bluuebunny/crossref_metadata_2025 huggingface dataset:
HIV infection is associated with reduced serum alpha-1-antitrypsin concentrations
Authors: Bryan Courtney L , Beard K Scott , Pott Gregory B , Rahkola Jeremy , Gardner Edward M , Janoff Edward N , Shapiro Leland
Published: May 2017

Purpose: Several observations suggest the presence of HIV-suppressive factors in the fluid phase of blood. Alpha-1-antitrypsin (AAT), the most abundant serine protease inhibitor in the circulation, has potent anti-HIV activity in vitro, and may function as an endogenous HIV suppressor. Therefore, we assessed serum AAT concentrations for association with HIV infection.

Methods: In this cross-sectional study, serum AAT concentrations were measured in 66 persons with HIV infection and in 45 healthy persons (Controls). In the HIV-infected group, antiretroviral therapy (ART) use was assessed and CD4+ T cell levels and plasma HIV RNA were quantified.

Results: Median AAT concentration was significantly lower in the HIV-infected group (1.64 mg/mL) in comparison with Controls (1.94 mg/mL; p=0.001). AAT reduction was most pronounced in the HIV-infected subgroup with CD4+ T cell levels > 200 cells/µL in comparison with Controls (p < 0.01). Serum AAT concentrations < 1.0 mg/mL are clinically significant, and concentrations below this level were identified in 4.5% of the HIV-infected group and in no Control subjects. No association between AAT levels and viral load or use of ART was observed in HIV-infected subjects.

Conclusion: The association between reduced serum AAT concentration and HIV infection is consistent with a role for AAT as an endogenous HIV suppressor.
Expression and significance of FOXM1 in human cervical cancer: A tissue micro-array study
Authors: Guan Ping , Chen Hong , Li Hua-Ju , Duan Jie , Chen Jing-Yi
Published: May 2017

Objective: This study was designed to investigate the expression and significance of the Forkhead Box M1 (FOXM1) transcription factor in human cervical cancer.

Methods: The expression of FOXM1 protein was assessed in tissue microarrays containing 102 cervical cancer tissues by the Streptavidin–Peroxidase (SP) immunohistochemitry technique. The relationship between FOXM1 protein and clinico-pathological features (pathological stages, pathological types, TNM stage) was analyzed.

Results: FOXM1 protein was located in the cytoplasma and/or nucleus. The overall expression of FOXM1 in the cytoplasm and nucleus was not associated with T stages (P=0.217) or lymph node status (P=0.313). The nuclear expression of FOXM1 protein was not associated with T stage (P=0.508) or lymph node status (P=0.345). Elevated translocation and activity of FOXM1 were discovered with a secondary analysis that showed that the differences of the nuclear expression of FOXM1, among different pathological stages, were statistically significant (P < 0.05). The nuclear expression of FOXM1 in low differential cervical cancer tissues was significantly higher than in high differential cervical cancer tissues (P < 0.05).

Conclusion: The overexpression of FOXM1 protein in cervical cancer maybe associated with the progression of cervical cancer, and could be a potentially novel tumor marker useful for diagnosis and therapy of cervical cancer.
Use of complementary and alternative medicine in a pediatric population in southern Turkey
Authors: Araz Nilgun , Bulbul Selda
Published: May 2017

Purpose: The use of complementary and alternative medicine (CAM) in children is becoming increasingly acceptable and popular. The aim of this questionnaire-based study was to determine the prevalence, patterns of use, types, perceived effectiveness and associated factors of CAM in children.

Methods: Parents of children (n= 268) who attended the Pediatric Outpatient Department of the Faculty of Medicine at Gaziantep University in June and July 2008 were asked to complete a questionnaire.

Results: The prevalence of CAM use, at least once in the previous year, was 58.6%. The most commonly used CAM modality was herbal preparations (82.7%), which were used to treat cough (42.0%), diarrhea (30.0%) and gas (colic) pains (34.4%). These products were recommended by the respondents’ mother/mother-in-law (52.5%), neighbors (20.0%), friends (14.7%) and doctors (12.8%). Only 31.6% (61) of these parents informed their doctor about their use of CAM to treat their children. Thirty-eight percent (n=102) of the participants stated that they preferred to use CAM modalities rather than referring to a doctor when their child was sick. While most of the families (57.7 %) stated that the method they used was “slightly” useful, 18.6% of them stated the method to be “fairly” useful. The parental use of CAM and the educational level of the parents were among the factors of affecting the use of CAM in children. No correlation was found between the use of CAM and the sex, social security status, income level and other sociodemographic properties of the respondents.

Conclusion: This study showed that a great majority of parents of children in this population used CAM modalities and that herbal products were preferred. Most parents did not inform their physicians of their use of CAM. In the light of these findings, pediatricians should be prepared to discuss alternative therapies with parents, since talking about CAM may be helpful in minimizing associated risks.
Pandrug-resistant isolate of Klebsiella pneumoniae causes less damage than drug-susceptible isolates in a rabbit model
Authors: Zhou Zheng , Ren Jianan , Liu Haiyan , Gu Guosheng , Li Jieshou
Published: May 2017

Purpose: Bacterial infections induce a series of inflammatory responses and lead to longer hospital stays and increased mortality. In clinical work, we often find that infections caused by drug-susceptible isolates have a worse outcome than those caused by pandrug-resistant isolates. To goal of this study was to assess the impact of drug resistant in a rabbit model of Klebsiella pneumoniae infection.

