bluuebunny/crossref_metadata_2025_split huggingface dataset:
Block of Neuronal Na+Channels by Antidepressant Duloxetine in a State-dependent Manner
Authors: Wang Sho-Ya , Calderon Joanna , Kuo Wang Ging 
Published: August 2010

Background
Duloxetine is a mixed serotonin-norepinephrine reuptake inhibitor used for major depressive disorder. Duloxetine is also beneficial for patients with diabetic peripheral neuropathy and with fibromyalgia, but how it works remains unclear.

Methods
We used the whole cell, patch clamp technique to test whether duloxetine interacts with the neuronal Nav1.7 Na+ channel as a potential target. Resting and inactivated Nav1.7 Na+ channel block by duloxetine were measured by conventional pulse protocols in transfected human embryonic kidney cells. The open-channel block was determined directly using inactivation-deficient mutant Nav1.7 Na+ channels.

Results
The 50% inhibitory concentration (IC50) of duloxetine for the resting and inactivated wild-type hNav1.7 Na+ channel were 22.1+/-0.4 and 1.79+/-0.10 microM, respectively (mean+/-SE, n=5). The IC50 for the open Na+ channel was 0.25+/-0.02 microM (n=5), as determined by the block of persistent late Nav1.7 Na+ currents. Similar open-channel block by duloxetine was found in the muscle Nav1.4 isoform (IC50=0.51+/-0.05 microM; n=5). Block by duloxetine appeared via the conserved local anesthetic receptor as determined by site-directed mutagenesis. Finally, duloxetine elicited strong use-dependent block of neuronal transient Nav1.7 Na+ currents during repetitive stimulations.

Conclusions
Duloxetine blocks persistent late Nav1.7 Na+ currents preferentially, which may in part account for its analgesic action.
Influence of Tidal Volume on Pulse Pressure Variations in Hypovolemic Ventilated Pigs with Acute Respiratory Distress-like Syndrome
Authors: Wiklund Claes U. , Morel Denis R. , Orbring-Wiklund Hélène , Romand Jacques-Andre , Piriou Vincent , Teboul Jean-Louis , Bendjelid Karim 
Published: August 2010

Background
Sensitivity and specificity of respiratory change in pulse pressure (DeltaPP) to predict preload dependency has been questioned at small tidal volumes (VT) in critically ill patients suffering from acute respiratory distress syndrome (ARDS). We studied DeltaPP in pigs with ARDS-like syndrome during reversible hemorrhagic shock.

Methods
Prospective, observational animal study in a Laboratory Investigation Unit. Sixteen deeply sedated mechanically ventilated pigs were successively ventilated with VT of 10 ml/kg at a respiratory rate of 15 breaths/min (RR15) and VT of 6 ml/kg at RR15 and RR25. ARDS-like syndrome was produced by lung lavage in eight pigs (ARDS group). Severe hemorrhagic shock was induced by removal of 40% of total blood volume followed by restoration.

Results
After bleeding, in the control group ventilated with a VT of 10 ml/kg, DeltaPP increased from 8.5 (95% confidence interval [CI], 7.1 to 9.9%) to 18.5% (CI, 15.3 to 21.7%; P&lt;0.05). In the ARDS group, this index increased similarly, from 7.1% (95% CI, 5.3 to 9.0%) to 20.1% (CI, 15.3 to 24.9%; P&lt;0.05). In control lungs, reduction in VT from 10 to 6 ml/kg reduced the DeltaPP reaction by 40%, although it remained a statistically valid indicator of hypovolemia regardless of the RR value. In contrast, in the ARDS group, DeltaPP was an unreliable hypovolemia marker at low VT ventilation, regardless of the RR value (p=not statistically significant).

Conclusions
The present study suggests that DeltaPP is a reliable indicator of severe hypovolemia in pigs with healthy lungs regardless of VT or RR. In contrast, in pigs with ARDS-like syndrome ventilated with small VT, DeltaPP is not a good indicator of severe hemorrhage. However, in this setting, indexing DeltaPP to respiratory changes in transpulmonary pressure allows this marker to significantly indicate the occurrence of hypovolemia.
Intraoperative Ketamine Reduces Perioperative Opiate Consumption in Opiate-dependent Patients with Chronic Back Pain Undergoing Back Surgery
Authors: Loftus Randy W. , Yeager Mark P. , Clark Jeffrey A. , Brown Jeremiah R. , Abdu William A. , Sengupta Dilip K. , Beach Michael L. 
Published: August 2010

Background
Ketamine is an N-methyl-d-aspartate receptor antagonist that has been shown to be useful in the reduction of acute postoperative pain and analgesic consumption in a variety of surgical interventions with variable routes of administration. Little is known regarding its efficacy in opiate-dependent patients with a history of chronic pain. We hypothesized that ketamine would reduce postoperative opiate consumption in this patient population.

