Miracle-dz/UniFAR-FTUs huggingface dataset:
The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenuous exercise in dogs.

UNLABELLED In order to elucidate the role of insulin and glucagon during strenuous exercise (100 m/min, slope 10-12 degrees), we have determined the rates of production (Ra), utilization (Rd), and metabolic clearance (M) of glucose in normal dogs before pancreatectomy and 2 wk after total pancreatectomy (a) when they were being maintained on constant intraportal basal insulin infusion, (245 muU/kg-min) and (b) when insulin supply had been withheld before and during exercise. Such an intense exercise induced in normal dogs a prompt decrease in mean immunoreactive serum insulin (IRI) from 20 +/- 3 to 11 +/- 2 muU/ml. In depancreatized insulin-infused dogs serum IRI during rest and exercise was between 14 +/- 1 and 12 +/- 2 muU/ml. In the third group, after cessation of insulin infusion, IRI decreased by 76% (from 17 +/- 5 to 4 +/- 1) and did not decrease futher during exercise. During exercise, serum immunoreactive glucagon (IRG) increased threefold in normal dogs. In depancreatized dogs serum IRG was the same as in normal resting dogs (indicating a nonpancreatic source of the hormone) but it did not increase during exercise. In normal dogs exercise induced proportional increases in Ra, Rd, and M (threefold) and normoglycemia was maintained. Changes in glucose turnover in depancreatized insulin-infused dogs were similar to those seen in normal dogs suggesting that a decrease in insulin secretion and a rise in IRG are not essential to prevent hypoglycemia in diabetic dogs. With the cessation of insulin infusion in resting depancreatized dogs, Ra increased, M decreased, and hyperglycemia ensued. During exercise, Ra continued to rise, but M did not increase significantly. CONCLUSIONS (a) Regulation of glucose production by liver during exercise is multifactorial. A decrease in IRI and an increase in IRG are not the only factors which can promote delivery of glucose to the peripheral tissues. The insulin glucagon molar ratio was found not to be an essential metabolic functional unit in regulating glucose metabolism during exercise. (b) It is hypothesized that increases in blood flow and capillary surface area can lead to an increase in the amount of insulin delivered to the muscle even when serum levels of IRI are reduced during exercies. It is suggested that small, but adequate amounts of insulin (as found in normal and depancreatized insulin-infused dogs) are essential in regulating glucose uptake in the working muscle. (c) Since totally depancreatized dogs had normal serum levels of IRG (originating presumably from the gastrointestinal tract), the question of essentiality of basal glucagon activity in glucose homeostasis during exercise could not be resolved by these experiments. It appears, however, that regulation of secretion of nonpancreatic glucagon differs from that of pancreatic glucagon.
The Unexpected Appearance of a New German Model

Most Continental European labour markets and welfare states underwent a substantial transformation over the last two decades moving from a situation of low employment and limited labour market inequality to higher employment, but also more inequality. Germany is a case in point as it exhibits growing employment figures and growing shares of low pay and non-standard work. Furthermore, the German labour market has been remarkably resilient during the recent crisis. How can this be explained? The paper claims that changes in labour market institutions such as unemployment benefits, active labour market policies and employment protection play a major role, but changes in industrial relations at the sectoral level and individual firms' staffing practices are equally important in explaining actual labour market outcomes. Regarding labour market institutions, the pattern found in Germany shows sequences of de- and re-regulatory reforms of employment protection and increasing or decreasing unemployment benefit generosity, both mostly addressing the margins of the labour market, i.e. 'outsiders', and contributing to a growing dualisation of the employment system. The institutional status of 'insiders' was hardly affected by legislative changes. This dualisation trend was reinforced by micro-level dynamics in industrial relations and company employment practices where we can observe growing reliance on mechanisms of internal flexibility for the skilled core work force and increasing use of non-standard types of employment in less specifically skilled occupations.
Unifying Underreaction Anomalies

This paper asks whether momentum and postevent drift are manifestations of the same underlying mechanism or are separate phenomena. We find that both effects can be attributed to persistence in returns following news that affects expected earnings or earnings growth. Holding these quantities fixed, there is no momentum effect, nor is there postevent drift for our sample of events, which includes seasoned equity offerings, repurchases, equity-financed mergers, and dividend initiations and omissions. The implication is that return continuation follows fundamental news in general, and in aggregate, this explains momentum.
Ischemic and Pharmacological Preconditioning in Girardi Cells and C2C12 Myotubes Induce Mitochondrial Uncoupling

