Miracle-dz/UniFAR-FTUs huggingface dataset:
Cardiac Dysfunction in Pneumovirus-Induced Lung Injury in Mice

Objective: To determine biventricular cardiac function in pneumovirus-induced acute lung injury in spontaneously breathing mice. Design: Experimental animal study. Setting: Animal laboratory. Subjects: C57Bl/6 mice. Intervention: Mice were inoculated with the rodent pneumovirus, pneumonia virus of mice. Measurements and Main Results: Pneumonia virus of mice-infected mice were studied for right and left ventricular function variables by high-field strength (7 Tesla) cardiac MRI at specific time points during the course of disease compared with baseline. One day before and at peak disease severity, pneumonia virus of mice-infected mice showed significant right and left ventricular systolic and diastolic volume changes, with a progressive decrease in stroke volume and ejection fraction. No evidence for viral myocarditis or viral presence in heart tissue was found. Conclusions: These findings show adverse pulmonary-cardiac interaction in pneumovirus-induced acute lung injury, unrelated to direct virus-mediated effects on the heart.
A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study.

BACKGROUND Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD. METHODS The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005. RESULTS A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03). CONCLUSION There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.
Non-BAC Component but not Epidermal Growth Factor Receptor Gene Mutation is Associated with Poor Outcomes in Small Adenocarcinoma of the Lung

Objective: The purpose of this study was to identify risk factors for poor clinical outcome after surgical resection of small lung adenocarcinoma. Materials and Methods: Clinical records of 127 patients who had pathologic stage IA lung adenocarcinoma 20 mm or less and who had undergone a lobectomy with mediastinal lymph node dissection were reviewed. The percentage of non-bronchioloalveolar carcinoma (non-BAC) components quantified objectively, and epidermal growth factor receptor gene (EGFR) mutation determined by polymerase chain reaction-based assay were retrospectively linked with clinical data. Results: Based on the percentage of non-BAC component, 127 patients were classified as follows: 26 in group I, BAC, 46 in group II mixed subtype with ≥ 50% BAC, 18 in group III, mixed subtype with under 50% BAC, and 37 in group IV, mixed subtype with all non-BAC components or a pure pattern of one of the non-BAC components. Groups I and II were considered to be a “low non-BAC component type” and groups III and IV were considered to be a “high non-BAC component type. ” EGFR mutations in exon19 and exon21 were observed in 64 patients (50.4%). In terms of recurrence, the high non-BAC component type was the only independent factor for recurrence (p = 0.029). Regarding survival, the high age (p = 0.028) and high non-BAC component type (p = 0.046) were independent risk factors for poor overall survival. They were also independent risk factors for poor disease-free survival (p = 0.025 and p = 0.027, respectively). Conclusion: The high non-BAC component but not EGFR mutation status, is an independent risk factor for both recurrence and poor prognosis in patients with stage IA lung adenocarcinoma ≤20 mm.
The Effect of Environmental Degradation on the Financing of Healthcare

ABSTRACT Empirical work on the relation between health expenditure and environmental degradation is based predominantly on the ARDL approach to co-integration and to a lesser extent on panel co-integration as applied to a log-log specification. The results invariably show that environmental degradation has a positive effect on health expenditure. In this article, we examine the bivariate relation between environmental degradation and health expenditure, since this relation seems to hold strongly, which can be explained in terms of the environmental Kuznets curve. We cast a shadow of doubt on the practice of using the log-log specification without any theoretical or empirical justification. Our results show that the relation between health expenditure and environmental degradation can be either positive or negative, depending on the level of per capita income.
Effects of an Age-Specific Anterior Cruciate Ligament Injury Prevention Program on Lower Extremity Biomechanics in Children

