bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo physiological recording from the lateral line of juvenile zebrafish
Authors: Olt Jennifer , Allen Claire E. , Marcotti Walter
Published: May 2016

Key points

Zebrafish provide a unique opportunity to investigate in vivo sensory transduction in mature hair cells.

We have developed a method for studying the biophysical properties of mature hair cells from the lateral line of juvenile zebrafish.

The method involves application of the anaesthetic benzocaine and intubation to maintain ventilation and oxygenation through the gills.

The same approach could be used for in vivo functional studies in other sensory and non‐sensory systems from juvenile and adult zebrafish.

Hair cells are sensory receptors responsible for transducing auditory and vestibular information into electrical signals, which are then transmitted with remarkable precision to afferent neurons. The zebrafish lateral line is emerging as an excellent in vivo model for genetic and physiological analysis of hair cells and neurons. However, research has been limited to larval stages because zebrafish become protected from the time of independent feeding under European law (from 5.2 days post‐fertilization (dpf) at 28.5°C). In larval zebrafish, the functional properties of most of hair cells, as well as those of other excitable cells, are still immature. We have developed an experimental protocol to record electrophysiological properties from hair cells of the lateral line in juvenile zebrafish. We found that the anaesthetic benzocaine at 50 mg l−1 was an effective and safe anaesthetic to use on juvenile zebrafish. Concentrations up to 300 mg l−1 did not affect the electrical properties or synaptic vesicle release of juvenile hair cells, unlike the commonly used anaesthetic MS‐222, which reduces the size of basolateral membrane K+ currents. Additionally, we implemented a method to maintain gill movement, and as such respiration and blood oxygenation, via the intubation of > 21 dpf zebrafish. The combination of benzocaine and intubation provides an experimental platform to investigate the physiology of mature hair cells from live zebrafish. More generally, this method would allow functional studies involving live imaging and electrophysiology from juvenile and adult zebrafish.
Phonetic correlates of phonological vowel quantity in Yakut read and spontaneous speech
Authors: Vasilyeva Lena , Arnhold Anja , Järvikivi Juhani
Published: May 2016

The quantity language Yakut (Sakha) has a binary distinction between short and long vowels. Disyllabic words with short and long vowels in one or both syllables were extracted from spontaneous speech of native Yakut speakers. In addition, a controlled production by a native speaker of disyllabic words with different short and long vowel combinations along with contrastive minimal pairs was recorded in a phonetics laboratory. Acoustic measurements of the vowels' fundamental frequency, duration, and intensity showed a significant consistent lengthening of phonologically long vowels compared to their short counterparts. However, in addition to evident durational differences between long and short quantities, fundamental frequency and intensity also showed effects of quantity. These results allow the interpretation that similarly to other non-tonal quantity languages like Finnish or Estonian, the Yakut vowel quantity opposition is not based exclusively on durational differences. The data furthermore revealed differences in F0 contours between spontaneous and read speech, providing some first indications of utterance-level prosody in Yakut.
Multicenter Investigation of Gepotidacin (GSK2140944) Agar Dilution Quality Control Determinations for Neisseria gonorrhoeae ATCC 49226
Authors: Jones Ronald N. , Fedler Kelley A. , Scangarella-Oman Nicole E. , Ross James E. , Flamm Robert K.
Published: May 2016

Gepotidacin, a novel triazaacenaphthylene antibacterial agent, is the first in a new class of type IIA topoisomerase inhibitors with activity against many biothreat and conventional pathogens, including
Neisseria gonorrhoeae
. To assist ongoing clinical studies of gepotidacin to treat gonorrhea, a multilaboratory quality assurance investigation determined the reference organism (
N. gonorrhoeae
ATCC 49226) quality control MIC range to be 0.25 to 1 μg/ml (88.8% of gepotidacin MIC results at the 0.5 μg/ml mode).
Simulation in the medical undergraduate curriculum to promote interprofessional collaboration for acute care: a systematic review
Authors: Yu Tzu-Chieh , Webster Craig S , Weller Jennifer M
Published: May 2016

This literature review summarises interprofessional, simulation-based interventions in the context of preparing undergraduate and prelicensure healthcare students for the management of acutely unstable patients. There was a particular focus on the impact of such interventions on medical students. The review sought to identify the range of described interprofessional education (IPE) learning outcomes, types of learners, methods used to evaluate intervention effectiveness and study conclusions. We systematically compiled this information and generated review findings through narrative summary. A total of 18 articles fulfilled the review criteria. The diversity of IPE interventions described suggests a developing field where the opportunities provided by simulation are still being explored. With significant heterogeneity among the studies, comparison between them was unfeasible, but each study provided a unique narrative on the complex interplay between intervention, curriculum, learning activities, learners and facilitators. Together, the narratives provided in these studies reflect positively on undergraduate simulation-based interventions to promote interprofessional collaboration in acute care settings, and provide the basis for recommendations for future IPE design and delivery, and areas requiring further research.
Triglyceride Levels and Risk of Type 2 Diabetes Mellitus: A Longitudinal Large Study
Authors: Beshara Amani , Cohen Eytan , Goldberg Elad , Lilos Pearl , Garty Moshe , Krause Ilan
Published: May 2016

