Miracle-dz/UniFAR-FTUs huggingface dataset:
Serum and CSF PDGF‐AA and FGF‐2 in relapsing‐remitting multiple sclerosis: a case–control study

Background and purpose: Fibroblast growth factor‐2 (FGF‐2) and platelet‐derived growth factor‐A (PDGF‐AA) are potent modulators of oligodendrocytes, the main responsible cells for myelin regeneration. We measured FGF‐2 and PDGF‐AA in the sera and cerebrospinal fluid (CSF) of patients with relapsing‐remitting multiple sclerosis (RR‐MS) and compared these values with control subjects.
Guidelines and the adoption of ‘lipid rescue’ therapy for local anaesthetic toxicity

Gathering evidence from animal experiments, an editorial in this journal and published human case reports culminated in the Association of Anaesthetists of Great Britain and Ireland recommending in August 2007 that lipid emulsion be immediately available to all patients given potentially cardiotoxic doses of local anaesthetic drugs. This development offered an opportunity to track the adoption of an innovation by anaesthetists in the UK and to gauge the effects of guidelines. Two surveys, each of 66 NHS hospitals delivering acute care within London and its penumbra, examined the adoption of lipid emulsion therapy. After the publication of the editorial in autumn 2006, the spread of ‘lipid rescue’ was rapid. The timing of the adoption and the impetus for innovation varied substantially between the sampled hospitals. When the formal guidelines were published, approximately half of the hospitals surveyed did not have lipid rescue. Of those that subsequently adopted it, half attributed their decision to the guidelines. At the end of 2007, there remained a small number of hospitals that had yet to adopt lipid rescue. Lipid rescue’s adoption by anaesthetists in the UK offers a rare example of swift uptake of an innovation. National guidelines accelerated the adoption of innovation by some hospitals.
An Unidentified Pancreatic Cancer Cell Product Alters Some Intracellular Pathways of Glucose Metabolism in Isolated Rat Hepatocytes

In this study we assessed whether conditioned media from a human pancreatic cancer cell line (MIA PaCa 2) can interfere with some intracellular pathways involved in glucose metabolism in isolated rat hepatocytes. The hepatocytes, isolated from Male Wistar rats, were incubated with MIA PaCa 2-conditioned or nonconditioned media. Conditioned and nonconditioned hepatocytes were run for 120 min in the presence or absence of insulin (100 mM) and were sampled at fixed time intervals. Supernatant glucose levels decreased to a similar extent over time in both conditioned and nonconditioned hepatocytes, while lactate levels significantly increased in nonconditioned hepatocytes with respect to conditioned hepatocytes. A pyruvate kinase activity increase was observed only in nonconditioned hepatocytes and was biphasic in nature, since this increased activity was detected both after a few and after 30 min following insulin stimulation. The cyclic AMP level increase was significantly higher in conditioned than in non-conditioned hepatocytes. It appears that MIA PaCa 2 cells produce a factor(s) that may interfere with one of the insulin-mediated intracellular pathways of glucose metabolism, namely, glycolysis. This detrimental effect on glycolysis is supported by the blunted rise in lactate concentration in the medium after the glucose challenge. This substance(s) probably transfers its signal inside the target cells, activating the adenylate cyclase pathway. These results support the hypothesis that pancreatic cancer is the cause rather than the consequence of diabetes mellitus.
Identification of larval cross-reactive and egg-specific antigens involved in granuloma formation in murine schistosomiasis mansoni

