bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of metabolic syndrome in never treated mood disordered patientss
Authors: Taylor Valerie , MacQueen Glenda M.
Published: May 2017

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses.

Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality.

Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR]

Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%.

Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention.

References

1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850

2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158
Mast cells release cytokines in response to mediators produced by virus-infected epithelial cellss
Authors: Tsang Candy , Befus A. D.
Published: May 2017

Background: Mast cells have long been recognized for their involvement in allergic diseases. In the last decade, the importance of mast cells in innate responses against bacteria has been established, but little is known about their contribution in viral infections. Mast cells are abundant at mucosal surfaces such as the lungs in close proximity to the epithelium. In the lung, the epithelium is a primary target for viral infections. Mast cells are secondarily exposed to newly formed virions released from epithelial cells. Mast cells have toll-like receptors (TLRs) that detect various pathogen components. Our first hypothesis is that viral TLR agonists will induce mast cells to release cytokines thought to be involved in viral infections. Both the pro-inflammatory cytokine IL-6 and the chemokine IL-8 are produced during viral infections. TGF-β is an immunoregulatory cytokine that modulates the activity of various immune cells and could also play a role in viral infections.

Methods: We used polyI:C, a synthetic double-stranded RNA (dsRNA), as a TLR3 agonist, loxoribine as a TLR7 agonist, and unmethylated CpG DNA as a TLR9 agonist. We treated mast cells from the cell line HMC-1 (Human Mast cell-1) for 0.5 – 24hr with the TLR agonists and performed dose response studies for all stimuli. Supernatants from treated mast cells were measured for IL-6, IL-8, and TGF-β by ELISA.

Results: Cytokine release was highest at the 24hr time point. Mast cells released IL-6, IL-8, and TGF-β in response to the TLR3 agonist polyI:C in a dose-dependent manner, but not to the other viral TLR agonists. PolyI:C (10μg/mL) versus unstimulated controls significantly increased mast cell release of IL-6 (224.7±57.4 vs. 39.0±5.7, p≤0.001) and TGF-β (240.2±28.9 vs. 116.1±16.7, p≤0.05). PolyI:C induced release of IL-8 from mast cells was increased but not significant. Viral exposure also induces epithelial cells to produce type I interferons, IFNα and β. These interferons have potent antiviral activity, but also have effects on mast cells, decreasing mast cell adhesion to extracellular matrix and reducing co-stimulatory activity on T cells. Our second hypothesis is that IFNα and β will induce mast cells to release cytokines similar to stimulation with polyI:C. Our preliminary data showed that IFNα, IFNβ , and IFNα and β in combination induced a low level of IL-8 and TGF-β release from mast cells, but had no effect on IL-6 release.

Conclusion: HMC-1 responds to dsRNA, a TLR3 agonist produced in epithelial cells during viral replication, by releasing IL-6 and TGF-β. HMC-1 also responds to IFNα and β by releasing IL-8 and TGF-β, indicating that human mast cells respond to epithelial mediators produced during viral infections. Our results show that mast cells contribute to the innate response against viruses by responding to mediators released by virus-infected epithelial cells.
Gene transfer of endothelial NO-synthase restores migratory capacity of endothelial progenitor cells from patients with coronary artery diseases
Authors: Ward Michael R. , Zhang Qiuwang , Stewart Duncan J. , Kutryk Michael J.B.
Published: May 2017

Autologous endothelial progenitor cells (EPCs) have been used extensively in the development of cell-based therapy for acute MI. However, EPCs isolated from patients with CAD and/or CAD risk factors have reduced regenerative activity compared to cells from healthy subjects. As in endothelial cells, endothelial NO synthase (eNOS) expression and subsequent NO production are believed to be critical determinants of EPC function. Recently, the ability of EPCs to migrate in vitro in response to chemotactic stimuli has been shown to predict their regenerative capacity in clinical studies. Therefore, we hypothesized that the regenerative function of EPCs from patients with or at high risk for CAD will be enhanced by overexpression of eNOS, as assessed by migratory capacity.

Methods: EPCs were isolated from the blood of human subjects with CAD risk factors (>15% Framingham risk score; FRS) (± CAD) by Ficoll gradient separation and differential culture. Following 3 days in culture, cells were transduced using lentivirus vectors containing either eNOS or GFP (sham) at an MOI of 3. The cells were cultured for an additional 5 days before being used in functional assays. Cell migration and chemotaxis in response to VEGF (50 ng/mL) and SDF-1 (100 ng/mL) were assessed using a modified Boyden Chamber assay.

Results: Transduction at an MOI of 3 led to a ~90-100-fold increase in eNOS mRNA expression and a 5-6 fold increase in eNOS protein expression, as assessed by qRT-PCR and Western Blotting. Moreover, there was a significant improvement in the migration of EPCs following eNOS transduction compared to sham-transduced EPCs in response to both VEGF (44.3 ± 8.4 vs. 31.1 ± 4.6 cells/high power field; n=10, p < 0.05) and SDF-1 (51.9 ± 11.1 vs. 34.5 ± 3.3 cells/HPF; n=10, p < 0.05).