Pharmacological uncoupling of mitochondrial oxidation from phosphorylation promotes preconditioning-like cardioprotection in the isolated rat heart. We hypothesized that modest mitochondrial uncoupling may be a critical cellular event in orchestrating preconditioning. Human-derived Girardi cells and murine C2C12 skeletal myotubes were preconditioned using simulated ischemia, adenosine, and diazoxide. Cell viability after 6 hours of simulated ischemia was measured using lactate dehydrogenase release and propidium iodide uptake. Mitochondrial inner membrane potential (&Dgr;&PSgr;m) was investigated by flow cytometry, cellular ATP by recombinant firefly-luciferase bioluminescence, and cellular oxygen consumption using oximetry. Preconditioning enhanced cell viability with attenuation of lactate dehydrogenase release (≥30%, P <0.05 versus ischemic controls) and a reduction in propidium iodide uptake by ≥26% versus ischemic controls after simulated ischemia in both cell lines. In Girardi cells, preconditioning induced the following phenotype immediately before index ischemia: (1) decreased &Dgr;&PSgr;m (JC-1: simulated ischemia 90±3%, adenosine 82±7%, diazoxide 87±4%, versus control 100%, P <0.05); (2) attenuation in cellular ATP levels (CTL 0.21±0.03 nmol/L ATP/&mgr;g protein, simulated ischemia 0.12±0.02, adenosine 0.15±0.02, diazoxide 0.11±0.02, P <0.05); and (3) enhanced cellular oxygen consumption (control 2.3±0.1 nmol/L oxygen/min/1×106 cells, simulated ischemia 3.1±0.1, adenosine 3.1±0.3, diazoxide 2.6±0.2, P <0.05). Cytoprotection, mitochondrial depolarization, and enhanced oxygen consumption were attenuated by the putative mitochondrial KATP-channel antagonist 5-hydroxydecanoate. The uncoupled phenotype in response to preconditioning was similarly observed in C2C12 myotubes. The present study suggests that modest mitochondrial uncoupling represents a unifying cellular response which may be important in directing preconditioning-mediated cytoprotection.
Comparative Study of Efficacy and Safety of Botulinum Toxin a Injections and Subcutaneous Curettage in the Treatment of Axillary Hyperhidrosis

Background: Primary focal axillary hyperhidrosis is a chronic distressing disorder affecting both the sexes. When the condition is refractory to conservative management, we should go for more promising therapies like intradermal botulinum toxin A (BtxA) injections in the axilla, and surgical therapies like subcutaneous curettage of sweat glands. Aims and Objectives: The aim of this study is to compare the efficacy, safety and duration of action of intradermal BtxA injections in one axilla and subcutaneous curettage of sweat glands in the other axilla of the same patient with axillary hyperhidrosis. Materials and Methods: Twenty patients (40 axillae) received intradermal BtxA injections on the right side (20 axillae) and underwent tumescent subcutaneous curettage of sweat glands on the left side (20 axillae). Sweat production rate was measured using gravimetry analyses at baseline and at 3 months after the procedure. Subjective analyses were done using hyperhidrosis disease severity scale (HDSS) score at baseline, at 3rd and 6th month after the procedure. Results: At 3 months post-treatment, the resting sweat rate in the toxin group improved by 80.32% versus 79.79% in the subcutaneous curettage method (P = 0.21). Exercise-induced sweat rate in the toxin group improved by 88.76% versus 88.8% in the subcutaneous curettage group (P = 0.9). There was a significant difference in the HDSS score after treatment with both the modalities. There were no adverse events with BtxA treatment compared to very minor adverse events with the surgical method. Conclusion: Both intradermal BtxA injections and tumescent subcutaneous curettage of sweat glands had a significant decrease in the sweat rates with no significant difference between the two modalities. Hence, in resource poor settings where affordability of BtxA injection is a constraint, subcutaneous curettage of sweat glands can be preferred which has been found equally effective with no or minimal adverse events.
Physical fitness in lignite miners.