Methods:This study used a rabbit model of experimental bacteremia, challenged by susceptible (A), multidrug-resistant (B) and pandrug-resistant (C) isolates of Klebsiella pneumoniae. Mimimal inhibitory concentrations (MIC), leukocyte, TNFα, IL-17, and HMGB-1 levels and survival times were measured.

Results: Mean survival times after challenge by isolates A, B and C were 10.5 ± 3.63, 12.7 ± 2.31 and 13.9 ± 0.32 days, respectively. Leukocytes levels after challenge with isolate C were lower compared with those after challenge with isolate A (p = 0.002). Blood counts of the offending pathogens and concentrations of TNFα, IL-17, and HMGB-1 were higher in the group challenged by isolate A in comparison with isolate B or C. Tissue bacterial load after animal death was significantly higher in rabbits of group A in comparison with isolates B and C.

Conclusion: Bacteremia induced by pandrug-resistant isolates is accompanied by less damage compared with bacteremia by drug-susceptible isolates. Rabbits infected with a pandrug-resistant isolate of K. pneumoniae survived longer and had a lower inflammatory response than did animals infected with drug-susceptible isolates.
N-glycan-defective breast cancer cells induce a phenotypic switch in polarization of bone marrow-derived macrophages
Authors: Chen Haidan , Cai Huili , Chen Liang , Wu Xianglei , Li Dongqing
Published: May 2017

Purpose: To investigate the effect of N-glycan-defective mammary adenocarcinoma cells on the polarization of macrophages.

Methods: N-glycan-defective breast cancer cells (MA782 cells) were prepared by swainsonine (SW) treatment and the cytotoxicity of SW to MA782 cells was evaluated using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. The N-glycan-defective MA782 cells were co-cultured with bone marrow-derived macrophages (BMDMs) for 48 h in vitro, and then the BMDMs and the co-cultured supernatant were analyzed for macrophage phenotypic using FQRT-PCR, FCM and ELISA.

Results: SW-treated MA782 cells expressed defective N-glycan on the cell surface in a dose-dependent manner (*p < 0.05). MTT assays showed that neither the 1 μg/mL nor 5μg/mL SW treatments showed significant inhibition of MA782 cell growth in vitro. The expression of iNOS and agr-1 in the 5 μg/mL SW-treated group were 4.75-fold higher and 3.7-fold lower than that in the untreated group, respectively (*p < 0.05). Mean fluorescence intensity of CD16/32 expressed in the cells treated with 5 μg/mL SW was significantly higher in comparison with the untreated group (65 vs. 7, *p < 0.05), though the percentage of CD16/32-positive cells were not significantly different. Furthermore, the expression of CD206 and dectin-1 in the 5 μg/mL SW-treated group was significantly decreased (3.1±0.3% and 4.1±1.1%, respectively) in comparison with the untreated group (40±3% and 8.9±1.2%, respectively, both p < 0.05). In addition, the 5 μg/mL SW-treated group secreted more TNF-alpha (350 ±25 pg/mL) and less IL-10 (89±7.2 pg/mL) than the untreated group (80 ±3 pg/mL and 150 ±10 pg/mL, respectively, both p < 0.05).

Conclusion: N-glycan-defective MA782 cells can induce the differentiation of BMDM into proinflammatory M1 macrophages in vitro.
Comparison between arterial and venous sampling of circulating hormones, substrates and peptides in severe obesity
Authors: Martin Julie , Smith Jessica , Bastien Marjorie , Cianflone Katherine , Bussières Jean , Marceau Simon , Hould Frédéric-Simon , Lebel Stéfane , Biertho Laurent , Lescelleur Odette , Biron Simon , Bertrand Fernand , Poirier Paul
Published: May 2017

Purpose: Severely obese patients are being encountered more frequently in clinical practice. Factors implicated in the relationship between obesity and cardiovascular disease may be measured from a blood sample obtained through arterial access in a cardiology setting, such as during cardiac catheterization or heart surgery. The comparability of a given sample site (arterial vs. venous) with regards to blood parameters is yet to be established.

Methods: Fifteen severely obese patients undergoing bariatric surgery were recruited. Fasting blood samples were collected simultaneously from the radial artery (A) and the superior vena cava (V), both representing general circulating levels, after anesthesia but before the surgical procedure. Blood samples were analysed for glucose, insulin, non-esterified fatty acids (NEFA), leptin, adiponectin, total ghrelin, high sensitive C-reactive protein (hs-CRP) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations.

Results: Arterial and venous concentrations of all factors analysed showed no statistical difference (all p values > 0.1); leptin A: 39 ± 16 vs. V: 42 ± 18 ng/mL; total ghrelin A : 0.86 ± 0.27 vs. V : 0.76 ± 0.35 ng/mL; adiponectin A: 7.7 ± 3.3 vs. V: 7.7 ± 3.6 μg/mL; insulin A: 17.9 ± 9.7 vs. V: 18.6 ± 10.5 μU/mL; glucose A: 8.3 ± 2.1 vs. V: 7.9 ± 2.2 mM; NEFA A: 0.98 ± 0.93 vs. V: 0.89 ± 0.38 mM ; hs-CRP A: 10.17 ± 7.68 vs. V: 10.27 ± 7.30 μg/mL and NT-proBNP A: 54.3 ± 47.9 vs. V: 54.7 ± 49.3 pg/mL.

