tbuckley/cabot-search huggingface dataset:
T4 Mutations in BMPR-II Promote Inflammation Via Altered Superoxide Signalling: Insights into the Mechanisms Underlying Pulmonary Arterial Hypertension
Authors: E Soon, A Crosby, M Southwood, J Pepke-Zaba, P Upton, NW Morrell
Journal: Thorax (2012)

<h3>Introduction</h3> Although the presence of inflammation is well recognised in pulmonary arterial hypertension (PAH), the underlying mechanisms remain poorly understood. Mutations in the bone morphogenetic protein type II receptor gene, <i>BMPR2</i>, underlie the majority of heritable and a significant fraction of idiopathic PAH Here, we sought to determine whether loss of <i>BMPR2</i> was directly associated with inflammation, the underlying mechanisms, and possible therapeutic interventions. <h3>Methods</h3> The initial approach employed human and mouse pulmonary arterial smooth muscle cells (PASMCs) from controls and subjects with a mutation in <i>BMPR2</i>. Cells were studied at baseline and in response to lipopolysaccharide (LPS), in the presence or absence of pharmacological inhibitors of known pro-inflammatory pathways. Cytokines were measured by ELISA Reactive oxygen species were measured using dihydroethidium staining. For <i>in vivo</i> studies, we employed the heterozygous null <i>bmpr2</i> mouse (<i>bmpr2+/–</i>) and wild-type littermates. <h3>Results</h3> Chronic low dose LPS resulted in a marked elevation of right ventricular systolic pressure to ∼40 mmHg in <i>bmpr2+/–</i> mice, but not in wild-type mice (Fig.1). <i>In vitro</i> studies showed that mouse <i>bmpr2+/–</i> and human <i>BMPR2mut</i> PASMCs produced more IL-6 and IL-8 at baseline and after stimulation with LPS For example, <i>bmpr2+/–</i> PASMCs produced 1533±280 pg/ml of IL-6 (<i>versus</i> 341±10 pg/ml in controls, <i>P</i>&lt;0.01) after LPS stimulation. Reduced <i>BMPR2</i> was also associated with increased phospho-STAT3 levels and an abnormal pro-proliferative response to IL-6. Acute administration of LPS to the <i>bmpr2+/–</i> mouse reproduced these results <i>in vivo,</i> with increased lung and serum IL-6 and IL-8. The link between reduced <i>BMPR2</i> and increased cytokine expression was found to be associated with increased superoxide generation and loss of extracellular superoxide dismutase (SOD3). Treatment of <i>BMPR2</i> deficient PASMCs with the superoxide dismutase mimetic, Tempol, normalised the exaggerated secretion of IL-6 and IL-8. Co-administration of Tempol prevented the PAH phenotype in <i>bmpr2+/–</i> mice exposed to low dose LPS (Fig. 1). <h3>Conclusions</h3> We have determined a novel link between <i>BMPR2</i> loss and increased expression of pro-inflammatory cytokines, which is dependent on mishandling of superoxide. Our results suggest that pro-inflammatory stimuli may represent disease-provoking triggers for patients with <i>BMPR2</i> deficiency. Promotion of SOD3 activity may represent a novel therapeutic approach in PAH.
Integrated Analyses Identify a Master MicroRNA Regulatory Network for the Mesenchymal Subtype in Serous Ovarian Cancer
Authors: Da Yang, Yan Sun, Limei Hu, Hong Zheng, Ping Ji, Chad V. Pecot, Yanrui Zhao, Sheila Reynolds, Hanyin Cheng, Rajesha Rupaimoole, David Cogdell, Matti Nykter, Russell Broaddus, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Jinsong Liu, Ilya Shmulevich, Anil K. Sood, Kexin Chen, Wei Zhang
Journal: Cancer Cell (2013)
Increasing Use of Cardiopulmonary Resuscitation During Out-of-Hospital Ventricular Fibrillation Arrest
Authors: Thomas D. Rea, Michael Helbock, Stephen Perry, Michele Garcia, Don Cloyd, Linda Becker, Mickey Eisenberg
Journal: Circulation (2006)