Conclusions: These data show that the reduced migration capacity of EPCs isolated from patients with CAD and/or CAD risk factors can be significantly improved through eNOS overexpression in these cells. Thus, eNOS transduction of autologous EPCs may enhance their ability to restore myocardial perfusion and function following acute MI. We intend to further explore the regenerative potential of eNOS-transduced EPCs using various in vitro and in vivo models.
The warburg effect and tumour cell survival in human GBMs
Authors: Wolf A , Mukherjee J , Guha A
Published: May 2017

Introduction: GBMs are resistant to apoptosis induced by the hypoxic microenvironment and standard therapies including radiation and chemotherapy. We postulate that the Warburg effect, a preferential glycolytic phenotype of tumor cells even under aerobic conditions, plays a role in these aberrant pro-survival signals. In this study we quantitatively examined the expression profile of hypoxia-related glycolytic genes within pathologically- and MRI-defined “centre” and “periphery” of GBMs. We hypothesize that expression of hypoxia-induced glycolytic genes, particularly hexokinase 2 (HK2), favours cell survival and modulates resistance to tumour cell apoptosis by inhibiting the intrinsic mitochondrial apoptotic pathway.

Methods: GBM patients underwent conventional T1-weighted contrast-enhanced MRI and MR spectroscopy studies on a 3.0T GE scanner, prior to stereotactic sampling (formalin and frozen) from regions which were T1-Gad enhancing (“centre”) and T2-positive, T1-Gad negative (“periphery”). Real-time qRT-PCR was performed to quantify regional gene expression of glycolytic genes including HK2. In vitro functional studies were performed in U87 and U373 GBM cell lines grown in normoxic (21% pO2) and hypoxic (< 1%pO2) conditions, transfected with HK2 siRNA followed by measurement of cell proliferation (BrdU), apoptosis (activated caspase 3/7, TUNEL, cytochrome c release) and viability (MTS assay).

Results: There exists a differential expression profile of glycolytic enzymes between the hypoxic center and relatively normoxic periphery of GBMs. Under hypoxic conditions, there is increased expression of HK2 at the mitochondrial membrane in GBM cells. In vitro HK2 knockdown led to decreased cell survival and increased apoptosis via the intrinsic mitochondrial pathway, as seen by increased mitochondrial release of cytochrome-C.

Conclusions: Increased expression of HK2 in the centre of GBMs promotes cell survival and confers resistance to apoptosis, as confirmed by in vitro studies. In vivo intracranial xenograft studies with injection of HK2-shRNA are currently being performed. HK2 and possibly other glycolytic enzymes may provide a target for enhanced therapeutic responsiveness thereby improving prognosis of patients with GBMs.
Regulation of huntingtin palmitoylation and its role in Huntington Diseases
Authors: Young F BJ , Hayden M R
Published: May 2017

Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disorder characterized by motor, cognitive, and psychiatric deficits and selective neuronal cell death. The causative mutation in HD is an expansion of the N-terminal polyglutamine tract in huntingtin (htt), which results in altered trafficking of mutant htt and enhanced toxicity to striatal neurons.

Post-translational modification by the lipid palmitate has been shown to play a critical role in the trafficking and function of many proteins, including htt. It has been previously demonstrated that huntingtin-interacting protein 14 (HIP14) is a palmitoyl transferase that palmitoylates htt. Previous characterization of HIP14 demonstrated a reduced interaction with mutant htt resulting in reduced palmitoylation, suggesting that palmitoylation may play a role in the pathogenesis of HD. Most recently, we have identified cysteine 214 as a major site of htt palmitoylation in the N-terminus of htt, close to the site of polyglutamine expansion. It was demonstrated that mutation of this site, rendering htt palmitoylation-resistant, results in increased neuronal toxicity, enhanced inclusion formation, and in altered trafficking of htt. Remarkably, mutation of the palmitoylation site in wild type htt also resulted in enhanced toxicity similar to that seen in mutant htt. Together, these previous studies suggest a critical role of palmitoylation in htt trafficking and function.

Based on this preliminary work, we are characterizing the enzymatic regulation of huntingtin palmitoylation. Exploring htt palmitoylation in a number of existing and new mouse models imparts key insights into how this process is regulated in vivo. We are also exploring the relationship between palmitoylation and other post-translational modifications of htt. These studies will lead to an understanding of the regulation of palmitoylation of huntingtin in vivo, as well as setting the precedent to understand the general role of palmitoylation in a wide range of other human diseases. Ultimately, this may lead to identification of new therapeutic targets and treatments for patients.

F.B.J.Y. is supported by a Canadian Institutes of Health Research Walter and Jessie Boyd & Charles Scriver - Child and Family Research Institute - UBC MD/PhD Studentship Award. She also receives funding from the Michael Smith Foundation for Health Research as a Junior Trainee.
Do elective surgical and medical admissions impact emergency department length of stay measurements?
Authors: Langhan Trevor S
Published: May 2017

Background: Emergency department access block is a growing problem in emergency departments across Canada. Access block is defined as hospital occupancy >85% causing emergency department overcrowding. Hospital overcrowding leads to prolonged emergency department wait times, and delays in the transfer of admitted patients from the emergency department to inpatient beds. The relationship between elective admissions to hospital and emergency department wait times has not been adequately assessed. We undertook a simple linear regression analysis of the impact of elective admissions to hospital on emergency department length of stay.

Methods: Linear regression analysis of the number of daily elective admissions to adult acute care beds in the Calgary Health Region in the year 2004 and the daily median emergency department length of stay was done to establish the relationship between elective admissions and Emergency Department length of stay.

Results: 37,007 patients were admitted to adult acute care beds via the emergency department and 46,020 patients were admitted to adult acute care beds by all other routes. Regression analysis determined that there was no relationship between daily emergency department length of stay and the number of elective admissions per day.