Conclusion: These results suggest that radial artery and superior vena cava blood collection sites are comparable and may be used clinically with respect to fasting glucose, NEFA, leptin, adiponectin, total ghrelin, hs-CRP and NT-proBNP concentrations in a group of severely obese patients.
Measurement of D-dimer as aid in risk evaluation of VTE in elderly patients hospitalized for acute illness: A prospective, multicenter study in China
Authors: Fan Jin , Li Xiaoying , Cheng Youqin , Yao Chen , Zhong Nanshan
Published: May 2017

Purpose: Advanced age and hospitalization are associated with increasing risk of venous thromboembolic (VTE) events. The aim of this study was to investigate whether elevated D-dimer levels could predict VTE events in elderly patients hospitalized for acute illness.

Methods: 458 consecutive patients (65% men; mean age, 77 ± 7 years) who were older than 60 years, immobilized for ≥ 3 days, and hospitalized for heart failure, respiratory failure, acute ischemic stroke, or acute infectious disease without pharmacological prophylaxis or recent major surgery, were enrolled. Elevated D-dimer levels were defined as > 500 ng/ml. VTE events included symptomatic VTE within 90 days or asymptomatic deep venous thrombosis screened by compression ultrasonography at enrollment and 3-week follow-up. The association between baseline D-dimer levels and subsequent VTE events, adjusted for age, sex, ethnicity, body mass index, co-morbidities, and acute disease status, was assessed using multivariate Cox proportional hazard models.

Results: 49.1% (n = 225) of patients had elevated baseline D-dimer levels, and of these patients, 14.2% (n = 32) developed VTE during the 90-day follow-up. In contrast,only 5.6% (n = 13) of patients with normal D-dimer levels developed VTE. Multivariate analysis showed that patients with elevated D-dimer levels had a 3.2-fold increased risk of developing VTE (95% confidence interval, 1.5-6.5; P = 0.002) in comparison with patients with normal levels.

Conclusions: In elderly patients who were hospitalized for acute medical illness, elevated D-dimer levels are associated with subsequent VTE events. Our data suggest that measurement of D-dimer, a widely-performed objective test, may help clinicians address high-risk individuals for VTE.
Report and abstracts of the Joint Annual Congress of the AMBQ-CAMB 2010
Authors: Gilfix Brian M
Published: May 2017

The third joint congress of l’Association des Médicins Biochimistes du Québec (AMBQ) and the Canadian Association of Medical Biochemists (CAMB) was held this year from October 19 to 22 in Montreal. The setting was like last year the picturesque Hôtel Place d’Armes, which is situated in the historic Old Montreal district. There were over 60 attendees comprising both Specialists and Medical residents-in-training and representing the breadth of Canada from the Atlantic to the Pacific.

The scientific committee composed of Drs. Shaun Eintracht (SMBD-Jewish General Hospital (JGH)), Brian M. Gilfix (McGill University Health Centre (MUHC)), David Blank (MUHC), Elizabeth MacNamara (JGH), and Julie St-Cyr (St. Mary’s Hospital (SMH)) arranged a series of informative and interesting scientific sessions.
Molecular aspects of chronic radiation enteritis
Authors: Zhu Yanfei , Zhou Jing , Tao Guoqing
Published: May 2017

Purpose: Chronic radiation enteritis (CRE) is one of the most feared complications of abdominal or pelvic radiation therapy and the treatment of CRE is difficult and often controversial. Recent progress in molecular biology has shed some light on the pathogenesis of CRE, which is characterized by fibrosis. The purpose of this article is to summarize the current state of knowledge of molecular aspects of radiation induced intestinal fibrosis and to discuss potential therapeutic targets.

Methods: A review of the up-to-date published literature involving the possible molecular cascades in radiation-induced intestinal fibrosis and prospective targets for CRE were performed using the Pub-Med search engine.

Results: Fibrosis development is correlated with transforming growth factor β1 (TGF-β1) and its downstream effector Smad3, which stimulates ﬁbrogenic downstream mediators, such as connective tissue growth factor (CTGF). Ras homologue (Rho) and Rho-associated kinase (ROCK) signaling pathway have been shown to play important roles in the development of CRE. The inhibition of these pathways ameliorated radiation-induced intestinal fibrosis in vitro and in animal studies; however, the relationship between the Smad3 and Rho signaling pathways has not been elucidated.

Conclusions: Rho/ROCK and TGF-β1/Smad3 signaling pathways have been shown to play a key role in intestinal fibrogenesis, which might provide with effective possibilities for clinical intervention. Understanding the cooperation between Smad3 and Rho, may therefore be critical to our overall understanding of fibrosis development and maintenance of CRE.
Association of serum cortisol levels with parameters of metabolic syndrome in men and women
Authors: Esteghamati Alireza , Morteza Afsaneh , Khalilzadeh Omid , Noshad Sina , Novin Leila , Nakhjavani Manouchehr
Published: May 2017

Purpose: Central fat distribution is significantly associated with an increased cortisol levels. We hypothesized that men with metabolic syndrome have a higher serum cortisol levels compared to women. The purpose of this study was to compare serum cortisol levels, and its correlation with serum leptin levels, between men and women with and without metabolic syndrome.

Methods: A cross sectional study was performed with 120 untreated patients with metabolic syndrome and 165 healthy volunteers as controls. Serum lipid profile, fasting blood sugar, insulin, cortisol and leptin levels were measured for both groups.

