Miracle-dz/UniFAR-FTUs huggingface dataset:
The hyperthermic and neurotoxic effects of ‘Ecstasy’ (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype

1 The effect of administration of 3,4‐methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) and its N‐demethylated product, 3,4‐methylenedioxyamphetamine (MDA) on both rectal temperature and long term neurotoxic loss of cerebral 5‐hydroxytryptamine (5‐HT) has been studied in male and female Dark Agouti (DA) rats. The female metabolizes debrisoquine more slowly than the male and its use has been suggested as a model of the human debrisoquine 4‐hydroxylase poor metabolizer phenotype. 2 A novel h.p.l.c. method was developed and used to measure plasma MDMA and MDA concentrations in the DA rats. 3 The hyperthermic response following MDMA was enhanced in female rats. Plasma MDMA concentrations were also 57% higher than in males 45 min post‐injection, while plasma concentrations of MDA were 48% lower. 4 Plasma concentrations of MDMA and MDA in male rats were unaffected by pretreatment with proadifen (15 mg kg−1) or quinidine (60 mg kg−1), but the hyperthermic response to MDMA (10 mg kg−1, i.p.) was enhanced by quinidine pretreatment. 5 The hyperthermic response following MDA was greater in male DA rats, despite plasma drug concentrations being 40% higher in females 60 min after injection. 6 Seven days after a single dose of MDMA (10 mg kg−1, i.p.) there was a substantial loss in the concentration of 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIA) in cortex and hippocampus. [3H]‐paroxetine binding was also decreased by 27% in the cortex, indicating that the amine loss reflected a neurodegenerative change. MDMA (5 mg kg−1, i.p.) was without effect on brain 5‐HT content. 7 A single dose of MDA (5 mg kg−1, i.p.) produced a major (approximately 40%) loss of 5‐HT content of cortex and hippocampus 7 days later. The loss was similar in males and females. 8 These data demonstrate that female DA rats are more susceptible to the acute hyperthermic effects of MDMA, probably because of impaired N‐demethylation and indicate that in human subjects acute MDMA‐induced toxicity may be exacerbated in poor metabolizer phenotypes. Low debrisoquine hydroxylase activity did not appear to impair the formation of a MDMA or MDA neurotoxic metabolite. Both severe acute hyperthermia and delayed neurotoxicity occurred following plasma levels of MDMA comparable to those reported in persons misusing the drug.
Exosomes and immune surveillance of neoplastic lesions: a review

Abstract The immune system has been reported to suppress the development and progression of neoplastic lesions; however, the exact mechanisms by which neoplastic lesions and the immune system interact are not well understood. Within the last decade, tiny membrane bound particles, approximately 30–100 nm in diameter, have been observed in the blood and other body fluids. These particles, currently called exosomes, are released from many types of tissues including tumors, and they contain and carry many proteins, and mRNAs and microRNA species. We review here how tumors suppress the immune system, especially by the formation of exosomes. Exosomes released from tumors are carried in part by the vascular system to distant cells, which phagocytose them. Depending on the proteins, mRNAs or microRNAs in the exosomes and the cell type, phagocytosis of exosomes may provide a modulating signal to the cell. In the case of exosomes from tumors, uptake of the exosomes by cells of the immune system has been reported to have three main effects: 1) suppression of the number and activity of natural killer cells, 2) suppression of the activity of T cells and 3) suppression of the number and maturation of mature dendritic cells.
The Spatial Distribution and Quantification of Food Insecurity in the North Central Health District of Idaho

ABSTRACT This study examines the complexity of community food insecurity in a rural region of the United States. In this country, food insecurity is more about improper distribution than about scarcity. Quantifying why and where food distribution is not equitable or adequate depends on the context. We analyzed multiple indicators of food security at the ZIP code level to create a food insecurity index. With the index we used geographic information systems (GIS) technology to test for spatial autocorrelation. This technique shows spatial patterns of clustering or dispersal of food insecurity. The results conclude significant clustering of food insecurity and security in the study region.
Tasmanian devil facial tumor disease: Insights into reduced tumor surveillance from an unusual malignancy