Background— The most recent resuscitation guidelines have sought to improve the interface between defibrillation and cardiopulmonary resuscitation; the survival impact of these changes is unknown, however. A year before issuance of the most recent guidelines, we implemented protocol changes that provided a single shock without rhythm reanalysis, stacked shocks, or postdefibrillation pulse check, and extended the period of cardiopulmonary resuscitation from 1 to 2 minutes. We hypothesized that survival would be better with the new protocol. Methods and Results— The present study took place in a community with a 2-tiered emergency medical services response and an established system of cardiac arrest surveillance, training, and review. The investigation was a cohort study of persons who had bystander-witnessed out-of-hospital ventricular fibrillation arrest because of heart disease, comparing a prospectively defined intervention group (January 1, 2005, to January 31, 2006) with a historical control group that was treated according to previous guidelines of rhythm reanalysis, stacked shocks, and postdefibrillation pulse checks (January 1, 2002, to December 31, 2004). The primary outcome was survival to hospital discharge. The proportion of treated arrests that met inclusion criteria was similar for intervention and control periods (15.4% [134/869] versus 16.6% [374/2255]). Survival to hospital discharge was significantly greater during the intervention period compared with the control period (46% [61/134] versus 33% [122/374], P =0.008) and corresponded to a decrease in the interval from shock to start of chest compressions (28 versus 7 seconds). Adjustment for covariates did not alter the survival association. Conclusions— These results suggest the new resuscitation guidelines will alter the interface between defibrillation and cardiopulmonary resuscitation and in turn may improve outcomes.
Folic Acid Fortification of Food-Reply
Authors: Shirley A. A. Beresford
Journal: JAMA (1996)

In Reply.  —In response to Dr Bostom, we did state that vitamins B 12 , B 6 , and folic acid regulate plasma homocysteine levels, and we summarized and included PML studies in our meta-analysis. Although the ORs for elevated PML homocysteine tended to be higher than those for elevated fasting homocysteine, our analysis (p 1050, Table 1, and Figure 1) showed little difference in the pooled ORs for coronary and cerebrovascular diseases with inclusion or omission of the PML data (OR, 1.7 vs 1.8 for coronary artery disease; OR, 2.5 vs 2.3 for cerebrovascular disease). Increasing folic acid intake directly and independently reduces fasting plasma total homocysteine; such folic acid effects are stronger and more consistent than those of vitamin B 12 or vitamin B 6 . 1 We stated that vitamin B 6 can reduce elevated homocysteine PML. Different treatment for different patterns of elevated homocysteine deserves further investigation. On a
Use of Angiotensin Receptor Blockers and the Risk of Cancer
Authors: Björn Pasternak, Henrik Svanström, Torbjörn Callréus, Mads Melbye, Anders Hviid
Journal: Circulation (2011)

A recent meta-analysis of randomized trials suggested that use of angiotensin receptor blockers (ARBs) may be associated with a modestly increased risk of incident cancer, particularly lung cancer.We linked individual-level data from Danish registries on filled drug prescriptions, diagnostic information, and covariates. In a nationwide cohort of new users of ARBs and angiotensin-converting enzyme inhibitors ≥35 years of age during 1998 to 2006, we compared incidence rates of all cancer, cancer subgroups by anatomic site, and cancer mortality. Among 107 466 ARB users, 3954 cases of cancer were detected during 312 753 person-years of follow-up compared with 6214 cases during 435 207 person-years of follow-up in 209 692 angiotensin-converting enzyme inhibitor users (adjusted rate ratio, 0.99; 95% confidence interval, 0.95 to 1.03). Cancer risk did not increase with increasing duration of ARB exposure (increase in rate ratio per year, 0.99; 95% confidence interval, 0.99 to 1.00,) and was similar across individual ARBs. In subgroup analyses, there was a significant association between ARB use and cancer of male genital organs (rate ratio, 1.15; 95% confidence interval, 1.02 to 1.28), but no significantly increased risk of any of the other 15 cancer subgroups, including lung cancer (rate ratio, 0.92; 95% confidence interval, 0.82 to 1.02). For cancer mortality, the rate ratio was 0.77 (95% confidence interval, 0.72 to 0.82).In this large nationwide cohort, use of ARBs was not significantly associated with increased risk of incident cancer overall or of lung cancer.
Preventing Low Birthweight
Authors: Robert T. Brouillette
Journal: JAMA (1985)