Results: Men with metabolic syndrome had a higher serum cortisol levels, while serum leptin levels were significantly higher in women. The higher serum cortisol level in men with metabolic syndrome was significant after multiple adjustments for age, BMI and waist circumference (17.74±5.1 vs 14.07±4.3; p < 0.05) using general linear model; however, these difference were no longer significant when the waist-to-hip ratio was added as one of the adjustment factors (16.7±1.2 vs. 14.9±0.5; p < 0.2). Serum cortisol levels was significantly correlated with serum leptin (r=0.33, p < 0.05), cholesterol (r=0.35, p < 0.05), triglyceride (r=0.25, p < 0.05), waist circumference (r=0.41, p < 0.01) and waist-to-hip ratio (r=0.32, p < 0.01) in women with metabolic syndrome, after controlling for age and BMI.

Conclusion: Serum cortisol levels are significantly higher in men with metabolic syndrome. This effect is independent of waist circumference.
IL-8 reduces VCAM-1 secretion of smooth muscle cells by increasing p-ERK expression when 3-D co-cultured with vascular endothelial cells
Authors: Zhang Zhi , Chu Guang , Wu Hong-Xian , Zou Ni , Sun Bao-Gui , Dai Qiu-Yan
Published: May 2017

Objective: The goal of this study was to investigate the crosstalk between vascular endothelial cells (ECs) and smooth muscle cells (SMCs) using a three-dimensional (3-D) co-culture model. In addition, the role of IL-8 in this crosstalk was investigated.

Methods: A 3-D co-culture model was constructed using a Transwell chamber system and type I collagen gel. Human umbilical artery smooth muscle cells (HUASMCs) were suspended in the gel and added to the upper compartment of the Transwell. Human umbilical vein endothelial cells (HUVECs) were then grown on the surface of the gel. The growth of HUASMCs was tested with a CFDA SE cell proliferation kit. IL-8 and other bioactive substances were investigated by ELISA and real-time PCR. The alteration of p-ERK expression related to the change in IL-8 levels was also examined by Western blot analysis.

Results: The proliferation rate of HUASMCs in the 3-D co-culture model was 0.679 ± 0.057. Secretion and transcription of VEGF, t-PA, NO and VCAM-1 in the 3-D co-culture model were different than in single (2-D) culture. When 3-D co-cultured, IL-8 released by HUVECs was significantly increased (2.35 ± 0.16 fold) (P﹤0.05) and the expression of VCAM-1 from HUASMCs was reduced accordingly (0.55±0.09 fold). In addition, increasing or decreasing the level of IL-8 changed the level of p-ERK and VCAM-1 expression. The reduction of VCAM-1, resulting from increased IL-8, could be blocked by the MEK inhibitor, PD98059.

Conclusion: Crosstalk between HUVECs and HUASMCs occurred and was probably mediated by IL-8 in this 3-D co-culture model.
Vitamin D and hypertension in pregnancy
Authors: Ringrose Jennifer S , PausJenssen Anne M , Wilson Merne , Blanco Lara , Ward Heather , Wilson Thomas W
Published: May 2017

Purpose: Vitamin D Deficiency is common, particularly in northern latitudes. We examined the association between vitamin D status and hypertension in late pregnancy.

Methods: A case-control study was conducted during two time periods: September-October, 2008, and January-March, 2009, in women near term. A case was defined as having two or more documented blood pressure readings above 140/90 (either/or) at any time during pregnancy (n=78). Controls had at least two blood pressure readings, with none above 140/90 during pregnancy (n=109). Serum 25-hydroxyvitamin D (25(OH)D) was measured in all participants.

Results: In the summer, 13% of controls and 29% of the cases had 25(OH) D levels < 50 nmol/L. During the winter, these numbers rose to 44% and 49% respectively. Both cases and controls were more likely to be vitamin D deficient in the winter (p=0.002). There was a negative correlation between BMI and 25(OH)D (r=-0.202, p=0.002). In univariate analysis, cases had lower 25(OH)D (p=0.046), but also higher body mass index, so that in multivariate analysis 25(OH)D status was no longer significant. There was no difference in mean oral daily vitamin D intake (dietary intake and supplements, 746 and 785 IU respectively). Controls gained less weight in pregnancy. There was a negative correlation between the highest blood pressure measured in pregnancy and 25(OH)D levels (r= -0.118; p=0.012).

Conclusion: There is a high prevalence of vitamin D deficiency in pregnant women recruited in Saskatoon, Saskatchewan. Women with low circulating vitamin D concentrations are more likely to have hypertension.
Knockdown of Mgat5 inhibits CD133+ human pulmonary adenocarcinoma cell growth in vitro and in vivo
Authors: Zhou Xuefeng , Chen Haidan , Wang Qilong , Zhang Li , Zhao Jinping
Published: May 2017

Purpose: In spite of many therapeutic advances, the prognosis of lung cancer remains poor. Therefore, understanding the molecular mechanisms underlying cancer progression, invasion and metastasis is needed. Accumulating evidence indicate that N-acetylglucosaminyltransferase V (Mgat5 or GnT-V) is involved in cancer develpement. The purpose of this study was to characterize the expression and function of Mgat5 in CD133+ pulmonary adenocarcinoma cells.

Methods: CD133+ pulmonary adenocarcinoma cells were separated by magnetic activated cell sorting (MACS) from excised pulmonary adenocarcinoma specimens from 10 patients. Expression of Mgat5 in CD133+ cells was detected by fluorescent quantitative RT-PCR (FQRT-PCR) and Western blot. Subsequently, CD133+ cells were transfected with specific siRNA of Mgat5 to evaluate the effects of Mgat5 inhibition on cancer cell growth in vivo and in vitro.