Background: Implementing an anterior cruciate ligament injury prevention program to athletes before the age at which the greatest injury risk occurs (15-17 years) is important from a prevention standpoint. However, it is unknown whether standard programs can modify lower extremity biomechanics in pediatric populations or if specialized training is required. Hypothesis/Purpose: To compare the effects of traditional and age-specific pediatric anterior cruciate ligament injury prevention programs on lower extremity biomechanics during a cutting task in youth athletes. The authors hypothesized that the age-specific pediatric program would result in greater sagittal plane motion (ie, hip and knee flexion) and less motion in the transverse and frontal plane (ie, knee valgus, knee and hip rotation) as compared with the traditional program. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Sixty-five youth soccer athletes (38 boys, 27 girls) volunteered to participate. The mean age of participants was 10 ± 1 years. Teams (n, 7) were cluster randomized to a pediatric injury prevention program, a traditional injury prevention program, or a control group. The pediatric program was modified from the traditional program to include more feedback, progressions, and variety. Teams performed their programs as part of their normal warm-up routine. Three-dimensional lower extremity biomechanics were assessed during a sidestep cutting task before and after completion of the 9-week intervention period. Results: The pediatric program reduced the amount of knee external rotation at initial ground contact during the cutting task, F (2,62) = 3.79, P = . 03 (change: pediatric, 7.73° ± 10.71°; control, –0.35° ± 7.76°), as compared with the control group after the intervention period. No other changes were observed. Conclusion: The injury prevention program designed for a pediatric population modified only knee rotation during the cutting task, whereas the traditional program did not result in any changes in cutting biomechanics. These findings suggest limited effectiveness of both programs for athletes younger than 12 years of age in terms of biomechanics during a cutting task.
Functional IL-2 Receptor β (CD122) and γ (CD132) Chains Are Expressed by Fibroblast-Like Synoviocytes: Activation by IL-2 Stimulates Monocyte Chemoattractant Protein-1 Production1

The expression of the IL-2R α-, β-, and γ-chains, CD25, CD122, and CD132, respectively, was investigated on fibroblast-like synoviocytes (FLS) and dermal fibroblasts (DF). Both protein and mRNA for CD122 and CD132 were observed but there was no evidence of CD25 expression. Quantification of the Ag binding sites for CD122 showed that FLS expressed 4 times more receptor molecules than DF. The functional capability of these receptors was confirmed by the production of monocyte chemoattractant protein-1 (MCP-1) in direct response to stimulation by IL-2, which could be inhibited by neutralizing anti-CD122 mAb. Both rheumatoid arthritis (RA) and osteoarthritis (OA) FLS and DF spontaneously produced MCP-1 in culture over a similar range of concentrations. However, RA and OA FLS produced significantly greater levels of MCP-1 following stimulation by IL-2 and IL-1β; RA FLS produced significantly more MCP-1 than OA FLS. Addition of exogenous IL-2 caused a slight, but significant, decrease in MCP-1 production by DF. The addition of neutralizing anti-CD122 mAb to FLS cultures partially, but significantly, reduced the IL-2-induced MCP-1 secretion, but did not effect either the spontaneous or IL-1β-induced secretion of MCP-1. Increased tyrosine phosphorylation was observed in FLS lysates following 30-min incubation with IL-2. In conclusion, in the inflamed synovium, as activated T cells migrate through the sublining and lining layer, T cell-derived IL-2 may activate FLS to secrete MCP-1, thus recruiting macrophages into the rheumatoid synovium and perpetuating inflammation.
Problems in comparisons of data for the prevalence of myopia and the frequency distribution of ametropia

There is currently great interest in comparing data for the prevalence of myopia in different parts of the world, particularly in view of the suggestion that, in recent decades, marked increases have occurred in prevalence among children and young adults in some areas. This work investigates the factors that affect the comparison and interpretation of sets of myopia prevalence data for different age groups, locations and dates.
Pancreatic bicarbonate response to HCl before and after cutting the extrinsic nerves of the pancreas in dogs.

In two sets of dogs with gastric and pancreatic fistulas, we studied the effect of atropine on pancreatic bicarbonate output and release of secretin in response to intraduodenal HCl before and after stepwise removal of the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy alone and truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Ganglionectomy alone did not alter the incremental bicarbonate response to HCl. Truncal vagotomy alone significantly (P less than 0.05) decreased the incremental bicarbonate response to low (1.5 and 3 mmol/h) but not high (6 to 24 mmol/h) loads of HCl. Additional ganglionectomy restored the bicarbonate response to prevagotomy levels. With the extrinsic nerves intact and after ganglionectomy, but not after truncal vagotomy and truncal vagotomy plus ganglionectomy, intravenous atropine (14 nmol.kg-1.h-1) significantly reduced the incremental bicarbonate response to low (1.5 and 3 mmol/h) but not high loads of HCl. Neither the different surgical procedures nor atropine significantly altered plasma levels of secretin basally and in response to intestinal HCl. We conclude that 1) cholinergic fibers within the vagus nerves but not the splanchnic nerves are important mediators of the pancreatic bicarbonate response to low loads of HCl and 2) release of secretin by intestinal HCl is not under cholinergic and splanchnic control.
Net Innovation Pressure in Merger Analysis

I derive a Net Innovation Pressure (NIP) formula based on logic that is similar to the logic underlying Upward Pricing Pressure (UPP) and that takes account of R&amp;D spillovers. As with UPP, diversion is a key determinant of NIP, but the price-cost margin is not. The formula, which is quite simple, reveals that whether a merger decreases or increases the incentive to innovate depends on whether the diversion rate is greater or less than the R&amp;D spillover rate.
Thrombin Hydrolysis of Human Osteopontin Is Dependent on Thrombin Anion-binding Exosites*