Tasmanian devil facial tumor disease (DFTD) is a highly aggressive cancer involving the facial tissues that currently presents a serious extinction risk for the Tasmanian devil population. Although the histogenesis is uncertain, an origin from a neural crest cell‐lineage is considered likely. Epidemiological, cytogenetic and immunological data all support the premise that DFTD arose from a single tumor clone from an individual diseased animal, and is being transmitted between individual animals as a tumor “allograft” by biting during social interaction. The spread of this cancer throughout the species is believed to be facilitated by a reduced MHC diversity, possibly as a result of an evolutionary bottleneck. The pathogenesis of DFTD has some similarities with certain human cancers, including donor‐recipient tumor transmission, which may complicate organ transplantation, and certain forms of malignancy at the maternal/fetal interface. The natural history and pathology of DFTD, and the data describing this highly unusual tumor biology are discussed.
"Red complex" (Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola) in endodontic infections: a molecular approach.

OBJECTIVE The "red complex," composed of Bacteroides forsythus, Porphyromonas gingivalis, and Treponema denticola, is implicated in severe forms of periodontal diseases. The purpose of this study was to assess the occurrence of the red complex in root canal infections through the use of a sensitive technique-the 16S rDNA-directed polymerase chain reaction (PCR). STUDY DESIGN Samples were obtained from 50 necrotic pulps with periradicular pathosis. Ten cases were diagnosed as acute periradicular abscesses. DNA was extracted from the samples and analyzed with a PCR-based identification assay. RESULTS At least 1 member of the red complex was found in 33 of 50 cases. T denticola, P gingivalis, and B forsythus were detected in 44%, 30%, and 26% of the cases, respectively. The red complex was found in 4 of 50 cases. No particular signs or symptoms were associated with the presence of these bacterial species. CONCLUSIONS Despite what is indicated in reports with respect to marginal periodontitis, red complex bacteria-either singularly or collectively-was not associated with any particular pattern of clinical symptoms. However, because the bacterial species from the red complex are recognized oral pathogens, their occurrence in root canal infections suggests that they may play a role in the pathogenesis of periradicular diseases.
Liver transplantation using uncontrolled non–heart‐beating donors under normothermic extracorporeal membrane oxygenation

Because of the organ shortage, non–heart‐beating donors have been proposed as a possible source of grafts for orthotopic liver transplantation (OLT). Despite the widespread use of controlled non–heart‐beating donors, there are only a few published studies reporting the outcomes with uncontrolled non–heart‐beating donors (UNHBDs). A prospective case‐control study on adult patients undergoing OLT was designed. We used normothermic extracorporeal membrane oxygenation (NECMO) in all UNHBDs. Matching 2:1 ratio comparison was performed between a study group (UNHBDs) and a brain death donor (BDD) control group. Between January 2006 and March 2008, a total of 60 patients were included: 20 in the UNHBD group and 40 in the control group. The incidence of ischemic cholangiopathy was 5% (n = 1) for the UNHBD group and 0% for the BDD group (P = 0.15). The rate of primary nonfunction was 10% (n = 2) in UNHBD recipients and 2.5% (n = 1) in BDD recipients (P = 0.21), with graft loss in all of them. Three patients were retransplanted in the UNHBD group (15%), 2 of them because of primary nonfunction and 1 because of ischemic cholangiopathy; no patient was retransplanted in the control group (P = 0.012). After a mean follow‐up of 330.4 ± 224.9 days, 1‐year cumulative patient survival was 85.5% for the UNHBD group and 87.5% for the BDD group (P = 0.768). One‐year cumulative graft survival was 80% in the UNHBD group and 87.5% in the BDD group (P = 0.774). In conclusion, UNHBDs under NECMO are a potential source of organs for OLT with encouraging outcomes potentially comparable to those obtained with BDDs. Liver Transpl 15:1110–1118, 2009. © 2009 AASLD.
Experimental Assessment and Future Applications of the Shikani Tracheostomy Speaking Valve.