Methods
This was a randomized, prospective, double-blinded, and placebo-controlled trial involving opiate-dependent patients undergoing major lumbar spine surgery. Fifty-two patients in the treatment group were administered 0.5 mg/kg intravenous ketamine on induction of anesthesia, and a continuous infusion at 10 microg kg(-1) min(-1) was begun on induction and terminated at wound closure. Fifty patients in the placebo group received saline of equivalent volume. Patients were observed for 48 h postoperatively and followed up at 6 weeks. The primary outcome was 48-h morphine consumption.

Results
Total morphine consumption (morphine equivalents) was significantly reduced in the treatment group 48 h after the procedure. It was also reduced at 24 h and at 6 weeks. The average reported pain intensity was significantly reduced in the postanesthesia care unit and at 6 weeks. The groups had no differences in known ketamine- or opiate-related side effects.

Conclusions
Intraoperative ketamine reduces opiate consumption in the 48-h postoperative period in opiate-dependent patients with chronic pain. Ketamine may also reduce opioid consumption and pain intensity throughout the postoperative period in this patient population. This benefit is without an increase in side effects.
A Role for Acid-sensing Ion Channel 3, but Not Acid-sensing Ion Channel 2, in Sensing Dynamic Mechanical Stimuli
Authors: Borzan Jasenka , Zhao Chengshui , Meyer Richard A. , Raja Srinivasa N. 
Published: August 2010

Background
Acid-sensing ion channels 2 and 3 (ASIC2 and ASIC3, respectively) have been implicated as putative mechanotransducers. Because mechanical hyperalgesia is a prominent consequence of nerve injury, we tested whether male and female ASIC2 or ASIC3 knockout mice have altered responses to mechanical and heat stimuli at baseline and during the 5 weeks after spinal nerve ligation.

Methods
Age-matched, adult male and female ASIC2 knockout (n=21) and wild-type (WT; n=24) mice or ASIC3 knockout (n=20) and WT (n=19) mice were tested for sensitivity to natural stimuli before and after spinal nerve ligation surgery. All animals were first tested for baseline sensitivity to mechanical and heat stimuli and in a novel dynamic mechanical stimulation test. The same testing procedures were then repeated weekly after spinal nerve injury.

Results
Compared with their respective WT counterparts, ASIC2 and ASIC3 knockout mice had normal baseline sensitivity to standard mechanical and heat stimuli. However, when exposed to a novel stroking stimulus to test sensitivity to dynamic mechanical stimulation, ASIC3 knockout mice were significantly more sensitive than were WT mice. After spinal nerve ligation, ASIC2 and ASIC3 knockout mice developed mechanical and heat hyperalgesia comparable with that of their respective WT controls. In addition, in both experiments, female mice were more sensitive than male mice to heat at baseline and after the nerve injury.

Conclusions
We conclude that ASIC2 and ASIC3 channels are not directly involved in the development or maintenance of neuropathic pain after spinal nerve ligation. However, the ASIC3 channel significantly modulates the sensing of dynamic mechanical stimuli in physiologic condition.
Clinical Teaching Improves with Resident Evaluation and Feedback
Authors: Baker Keith 
Published: August 2010

Background
The literature is mixed on whether evaluation and feedback to clinical teachers improves clinical teaching. This study sought to determine whether resident-provided numerical evaluation and written feedback to clinical teachers improved clinical teaching scores.

Methods
Anesthesia residents anonymously provided numerical scores and narrative comments to faculty members who provided clinical teaching. Residents returned 19,306 evaluations between December 2000 and May 2006. Faculty members received a quantitative summary report and all narrative comments every 6 months. Residents also filled out annual residency program evaluations in which they listed the best and worst teachers in the department.

Results
The average teaching score for the entire faculty rose over time and reached a plateau with a time constant of approximately 1 yr. At first, individual faculty members had average teaching scores that were numerically diverse. Over time, the average scores became more homogeneous. Faculty members ranked highest by teaching scores were also most frequently named as the best teachers. Faculty members ranked lowest by teaching scores were most frequently named as the worst teachers. Analysis of ranks, differential improvement in scores, and a decrease in score diversity effectively ruled out simple score inflation as the cause for increased scores. An increase in teaching scores was most likely due to improved teaching.