Conclusion: For the year 2004, in the Calgary Health Region, elective acute care admissions to hospital had no relationship to emergency department length of stay for patients admitted via the emergency department. Further study is required to determine causative factors that prolong Emergency Department length of stay. Emergency departments across Canada continue to struggle with the demands of providing high quality care with diminishing resources.
Phosphate balance in phosphate supplemented and unsupplemented health subjects during and after hypokinesia
Authors: Kakuris Kostas K , Yerullis Kosmas B , Afoninos Eugenios A , Fedorov Andrei K
Published: May 2017

Objective: To demonstrate the effect of hypokinesia (HK) and post-HK on phosphate (Pi) imbalance and use of Pi with different Pi imbalance and different Pi consumption: were measured Pi balance, plasma Pi level and Pi loss during HK.

Methods: Experiments were conducted during the pre-experimental period of 30 days, and the HK period of 364-days and post-HK period of 30-days. Forty healthy male volunteers 24.2 ± 2.0 yr, were divided into four groups: unsupplemented active control subjects (UACS), unsupplemented hypokinetic subjects (UHKS), supplemented active control subjects (SACS), and supplemented hypokinetic subjects (SHKS). All SACS and SHKS were supplemented with 0.6 mmol dicalcium-phosphate per kg body weight daily.

Results: During HK, Pi imbalance, serum Pi and calcium (Ca2+) levels, fecal Pi loss, and urine Ca2+ and Pi loss increased (P < 0.05) in SHKS and UHKS compared with pre-experimental values and the values in their respective active controls (SACS and UACS). The measured parameters were changed (P < 0.05) more in SHKS than in UHKS. During the initial 20-days of post-HK, serum Pi and Ca2+ levels, fecal P loss, and urine Pi and Ca2+ losses decreased (P < 0.05), while Pi imbalance remained (P < 0.05) depressed in SHKS and UHKS compared with UACS and SACS. The measured parameters were changed (P < 0.05) more in SHKS than in UHKS.

Conclusion: The greater Pi imbalance with than without Pi supplementation shows that the risk of higher Pi imbalance is directly related to the magnitude of Pi intake. The higher Pi loss with higher than lower Pi imbalance shows that the risk of greater Pi loss is directly related to the magnitude of Pi imbalance. It is concluded that Pi imbalance increases more when the Pi consumption is higher and that Pi loss increases more with higher than lower Pi imbalance indicating that during HK Pi imbalance is due to the inability of the body to use Pi but not to the Pi shortage in the diet.
Clinical predictors of facial nerve outcome after translabyrinthine resection of acoustic neuromas
Authors: Shamji Mohammed F. , Schramm David R. , Benoit Brien G.
Published: May 2017

Purpose: The translabyrinthine approach to acoustic neuroma resection offers excellent exposure for facial nerve dissection with 95% preservation of anatomic continuity. Acceptable outcome in facial asymptomatic patients is reported at 64-90%, but transient postoperative deterioration often occurs. The objective of this study was to identify preoperative clinical presentation and intraoperative surgical findings that predispose patients to facial nerve dysfunction after acoustic neuroma surgery.

Methods: The charts of 128 consecutive translabyrinthine patients were examined retrospectively to identify new clinical and intraoperative predictors of facial nerve outcome. Postoperative evaluation of patients to normal function or mild asymmetry upon close inspection (House-Brackmann grades of I or II) was defined as an acceptable outcome, with obvious asymmetry to no movement (grades III to VI) defined as unacceptable. Intraoperative nerve stimulation was performed in all cases, and clinical grading was performed by a single neurosurgeon in all cases.

Results: Among patients with no preoperative facial nerve deficit, 87% had an acceptable result. Small size (P < 0.01) and low intraoperative nerve stimulation of

< 0.10 mA (P< 0.01) were reaffirmed as predictive of functional nerve preservation. Additionally, preoperative tinnitus (P = 0.03), short duration of hearing loss (P< 0. 01), and lack of subjective tumour adherence to the facial nerve (P = 0.02) were independently correlated with positive outcome.

Conclusions: Our experience with the translabyrinthine approach reveals the previously unestablished associations of facial nerve outcome to include presence of tinnitus and duration of hypoacusis. Independent predictors of tumour size and nerve stimulation thresholds were reaffirmed, and the subjective description of tumour adherence to the facial nerve making dissection more difficult appears to be important.
CSCI/RCPSC Henry Friesen Lecture: The Past and the Future of Neurogenetics
Authors: Rouleau Guy , Meijer Inge
Published: May 2017

“To wrest from nature the secrets which have perplexed philosophers in all ages, to track to their sources the cause of disease … these are our ambitions” - Sir William Osler

The main aim in neurogenetics is to characterize and understand the genetic causes underlying neurological diseases. Over time, progress has been made in several aspects of neurogenetics. In fact, the evolution of neurogenetics largely resembles the steps currently undertaken when executing a neurogenetics study. These steps include identification of a disease in a family, clinical description and characterization of the family, genetic analysis, and finally understanding the function of the causative gene. Along those lines, the evolution of neurogenetics could be divided in four eras namely the descriptive, the medical technological, the molecular genetics and the personalized medicine era.
YIF Poster Awards 2007
Authors: CSCI _
Published: May 2017

The Annual Meeting of the Canadian Society for Clinical Investigation once again featured the Young Investigators Forum, an opportunity for students from Canadian MD/PhD and Clinician Investigator Programs to present their research in poster and oral format. Here are this year’s award recipients.
Ki-67 and PCNA expression in prostate cancer and benign prostatic hyperplasia
Authors: Zhong WeiDe , Peng Jinyu , He HuiChan , Wu Dinglan , Han ZhaoDong , Bi XueCheng , Dai QiShan
Published: May 2017

Objective: Ki-67 is a proliferation-associated nuclear antigen and is expressed in all cycling cells except for resting cells in the G0-phase. PCNA is an acidic nuclear protein and has been recognized as a histologic marker for the G1/S phase in the cell cycle. Ki-67and PCNA labeling indices are considered to reflect cell proliferation, particularly, growth fraction. The purpose of this study is to investigate the expression levels of Ki-67 and PCNA in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) and their potential on the early diagnosis of PCa.

