Miracle-dz/UniFAR-FTUs huggingface dataset:
Pentoxifylline inhibits the proliferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin

Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (100–1000 μg/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non‐lethal, dose‐dependent reductions in serum‐driven fibroblast proliferation, with 1000 μg/ml pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity.
Do endomyocardial biopsies represent the morphology of the rest of the myocardium? A quantitative light microscopic study of single v. multiple biopsies with the King's bioptome.

In this paper some possibilities have been explored for the contradictory reported results correlating morphological findings on tissue obtained by bioptome to haemodynamic and other clinical parameters. To illustrate the problem endomyocardial biopsies obtained from 79 patients, either from the right or left ventricle, have been analysed quantitatively. Emphasis was placed on the size of the biopsy, cell diameter and volume fraction of collagen as well as volume fraction of interstitium. The results have shown that great variability exists when comparing two biopsies from the same ventricle. The coefficient of variance regarding fibre diameter and volume fraction of interstitium was 18.6 and 28.9%, respectively, and amounts to 80.5% for the volume fraction of collagen. In addition, investigations as to whether or not the small tissue samples obtained by bioptome are representative of the rest of the myocardium, have been undertaken. For this purpose 23 hearts obtained at post-mortem have been analysed quantitatively, measuring the volume fraction of collagen. The results have shown that when five or more tissue samples have been obtained, quantitative representation of the interventricular septum (the rest of the myocardium? ) is mirrored in the small tissue samples. It is, therefore, concluded that at least five biopsies are necessary to establish whether or not correlation between structural changes and the functional state of the heart exists. Unless this number of biopsies has been obtained, extreme caution in assessing prognosis must be exercised.
The behavioral economics of cigarette smoking: The concurrent presence of a substitute and an independent reinforcer

The present study examined the consumption of cigarettes and two alternative reinforcers in dependent smokers. Cigarette price (response requirement) increased across sessions while alternatives were available at a fixed price in four phases of availability: (1) cigarettes alone; (2) cigarettes and nicotine gum; (3) cigarettes and money; and (4) cigarettes, nicotine gum, and money. Cigarette consumption decreased with increasing price throughout. In the cigarette and nicotine gum phase, nicotine gum consumption increased with cigarette price, indicating nicotine gum to be a substitute for cigarettes. In the cigarette and money phase, money consumption increased slightly with cigarette price, indicating money to be an independent reinforcer for cigarettes. When all three reinforcers were present, money again served as an independent reinforcer. During this phase, nicotine gum consumption increased marginally, but the small magnitude of increase suggests that nicotine gum functioned as an independent reinforcer rather than a substitute. Cigarette consumption decreased modestly when nicotine gum was available, and to a larger extent when money or both alternatives were available. The results highlight the potential for an independent reinforcer such as money to be more effective at reducing drug use than a pharmacological substitute.
The cellular basis for allergic rhinitis

In both seasonal and perennial rhinitis there is epithelial mast cell accumulation and tissue infiltration by eosinophils. Activation of these cells can be observed by electron microscopy and by elevated levels of tryptase and eosinophil cationic protein in nasal lavage fluid. Furthermore, seasonal increases in the antigen presenting cell (Langerhans’cell) are also evident. Investigations into the mechanisms involved in cell accumulation and activation reveals upregulation of leucocyte endothelial adhesion molecules and an increase in interleukin‐4 (IL‐4) in naturally occurring rhinitis, while mRNA for IL‐4, IL‐5 and granulocyte macrophage colony stimulating factor activity and lavage tumour necrosis factor‐alpha (TNFα) levels are increased following local allergen challenge. These cytokines may be derived from a variety of sources, including mast cells, eosinophils and T‐lymphocytes, and contribute to the underlying inflammatory process in rhinitis.
The cost–effectiveness of point-of-care D-dimer tests compared with a laboratory test to rule out deep venous thrombosis in primary care

Objective: Point-of-care (POC) D-dimer tests have been developed to exclude deep venous thrombosis quickly and on the spot, but are known to have lower sensitivity compared with laboratory-based tests. Their cost–effectiveness is still unknown. Methods: We updated and extended a previously published Markov model to assess the cost–effectiveness of POC D-dimer tests (‘Simplify’, ‘Cardiac’, ‘Triage’ and ‘Nycocard’) compared with a laboratory-based latex assay to diagnose deep venous thrombosis in primary care. Results: The ‘Laboratory’ strategy resulted in 6.986 quality-adjusted life years at the cost of €8354 per patient. All POC D-dimer tests resulted in health outcomes similar to the ‘Laboratory’ strategy. The ‘Simplify’ strategy maximized cost savings (–€155 [95% CI: –€246 to –€83]). Conclusions: POC D-dimer tests yield similar health outcomes as laboratory-based testing procedures but can be performed more easily and at lower costs. Therefore, these tests are an alternative to laboratory-based testing and might be considered for exclusion of deep venous thrombosis in primary care.
PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation.