Conclusions
A combination of evaluation and feedback, including comments on areas for improvement, was related to a substantial improvement in teaching scores. Clinical teachers are able to improve by using feedback from residents.
The Metabolic and Developmental Roles of Carotenoid Cleavage Dioxygenase4 from Potato
Authors: Campbell Raymond , Ducreux Laurence J.M. , Morris Wayne L. , Morris Jenny A. , Suttle Jeffrey C. , Ramsay Gavin , Bryan Glenn J. , Hedley Pete E. , Taylor Mark A. 
Published: August 2010

Abstract
The factors that regulate storage organ carotenoid content remain to be fully elucidated, despite the nutritional and economic importance of this class of compound. Recent findings suggest that carotenoid pool size is determined, at least in part, by the activity of carotenoid cleavage dioxygenases. The aim of this study was to investigate whether Carotenoid Cleavage Dioxygenase4 (CCD4) activity affects potato (Solanum tuberosum) tuber carotenoid content. Microarray analysis revealed elevated expression of the potato CCD4 gene in mature tubers from white-fleshed cultivars compared with higher carotenoid yellow-fleshed tubers. The expression level of the potato CCD4 gene was down-regulated using an RNA interference (RNAi) approach in stable transgenic lines. Down-regulation in tubers resulted in an increased carotenoid content, 2- to 5-fold higher than in control plants. The increase in carotenoid content was mainly due to elevated violaxanthin content, implying that this carotenoid may act as the in vivo substrate. Although transcript level was also reduced in plant organs other than tubers, such as leaves, stems, and roots , there was no change in carotenoid content in these organs. However, carotenoid levels were elevated in flower petals from RNAi lines. As well as changes in tuber carotenoid content, tubers from RNAi lines exhibited phenotypes such as heat sprouting, formation of chain tubers, and an elongated shape. These results suggest that the product of the CCD4 reaction may be an important factor in tuber heat responses.
Helping the police with their inquiries: the development of special care questioning techniques
Authors: TULLY BRYAN , TAM KAM‐OI 
Published: August 2010

SUMMARY. When children are dealt with in the justice system, by the police or the courts, the results are often highly emotionally distressing, and damaging to the true purpose of testimony. This paper describes a training programme of ‘special care questioning’ developed by a police force which employs clinical pychologists. An outline rationale is described, and the results discussed. It concludes that the task of protecting children cannot be the exclusive domain of either Clinical* social service practitioners or legal officers. Creative and ethical cooperation is possible and necessary.The special care questioning programme was developed from experimental work previously carried out with the Metropolitan Police with funding from the Police Foundation, UK.
Foster families and residential care for older children: some interpersonal dynamics
Authors: ALDGATE JANE 
Published: August 2010

SummaryThis paper compares the interpersonal dynamics of the family and residential care for older children within the context of ecologically based permanency planning where the birth family will be the preferred source of permanence in most cases. The author argues, on the basis of a review of the research, that foster care has a great deal to offer many children and is undoubtedly preferable for young children, but residential care is a genuine and important alternative for some older children. She concludes that the decision for placement should rest on a comprehensive assessment, taking into account consumer views.
New Vocational Qualifications in Child Care and Education in the UK
Authors: Calder Pamela 
Published: August 2010

SUMMARY: This paper explores the implications of the introduction of the new system of National Vocational Qualifications (NVQs) in Child Care and Education.The historical context of provision and the dual system of training of early childhood workers in Britain, split between care and education, is briefly described to show why pressures for change have come about. The background to the development of the qualifications is examined to see what light this throws on their current implementation.The paper argues that, compared with Europe where most countries are moving towards graduate status for early childhood education workers and many are thinking about an integration between care and education, with the introduction of our new child care NVQs we are moving in the opposite direction. Their introduction is likely to entrench the current split and does nothing to encourage the development of higher level qualifications which integrate care and education.
Failure to improve cigarette smoking abstinence with transdermal selegiline + cognitive behavior therapy
Authors: Killen Joel D. , Fortmann Stephen P. , Murphy Greer M. , Hayward Chris , Fong Dalea , Lowenthal Kimberly , Bryson Susan W. , Killen Diana T. , Schatzberg Alan F. 
Published: August 2010

