tbuckley/cabot-search huggingface dataset:
The fascinating and elusive life of cardiac fatty acids
Authors: G. J. van der Vusse
Journal: Cardiovascular Research (2011)

This editorial refers to 'Second window of preconditioning normalizes palmitate use for oxidation and improves function during low-flow ischaemia' by R.K. Kudej et al., this issue.Kudej et al. 1 attempted to elucidate the role of fatty acids (FAs) in the second window of protection of the chronically underperfused myocardium.Using the in vivo conscious swine heart model, they elegantly showed that ischaemic preconditioning resulted in less severe thinning of the left ventricular (LV) wall 24 h after the onset of ischaemia.The improved mechanical function of the ischaemic region was not due to changes in residual blood flow and, hence, increased supply of oxygen.The contribution of FAs to cardiac oxidative ATP production was estimated by infusion of 13 C-palmitate and subsequent in vitro NMR analysis of palmitate-derived acetyl-CoA.The contribution of FA to oxidative energy production declined in the ischaemic LV wall accompanied by decreased malonyl-CoA levels in the ischaemic subendocardium. Iterestingly, preconditioning substantially enhanced the relative contribution of FA oxidation to oxidative energy production in association with a three-fold increase in malonyl-CoA concentration.The study of Kudej et al. 1 deserves special attention especially for its iconoclastic message.Two important paradigms concerning cardiac FA utilization read that first, myocardial FA oxidation is detrimental under challenging conditions 2,3 and, secondly, cardiac FA oxidation is controlled by malonyl-CoA, in that elevated malonyl-CoA levels are inhibitory. 4,5The present study, however, clearly shows that improvement of regional myocardial function under chronically ischaemic conditions is associated with enhanced FA utilization and that increased FA oxidation coincides with increased tissue malonyl-CoA levels.Agreement exists that FAs are important fuel for the myocardium.Blood-borne FAs are efficiently extracted during a single passage of blood through the coronary system and preferentially oxidized in the working heart. 6Under challenging conditions such as ischaemia and/or reperfusion, FA could exert a detrimental effect on cardiac function. 3Theoretically, the negative effect of FA oxidation may relate to the fact that FAs require 10% more oxygen than glucose to produce the same amount of ATP.This property renders FAs less favourable as substrates when oxygen supply is limited.
Measurement of endothelial cytosolic calcium concentration and nitric oxide production reveals discrete mechanisms of endothelium-dependent pulmonary vasodilatation.
Authors: S L Archer, N J Cowan
Journal: Circulation Research (1991)

Nitric oxide is an endothelium-derived relaxing factor. Conversion of L-arginine to nitric oxide follows mediator-induced elevation of endothelial cytosolic calcium concentration. However, not all endothelium-dependent vasodilatation is caused by endothelium-derived relaxing factor, and few studies have correlated changes in vascular tone with measurement of free cytosolic calcium concentration or nitric oxide. The effects of three endothelium-dependent vasodilators (acetylcholine, bradykinin, and A23187) on vascular tone and nitric oxide production were studied in proximal rat pulmonary artery rings. Changes in free cytosolic calcium concentration and nitric oxide production were also studied in bovine pulmonary artery endothelial cells. A23187 and bradykinin caused pulmonary vasodilatation, nitric oxide production, and elevation of endothelial calcium concentrations. Although acetylcholine caused endothelium-dependent vasodilatation, it reduced free cytosolic calcium concentration and failed to increase nitric oxide levels. Acetylcholine-induced dilatation was partially inhibited by meclofenamate but was unaffected by ouabain. Acetylcholine, unlike bradykinin and A23187, does not act through a nitric oxide-dependent mechanism in the rat pulmonary vasculature.
Parental Monitoring of Children’s Media Consumption
Authors: Stacey S. Tiberio, David C. R. Kerr, Deborah M. Capaldi, Katherine C. Pears, Hyoun K. Kim, Paulina Nowicka
Journal: JAMA Pediatrics (2014)