Pulmonary hypertension frequently complicates interstitial lung disease, where it is associated with a high mortality. Patients with this dual diagnosis often fare worse than those with pulmonary arterial hypertension (PAH) alone and respond poorly to standard PAH therapy, often dying of right ventricular (RV) failure. We hypothesize that nitric oxide synthase (NOS) uncoupling is important in the pathogenesis of interstitial lung disease-associated pulmonary hypertension, and this process can be abrogated by phosphodiesterase type 5 (PDE5) inhibition to improve pulmonary vascular remodeling and right ventricular function. Intratracheal bleomycin (4 U/kg) or saline control was administered to C57/BL6 mice after anesthesia. After recovery, animals were fed a diet of sildenafil (100 mg.kg(-1). day(-1)) or vehicle for 2 wk when they underwent hemodynamic measurements, and tissues were harvested. Survival was reduced in animals treated with bleomycin compared with controls and was improved with sildenafil (100.0 vs. 73.7 vs. 84.2%, P < 0.05). RV/LV+S ratio was higher in bleomycin-alone mice with improvement in ratio when sildenafil was administered (33.00 +/- 0.01% vs. 20.98 +/- 0.01% P < 0.05). Histology showed less pulmonary vascular and RV fibrosis in the group cotreated with sildenafil. Bleomycin was associated with a marked increase in superoxide generation by DHE histological staining and luminol activity in both heart and lung. Treatment with sildenafil resulted in a concomitant reduction in superoxide levels in both heart and lung. These data demonstrate that PDE5 inhibition ameliorates RV hypertrophy and pulmonary fibrosis associated with intratracheal bleomycin in a manner that is associated with improved NOS coupling and a reduction in reactive oxygen species signaling.
Why Research on Women Entrepreneurs Needs New Directions

Research articles on women's entrepreneurship reveal, in spite of intentions to the contrary and in spite of inconclusive research results, a tendency to recreate the idea of women as being secondary to men and of women's businesses being of less significance or, at best, as being a complement. Based on a discourse analysis, this article discusses what research practices cause these results. It suggests new research directions that do not reproduce women's subordination but capture more and richer aspects of women's entrepreneurship.
Establishing intravenous access: a study of local anesthetic efficacy.

We performed a double-blind, randomized, prospective study to determine the local anesthetic that provided the best analgesia for insertion of an 18-gauge intravenous (i.v.) catheter and to determine whether alkalinization of lidocaine decreases the pain of intradermal injection. There were 280 healthy adult patients assigned randomly to seven different groups: benzyl alcohol 0.9% in normal saline, 2-chloroprocaine 3%, lidocaine 1%, lidocaine 1% with preservative, alkalinized lidocaine 1% with preservative, normal saline, and a control group that received i.v. catheter placement without previous drug injection. A 10-cm visual analog pain scale (VAPS) was used to obtain pain scores after pre-i.v. drug injection and after iv catheter insertion. Benzyl alcohol in normal saline (0.61 +/- 0.11) and alkalinized lidocaine (0.69 +/- 0.10) had the lowest mean pain scores for drug injection and these were significantly different from other drugs (P < 0.05). Alkalinized lidocaine (0.7 +/- 0.18) had the lowest mean pain score for i.v. catheter insertion with nothing (no previous drug injected) (3.47 +/- 0.38) and normal saline (3.97 +/- 0.18) had the highest mean pain scores (P < 0.05). We conclude that alkalinized lidocaine decreased the pain associated with its injection. Alkalinized lidocaine was the best local anesthetic for i.v. catheter placement. Benzyl alcohol in normal saline was also effective.
Contribution IMPLEMENTATION ISSUES IN ULTRASONIC FLOW IMAGING

This article addresses several implementation issues in ultrasonic flow imaging. We discuss frequencydependent scattering and attenuation, use of interpolation for computation intensive methods and implications of the use of chirps to increase bandwidth. We also discuss wall filtering issues; our observations show that the butterfly search estimator may be capable ofdetecting flow in the vicinity of strong stationary scatterers (clutter) without additional processing such as wall-filtering. Illustrative examples are given for simulated and experimental data. (e-mail: parker@ece.rochester.edu) © 2003 World Federation for Ultrasound in Medicine & Biology.
Low-cost Gaze and Pulse Analysis using RealSense

Intel’s newly-announced low-cost and high precision RealSense 3D (RGBD) camera is becoming ubiquitous in laptops and mobile devices starting this year, opening the door for new applications in the mobile health arena. In this paper, we demonstrate how the Intel RealSense 3D camera can be used for low-cost gaze tracking and passive pulse rate estimation. We develop a novel 3D gaze and ﬁxation tracker based on the eye surface geometry as well as an illumination invariant pulse rate estimation method using near-infrared images captured with RealSense. We achieve a mean error of 1cm at 20 − 30cm for the gaze tracker and 2.26bpm (beats per minute) for pulse estimation, which is adequate in many medical applications, demonstrating the great potential of novel consumer-grade RGBD technology in mobile health.
Underlying causes and long-term survival in patients with initially unexplained cardiomyopathy.