The purpose of this study was to determine physical fitness level of lignite miners in the Czech Republic. The authors have examined a representative group of 152 active lignite miners by bicycle spiroergometry. The duration of employment in coal mines ranged between 5 and 32 years. The average age was 43.1 +/- 4.7 years. The miners had an average peak oxygen consumption 2.9 +/- 0.5 l.min-1, corresponding to 99.7 +/- 20.4% of the predicted maximal oxygen consumption. Physical fitness of lignite miners was comparable with reference values for healthy men in Czech population. The level of physical fitness did not correlate with the length of exposure to underground work.
Effects of Phenytoin, Carbamazepine, and Gabapentin on Calcium Channels in Hippocampal Granule Cells from Patients with Temporal Lobe Epilepsy

Summary: Purpose: The anticonvulsants phenytoin (PHT), carbamazepine (CBZ), and gabapentin (GBP) are commonly used in the treatment of temporal lobe epilepsy. Ca2+ current modulation has been proposed to contribute to the antiepileptic activity of these drugs. The purpose of this study was to determine the effects of these anticonvulsants on voltage‐dependent calcium channels in pathologically altered neurons from patients with chronic temporal lobe epilepsy.
NORMA: Network Operator Revenues Maximization

A great part of core network operators' gross profit comes from the provisioned connectivity services. In this work, we analyze the provisioning of differentiated services in current Shared Path Protection (SPP) environments. This analysis concludes that, with current resource assignment policies, only a very poor grade of service can be provided to the carried best effort traffic. Hence, we propose diff-WS, a resource partitioning scheme that differentiates those wavelengths supporting each class of service in the network. The benefits of diff-WS in front of current resource assignment policies are afterwards evaluated from an economic perspective. To this goal, we define the NORMA problem as a revenue maximization problem. To solve NORMA, we introduce statistical models to obtain, for a given grade of service, the highest traffic intensity for each supported class of service and resource assignment scheme. From the numerical results, we show that diff-WS maximizes resource utilization in the network and, thus, network operator's profit.
Elevated Expression of Osteopontin May Be Related to Adipose Tissue Macrophage Accumulation and Liver Steatosis in Morbid Obesity

OBJECTIVE—Osteopontin (OPN) plays an important role in the development of insulin resistance and liver complications in dietary murine models. We aimed to determine the expression pattern of OPN and its receptor CD44 in obese patients and mice according to insulin resistance and liver steatosis. RESEARCH DESIGN AND METHODS—OPN and CD44 expressions were studied in 52 morbidly obese patients and in mice. Cellular studies were performed in HepG2 cells. RESULTS—Hepatic OPN and CD44 expressions were strongly correlated with liver steatosis and insulin resistance in obese patients and mice. This increased OPN expression could be due to the accumulation of triglycerides, since fat loading in HepG2 promotes OPN expression. In contrast, OPN expression in adipose tissue (AT) was enhanced independently of insulin resistance and hepatic steatosis in obese patients. The elevated OPN expression in AT was paralleled with the AT macrophage infiltration, and both phenomena were reversed after weight loss. The circulating OPN level was slightly elevated in obese patients and was not related to liver steatosis. Further, AT did not appear to secrete OPN. In contrast, bariatric surgery–induced weight loss induced a strong increase in circulating OPN. CONCLUSIONS—The modestly elevated circulating OPN levels in morbidly obese patients were not related to liver steatosis and did not appear to result from adipose tissue secretion. In subcutaneous AT, expression of OPN was directly related to macrophage accumulation independently from liver complications. In contrast, hepatic OPN and CD44 expressions were related to insulin resistance and steatosis, suggesting their local implication in the progression of liver injury.
The role of regulated clinical trials in the development of bacteriophage therapeutics

Antibiotic resistance is now recognized as a major, global threat to human health and the need for the development of novel antibacterial therapies has become urgent. Lytic bacteriophages (phages) targeting individual bacterial pathogens have therapeutic potential as an alternative or adjunct to antibiotic use. Bacteriophage therapy has been used for decades, but clinical trials in this field are rare, leaving many questions unanswered as to its effectiveness for many infectious diseases. As a consequence bacteriophage therapy is not used or accepted in most parts of the world. The increasing need for new antimicrobial therapies is driving the development of bacteriophage therapies for a number of diseases but these require the successful completion of large-scale clinical trials in accordance with US FDA or European EMA guidelines. Bacteriophages are considered as biological agents by regulatory authorities and they are managed by biological medicinal products guidelines for European trials and guidelines of the division of vaccines and related product applications in the USA. Bacteriophage therapy is typically an ‘active’ treatment requiring multiplication in the bacterial host and therefore the factors that govern its success are different from those of conventional antibiotics. From the pharmacokinetic and pharmacodynamic points of view, time of treatment, dosage depending on the site of infection and the composition of the bacteriophage formulation (single vs multiple strains) need careful consideration when designing clinical trials. Scientific evidence regarding inflammatory effects, potential for gene transfer and phage resistance, need to be evaluated through such trials. However purity, stability and sterility of preparations for human use can be addressed through Good Manufacturing Practises to reduce many potential safety concerns. In this review we discuss the potential for the development of bacteriophage therapy in the context of critical aspects of modern, regulated clinical trials.
Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women: three-year data from 2 double-blind, randomized, placebo-controlled trials.