Methods: Human prostate cancer cell lines LNCaP and PC-3, human normal prostate epithelial cell line HuPEC, tissues from patients with PCa (121 cases) and BPH (45) and 36 normal cases were examined for the expression of Ki-67 and PCNA by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Then, the association of Ki-67 and PCNA expression with clinical grading of PCa was analyzed by immunohistochemistry staining.

Results: The ratios of PCNA and Ki-67 expression levels in LNCaP and PC-3 were higher (P < 0.05, P < 0.001) than that in HuPEC. The two markers were differentially expressed in three tissues and showed increased expression in PCa (P < 0.05) and BPH (P < 0.05), relative to human normal prostate tissues. Compared with BPH, the ratio of Ki-67 and PCNA expressed in tumour tissue was increased (P < 0.05). The increase of Ki-67 was greater than that of PCNA. Expression of the two markers increased after different grading of PCa cases. The values of Ki-67/PCNA were: 0.073 in grade I PCa tissues, 0.119 in grade IIa PCa tissues, 0.141 in grade IIa PCa tissues, 0.234 in grade III PCa tissues.

Conclusion: The combination of Ki-67 and PCNA, specific proliferative markers of PCa, may improve the accuracy of early diagnosis of prostatic cancer.
Basal metabolic rate in morbidly obese patients with non-alcoholic fatty liver disease
Authors: Tarantino Giovanni , Marra Maurizio , Contaldo Franco , Pasanisi Fabrizio
Published: May 2017

Background. Non-Alcoholic Fatty Liver Disease occurs mainly in severly obese patients and its relationship to Metabolic Syndrome is increasingly recognized. The aim of this study was to determine energy production-utilization by measuring the Basal Metabolic Rate in severely obese patients, characterized by NAFLD, with or without Metabolic Syndrome. Then, the role of systemic inflammation was assessed.

Patients and methods. Twenty severly obese men with Metabolic Syndrome were compared with a well-matched cohort of patients without Metabolic Syndrome. All showed hepatic steatosis at UltraSonography. Basal Metabolic Rate was measured by indirect calorimetry using a canopy system and single-frequency bio-impedance analysis. Serum Interleukin-6 and fibrinogen levels were measured as markers of inflammation

Results. Basal Metabolic Rate was higher in severely obese patients with Metabolic Syndrome than in those without it: 2,496±358 kcal/d vs 2,126±253 kcal/d, P = 0 .001. Laboratory findings of concurrent chronic inflammation were also higher in these patients, i.e., Il6 4.35±1.34 pg/ml vs 6.23±2.1 pg/ml, P = 0.034; fibrinogenemia 285±40 mg/dL vs 376±91 mg/dL, P = 0.020; these of of cytonecrosis, i.e., AlaninaminoTransferase, equally behaved 32.3±7.9 UI vs 65.7±28.2 UI, P < 0.001. Visceral adiposity and arterial hypertension were more frequently detected in patients with Metabolic Syndrome.

Conclusion. Increased energy expenditure, observed in morbidly obese patients as a consequence of a systemic, low-grade, inflammatory process, may explain progression from obesity to Metabolic Syndrome, independent of the presence of NAFLD. In this context, increased Basal Metabolic Rate may be a clue of Metabolic Syndrome.
Aquatic therapies in patients with compromised left ventricular function and heart failure
Authors: Meyer Katharina , Leblanc Marie-Claude
Published: May 2017

With water immersion, gravity is partly eliminated, and the water exerts a pressure on the body surface. Consequently there is a blood volume shift from the periphery to the central circulation, resulting in marked volume loading of the thorax and heart. This paper presents a selection of published literature on water immersion, balneotherapy, aqua exercises, and swimming, in patients with left ventricular dysfunction (LVD) and/or stable chronic heart failure (CHF). Based on exploratory studies, central hemodynamic and neurohumoral responses of aquatic therapies will be illustrated. Major findings are:

1. In LVD and CHF, a positive effect of therapeutic warm-water tub bathing has been observed, which is assumed to be from afterload reduction due to peripheral vasodilatation caused by the warm water.

2. In coronary patients with LVD, at low-level water cycling the heart is working more efficiently than at lowlevel cycling outside of water.

3. In patients with previous extensive myocardial infarction, upright immersion to the neck resulted in temporary pathological increases in mean pulmonary artery pressure (mPAP) and mean pulmonary capillary pressures (mPCP).

4. Additionally, during slow swimming (20-25m/min) the mPAP and/or PCP were higher than during supine cycling outside water at a 100W load.

5. In CHF patients, neck- deep immersion resulted in a decrease or no change in stroke volume.

6. Although patients are hemodynamically compromised, they usually maintain a feeling of well-being during aquatic therapy.