The cytokine osteopontin (OPN) can be hydrolyzed by thrombin exposing a cryptic α4β1/α9β1 integrin-binding motif (SVVYGLR), thereby acting as a potent cytokine for cells bearing these activated integrins. We show that purified milk OPN is a substrate for thrombin with a kcat/Km value of 1.14 × 105 m–1 s–1. Thrombin cleavage of OPN was inhibited by unsulfated hirugen (IC50 = 1.2 ± 0.2 μm), unfractionated heparin (IC50 = 56.6 ± 8.4 μg/ml) and low molecular weight (5 kDa) heparin (IC50 = 31.0 ± 7.9 μg/ml), indicating the involvement of both anion-binding exosite I (ABE-I) and anion-binding exosite II (ABE-II). Using a thrombin mutant library, we mapped residues important for recognition and cleavage of OPN within ABE-I and ABE-II. A peptide (OPN-(162–197)) was designed spanning the OPN thrombin cleavage site and a hirudin-like C-terminal tail domain. Thrombin cleaved OPN-(162–197) with a specificity constant of kcat/Km = 1.64 × 104 m–1 s–1. Representative ABE-I mutants (K65A, H66A, R68A, Y71A, and R73A) showed greatly impaired cleavage, whereas the ABE-II mutants were unaffected, suggesting that ABE-I interacts principally with the hirudin-like OPN domain C-terminal and contiguous to the thrombin cleavage site. Debye-Hückel slopes for milk OPN (–4.1 ± 1.0) and OPN-(162–197) (–2.4 ± 0.2) suggest that electrostatic interactions play an important role in thrombin recognition and cleavage of OPN. Thus, OPN is a bona fide substrate for thrombin, and generation of thrombin-cleaved OPN with enhanced pro-inflammatory properties provides another molecular link between coagulation and inflammation.
Increased P‐glycoprotein messenger RNA stability in rat liver tumors in vivo

P‐glycoproteins (Pgp) are comprised of a small family of plasma membrane proteins whose abundance in cultured cells is often associated with the multidrug resistance phenotype. Overexpression of Pgp has been observed in many types of human cancers, but the molecular basis for this overexpression has not been established. We have used primary monolayer cultures of adult rat hepatocytes and a stepwise model of rat liver carcinogenesis to study the regulation of Pgp gene expression. We observed a marked overexpression of Pgp, specifically the class II Pgp, in both systems. In addition, we observed that a number of unrelated genes including α‐tubulin, β‐actin, γ‐actin, cytokeratin 8, cytokeratin 18, and c‐myc are overexpressed in cultured hepatocytes, and they are also overexpressed during liver carcinogenesis and in transplantable tumors. Nuclear run‐on assays showed no increase in the transcriptional activity of Pgp genes in transplantable liver tumors compared to normal liver. Studies of in vivo mRNA stability, however, revealed that all three Pgp mRNAs were relatively stable in transplantable liver tumors (t1/2 > 12 h), in contrast to what was found in normal liver (t1/2 < 2 h). In addition, mRNA for several other genes, including α‐tubulin, c‐myc, and cyclin D1, all appear to be stabilized in the tumors. These findings suggest that the overexpression of Pgp genes in rat liver tumors may be the result of a mechanism involving stabilization of a diverse group of mRNAs. J. Cell. Physiol. 177:1–12, 1998. © 1998 Wiley‐Liss, Inc.
Prostatic enlargement, symptomatology and pressure/flow evaluation: interrelations in patients with symptomatic BPH.

INTRODUCTION Benign prostatic hyperplasia (BPH) is the most common pathologic condition to afflict the aging male. Many patients with symptomatic BPH undergo prostatectomy without rigorous evaluation. Three concepts should be considered before any treatment of a patient with symptomatic BPH; Prostatic enlargement, symptomatology and bladder outflow obstruction. PATIENTS AND METHODS The study comprised 188 consecutive patients with symptomatic BPH, all eligible after pressure/flow examination. One-hundred-seventy-four of the patients answered the DAN-PSS questionnaire, 140 of the patients had their prostate size measured by transrectal ultrasonography. One-hundred-fifty-three patients were able to perform a free flow measurement upon arrival. Uroflowmetry, symptomatology and prostate size were matched with the results of pressure/flow examination. RESULTS Neither uroflowmetry, symptomatology nor prostate size correlated well with bladder outlet obstruction. The positive predictive value for infravesical obstruction was 88% if a maximum flow rate under 10 ml/s was used. Symptomatology could not be used to differentiate between patients with bladder outlet obstruction and patients without obstruction. The positive predictive value for infravesical obstruction was 76% if a prostate volume over 40 ml was chosen. DISCUSSION The purpose of diagnostic evaluation in patients with BPH, is to identify precisely the pathophysiology underlying the patients condition, so that rational therapy can be selected. CONCLUSION The disease entity of BPH is characterized by the interaction of prostate enlargement, the subjective symptom complex of prostatism, and urodynamic infravesical obstruction. Since it is impossible to interpolate from one to another of these conditions, a comprehensive evaluation of a patient with symptomatic BPH should include an assessment of all of these conditions.
Is Consumption Too Smooth?