In recent years approximately 7% of liveborn infants in the United States weighed less than 2,500 g (low birth weight) and slightly more than 1% weighed less than 1,500 g (very low birth weight). These percentages translate to roughly a quarter million low-birth weight infants per year and 40,000 very low-birth weight infants per year. This report, commissioned by the Institute of Medicine, is an excellent summary of the current knowledge about low birth weight and of several approaches toward reducing its incidence. The report should provide a readable synthesis of the low-birth weight problem for experts and more general readers alike. Experts will find useful the appendix material and suggested areas for future research. The report is divided into two major parts. The first part covers definitions, the significance of low birth weight, etiology and risk factors, and recent trends. The second part discusses promising interventions to reduce the
The <i>α</i>‐chain of high‐affinity receptor for IgE (Fc<i>ɛ</i>RI<i>α</i>) gene polymorphisms and serum IgE levels
Authors: D. P. Potaczek, M. Sanak, L. Mastalerz, M. Setkowicz, M. Kaczor, E. Nizankowska, A. Szczeklik
Journal: Allergy (2006)

Background: The high‐affinity receptor for immunoglobulin‐E (IgE) (Fc ɛ RI) plays a major role in the pathogenesis of allergy, but there are only two published studies on its α subunit (Fc ɛ RI α ) genetic variability in allergic diseases. Aims of the study: Mutational screening in the region of the Fc ɛ RIα gene promoter and the first exon with subsequent genetic variability assessment in allergic patients and a random population sample. Methods: Allergic subjects were individuals with asthma or urticaria. Age‐ and sex‐matched controls were randomly selected from a large population sample. Mutational screening was performed using a single‐stranded conformational polymorphism and subsequent sequencing. Detected polymorphisms were genotyped by restriction fragment length polymorphism. Total serum IgE was measured in allergic subjects and controls. Skin prick tests, blood eosinophil count and aspirin challenge test were performed only in the subjects. A subgroup of the subjects was further characterized by autologous serum skin test, histamine release test, Phadiatop and IgE antibodies against staphylococcal enterotoxins. Results: Two linked polymorphisms −344 C&gt;T and −95 T&gt;C were found within the Fc ɛ RI α gene. The allele −344 T frequency was 0.45 vs 0.37 ( P = 0.33), and the allele −95 C frequency was 0.26 in subjects vs 0.30 in controls ( P = 0.62). Serum IgE was significantly higher in subjects homozygous for the −344T allele (TT genotype) than in those carrying the −344 C allele (CT or CC genotype; P = 0.003), but this association was not detectable in controls. Conclusions: Our findings of genotype‐related differences in IgE levels in allergic patients suggest an impact of −344 C&gt;T but not −95 T&gt;C gene polymorphism of Fc ɛ RI α on total levels of IgE. The genetic variability in Fc ɛ RI α at the −344 nucleotide of its regulatory sequence, though not related to atopy, predicts higher levels of the immunoglobulin.
F-18 FDG PET/CT Imaging of Anal Canal Squamous Cell Carcinoma
Authors: Ba D. Nguyen, Panol C. Ram, Michael C. Roarke
Journal: Clinical Nuclear Medicine (2007)

Squamous cell carcinoma of the anal canal is an uncommon malignancy of the gastrointestinal tract predominantly encountered in a patient population with human papillomavirus and human immunodeficiency virus infection. Imaging and staging of this neoplasm is best evaluated with F-18 FDG PET/CT. The authors present 2 cases of anal cancer with PET/CT demonstration of an expected pattern of nodal metastasis in the first patient and atypical musculoskeletal dissemination in the second patient.
Anti-Tau Antibodies that Block Tau Aggregate Seeding In Vitro Markedly Decrease Pathology and Improve Cognition In Vivo
Authors: Kiran Yanamandra, Najla Kfoury, Hong Jiang, Thomas E. Mahan, Shengmei Ma, Susan E. Maloney, David F. Wozniak, Marc I. Diamond, David M. Holtzman
Journal: Neuron (2013)
Patient-ventilator interaction during synchronized intermittent mandatory ventilation. Effects of flow triggering.
Authors: R Giuliani, L Mascia, F Recchia, A Caracciolo, T Fiore, V M Ranieri
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Synchronized intermittent mandatory ventilation (SIMV) intermixes assisted and spontaneous breaths. Its ability as a weaning technique has been questioned on the basis that patients show little adaptation to ventilator assistance. We studied inspiratory effort and patient-ventilator interaction at different levels (SIMV, 100, 50, and 0%) of flow-triggered SIMV versus pressure-triggered SIMV in patients during the weaning period. The two triggering systems were evaluated during constant flow and constant pressure mandatory SIMV breaths. Inspiratory effort was estimated as the esophageal pressure time product (PTP) per breath (PTP/b) and per minute (PTP/min). The PTP/b and PTP/min of both mandatory and spontaneous breaths were significantly lower during flow triggering than during pressure triggering SIMV, irrespective of the ventilatory mode. During pressure-triggered SIMV PTP/b and PTP/min were identical for mandatory and spontaneous breaths, whereas during flow-triggered SIMV PTP/b and PTP/min were significantly lower for mandatory than for spontaneous breaths. This difference was greatest when flow triggering and constant pressure ventilation were associated. These data show that flow triggering reduces inspiratory effort during both mandatory and spontaneous SIMV breaths and obtains a better patient-ventilator interaction.
Giga-Ohm Seals on Intracellular Membranes: A Technique for Studying Intracellular Ion Channels in Intact Cells
Authors: Elizabeth A Jonas, Ronald J Knox, Leonard K Kaczmarek
Journal: Neuron (1997)