Based on these findings, clinical indications for aquatic therapies are proposed and ideas are presented to provoke further research.
Gestational diabetes in Manitoba during a twenty-year period
Authors: Aljohani Naji , Rempel Brenda M. , Ludwig Sora , Morris Margaret , McQuillen Kelly , Cheang Mary , Murray Robert , Shen Garry X.
Published: May 2017

Purpose: This retrospective cohort study was designed to examine the prevalence and risk factors of gestational diabetes mellitus (GDM) in Manitoba.

Methods: A total of 324,605 deliveries by 165,969 women were reported to Manitoba Health in the years 1985-2004. Data on maternal ages, delivery dates, GDM, self-declared First Nation (FN) status, rural or urban residence and previous GDM were collected for the study. Data were analyzed using multivariate logistic regression models.

Results: The prevalence of GDM during the 20-year period was 2.9%, which was 2.3% in 1985-1989 and 3.7% in 1999-2004 (P < 0.01). The trend of increase in the prevalence of GDM continued after major modifications on the screening and diagnostic criteria for GDM in 1998. The prevalence of GDM in FN women was 3-times greater than that in non-FN women. Higher prevalence of GDM was detected in FN pregnant women living in rural areas compared to those in urban areas (P < 0.01), which was opposite for non-FN pregnant women living in rural and urban areas. The prevalence of GDM in pregnant women ?35 yr was 2.3-fold higher than that in those < 35 yr (P < 0.01). The recurrent rate of GDM was 44.4%. Adjusted odds ratios of GDM for FN status, advanced age, a history of GDM and rural living were 2.2, 2.4, 25.1 and 0.8, respectively.

Conclusions: The prevalence of GDM is increased in Manitoba. FN status, advanced age and a history of GDM, but not rural living, are independent predictors for GDM.
Cigarette smoking exacerbates health problems in young men
Authors: Kung Chien-Min , Wang Hai-Lung , Tseng Zu-Lin
Published: May 2017

Purpose: To examines the hypothesis that smoking exacerbates health problems in young male smokers (age range, 18.6-22.8 yr; mean, 19.4 yr).

Methods: 1169 subjects were recruited, 25.41 % were smokers (2-15 cigarettes daily). All subjects were examined for body mass index, blood pressure, exhaled carbon monoxide content (carboxyl hemoglobin), blood hematology and biochemistry.

Results: Data for WBC (P < 0.001), hemoglobin (P=0.001), hematocrit (P=0.004), MCV (P=0.001), MCH (P=0.003), COHB% (P < 0.001), albumin/globulin (P < 0.001) and triglyceride (P < 0.001) were higher for smokers than non-smokers, while total-bilirubin (P < 0.001), total protein (P < 0.001) and globulin (P < 0.001) were markedly lower. The results of WBC (r=0.164, P < 0.004), COHB% (r=0.958, P < 0.001), gamma glutamyl transpeptidase (r=0.159, P=0.006), alkaline-phosphatase (r=-0.154, P=0.008) and triglyceride (r=0.144, P < 0.001) were closely correlated with number of cigarettes smoked daily. Investigation of associations with illness revealed that young smokers had an increased risk of hypertriglyceridemia to young non-smokers (adjusted ORs, 2.124; 95% CIs, 1.414-3.190), hyperglycemia (adjusted ORs, 1.980; 95% CIs, 0.803-4.901), neutrophilia (adjusted ORs, 1.947; 95% CIs, 1.248-3.037), RBC macrocytosis (adjusted ORs, 1.929; 95% CIs, 1.137-3.275), hyperchromia (adjusted ORs, 1.844; 95% CIs, 1.412-2.407) and polycythemia (adjusted ORs, 1.314; 95% CIs, 0.805-2.145) (all P < 0.05 for linear trends).

Conclusion: The findings emphasize the importance of increasing surveillance of diseases exacerbated by smoking and reducing smoking in the young to prevent cardiovascular illnesses, metabolite disorders and other clinical diseases.
Potentiation of the immunotherapeutic effect of autologous dendritic cells by pretreating hepatocellular carcinoma with low-dose radiation
Authors: Lin Ching-Chung , Wang Tsang-En , Liu Chia-Yuan , Lin Chin-Ping , Liu Tsang-Pai , Chen Ming-Jen , Chang Wen-Hsiung , Lin Jiunn-Chang , Chang Kuo-Ming , Chu Cheng-Hsin , Shih Shou-Chuan , Chao K. S. Clifford , Chen Yu-Jen
Published: May 2017

Purpose: To determine whether exposing hepatocellular carcinoma (HCC) to low dose radiation increases the efficacy of dendritic cell-mediated immunotherapy for HCC.

Methods: Tumour specimens collected from 20 recruited patients with HCC were cultured in primary culture (half successfully) and then exposed to low-dose radiation (0.5 Gy). Immature DCs derived from peripheral blood monocytes of patients were pulsed with autologous HCC cell lysates and matured with a cytokine cocktail. Autologous tumour lysate-pulsed DCs (TLP-DCs) were used to stimulate mixed lymphocytes, which were then tested for inhibitory effect on the growth of HCC cells. Surface markers of immunogenicity on primary HCC cells, MHC, and Fas were investigated before and after low-dose irradiation.

Results: Exposing HCC cells to low-dose (0.5 Gy) radiation enhanced the immunotherapeutic effect of TLP-DC-stimulated lymphocytes. Growth inhibition increased from 50.6±7.5% without irradiation to 74.3±4.3% with radiation. The expression of MHC class ll and Fas was upregulated after irradiating HCC cells.