Although children's media consumption has been one of the most robust risk factors for childhood obesity, effects of specific parenting influences, such as parental media monitoring, have not been effectively investigated.To examine the potential influences of maternal and paternal monitoring of child media exposure and children's general activities on body mass index (BMI) in middle childhood.A longitudinal study, taken from a subsample of the Three Generational Study, a predominantly white, Pacific Northwest community sample (overall participation rate, 89.6%), included assessments performed from June 1998 to September 2012. Analyses included 112 mothers, 103 fathers, and their 213 children (55.4% girls) at age 5, 7, and/or 9 years. Participation rates ranged from 66.7% to 72.0% of all eligible Three Generational Study children across the 3 assessments.Parents reported on their general monitoring of their children (whereabouts and activities), specific monitoring of child media exposure, children's participation in sports and recreational activities, children's media time (hours per week), annual income, and educational level. Parental BMI was recorded.Predictions to level and change in child BMI z scores were tested.Linear mixed-effects modeling indicated that more maternal, but not paternal, monitoring of child media exposure predicted lower child BMI z scores at age 7 years (95% CI, -0.39 to -0.07) and less steeply increasing child BMI z scores from 5 to 9 years (95% CI, -0.11 to -0.01). These effects held when more general parental monitoring, and parent BMI, annual income, and educational level were controlled for. The significant negative effect of maternal media monitoring on children's BMI z scores at age 7 years was marginally accounted for by the effect of child media time. The maternal media monitoring effect on children's BMI z score slopes remained significant after adjustment for children's media time and sports and recreational activity.These findings suggest that parental behaviors related to children's media consumption may have long-term effects on children's BMI in middle childhood. They underscore the importance of targeting parental media monitoring in efforts to prevent childhood obesity.
PredAlgo: A New Subcellular Localization Prediction Tool Dedicated to Green Algae
Authors: Marianne Tardif, Ariane Atteia, Michael Specht, Guillaume Cogne, Norbert Rolland, Sabine Brugière, Michael Hippler, Myriam Ferro, Christophe Bruley, Gilles Peltier, Olivier Vallon, Laurent Cournac
Journal: Molecular Biology and Evolution (2012)

The unicellular green alga Chlamydomonas reinhardtii is a prime model for deciphering processes occurring in the intracellular compartments of the photosynthetic cell. Organelle-specific proteomic studies have started to delineate its various subproteomes, but sequence-based prediction software is necessary to assign proteins subcellular localizations at whole genome scale. Unfortunately, existing tools are oriented toward land plants and tend to mispredict the localization of nuclear-encoded algal proteins, predicting many chloroplast proteins as mitochondrion targeted. We thus developed a new tool called PredAlgo that predicts intracellular localization of those proteins to one of three intracellular compartments in green algae: the mitochondrion, the chloroplast, and the secretory pathway. At its core, a neural network, trained using carefully curated sets of C. reinhardtii proteins, divides the N-terminal sequence into overlapping 19-residue windows and scores the probability that they belong to a cleavable targeting sequence for one of the aforementioned organelles. A targeting prediction is then deduced for the protein, and a likely cleavage site is predicted based on the shape of the scoring function along the N-terminal sequence. When assessed on an independent benchmarking set of C. reinhardtii sequences, PredAlgo showed a highly improved discrimination capacity between chloroplast- and mitochondrion-localized proteins. Its predictions matched well the results of chloroplast proteomics studies. When tested on other green algae, it gave good results with Chlorophyceae and Trebouxiophyceae but tended to underpredict mitochondrial proteins in Prasinophyceae. Approximately 18% of the nuclear-encoded C. reinhardtii proteome was predicted to be targeted to the chloroplast and 15% to the mitochondrion.
Gout in the elderly, a separate entity?
Authors: E J ter Borg, J J Rasker
Journal: Annals of the Rheumatic Diseases (1987)

To evaluate whether the clinical pattern of gout differed between elderly women and men a retrospective study was performed in all women (22) and men (18) in our rheumatological clinics who developed gout after the age of 60. The diagnosis was made after a mean of 2.6 years of joint complaints in women and after 1.2 years in men. In about half the patients complaints started in more than one joint, often including the big toe. In five women, but none of the men, complaints started in the fingers. No correlation was found between gout and the presence of tophi or Heberden's nodes in the finger joints. The mean uric acid level was higher in women (0.61 mmol/l) than in men (0.53 mmol/l), and almost all the women (95%) used diuretics and only 56% of the men did so.
ETHNOPHARMACOLOGY OF MEXICAN ASTERACEAE (COMPOSITAE)
Authors: Michael Heinrich, Mario Robles, Jan E. West, Bernardo R. Ortiz de Montellano, Eloy Rodriguez
Journal: The Annual Review of Pharmacology and Toxicology (1998)