A method is outlined for obtaining giga-ohm seals on intracellular membranes in intact cells. The technique employs a variant of the patch-clamp technique: a concentric electrode arrangement protects an inner patch pipette during penetration of the plasma membrane, after which a seal can be formed on an internal organelle membrane. Using this technique, successful recordings can be obtained with the same frequency as with conventional patch clamping. To localize the position of the pipette within cells, lipophilic fluorescent dyes are included in the pipette solution. These dyes stain the membrane of internal organelles during seal formation and can then be visualized by video-enhanced or confocal imaging. The method can detect channels activated by inositol trisphosphate, as well as other types of intracellular membrane ion channel activity, and should facilitate studies of internal membranes in intact neurons and other cell types.
Prevalence of financial conflicts of interest among panel members producing clinical practice guidelines in Canada and United States: cross sectional study
Authors: J. Neuman, D. Korenstein, J. S. Ross, S. Keyhani
Journal: BMJ (2011)

<b>Objective</b> To determine the prevalence of financial conflicts of interest among members of panels producing clinical practice guidelines on screening, treatment, or both for hyperlipidaemia or diabetes. <b>Design</b> Cross sectional study. <b>Setting</b> Relevant guidelines published by national organisations in the United States and Canada between 2000 and 2010. <b>Participants</b> Members of guideline panels. <b>Main outcome measures</b> Prevalence of financial conflicts of interest among members of guideline panels and chairs of panels. <b>Results</b> Fourteen guidelines met our search criteria, of which five had no accompanying declaration of conflicts of interest by panel members. 288 panel members had participated in the guideline development process. Among the 288 panel members, 138 (48%) reported conflicts of interest at the time of the publication of the guideline and 150 (52%) either stated that they had no such conflicts or did not have an opportunity to declare any. Among 73 panellists who formally declared no conflicts, 8 (11%) were found to have one or more. Twelve of the 14 guideline panels evaluated identified chairs, among whom six had financial conflicts of interest. Overall, 150 (52%) panel members had conflicts, of which 138 were declared and 12 were undeclared. Panel members from government sponsored guidelines were less likely to have conflicts of interest compared with guidelines sponsored by non-government sources (15/92 (16%) <i>v</i> 135/196 (69%); P&lt;0.001). <b>Conclusions</b> The prevalence of financial conflicts of interest and their under-reporting by members of panels producing clinical practice guidelines on hyperlipidaemia or diabetes was high, and a relatively high proportion of guidelines did not have public disclosure of conflicts of interest. Organisations that produce guidelines should minimise conflicts of interest among panel members to ensure the credibility and evidence based nature of the guidelines9 content.
Procoagulant activity of bronchoalveolar lavage fluids taken from the site of tuberculous lesions
Authors: P Selvaraj, N Venkataprasad, VK Vijayan, R Prabhakar, PR Narayanan
Journal: European Respiratory Journal (1994)

We wanted to determine the procoagulant activity (PCA) of bronchoalveolar lavage fluids, in order to understand the macrophage-mediated lung injury at the site of tuberculous lesion. Alveolar lavage fluids taken from the site of a lesion (radiologically abnormal site (RAS)) and an unaffected site (radiologically normal site (RNS)) of active pulmonary tuberculosis (TB) patients (n = 7) and inactive (cured) patients (n = 9) were studied for their PCA producing potential. The observed results were not significant using Mann-Whitney test, and thus all increases/decreases reported below are trends/tendencies only. An increased PCA was seen in 4 out of 7 cell-free lavage supernatants of active-TB taken from the site of lesion (RAS), compared to only 1 out of 9 in inactive-TB. The PCA producing potential of the alveolar macrophages of RAS and RNS of active-TB patients was enhanced when the alveolar macrophages were co-cultured with autologous peripheral blood lymphocytes under in vitro condition. Stimulation with purified protein derivative (PPD) of M. tuberculosis showed a variable (increased or decreased) PCA production. Peripheral blood monocytes and total mononuclear cells (monocytes+lymphocytes) of active-TB patients stimulated with or without PPD showed increased PCA production, compared with normal individuals and inactive-TB patients. The present study suggests that increased production of PCA by the alveolar macrophages, in collaboration with lymphocytes and other cells at the site of tuberculous lesions will result in fibrin formation. The deposition of fibrin in the alveoli may lead to further lung injury.
Primer on Imaging Technologies for Cancer
Authors: Mitchell Schnall, Mark Rosen
Journal: Journal of Clinical Oncology (2006)

