bluuebunny/crossref_metadata_2025 huggingface dataset:
Correlates of (inappropriate) benzodiazepine use: the Netherlands Study of Depression and Anxiety (NESDA)
Authors: Manthey Leonie , van Veen Tineke , Giltay Erik J. , Stoop José E. , Neven Arie Knuistingh , Penninx Brenda W. J. H. , Zitman Frans G.
Published: October 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Benzodiazepines (BZDs) are not only used as a treatment for anxiety and depression (besides epilepsy), but also inappropriately for chronic insomnia, pain, somatic illnesses[1]and uncontrollable stress.

• In spite of lack of effectiveness and adverse health consequences in chronic BZD use, over 50% are long‐term users.

• The relative importance of sociodemographic, psychological and physical determinants of BZD use in general and inappropriate use has never been investigated in a comprehensive, multivariable model.

WHAT THIS STUDY ADDS

• BZDs were used by a considerable proportion of the NESDA participants and BZD use was rarely in accordance with all guidelines, mainly because of an extended duration of use.

• Mentally or physically vulnerable subjects were most likely to use BZDs as well as to use it inappropriately.

• Clinicians should be vigilant when initiating BZD prescriptions for vulnerable subjects, particularly when patients are chronically ill and old, as those subjects are at high risk of inappropriate use.

AIMResults on determinants of benzodiazepine (BZD) use in general and inappropriate use were inconsistent and mostly univariate. The relative importance of sociodemographic, psychological and physical determinants has never been investigated in a comprehensive, multivariate model.

METHODSWe included 429 BZD users and 2423 non‐users from the Netherlands Study of Depression and Anxiety (NESDA) in order to investigate sociodemographic, psychological and physical determinants of BZD use and inappropriate use by logistic and linear regression analyses.

RESULTSBZDs were used by a considerable proportion of the 2852 NESDA participants (15.0%). BZD use was independently associated with older age, singleness, unemployment, treatment in secondary care, higher medical consumption (more severe) anxiety, depression (OR [95% CI]= 1.95 [1.29, 2.93]), comorbidity, insomnia, SSRI (OR [95% CI]= 2.05 [1.55, 2.70]), TCA and other antidepressant (OR [95% CI]= 2.44 [1.64, 3.62]) use. Overall, BZD use was rarely in accordance with all guidelines, mainly because most users (82.5%) exceeded the recommended duration of safe use. Inappropriate use was independently associated with older age (β= 0.130) and chronic illnesses (β= 0.120). Higher scores on agreeableness were associated with less inappropriate use.

CONCLUSIONSMentally or physically vulnerable subjects were most likely to use BZDs. The most vulnerable (i.e. the old and physically ill) BZD users were at highest risk of inappropriate BZD use. Without further evidence of the effectiveness of BZDs in long‐term use, caution in initiating BZD prescriptions is recommended, particularly when patients are chronically ill and old, as those are most likely to display inappropriate use.
Case series on a diversity of illicit weight‐reducing agents: from the well known to the unexpected
Authors: Tang Magdalene H. Y. , Chen Sammy P. L. , Ng Sau W. , Chan Albert Y. W. , Mak Tony W. L.
Published: October 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

Adulteration of over‐the‐counter proprietary medications has been reported previously. However, to date a detailed study specifically on illicit slimming products has been lacking.

WHAT THIS STUDY ADDS

This study showed the presence of a wide variety of illicit weight‐reducing agents in over‐the‐counter slimming products, including registered or banned drugs and pharmaceutical analogues. These products may result in significant toxicities and even mortality.

AIMS To provide an overview of illicit weight‐reducing agents found in over‐the‐counter slimming products ingested by poisoned patients.

METHODS The clinical details and analytical findings of slimming products involved in poisoning cases between 2004 and 2009 were reviewed.

RESULTS Sixty‐six (including one fatal) poisoning cases were encountered. Eighty‐one products were analysed and found to contain undeclared prescription weight‐loss drugs, drug analogues, banned drugs, drugs used for an inappropriate indication or animal thyroid tissue, with up to six illicit agents within the same product. Many products were readily available from shops or the Internet.

CONCLUSIONS A rich diversity of illicit, potentially harmful weight‐reducing agents was found in over‐the‐counter slimming products.
Lack of efficacy of low‐dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs
Authors: SCHULLER S. , VAN ISRAËL N. , VANBELLE S. , CLERCX C. , McENTEE K.
Published: October 2010

Schuller, S., Van Israël, N., Vanbelle, S., Clercx, C., McEntee, K. Lack of efficacy of low‐dose spironolactone as adjunct treatment to conventional congestive heart failure treatment in dogs.J. vet. Pharmacol. Therap.34,322–331.

Aldosterone plays an important role in the pathophysiology of heart failure. Aldosterone receptor blockade has been shown to reduce morbidity and mortality in human patients with advanced congestive left ventricular heart failure. This study was designed to assess the efficacy and tolerance of long‐term low‐dose spironolactone when added to conventional heart failure treatment in dogs with advanced heart failure. Eighteen client‐owned dogs with advanced congestive heart failure due to either degenerative valve disease (n = 11) or dilated cardiomyopathy (n = 7) were included in this prospective, placebo‐controlled, double‐blinded, randomized clinical study. After initial stabilization including furosemide, angiotensin‐converting enzyme inhibitors, pimobendan and digoxin, spironolactone at a median dose of 0.52 mg/kg (range 0.49–0.8 mg/kg) once daily (n = 9) or placebo (n = 9) was added to the treatment, and the dogs were reassessed 3 and 6 months later. Clinical scoring, echocardiography, electrocardiogram, systolic blood pressure measurement, thoracic radiography, sodium, potassium, urea, creatinine, alanine aminotransferase, aldosterone and aminoterminal atrial natriuretic propeptide were assessed at baseline, 3 and 6 months. Survival times were not significantly different between the two treatment groups. Spironolactone was well tolerated when combined with conventional heart failure treatment.
Review: Molecular pathogenesis of blood–brain barrier breakdown in acute brain injury
Authors: Nag S. , Kapadia A. , Stewart D. J.
Published: October 2010