Conclusion: Exposing tumour cells to a low dose of radiation can enhance the immunotherapeutic effect of the autologous tumor lysate-pulsed DC vaccine.
Enhanced radiation sensitivity in prostate cancer by gold-nanoparticles
Authors: Zhang Xiaojing , Xing James Z. , Chen Jie , Ko Lawrence , Amanie John , Gulavita Sunil , Pervez Nadeem , Yee Don , Moore Ronald , Roa Wilson
Published: May 2017

Purpose: Nanotechnology is an emerging field with significant translational potential in medicine. In this study, we applied gold nanoparticles (GNP) to enhance radiation sensitivity and growth inhibition in radiation-resistant human prostate cancer cells.

Methods: Gold nanoparticles (GNPs) were synthesized using HAuCl4 as the gold particle source and NaBH4 as the reductant. Either thio-glucose or sodium citrate was then added to the solution separately to bind the GNPs to form thio-glucose-capped gold nanoparticles (Glu-GNP) and neutral gold nanoparticles (TGS-GNPs). Human prostate carcinoma DU-145 cells were exposed to vehicle, irradiation, 15nM TGS-GNPs, or 15nM Glu-GNPs, or GNPs plus irradiation. The uptake assays of GNP were performed using hemocytometer to count cells and the mass spectrometry was applied to calculate gold mass. The cytotoxicity induced by GNPs, irradiation, or GNPs plus irradiation was measured using a standard colorimetric MTT assay.

Results: Exposure to Glu-GNPs resulted in a three times increase of nanoparticle uptake compared to that of TGS-GNPs in each target cell (p < 0.005). Cytoplasmic intracellular uptake of both TGS-GNPs and Glu-GNPs resulted in a growth inhibition by 30.57% and 45.97% respectively, comparing to 15.88% induced by irradiation alone, in prostate cancer cells after exposure to the irradiation. Glu-GNPs showed a greater enhancement, 1.5 to 2 fold increases within 72 hours, on irradiation cytotoxicity compared to TGS-GNPs. Tumour killing, however, did not appear to correlate linearly with nanoparticle uptake concentrations.

Conclusion: These results showed that functional glucose-bound gold nanoparticles enhanced radiation sensitivity and toxicity in prostate cancer cells. In vivo studies will be followed to verify our research findings.
Current management of patients with ST elevation myocardial infarction in Metropolitan Beijing, China
Authors: Zhang Shou-Yan , Hu Da-Yi , Sun Yi-Hong , Yang Jin-Gang
Published: May 2017

Purpose: To assess clinical practices and in-hospital outcomes of patients with ST elevation myocardial infarction (STEMI) in Beijing, China.

Methods: This study was a prospective multicentre registry study in Metropolitan Beijing, China. Demographics, delay time, management strategy and in-hospital outcome data were collected from patients with STEMI enrolled in 19 hospitals.

Results: A total of 803 patients (mean age 61±13 yr ,22% women and 42.1% ? 65 yr) with STEMI were enrolled. More than half had a history of hypertension (50.4%) and current smoking (55.2%). Six hundred and fifty patients (80.9%) received reperfusion trerapy: 124 (15.4% ) treated with thrombolysis and 526 (65.5% ) with primary percutaneous coronary intervention (PCI). The median door-to-needle time for thrombolysis was 83 min and door-to-balloon time for primary PCI was 132 min. Only 7% of patients treated with thrombolysis met the guidelines goal of the door-to-needle time ? 30min and 22% of patients had PCI performed in ? 90 min. Aspirin was prescribed in 97.8% of patients, low molecular weigh heparin in 92%, statins in 91.0%, ?-blockers in 76.7%, ACE inhibitors in 73.5%, clopidogrel in 89.7% and GP IIb/IIIa antagonists in 19.3%. In-hospital mortality was 5.4%.

Conclusion: Recommended Clinical Guidelines treatments are largely implemented in patients with STEMI in Beijing. However, many patients were not reperfused within the recommended times. There remains important potential for improvement in the administration of reperfusion therapy.
Effects of angiotensin converting enzyme inhibition on cardiac innervation and ventricular arrhythmias after myocardial infarction
Authors: Yan Su-hua , Hu He-sheng , Wang Le-xin , Xing Qi-chong , Cheng Wen-juan , Xue Mei
Published: May 2017

Purpose: To investigate the influence of angiotensin-converting enzyme inhibitor (ACEI) on cardiac innervation and inducible ventricular arrhythmias (VAs) in healed myocardial infarction (MI).

Methods: Left anterior descending coronary artery was ligated to induce MI in 30 rabbits. After oral captopril (10mg/kg/d) for 8 weeks, electrophysiological study was performed to evaluate the incidence of inducible VAs. RT-PCR and immunohistochemistry were used to measure the cardiac innervation.

Results: Eight weeks after the operation, the incidence of inducible VAs in the MI-placebo group was higher (58.3%, 7/12) than in the sham operation group (16.7%, 2/12, P < 0.05). However, the incidence of inducible VAs in the MI-captopril group was lower (27.2%, 3/11) than in the MI-placebo group (P < 0.05). Proliferation and growth of nerve fibres in the MI-placebo group were mainly distributed at the periphery of the infarcted and perivascular regions of the myocardium. The density of nerve fibres increased in the MI-placebo group (3889±521 ?m2/mm2) compared with the sham group (1727±304 ?m2/mm2, P < 0.01) at the infarct border. In the MI-captopril group, the density of nerve fibres (3507±433 ?m2/mm2) at the infarct border did not differ from that in the MI-placebo group (P=0.07). MI-induced abnormal nerve fibre distribution was partly restored by captopril treatment.