The relationship between triglyceridemia and diabetes mellitus remains unclear. This study evaluated the risk of diabetes and impaired fasting glucose associated with a wide range of triglyceride levels. A longitudinal retrospective study was carried out employing data from a screening center between the years 2000 and 2012. Inclusion criteria were absence of diabetes at baseline and attendance at the center at least twice over a 5-year period. Participants were divided by fasting blood glucose level (normal/impaired) at the first visit. A total of 5085 participants were eligible for the study. Of the 4164 normoglycemic participants at baseline, 40 (0.96%) had diabetes and 998 (24%) had impaired fasting glucose by the end of the study. On stepwise logistic regression analysis, every 10 mg/dL increase in triglyceride level significantly increased the risk of diabetes by 4% and of impaired fasting glucose by 2% (p<0.001). This association held true even when rising triglyceride levels remained within the accepted normal range (<150 mg/dL, p<0.001). Sustained increments in serum triglyceride level, even within the accepted normal range, are an independent risk factor for diabetes mellitus and impaired fasting glucose in normoglycemic participants.
Endothelin-1 Concentrations are Correlated with the Severity of Knee Osteoarthritis
Authors: Zhao Zhe , Li Enqi , Cao Qing , Sun Jie , Ma Baotong
Published: May 2016

Endothelin-1, a potent vasoconstrictor regulator, contributes to articular cartilage destruction. Therefore, we aim to assess the correlation of endothelin-1 concentrations with the development and severity of knee osteoarthritis (OA). This study included a population of 209 patients with knee OA. Kellgren-Lawrence (KL) grading was utilized to score the severity of OA. The case group had higher serum endothelin-1 concentrations than controls. Patients with knee OA with a relatively higher grade showed significantly elevated serum and synovial fluid (SF) endothelin-1 concentrations compared with those with lower KL grades. A significant correlation was found between serum and SF endothelin-1 concentrations and KL grades. Serum and SF endothelin-1 concentrations are correlated with the development and progression of knee OA.
Is Galectin-3 a Biomarker, a Player—or Both—in the Presence of Coronary Atherosclerosis?
Authors: Aksan Gökhan , Gedikli Ömer , Keskin Kudret , Nar Gökay , İnci Sinan , Yıldız Süleyman Sezai , Kaplan Özgür , Soylu Korhan , Kılıçkesmez Kadriye Orta , Şahin Mahmut
Published: May 2016

Atherosclerosis is a complex process mediated by leukocytes, macrophages and various inflammatory markers. Galectin-3 is secreted by activated macrophages and is involved in cardiac fibrosis, cardiac remodeling, and inflammation. The present study aimed to determine the relationship between the presence and severity of coronary artery disease (CAD) and serum galectin-3 levels. The study included 82 patients with CAD confirmed via coronary angiography and 82 healthy participants as control group. Angiographic CAD was defined as ≥50% luminal diameter stenosis of at least one major epicardial coronary artery. The severity of CAD was determined by the Gensini score; and the serum galectin-3 levels were measured via ELISA. Serum galectin-3 levels were significantly higher in the patient group with CAD than in the control group (12.96±4.92 vs 5.52±1.9 ng/mL, p<0.001). In the correlation analysis, serum galectin-3 showed significant correlation with the Gensini score (r=0.715, p<0.001), number of diseased vessels (r=0.752, p<0.001) and serum hs-CRP level (r=0.607, p<0.001). In addition, multivariate logistic regression analysis showed that the serum galectin-3 levels were significant and independent predictors of the presence of angiographic CAD (OR=3.933, 95% CI 2.395 to 6.457; p<0.001). In the present study, the serum galectin-3 levels were higher in the patients with CAD than in healthy controls. Also, serum galectin-3 levels showed a significant positive correlation with the severity of CAD. An increased serum galectin-3 level may be considered an important activator and a marker of the atherosclerotic inflammatory process in CAD.
Bone Mineral Density and Biochemical Markers of Bone Metabolism in Predialysis Patients with Chronic Kidney Disease
Authors: Fidan Nuri , Inci Ayca , Coban Melahat , Ulman Cevval , Kursat Seyhun
Published: May 2016

The aim of the study was to evaluate the usefulness of serum bone turnover markers (BTM) and bone mineral density (BMD) determined by dual-energy X-ray absorptiometry (DEXA) in predialysis patients with chronic kidney disease (CKD). We enrolled 83 patients with CKD, 41 (49.4%) males, 42 (50.6%) females, with mean estimated glomerular filtration rate (eGFR) 23.90±12 (range=6.0–56.0). BMD of the lumbar spine (LS) (anteroposterior, L2 through L4), femoral neck (FN) and femoral trochanter (FT) were measured by DEXA. Biochemical BTM, including calcium (Ca), phosphorus (P), intact parathyroid hormone (PTH), serum specific alkaline phosphatase (serum AP), bone-specific AP (BSAP), plasma bicarbonate and 25-hydroxy-vitamin D (25hD) were used for the prediction of BMD loss. T score results of LS and FN were worse than FT. BMD levels were lower in females than in males (all p<0.05). According to different BMD T score levels, patients with age ≥65 years and patients in menopause were significantly more osteopenic (p=0.026) and there was no relation between different BMD T scores and presence of diabetes (p=0.654). A positive correlation was identified between the BMD of FN T-Z scores (r=0.270, p=0.029, r=0.306, p=0.012), FT T-Z scores (r=0.220, p=0.076, r:0.250, p=0.043) and serum HCO3, while the correlation with serum alkaline phosphatase (AP) and BSAP was considered to be negative. No statistically significant association was found between BMD of all the measured skeletal sites and eGFR. Loss of BMD was identified mostly in females over ≥65 years of age and after menopause. Higher serum levels of BSAP and AP can be determined in the advanced stages of renal failure and they reflect fracture risk of the femur, but not spine. Measurements of BMD by DEXA are useful to demonstrate bone loss, but not technical enough to distinguish the quantity of bone loss between different stages of CKD.
Performance of Rapid Sofia Influenza A+B Test Compared to Luminex X-Tag Respiratory Viral Panel Assay in the Diagnosis of Influenza A, B, and Subtype H3
Authors: Selove W , Rao L V
Published: May 2016