Results: Expression of Mgat5 was 1.2-fold and 1.4-fold higher in CD133+cells than in CD133– cells detected by FQRT-PCR and Western Blot, respectively (p < 0.05). The L-PHA binding assay also showed higher reactivity in CD133+ cells than in CD133- cells. In addition, Mgat5-specific siRNA efficiently knocked down the expression of Mgat5 in CD133+ cells. Interestingly, downregulation of Mgat5 resulted in significant inhibition of cancer cell growth in vitro and in vivo.

Conclusion: Mgat5 is expressed at a relatively high level in CD133+ lung adenocarcinoma cells, and knockdown of Mgat5 in CD133+ cells inhibits cancer cell growth both in vitro and in vivo. These findings suggest Mgat5 may play an important role during oncogenesis, identifying a potential therapeutic target for pulmonary adenocarcinoma.
Oxidative lipid, protein, and DNA damage as oxidative stress markers in vascular complications of diabetes mellitus
Authors: Tabak Omur , Gelisgen Remise , Erman Hayriye , Erdenen Fusun , Muderrisoglu Cüneyt , Aral Hale , Uzun Hafize
Published: May 2017

Purpose: The purpose of this study was to determine the effects of diabetic complications on oxidation of proteins, lipids, and DNA and to investigate the relationship between oxidative damage markers and clinical parameters.

Methods: The study group consisted of 69 type 2 diabetic patients (20 patients without complication, 49 patients with complication) who attended internal medicine outpatient clinics of Istanbul Education and Research Hospital and 19 healthy control subjects. In serum samples of both diabetic patients and healthy subjects, 8-hydroxy-2’deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, Nε-(hexanoyl)lysine (HEL) and 15-F2t-iso-prostaglandin (15-F2t-IsoP). as products of lipooxidative damage, advanced oxidation protein products (AOPP), as markers of protein damage, and paraoxonase1 (PON1) as antioxidant were studied.

Results: 15-F2t-IsoP (p < 0.005) and AOPP (p < 0.001) levels were significantly higher in diabetic group than control group while there were no significant differences in levels of 8-OHdG and HEL between the two groups. AOPP (p < 0.001) and 8-OHdG (p < 0.001) were significantly higher in diabetic group with complications compared to diabetic group without complications.

Conclusions: Increased formation of free radicals and oxidative stress, under conditions of hyperglycaemia, is one of the probable causes for evolution of complications in diabetes mellitus. Our study supports the hypothesis that oxidant/antioxidant balance is disturbed in diabetic patients.
New laser-treated implant surfaces: A histologic and histomorphometric pilot study in rabbits
Authors: Berardi Davide , De Benedittis Simona , Scoccia Andrea , Perfetti Giorgio , Conti Pio
Published: May 2017

Purpose: The purpose of this study was to confirm the validity of laser treated implant surfaces, with regard to high superficial purity preservation and to extremely regular and uniform roughness surfaces.

Methods: In this in vivo study, seven different laser treated implant surfaces were analyzed. A diode-pumped solid state source laser, in a Q-Switch output mode, was used at various wavelengths, which were chosen to generate surface irregularities of varying diameter, depth and pitch. Twenty one implants were placed in 11 New Zealand rabbits. Eight weeks after surgery, implants were harvested for histometric analysis: total, threads and body bone-to-implant, and bone-to-implant contacts were measured. The morphologic analysis of the surface was carried out using a Scanning Electron Microscope.

Results: Average bone-implant contact values were approximately 50% for all tested surfaces. Both total and threads values, within the same processing pattern group, had a high variance. Bone-implant contact thread and body variances were different, so that is possible that laser beam angle is able to modify the superficial roughness and thus the histological response.

Conclusions: Implants provided with pores of 20 and 25 µm achieved more than satisfactory bone-implant contact partial peaks. Further statistically significant experiments are needed in order to study, in depth, these surfaces.
The effect of Lactobacillus johnsonii Ncc533 (La1) on the balance of Th1/Th2 cells in BALB/c mice
Authors: Yang Junli , Li Wen , Sun Ruopeng , Li Baomin
Published: May 2017

Purpose: To determine the effect of Lactobacillus johnsonii Ncc533 (La1) on Th1/Th2 balance, the production of IL-4 and IFN-γ by splenocytes was evaluated following its administration to mice from newborn to adult. Changes in IL-4 and IFN-γ expression and serum levels of OVA-specific-IgE were then investigated in an asthma model.

Methods: Using flow cytometry (FCM) and ELISA, the percentage of IL-4 and IFN-γ expressing splenocytes and serum levels of OVA-specific-IgE were measured in different groups of mice.

Results: The percentages of IL-4 and IFN-γ expressing splenocytes in the offspring and in the adults of the La1-treated group were not significantly different when compared with the water-treated group. In the asthma model, the percentages of IL-4 expressing cells and the serum levels of OVA-specific-IgE in the La1-treated and water-treated group were significantly increased compared with those in the control group. The percentage of IFN-γ expressing cells was significantly lower in the La1-treated and water-treated groups. The percentage of IL-4 expressing cells and the serum levels of OVA-specific-IgE in the La1-treated group were significantly lower compared with those in the water-treated group, whereas the percentage of IFN-γ expressing cells was significantly higher.

Conclusion: Administration of La1 had no effect on the immune system from the neonate to the adult in the normal mice. It did, however, significantly alter the percentages of IL-4 or IFN-γ expressing CD4+ T lymphocytes in the asthma model, suggesting that administration of La1 might regulate the immune response.
Institute of Social Justice and Medicine: Developing a think tank to promote policy formation
Authors: Boozary Andrew , Dugani Sagar B
Published: May 2017

The World Health Organization (WHO) defines health as a “resource for everyday living, not the objective of living”; however, worldwide, there remains an unmistakable inequity in level of health and access to healthcare. The WHO has published documents on financing health systems towards universal health coverage [1], promoting healthy life [2], improving performance of health systems [3], and enriching humanity [4], highlighting our shared responsibility towards improving both national and global health and access to healthcare. These documents also recognize that, despite our local and regional priorities, there is a global desire to develop international strategies to improve healthcare.