Conclusion: In this study, prolonged captopril treatment was effective in preventing VAs in healed MI, partly by attenuating the spatial heterogeneity of cardiac innervation.
SOLUBLE PHOSPHOLIPASEA_2 IN THE LIFE AND DEATH OF OSTEOCLASTS
Authors: Allard-Chamard H , Dufort P , De Brum-Fernandes A J
Published: May 2017

Background: Prostaglandins are important for the control of bone remodeling; phospholipases A_2 are essential for prostaglandin synthesis and could be an important mediator for bone health. Our objective was to determine the role of sPLA_2 on osteoclastogenesis and osteoclast (OC) apoptosis.

Methods: Human osteoclasts were differentiated in vitro from PBMC in the presence of RANKL and M-CSF. The presence of sPLA_2 was confirmed by immunohistochemistry in OCs in culture and on bone slices. The role of sPLA2 II on osteoclastogenesis and on OC apoptosis was studied using sPLA2 inhibitors The implication of sPLA2 II in bone remodeling in vivo was determined by comparing levels of the enzyme in the peripheral blood ofpatients with traumatic fracture compared to age- and sex-matched controls.

Results: In vitrodifferentiated osteoclasts and in situ fetal and Pagetic bone osteoclasts express sPLA_2 II. sPLA_2II inhibition during osteoclastogenesis reduces the capacity to generateosteoclasts and increases apoptosis rate of osteoclastic precursors; it also induces apoptosis on mature OCs. Patients with bone fractures have significantly less circulating sPLA_2 II than controls.

Conclusion: sPLA_2 II is present in OCs both invitro and in vivo, in normal as well as in pathologic situations. Its inhibition reduces osteoclastogenesis and increases apoptosis rate in vitro. Plasmatic sPLA_2 II levels are lower post-fracture than in controls. These results strongly suggest a role for sPLA2in the control of bone metabolism but the mechanisms implicated in this effects still need to be clarified.
MANAGEMENT AND OUTCOME OF STAGE I SEMINOMA IN ONTARIO.
Authors: An Howard H , Peng Paul Y , Mackillop William J
Published: May 2017

Purpose: To describe the uptake and use of surveillance andirradiation in stage I seminoma post-orchiectomy in Ontario and to evaluate theimpact of these management strategies on patient outcomes.

Background: Testicular cancer is the most common cancer in menbetween the ages of 20 and 44 (1). About half of testicular cancers areseminomas (2). Overall 85% of seminoma patients present with stage I disease with10-year survival over 99%. Adjuvant radiation therapy once constituted thestandard of care but surveillance as a post-orchiectomy management strategy isnow preferred in Ontario (3). Treatment with radiation results in importantlong-term toxicities (2). The actual management patterns and the effect ofthese patterns on seminoma patient outcomes is unknown. This will be the firstphase IV study to describe the management of stage I seminoma and to evaluateit’s effect on patient outcomes.

Methods: This is a retrospective, population based cohort studyof seminoma patients in Ontario. Cases of seminoma are identified through theOntario Cancer Registry and linked with patient data from the CanadianInstitute of Health Information and Ontario radiotherapy data. An instrumentalvariable approach will be taken with time and location of treatment as theinstruments. Mantel-Haensel Chi-Squared tests, Student’s T-test, and Log ranktests will be used to find differences in patient characteristics, morbidity andsurvival. The Kaplan-Meier method will be used to model overall survival.

Results and Conclusions:Pending data analysis.

References:

1. Warde P, Srugeon J,Gospodarowicz M. Testicular Cancer. In: Gunderson L, Tepper J, eds. Clinicalradiation oncology. Philadelphia: Chruchill Livingstone; 2000: 844-862.

2. Nichols CR, Hung A, Corless CL, Foster RS, Roth BJ, Einhorn LH.Testis cancer. In: Kufe DW, Frei III E, Holland JF, Weichselbaum RR, PollockRE, Bast Jr RC, Hong WK, Hait WN, eds. Holland-Frei cancer medicine – 7^thEd.[e-book], Columbia: BC Decker; 2006 [cited 2008 Mar 17]: ch. 99. Availablefrom: Stat!Ref.

3. Chung P, Mayhew LA, Warde P, Winquist E, Lukka H et al. Management of stage I seminoma: Guidelinerecommendations. Cancer Care Ontario, Evidence-Based Series #3-18: Section1; Report date: 30 Jan 2008.
XMODULATION IN MICEAND MEN: IL-10 PRODUCING CELLS INBLOOD AND LYMPHOID TISSUE
Authors: Barrett L , Grant M , Liwski R , West K
Published: May 2017

Background: The human immune system provides remarkable protection from a plethora of pathogens, but can cause damage when activated for a prolonged time (as inpersistent infections) or against self (autoimmunity). Therefore, mechanisms of immune system downregulation and control are imperative. There is little data on how the immune system is controlled in healthy individuals. We recently described a novel population of white blood cells that constitutively produce the immunomodulatory cytokine interleukin-10 (IL-10). Our objective was to further delineate the distribution of these cells in human and mouse models, as well as potential triggers for interleukin-10 production in vitro.