Influenza is an acute respiratory illness caused by influenza A or B viruses that occur in outbreaks, mainly during the winter season. Rapid laboratory diagnosis of influenza can help guide the clinical management of suspected patients effectively. Clinical sensitivities and specificities of the rapid influenza diagnostic tests have varied considerably in the literature. Most of these studies are evaluated using previously frozen or stored specimens that had previously tested positive. This study compares the performance of the rapid SOFIA Influenza A+B test to nucleic acid multiplex test x-TAG respiratory viral panel (RVP) assay in freshly collected nasal aspirates and measured simultaneously by both assays. Retrospective data from 1649 nasal aspirates (September 2014 to May 2015) collected from adults as well as from children tested simultaneously by both rapid SOFIA Influenza A+B FIA immunofluorescence (Quidel, San Diego, CA) and qualitative nucleic acid multiplex RVP assay X-TAG Luminex technology (Luminex, Austin, Texas, USA) were analyzed. Concordance, and analytical sensitivity and specificity were evaluated for influenza A, subtypes H1 and H3, and influenza B. Prevalence for influenza A by RVP was 15%, for subtype H3 it was 11.2%, and for influenza B, 2.9%. None of the aspirates were positive for influenza A subtype H1. SOFIA Influenza rapid test demonstrated good specificity and low sensitivity compared with a nucleic acid test for influenza A, subtype H3, and for influenza B. SOFIA Influenza A + B test performed well in providing a rapid diagnosis, however, confirmatory molecular testing is recommended for negative test results. Re-evaluation of test performance should be periodically carried out during outbreaks with the emergence and circulation of new influenza strains.
Serum St2 in Inflammatory Bowel Disease: A Potential Biomarker for Disease Activity
Authors: Boga Salih , Alkim Huseyin , Koksal Ali Riza , Ozagari Ayse Aysim , Bayram Mehmet , Tekin Neijmann Sebnem , Sen Ilker , Alkim Canan
Published: May 2016

ST2, a specific ligand of interleukin 33, was described as a biomarker protein of inflammatory processes and overexpression of ST2 in ulcerative colitis (UC) was shown previously. We aimed to investigate the potential relationship of serum ST2 levels with the clinical, endoscopic and histopathological activity scores in UC and Crohn's disease (CD). Serum ST2 levels were determined in 143 patients with inflammatory bowel disease (IBD) (83 UC and 60 CD), in 50 healthy controls (HC), and in 32 patients with irritable bowel syndrome (IBS). Serum ST2 levels were elevated in IBD (56.8 (41.9–87.2) pg/mL) compared to HC and IBS (30.7 (20.2–54.3), p<0.001 and 39.9 (25.9–68.7) pg/mL, p=0.002, respectively). No significant difference was found between UC (54.2 (41.3–93.0) pg/mL) and CD (63.8 (42.7–88.4) pg/mL) and between IBS and HC. Serum ST2 levels were significantly increased in active UC compared to inactive UC (72.5 (44.1–99.5) vs 40.0 (34.7–51.6) pg/mL, p<0.001) and in active CD in comparison with inactive CD (63.8 (42.7–88.4) vs 48.4 (29.6–56.9) pg/mL, p=0.036). Patients with CD showing fistulizing behavior had significantly higher ST2 levels compared to patients with inflammatory and stricturing CD (p<0.001). Clinical activity scores of patients with UC and CD were correlated with serum ST2 levels (r=0.692, p<0.001 and r=0.242, p=0.043, respectively). Serum ST2 levels showed stepwise increases with the increasing histopathological scores of patients with UC and CD (p<0.001 for both). The present study highlights significant associations between ST2 and IBD presence and activity and demonstrates elevated serum ST2 levels in patients with active CD as a novel finding.
Fine-Tuning Patient-Derived Xenograft Models for Precision Medicine Approaches in Leukemia
Authors: Francis Olivia L , Milford Terry-Ann M , Beldiman Cornelia , Payne Kimberly J
Published: May 2016