[1] WHO Report. Health systems financing and the path to universal coverage. 2010. http://www.who.int/bulletin/health_financing/en/index.html
[2] WHO Report. Reducing risks, promoting healthy life. 2002. http://www.who.int/whr/2002/en/index.html
[3] WHO Bulletin. Health systems: improving performance. 2000. http://www.who.int/whr/2000/en/index.html
[4] WHO Bulletin. Conquering suffering, enriching humanity 1997. http://www.who.int/whr/1997/en/index.html
Short-term effect of radioactive iodine therapy on CXCL-10 production in Graves’ disease
Authors: Dong Qing-Yu , Li Shou-jie , Gao Guan-Qi , Liu Xiao-meng , Li Wen-xia , Liang Cui-ge , Du Wen-hua , Wsng Yue-li
Published: May 2017

Purpose: To observe the short-term dynamic change in serum CXC chemokine ligand-10 (CXCL10) levels in patients with Graves' disease (GD) before and after iodine therapy and to analyze the relationship between CXCL10 levels and clinical disease indices.

Methods: ELISA was used to determine serum levels of CXCL10 in 43 patients with GD shortly before radioiodine therapy and on days six, 14, and 60, post-therapy.

Results: Patients with newly diagnosed GD showed significantly higher levels of serum CXCL10 compared with the control group (P < 0.01). The serum CXCL10 level increased slightly on day six after treatment of radioactive iodine (P < 0.01). There was no significant statistical difference in serum CXCL10 levels pre-treatment and on day 14 post-treatment. A significant reduction in serum CXCL10 level was observed on day 60 (P < 0.01). GD patients with exophthalmia showed higher serum CXCL10 level than GD patients without exophthalmia. No correlation was found between levels of CXCL10 and FT3, FT4 or TSH at any time point, but significant positive correlation was shown between thyroid peroxidase antibodies (TPOAb) and CXCL10 (r=0.50, P < 0.01).

Conclusion: CXCL10 participates in the early inflammatory response after radioactive iodine therapy in patients with Graves’ disease and shows a strong association with the autoimmune process.
miR-21 down-regulation promotes apoptosis and inhibits invasion and migration abilities of OVCAR3 cells
Authors: Lou Yanhui , Cui Zhumei , Wang Fuling , Yang Xingsheng , Qian Jinhua
Published: May 2017

Purpose: To investigate the influence of miR-21 down-regulation on cell proliferation, apoptosis, invasion and migration of ovarian papillary adenocarcinoma cell lines (OVCAR3).

Methods: Short-hairpin RNA (shRNA), specifically targeting miR-21, was constructed and transfected into OVCAR3 cells using the pSIREN-RetroQ linear vector (pSIREN-miR-21). The expression of miR-21 was detected with stem-loop real-time RT-PCR in OVCAR3 cells. Cell proliferation and apoptosis were monitored using the MTT assay and flow cytometry, respectively. Cell migration and invasion were assessed using the transwell migration and scratch-wound assay, respectively. Western-bloting was used for PDCD4 protein expression.

Results: pSIREN-miR-21 suppressed miR-21 expression in OVCAR3 cells. miR-21 expression levels in pSIREN-miR-21 cells was 0.3 ± 0.1, which was significantly lower when compared with pSIREN-miR-21-Neg and control groups (P < 0.01). Cell inhibition rate in the pSIREN-miR-21 group was higher than the control group (29.4% vs 9.0%, P < 0.01), as was the percentage of apoptotic and necrotic cells. By transwell migration assay, the number of cells migrating in the pSIREN-miR-21 group was significantly lower than in the control group. In addition, fewer cells were observed in the wounded area of the pSIREN-miR-21 group following the scratch-wound assay. PDCD4 expression was increased in OVCAR-3 cells transfected by pSIREN-miR-21 compared with vector-control transfected cells. Moreover, the optical density of the transfected cells was significantly lower than the two control groups.
CSCI President’s Message
Authors: Winston Brent W
Published: May 2017

Dear Clinical and Investigative Medicine (CIM) readers,

I write this message to solicit your help in making the Canadian Society for Clinical Investigation a vital society for medicine in Canada and to inform CIM readers about the CSCI. The CSCI plays an important role in maintaining the sustainability of our health care system. The only way to improve health care for Canadians is to continually optimize our methods of treatment and to gain a better understanding of the illnesses that face our population. Systematic research in all facets of healthcare, be it the molecular mechanisms of disease, the efficacy of treatment alternatives or the functioning of the health care system is the only way to guarantee a better system for the next generation of Canadians.

As the only Society in Canada with a dedicated focus on the profession of clinician-researchers and our young clinician-investigator trainees, we provide crucial support for the enterprise of clinical investigation in Canada.

The CSCI’s mandate is to promote clinical and basic research in the field of human health throughout Canada, to lobby for adequate research funding at the federal, regional and local levels, and to support Canadian researchers in their endeavours and at all stages of their careers. 