S. Nag, A. Kapadia and D. J. Stewart (2011) Neuropathology and Applied Neurobiology37, 3–23 Molecular pathogenesis of blood–brain barrier breakdown in acute brain injury

Historically, the blood–brain barrier (BBB) was considered to be at the level of cerebral endothelium. Currently, the interaction of endothelium with other components of the vessel wall and with neurones and glial cells is considered to constitute a functional unit, termed the neurovascular unit that maintains cerebral homeostasis in steady states and brain injury. The emphasis of this review is on cerebral endothelium, the best‐studied component of the neurovascular unit, and its permeability mechanisms in health and acute brain injury. Major advances have been made in unravelling the molecular structure of caveolae and tight junctions, both of which are components of the structural barrier to the entry of plasma proteins into brain. Time course studies suggest that caveolar changes precede junctional changes in acute brain injury. Additional factors modulating BBB permeability in acute brain injury are matrix metalloproteinases‐2 and 9 and angiogenic factors, the most notable being vascular endothelial growth factor‐A and angiopoietins (Ang) 1 and 2. Vascular endothelial growth factor‐A and Ang2 have emerged as potent inducers of BBB breakdown while Ang1 is a potent anti‐leakage factor. These factors have the potential to modulate permeability in acute brain injury and this is an area of ongoing research. Overall, a combination of haemodynamic, structural and molecular alterations affecting brain endothelium results in BBB breakdown in acute brain injury.
Splenectomy Increases Mortality in Murine Trypanosoma cruzi Infection
Authors: Maioli T. U. , Assis F. A. , Vieira P. M. A. , Borelli P. , Santiago H. , Alves R. , Romanha A. J. , Carneiro C. M. , Faria A. M. C.
Published: October 2010

The spleen is a secondary lymphoid organ that harbours a variety of cells such as T and B lymphocytes and antigen‐presenting cells important to immune response development. In this study, we evaluated the impact of spleen removal in the immune response to experimental Trypanosoma cruzi infection. C57BL/6 mice were infected with Y strain of the parasite and infection was followed daily. Mice that underwent splenectomy had fewer parasites in peripheral blood at the peak of infection; however, mortality was increased. Histological analysis of heart and liver tissues revealed an increased number of parasites and inflammatory infiltrates at these sites. Spleen removal was associated with reduction in IFN‐γ and TNF‐α production during infection as well as with a decrease in specific antibody secretion. Haematological disorders were also detected. Splenectomized mice exhibited severe anaemia and decreased bone marrow cell numbers. Our results indicate that spleen integrity is critical in T. cruzi infection for the immune response against the parasite, as well as for the control of bone marrow haematological function.
Nodulation factor receptor kinase 1α controls nodule organ number in soybean (Glycine max L. Merr)
Authors: Indrasumunar Arief , Searle Iain , Lin Meng‐Han , Kereszt Attila , Men Artem , Carroll Bernard J. , Gresshoff Peter M.
Published: October 2010

Two allelic non‐nodulating mutants, nod49 and rj1, were characterized using map‐based cloning and candidate gene approaches, and genetic complementation. From our results we propose two highly related lipo‐oligochitin LysM‐type receptor kinase genes (GmNFR1α and GmNFR1β) as putative Nod factor receptor components in soybean. Both mutants contained frameshift mutations in GmNFR1α that would yield protein truncations. Both mutants contained a seemingly functional GmNFR1β homeologue, characterized by a 374‐bp deletion in intron 6 and 20–100 times lower transcript levels than GmNFR1α, yet both mutants were unable to form nodules. Mutations in GmNFR1β within other genotypes had no defects in nodulation, showing that GmNFR1β was redundant. Transgenic overexpression of GmNFR1α, but not of GmNFR1β, increased nodule number per plant, plant nitrogen content and the ability to form nodules with restrictive, ultra‐low Bradyrhizobium japonicum titres in transgenic roots of both nod49 and rj1. GmNFR1α overexpressing roots also formed nodules in nodulation‐restrictive acid soil (pH 4.7). Our results show that: (i) NFR1α expression controls nodule number in soybean, and (ii) acid soil tolerance for nodulation and suppression of nodulation deficiency at low titre can be achieved by overexpression of GmNFR1α.
Characterization of the programmed cell death induced by metabolic products of Alternaria alternata in tobacco BY‐2 cells
Authors: Cheng Dan‐Dan , Jia Yu‐Jiao , Gao Hui‐Yuan , Zhang Li‐Tao , Zhang Zi‐Shan , Xue Zhong‐Cai , Meng Qing‐Wei
Published: October 2010

