tbuckley/cabot-search huggingface dataset:
Designing an Equitable Strategy for Allocating Antiretroviral Treatments
Authors: Alexander M Capron, Andreas Reis
Journal: PLoS Medicine (2005)

Of the roughly 40 million people living with HIV [1], an estimated 6 million in developing countries urgently need life-saving antiretroviral therapy (ART) [2]. Yet when the 3 by 5 Initiative was launched by the World Health Organization (WHO) and the Joint United Nations Programme on HIV/AIDS (UNAIDS) in December 2003—an initiative that aims to treat 3 million people with HIV in developing countries with ART by the end of 2005—most people with HIV in these countries did not even know their HIV status, and less than 8% were receiving ART. Moreover, even the success of the initiative would still mean that fewer than half of the people who could beneﬁ t from such treatment would be receiving it. Given this gap between what can be done and what needs to be done, the people who set policies and administer programs to provide ART in high-burden countries are faced with difﬁ cult questions of distributive justice. Decisions regarding the pricing of ARTs and other care for patients with HIV/AIDS, the distribution of treatment centers, and potential measures to overcome barriers for vulnerable populations will determine who will get access to treatment and who will die. In order to deal with these crucial issues, decision-makers need guidance on how to design policies on equitable access to ART that respect human rights norms and ethical standards.
Gender differences in regional fatty acid metabolism before and after meal ingestion.
Authors: M D Jensen
Journal: Journal of Clinical Investigation (1995)

These studies were conducted to determine whether men and women differ with regards to their overnight postabsorptive (basal) and postprandial fatty acid kinetics. Systemic oleate turnover ([9,10(3)H]oleate) was measured before and after the consumption of a mixed meal. Leg and splanchnic free fatty acid (FFA) uptake and release were measured, allowing the calculation of upper-body subcutaneous FFA release. RESULTS: basal oleate flux was virtually identical in men and women (3.0 +/- 3 versus 2.9 +/- 0.4 mumol.kg FFM-1.min-1), however, oleate Ra suppressed more in women than in men following meal ingestion (0.5 +/- 0.1 versus 0.8 +/- 0.1 mumol.kg FFM-1.min-1, P < 0.05). The fractional contribution of basal, regional FFA release to total FFA flux was not significantly different between men and women. In contrast, oleate release by upper-body subcutaneous adipose tissue was significantly greater (30 +/- 5 vs 8 +/- 3 mumol/min, respectively, P < 0.01) in men than in women during the meal nadir of FFA flux, whereas splanchnic oleate release was a greater percentage (39 +/- 7% vs 20 +/- 3%, respectively, P < 0.05) of nadir oleate Ra in women than in men. Thus, normal weight men and women differ significantly in the postprandial regulation of adipose tissue lipolysis in that men's upper-body subcutaneous adipose tissue is more resistant to the antilipolytic effects of meal ingestion. Differential regulation of regional adipose tissue lipolysis could contribute to the gender based differences in body fat distribution.
Social Outcomes in the Childhood Cancer Survivor Study Cohort
Authors: James G. Gurney, Kevin R. Krull, Nina Kadan-Lottick, H. Stacy Nicholson, Paul C. Nathan, Brad Zebrack, Jean M. Tersak, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2009)

Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.
High dietary K + inhibits formation of restenosis lesion in the swine coronary artery
Authors: N.T. Srivastava, D.B. Young, P.G. Anderson, M. Ge, T.N. Skelton, A.W. Grady, C. Hayes, K. Lyle, J. Luo, H.C. Waterer, H. Lin
Journal: Journal of the American College of Cardiology (1998)
Maturation of normal human epidermis without an ordered structure
Authors: PAUL R. BERGSTRESSER, SARA L. CHAPMAN
Journal: British Journal of Dermatology (1980)

Whole mounts of epidermis were prepared from hamster and mouse ears and from three sites on six normal human volunteers. Corneocyte columns were sought visually with the light microscope and statistically with cluster analysis applied to the surface distribution of superficial nucleated keratinocytes. In fifteen consecutive fields of hamster and mouse epidermis, both cell columns and clustering of nuclei were detected. In eighteen consecutive biopsies from the forearm, back and thigh of six normal adult men, stacking was never seen and clustering could not be demonstrated statistically. Corneocyte columns do occur regularly in some mammalian species and they have been reported to occur in human skin, but such columns are not common in these sites from normal human skin.
Cardiac depression after experimental air embolism in pigs: role of addition of a surface-active agent1
Authors: Jan Heim van Blankenstein, Cornelis J Slager, Lou Kie Soei, H Boersma, Th Stijnen, J.C.H Schuurbiers, Rob Krams, B Lachmann, Pieter D Verdouw
Journal: Cardiovascular Research (1997)