Cross-reactive humoral immune responses between antigens of different developmental stages of the worm Schistosoma mansoni have previously been demonstrated. In contrast, information on antigenic cross-reactivity at the T-cell level is still very sparse. The present study examined the cross-reactive T-cell responses to eggs and crude and fractionated soluble egg antigens (SEA) in infected mice prior to (from 0 to 4 weeks of infection) and after (5 weeks and onwards) egg deposition. Splenic lymphocyte proliferation to unfractionated SEA was detected as early as 2 weeks postinfection and increased rapidly by 4 weeks postinfection. Injections of live eggs into the lungs of infected mice at 4 weeks postinfection demonstrated enhanced granuloma formation, indicating the presence of primed T cells that respond to egg antigens. Further experiments with the artificial granuloma model and polyacrylamide gel electrophoresis-separated SEA fractions demonstrated that in mice infected for 4 weeks the 60- to 66-, 93- to 125-, and greater than 200-kDa SEA fraction-coated beads elicited significant pulmonary granulomas. By 6 weeks postinfection, when eggs are deposited in the livers, in addition to the cross-reactive fractions (60 to 66, 93 to 125, and greater than 200 kDa), beads coated with fractions of 25 to 30, 32 to 38, and 70 to 90 kDa also elicited significant granulomatous reactions. These antigenic fractions are considered to have elicited egg stage-specific T-cell responsiveness. In addition hepatic granuloma T cells from the 6th week of infection demonstrated the strongest blastogenic response to the 60- to 66-kDa cross-reactive fraction. Thus, in vitro and in vivo experiments demonstrated T-cell cross-reactivity between the larval and egg stages of the worm. On the basis of these observations, the appearance of the primary circumovum granulomatous response in infected mice is considered to represent the sum of larval cross-reactive and egg-specific T-cell responsiveness.
Post-traumatic Stress Reactions in Children After the 1988 Armenian Earthquake

One and a half years after the devastating earthquake in Armenia in 1988, 231 children from three cities at increasing distances from the epicentre were randomly screened in their schools to determine the frequency and severity of post-traumatic stress reactions, using the Children's Post-traumatic Stress Disorder Reaction Index (CPTSD-RI). A systematic clinical assessment of PTSD based on DSM-III-R criteria was also conducted on approximately half of this sample. A high CPTSD-RI score was strongly correlated with a clinical diagnosis of PTSD. A strong positive correlation was found between proximity to the epicentre and overall severity of post-traumatic stress reaction, as well as severity of core component symptoms of PTSD. High rates of chronic, severe post-traumatic stress reactions were found among children in the two most damaged cities, Spitak and Gumri. Analyses controlling for exposure revealed that girls reported more persistent fears than boys. These findings indicate that after catastrophic natural disaster, post-traumatic reactions in children may reach epidemic proportions, remain high for a prolonged period, and jeopardise the well-being of the child population of a large region. Systematic screening of children for PTSD can provide critical information for a rational public mental health programme after such a disaster.
PEGylated interferon-alpha2b: a branched 40K polyethylene glycol derivative.

PURPOSE The conjugation of interferon-alpha2b (IFN-alpha2b) to a branched-chain (40,000) polyethylene glycol (PEG2,40K) was studied. METHODS We studied the conjugation of IFN-alpha2b at different pH values (6.5, 7, and 8), using the PEG2,40K reagent in either solution or solid state. MonoPEGylated interferon was isolated by ion-exchange chromatography and characterized using (1) sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (2) cation exchange high-performance liquid chromatography, (3) bicinchoninic acid protein assay, (4) enzyme-linked immunosorbent assay, (5) cell-based bioassays, (6) thermal stability (at 60 degrees C), (7) tryptic digestion, and (8) pharmacokinetics in rats. RESULTS PEGylation reaction gave 30-55% PEG2,40K-IFN-alpha2b, 1-10% polyPEGylated interferon, and 35-70% unmodified IFN-alpha2b. Compared to the polyPEGylated IFN-alpha2b species, the pure (96%) monoPEGylated conjugate retained a significantly higher bioactivity (IU/mg): 1.7x10(4)+/-8.5x10(3) vs. 2.8x10(6)+/-1.4x10(6) for antiviral and 1.9x10(4)+/-9.5x10(3) vs. 3.1x10(6)+/-1.6x10(6) for antiproliferative activity. Immunorecognition against IFN was reduced by the PEG2,40K moiety in the conjugate. This monoPEGylated IFN-alpha2b, which migrated as a single band in gel electrophoresis, was found to be a heterogeneous, complex mixture of different positional isomers. PEGylation markedly enhanced both the resistance to tryptic degradation and the thermal stability of IFN-alpha2b. The serum half-life of 40K PEG-IFN was 330-fold longer, while plasma residence time was increased 708 times compared to native IFN. CONCLUSION The PEG2,40K conjugate of IFN-alpha2b has increased in vitroand in vivo stability as compared to the native cytokine.
Autotrophic, Hydrogen-Oxidizing, Denitrifying Bacteria in Groundwater, Potential Agents for Bioremediation of Nitrate Contamination