Alternaria alternata has received considerable attention in current literature and most of the studies are focused on its pathogenic effects on plant chloroplasts, but little is known about the characteristics of programmed cell death (PCD) induced by metabolic products (MP) of A. alternata, the effects of the MP on mitochondrial respiration and its relation to PCD. The purpose of this study was to explore the mechanism of MP‐induced PCD in non‐green tobacco BY‐2 cells and to explore the role of mitochondrial inhibitory processes in the PCD of tobacco BY‐2 cells. MP treatment led to significant cell death that was proven to be PCD by the concurrent cytoplasm shrinkage, chromatin condensation and DNA laddering observed in the cells. Moreover, MP treatment resulted in the overproduction of reactive oxygen species (ROS), rapid ATP depletion and a respiratory decline in the tobacco BY‐2 cells. It was concluded that the direct inhibition of the mitochondrial electron transport chain (ETC), alternative pathway (AOX) capacity and catalase (CAT) activity by the MP might be the main contributors to the MP‐induced ROS burst observed in tobacco BY‐2 cells. The addition of adenosine together with the MP significantly inhibited ATP depletion without preventing PCD; however, when the cells were treated with the MP plus CAT, ROS overproduction was blocked and PCD did not occur. The data presented here demonstrate that the ROS burst played an important role in MP‐induced PCD in the tobacco BY‐2 cells.
Acute kidney injury requiring dialysis secondary to adenovirus nephritis in renal transplant recipient
Authors: Sujeet K. , Vasudev B. , Desai P. , Bellizzi J. , Novoa‐Takara L. , He C. , El‐Meanawy A.
Published: October 2010

K. Sujeet, B. Vasudev, P. Desai, J. Bellizzi, L. Novoa‐Takara, C. He, A. El‐Meanawy. Acute kidney injury requiring dialysis secondary to adenovirus nephritis in renal transplant recipient Transpl Infect Dis 2011: 13: 174–177. All rights reserved

Abstract: Disseminated adenoviral infection is a serious problem, especially in an immunocompromised host. The disease carries a mortality rate reaching as high as 80%. It is seen most frequently in bone marrow transplant recipients, where it causes pneumonia and disseminated disease. In solid organ transplant recipients it causes graft infection. We report the case of a renal transplant recipient with disseminated adenoviral infection and acute kidney failure requiring dialysis. Reduction of immunosuppression and 1 dose of cidofovir were associated with resolution of viremia and viruria and return of kidney function to near baseline.
Sealevel history recorded in the Pleistocene carbonate sequence in IODP Hole 310‐M0005D, off Tahiti
Authors: Iryu Yasufumi , Takahashi Yasunari , Fujita Kazuhiko , Camoin Gilbert , Cabioch Guy , Matsuda Hiroki , Sato Tokiyuki , Sugihara Kaoru , Webster Jody M. , Westphal Hildegard
Published: October 2010

Material cored during the Integrated Ocean Drilling Program (IODP) Expedition 310 ‘Tahiti Sea Level’ revealed that the fossil reef systems around Tahiti are composed of two major stratigraphic sequences: (i) a last deglacial sequence; and (ii) an older Pleistocene sequence. The older Pleistocene carbonate sequence is composed of reef deposits associated with volcaniclastic sediments and was preserved in Hole 310‐M0005D drilled off Maraa. Within an approximately 70‐m‐thick older Pleistocene sequence (33.22–101.93 m below seafloor; 92.85–161.56 m below present sealevel) in this hole, 11 depositional units are defined by lithological changes, sedimentological features, and paleontological characteristics and are numbered sequentially from the top of the hole downward (Subunits P1–P11). Paleowater depths inferred from nongeniculate coralline algae, combined with those determined by using corals and larger foraminifers, suggest two major sealevel rises during the deposition of the older Pleistocene sequence. Of these, the second sealevel rise is associated with an intervening sealevel drop. It is likely that the second sealevel rise corresponds to that during Termination II (TII, the penultimate deglaciation, from Marine Isotope Stages 6 to 5e). Therefore, the intervening sealevel drop can be correlated with that known as the ‘sealevel reversal’ during TII. Because there are limited data on the Pleistocene reef systems in the tropical South Pacific Ocean, this study provides important information about Pleistocene sealevel history, the evolution of coral reef ecosystems, and the responses of coral reefs to Quaternary climate changes.
Amphibolitization within the lower crust in the termination area of the Godzilla Megamullion, an oceanic core complex in the Parece Vela Basin
Authors: Harigane Yumiko , Michibayashi Katsuyoshi , Ohara Yasuhiko
Published: October 2010

Gabbroic rocks and amphibolites were collected from the KR03‐01‐D10 dredge site located on the West Arm Rise of the Godzilla Megamullion, close to the Parece Vela Rift which appears to correspond to the termination area of a detachment fault, the Philippine Sea. The gabbroic rocks and amphibolites reveal the occurrence of a high hydrothermal activity in the lower crust close to a paleo‐ridge. In the gabbroic rocks, plagioclase compositions of both porphyroclasts and matrix were transformed into sodium‐rich compositions close to albite. Amphiboles are of secondary rather than igneous origin based on their microstructural occurrences. In the amphibolites, anorthite contents of porphyroclasts and matrix plagioclase are relatively lower than those of the gabbroic rocks, whereas the chemical compositions of amphibole within the amphibolites are similar to those of amphibole within the gabbroic rocks. Amphibolites represent the product of retrograde metamorphism associated with hydrothermal alteration of the gabbroic body by the reaction: clinopyroxene + calcic plagioclase + fluid → amphibole + sodic plagioclase. The estimated temperatures of the amphibolites derived from the amphibole thermobarometer and the gabbroic rocks derived from the hornblende–plagioclase geothermometer show ∼700–950°C and 650–840°C, respectively. The hydrothermal alteration recorded in the gabbroic rocks possibly occurred under high‐T conditions; the rocks were then metamorphosed to the amphibolites during a retrogressive stage. Our study indicates that amphibolitization took place with various degrees of deformation. It may imply that the hydrothermal activity increased as the Godzilla Megamullion developed as an oceanic core complex in the paleo‐ridge.
Comparison of Fcγ receptor expression on neutrophils with procalcitonin for the diagnosis of sepsis in critically ill patients
Authors: HSU Kuo‐Hsuan , CHAN Ming‐Chen , WANG Jiunn‐Min , LIN Liang‐Yi , WU Chieh‐Liang
Published: October 2010

Background and objective:  The expression of Fc receptors for IgG (FcγRs) on neutrophils, including CD16, CD32 and CD64, may be modulated in response to sepsis. We investigated the expression of FcγRs on neutrophils and procalcitonin (PCT) as biomarkers of sepsis among critically ill patients.