ABSTRACTAims  To examine the effectiveness of transdermal selegiline for producing cigarette smoking abstinence.Design  Adult smokers were randomly assigned to receive selegiline transdermal system (STS) or placebo given for 8 weeks. All participants received cognitive behavior therapy (CBT). Follow‐ups were conducted at 25 and 52 weeks.Setting  Community smoking cessation clinic.Participants  243 adult smokers (≥18 years of age; ≥10 cigarettes/day).Measures  Expired‐air carbon monoxide confirmed 7‐day point prevalence abstinence.Findings  STS was not superior to placebo. More women than men were abstinent at 52 week follow‐up (28% vs 16%, P < 0.05). Behavioral activation (BAS) moderated treatment response (P = 0.01). The survival rate through week 52 for those with high ‘drive’ scores on the BAS was 47% if assigned to selegiline and 34% if assigned to placebo. The survival rate for those with low ‘drive scores’ on the BAS was 35% if assigned to selegiline compared to 53% if assigned to placebo.Conclusion  Transdermal selegiline does not appear generally effective in aiding smoking cessation though there may be a selective effect in those smokers with low ‘behavioral activation’.
Genetic polymorphisms of proteins in different breeds and different populations of chickens
Authors: Stratil A. 
Published: August 2010

SummarySix polymorphic protein systems in 15 chicken breeds have been investigated. In the Silkie breed another variant of G3 proteins (G3 AF Silkie) has been observed characterized by higher electrophoretic mobility than G3 A. The frequencies of individual alleles in various lines and different generations have been determined in two breeds (White Leghorn and White Cornish).
Polymorphism in glucose‐6‐phosphate dehydrogenase in the German Large‐White
Authors: Verhorst D. 
Published: August 2010

SummaryGlucose‐6‐phosphate dehydrogenase was tested in haemolysed swine erythrocytes by starch gel electrophoresis. In the German Large‐White this system is genetically controlled by two alleles, G‐6‐PDA and G‐6‐PDB.
The AB blood group system of cats
Authors: Auer L. , Bell K. 
Published: August 2010

SummaryHolmes (1950) and Eyquem. Podliachouk & Milot (1962) classified feline erythrocytes into two types according to their reactions with naturally occurring antibodies in cats' plasmas. Eyquem et al. (1962) designated the two antigens, A and B. and this nomenclature has been retained in the present study. The blood group system. AB. was investigated in more detail, both genetically and serologically. Frequencies of 73.3 % A and 26.3 % B were found in a survey of 1895 Brisbane cats and in addition, a new phenotype. AB. was discovered with a low incidence of 0.4 %.The results of the serological testing and limited family information suggested that the AB phenotype is inherited and not due to blood chimaerism. Preliminary genetic studies indicated that the A gene is dominant to the B in the usual situation and hypotheses to explain the occurrence of the AB phenotype are discussed.The incidence of naturally occurring antibodies was investigated in cats, with 1895 of blood type B having anti‐A and only 35 % of type A having anti‐B. No subgroups of the A and B antigens were detected and no blood group substances were found in the salivas of 37 cats. There was no evidence of any serological relationship of the feline A and B antigens with the human ABO antigens.
The swine histo compatibility system SLA: serological studies in the common Swiss and Danish swine breeds
Authors: Kristensen Birte , Philipsen Merete , Lazary S. , Renard Christine , de Weck A. L. 
Published: August 2010

SummaryAlloantisera were produced in common Swiss and Danish swine breeds by immunization with leucocytes or skin‐grafts. Out of the 126 antisera, 66 were chosen for further study based on titrations employing lymphocytes from unrelated pigs typed with French SLA antisera (Vaiman, Chardon & Renard, 1979). The 66 selected antisera and the French reagents defining 26 SLA specificities were used to type lymphocytes from 595 unrelated pigs of the common Swiss and Danish breeds. The reaction‐patterns of the French, Swiss and Danish antisera were adequately correlated for the French SLA specificities Nos FJ 2, 3, 6, 7, 8, 9, 11, 14, 19, 20 and 24 and for the haplotypes FJ 15.1.18 and FJ 5.4. In addition, a cluster of correlated Danish and Swiss antisera characterized a new specificity, provisionally designated CPH 31. This specificity was frequent in the Danish Landrace pigs.Using the reagents identified in this report, the segregation of SLA markers was studied. Back‐cross families demonstrated segregation of 15 distinct SLA haplotypes of which 14 are common in French Landrace or Large White. Differences were found in haplotype frequencies in both the Swiss and the Danish Landrace and Large White breeds.
Advances in understanding the pulmonary infiltration in acute promyelocytic leukaemia
Authors: Luesink Maaike , Jansen Joop H. 
Published: August 2010