For thirty years, it has been accepted that consumption is smooth because permanent income is smoother than measured income. This paper considers the evidence for the contrary position, that permanent income is in fact less smooth than measured income, so that the smoothness of consumption cannot be straightforwardly explained by permanent income theory. Quarterly first differences of labor income in the United States are well described by an AR(1) with a positive autoregressive parameter. Innovations to such a process are "more than permanent;" there is no deterministic trend to which the series must eventually return, and good or bad fortune in one period can be expected to be at least partially repeated in the next. Changes to permanent income should therefore be greater than the innovations to measured income, and changes in consumption should be more variable than innovations to measured income. In fact, changes in consumption are much less variable than are income innovations. We consider two possible explanations for this paradox, first, that innovations to labor income are in reality much less persistent than appears from an AR(l), and second, that consumers have more information than do econometricians, so that only a fraction of the estimated innovations are actually unexpected by consumers. The univariate time series results are less than decisive, but the balance of the evidence, whether from fitting ARMA models or from examining the spectral density, is more favorable to the view that innovations are persistent than to the opposite view, that there is slow reversion to trend. The information question is taken up within a bivariate model of income and savings that can accommodate the feedback from saving to income that is predicted by the permanent income theory if consumers have superior information. Nevertheless, our results are the same; changes in consumption are typically smaller than those warranted by the change in permanent income. We show that our finding of "excess smoothness" is consistent with the earlier findings of "excess sensitivity" of consumption to income. Our analysis is conducted within a "logarithmic" version of the permanent income hypothesis, a formulation that recognizes that rates of growth of income and saving ratios have greater claim to stationarity than do changes in income and saving flows.
Pharmacokinetic predictions for patients with renal impairment: focus on peptides and protein drugs.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Renal impairment may affect the pharmacokinetics of peptide and protein drugs. • Molecular size is a predictor. Small molecules are eliminated by the kidneys, whereas large molecules (>67 kDa) are not. • Urinary recovery of peptide and protein drugs in healthy volunteers is not predictive for pharmacokinetic changes in patients with renal impairment. WHAT THIS STUDY ADDS • An apparently continuous non-linear relationship between molecular weight and pharmacokinetic alterations as observed in patients with severe renal impairment or end-stage renal disease is described. • Potentially relevant pharmacokinetic changes were found for drugs with a molecular weight below 50 kDa. • Analysis of observed pharmacokinetics in patients with severe renal impairment may be a useful approach, especially when urinary recovery in healthy volunteers is not predictive. AIM Drug dosage adjustments in renal impairment are usually based on estimated individual pharmacokinetics. The extent of pharmacokinetic changes in patients with renal impairment must be known for this estimation. If measured data are not available, an estimate based on drug elimination in urine of healthy subjects or patients with normal renal function is commonly made. This is not reliable, however, if renal drug metabolism is involved, as is presumably the case for many peptide and protein drugs. In the present study a new method to predict pharmacokinetic changes for such drugs based on molecular weight was derived. METHODS Articles reporting measured pharmacokinetics of peptide and protein drugs in patients with severe renal impairment or end-stage renal disease were identified from the scientific literature, the pharmacokinetic parameter values were extracted and a statistical data synthesis was performed. A sigmoid E(max) model was applied and fitted to the data and the prediction error was analyzed. RESULTS Overall, 98 peptide and protein drugs were identified. Relevant pharmacokinetic data in patients with renal impairment were found for 21 of these drugs. The average drug clearance was 30% and the average prolongation in half-life was 3.1-fold for low molecular weight peptides or proteins. The median root squared percentage of the prediction error was 18% (drug clearance) and 12% (half-life). CONCLUSION An apparently continuous non-linear relationship between molecular weight and pharmacokinetic alterations in patients with severe renal impairment was found. The derived equations could be used as a rough guide for decisions on drug dosage adjustments in such patients.