PURPOSE Tracheostomy speaking valve use may increase airflow resistance and work of breathing. It remains unclear which valve offers the best performance characteristics. We compared the performance characteristics of the Shikani speaking valve (SSV; unidirectional-flow ball valve) with those of the Passy-Muir valve (PMV; bias-closed flapper valve). METHOD Airflow resistance was measured for both the SSV and the PMV at 8 flow amplitudes and in 3 orientations (-15°, 0°, +20°) in the bias-open and bias-closed configurations. RESULTS Significantly lower airflow resistance was observed for the SSV (bias open) compared with the PMV at -15° (p < .001), 0° (p < .001), and +20° (p = .006) from the horizon. No significant difference was observed between the PMV and the SSV (bias-closed) configuration at any of the tested angles. A nonsignificant trend toward decreased airflow resistance was observed between the SSV bias-open and bias-closed configurations at each of the angles tested. CONCLUSIONS The SSV demonstrated lower airflow resistance compared with the PMV across 8 flow amplitudes in the bias-open configuration at -15°, 0°, and +20° from the horizon. Further investigation is needed to determine the clinical impact of these findings on patient comfort, work of breathing, phonation, and airway protection during swallowing.
Public Debt and Interest Rate Spread in the European Union

The goal of this paper is to assess the debt sustainability in the EU measuring the impact of public debt on the interest rate spreads. The results show that public debt has positive and significant influence on interest rate spreads but its influence is not the same for all observed groups of countries within the EU. The highest influence is in the Eurozone countries and in the group of peripheral EU countries (that are most affected by crisis: Portugal, Italy, Ireland, Greece and Spain). The lowest impact of public debt on interest rate spread is registered in non-Eurozone countries. Other important variables in explanation of interest rate spread are inflation differentials, FDI inflows, current account deficit and GDP growth rate.
A New Look at Blockade of T‐cell Costimulation: A Therapeutic Strategy for Long‐term Maintenance Immunosuppression

Activated T cells orchestrate the immune response that results in graft rejection; therefore, a common goal among current immunosuppressive therapies is to block T‐cell activation, proliferation and function. Current immunosuppressive regimens that inhibit T cells and immune cells have greatly reduced the incidence of acute rejection following solid‐organ transplant. However, the expected improvements in long‐term outcomes have not been realized. This may be related to the non‐immune side effects of current maintenance immunosuppressants, which target ubiquitously expressed molecules. The focus in transplantation research is shifting in search of maintenance immunosuppressive regimens that might offer improved long‐term outcomes by providing efficacy in prevention of acute rejection combined with reduced toxicities. An emerging therapeutic strategy involves an immunoselective maintenance immunosuppressant that inhibits full T‐cell activation by blocking the interaction between costimulatory receptor–ligand pairs. This review describes costimulatory pathways and the development of molecules, which inhibit them in the context of transplantation research. Recent clinical data using the selective costimulation blocker, belatacept (LEA29Y), as a part of a CNI‐free maintenance immunosuppressive regimen in renal transplantation is highlighted.
A light microscopic and electron microscopic study of the superficial layers of the superior colliculus of the tree shrew (Tupaia glis)

Histochemical, Golgi, and electron microscopic methods were used to study the superficial layers of the superior colliculus of the tree shrew. Following horseradish peroxidase injections in the dorsal lateral geniculate nucleus (LGd) and the pulvinar (Pul), retrogradely labeled somata were found in the upper two‐thirds and the lower third of the stratum griseum superficiale (SGS), respectively, as has been described by Albano et al. ('79). In tissue prepared with Golgi methods, somata, similar in location and shape to those projecting to the LGd, had narrow, vertically oriented dendritic arbors, which were confined to the upper two‐thirds of the SGS. Cells located in the lower third of the SGS had larger somata, similar to those projecting to the Pul, and wider dendritic arbors, which were confined to the lower two‐thirds of the SGS. Electron microscopic comparison of the number of degenerating terminals following enucleation and striate cortex lesion indicated that within the SGS terminals from the retina overwhelmingly outnumbered those from the cortex. In both types of material, degenerating terminals were observed throughout the SGS. However, the majority of the degenerating optic terminals were located in the upper SGS, whereas most of the degenerating striate terminals were found in the lower SGS. Thus, cells that project to the LGd and those that project to the Pul differ not only with respect to location, size, and dendritic morphology, but also with respect to the proportion of retinal and striate afferents which terminate in the region of their dendritic trees.
Abnormalities of Gq-mediated cell signaling in Bartter and Gitelman syndromes.

