaths. This intensive therapy was also found to be cost-effective (5).

Nevertheless, questions are now being raised regarding the importance of glycemia relevant to the prevention and/or progression of cardiovascular disease. To begin answering these questions, we first need to ask: Is there any reason not to believe there is a link between hyperglycemia and cardiovascular disease?

We have strong evidence from large randomized controlled trials that clearly establish a causal relationship between poor glycemic control and the development of microvascular disease (6,7). Why should we assume that large blood vessels are immune to the same damaging effect of hyperglycemia? We should not: there is plenty of evidence linking hyperglycemia to macrovascular risk.

Analysis of data from 3,642 U.K. Prospective Diabetes Study subjects (for whom complete data for potential confounders were available) showed a significant 14% ( P < 0.0001) reduction in myocardial infarction for each 1% reduction in mean A1C (8).

An early meta-regression analysis by Coutinho et al. (9) showed that the progressive relationship between glucose levels and cardiovascular …
Diversity of Myocardial Interstitial Proteolytic Pathways
Authors: Francis G. Spinale
Journal: Circulation (2011)

A fundamental objective of cardiovascular medicine is the early detection of structural changes within the heart and vasculature that would be harbingers of disease.For example, a much greater emphasis has been placed on identifying patients with underlying changes in left ventricular (LV) myocardial structure before the onset of occult LV dysfunction and symptomatic heart failure. 1 These changes in LV myocardial form and function have been generically termed LV remodeling, and an important research direction is to identify critical pathways that contribute to this adverse remodeling process.Although significant past research efforts have been made to identify changes in cardiocyte structure and function, LV remodeling is a multifactorial process involving both cellular and extracellular pathways.An evolving concept is that a significant interplay exists among biological signaling molecules, transmembrane proteins, and proteases within the myocardial interstitial space, which in turn promulgates LV remodeling.In the present issue of Circulation, a pair of studies is presented that further demonstrate the diverse functionality of proteases that exist within the myocardial interstitial space and how genetically altering these proteolytic pathways can result in unexpected consequences for LV remodeling process. 2,
Myeloid and monocytic dyspoiesis as determined by flow cytometric scoring in myelodysplastic syndrome correlates with the IPSS and with outcome after hematopoietic stem cell transplantation
Authors: Denise A. Wells, Martin Benesch, Michael R. Loken, Carlos Vallejo, David Myerson, Wendy M. Leisenring, H. Joachim Deeg
Journal: Blood (2003)
Junior Doctors' Hours: What Do They Really Think?
Authors: S West, S Weight, B J Jenkins, T P Stephenson
Journal: Journal of the Royal Society of Medicine (1994)

Junior doctors' hours are one of the most controversial topics under debate in the health service today. We undertook a detailed postal questionnaire of hospital doctors in training within a major teaching unit in order to assess the awareness and perceived implications of the incipient changes and to elucidate how it was felt these changes would affect both the doctors and patients. The questionnaire focused specifically on the effect of the changes on quality and continuity of patient care, junior training and socio-economic factors relating to the medical staff. The questionnaire was entirely anonymous and carried only the first author name but provision was made to determine current grade, specialty, age, sex and career plans of the respondents. Importantly, space was included at the end for pertinent comments. All junior staff in training in all specialties in the Cardiff area were circulated. Three hundred and twenty-six questionnaires were sent out and 202 were returned of which 192 were properly completed (59%). Almost everyone was au fait with the proposed changes. There was a surprisingly high level of support for changes among non-surgical trainees, and half felt that quality of care would improve, though the more senior the trainee, the less enthusiastic they were in all aspects. Many felt that far too little consultation with junior staff had taken place and there was generalized criticism of general practitioner trainees by their specializing counterparts, partly because of a perceived lack of commitment and partly because of blame of this group for the inception of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Ces3/TGH Deficiency Improves Dyslipidemia and Reduces Atherosclerosis in <i>Ldlr</i> <sup>−/−</sup> Mice
Authors: Jihong Lian, Ariel D. Quiroga, Lena Li, Richard Lehner
Journal: Circulation Research (2012)