Methods:  This prospective study was conducted in a 24‐bed respiratory intensive care unit between July 2007 and June 2008. Critically ill patients requiring mechanical ventilation were enrolled and categorized into three groups: those with systemic inflammatory response syndrome (SIRS), those with severe sepsis and those with septic shock. Expression of FcγRs on neutrophils was quantitatively measured by flow cytometry immediately after enrolment of the patient. Serum PCT levels were also measured. Receiver operating characteristic (ROC) curves were used to evaluate the performance of FcγR expression and PCT as biomarkers of sepsis.

Results:  Sixty‐six patients were enrolled, including 11 with SIRS, 31 with severe sepsis and 24 with septic shock. Nineteen healthy volunteers served as normal controls. CD64 was upregulated, CD16 was downregulated and CD32 remained unchanged during sepsis. CD64 expression and the ratio of CD64/CD16 increased significantly with the severity of sepsis. However, serum PCT levels were not significantly different between SIRS and severe sepsis patients. CD64, CD64/CD16 and PCT all significantly predicted sepsis, septic shock and bacteraemia. As assessed using ROC curves, CD64 was better than PCT for differentiating SIRS from severe sepsis and septic shock. CD64 and CD64/CD16 were associated with mortality.

Conclusions:  CD64 and CD16 were differentially modulated by sepsis. CD64, CD64/CD16 and PCT may be biomarkers of sepsis. CD64 was better than PCT for identifying patients who required treatment with antibiotics.
The Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation is less accurate in patients with Type 2 diabetes when compared with healthy individuals
Authors: Camargo E. G. , Soares A. A. , Detanico A. B. , Weinert L. S. , Veronese F. V. , Gomes E. C. , Silveiro S. P.
Published: October 2010

Diabet. Med. 28, 90–95 (2011)

Aims  To analyse the performances of Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) and of Modification of Diet in Renal Disease (MDRD) study equations to estimate glomerular filtration rate (GFR) in patients with Type 2 diabetes mellitus with GFRs >60 ml/min and in healthy volunteers.

Methods  This cross‐sectional study included 111 individuals (56 patients with Type 2 diabetes and 55 healthy volunteers), aged 58 ± 9 years; 54 individuals were men (49%) and ninety‐eight (88%) were white. Glomerular filtration rate was measured by the 51Cr‐EDTA single‐injection method (51Cr‐GFR) and estimated according to the standardized MDRD and CKD‐EPI equations. Serum creatinine was measured by a traceable Jaffe method. Bland–Altman analysis was used to examine the agreement between measured and estimated GFR. Bias, accuracy and precision were evaluated.

Results  In diabetic individuals, 51Cr‐GFR was 106 ± 27 ml/min/1.73 m2, CKD‐EPI‐estimated GFR 82 ± 18 ml/min/1.73 m2 and MDRD‐estimated GFR 80 ± 21 ml/min/1.73 m2 (P < 0.001). In healthy volunteers, the corresponding values were 98 ± 20, 89 ± 13 and 84 ± 14 ml/min/1.73 m2 (P < 0.001). The accuracy of CKD‐EPI (P30) was higher in healthy volunteers than in diabetic patients (90 vs. 66%, respectively, P < 0.001). The MDRD equation performed as poorly as the CKD‐EPI equation in individuals with Type 2 diabetes.

Conclusions  The CKD‐EPI equation is less accurate in patients with Type 2 diabetes when compared with healthy individuals, with a 2.5‐fold greater bias.
Impact of pre‐exercise rapid‐acting insulin reductions on ketogenesis following running in Type 1 diabetes
Authors: Bracken R. M. , West D. J. , Stephens J. W. , Kilduff L. P. , Luzio S. , Bain S. C.
Published: October 2010

Diabet. Med. 28, 218–222 (2011)

Aim  This study examined the effects of reductions to pre‐exercise rapid‐acting insulin dose on changes in blood beta‐hydroxybutyrate, glucose, acid‐base balance and counter‐regulatory hormone responses to prolonged running in individuals with Type 1 diabetes.

Methods  Following ethical approval, seven participants with Type 1 diabetes (34 ± 2 years, BMI 27 ± 1 kg/m2) completed this study. After preliminary testing, participants attended the laboratory four times, each time consuming a 1.12MJ meal (60 g carbohydrate, 2 g fat, 2 g protein), with randomized amounts of their rapid‐acting insulin: Full dose (mean 7.3 ± 0.2 units), 75% dose (mean 5.4 ± 0.1 units), 50% dose (mean 3.7 ± 0.1 units) or 25% dose (mean 1.8 ± 0.1 units). After 2‐h rest, participants completed 45 min running at 70 ± 1% peak rate of oxygen consumption (VO2peak). Blood metabolites and hormones were recorded over the 2‐h rest and 3‐h recovery. Data were analysed using repeated‐measures ANOVA.

Results  Serum insulin peaked at 60 min in all conditions and was lowest after 25% insulin dose compared with full dose (P = 0.03). After the 25% insulin dose immediately pre‐exercise glucose concentration was higher than after the full or 50% dose (P < 0.05). Resting beta‐hydroxybutyrate gradually decreased during 2‐h rest (P < 0.05) with a similar post‐exercise peak of beta‐hydroxybutyrate at 3 h (P > 0.05). Post‐exercise blood pH increased for 5 min to a similar extent with all insulin doses , but the rise with the 25% dose was less compared with the full dose (P = 0.01). Blood lactate and plasma catecholamines increased after running similarly with all insulin reduction conditions (P < 0.05). Blood glucose area under the curve (BGauc) after the 25% insulin dose was greater than after the 75% dose (P = 0.02).