Many leukemias are characterized by well-known mutations that drive oncogenesis. Mice engineered with these mutations provide a foundation for understanding leukemogenesis and identifying therapies. However, data from whole genome studies provide evidence that malignancies are characterized by multiple genetic alterations that vary between patients, as well as inherited genetic variation that can also contribute to oncogenesis. Improved outcomes will require precision medicine approaches–targeted therapies tailored to malignancies in each patient. Preclinical models that reflect the range of mutations and the genetic background present in patient populations are required to develop and test the combinations of therapies that will be used to provide precision medicine therapeutic strategies. Patient-derived xenografts (PDX) produced by transplanting leukemia cells from patients into immune deficient mice provide preclinical models where disease mechanisms and therapeutic efficacy can be studied in vivo in context of the genetic variability present in patient tumors. PDX models are possible because many elements in the bone marrow microenvironment show cross-species activity between mice and humans. However, several cytokines likely to impact leukemia cells are species-specific with limited activity on transplanted human leukemia cells. In this review we discuss the importance of PDX models for developing precision medicine approaches to leukemia treatment. We illustrate how PDX models can be optimized to overcome a lack of cross-species cytokine activity by reviewing a recent strategy developed for use with a high-risk form of B-cell acute lymphoblastic leukemia (B-ALL) that is characterized by overexpression of CRLF2, a receptor component for the cytokine, TSLP.
Quantification of Adipose Tissue Insulin Sensitivity
Authors: Søndergaard Esben , Jensen Michael D
Published: May 2016

In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.
Adipose Tissue Hypoxia and Insulin Resistance
Authors: Rasouli Neda
Published: May 2016

Despite the well-established association of obesity with insulin resistance and inflammation, the underlying mechanisms and sequence of events leading to inflammation and insulin resistance remain unknown. Adipose tissue hypoxia has been proposed as one of the possible key events during the process of fat expansion that leads to adipose tissue dysfunction. The focus of this paper is reviewing the evidence on adipose tissue hypoxia in obesity and its relation to insulin resistance.
ID: 97: MYCOBACTERIUM MUCOGENICUM IN HEMATOPOEITIC STEM CELL TRANSPLANT RECIPIENTS AND IN HIGH-RISK PATIENTS WITH HEMATOLOGIC MALIGNANCIES, 2008–2013
Authors: Abidi M , Banerjee A , Ledeboer N , Hari P
Published: May 2016

Background

Rapidly growing nontuberculous mycobacteria can cause variety of clinical syndromes including catheter related blood stream infections (BSI).

Methods

We reviewed medical records of patients with blood cultures positive for Mycobacterium mucogenicum (MM) from 2008–2013. We defined 4 at-risk groups: Stem cell transplant recipients (SCT); patients with hematologic malignancy; patients with solid tumors and other's (patient's on treatment with tumor necrotic factor inhibitors). Descriptive analysis was performed, as well as comparative analysis of neutropenic patients (absolute neutrophil count ≤1000 /μL) with non-neutropenic patients.

Results

39 patients with MM bacteremia were identified. There were 27 SCT recipients (24 Allogeneic; 3 Autologous). 4 patients had hematologic malignancy and 4 patients had solid tumors. Others included 4 patients. At time of diagnosis, 12 were neutropenic, and 27 were non-neutropenic. No significant difference was noted in age (p=0.41) or gender (p=1.00) or rates of pure vs. mixed mycobacterial BSI (p=1.00) or more than single blood culture positivity (p=1.00) between these two groups.The predominant clinical feature was fever with mean temperature of 38 degrees C (range 37.8–40.1). There was a significant difference in presence of fever at the time of bacteremia (92% vs. 42%; p=0.005) between the neutropenic and non-neutropenic group. Central venous catheter (CVC) was present at time of bacteremia in 33 cases (P=0.15); there was no significant difference for presence of CVC between these two groups (100% vs. 78%). Median duration of antibiotic treatment was 42 days (p=0.44). All patients were treated with >1 antibiotic. Most used regimen involved clarithomycin and amikacin (n=16).While there were 15 deaths; none were attributed to MM BSI. No significant survival difference was seen at 3 years between the neutropenic and non-neutropenic group (62% vs. 56%; p=0.75).

Conclusions

MM is a rare cause of CVC-associated bacteremia. In our study MM BSI was seen in immune compromised patients, predominantly in SCT recipients. BSI resolved in all patients with CVC removal and combination antimicrobial treatment. None of the patients suffered a relapse.
Endogenous Glucose Production in Type 2 Diabetes: Basal and Postprandial. Role of Diurnal Rhythms
Authors: Radziuk Jerry , Pye Susan
Published: May 2016

Glycemia in type 2 diabetes is characterized by a nonsteady but stable diurnal cycle. This leads to morning fasting hyperglycemia. It arises from an underlying circadian pattern in endogenous glucose production because the metabolic clearance rate of glucose is decreased but constant. Therefore, it is important to use appropriate nonsteady tracer methods to measure this rate even under basal conditions. Postprandially, in diabetes, the endogenous glucose production continues to decrease, with only minor deviations from the slope of the basal curve. This suggests a decoupling of endogenous glucose production from the regulatory factors (insulin, glucose) that prevail under normal circumstances. As the duration of diabetes increases, metabolic clearance of glucose continues to deteriorate. This may be partially compensated by a decrease in glucose production. This rate remains, however, inappropriate because its impact on glycemia does not decline.
Monitoring Participant Safety in Phase I and II Interventional Trials: Options and Controversies
Authors: Hibberd Patricia L. , Weiner Debra L.
Published: May 2016

Background

The need for phase I and II clinical trials to have a data and safety monitoring plan (DSMP) is widely accepted; however, whether and/or when these trials should also have oversight by a data and safety monitoring board (DSMB) is controversial. Monitoring requirements also depend on whether the study is funded by the National Institutes of Health, funded and/or monitored by the US Food and Drug Administration (FDA), or funded by industry. However, there is little guidance about when and how to constitute a DSMB for phase I and II clinical trials.