BACKGROUND In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women. METHODS A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels. RESULTS Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change + SE), -1. 32% +0.22%; raloxifene, 30 mg, 0.71% +0.23%; raloxifene, 60 mg, 1. 28% +0.23%; and raloxifene, 150 mg, 1.20% +0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo). CONCLUSIONS Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450.
Optimizing the benefits and minimizing the risks of enteral nutrition in the critically ill: role of small bowel feeding.

BACKGROUND Strategies that maximize the delivery of enteral nutrition while minimizing the associated risks have the potential to improve the outcomes of critically ill patients. By delivering enteral feeds in the small bowel, beyond the pylorus, the frequency of regurgitation and the risk of aspiration is thought to be decreased while at the same time, nutrient delivery is maximized. The purpose of this paper is to systematically review those studies that compare gastric with small bowel feeding. METHODS We searched computerized bibliographic databases, personal files, and relevant reference lists to identify eligible studies. Only randomized, clinical trials of critically ill patients that compared small bowel and gastric feedings were included in this review. In an independent fashion, relevant data on the methodology and outcomes of primary studies were abstracted in duplicate. RESULTS There were 10 studies that met the inclusion criteria for this review. In 1 study, small bowel feeding was associated with a reduction in gastroesophageal regurgitation and a trend toward reduced pulmonary aspiration. Several studies document that small bowel feeding was associated with an increase in protein and calories delivered and a shorter time to target dose of nutrition. Compared with gastric feeding, when the results of 7 randomized trials were aggregated statistically, small bowel feeding was associated with a reduction in pneumonia (relative risk, 0.76; 95% confidence intervals, 0.59, 0.99). There was no difference in mortality rates between the 2 groups. CONCLUSIONS Small bowel feeding may be associated with a reduction in gastroesophageal regurgitation, an increase in nutrient delivery, a shorter time to achieve desired target nutrition, and a lower rate of ventilator-associated pneumonia.
Ant Colony Systems for Large Sequential Ordering Problems

The sequential ordering problem is a version of the asymmetric traveling salesman problem where precedence constraints on vertices are imposed. A tour is feasible if these constraints are respected, and the objective is to find a feasible solution with minimum cost. The sequential ordering problem models a lot of real world applications, mainly in the fields of transportation and production planning. In this paper we propose an extension of a well known ant colony system for the problem, aiming at making the approach more efficient on large problems. The extension is based on a problem manipulation technique that heuristically reduces the search space. Computational results, where the extended ant colony system is compared to the original one, are presented
Contrasting mechanisms of impaired attentional set-shifting in patients with frontal lobe damage or Parkinson's disease.

Tests which assess the ability to shift cognitive set modelled after the Wisconsin Card Sorting Test are particularly sensitive to impairments in patients with Parkinson's disease as well as in patients with frontal lobe damage. However, the underlying mechanisms responsible for the similar deficits observed in the two patient groups are not well understood and may not be identical. For example, an apparent deficit in set-shifting ability may reflect either an impairment in the ability to shift from a perceptual dimension which has previously commanded attention (i.e. 'perseveration'), or in the ability to shift to an alternative perceptual dimension which has previously been irrelevant (i.e. 'learned irrelevance'). In this study, the performance of both medicated and non-medicated patients with Parkinson's disease were compared with a group of neurosurgical patients with localized excisions of the frontal lobes on a novel task designed to assess the relative contribution of 'perseveration' and 'learned irrelevance' to impaired set-shifting ability. Patients with frontal lobe damage were worse than controls in their ability to shift attention from a previously relevant stimulus dimension. Medicated patients with Parkinson's disease were worse at shifting to a previously irrelevant dimension. In contrast to both groups, nonmedicated patients with Parkinson's disease were impaired in both conditions. These results suggest that the gross set-shifting deficits reported in both frontal lobe patients and patients with Parkinson's disease may involve fundamentally different, though related, cognitive processes, and that these may be differentially affected by medication. Specifically, L-dopa therapy may protect Parkinson's disease patients from preservation of attention to a formerly relevant stimulus dimension.