BACKGROUND Previous studies of the prognosis of patients with heart failure due to cardiomyopathy categorized patients according to whether they had ischemic or nonischemic disease. The prognostic value of identifying more specific underlying causes of cardiomyopathy is unknown. METHODS We evaluated the outcomes of 1230 patients with cardiomyopathy. The patients were grouped into the following categories according to underlying cause: idiopathic cardiomyopathy (616 patients), peripartum cardiomyopathy (51); and cardiomyopathy due to myocarditis (111), ischemic heart disease (91), infiltrative myocardial disease (59), hypertension (49), human immunodeficiency virus (HIV) infection (45), connective-tissue disease (39), substance abuse (37), therapy with doxorubicin (15), and other causes (117). Cox proportional-hazards analysis was used to assess the association between the underlying cause of cardiomyopathy and survival. RESULTS During a mean follow-up of 4.4 years, 417 patients died and 57 underwent cardiac transplantation. As compared with the patients with idiopathic cardiomyopathy, the patients with peripartum cardiomyopathy had better survival (adjusted hazard ratio for death, 0.31; 95 percent confidence interval, 0.09 to 0.98), and survival was significantly worse among the patients with cardiomyopathy due to infiltrative myocardial disease (adjusted hazard ratio, 4.40; 95 percent confidence interval, 3.04 to 6.39), HIV infection (adjusted hazard ratio, 5.86; 95 percent confidence interval, 3.92 to 8.77), therapy with doxorubicin (adjusted hazard ratio, 3.46; 95 percent confidence interval, 1.67 to 7.18), and ischemic heart disease (adjusted hazard ratio, 1.52; 95 percent confidence interval, 1.07 to 2.17). CONCLUSIONS The underlying cause of heart failure has prognostic value in patients with unexplained cardiomyopathy. Patients with peripartum cardiomyopathy appear to have a better prognosis than those with other forms of cardiomyopathy. Patients with cardiomyopathy due to infiltrative myocardial diseases, HIV infection, or doxorubicin therapy have an especially poor prognosis.
Noisy signalling over time

Many signalling situations feature noisy observation of the sender’s effort and multiple opportunities to signal. Noise and time generate novel features: in some equilibria, the high-cost type exerts more effort. Information release could be gradual or discrete. Gradual information revelation is modelled as the sender controlling the drift of a Brownian motion signal process, discrete information release as controlling the intensity of a Poisson process. If the intensity increases (decreases) in the effort, then the signal is called good (bad) news. The receivers observe the signals, but not the sender’s effort or type. Under bad news, there are Markov stationary perfect Bayesian equilibria in which the bad type exerts strictly higher effort than the good type. In these equilibria, if no signal occurs, then the types eventually pool on zero effort. If a signal occurs, then the play transitions irreversibly to a regime in which a single bad signal reveals the bad
Effect of calcium and fat intake on calcium metabolism in calves.

Ten male Holstein calves were fed diets with or without 5% added animal fat in combination with low and high dietary calcium (.15 or .98%) for 4 wk. After 3 wk, the animals were orally dosed with calcium-45. One week later they were killed and tissue samples taken. Except for lower calcium-45 in bile, added dietary fat had no marked influence on calcium metabolism. Net absorption of calcium-45 (not excreted in feces) ranged from 82% for calves fed low calcium to 53% for those given high calcium. Calcium-45 in bone was substantially higher in calves fed . 15% calcium. Tailbone biopsies revealed rapid uptake of calcium-45 with approximately as much incorporated during the 1st d as in the following 6 d. Calcium-45 in blood peaked 24 h following dosing. Calves fed . 15% calcium had higher calcium-45 in blood and bile than those receiving . 98% calcium. Calcium-45 values in soft tissue were low and did not differ materially among treatments. The decreases in radioactive calcium absorption and bone deposition with higher dietary calcium indicated that variable absorption was a major factor in calcium homeostasis. Added fat did not materially effect calcium metabolism with either low or high dietary calcium.
This material is the copyright of the original publisher. Unauthorised copying and distribution is prohibited. Biomarkers in Amyotrophic Lateral Sclerosis Facts and Future Horizons

