bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparison of three induction regimens using succinylcholine, vecuronium, or no muscle relaxant: impact on the intraoperative monitoring of the lateral spread response in hemifacial spasm surgery: study protocol for a randomised controlled trial
Authors: Fang Yuan , Zhang Heng , Liu Wenke , Li Yu 
Published: September 2012

Abstract

Background
Surgical microvascular decompression (MVD) is the curative treatment for hemifacial spasm (HFS). Monitoring MVD by recording the lateral spread response (LSR) intraoperatively can predict a successful clinical outcome. However, the rate of the LSR varies between trials, and the reason for this variation is unclear. The aim of our trial is to evaluate the rate of the LSR after intubation following treatment with succinylcholine, vecuronium, or no muscle relaxant.

Methods and design
This trial is a prospective randomised controlled trial of 96 patients with HFS (ASA status I or II) undergoing MVD under general anaesthesia. Patients are randomised to receive succinylcholine, vecuronium, or no muscle relaxant before intubation. Intraoperative LSR will be recorded until dural opening. The primary outcome of this study is the rate of the LSR, and the secondary outcomes are post-intubation pharyngolaryngeal symptoms, the rate of difficult intubations, the rate of adverse haemodynamic events and the relationship between the measurement of LSR or not, and clinical success rates at 30 days after surgery.

Discussion
This study aims to evaluate the impact of muscle relaxants on the rate of the LSR, and the study may provide evidence supporting the use of muscle relaxants before intubation in patients with HFS undergoing MVD surgery.

Trials registration

http://www.chictr.org/ ChiCTR-TRC-11001504 Date of registration: 24 June, 2011.
The date the first patient was randomised: 30 September, 2011.
Evaluation of antioxidant and cytoprotective activities of Arnica montana L. and Artemisia absinthiumL. ethanolic extracts
Authors: Craciunescu Oana , Constantin Daniel , Gaspar Alexandra , Toma Liana , Utoiu Elena , Moldovan Lucia 
Published: September 2012

AbstractBackgroundArnica montanaL. andArtemisia absinthiumL. (Asteraceae) are medicinal plants native to temperate regions of Europe, including Romania, traditionally used for treatment of skin wounds, bruises and contusions. In the present study,A. montanaandA. absinthiumethanolic extracts were evaluated for their chemical composition, antioxidant activity and protective effect against H2O2-induced oxidative stress in a mouse fibroblast-like NCTC cell line.ResultsA. absinthiumextract showed a higher antioxidant capacity thanA. montanaextract as Trolox equivalent antioxidant capacity, Oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging activity, in correlation with its flavonoids and phenolic acids content. Both plant extracts had significant effects on the growth of NCTC cells in the range of 10–100 mg/LA. montanaand 10–500 mg/LA. absinthium. They also protected fibroblast cells against hydrogen peroxide-induced oxidative damage, at the same doses. The best protection was observed in cell pre-treatment with 10 mg/LA. montanaand 10–300 mg/LA. absinthium, respectively, as determined by Neutral red and lactate dehydrogenase assays. In addition, cell pre-treatment with plant extracts, at these concentrations, prevented morphological changes induced by hydrogen peroxide. Flow-cytometry analysis showed that pre-treatment withA. montanaandA. absinthiumextracts restored the proportion of cells in each phase of the cell cycle.ConclusionsA. montanaandA. absinthiumextracts, rich in flavonoids and phenolic acids, showed a good antioxidant activity and cytoprotective effect against oxidative damage in fibroblast-like cells. These results provide scientific support for the traditional use ofA. montanaandA. absinthiumin treatment of skin disorders.
Neuropeptide complexity in the crustacean central olfactory pathway: immunolocalization of A-type allatostatins and RFamide-like peptides in the brain of a terrestrial hermit crab
Authors: Polanska Marta A , Tuchina Oksana , Agricola Hans , Hansson Bill S , Harzsch Steffen 
Published: September 2012