Addition of hydrogen or formate significantly enhanced the rate of consumption of nitrate in slurried core samples obtained from an active zone of denitrification in a nitrate-contaminated sand and gravel aquifer (Cape Cod, Mass.). Hydrogen uptake by the core material was immediate and rapid, with an apparent Km of 0.45 to 0.60 μM and a Vmax of 18.7 nmol cm-3 h-1 at 30°C. Nine strains of hydrogen-oxidizing denitrifying bacteria were subsequently isolated from the aquifer. Eight of the strains grew autotrophically on hydrogen with either oxygen or nitrate as the electron acceptor. One strain grew mixotrophically. All of the isolates were capable of heterotrophic growth, but none were similar to Paracoccus denitrificans, a well-characterized hydrogen-oxidizing denitrifier. The kinetics for hydrogen uptake during denitrification were determined for each isolate with substrate depletion progress curves; the Kms ranged from 0.30 to 3.32 μM, with Vmaxs of 1.85 to 13.29 fmol cell-1 h-1. Because these organisms appear to be common constituents of the in situ population of the aquifer, produce innocuous end products, and could be manipulated to sequentially consume oxygen and then nitrate when both were present, these results suggest that these organisms may have significant potential for in situ bioremediation of nitrate contamination in groundwater.
Octadecanoid and Jasmonate Signaling in Tomato (Lycopersicon esculentum Mill.) Leaves: Endogenous Jasmonates Do Not Induce Jasmonate Biosynthesis

Abstract Jasmonates and their precursors, the octadecanoids, are signals in stress-induced alteration of gene expression. Several mRNAs coding for enzymes of jasmonic acid (JA) biosynthesis are up-regulated upon JA treatment or endogenous increase of the JA level. Here we investigated the positive feedback of endogenous JA on JA formation, as well as its β-oxidation steps. JA-responsive gene expression was recorded in terms of proteinase inhibitor2 (pin2) mRNA accumulation. JA formed upon treatment of tomato (Lycopersicon esculentum cv. Moneymaker) leaves with JA derivatives carrying different lengths of the carboxylic acid side chain was quantified by gas chromatography-mass spectrometry (GC-MS). The data revealed that β-oxidation of the side chain occurs up to a butyric acid moiety. The amount of JA formed from side-chain modified JA derivatives correlated with pin2-mRNA accumulation. JA derivatives with a carboxylic side chain of 3, 5 or 7 carbon atoms were unable to form JA and to express on pin2, whereas evennumbered derivatives were active. After treatment of tomato leaves with (10-2H)-(–)-12-oxophytoenoic acid, (4-2H)-(–)-JA and its methyl ester were formed and could be quantified separately from the endogenously nonlabeled JA pool by GC-MS analysis via isotopic discrimination. The level of 8 nmol per g fresh weight JA and its methyl ester originated exclusively from labeled 12-oxophytoenic acid. This and further data indicate that endogenous synthesis of the JA precursor 12-oxophytodienoic acid, as well as of JA and its methyl ester, are not induced in tomato leaves, suggesting that positive feedback in JA biosynthesis does not function in vivo.
Interstitial cells of Cajal: a new perspective on smooth muscle function

Interstitial cells of Cajal (ICC) were described more than 100 years ago by Ramon y Cajal. For many years these cells were identified only by non‐specific histological stains and later, more reliably, by electron microscopy. Ultrastructural features and the anatomical locations of ICC suggested important physiological roles for these cells. A breakthrough occurred in our ability to study ICC when it was recognized that antibodies for Kit could be used to identify ICC, even in living tissues. Signalling via Kit, a receptor tyrosine kinase, is also necessary for ICC development and maintenance of phenotype. Thus, blocking Kit, by a variety of techniques, caused loss of ICC in experimental animals and demonstrated the critical physiological functions of these cells in gastrointestinal motility. Loss of ICC in human gastrointestinal diseases may contribute to the motor pathologies observed. Unrestrained Kit signalling leads to the transformation of ICC and the development of gastrointestinal stromal tumours. Now ICC‐like cells have been identified in a variety of smooth muscle tissues, and the race is on to discover whether these cells have equivalent or even novel functions in organs outside the gastrointestinal tract. This perspectives article gives a short overview of the history of ICC research and directions for future investigation.
Sustainability disclosure and a legitimacy crisis: Insights from two major cruise companies