The only specific marker of sporadic amyotrophic lateral sclerosis (ALS) is neuropathologic, namely the presence of inclusions staining positively for ubiquitin and TAR DNA-binding protein (TARDBP, also known as TDP-43) in degenerating motor neurons. Abnormalities in various physiopathologic pathways associated with ALS, such as oxidative stress, inflammation, and excitotoxicity, have been reported in blood, cerebrospinal fluid, and muscle biopsies. A number of studies in ALS patients have indicated that nuclear magnetic resonance (NMR) spectroscopy and diffusion tensor magnetic resonance imaging (MRI) can detect corticospinal lesions. However, because of their relative lack of sensitivity and specificity, these techniques are currently inadequate for use as diagnostic tools in individual patients. Recently, there has been much interest in the use of high-throughput techniques such as transcriptomics, proteomics, and metabolomics for the detection of biomarkers. In the future, a combination of biologic, radiologic, and electrophysiologic markers, rather than a single marker, may prove a useful tool for the diagnosis and follow-up of ALS patients. This article provides an overview of recently described biologic and radiologic markers of the disease.
Predicting blood donation intentions and behavior among Australian blood donors: testing an extended theory of planned behavior model

BACKGROUND: Donor retention poses a significant problem to blood collection agencies around the world. Previous research using an augmented theory of planned behavior (TPB) approach has demonstrated that attitude, subjective norm, self‐efficacy, moral norm, anticipated regret, donation anxiety from prior blood donations, and self‐identity as a blood donor predicts experienced donors' intentions and that intentions, self‐efficacy, moral norm, and anticipated regret may impact upon people's actual blood donation behavior.
Comparison of binge eating disorder and bulimia nervosa in a community sample.

OBJECTIVE This study examined the relationship between binge eating disorder (BED), a newly proposed eating disorder, and bulimia nervosa (BN). METHOD Three groups recruited from the community were compared: women with BED (n = 150), women with purging BN (n = 48), and women with nonpurging BN (n = 14). RESULTS The three groups did not differ significantly in education, weight or shape concern, and current or lifetime prevalence of nine major mental disorders. Women with BED, compared with women with purging BN, were older, less likely to have a history of anorexia nervosa, and less likely to have been treated for an eating disorder. Obesity was more commonly associated with BED than with either subtype of BN. DISCUSSION Our results lend some support to BED as an eating disorder distinct from purging BN. More research is needed to clarify the position of nonpurging BN relative to BED and purging BN.
Some gating potentiators, including VX-770, diminish ΔF508-CFTR functional expression

Ivacaftor, a potentiator of ΔF508-CFTR channel function in cystic fibrosis, reduces the ability of corrector drugs to rescue the ΔF508-CFTR membrane trafficking defect. Potentiating Trouble Cystic fibrosis is a genetic disease caused by mutations of the CFTR ion channel, resulting in pulmonary and other complications. Ivacaftor is the only targeted drug approved for cystic fibrosis, but it is not effective enough to treat the severest and most common form of this disease. Ivacaftor is a “potentiator,” which means that it improves the activity of mutant CFTR, but cannot work if there is no CFTR on the cell surface. Other drugs, called “correctors,” help bring mutant CFTR to the cell surface, but two manuscripts by Cholon and Veit and co-authors now show that combining the two types of drugs does not work effectively because potentiators make CFTR less stable, accelerating the removal of this channel from the cell membrane. Cystic fibrosis (CF) is caused by mutations in the CF transmembrane regulator (CFTR) that result in reduced anion conductance at the apical membrane of secretory epithelia. Treatment of CF patients carrying the G551D gating mutation with the potentiator VX-770 (ivacaftor) largely restores channel activity and has shown substantial clinical benefit. However, most CF patients carry the ΔF508 mutation, which impairs CFTR folding, processing, function, and stability. Studies in homozygous ΔF508 CF patients indicated little clinical benefit of monotherapy with the investigational corrector VX-809 (lumacaftor) or VX-770, whereas combination clinical trials show limited but significant improvements in lung function. We show that VX-770, as well as most other potentiators, reduces the correction efficacy of VX-809 and another investigational corrector, VX-661. To mimic the administration of VX-770 alone or in combination with VX-809, we examined its long-term effect in immortalized and primary human respiratory epithelia. VX-770 diminished the folding efficiency and the metabolic stability of ΔF508-CFTR at the endoplasmic reticulum (ER) and post-ER compartments, respectively, causing reduced cell surface ΔF508-CFTR density and function. VX-770–induced destabilization of ΔF508-CFTR was influenced by second-site suppressor mutations of the folding defect and was prevented by stabilization of the nucleotide-binding domain 1 (NBD1)–NBD2 interface. The reduced correction efficiency of ΔF508-CFTR, as well as of two other processing mutations in the presence of VX-770, suggests the need for further optimization of potentiators to maximize the clinical benefit of corrector-potentiator combination therapy in CF.