BACKGROUND The constitutive endothelial isoform of nitric oxide synthase (ecNOS) and nitric oxide (NO) production are increased in patients with Bartter syndrome (BS) and Gitelman (GS) syndrome and may reduce vascular tone. Moreover, these patients present an abnormal cell signaling [reduced stimulated intracellular calcium ([Ca(2+)](i)) and inositol-1,4,5,triphosphate ([IP(3)](i)) in neutrophils], suggesting the presence of a generalized reduction of protein kinase C (PKC) and cell reactivity. Since PKC regulates ecNOS gene expression, we evaluated the signal transduction system involving Gq protein, PKC, and ecNOS in circulating nucleated cells from patients with BS/GS. METHODS Nucleated blood cells from 2 BS and 7 GS and from 10 controls (C) were used. PKC activity was evaluated in neutrophils by radioenzymatic assay; PKC alpha concentration was evaluated in monocytes by Western blot analysis. ecNOS and G alpha q mRNA production was evaluated in monocytes by reverse transcription-polymerase chain reaction (RT-PCR) analysis using specific primers and quantitated by PCR-based semiquantitative analysis of ecNOS and G alpha q mRNA expression. RESULTS Cytosol and membrane basal PKC activity were similar in neutrophils from BS/GS and C (70 +/- 3 vs. 80 +/- 2; 37 +/- 3 vs. 46 +/- 2 pmol/min/mg protein, respectively), while fMLP-stimulated membrane PKC activity increased to a lower extent in BS/GS (from 43 +/- 2 to 53 +/- 3 vs. 38 +/- 2 to 66 +/- 3 pmol/min/mg protein, P < 0.05 for the difference). Membrane PKC alpha expression was similar in basal conditions (8.5 +/- 1.5 vs. 12.4 +/- 4.0 densitometric units), but increased after fMLP was reduced in BS/GS (4.5 +/- 1.4 vs. 9.5 +/- 2.1, P < 0.01). In BS/GS, PKC stimulation with PMA dose dependently reduced ecNOS gene expression (from 0.80 +/- 0.05 to 0.78 +/- 0.03 densitometric units; PMA 50 nmol/L, P = NS; to 0.55 +/- 0.07, PMA 100 nmol/L, P < 0.001) to an undetectable expression (PMA 200 nmol/L). Qualitatively similar effects were seen in monocytes from control subjects. Incubation of monocytes from patients and controls with the PKC inhibitor GF109203X increased ecNOS mRNA, with no difference between patients and controls. G alpha q mRNA was reduced in BS/GS versus controls (0.87 +/- 0.013 vs. 0.98 +/- 0.005 densitometric units, P < 0.0004). CONCLUSION An abnormal G alpha q expression blunts cell signaling and PKC production in BS/GS. A reduced PKC up-regulated NO system may contribute to the vascular hyporeactivity of BS/GS.
Low‐power helium: Neon laser irradiation enhances production of vascular endothelial growth factor and promotes growth of endothelial cells in vitro

Numerous reports suggest that low‐power laser irradiation (LPLI) is capable of affecting cellular processes in the absence of significant thermal effect. The objective of the present study was to determine the effect of LPLI on secretion of vascular endothelial growth factor (VEGF) and proliferation of human endothelial cells (EC) in vitro.
The Developing Role of Unions in China's Foreign‐Invested Enterprises

This article evaluates the development of Chinese enterprise unions, drawing on case-study evidence from foreign-invested enterprises in the Pearl River Delta. Findings suggest that it was difficult for such employers to resist the establishment of an enterprise union. However, they generally sought to co-opt the union to meet organizational needs. Management strategy was critical in shaping the union's role, and our evidence suggests that this was influenced by factors such as home-country policies, the expectations of overseas customers, management ideology and pressures from the ACFTU and the Party-State to comply with the requirement for a union. The implications for the role of unions are evaluated.
[Laparoscopic splenectomy as an alternative to open surgery in the treatment of autoimmune thrombocytopenia].