The main aim of this paper is to analyse company sustainability disclosure in case of a legitimacy crisis. This work sets out to investigate how the negative externalities of an event reported widely in the media, such as the sinking of the Costa Concordia class cruise ship, have affected sustainability communication, for not only Carnival Corporation & PLC (the parent company of Costa) but also its most direct competitor Royal Caribbean Cruises Ltd. The paper relies on text analysis focusing on the sustainability reports of the two major companies (in terms of market share) in the cruise sector. Authors compared the reports of Carnival Corporation & PLC and its most direct competitor for a five-year period using text mining techniques. Results indicate that an event with social and environmental negative externalities, dominating international media and capable to bring discredit in the eyes of stakeholders, generates a change in the sustainability communication of both companies. Thus, repercussions are larger than one might suppose. Companies reduced the amount of information disclosed as a strategy to influence the perception of their audience, demonstrating that the provision of justifications, explanations and announcements of new sustainable policies (which increase the quantity of information) is not a predictable reaction. This paper undertakes empirical research on the sustainability reports of cruise line companies - which have been largely overlooked - and contributes to better understand company sustainability reporting praxis after an industrial disaster.
Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis.

OBJECTIVE To identify whether cytokines, cytokine-related factors, and chemokines are up-regulated prior to the development of rheumatoid arthritis (RA). METHODS A nested case-control study was performed in 86 individuals who had donated blood samples before experiencing any symptoms of disease (pre-patients) and 256 matched control subjects (1:3 ratio). In 69 of the pre-patients, blood samples were also obtained at the time of the diagnosis of RA. The plasma levels of 30 cytokines, related factors, and chemokines were measured using a multiplex system. RESULTS The levels of several of the cytokines, cytokine receptors, and chemokines were significantly increased in individuals before disease onset compared with the levels in control subjects; i.e., those representing signs of general immune activation (interleukin-1beta [IL-1beta], IL-2, IL-6, IL-1 receptor antagonist, and tumor necrosis factor), activation of Th1 cells (interferon-gamma, IL-12), Th2 cells (IL-4, eotaxin), Treg cells (IL-10), bone marrow-derived factors (IL-7, granulocyte-macrophage colony-stimulating factor, and granulocyte colony-stimulating factor), as well as chemokines (monocyte chemotactic protein 1 and macrophage inflammatory protein 1alpha). The levels were particularly increased in anti-cyclic citrullinated peptide antibody- and rheumatoid factor-positive individuals, and the concentration of most of these increased further after disease onset. The concentration of IL-17 in individuals before disease onset was significantly higher than that in patients after disease onset. Individuals in whom RA subsequently developed were discriminated from control subjects mainly by the presence of Th1 cells, Th2 cells, and Treg cell-related cytokines, while chemokines, stromal cell-derived cytokines, and angiogenic-related markers separated patients after the development of RA from individuals before the onset of RA. CONCLUSION Individuals in whom RA later developed had significantly increased levels of several cytokines, cytokine-related factors, and chemokines representing the adaptive immune system (Th1, Th2, and Treg cell-related factors); after disease onset, the involvement and activation of the immune system was more general and widespread.
Oesophageal emptying in patients with gastro‐oesophageal reflux

A reproducible radionuclide technique for measurement of oesophageal emptying of a solid bolus has been used to study normal control subjects, patients with gastro‐oesophageal reflux and a subgroup of these patients before and after fundoplication. The number of swallows to empty the oesophagus was significantly delayed in the gastro‐oesophageal reflux group compared to controls (P < 0.001). As a group, patients describing dysphagia had slower oesophageal emptying than patients without dysphagia (P < 0.001). The presence or absence of pre‐existing oesophagitis did not influence oesophageal emptying significantly. Following fundoplication patients did not show any significant alteration in their oesophageal emptying compared with their pre‐operative studies, although individually changes were noted in two patients. The solid bolus oesophageal emptying test is easily performed, well tolerated by patients and is a useful method for studying oesophageal dysfunction.
Efficacy of moxonidine in the treatment of hypertension in obese, noncontrolled hypertensive patients.