SummaryIn acute promyelocytic leukaemia (APL), differentiation therapy can be complicated by the development of a differentiation syndrome (DS). Pulmonary infiltration of differentiating leukaemic cells is a key event in the development of DS. Several mediators have been identified that may promote migration and extravasation of differentiating APL cells from the bloodstream into the tissue. Adhesion of APL cells to each other and to the endothelium is induced by upregulation of the expression of adhesion molecules and constitutively active β2‐integrins during differentiation therapy. The expression of chemokines and their receptors is significantly upregulated as well. Pulmonary chemokine production can trigger transendothelial migration of differentiating APL cells from the bloodstream into the underlying tissue (initiation phase of DS). Massive production of chemokines by infiltrated APL cells can further enhance transendothelial migration of differentiating APL cells, causing an uncontrollable hyperinflammatory reaction in the lung (aggravation phase), which is not efficiently switched‐off by corticosteroids.
Thrombopoietic effect of VPAC1 inhibition during megakaryopoiesis
Authors: Peeters Karen , Loyen Serena , Van kerckhoven Soetkin , Stoffels Katinka , Hoylaerts Marc F. , Van Geet Chris , Freson Kathleen 
Published: August 2010

SummaryMegakaryocytes and platelets express the stimulatory G protein (Gs)‐coupled VPAC1 receptor, for which the pituitary adenylyl cyclase‐activating peptide (PACAP) and vasoactive intestinal peptide (VIP) are agonists. The neuropeptide PACAP and VPAC1 were previously found to negatively regulate megakaryopoiesis, and inhibition of their physiological pathway was found to have a thrombopoietic effect in conditions where megakaryo‐poiesis and thrombopoiesis were impaired, such as chemotherapy‐induced thrombocytopenia and congenital thrombocytopenia. The present study explored the thrombopoietic effect of VPAC1 inhibition in a murine model of syngeneic bone marrow transplantation (BMT) and in passive immune thrombocytopenia. Treatment of donor mice with a neutralizing anti‐VPAC1 antibody stimulated the initial, most critical recovery of the platelets in irradiated mice. In the passive immune thrombocytopenia model, we observed a thrombopoietic effect, resulting in a less severe platelet drop after induction of their removal in the spleen by an anti‐platelet antibody. We concluded that inhibition of the physiological PACAP/VPAC1 pathway could stimulate in vivo megakaryopoiesis. This inhibition can be applied to attenuate thrombocytopenia in conditions where platelets are destroyed as the major pathogenetic mechanism, e.g. immune thrombocytopenia purpura, or need to be produced de novo, e.g. after irradiation and BMT.
Prospective study of a therapeutic regimen with all‐trans retinoic acid and anthracyclines in combination of cytarabine in children with acute promyelocytic leukaemia: the Japanese childhood acute myeloid leukaemia cooperative study
Authors: Imaizumi Masue , Tawa Akio , Hanada Ryoji , Tsuchida Masahiro , Tabuchi Ken , Kigasawa Hisato , Kobayashi Ryoji , Morimoto Akira , Nakayama Hideki , Hamamoto Kazuko , Kudo Kazuko , Yabe Hiromasa , Horibe Keizo , Tsuchiya Shigeru , Tsukimoto Ichiro 
Published: August 2010

SummaryIn childhood acute promyelocytic leukaemia (APL), the efficacy of therapy combining cytarabine with all‐trans retinoic acid (ATRA) and anthracyclines remains unclear in terms of long‐term prognosis. Between August 1997 and March 2004, 58 children with APL (median age: 11 years) were enrolled into an acute myeloid leukaemia (AML) study (AML99‐M3) and followed up for a median time of 86 months. The regimen included ATRA and anthracyclines combined with cytarabine in both induction and consolidation. In induction, two patients died of haemorrhage and four patients developed retinoic acid syndrome. Of 58 patients, 56 (96·6%) achieved complete remission, two of whom relapsed in the bone marrow after 15 and 19 months respectively. Sepsis was a major complication, with an incidence of 5·6–10·9% in the consolidation blocks, from which all but one of patients recovered. Consequently, 7‐year overall and event‐free survival rates were 93·1% and 91·4% respectively, and cumulative incidence of relapse plateaued at 3·6% after 2 years. Follow‐up survey of 54 patients revealed no patients with late cardiotoxicity or secondary malignancy, except one with asymptomatic prolongation of QTc interval. This study suggests that the combination of cytarabine with ATRA and anthracycline‐based therapy may have useful implications in the perspective of long‐term prognosis and late adverse effects for childhood APL.