▪ Abstract Traditional herbal remedies have increased in popularity in Europe and the United States in recent years but have always been important to people living in rural Mexico and to their Mexican American/Chicano descendants in the United States. Mexican American patients will often be ingesting herbal teas at the same time that they are being treated for their ailments with antibiotics or antiinflammatory agents. The plant family Asteraceae (Compositae) has contributed the largest number of plants to this pharmacopoeia; the reasons for the importance of this family include its large number of species in Mexico and its wide array of natural products that are useful in the treatment of the maladies that have afflicted the inhabitants of rural Mexico. These natural products include sesquiterpene lactones, polyacetylenes, alkaloids, monoterpenes, and various phenolics such as flavonoids. In this review, we emphasize the sesquiterpene lactones, a large group of compounds with antiinflammatory properties and the ability to relax smooth muscles and thereby relieve gastrointestinal distress. These compounds also readily form adducts with glutathione or free thiols and can thereby affect the metabolism, activity, and toxicology of a wide array of pharmacological agents.
UN questions China over organ harvesting
Authors: John Zarocostas
Journal: BMJ (2006)

Manfred Nowak, a human rights lawyer and the United Nations independent expert on torture, has asked China to respond to allegations of harvesting organs from dead prisoners.

The move comes after Mr Nowak received “quite a number” of allegations of the practice from human rights groups and members of the European parliament, among others.