BACKGROUND Several studies have shown the potential advantages laparoscopic splenectomy (LS) over open surgery. The aim of this study has been to evaluate the advantages of LS over open surgery in the treatment of autoimmune thrombocytopenia. PATIENTS AND METHODS 54 consecutive patients splenectomized for the treatment of idiopathic thrombocytopenic purpura (ITP) or HIV-related thrombocytopenia were analyzed. Operative features (operative time, conversion to open surgery, accessory spleens), immediate (stay, analgesia and blood transfusion requirements) and late postoperative features (platelet count), as well as splenectomy-related complications in both surgical procedures were compared. RESULTS Between February 1990 and February 1997, 54 splenctomies were performed for the treatment of autoimmune thrombocytopenia (ITP, n = 47, and HIV-related thrombocytopenia, n = 7). Eighteen were performed through an open approach, and 36 by laparoscopy. Both groups were comparable with regard to age, sex, platelet count, disease duration and body mass index. LS was completed in 34 cases (conversion to open surgery: 5.5%). The incidence of accessory spleens was 11% in the LS group and 5.5% in the open surgery group. Postoperative morbidity (16% vs 28%) and blood requirements (25% vs 33%) were lower after LS, but the differences did not reach statistical significance. Analgesia requirements (7 [SD 3] vs 11 [6]; p < 0.01) and postoperative stay (3.8 [2.6] vs 7.4 [3] days; p < 0.01) were significantly shorter after LS. Following splenectomy, the platelet counts became normal in 72% of patients submitted to LS and 78% of patients in the open surgery group. After 20 and 63 months mean follow-up, one patient in each group developed late complications. CONCLUSION As compared to open surgery, LS offers a better immediate clinical outcome, with similar long-term results.
Preoperative plasmapheresis in patients undergoing cardiac surgery procedures.

Donor plasmapheresis that is carried out weeks before the operation has proven to be of benefit in elective orthopedic patients with regard to reducing homologous blood consumption and preserving coagulation. In this study acute preoperatively performed plasmapheresis (APP) was investigated in cardiac surgery patients. Forty-five patients scheduled for elective aortocoronary bypass surgery were randomly divided into three groups of 15 patients each: 1) removal of platelet-poor plasma (PPP), 2) removal of platelet-rich plasma (PRP), and 3) no plasmapheresis (control group). Plasma volume removed was 10 ml/kg in all APP patients, and plasma was replaced by the same amount of low-molecular weight hydroxyethylstarch solution (6% HES 200/0.5). Various laboratory data were investigated before, during, and after extracorporeal circulation (ECC). Blood loss in control patients was more pronounced than in the two APP groups; two of the control patients needed packed red cells. APP itself did not affect coagulation variables, free hemoglobin, or polymorphonuclear (PMN) elastase. At the end of the operation, 5 h after ECC, and at the first postoperative day the number of platelets was significantly lower in the control group; PRP patients showed the highest values. Fibrinogen and AT-III levels were less compromised in APP patients than in the control group. Global coagulation parameters did not differ between the groups within the whole investigation period. PMN elastase increased significantly during ECC in all groups with the greatest increase in the control group (722%) and the smallest increase in PRP patients (280%), possibly due to the removal of cellular elements in this group. (ABSTRACT TRUNCATED AT 250 WORDS)
[Impact of PTTG1 downregulation on cell proliferation, cell cycle and cell invasion of osteosarcoma and related molecular mechanisms].

OBJECTIVE To downregulate the expression of pituitary tumor transforming gene 1 (PTTG1) in osteosarcoma (OS) cells by siRNA technology and to investigate related biological impact on cell proliferation, cell cycle and cell invasion of OS. METHODS Three OS cell lines and osteoblast hFOB1.19 cell line were used in this study. Control siRNA and PTTG1 siRNA were employed to transfect OS U2OS cells, and PTTG1 protein level was detected by Western blot after the transfection. Effects of PTTG1 siRNA on cell proliferation, cell cycle and cell invasion were investigated by CCK-8, flow cytometry and Boyden chamber, respectively. Finally, activity of Akt and its downstream target gene expression were analyzed by Western blot in U2OS cells upon various treatments. RESULTS Expression of PTTG1 protein in 3 OS cells (MG-63, SaOS-2 and U2OS) was significantly higher than that in osteoblast hFOB1.19, among which U2OS cells displayed the highest level. PTTG1 siRNA markedly downregulated the expression of PTTG1 protein in U2OS cells, leading to obvious inhibition of cell proliferation, altered cell cycle distribution and reduced ability of invasion of U2OS cells. Moreover, downregulation of PTTG1 reduced the expression of p-Akt (S473 and T308), MMP-2 and MMP-9 proteins, along with enhanced expression of p21 and E-cadherin proteins. CONCLUSIONS PTTG1 may be tightly linked to the development of OS and therefore may serve as a novel target for precision therapy of OS.