Objectives

The objectives of this article are to suggest guidelines for when and how to constitute a DSMB for phase I and II studies and to highlight the similarities and differences between DSMBs monitoring phase I and II versus phase III clinical studies. We highlight the utility of these guidelines in the safety monitoring of a mechanism of disease-based study of inhaled nitric oxide for acute vaso-occlusive crisis in pediatric patients with sickle cell disease that was funded and regulated by the FDA.

Conclusion

The goal of DSMPs regardless of the phase of the clinical trial is to protect participant safety and ensure the integrity and validity of the data. A DSMB can ensure that risks and data are evaluated in a timely, efficient, and unbiased manner. We describe “risk-based” guidelines to determine situations in which a DSMB may be an appropriate addition to a DSMP for phase I and II clinical trials. We also address the roles and responsibilities of the DSMB for these studies.
Oxidative Stress in Nonalcoholic Fatty Liver Disease: Pathogenesis and Antioxidant Therapies
Authors: Gawrieh Samer , Opara Emmanuel C. , Koch Timothy R.
Published: May 2016

Nonalcoholic fatty liver disease is a common cause of chronic liver disease, a common finding on liver biopsy in those patients with abnormal blood transaminase levels, and a common cause of cryptogenic cirrhosis in the United States. The prevalence of this disorder is expected to rise with the increase in obesity, and the clinical spectrum can range from simple steatosis (fatty liver) to cirrhosis of the liver. Insulin resistance is thought to be pivotal for the development of steatosis, and oxidative stress may be a potential factor that can promote hepatic necroinflammation and fibrosis. Preliminary studies have examined the role of oxidative stress and antioxidants in animal and human studies of this disorder. Efforts to improve the hepatic antioxidant system could be achieved by optimizing the patient's diet, by supplementation with precursors for antioxidants, or by supplementation with essential metals and/or antioxidants. Randomized, controlled trials are required to examine these potential approaches using patients with this disorder.
Mibefradil Suppresses the Proliferation of Pulmonary Artery Smooth Muscle Cells
Authors: Li Hong-Hong , Xie Li-Jian , Xiao Ting-Ting , Huang Min , Shen Jie
Published: May 2016

Intracellular Ca2+ levels play a critical role in the regulation of vasodilation and vasoconstriction by stimulating pulmonary artery smooth muscle cell (PASMC) proliferation, which is important in the pathogenesis of pulmonary arterial hypertension (PAH); however, L-type Ca2+ channel antagonists are useful in only few patients with PAH. The present study sought to assess the effect of mibefradil, which blocks T-type Ca2+ channels, on PASMC proliferation and Ca2+ channel profile. Human PASMCs were stimulated with 25 ng/mL platelet-derived growth factor-BB (PDGF-BB) with and without 10 µM mibefradil or 100 nM sildenafil. After 48 or 72 h, PASMC proliferation and Ca2+ channel expression were assessed by MTT assays and western blot analysis, respectively. PDGF-BB-induced PASMC proliferation at 72 h (p<0.01), which was inhibited by both sildenafil and mibefradil (p<0.01). Transient receptor potential Ca2+ channel 6 (TRPC6) expression was significantly increased with PDGF-BB stimulation (p=0.009); however, no changes in TRPC1, TRPC3, CAV1.2, and CAV3.2 levels were observed. Although both TRPC1 and CAV1.2 expression levels were increased in PDGF-stimulated PASMCs on mibefradil and sildenafil treatment, it was not statistically significant (p=0.086 and 1.000, respectively). Mibefradil inhibits PDGF-BB-stimulated PASMC proliferation; however, the mechanism through which it functions remains to be determined. Further studies are required to elucidate the full therapeutic value of mibefradil for PAH.
Harnessing Immune Cells to Enhance β-Cell Mass in Type 1 Diabetes
Authors: Dirice Ercument , Kulkarni Rohit N
Published: May 2016

Type 1 diabetes is characterized by early β-cell loss leading to insulin dependence in virtually all patients with the disease in order to maintain glucose homeostasis. Most studies over the past few decades have focused on limiting the autoimmune attack on the β cells. However, emerging data from patients with long-standing diabetes who continue to harbor functional insulin-producing cells in their diseased pancreas have prompted scientists to examine whether proliferation of existing β cells can be enhanced to promote better glycemic control. In support of this concept, several studies indicate that mononuclear cells that infiltrate the islets have the capacity to trigger proliferation of islet cells including β cells. These observations indicate the exciting possibility of identifying those mononuclear cell types and their soluble factors and harnessing their ability to promote β-cell growth concomitant with autoimmune therapy to prevent the onset and/or halt the progression of the disease.
An extended Dirac equation in noncommutative spacetime
Authors: Mendes R. Vilela
Published: May 2016

Stabilizing, by deformation, the algebra of relativistic quantum mechanics a noncommutative spacetime geometry is obtained. The exterior algebra of this geometry leads to an extended massless Dirac equation which has both a massless and a large mass solution. The nature of the solutions is discussed as well as the effects of coupling the two solutions.
Stress and Visceral Perception
Authors: Delvaux Michel M
Published: May 2016