Objective: Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood–air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial function from air embolism by lowering the surface tension of air bubbles. Methods: The effect of using antifoam as a surface-tension-reducing agent on air bubble entrapment and cardiac function was investigated in 6 anesthetized pigs (27±1 kg) and analyzed using a two-compartment diffusion model. Air bubbles with a diameter of 150 μm were selectively injected into the left anterior descending coronary artery (LADCA) in a carrying fluid in the presence or absence of antifoam. Myocardial systolic segment shortening in the LADCA region (SS-LADCA) was measured by sonomicrometry. Presence of emboli was detected by measuring the amount of reverberation of ultrasound scattered by trapped air bubbles. Results: SS-LADCA transiently decreased after injections of air bubbles in both the absence and presence of antifoam. However, in the presence of antifoam the regional depression recovered to normal sooner, the average depth of the depression was reduced, and bubbles from the embolized area cleared faster. These observations can be explained by a model derived from Laplace's law.
The Angiotensin-Converting Enzyme Genotype and Microalbuminuria in Autosomal Dominant Polycystic Kidney Disease
Authors: MARJAN A. VAN DIJK, DORIEN J.M. PETERS, MARTIJN H. BREUNING, PETER C. CHANG
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Autosomal dominant polycystic kidney disease (ADPKD) has a variable clinical course. Clinical parameters associated with a worse prognosis are hypertension and proteinuria or microalbuminuria (MA). Because chronic stimulation of the renin-angiotensin system is likely to be present in ADPKD patients, the effect of the angiotensin-converting enzyme insertion/deletion (ACE I/D) genotype on the variability of these clinical parameters was examined in untreated ADPKD patients. Proteinuria and MA were determined in 24-h urine collections. BP measurements were performed with an ambulatory monitor, over 24 h. With analysis of covariance, the ACE genotype was found to be significantly associated with MA, corrected for age, gender, GFR, mean arterial pressure, body surface area, and urinary Na + excretion ( P &lt; 0.05). The patients homozygous for the deletion (DD) had the highest rate of MA ( P &lt; 0.05) compared to the patients homozygous for the insertion (II). There was no relationship between the ACE genotype and BP or renal function. A significant positive correlation was found between MA and mean arterial pressure ( r = 0.31, P &lt; 0.05), whereas a significant negative correlation was found between MA and renal function ( r = -0.28, P &lt; 0.05). In conclusion, in ADPKD patients, MA is partly determined by the ACE I/D polymorphism. Because MA is associated with an enhanced progression toward renal failure, the ACE genotype could help in identifying patients at risk for a worse prognosis.
Theoretical and experimental basis for the development of a dynamic airway stent
Authors: L Freitag, R Eicker, B Linz, D Greschuchna
Journal: European Respiratory Journal (1994)

Three major problems are currently associated with airway stents: mucostasis, formation of granulation tissue, and migration. We wanted to determine whether these problems could be solved by a different stent design. Based on theoretical considerations of an idealized trachea, we developed a dynamic bifurcation stent made of silicone which incorporates horseshoe-shaped steel struts. A flexible posterior membrane enables dynamic compression during cough, whilst the clasps maintain the airway lumen in the face of external compression. The design of the stent cast was based upon computed tomographic (CT)-scan studies of the central airways. Its complex shape provides a smoother distribution of pressure on the mucosa; thereby, lowering the stimulus for granulation formation. The bronchial limbs saddle on the carina, preventing displacement. The mechanical behaviours of the new stent and two commercially available stents were compared in an ex-vivo model, utilizing freshly excised tracheae and new visualization techniques. Dynamic (artificial coughs) and static loads (simulating tumour compression or pleural pressures) were applied on excised human tracheae with different stents. Our dynamic stent preserved effective compression of the posterior membrane in response to cough, and also provided lumen stability against extrinsic compression. In comparison, the two commercially available stents did not provide both functions equally well. In conclusion, our newly designed dynamic bifurcation stent shows characteristics which should prove useful in avoiding problems currently associated with airway stents.
Therapy of Marfan Syndrome
Authors: Daniel P. Judge, Harry C. Dietz
Journal: Annual Review of Medicine (2007)