The CSCI organizes an annual meeting that highlights research work by its members and guest lecturers that speak with authority on issues that face Clinician-Investigators in Canada.   CSCI is currently in the midst of a reorganization that started several years ago and has resulted in the establishment of an independent meeting, a renewed Young Investigators Forum and establishing close ties with the Clinician Investigator Trainee Association of Canada (CITAC).  Reinforcing our efforts to revitalize our organization, we recently hired a new organization, Gallaher Membership Services and together we are streamlining our Society’s operations. The new CSCI website address is www.csci-scrc.ca. The website contains vital information about the CSCI, CIM and information about becoming a member of the CSCI.

Our Society’s journal, Clinical and Investigative Medicine (CIM), has also undergone a transformation and is under the leadership of Dr. Jonathan Angel of Ottawa.  We are proud of the changes that have occurred at CIM and look forward to the continued success of this journal. 

I sincerely hope that all Clinician-Investigators in Canada, irrespective of their stage of training or career, will adopt the changes that have been made and those that will continue to be made at CSCI by joining CSCI and participating in strengthening the voice for Clinical-Investigation in Canada. Joining CSCI allows members to publish in CIM at no charge. This is a tremendous value for our members. Communication with CSCI members will continue through CIM where we will give updates announcing further developments at the CSCI.  I welcome any feedback or suggestions and hope that you enjoy reading CIM as much as I do.

Sincerely,

Brent W. Winston, MD, FRCPC, FACP, FCCM
President, CSCI
Targeting the oncogene eIF4E in cancer: From the bench to clinical trials
Authors: Borden Katherine LB
Published: May 2017

Identifying and targeting specific oncogenes, with the hope that the resultant therapies may eventually prove to exert positive clinical effects, is a major effort in the area of cancer therapeutics. The eukaryotic translation initiation factor, eIF4E, is overexpressed in many cancers, including acute myeloid leukemia. The role of eIF4E in oncogenic transformation and the development of a means to directly target its activity with ribavirin are discussed here. Results from early stage clinical trials and factors contributing to the development of clinical resistance to ribavirin are also described.
Clinician-Scientist Trainee: A German Perspective
Authors: Bossé Dominick , Milger Katrin , Morty Rory E
Published: May 2017

Clinician-scientists are particularly well positioned to bring basic science findings to the patient’s bedside; the ultimate objective of basic research in the health sciences. Concerns have recently been raised about the decreasing workforce of clinician-scientists in both the United States of America and in Canada; however, little is known about clinician-scientists elsewhere around the globe. The purpose of this article is two-fold: 1) to feature clinician-scientist training in Germany; and 2) to provide a comparison with the Canadian system. In a question/answer interview, Rory E. Morty, director of a leading clinician-scientist training program in Germany, and Katrin Milger, a physician and graduate from that program, draw a picture of clinician-scientist training and career opportunities in Germany, outlining the place of clinician-scientists in the German medical system, the advantages and drawbacks of this training, and government initiatives to promote training and career development of clinician-scientists. The interview is followed by a discussion comparing the German and Canadian clinician-scientist development programs, focusing on barriers to trainee recruitment and career progress, and efforts to eliminate the barriers encountered along this very demanding but also very rewarding career path.
Histopathological effects of fibrin glue on penile fracture in a rat model
Authors: Tasdemir Cemal , Samdanci Emine T , Turtay Muhammet G , Firat Cemal , Oguzturk Hakan , Ozdemir Hulya
Published: May 2017

Purpose: To evaluate both histopathological effects and potential clinical application of fibrin glue on the penile cavernosal tissue.

Methods: Experimental penile fracture was formed by incising from the proximal dorsal side of the penis in 32 Wistar Albino rats. The rats were randomly assigned to four main groups of eight animals each. In the control group, the incision was not repaired and it was left to secondary healing. In the primary repair group, the incision was primarily repaired. In the fibrin glue group, glue was applied only to the incision. In the final group, fibrin glue was applied to the incision following primary repair. Three weeks later, penectomy tissue was examined histopathologically.

Results: When the control group was compared with primary repair+fibrin glue group, the differences in cavernous tissue healing with fibrosis and inflammation were statistically significant (p = 0.04 and 0.01, respectively). The primary repair+fibrin glue group, showed the best cavernous healing with fibrosis observed in only one rat. . There was no significant difference between the control group and the other groups according to cavernous tissue healing with fibrosis and inflammation (p = 0.11 and 0.12). Hyperemia was observed in the all groups of rats.

Conclusions: Fibrin glue can be used in cavernoseal surgeries due to its adhesive and potentially anti-inflammatory features.
A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: A phase II double-blind, randomized placebo-controlled study
Authors: Chen Hong-Wen , Lin I-Hsin , Chen Yu-Jen , Chang Kao-Hwa , Wu Meng-Hao , Su Wen-Hao , Huang Gwo-Che , Lai Yuen-Liang
Published: May 2017

Purpose: This study investigated the efficacy of the botanical-derived drug, PG2, a partially purified extract of Astragalus membranaceus, as a complementary and palliative medicine for managing cancer-related fatigue (CRF).

Methods: Patients with advanced cancer and moderate to severe CRF were randomized to receive either PG2 or a placebo (normal saline, NS) in the first treatment cycle (four weeks) in a double-blind manner; thereafter, on the next cycle (four weeks), all patients received open-label treatment with PG2.

Results: PG2 significantly improved CRF in the NS-primed group. In the first four week cycle, PG2 administration resulted in a greater fatigue-improvement response rate than seen with NS alone. In addition, approximately 82% of patients who reported an improvement of fatigue symptoms following the first cycle of PG2 experienced sustained benefits after administration of the second treatment cycle. Among patients treated with PG2 who did not report an improvement in symptoms throughout the first treatment cycle, approximately 71% showed significant improvement after the second treatment cycle. No major or irreversible toxicities were observed with PG2 treatment.