Functional bowel disorders are characterized by the presence of a visceral hyperalgesia in most patients. This visceral hyperalgesia is related to an enhanced perception of sensations originating from the gut. Stressful events can dramatically influence the course of functional bowel disorders, and patients suffering from these syndromes appear to be more susceptible to the stressful events of daily life. However, until now, few studies have evaluated the relationship between stress and visceral perception. Some studies of healthy volunteers indicated contradictory results, but the studies used different methodologies. During stress conditions, either physical or mental, thresholds of perception of rectal distension were increased, suggesting a ‘distraction effect’, or were decreased, supporting a sensitizing effect of stress. In most studies, rectal compliance was not affected, but stress has been shown to alter the rectal tone, as measured by a barostat. One study comparing irritable bowel syndrome patients with controls demonstrated the importance of cognitive processes in the modulation of visceral perception by stress. Animal studies have also demonstrated the sensitizing effect of stress on the perception of rectal distension. Mediators involved may be numerous, but corticotropin‐releasing factor has been demonstrated to play a major role at the central level. Mast cells and histamine release may play a role at the peripheral level. Stress can thus be included in an integrative model explaining the pathophysiology of functional bowel disorders. Advances in the understanding of the relationship between stress and visceral perception may constitute a basis for a therapeutic approach of functional bowel disorders targeted on the central nervous system.
Motor Function in Irritable Bowel Syndrome
Authors: Camilleri Michael
Published: May 2016

The evidence supporting
a role of abnormal motor function in irritable bowel syndrome
(IBS) is reviewed. Symptoms commonly present in IBS
patients, such as vomiting, diarrhea, constipation or incomplete
rectal evacuation, indicate that a motor disorder is implicit as either
a primary or secondary disturbance. Physiological studies implicate
a disturbance of transit through the small bowel and
proximal colon, and abnormal motor responses of the rectum to
distention in IBS patients. Intestinal contractions (physiological
or ‘abnormal’) are associated with the sensation of pain, suggesting
that these contractions are interactions between abnormal motor
and sensory functions in IBS. Therapies aimed at correcting abnormal
transit or antispasmodics are the main pharmacological
approaches to the relief of IBS, and, although the latter are not always
effective in the long term response to treatment, they support
the role of dysmotility in IBS. Most novel therapies under trial
probably modulate both sensory and motor functions, and are discussed
briefly. In summary, the weight of clinical, physiological
and pharmacological evidence supports a role of abnormal motility
in IBS.
The Economic Burden of Irritable Bowel Syndrome in Canada
Authors: Bentkover Judith D , Field Christopher , Greene Evelyn M , Plourde Victor , Casciano Julian P
Published: May 2016

In the treatment
of irritable bowel syndrome (IBS), medical practitioners and
policymakers face the task of providing both high quality and cost
effective medical care for a condition with no certain cure. To
date, studies have examined only total medical costs to patients
with symptoms consistent with an IBS diagnosis. However, these
studies have not examined the direct and indirect costs incurred in
the course of treatment for IBS, excluding the costs of unrelated
medical conditions. Because patients with IBS have been shown
to differ significantly from non‐IBS patients in their desire to seek
medical care, one cannot consider solely the cost differential in
medical costs for IBS and non‐IBS patients. The present study examines
a set of patients who have been diagnosed with IBS and
seek medical care for IBS.
The Autonomic Nervous System in Functional Bowel Disorders
Authors: Tougas Gervais
Published: May 2016

Communications along the brain‐gut axis involve neural pathways
as well as immune and endocrine mechanisms. The two
branches of the autonomic nervous system are integrated anatomically
and functionally with visceral sensory pathways, and are responsible
for the homeostatic regulation of gut function. The
autonomic nervous system is also a major mediator of the visceral
response to central influences such as psychological stress. As defined,
functional disorders comprise a constellation of symptoms,
some of which suggest the presence of altered perception, while
other symptoms point to disordered gastrointestinal function as
the cause of the symptoms. A growing number of reports have
demonstrated disordered autonomic function in subgroups of
functional bowel patients. While a number of different methods
were used to assess autonomic function, the reports point to a generally
decreased vagal (parasympathetic) outflow or increased
sympathetic activity in conditions usually associated with slow or
decreased gastrointestinal motility, while other studies found either
an increased cholinergic activity or a decreased sympathetic
activity in patients with symptoms compatible with an increased
motor activity. Under certain conditions, altered autonomic balance
(including low vagal tone and increased sympathetic activity)
may alter visceral perception. Autonomic dysfunction may
also represent the physiological pathway accounting for many of
the extraintestinal symptoms seen in irritable bowel syndrome patients
and some of the frequent gastrointestinal complaints reported
by patients with disorders such as chronic fatigue and
fibromyalgia.
Effects of Inflammatory Mediators on Gut Sensititvity
Authors: Bueno Lionel , Fioramonti Jean
Published: May 2016