Mr Nowak said that he has had oral confirmation from China that it is …
Increased Bioavailability of Intravenous Versus Oral CI-1033, a Pan erbB Tyrosine Kinase Inhibitor: Results of a Phase I Pharmacokinetic Study
Authors: George R. Simon, Christopher R. Garrett, Stephen C. Olson, Michael Langevin, Irene A. Eiseman, John J. Mahany, Charles C. Williams, Richard Lush, Adil Daud, Pamela Munster, Alberto Chiappori, Mayer Fishman, Gerold Bepler, Peter F. Lenehan, Daniel M. Sullivan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In phase I studies with oral CI-1033, dose-limiting toxicities were primarily gastrointestinal, supporting the exploration of i.v. dosing to achieve optimal drug exposures by increasing bioavailability. Experimental Design: Fifty-three patients with advanced nonhematologic malignancies received i.v. CI-1033 via 30-minute infusions (10-500 mg) on a thrice-weekly schedule. Pharmacokinetic samples were collected on days 1 and 8 and evaluated using noncompartmental analysis. Results: Dose levels evaluated were 10, 20, 30, 45, 67.5, 100, 150, 225, 337.5, and 500 mg. The maximum administered dose was 500 mg, whereas the maximum tolerated dose was 225 mg. The most common treatment-related grade 1 to 2 adverse events were rashes (38% of patients), nausea (17%), vomiting (17%), stomatitis (14%), and diarrhea (13%). Most common grade 3 adverse events were hypersensitivity reactions (7.5%), rashes (3.8%), and diarrhea (3.8%). No grade 4 toxicities were observed. Ten of the 53 (19%) patients had disease stabilization at their first efficacy evaluation visit (including two with minor responses). A 5- to 10-fold increase in i.v. Cmax was noted with a 3-fold increase in AUC compared with oral CI-1033 at equivalent doses. Treatment-related gastrointestinal adverse events were notably less frequent with this i.v. regimen. Conclusions: CI-1033 was safely given i.v. up to 225 mg/dose on a thrice-weekly schedule, with evidence of antitumor activity. At equivalent doses, the bioavailability of i.v. CI-1033 is thrice that of the oral formulation. Treatment with i.v. CI-1033 is feasible and may be warranted when increased drug exposures are desired.
Comprehensive clinical and epidemiological assessment of colonisation and infection due to carbapenemase-producing Enterobacteriaceae in Spain
Authors: Zaira R. Palacios-Baena, Jesús Oteo, Carmen Conejo, M. Nieves Larrosa, Germán Bou, Marta Fernández-Martínez, Juan José González-López, Vicente Pintado, Luis Martínez-Martínez, María Merino, Virginia Pomar, Marta Mora-Rillo, María Alba Rivera, Antonio Oliver, Guillermo Ruiz-Carrascoso, Patricia Ruiz-Garbajosa, Laura Zamorano, Verónica Bautista, Adriana Ortega, Isabel Morales, Álvaro Pascual, José Campos, Jesús Rodríguez-Baño, Ángel Zaballos, Rafael Cantón, Laura Martínez-García, Ana María Fleites, Carlos Rodríguez-Lucas, Ma Isabel Sánchez-Romero, Luisa García-Picazo, Esteban Aznar, Carolina Campelo, Alejandro González-Praetorius, Sonia Solís, Salvador Giner, Miguel Salavert, Juan Manuel Hernández, Josep Vilaró Pujals, Anna Vilamala Bastarras, Ma Ángeles Orellana, Emilia Cercenado, Mateu Espasa, Dionisia Fontanals, Ma Victoria García-López, José Luis Hernández-Almaraz, Carmina Martí-Sala, Adelina Gimeno, Teresa Alarcón, Laura Llorca, Concepción Segura, Raquel Clivillé-Abad, Montse Motjé, Delia Garcia i Parés, Pedro de la Iglesia, Beatriz Iglesias, Juanjo Castón, María Dolores Romero, José Antonio Rodríguez-Polo, Gloria Trujillo, Montserrat Morta, Alberto Gil Setas, Carmen Ezpeleta, Ma Dolores Miguel-Martínez, Antonio Sánchez-Porto, Javier Casas, David Molina, Eugenio Garduño, Juan Carlos Alados, Pepa Pérez-Jové, Goretti Sauca, Carmen Gallés, Fátima Galánand, Francisca Guerrero, Ma Fe Brezmes, Ma Pilar Ortega, Francisco Javier Castillo, Cristina Seral, Alberto Delgado-Iribarren, Alberto Yagüe, Carmen Aspiroz, Ma Isabel Fernández-Natal, Isabel Wilhelmi, Pilar Reyes, Ma Dolores Pérez-Ramírez, Inocente Cuesta, Mar Olga Pérez Moreno, Amparo García, Frederic Ballester, Isabel Pujol, Montserrat Sierra, Araceli González-Cuevas, Pilar López García, Lluís Carbó Saladrigas, Jesús Martínez-López, Lucía Martínez-Lamas, Jorge Julio Cabrera, Susana García de Cruz, Carmen Raya, Ana Belén Campo, Inés de Benito, Andrés Canut, Pilar Berdonces, María Concepción Lecaroz Agara, Susana Hernando Real, Belén Hernández, Ma Teresa Ledo, Firdaous El Knaichi, Carlos García Tejero, Jose Manuel Azcona, Isabel Ferrer, Marta Lamata, Carmen Pazos, Ma Pilar Chocarro, Javier Murillas, Elisenda Miró, Ferrán Navarro, Rosa M. Bartolomé
Journal: Journal of Infection (2015)
Evaluation of the Early Extraction Method of Determining Capillary Permeability by Theoretical Capillary and Organ Models
Authors: DAVID G. LEVITT
Journal: Circulation Research (1970)