Abstract

Background
In the olfactory system of malacostracan crustaceans, axonal input from olfactory receptor neurons associated with aesthetascs on the animal’s first pair of antennae target primary processing centers in the median brain, the olfactory lobes. The olfactory lobes are divided into cone-shaped synaptic areas, the olfactory glomeruli where afferents interact with local olfactory interneurons and olfactory projection neurons. The local olfactory interneurons display a large diversity of neurotransmitter phenotypes including biogenic amines and neuropeptides. Furthermore, the malacostracan olfactory glomeruli are regionalized into cap, subcap, and base regions and these compartments are defined by the projection patterns of the afferent olfactory receptor neurons, the local olfactory interneurons, and the olfactory projection neurons. We wanted to know how neurons expressing A-type allatostatins (A-ASTs; synonym dip-allatostatins) integrate into this system, a large family of neuropeptides that share the C-terminal motif –YX FGLamide.

Results
We used an antiserum that was raised against the A-type Diploptera punctata (Dip)-allatostatin I to analyse the distribution of this peptide in the brain of a terrestrial hermit crab, Coenobita clypeatus (Anomura, Coenobitidae). Allatostatin A-like immunoreactivity (ASTir) was widely distributed in the animal’s brain, including the visual system, central complex and olfactory system. We focussed our analysis on the central olfactory pathway in which ASTir was abundant in the primary processing centers, the olfactory lobes, and also in the secondary centers, the hemiellipsoid bodies. In the olfactory lobes, we further explored the spatial relationship of olfactory interneurons with ASTir to interneurons that synthesize RFamide-like peptides. We found that these two peptides are present in distinct populations of local olfactory interneurons and that their synaptic fields within the olfactory glomeruli are also mostly distinct.

Conclusions
We discuss our findings against the background of the known neurotransmitter complexity in the crustacean olfactory pathway and summarize what is now about the neuronal connectivity in the olfactory glomeruli. A-type allatostatins, in addition to their localization in protocerebral brain areas, seem to be involved in modulating the olfactory signal at the level of the deutocerebrum. They contribute to the complex local circuits within the crustacean olfactory glomeruli the connectivity within which as yet is completely unclear. Because the glomeruli of C. clypeatus display a distinct pattern of regionalization, their olfactory systems form an ideal model to explore the functional relevance of glomerular compartments and diversity of local olfactory interneurons for olfactory processing in crustaceans.
Targeting the Th17 pathway in psoriasis
Authors: Elloso M Merle , Gomez-Angelats Mireia , Fourie Anne M 
Published: September 2012

Abstract
Review of preclinical and clinical evidence implicating Th17 cells in psoriasis, and the therapeutic approaches to target this pathway.
In recent years, the classic paradigm of Th1/Th2 CD4+ T cell-mediated immunity has evolved to include the IL-17A-producing Th17 subset, a distinct proinflammatory CD4+ T cell lineage. Accumulating evidence suggests that IL-17A and the Th17 pathway may play an important role in the pathology of psoriasis and in other immune-mediated inflammatory diseases. This review summarizes the preclinical and clinical evidence implicating Th17 cells in psoriasis and the therapeutic approaches, approved or under investigation, to target this pathway in psoriasis.
The mannose receptor
Authors: Martinez-Pomares Luisa 
Published: September 2012

Abstract
Review on mannose receptor as an endocytic receptor in antigen delivery that is co-expressed with the microRNA miR-511-3p encoded within the Mrc1 gene.
The MR is a highly effective endocytic receptor with a broad binding specificity encompassing ligands of microbial and endogenous origin and a poorly characterized ability to modulate cellular activation. This review provides an update of the latest developments in the field. It discusses how MR biology might be affected by glycosylation and proteolytic processing, MR involvement in antigen delivery, and the potential contribution of MR to T cell differentiation and cellular activation. Further understanding of these areas will, no doubt, inform the design of novel, therapeutic tools for improved vaccination, control of inflammation, and tumor chemotherapy, which will benefit from exploiting MR-efficient internalization properties and unique pattern of expression.
Targeting p53 in Vivo: A First-in-Human Study With p53-Targeting Compound APR-246 in Refractory Hematologic Malignancies and Prostate Cancer
Authors: Lehmann Sören , Bykov Vladimir J.N. , Ali Dina , Andrén Ove , Cherif Honar , Tidefelt Ulf , Uggla Bertil , Yachnin Jeffrey , Juliusson Gunnar , Moshfegh Ali , Paul Christer , Wiman Klas G. , Andersson Per-Ola 
Published: September 2012