Conclusion  Ketogenesis following running was not influenced by reductions in pre‐exercise rapid‐acting insulin dose. This important preparatory strategy aids preservation of blood glucose but poses no greater risk to exercise‐induced ketone body formation.
CAN WE PUT POOR MEN TO WORK?
Authors: Mead Lawrence M.
Published: October 2010

Compared with Britain, welfare reform in the United States has relied less on incentives and more on administrative work tests. Parallel to welfare reform, American states have begun requiring men to work who owe child support or are on parole from prison. Evaluations of men's work programmes to date are encouraging, but implementing these programmes is demanding. The federal government should promote their further expansion and evaluation. Britain has yet to take serious steps in the same directions.
THE CHARITY COMMISSION – POLITICISED AND POLITICISING
Authors: Brodie Stanley
Published: October 2010

Charities have always had to show that they provide a ‘public benefit’, the meaning of which has been developed by case law. The Charity Commission, a body created by the last government, has provided guidance on the meaning of ‘public benefit’ which is at odds with the meaning developed in case law – and therefore in conflict with the statute under which the guidance was ostensibly provided. The Charity Commission has also allowed charities to engage in political campaigning, an activity which the House of Lords has held no charity can lawfully pursue without losing its charitable status. The Charity Commission and its guidance should be scrapped. Professionally qualified and independent Charity Commissioners should be appointed.
Beyond Family Remittances: Assessing the Prospects of Alternative Approaches to “Remittances for Development” in Africa
Authors: Ngomba Teke
Published: October 2010

This article examines the remittance patterns of Cameroonians residing in Aarhus, Denmark and discusses the findings in relation to those from earlier studies on migrants’ remittances. Based on analyses of the inclination of these Cameroonians to support development projects in Cameroon, it is argued that a strengthened partnership between local non‐state actors in Cameroon and the Cameroonian diaspora will significantly improve the role remittances can play in the country’s development. The article also highlights the framework, benefits and challenges of such potential partnership and suggests ways in which remittances from the Cameroonian diaspora in particular and African migrants in general, could be effectively channelled beyond migrants’ families to further the continent’s development drive.
Cis‐acting Allelic Variation in MUC5B mRNA Expression is Associated with Different Promoter Haplotypes
Authors: Loh Andrew X. , Johnson Lauren , Ng Wendy , Swallow Dallas M.
Published: October 2010

Mucins play a critical role in protecting and clearing the airways of noxious materials. Genetic variation that influences this environmental response is likely to affect respiratory disease susceptibility. It has been reported previously that variation in the promoter of MUC5B, the gene that encodes one of the two major gel‐forming mucins (MUC5B) of the mucus of the respiratory tract, is associated with susceptibility to diffuse panbronchiolitis, and that a genetic difference in promoter activity can be detected in vitro. The aim of this study was to determine whether this genetic difference in promoter activity can be detected in vivo. Here, we undertake RNA transcript expression studies, making use of human fetal tissue to explore constitutive differences. We compare in vivo transcript expression levels in heterozygotes and use the Bayesian method, PHASE to associate exonic simple nucleotide polymorphisms (SNPs) with promoter SNPs to generate haplotypes. We successfully show haplotypic differences in MUC5B expression in vivo. This genetic variation should be taken into account in future studies on MUC5B in respiratory disease.
Neurochemical profile of the developing mouse cortex determined by in vivo1H NMR spectroscopy at 14.1 T and the effect of recurrent anaesthesia
Authors: Kulak Anita , Duarte João M. N. , Do Kim Q. , Gruetter Rolf
Published: October 2010

J. Neurochem. (2010) 115, 1466–1477.

The neurochemical profile of the cortex develops in a region and time specific manner, which can be distorted by psychiatric and other neurological pathologies. Pre‐clinical studies often involve experimental mouse models. In this study, we determined the neurochemical profile of C57BL/6 mice in a longitudinal study design to provide a reference frame for the normal developing mouse cortex. Using in vivo proton NMR spectroscopy at 14 T, we measured the concentrations of 18 metabolites in the anterior and posterior cortex on postnatal days (P) 10, 20, 30, 60 and 90. Cortical development was marked by alterations of highly concentrated metabolites, such as N‐acetylaspartate, glutamate, taurine and creatine. Regional specificity was represented by early variations in the concentration of glutamine, aspartate and choline. In adult animals, regional concentration differences were found for N‐acetylaspartate, creatine and myo‐inositol. In this study, animals were exposed to recurrent isoflurane anaesthesia. Additional experiments showed that the latter was devoid of major effects on behaviour or cortical neurochemical profile. In conclusion, the high sensitivity and reproducibility of the measurements achieved at 14 T allowed us to identify developmental variations of cortical areas within the mouse cortex.
Macroscale spatial variation in chronic wound microbiota: A cross‐sectional study
Authors: Price Lance B. , Liu Cindy M. , Frankel Yelena M. , Melendez Johan H. , Aziz Maliha , Buchhagen Jordan , Contente‐Cuomo Tania , Engelthaler David M. , Keim Paul S. , Ravel Jacques , Lazarus Gerald S. , Zenilman Jonathan M.
Published: October 2010