Over the past decade, attention has been paid to the role of
visceral sensitivity in the pathophysiology of functional bowel disorders,
especially irritable bowel syndrome, and visceral hypersensitivity
is the most widely accepted mechanism responsible for
both motor alterations and abdominal pain. Inflammatory mediators
sensitize primary afferents, especially C‐fibre polymodal nociceptors,
favouring the recruitment of silent nociceptors that give
rise to secondary spinal sensitization. After local tissue injury, the
release of chemical mediators such as potassium ions, ATP,
bradykinin and prostaglandin E2 directly activate nerve endings
and indirectly trigger the release of algesic mediators such as histamine,
5‐hydroxytryptamine and nerve growth factor from other
cells, which, in turn, stimulate proximal afferent nerve endings
and silent nociceptors. Among the intermediary structures activated
by inflammatory mediators and susceptible to the release of
proalgesic substances, mast cells and platelets play a crucial role;
however, immunocytes such as macrophages and neutrophils or
sympathetic nerve terminals are also candidates. Moreover,
events likely to activate synthesis of mediators by mast cells, such
as stress and septic shock, also trigger colonic hypersensitivity.
Prolonged visceral hyperalgesia may also depend on spinal sensitization.
Anumber of substances are candidates to play a role at the
spinal cord level in mediating painful and nonpainful sensations.
Among them, substance P, dynorphins and glutamate play a pivotal
role in postsynaptic sensitization, particularly during and after
gut inflammation. Finally, despite the complexity of the relationship
between inflammatory mediators and gut hypersensitivity,
numerous results strongly suggest that alteration neuroimmune
communications at the gut level may trigger a series of events that
give rise to chronic changes in visceral sensitivity.
Dimensions of Gut Dysfunction in Irritable Bowel Syndrome: Altered Sensory Function
Authors: Azpiroz Fernando
Published: May 2016

Growing evidence suggests that
symptoms in patients with irritable bowel syndrome (IBS) may be
due to a visceral sensory dysfunction. Specifically, it has been
shown that patients with IBS have hypersensitive responses to distension
of the rectum, whereas their tolerance to somatic stimuli is
normal or even increased. Furthermore, patients with IBS have
hypersensitivity of the small bowel, which selectively affects
mechanosensitive afferents, with normal perception of electrical
stimulation of the gut. Sensory dysfunctions may also be associated
with altered reflex activity, which may contribute to the clinical
symptoms. Normally, a series of mechanisms at different strata
of the nervous system modulate visceral afferent input and determine
conscious perception. Conceivably, a dysfunction of these
regulatory mechanisms may alter sensitivity in clinical conditions.
To date, neither the origin nor the clinical significance of
visceral hyperalgesia has been elucidated. However, it seems likely
that the sensory and reflex dysfunctions of the gut in IBS may
combine to different degrees, and their interaction may explain
the clinical pleomorphism of the syndrome.
What Is New Since the Last (1999) Canadian Asthma Consensus Guidelines?
Authors: Boulet Louis-Philippe , Bai Tony R , Becker Allan , Bérubé Denis , Beveridge Robert , Bowie Dennis M , Chapman Kenneth R , Côté Johanne , Cockcroft Donald , Ducharme Francine M , Ernst Pierre , FitzGerald J Mark , Kovesi Thomas , Hodder Richard V , O’Byrne Paul , Rowe Brian , Sears Malcolm R , Simons F Estelle R , Spier Sheldon
Published: May 2016

The objective of the present document is to review the impact of new information on the recommendations made in the last (1999) Canadian Asthma Consensus Guidelines. It includes relevant published studies and observations or comments regarding what are considered to be the main issues in asthma management in children and adults in office, emergency department, hospital and clinical settings. Asthma is still insufficiently controlled in a large number of patients, and practice guidelines need to be integrated better with current care. This report re‐emphasises the need for the following: objective measures of airflow obstruction to confirm the diagnosis of asthma suggested by the clinical evaluation; identification of contributing factors; and the establishment of a treatment plan to rapidly obtain and maintain optimal asthma control according to specific criteria. Recent publications support the essential role of asthma education and environmental control in asthma management. They further support the role of inhaled corticosteroids as the mainstay of anti‐inflammatory therapy of asthma, and of both long acting beta2‐agonists and leukotriene antagonists as effective means to improve asthma control when inhaled corticosteroids are insufficient. New developments, such as combination therapy, and recent major trials, such as the Children’s Asthma Management Project (CAMP) study, are discussed.
Implementing Practice Guidelines: A Workshop on Guidelines Dissemination and Implementation with a Focus on Asthma and COPD
Authors: Boulet Louis-Philippe , Becker Allan , Bowie Dennis , Hernandez Paul , McIvor Andrew , Rouleau Michel
Published: May 2016

The present supplement summarizes the proceedings of the symposium “Implementing practice guidelines: A workshop on guidelines dissemination and implementation with a focus on asthma and COPD”, which took place in Quebec City, Quebec, from April 14 to 16, 2005. This international symposium was a joint initiative of the Laval University Office of Continuing Medical Education (Bureau de la Formation Médicale Continue), the Canadian Thoracic Society and the Canadian Network for Asthma Care, and was supported by many other organizations and by industrial partners. The objectives of this meeting were to examine the optimal implementation of practice guidelines, review current initiatives for the implementation of asthma and chronic obstructive pulmonary disease (COPD) guidelines in Canada and in the rest of the world, and develop an optimal strategy for future guideline implementation. An impressive group of scientists, physicians and other health care providers, as well as policy makers and representatives of patients’ associations, the pharmaceutical industry, research and health networks, and communications specialists, conveyed their perspectives on how to achieve these goals.