Marfan syndrome is a common inherited disorder of connective tissue caused by deficiency of the matrix protein fibrillin-1. Effective surgical therapy for the most life-threatening manifestation, aortic root aneurysm, has led to a nearly normal lifespan for affected individuals who are appropriately recognized and treated. Traditional medical therapies, such as beta-adrenergic receptor blockade, are used to slow pathologic aortic growth and decrease the risk of aortic dissection by decreasing hemodynamic stress. New insights regarding the pathogenesis of Marfan syndrome have developed from investigation of murine models of this disorder. Fibrillin-1 deficiency is associated with excess signaling by transforming growth factor beta (TGFbeta). TGFbeta antagonists have shown great success in improving or preventing several manifestations of Marfan syndrome in these mice, including aortic aneurysm. These results highlight the potential for development of targeted therapies based on discovery of disease genes and interrogation of pathogenesis in murine models.
Mesenchymal stem cells in the treatment of autoimmune diseases
Authors: A. Tyndall, F. A. Houssiau
Journal: Annals of the Rheumatic Diseases (2010)

Mesenchymal stem cells (MSCs), more accurately called multipotent mesenchymal stromal cells, are being increasingly used in the treatment or amelioration of inflammatory and ischaemic conditions, including autoimmune diseases.1 This developed from the observation of the in vitro antiproliferative properties of MSCs, involving soluble factors and cell–cell contact-dependent events first observed in mixed lymphocyte reactions.2 Currently there are data involving nearly all known immune competent cells showing an antiproliferative and/or cell survival effect derived from MSCs,3 in some cases involving crosstalk and gene expression reprogramming.4 In addition, a plethora of animal model data have mostly been positive, but not all: notable exceptions being some rodent collagen induced arthritis models5 and murine systemic lupus erythematosus (SLE).6

The first use of MSCs in humans was as graft enhancing agents in patients with malignancies receiving haematopoietic stem cell transplants.7 An amelioration of acute graft versus host disease (GvHD) was observed, leading to successful targeted use of MSCs for acute GvHD.8 Due to their low acute toxicity and apparent immune privilege (allogeneic MSCs neither induce nor are subject to immune reaction), and relative ease of availability (eg, bone marrow, adipose tissue, placental products) and ex vivo expansion, the …
Genetic risk factors for soft-tissue injuries 101: a practical summary to help clinicians understand the role of genetics and ‘personalised medicine’
Authors: M Collins
Journal: British Journal of Sports Medicine (2009)

Acute and chronic (overuse) musculoskeletal soft-tissue injuries are common as a result of sports and occupationally related physical activities. These injuries have no single cause—instead, they result from a complex interaction of intrinsic and extrinsic factors which include genetic factors.1 2 Specific genetic elements have been identified for certain soft-tissue injuries,3,–,7 and I will summarise those in this editorial. I also explore the possible clinical implications of including genetic risk factors in multifactorial models developed to understand the molecular mechanisms of musculoskeletal soft-tissue injuries.

A familial predisposition and/or an association of specific genetic sequence variants have been proposed for conditions affecting the Achilles and rotator cuff tendons, as well as for shoulder dislocation and cruciate ligament ruptures.3 6 As summarised in table 1, initial investigations using genetic association (case–control) study designs showed that sequence variants (or polymorphisms) within several genes that encode for extracellular matrix proteins are likely associated with some of the previously mentioned injuries.3,–,8

View this table:

Table 1 
Genes associated with soft-tissue injuries



The results of these pioneering sports medicine genetics studies suggest that soft-tissue injuries, like other more extensively investigated complex disorders (eg, obesity, type 2 diabetes), are caused by the interaction of multiple genetic and environmental factors. They also suggest that there might be similarities and differences with respect to the genetic sequence variants associated with (1) tendon and ligament injuries, (2) acute and chronic injuries and (3) injuries within males and females. Further work is required to better understand these …
Dominant-Negative Control of cAMP-Dependent I <sub>Ks</sub> Upregulation in Human Long-QT Syndrome Type 1
Authors: Jordi Heijman, Roel L.H.M.G. Spätjens, Sandrine R.M. Seyen, Viola Lentink, Helma J.H. Kuijpers, Inge R. Boulet, Leon J. de Windt, Miren David, Paul G.A. Volders
Journal: Circulation Research (2011)