Carboxylesterase 3/triacylglycerol hydrolase (TGH) has been shown to participate in hepatic very low-density lipoprotein (VLDL) assembly. Deficiency of TGH in mice lowers plasma lipids and atherogenic lipoproteins without inducing hepatic steatosis.To investigate the contribution of TGH to atherosclerotic lesion development in mice that lack low-density lipoprotein receptor (LDLR).Mice deficient in LDL receptor (Ldlr(-/-)) and mice lacking both TGH and LDLR (Tgh(-/-)/Ldlr(-/-)) were fed with a Western-type diet for 12 weeks. Analysis of Tgh(-/-)/Ldlr(-/-) plasma showed an atheroprotective lipoprotein profile with decreased cholesterol in the VLDL and the LDL fractions, concomitant with elevated high-density lipoprotein cholesterol. Significantly reduced plasma apolipoprotein B levels were also observed in Tgh(-/-)/Ldlr(-/-) mice. Consequently, Tgh(-/-)/Ldlr(-/-) mice presented with a significant reduction (54%, P<0.01) of the high-fat, high-cholesterol dieteninduced atherosclerotic plaques when compared with Tgh(+/+)/Ldlr(-/-) mice in the cross-sectional aortic root analysis. TGH deficiency did not further increase liver steatosis despite lowering plasma lipids, mainly due to reduced hepatic lipogenesis. The ameliorated dyslipidemia in Tgh(-/-)/Ldlr(-/-) mice was accompanied with significantly improved insulin sensitivity.Inhibition of TGH activity ameliorates atherosclerosis development and improves insulin sensitivity in Ldlr(-/-) mice.
PLACENTA PRAEVIA AND ITS RESULTING FOETAL MORTALITY
Authors: F. N. Reynolds
Journal: BMJ (1929)

Bitmm 387 is the site of a miiild infective process, suclh as we finid in osteo-artlhritis.The pr-obllem of treatmenit is by no mneans easy.It would seemii a mliinor andi( satisfactory lpro(ce(liure to remiiove the spur, btut w-e lhave nio guarantee thalt it will niot r-e-formll, and in a more extensive degree.Wheni we recall that these spurs may disappear sp)ontaneously, we feel that there is room for0 non-operative treatment.This takes the formil of "protection."A thick felt is placed below the situtation of the spine,a cup-shaped hollowi-ensuring freedom fromi pres- surte on the offending lproninonce.I am told that diathermy is of great value in hastening absorption of the deposit, but I cannot speak of this fromI personal exp'erieice.
Phase I Combination Study of Trabectedin and Doxorubicin in Patients with Soft-Tissue Sarcoma
Authors: Jean-Yves Blay, Margaret von Mehren, Brian L. Samuels, Michael P. Fanucchi, Isabelle Ray-Coquard, Brigid Buckley, Leen Gilles, Claudia Lebedinsky, Yusri A. Elsayed, Axel Le Cesne
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To determine the dose of trabectedin plus doxorubicin with granulocyte colony-stimulating factor support associated with manageable neutropenia and acceptable dose-limiting toxicities (DLT) in patients with recurrent or persistent soft-tissue sarcoma. Methods: In this phase I, open-label, multicenter trial, patients previously treated with 0-1 prior chemotherapy regimens excluding doxorubicin, an Eastern Cooperative Oncology Group performance status 0-1, and adequate organ function received a 10- to 15-min i.v. infusion of doxorubicin 60 mg/m2 immediately followed by a 3-h i.v. infusion of trabectedin 0.9 to 1.3 mg/m2 on day 1 of a 3-week cycle. Because four of the first six patients experienced DLT-defining neutropenia during cycle 1, all subsequent patients received primary prophylactic granulocyte colony-stimulating factor. The maximum tolerated dose was the highest dose level with six or more patients in which less than one-third of the patients experienced severe neutropenia or DLT. Blood was collected during cycle 1 for pharmacokinetic analyses. Adverse events, tumor response, and survival were assessed. Results: Patients (N = 41) received a median of six cycles of treatment (range, 2-13). The maximum tolerated dose was trabectedin 1.1 mg/m2 and doxorubicin 60 mg/m2. Common grade 3/4 treatment-emergent adverse events were neutropenia (71%), alanine aminotransferase increase (46%), and thrombocytopenia (37%). Overall, 5 (12%) patients achieved a partial response and 34 (83%) maintained stable disease. Median progression-free survival was 9.2 months. Doxorubicin and trabectedin pharmacokinetics were not altered substantially with concomitant administration. Conclusion: The combination of doxorubicin 60 mg/m2 followed by trabectedin 1.1 mg/m2 every 21 days is safe and active in patients with soft-tissue sarcoma.
Activation of Antioxidant Pathways in Ras-Mediated Oncogenic Transformation of Human Surface Ovarian Epithelial Cells Revealed by Functional Proteomics and Mass Spectrometry
Authors: Travis W. Young, Fang C. Mei, Gong Yang, Jennifer A. Thompson-Lanza, Jinsong Liu, Xiaodong Cheng
Journal: Cancer Research (2004)