Controlling for sample site is considered to be an important aspect of chronic wound microbiological investigations; yet, macroscale spatial variation in wound microbiota has not been well characterized. A total of 31 curette samples were collected at the leading edge, opposing leading edge, and/or center of 13 chronic wounds. Bacterial community composition was characterized using a combination of 16S rRNA gene‐based pyrosequencing; heat map display; hierarchical clustering; nonmetric multidimensional scaling; and permutation multivariate analysis of variance. A total of 58 bacterial families and 91 bacterial genera were characterized among the 13 wounds. While substantial macroscale spatial variation was observed among the wounds, bacterial communities at different sites within individual wounds were significantly more similar than those in different wounds (p=0.001). Our results support the prevalent opinion that controlling for sample site may improve the quality of wound microbiota studies; however, the significant similarity in bacterial communities from different sites within individual wounds indicates that studies failing to control for sampling site should not be disregarded based solely on this criterion. A composite sample from multiple sites across the surface of individual wounds may provide the most robust characterization of wound microbiota.
Monitoring of Diabetic Foot Syndrome Treatment: Some New Perspectives
Authors: Foltynski Piotr , Wojcicki Jan M. , Ladyzynski Piotr , Migalska‐Musial Karolina , Rosinski Grzegorz , Krzymien Janusz , Karnafel Waldemar
Published: October 2010

Diabetic foot syndrome (DFS) is one of the major complications of diabetes, and it can lead to foot amputations. It is very important to assure good medical care for diabetic patients not only during their stay at hospital but also at home. Telecare can be one good solution for extending medical care to patients’ homes. There are some reports regarding the application of new technologies in this field. The standard current model of telecare of DFS includes experts at hospital who conduct clinical examinations and decision making at a distance, in close cooperation with a visiting nurse and the patient. In the present paper a new paradigm of the DFS's telecare is introduced, which eliminates the visiting nurse. The designed and developed TeleDiaFoS system consists of a traditional database and mobile patient's module (PM) allowing for documentation of the foot images as well as the results of blood glucose and blood pressure measurements taken by the patient himself at home. A 2‐year validation of the TeleDiaFoS system on 10 DFS patients (3 months each) proved its usefulness and led to acceptance of this type of technical support by patients and physicians. The designed and developed system and proposed sterilization procedure of the PM have been found to be easy to use by the patient at home.
Possibility of Skin Epithelial Cell Transdifferentiation in Tracheal Reconstruction
Authors: Kim Jin Hoon , Kong Won Ho , Kim Jhin Gook , Kim Ho Joong , Seo Soo Won
Published: October 2010

In tissue engineering, injured tissue is normally reconstructed with cells obtained from that tissue itself. However, it is difficult to obtain cells for reconstruction of the trachea because of its shape and limited accessibility. Therefore, other cell sources having similar form and function or stem cells are used for tracheal reconstruction. In a previous study, we used autologous skin epithelial cells and successfully reconstructed canine tracheas. We found that the tracheal epithelial layer was completely covered with ciliated cells, which is a remarkable finding because skin and tracheal epithelial cells originate from different germinal layers and have very different forms. In this study, to elucidate the origin of the ciliated cells, we identified the stem cell contents of skin epithelial cells on primary culture, marked the skin epithelial cells with PKH26 dye, and transplanted them onto canine tracheas. After 5 months, we identified PKH26 fluorescence on the tracheal epithelial layers, especially over the tracheal cartilages. Consequently, we demonstrated that transplanted autologous skin epithelial stem cells can remain viable on the trachea for a few months and can transdifferentiate into tracheal epithelial cells and chondrocytes.
A Highly Accurate and Consistent Microfluidic Viscometer for Continuous Blood Viscosity Measurement
Authors: Kang Yang Jun , Yoon Sang Youl , Lee Kyeong‐Hwan , Yang Sung
Published: October 2010

A high‐precision microfluidic viscometer with a microfluidic channel array composed of 100 indicating channels is demonstrated in this study. The relative viscosity of the sample fluid could be measured by simply counting the number of the indicating channels occupied by the sample and the reference fluids. Using lumped parameter modeling, an analytical solution of the relative viscosity is derived. In order to evaluate the performance of the developed microfluidic viscometer, the viscosity values obtained by the microfluidic viscometer are compared with the ones obtained by a conventional viscometer. In Newtonian fluid (sodium dodecyl sulfate [SDS] solution) tests, the normalized differences in the viscosities measured by two methods are less than 2.5%. In non‐Newtonian fluid (whole blood, 45% hematocrit) tests at various shear rates, the viscosities measured by two methods are evaluated by a regression analysis via power law (). The k values for both the microfluidic viscometer and the conventional viscometer are 12.953 and 13.175, respectively; the n values are 0.797 and 0.807, respectively. The normalized differences in two parameters measured by two methods are less than 2%. Thus, it could be concluded that the microfluidic viscometer developed in this study is capable of measuring viscosity of both Newtonian fluid (SDS solution) and non‐Newtonian fluid (whole blood) with a relatively high accuracy in a continuous and near real‐time fashion. Furthermore, the viscometer could be potentially employed in cardiopulmonary bypass procedures by continuously monitoring viscosity changes due to blood damages and hemodilution.
Effects of Low Intensity Pulsed Ultrasound on Rat Schwann Cells Metabolism
Authors: Tsuang Yang‐Hwei , Liao Li‐Wen , Chao Yuan‐Hung , Sun Jui‐Sheng , Cheng Cheng‐Kung , Chen Ming‐Hong , Weng Pei‐Wei
Published: October 2010