This important event provided a unique opportunity for all participants to discuss key issues in improving the care of patients with asthma and COPD. These two diseases are responsible for an enormous human and socioeconomic burden around the world. Many reports have indicated that current evidence-based guidelines are underused by physicians and others, and that there are many barriers to an effective translation of recommendations into day-to-day care. There is therefore a need to develop more effective ways to communicate key information to both caregivers and patients, and to promote appropriate health behaviours. This symposium contributed to the initiation of what could become the “Canadian Asthma and COPD Campaign”, aimed at improving care and, hence, the quality of life of those suffering from these diseases.

It is hoped that this event will be followed by other meetings that focus on how to improve the transfer of key recommendations from evidence-based guidelines into current care, and how to stimulate research to accomplish this.
Sampson’s Artery Hemorrhage after Inguinal Hernia Repair: Second Case Reported
Authors: Adjei Boachie Joseph , Smith-Singares Eduardo
Published: May 2016

Sampson artery is normally obliterated in postembryonic development. In rare cases it can remain patent and complicate a routine outpatient herniorrhaphy when severed. This is the second reported case in the available English literature of hemoperitoneum due to bleeding from a patent Sampson’s artery following an open inguinal hernia repair.
Studies on Structural and Morphological Properties of Multidoped Ceria Ce0.8Nd0.0025Sm0.0025Gd0.005Dy0.095Y0.095O2-δ(x=0.2) as Solid Solutions
Authors: Stojmenović Marija , Pagnacco Maja C. , Dodevski Vladimir , Gulicovski Jelena , Žunić Milan , Bošković Snežana
Published: May 2016

The nanopowdery solid solutions of multidoped ceria Ce0.8Nd0.0025Sm0.0025Gd0.005Dy0.095Y0.095O2-δ(x=0.2) with the fluorite type crystal structure of CeO2were synthesized for the first time. Two synthesis procedures were applied: the modified glycine-nitrate procedure (MGNP method) and room temperature self-propagating reaction (SPRT method). All nanopowders were characterized by XRPD analysis, Raman spectroscopy, low temperature nitrogen physisorption, TEM, and SEM methods. According to the XRPD and Raman spectroscopy results, single phase solid solutions of fluorite structure were evidenced regardless of the number of dopants and synthesis procedure. Both XRPD and TEM were analyses evidenced nanometer particle dimensions. The SPRT method results in obtaining sample with higher specific surface area, smaller crystallite and particles sizes, and the same values of the lattice parameter in comparison to pure CeO2. Raman spectroscopy was confirmed to the oxygen vacancies introduced into the ceria lattice when Ce4+ions were replaced with cations (dopants) of lower valence state (3+), which may indicate the potential improvement of ionic conductivity. Additionally, the presence of oxygen vacancies in the lattice ceria, as well as very developed grain boundaries, gives a new possibility for potential application of obtained nanopowders in the area of room temperature ferromagnetism as spintronics.
Longitudinal Comparison of Enzyme- and Laser-Treated Intervertebral Disc by MRI, X-Ray, and Histological Analyses Reveals Discrepancies in the Progression of Disc Degeneration: A Rabbit Study
Authors: Fusellier Marion , Colombier Pauline , Lesoeur Julie , Youl Samy , Madec Stéphane , Gauthier Olivier , Hamel Olivier , Guicheux Jérôme , Clouet Johann
Published: May 2016

Regenerative medicine is considered an attractive prospect for the treatment of intervertebral disc (IVD) degeneration. To assess the efficacy of the regenerative approach, animal models of IVD degeneration are needed. Among these animal models, chemonucleolysis based on the enzymatic degradation of the Nucleus Pulposus (NP) is often used, but this technique remains far from the natural physiopathological process of IVD degeneration. Recently, we developed an innovative animal model of IVD degeneration based on the use of a laser beam. In the present study, this laser model was compared with the chemonucleolysis model in a longitudinal study in rabbits. The effects of the treatments were studied by MRI (T2-weighted signal intensity (T2wsi)), radiography (IVD height index), and histology (NP area and Boos’ scoring). The results showed that both treatments induced a degeneration of the IVD with a decrease in IVD height and T2wsi as well as NP area and an increase in Boos’ scoring. The enzyme treatment leads to a rapid and acute process of IVD degeneration. Conversely, laser radiation induced more progressive and less pronounced degeneration. It can be concluded that laser treatment provides an instrumental in vivo model of slowly evolving IVD degenerative disease that can be of preclinical relevance for assessing new prophylactic biological treatments of disc degeneration.
Multifractal Analysis for Soft Fault Feature Extraction of Nonlinear Analog Circuits
Authors: Lu Xinmiao , Zhao Hong , Lin Haijun , Wu Qiong
Published: May 2016

Aiming at the nonstationarity and nonlinearity of soft fault signals of nonlinear analog circuits, the use of multifractal detrended fluctuation analysis can effectively reveal the dynamic behavior hidden in multiscale nonstationary signals. This paper adopts a new method that uses multifractal detrended fluctuation analysis to calculate the multifractal singularity spectrum of soft fault signals of nonlinear analog circuits. Moreover, this method endows the parameters of the spectrum with definite physical meanings including width, maximum singular index, minimum singular index, and corresponding singularity index of the extreme point. Therefore, this method can be applied to characterize the internal dynamic mechanism of the soft fault signals of nonlinear analog circuits, making it suitable for the feature extraction of fault circuits. All multifractal feature parameters can be organized into a feature set, which will be then input to a support vector machine, and fault detection for the nonlinear analog circuit can be conducted via the support vector machine.