BACKGROUND Obesity has become an epidemic problem, contributing to metabolic syndrome, type 2 diabetes, hypertension, and cardiovascular disease. An adequate blood pressure control in this population of obese individuals is extremely difficult to achieve, and in most cases, therapeutic combinations are required. Pharmacologic treatment with moxonidine, a central I(1) imidazole receptor agonist, is a very interesting option because it acts upon the mechanisms implicated in the development of arterial hypertension in these patients. In addition, the drug improves the peripheral insulin resistance often found in obese patents, which contributes to maintain high blood pressure. METHODS An interventional study has been designed, adding moxonidine to noncontrolled hypertensive, obese subjects in whom a hypocaloric diet was previously recommended. A total of 25 primary care centers participated in the study, with a total of 135 patients recruited. RESULTS One hundred twelve patients were included in the study; 25 of them had type 2 diabetes. The mean reduction in systolic and diastolic blood pressure after 6 months treatment with moxonidine was 23.0 and 12.9 mm Hg, respectively. The mean systolic and diastolic pressures were 158.5 +/- 10.6 and 95.1 +/- 9 mm Hg, respectively, at baseline, versus 135.5 +/- 11.6 and 82.2 +/- 5.8 mm Hg at the end of the study. Creatinine clearance was significantly decreased in hyperfiltrating obese patients (143.6 +/- 31 vs. 128.2 +/- 27.9, P < 0.0001), without any significant change in patients with normal or slightly decreased renal function (81.9 +/- 18.9 vs. 80.9 +/- 17.5). Only 8 mild adverse reactions in 7 patients were recorded during the study. CONCLUSION Moxonidine is useful and safe for controlling arterial hypertension in obese patients.
Suppression of Tumor Necrosis Factor-mediated Apoptosis by Nuclear Factor κB-independent Bone Morphogenetic Protein/Smad Signaling*

The activation of nuclear factor κB (NF-κ B) plays a pivotal role in the regulation of tumor necrosis factor (TNF)-mediated apoptosis. However, little is known about the regulation of TNF-mediated apoptosis by other signaling pathways or growth factors. Here, unexpectedly, we found that bone morphogenetic protein (BMP)-2 and BMP-4 inhibited TNF-mediated apoptosis by inhibition of caspase-8 activation in C2C12 cells, a pluripotent mesenchymal cell line that has the potential to differentiate into osteoblasts depending on BMP stimulation. Utilizing both a trans-dominant IκBα inhibitor of NF-κB expressed in C2C12 cells and IκB kinase β-deficient embryonic mouse fibroblast, we show that BMP-mediated survival was independent of NF-κB activation. Rather, the antiapoptotic activity of BMPs functioned through the Smad signaling pathway. Thus, these findings provide the first report of a BMP/Smad signaling pathway that can inhibit TNF-mediated apoptosis, independent of the prosurvival activity of NF-κB. Our results suggest that BMPs not only stimulate osteoblast differentiation but can also promote cell survival during the induction of bone formation, offering new insight into the biological functions of BMPs.
Distribution and Abundance of White-Fronted Spider Monkeys, Ateles belzebuth (Atelidae), and Threats to Their Survival in Peruvian Amazonia

The white-fronted spider monkey, Ateles belzebuth, is listed as ‘Endangered’ according to the IUCN classification. In Peru it is found in the departments of Loreto, San Martín, Amazonas and Cajamarca, but detailed data on its geographic distribution, population densities and conservation status are scarce. In order to obtain such information, we conducted transect censuses on the Río Aushiri and Río San Antonio (right bank of Río Napo), and between the Río Curaray and the Río Arabela and Río Nashiño, respectively, and made additional explorations on the northern and southern banks of the Río Marañón. We obtained 48 sightings along 761 km of census transect. Group size and population densities were lower in an area with high hunting pressure compared to areas with medium or low hunting pressure. Besides hunting, increasing deforestation is a major threat to the survival of A. belzebuth in Peruvian Amazonia.
Heart rate variability and complexity in people with diabetes associated cardiac autonomic neuropathy

Cardiac autonomic neuropathy (CAN) in diabetes has been called a “silent killer”, because so few patients realize that they suffer from it, and yet its effect can be lethal. Early sub clinical detection of CAN and intervention are of prime importance for risk stratification in preventing sudden death due to silent myocardial infarction. This study presents the usefulness of heart rate variability (HRV) and complexity analyses from short term ECG recordings as a screening tool for CAN. Poincaré plot indexes and sample entropy (SampEn) measure of HRV were used for analyzing variability (short and long term) and complexity respectively. Analyses were performed on the different length of HRV records during supine rest. Reduced Poincaré plot patterns and higher SampEn were found in CAN+ group. Significant changes in HRV parameters of CAN+ group during the course of supine rest were found in contrast to control group (CAN−). Our results demonstrated the potential utility of nonlinear HRV parameters in identifying asymptomatic CAN.