Purpose APR-246 (PRIMA-1MET) is a novel drug that restores transcriptional activity of unfolded wild-type or mutant p53. The main aims of this first-in-human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), and pharmacokinetics (PK) of APR-246. Patients and Methods APR-246 was administered as a 2-hour intravenous infusion once per day for 4 consecutive days in 22 patients with hematologic malignancies and prostate cancer. Acute myeloid leukemia (AML; n = 7) and prostate cancer (n = 7) were the most frequent diagnoses. Starting dose was 2 mg/kg with dose escalations up to 90 mg/kg. Results MTD was defined as 60 mg/kg. The drug was well tolerated, and the most common adverse effects were fatigue, dizziness, headache, and confusion. DLTs were increased ALT/AST (n = 1), dizziness, confusion, and sensory disturbances (n = 2). PK showed little interindividual variation and were neither dose nor time dependent; terminal half-life was 4 to 5 hours. Tumor cells showed cell cycle arrest, increased apoptosis, and upregulation of p53 target genes in several patients. Global gene expression analysis revealed changes in genes regulating proliferation and cell death. One patient with AML who had a p53 core domain mutation showed a reduction of blast percentage from 46% to 26% in the bone marrow, and one patient with non-Hodgkin's lymphoma with a p53 splice site mutation showed a minor response. Conclusion We conclude that APR-246 is safe at predicted therapeutic plasma levels, shows a favorable pharmacokinetic profile, and can induce p53-dependent biologic effects in tumor cells in vivo.
Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain
Authors: Hardy Janet , Quinn Stephen , Fazekas Belinda , Plummer John , Eckermann Simon , Agar Meera , Spruyt Odette , Rowett Debra , Currow David C. 
Published: September 2012

Purpose The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity. Patients and Methods In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days. Results In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, −0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P < .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13). Conclusion Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain.
Acute Myeloid Leukemia (AML): Different Treatment Strategies Versus a Common Standard Arm—Combined Prospective Analysis by the German AML Intergroup
Authors: Büchner Thomas , Schlenk Richard F. , Schaich Markus , Döhner Konstanze , Krahl Rainer , Krauter Jürgen , Heil Gerhard , Krug Utz , Sauerland Maria Cristina , Heinecke Achim , Späth Daniela , Kramer Michael , Scholl Sebastian , Berdel Wolfgang E. , Hiddemann Wolfgang , Hoelzer Dieter , Hehlmann Rüdiger , Hasford Joerg , Hoffmann Verena S. , Döhner Hartmut , Ehninger Gerhard , Ganser Arnold , Niederwieser Dietger W. , Pfirrmann Markus 
Published: September 2012

Purpose Identifying true therapeutic progress in patients with acute myeloid leukemia (AML) requires a comparison of treatment strategies and results on the basis of uniform patient selection. To foster comparability across five clinical studies, we introduced a common standard arm combined with a general upfront randomization and performed prospective analyses with adjustment for differences in prognostic baseline characteristics. Patients and Methods Whereas the studies' own regimens differed in chemotherapies, risk adaption, and guidelines for allogeneic stem-cell transplantation, the standard arm contained uniform cytarabine- and anthracycline-based standard-dose remission induction and high-dose consolidation courses. Results Of 2,995 evaluable patients aged 16 to 60 years, 290 patients were randomly assigned to the common standard arm. Seventy percent of the 290 achieved complete remissions (62% with complete recovery, 8% with incomplete recovery; 95% CI, 65% to 76%). Five-year survival probabilities were 44.3% (95% CI, 37.7% to 50.7%) for overall survival, 44.8% (95% CI, 37.0% to 52.2%) for relapse-free survival, and 31.5% (95% CI, 25.7% to 37.4%) for event-free survival. Neither the unadjusted survival probabilities of the Kaplan-Meier method nor their adjustment for prognostic variables in multiple Cox regression models led to statistically significant different results in the three survival end points when the outcomes of each study were compared with the standard arm. Conclusion A strictly prospective comparison of different treatment strategies in patients with AML did not show clinically relevant outcome differences when compared through a common standard treatment arm. The results provide a representative basis for further therapeutic approaches.
Prevention of Diabetes in db/db Mice by Dietary Soy Is Independent of Isoflavone Levels
Authors: Zimmermann Céline , Cederroth Christopher R. , Bourgoin Lucie , Foti Michelangelo , Nef Serge 
Published: September 2012