The mutation A341V in the S6 transmembrane segment of KCNQ1, the α-subunit of the slowly activating delayed-rectifier K(+) (I(Ks)) channel, predisposes to a severe long-QT1 syndrome with sympathetic-triggered ventricular tachyarrhythmias and sudden cardiac death.Several genetic risk modifiers have been identified in A341V patients, but the molecular mechanisms underlying the pronounced repolarization phenotype, particularly during β-adrenergic receptor stimulation, remain unclear. We aimed to elucidate these mechanisms and provide new insights into control of cAMP-dependent modulation of I(Ks).We characterized the effects of A341V on the I(Ks) macromolecular channel complex in transfected Chinese hamster ovary cells and found a dominant-negative suppression of cAMP-dependent Yotiao-mediated I(Ks) upregulation on top of a dominant-negative reduction in basal current. Phosphomimetic substitution of the N-terminal position S27 with aspartic acid rescued this loss of upregulation. Western blot analysis showed reduced phosphorylation of KCNQ1 at S27, even for heterozygous A341V, suggesting that phosphorylation defects in some (mutant) KCNQ1 subunits can completely suppress I(Ks) upregulation. Functional analyses of heterozygous KCNQ1 WT:G589D and heterozygous KCNQ1 WT:S27A, a phosphorylation-inert substitution, also showed such suppression. Immunoprecipitation of Yotiao with KCNQ1-A341V (in the presence of KCNE1) was not different from wild-type.Our results indicate the involvement of the KCNQ1-S6 region at/or around A341 in cAMP-dependent stimulation of I(Ks), a process that is under strong dominant-negative control, suggesting that tetrameric KCNQ1 phosphorylation is required. Specific long-QT1 mutations, including heterozygous A341V, disable this regulation.
Risks and Benefits of Antihypertensive Medications in Older Adults—Reply
Authors: Mary E. Tinetti, Ling Han, Gail J. McAvay
Journal: JAMA Internal Medicine (2014)

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Renin-Angiotensin-Aldosterone System During Chronic Thiazide Therapy of Benign Hypertension
Authors: J. J. BOURGOIGNIE, F. J. CATANZARO, H. M. PERRY, Esther Schoepfle, Linda Kurz
Journal: Circulation (1968)

Activity of the renin-angiotensin-aldosterone system was investigated in 53 patients with benign essential hypertension treated with thiazides. Following acute (less than 3 weeks) exposure to thiazide, renin activity was increased in peripheral plasma and sensitivity to infused angiotensin was decreased but only when dietary salt was simultaneously restricted. During chronic (more than 2 months) exposure to hydrochlorothiazide, 32 patients with unrestricted salt intake had normal renin activity in peripheral plasma (39 of 43 determinations), normal sensitivity to infused angiotensin (18 of 22 tests), and normal aldosterone excretion (nine of nine assays). Renin activity correlated well with angiotensin sensitivity (r=0.661; P &lt;0.001). Therefore, chronic ingestion of thiazide apparently induces no change in the renin-angiotensin-aldosterone system and hence presumably neither secondary aldosteronism nor negative sodium balance.
Ryanodine receptor cluster fragmentation and redistribution in persistent atrial fibrillation enhance calcium release
Authors: Niall Macquaide, Hoang-Trong Minh Tuan, Jun-ichi Hotta, Wouter Sempels, Ilse Lenaerts, Patricia Holemans, Johan Hofkens, M. Saleet Jafri, Rik Willems, Karin R. Sipido
Journal: Cardiovascular Research (2015)

AimsIn atrial fibrillation (AF), abnormalities in Ca2+ release contribute to arrhythmia generation and contractile dysfunction. We explore whether ryanodine receptor (RyR) cluster ultrastructure is altered and is associated with functional abnormalities in AF.
Inhibition of p38 mitogen activated protein kinase controls airway inflammation in cystic fibrosis
Authors: V Raia
Journal: Thorax (2005)

<b>Background:</b> Cystic fibrosis (CF) airways are characterised by chronic inflammation, increased interleukin (IL)-8 secretion, and neutrophil activation which are considered the principal factors of morbidity and mortality in CF patients. Optimising management of this chronic inflammatory response is therefore a key issue of basic and clinical CF research. Several reports have addressed ways to manage CF airways inflammation, and an attractive therapeutic strategy may be the inhibition of the p38-mitogen activated protein kinase (p38-MAP-k) pathway. <b>Methods:</b> A new ex vivo model was used to study the mucosal inflammatory response to environmental airways stimuli. Nasal biopsy tissues from CF patients and controls were cultured ex vivo for 20 minutes, 4 hours, and 24 hours in the presence of lipopolysaccharide (LPS) from <i>Pseudomonas aeruginosa</i> (PA) with and without the p38-MAP-k inhibitor SB203580. Quantitative mRNA assessment, immunohistochemistry, and Western blots were used to detect the expression and modulation of inflammatory markers. <b>Results:</b> PA-LPS challenge induced a time dependent mucosal inflammation indicated by rapid epithelial activation, IL-8 release, COX-2 upregulation, and neutrophil migration to the upper mucosal layers. Some of these LPS induced changes (IL-8 release and neutrophil migration) were specific to CF tissues. SB203580 significantly controlled all LPS induced mucosal changes in CF tissues. <b>Conclusion:</b> These findings provide a rationale and proof of principle for the potential use of p38-MAP-k inhibitors to control inflammation in patients with CF.