The early extraction method of measuring capillary permeability was evaluated with theoretical models of capillaries and organs. The organs consisted of feeder lines and a capillary bed that was either homogeneous or heterogeneous with respect to capillary length or flow. The capillary permeability of the model organ determined by the early extraction method was compared with the actual permeability of the capillaries from which the organ was constructed. The main results of this analysis are: (1) If all the capillaries are identical and if the extravascular volume of distribution of the diffusible indicator is at least three times as large as the capillary volume, then the early extraction method provides a satisfactory measure of the capillary permeability. (2) If the capillaries are identical but the extravascular volume is about the same size as the capillary volume, then the early extraction method can lead to a qualitative underestimate of the permeability, namely assigning a significant diffusion limitation to a substance which is actually flow limited. (3) If the capillaries are not identical, either through differences of flow or length, then the early extraction method can again lead to the assignment of a significant diffusion limitation to a substance which is actually flow limited.
A Multidimensional Meta-Analysis of Psychotherapy for PTSD
Authors: Rebekah Bradley, Jamelle Greene, Eric Russ, Lissa Dutra, Drew Westen
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: The authors present a multidimensional meta-analysis of studies published between 1980 and 2003 on psychotherapy for PTSD. METHOD: Data on variables not previously meta-analyzed such as inclusion and exclusion criteria and rates, recovery and improvement rates, and follow-up data were examined. RESULTS: Results suggest that psychotherapy for PTSD leads to a large initial improvement from baseline. More than half of patients who complete treatment with various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve. Reporting of metrics other than effect size provides a somewhat more nuanced account of outcome and generalizability. CONCLUSIONS: The majority of patients treated with psychotherapy for PTSD in randomized trials recover or improve, rendering these approaches some of the most effective psychosocial treatments devised to date. Several caveats, however, are important in applying these findings to patients treated in the community. Exclusion criteria and failure to address polysymptomatic presentations render generalizability to the population of PTSD patients indeterminate. The majority of patients posttreatment continue to have substantial residual symptoms, and follow-up data beyond very brief intervals have been largely absent. Future research intended to generalize to patients in practice should avoid exclusion criteria other than those a sensible clinician would impose in practice (e.g., schizophrenia), should avoid wait-list and other relatively inert control conditions, and should follow patients through at least 2 years.
Nursing Home Residents' Preferences for Life-Sustaining Treatments
Authors: Linda A. O'Brien
Journal: JAMA (1995)

To determine life-sustaining treatment preferences among nursing home residents, whether information regarding cardiopulmonary resuscitation (CPR) affected these preferences, and with whom treatment preferences had been discussed, and to identify factors associated with CPR preferences.In-person survey.Forty-nine randomly selected nursing homes.Four hundred twenty-one randomly selected nursing home residents capable of making decisions.Preferences regarding CPR, hospitalization, and enteral tube feedings, and individual factors associated with CPR preferences.Of 1458 randomly selected nursing home residents assessed for the ability to participate in the study, 552 residents (38%) were eligible to participate and 421 agreed to be interviewed. Sixty percent of participants able to participate in the decision reported that they would elect CPR, 89% would choose hospitalization if seriously ill, and 33% would elect enteral tube feedings if no longer able to eat because of permanent brain damage. Individual factors associated with preferences for CPR included the following: African-American ethnicity, high self-reported physical mobility, belief that most important medical care decisions should be made by the doctor, moderate-to-severe impairment in daily decision-making skills, and not having a spouse. Fourteen percent changed their preference from preferring CPR to not preferring CPR after receiving additional information about CPR procedures. Twelve percent reported having discussed preferences with health care providers, and 31% discussed preferences with family members.More than half of nursing home residents capable of making decisions preferred the use of CPR. Few had discussed their preferences with health care providers. Individual preferences should be assessed when considering the use of life-sustaining treatments.
Is the Renin-Sodium Profile Helpful in Evaluating Hypertension?
Authors: Ray W. Gifford
Journal: JAMA (1980)

LARAGH and colleagues<sup>1</sup>have long advocated measurement of plasma renin activity (PRA) routinely in the evaluation of hypertensive patients. They have presented an elaborate and somewhat complicated schema for using the PRA as an aid in diagnostic evaluation and in selecting drugs. Reliable measurements of PRA are not readily available to many physicians, and when they are, care must be taken to control, so far as is possible, those variables that influence PRA, such as physical activity, normal diurnal variations, drugs (eg, estrogens, diuretics, and antihypertensive agents), and sodium intake. Laragh et al recommend that blood be drawn at the same time of day (noon), after the patient has been ambulatory for several hours, and that the urinary sodium excretion for the previous 24 hours be measured to estimate the state of sodium balance. Does the information provided by a renin-sodium profile justify this meticulous attention to detail and the
B cell diversification and differentiation in the periphery.
Authors: G Kelsoe
Journal: The Journal of Experimental Medicine (1994)

T and B lymphocytes make physical contact (6). Though both swift and brief (4, 7), this encounter initiates a complex program of B cell differentiation leading to specialization for early antibody production or immune memory. In the spleen, B cells initially proliferate in the T cell-rich periarteriolar lymphoid sheath (PALS) and then either develop locally into foci of antibody-secreting cells or migrate to the nearby lymphoid follicle to initiate germinal center (GC) formation (3-5).