The effects of low intensity pulsed ultrasound to tenocytes and osteocytes are well understood and applied clinically. However, its effects on cultured Schwann cells are still not well elucidated. This study was designed to elucidate the effects of low intensity pulsed ultrasound on cultured Schwann cells and their possible molecular mechanism. Schwann cells were harvested from sciatic nerves of 3‐day‐old Sprague–Dawley rats. Low intensity pulsed ultrasound stimulator (frequency: 1 MHz, duration: 2 min, duty cycle: 20%, total treatment time: 3 min) was applied to three different culture conditions: regular culture medium containing 0, 5, or 10% fetal bovine serum. The viability, damage, and differentiation of Schwann cells were examined; gene expression was also analyzed. In the presence of 0.3 W/cm2 pulsed ultrasound stimulation, increases in cell viability and decreases in cell apoptosis were observed in the serum deprivation group; in this culture condition, interleukin‐1, tumor necrosis factor‐alpha, and protein zero genes expression were downregulated and Desert Hedgehog transcripts gene expression was upregulated. We concluded that intervention with low intensity pulsed ultrasound could promote Schwann cell proliferation, prevent cell death, and keep adequate phenotype presentation for peripheral nerve recovery. The low intensity pulsed ultrasound stimulation to an injured nerve site could be applied as early as possible especially when the microenvironment is almost serum‐free to obtain the most benefit.
Anatomofunctional organization of the insular cortex: A study using intracerebral electrical stimulation in epileptic patients
Authors: Afif Afif , Minotti Lorella , Kahane Philippe , Hoffmann Dominique
Published: October 2010

Purpose:  Different lines of evidence suggest that the insular cortex has many important functional roles. Direct electrical stimulation (ES) of the human insular cortex during surgical procedures for epilepsy, functional imaging techniques, and lesion studies also occasionally induces clinical responses.

Methods:  In this study, we evaluated 25 patients with drug‐refractory focal epilepsy by stereotactically implanting at least one electrode into the insular cortex using an oblique approach (transfrontal or transparietal). One hundred twenty‐eight insular sites (each situated between two contiguous contacts within the same electrode) were examined within the gyral substructures. We located each stimulation site by fusing preimplantation three‐dimensional (3D) magnetic resonance imaging (MRI) images with the postimplantation 3D computed tomography (CT) scans that revealed the electrode contacts.

Results:  Sixty‐seven stimulations induced at least one clinical response. Stimulation from within the insular cortex evoked 83 responses, without evidence of afterdischarge in the insular or extrainsular regions. We classified the principal responses as sensory (paresthesias and localized warm sensations), motor, pain, auditory, oropharyngeal, speech disturbances (including speech arrest and reduced voice intensity) and neurovegetative phenomena, such as facial reddening, generalized sensations of warmth or cold, hypogastric sensations, anxiety attacks, respiratory accelerations, sensations of rotation, and nausea.

Conclusions:  These findings may indicate a functional specificity for the insular gyri and show the need for exploring this structure during invasive presurgical evaluation of epileptic patients according to seizure manifestations.
Electrophysiological Differences between the Epicardium and the Endocardium of the Left Atrium
Authors: MICHOWITZ YOAV , NAKAHARA SHIRO , BOURKE TARA , BUCH ERIC , VASEGHI MARMAR , DE DIEGO CARLOS , WIENER ISAAC , MAHAJAN AMAN , SHIVKUMAR KALYANAM
Published: October 2010

Background: Electrophysiological properties of the atrial endocardium compared to epicardium are not well understood. The purpose of this study was to compare the electrophysiological properties and vulnerability to arrhythmia induction from these regions.

Methods and Results: Transseptal endocardial and percutaneous epicardial mapping were performed in a porcine model (n = 7). Two opposing 4‐mm electrophysiological catheters were positioned endocardially and epicardially. A circular mapping catheter (CMC) was positioned at the ostium of the common inferior pulmonary vein (CIPV) recording left atrial (LA)‐PV potentials. Endocardial and epicardial effective refractory periods (ERPs) at two basic cycle lengths (CLs) of 600 and 400 ms were recorded from four anatomic locations (CIPV, LA appendage, right superior PV, and LA posterior wall). Atrial repetitive response (ARR) induction was also tested from endocardial and epicardial sites. Overall, 254 ERP measurements (mean 36.3 per animal) and 84 induction attempts (mean 12 per animal) were performed. The ERP was significantly shorter in the epicardium compared to the endocardium at basic CL of 400 ms (P = 0.006) but not at CL of 600 ms (P = 0.2). In addition, only the epicardium demonstrated ERP shortening when the CL of the basic drive was shortened (P = 0.03). ARR could be induced more often from the epicardium (P = 0.002) and fibrillatory activity with epicardial/endocardial dissociation was recorded (n = 3). Also, the earliest PV activation site on the CMC was noted to be different in 16.5% of cases during epicardial and endocardial pacing.

Conclusion: The electrophysiological characteristics of the atrial epicardium are different from the endocardium with a shorter ERP and more frequent ARR induction by programed stimulation. (PACE 2011; 37–46)
Long‐Term Follow‐Up Data of Coronary Sinus Stenting for the Stabilization of the Left Ventricular Leads
Authors: DEMIR AHMET DURAN , CAY SERKAN , ERBAY ALI RIZA , MADEN ORHAN , ATAK RAMAZAN , BALBAY YUCEL
Published: October 2010

Background: Cardiac resynchronization therapy has been increasingly used for patients with heart failure. However, unstable and dislocated coronary sinus leads reduce the effectiveness of this important intervention.

Aim: To examine the long‐term effects of coronary sinus side branch stenting on sensing and pacing parameters of the left ventricular leads.

Methods: A total of eight patients (six males; two females; mean age, 56.6 ± 14.4 years) whose coronary sinus lead dislocated during the procedure were included in the study. Targeted coronary sinus side branch stenting was performed to stabilize the leads. Sensing and pacing parameters including lead impedance, capture threshold, and R‐wave amplitude were measured at implantation, first month, sixth month, and every 6‐month period.