Cellular transformation is a complex process involving genetic alterations associated with multiple signaling pathways. Development of a transformation model using defined genetic elements has provided an opportunity to elucidate the role of oncogenes and tumor suppressor genes in the initiation and development of ovarian cancer. To study the cellular and molecular mechanisms of Ras-mediated oncogenic transformation of ovarian epithelial cells, we used a proteomic approach involving two-dimensional electrophoresis and mass spectrometry to profile two ovarian epithelial cell lines, one immortalized with SV40 T/t antigens and the human catalytic subunit of telomerase and the other transformed with an additional oncogenic ras(V12) allele. Of approximately 2200 observed protein spots, we have identified >30 protein targets that showed significant changes between the immortalized and transformed cell lines using peptide mass fingerprinting. Among these identified targets, one most notable group of proteins altered significantly consists of enzymes involved in cellular redox balance. Detailed analysis of these protein targets suggests that activation of Ras-signaling pathways increases the threshold of reactive oxidative species (ROS) tolerance by up-regulating the overall antioxidant capacity of cells, especially in mitochondria. This enhanced antioxidant capacity protects the transformed cells from high levels of ROS associated with the uncontrolled growth potential of tumor cells. It is conceivable that an enhanced antioxidation capability may constitute a common mechanism for tumor cells to evade apoptosis induced by oxidative stresses at high ROS levels.
Ex-Vivo Allergen Stimulation In Whole Blood: A Novel Approach For Evaluating Mechanisms Of Action Of Synthetic Peptide Immuno-Regulatory Epitopes
Authors: Pascal LC. Hickey, Mark Larché, Rod Hafner, Kristen Armstrong, Eileen Lee, Elaine Lee, Stephen A. Kilfeather
Journal: Journal of Allergy and Clinical Immunology (2014)
Effects of azithromycin on ozone-induced airway neutrophilia and cytokine release
Authors: G.I. Criqui, C. Solomon, B.S. Welch, R.E. Ferrando, H.A Boushey, J.R Balmes
Journal: European Respiratory Journal (2000)

Exposure of humans to ozone causes increased neutrophils and inflammatory cytokines in airway lining fluid. Recent research shows that macrolide antibiotics may reduce interleukin (IL)-8 production by bronchial epithelial cells and inhibit neutrophil chemotaxis. A double-blind, cross-over study was performed in which 12 healthy subjects underwent two separate 4-h exposures to 0.2 parts per million ozone while exercising intermittently. In the 73.5 h before exposure, subjects were pretreated with either 1,250 mg azithromycin or placebo. Sputum induction conducted 74 h pre- and 18 h post-exposure was used to measure total cells, per cent neutrophils, IL-6, and IL-8. There were significant (p&lt;0.05) pre- to post-exposure increases in total cells, neutrophils, IL-6 and IL-8 in both the azithromycin and placebo arms. However, no significant differences were found between azithromycin and placebo conditions in the post- minus pre-exposure value for these variables. The results suggest that in healthy subjects, in the design used, azithromycin, in usual clinical doses, does not have anti-inflammatory effects on human airways as indicated in the measured variables.