Medical images represent maps of the spatial distribution of tissue properties. Each modality probes a specific set of tissue properties such as x-ray attenuation for computed tomography, transmission of sound for ultrasound, and the rate of glucose uptake for fluorodeoxyglucose-positron emission tomography. Understanding the basic principal underlying each modality is important for developing approaches to utilize imaging in cancer research and clinical care. In addition, each modality has specific challenges related to reliable quantitation that are important to appreciate.
A grading scale to evaluate colon cleansing for the PillCam COLON capsule: a reliability study
Authors: J. Leighton, D. Rex
Journal: Endoscopy (2010)

The PillCam COLON capsule (Given Imaging, Ltd., Yoqneam, Israel) is an emerging technology for colon visualization. The aim of this prospective study was to assess the interobserver agreement of a new grading scale to evaluate colon cleansing for capsule use.Healthy volunteers underwent colon preparation and ingested a PillCam COLON capsule. A RAPID 5 (Given Imaging, Ltd.) video was generated and de-identified, and the colon was divided into five segments. Two cleanliness grading scales were compared: a 2-point scale (adequate and inadequate) and a 4-point grading scale (poor, fair, good, and excellent). For assessment of interobserver variability, two experienced gastroenterologists independently rated the cleansing level for each colon segment and for the entire video. Investigators participated in a calibration session prior to reading the study videos.A total of 40 individuals (aged 40 - 74 years) completed the study. A total of 196 colon video segments were evaluated. Per segment, κ values for the 2-point and 4-point scales were 0.754 and 0.619, respectively, representing good interobserver agreement. For the overall grade of the 40 videos, κ values for the 2-point and 4-point scales were 0.647 and 0.44, respectively.This new cleanliness grading scale showed good interobserver agreement and may be used with the PillCam COLON capsule to assess preparation quality.
The disproportionate impact of environmental health threats on children of color.
Authors: L Mott
Journal: Environmental Health Perspectives (1995)

Children receive greater exposures to environmental pollutants present in air, food, and water because they inhale or ingest more air, food, or water on a body-weight basis than adults do. Communities of color are disproportionately exposed to hazardous wastes, dioxin, and air pollution. Existing data demonstrate that children of color are the subgroup of the population most exposed to certain pollutants, including lead, air pollution, and pesticides. Government standards do not take into account children's differential exposures or the cumulative nature of these exposures. Federal regulations fail to protect the most highly exposed and most sensitive subgroups of the population. More often than not this group is children of color.
Abdominal Binding During CPR-Reply
Authors: Myron L. Weisfeldt
Journal: JAMA (1982)

In Reply.—  In response to Dr Lerman's letter I have the following comments. I agree that manipulation of airway pressure with a tight thoracoabdominal binder is an effective means for using manipulation of intrathoracic pressure to create carotid blood flow during CPR. As we emphasized previously, in some experimental animals and perhaps in some humans direct cardiac compression appears to occur consistent with the original notion that the heart is compressed between the sternum and vertebral column. At this point it is unclear, but possible, that direct cardiac compression would improve myocardial blood flow over and above that achieved with manipulation of intrathoracic pressures alone. Therefore, until further studies in man and experimental animals have been completed, I would personally consider it inadvisable to abandon sternal displacement during CPR in man.  Our article does not deal with high airway pressure ventilation synchronous with chest compression in man but only with
70 HEPATITIS B AND DELTA IN BANGUI – CENTRAL AFRICAN REPUBLIC – 25 YEARS AFTER THE FIRST REPORTED HEPATITIS DELTA EPIDEMIC
Authors: N.P. Komas, A. Manirakiza, J.O. Ouavéné, C. Bekondi, G.L. Laghoe, F. Le Gal, M. Abdou-Chekaraou, E. Gordien, F. Zoulim, P. Deny
Journal: Journal of Hepatology (2012)