AbstractRecent evidence points towards the beneficial use of soy proteins and isoflavones to improve glucose control and slow the progression of type 2 diabetes. Here, we used diabetic db/db mice fed a high soy-containing diet (SD) or a casein soy-free diet to investigate the metabolic effects of soy and isoflavones consumption on glucose homeostasis, hepatic glucose production, and pancreatic islet function. Male db/db mice fed with a SD exhibited a robust reduction in hyperglycemia (50%), correlating with a reduction in hepatic glucose production and preserved pancreatic β-cell function. The rapid decrease in fasting glucose levels resulted from an inhibition of gluconeogenesis and an increase in glycolysis in the liver of db/db mice. Soy consumption also prevented the loss of pancreatic β-cell mass and thus improved glucose-stimulated insulin secretion (3-fold), which partly accounted for the overall improvements in glucose homeostasis. Comparison of SD effects on hyperglycemia with differing levels of isoflavones or with purified isoflavones indicate that the beneficial physiological effects of soy are not related to differences in their isoflavone content. Overall, these findings suggest that consumption of soy is beneficial for improving glucose homeostasis and delaying the progression of diabetes in the db/db mice but act independently of isoflavone concentration.
Estrogens and PTP1B Function in a Novel Pathway to Regulate Aromatase Enzymatic Activity in Breast Cancer Cells
Authors: Barone Ines , Giordano Cinzia , Malivindi Rocco , Lanzino Marilena , Rizza Pietro , Casaburi Ivan , Bonofiglio Daniela , Catalano Stefania , Andò Sebastiano 
Published: September 2012

Abstract
Local estrogen production by aromatase is an important mechanism of autocrine stimulation in hormone-dependent breast cancer. We have previously shown that 17-β estradiol (E2) rapidly enhances aromatase enzymatic activity through an increase of tyrosine protein phosphorylation controlled by the activity of the c-Src kinase in breast cancer cells. Here, we investigated the protein tyrosine phosphatase PTP1B (protein tyrosine phosphatase 1B) as a potential regulator of aromatase activity. We demonstrated a specific association between PTP1B and aromatase at protein-protein level and a reduction of aromatase activity in basal and E2-treated MCF-7 and ZR75 breast cancer cells when PTP1B was overexpressed. Indeed, a specific tyrosine phosphatase inhibitor increased basal and E2-induced enzymatic activity as well as tyrosine phosphorylation status of the purified aromatase protein. Moreover, E2 through phosphatidylinositol 3 kinase/Akt activation caused a significant decrease of PTP1B catalytic activity along with an increase in its serine phosphorylation. Concomitantly, the phosphatidylinositol 3 kinase inhibitor LY294002 or a dominant negative of Akt was able to reduce the E2 stimulatory effects on activity and tyrosine phosphorylation levels of aromatase. Taken together, our results suggest that E2 can impair PTP1B ability to dephosphorylate aromatase, and thus it increases its enzymatic activity, creating a positive feedback mechanism for estradiol signaling in breast cancer.
Recurrent non-small cell lung cancer: evaluation of CT-guided radiofrequency ablation as salvage therapy
Authors: Schoellnast Helmut , Deodhar Ajita , Hsu Meier , Moskowitz Chaya , Nehmeh Sadek A , Thornton Raymond H , Sofocleous Constantinos T , Alago William , Downey Robert J , Azzoli Christopher G , Rosenzweig Kenneth E , Solomon Stephen B 
Published: September 2012