Methods: Human and animal protocols were reviewed and approved by the institutional ethics board and animal care facilities, and informed consent was obtained from all human donors. The ex vivo percentage of peripheral blood CD36^+IL-10^+ mononuclear cells was assessed by intracellular flow cytometry in 10 healthy individuals. IL-10 production after exposure to twoCD36 ligands, thrombospondin and oxidized low density lipoprotein (oxLDL) was measured at 8 hours. Peripheral blood mononuclear cells and splenocytes from BL/6 (n=5) and Balb/c (n=1) micewere assessed for CD36^+IL-10^+ cells ex vivo as well.

Results: The percentage of CD36^+IL-10^+ cells in peripheral blood fromhealthy individuals ranges between 0.1% and 0.9%. The percentage was similar in mouse peripheral blood, with a range of 0.4%-1.1%. These cells were also found in mouse spleen at a higher frequency than peripherally (1.1-1.5%). Human CD36^+IL-10^+ cells have more IL-10 when exposed to thrombospondin, oxLDL.

Conclusions: Our novel population of IL-10 producing cells is found not only in healthy humans, but also in lymphoid tissue and blood from pathogen free mice. This highlights the evolutionary conservation of the cell across species, and suggests an important homeostatic function. The physiologic ligands for CD36 are ubiquitous in circulation, and ourin vitro data suggests a link between CD36 ligation and IL-10 production. IL-10 is a known immune system modulator, and its production by these cells may help maintain homeostaticcontrol of the immune system.
SELECTIVE USE OF MEMBRANE CD14, BUT NOT SOLUBLE CD14 ANDINHIBITION BY SERUM IN THE INFLAMMATORY CYTOKINE RESPONSE INDUCED BY A NOVELTLR LIGAND (P. AERUGINOSA EXOENZYME S)
Authors: Berenger B , Mody C H
Published: May 2017

Background/Purpose: Soluble andmembrane CD14 (sCD14 and mCD14) bind microbial products, are toll-like receptor(TLR) coreceptors, and induce inflammation. Clinical relevance is demonstrated by a correlation of sCD14 levels with morbidity and mortality in inflammatory diseases. Moreover, P. aeruginosa induces damaging inflammation in the lungs of cysticfibrosis patients and its virulence is often attributed to the TLR2 and TLR4ligand exoenzyme S (ExoS). Because of the importance of the response of CD14 toTLR ligands and its potential for therapeutic manipulation, its role inExoS-induced inflammatory cytokines was investigated.

Methods: The ability of ExoS to induce TNFand IL-6 cytokine production in cell lines that express TLR and either CD14 positive or negative was assessed (THP-1 or U373 cells, respectively). Recombinant CD14 or CD14 blocking agents were used to test the contribution ofmCD14 and sCD14.

Results: Enhancing expression of mCD14 on THP-1 cells increased TNF production, which was abrogated by blocking or removing mCD14. Transfecting mCD14 into U373 cells demonstrated that mCD14 was required for binding ExoS and subsequent IL-6 production. Unlike TLR ligands that only stimulate one TLR, such as lipopolysaccharide, neither sCD14 nor serum enhanced production of cytokine in response to ExoS. Uniquely, serum inhibited ExoS induced TNF.

Conclusion: This work demonstrates a fundamental difference in the requirement of ExoS and other TLR ligands for CD14, which must be considered when designing therapies to block microbe-induced inflammation. The presence of a potential therapeutic molecule in serum could help in the development of an ExoS neutralizing agent.
“IT’S MORE THAN A PILL DROP”: ADHERENCE SUPPORT AND THE CLINICAL GAZE IN INNER CITY HOME-BASED HIV CARE
Authors: Berkhout S , Brennan E , Giles S , Joyce B , Smyth S , Tyndall M
Published: May 2017

Background:Home-based HIV care has been identified as means of improving access to HIV care and reducing HIV-related stigma, while easing overload in facility-based care and providing cost effective community-based social supports. Few evaluations, however, focus on the impactof barriers such as homelessness, imprisonment and substance abuse to the continuity of this model of health care provision. This paper examines the challenges, strategies, and outcomes of a long-standing home-based HIV nursingprogram from a Foucauldian analytic perspective.

Methods: Findings are presented from the evaluation of a home care nursing team providing HIV care to unstably housed individuals in Vancouver’s inner city. Employing ethnographic methodology, participant observation was conducted over nine months, along with serial open-ended qualitative interviews with the nursing team (n=4) and home care clients (n=16). Interviews were audio recorded and transcribed; an interpretive thematic analysis of field notes and interview transcripts was conducted.

Results: Although adherence to antiretroviral therapy was consistent over the study course, men and women’s responses to care varied over time. Nurses who were sensitive to the ways in which enhanced surveillance within the private sphere of participants’ lives was cause for resistance to care employed a number of strategies to maintain these relationships. Variability among nurses regarding local (i.e. street) knowledge, along with understandings of what constitutes appropriate supportive measures, also impacted participants’ responses to care.

Conclusions: The type and extent of support services is continually negotiated between nurses and participants, creating a potential source of tension between the guiding of health-related decisions and participants’ constitution of themselves as autonomous. Foucault’s concept of governmentality is applicable here, and may elucidate how norms, capacities and subjectivities are mutually created through its processes. The findings support an understanding of autonomy that is interpersonally, as well as institutionally, relational. Successful programming requires careful attention to the everyday experiences of participants, facilitated by continuity of providers andmentorship for newer nurses engaging in home-based HIV care.

SuzeBerkhout is supported by the Canadian Institutes for Health Research, The Michael Smith Foundation for Health Research, Providence Health, and Vancouver Coastal Health Research Institute.