Results: Mean follow‐up period was 30.4 ± 7.4 months. At the time of implantation, lead impedance, capture threshold, and R‐wave amplitude were 656 ± 162 Ω, 1.1 ± 0.5 V, and 13.0 ± 6.8 mV, respectively. No statistically significant mean lead impedance, capture threshold, and R‐wave amplitude differences were observed between at the time of implantation and at the time of last follow‐up (697 ± 164 Ω, 1.1 ± 0.5 V, 12.8 ± 6.9 mV, respectively).

Conclusion: In this long‐term study, coronary sinus side branch stenting for the stabilization of dislocated leads seems to be effective. (PACE 2010; 33:1485–1489)
Percutaneous Closure and “Push‐Pull” Technique to Repair Arterial Lead and Sheath Placement Complicating Cardiac Resynchronization Therapy
Authors: ULLAH WAQAS , COOKLIN MICHAEL , SALTER RICHARD JAMES , SABHARWAL TARUN , RINALDI CHRISTOPHER ALDO
Published: October 2010

We present a case of inadvertent subclavian arterial puncture and lead placement to the left ventricle in a patient undergoing cardiac resynchronization therapy. We describe the use of a “push‐pull” technique within an arterial setting to allow removal of the lead, while maintaining access through the same puncture to allow an arterial‐closure device to then seal the artery at this site. As a result of this percutaneous approach, the patient avoided the need for a vascular surgical procedure. PACE 2012; 35:e35–e37)
Failure of Transvenous ICD to Terminate Ventricular Fibrillation in a Patient with Left Ventricular Noncompaction and Polycystic Kidneys
Authors: PASTORE GIANNI , ZANON FANCESCO , BARACCA ENRICO , PIVA MICHELE , BERNARDI ANNAMARIA , PIERGENTILI CHRISTIAN , RIGATELLI GIANLUCA , RONCON LORIS , BAROLD S. SERGE
Published: October 2010

Implantable cardioverter defibrillator (ICD) testing in patients with left ventricular noncompaction (LVNC) at the time of implantation and potential difficulties with ventricular fibrillation (VF) induction/termination in LVNC patients are often not stated in the literature. This report describes the failure of transvenous implantation of an ICD in a 40‐year‐old patient with LVNC and polycystic kidneys. A high defibrillation threshold (DFT) prevented termination of ICD‐induced VF. This case suggests that DFT testing should be considered in any LVNC patient during ICD implantation. The association of LVNC and polycystic kidneys is also discussed. PACE 2012; 35:e40–e42)
An Alternative Method of Assessing Bidirectional Block for Atrial Flutter
Authors: BENNETT MATTHEW T. , GULA LORNE J. , KLEIN GEORGE J. , YEE RAYMOND , KRAHN ANDREW D. , LEONG‐SIT PETER , SKANES ALLAN C.
Published: October 2010

V‐A and A‐V Intervals During Atrial Flutter Ablation. Background: The success of cavotricuspid (CTI) ablation depends on the achievement of bidirectional block. Previous investigators have shown that right ventricular (RV) pacing can replace proximal coronary sinus (pCS) pacing in assessing clockwise CTI conduction block.

Objective:
We sought to assess bidirectional conduction using antegrade (A‐V) and retrograde (V‐A) conduction times in the absence of coronary sinus (CS) pacing.

Methods:
Counterclockwise CTI conduction block was evaluated using conduction time to the QRS from 2 pacing sites (immediately lateral and further lateral to the CTI). This was compared to the conduction time to the pCS with pacing from the same 2 lateral points. This was measured prior to ablation in 7 patients and 41 patients following ablation. To evaluate clockwise CTI conduction block we measured the conduction time to the 2 lateral sites during RV pacing and pCS pacing. This was measured in 7 patients prior to ablation and 16 patients following successful ablation.

Results:
The abbreviated technique correctly indicated the presence or absence of bidirectional block in all patients. Furthermore, conduction times as assessed by the 2 methods correlated well both before and after creation of bidirectional block (correlation coefficients prior to ablation: clockwise direction r = 0.92, P = 0.0036; counterclockwise direction r = 0.86, P = 0.0132; after ablation: clockwise direction r = 0.82, P = 0.0001; counterclockwise direction r = 0.91, P < 0.0001).

Conclusion:
Bidirectional CTI conduction block can be successfully demonstrated using A‐V and V‐A conduction without the need for CS pacing. Patients need, however, to have intact A‐V and V‐A AV nodal conduction. (J Cardiovasc Electrophysiol, Vol. 22, pp. 431‐435)
Luminescence Properties of SrO–Al2O3:Eu2+,Dy3+ Prepared at Different Temperatures
Authors: Nagamani Suriyamurthy , Panigrahi Bhabani Shankar
Published: October 2010

The photoluminescence (PL) and afterglow (AGL) characteristics of SrO–Al2O3:Eu2+,Dy3+ phosphors are studied here. This phosphor was synthesized through solid‐state route with two different precursor materials. At the synthesis/annealing temperature of 1200°C and above, the phosphor prepared through either route exhibited similar PL and AGL emission. However, at different synthesis/annealing temperatures below 1200°C, the phosphor exhibited PL and AGL emissions at different wavelengths. X‐ray diffraction studies revealed the formation of different intermediate compounds like SrAl4O7 and SrAl2O4 to varying extent at different temperatures below 1200°C. The observed difference between the AGL and PL emission maxima is rationalized based on the presence of intermediate compounds and also on the diffusion of Eu and Dy in the sample matrices.