Background Radiofrequency ablation (RFA) is a potential application as a salvage tool after failure of surgery, chemotherapy, or radiotherapy of non-small cell lung cancer (NSCLC). Although several studies have evaluated the use of RFA in primary NSCLC, there is little literature on its potential application as a salvage tool. Purpose To evaluate CT-guided RFA employed as a salvage therapy for pulmonary recurrences of NSCLC after prior treatment with chemotherapy, radiation therapy, and/or surgery. Material and Methods A retrospective computer database search yielded 33 patients with biopsy proven primary NSCLC who underwent CT-guided RFA of 39 recurrent tumors following surgery, chemotherapy, and/or radiotherapy. Follow-up imaging was performed with CT and PET-CT. The endpoints of interest were progression-free survival (PFS) and time to local progression (TTLP). PFS and TTLP were compared by lesion size (<3 cm, ≥3 cm). Results The median PFS was 8 months. For patients with a tumor size <3 cm median PFS was 11 months, whereas the median PFS of patients with a tumor size ≥3 cm was 5 months. The difference did not reach statistical significance ( P = 0.09). The median TTLP of all tumors was 14 months. TTLP of ablated tumors <3 cm in size was 24 months, compared to 8 months for ablated tumors ≥3 cm in size. The difference did not reach statistical significance ( P = 0.07). Conclusion RFA of recurrent NSCLC may be a valuable salvage tool to achieve local tumor control, especially in tumors measuring <3 cm in size.
Radiofrequency ablation in a porcine kidney model: effect of occlusion of the arterial blood supply on ablation temperature, coagulation diameter, and histology
Authors: Nakasone Yutaka , Ikeda Osamu , Kawanaka Koichi , Yokoyama Koichi , Yamashita Yasuyuki 
Published: September 2012

Background Radiofrequency ablation (RFA) is susceptible to the cooling effect of flowing blood. The reduced efficacy of RFA in large tumors reflects the in vivo biophysiological limitations imposed by perfusion-mediated vascular cooling. Purpose To compare the effects of RFA alone and of RFA combined with occlusion of the arterial blood supply on the tissue temperature, coagulation diameter, and histological changes in the acute phase. Material and Methods The temperature at roll-off, the coagulated tissue diameter, and histologic tissue changes were compared in normal porcine kidneys subjected in situ to two pigs each were subjected to RFA alone (four kidneys) or to RFA plus balloon occlusion of the renal artery (four kidneys). The tissue temperature was measured at three sites: area I, the center of the RFA field; area II, the ischemic field 1 cm distant from the edge of the RFA field; and area III, the normal kidney. Tissue samples were stained with hematoxylin and eosin (H&E). Cell viability in the ablated zone was determined by nicotinamide adenine dinucleotide (NADH) staining of frozen sections. Results The tissue temperatures achieved by RFA in areas I, II, and III were 101°C, 58°C, and 40°C with and 92°C, 44°C, and 38°C without balloon occlusion, respectively. The maximal coagulation diameter was 31 mm with and 23 mm without occlusion. The coagulation diameter was significantly larger and the temperature in area II was significantly higher in kidneys subjected to RFA with renal artery occlusion. H&E staining showed preservation of the normal renal parenchymal structure outside the thermal lesion and an increase in eosinophilic cells with indistinct cell borders and nuclei within the thermal lesion. H&E and NADH staining demonstrated a sharp demarcation between the ablation and normal tissue area and showed that in area II the addition of balloon occlusion did not produce histologic changes different from those in kidneys subjected to RFA alone. Conclusion A technique that combines RFA and partial renal artery occlusion may be useful in treatment of the non-resectable renal tumors with sizes appropriate for RF ablation.