Conclusion: PG2 might be an effective and safe treatment for relieving CRF among advanced cancer patients.
The Value of P wave dispersion in predicting reperfusion and infarct related artery patency in acute anterior myocardial infarction
Authors: Karabag Turgut , Dogan Sait M , Aydin Mustafa , Sayin Muhammet R , Buyukuysal Cagatay , Gudul Naile E , Demirtas Abdullah O
Published: May 2017

Purpose: The aim of this study is to investigate whether P wave dispersion (PWD), measured before, during and after fibrinolytic therapy (FT,) is able to predict successful reperfusion and infarct related artery (IRA) patency in patients with acute anterior MI who received FT.

Methods: Sixty-eight patients who presented with acute anterior MI were enrolled in the study. An electrocardiogram was performed before and at 30, 60, 90 and 120 minutes after the start of FT. PWD was defined as the difference between maximum and minimum P wave duration on standard 12-lead surface electrocardiogram. A multivariate logistic regression model was used to assess whether PWD was predictor of IRA patency and ST-segment resolution (STR) on electrocardiogram.

Results: PWD120 was significantly lower in patients with STR on electrocardiogram (38 patients) compared with those without STR (30 patients) (44.8±11.5 vs. 52.9±10.3 ms; p < 0.001). PWD120 was found to be significantly lower in patients with patent IRA (31 patients) compared to those with occluded IRA (37 patients) (42.3±9.7 vs. 53.5±10.6 ms; p < 0.001). Logistic regression analysis revealed that PWD120 significantly predicted STR and IRA patency. A ≥51.6 ms PWD120 can predict an occluded IRA with a 87% sensitivity, ≥51 ms PWD120 can predict no reperfusion with a 74% sensitivity.

Conclusion: PWD values, which were higher than 51 ms and 51.6 ms in patients who received fibrinolytic therapy, can serve as a marker of failed reperfusion and occluded IRA. PWD values, in combination with other reperfusion parameters, can contribute to the identification of rescue PCI candidates.
Comparing health behaviours of internal medicine residents and medical students: An observational study
Authors: Rye Peter L , Reeson Marc E , Pekrul Christopher M , Asfour Nabil A , Kundapur Rekha , Wilson Merne P , PausJenssen Anne M , Wilson Thomas W
Published: May 2017

Purpose: During residency, many physicians find it difficult to maintain a healthy lifestyle; however, there is little objective data available. In this study, residents’ health behaviours and cardiovascular risk status were compared with those of medical students.

Methods: Medical residents (n=55, postgraduate years 1 to 4) were compared with medical students (n=62, years 1-4). The main dependent variable was the average number of steps per day (assessed using a pedometer) at work and leisure over three days, during which subjects were not on call or post-call. In addition, all subjects completed a three day food log. Frequency of vigorous exercise was assessed by a single question.
Body mass index (BMI), waist circumference, blood pressure, total and high-density lipoprotein cholesterol, smoking habits and random blood glucose were measured, and Framingham Risk Score coronary artery disease 10 year probabilities (FRS) were calculated.

Results: Residents recorded 8344±3520 steps per day while students recorded 10703±3986 (p < 0.002). 35% of residents and 52% of students averaged more than 10,000 steps per day and senior residents took fewer steps than junior residents. Both groups frequently failed to achieve the recommended daily servings of fruits and vegetables; on average, 3.5±2.0 servings for residents and 5.4±2.2 for students (p < 0.0001). BMI and FRS were higher among the residents in comparison with the students.

Conclusion: Medical residents at our institution appear less active and consume fewer servings of fruits and vegetables than undergraduate medical students. These differences are associated with higher BMI, waist circumference and cardiovascular risk.
Development of a sensitive prognostic scoring system for the evaluation of severity of acute-on-chronic hepatitis B liver failure: A retrospective cohort study
Authors: Zheng Yu-Bao , Xie Dong-Ying , Gu Yu-Rong , Yan Ying , Wu Ye-Bin , Lei Zi-Ying , Peng Liang , Xie Shi-Bin , Gao Zhi-liang , Ke Wei-min
Published: May 2017

Purpose: The purpose of the current study was to establish an objective, simple, and sensitive prognostic scoring system for estimating the severity of acute-on-chronic liver failure in hepatitis B (ACLFB).

Methods: A novel prognostic scoring system was calculated from six clinical indices including total bilirubin (TB), prothrombin activity (PTA), creatinine (Cr), hepatic encephalopathy (HE), infections, and the depth of ascites from 726 patients with ACLFB. Indices were scored from 1 to 4 according to their severity. Groups of the same patients were scored with three-indices (TB, PTA and Cr), four-indices (TB, PTA, Cr and HE), five-indices (TB, PTA, Cr, HE and the depth of ascites) or six-indices (TB, PTA, Cr, HE, the depth of ascites, and infections). The differences in the sensitivity and specificity of four scoring systems were analyzed.

Results: The demarcation points of the three-, four-, five- and six-indices scoring systems were 4.62, 6.12, 7.88 and 9.57, respectively. The analysis of the areas under the receiver operating characteristic (ROC) curve indicated that the four-, five- and six-indices scoring systems were more exact, and objective than the three-indices prognostic scoring system. In the six-indices scoring system, the survival rates of patients with scores from 2 to 6 was 98.31% (233/237), and the mortality rate of patients with scores of 16 and above was 100.00% (140/140), while the mortality rates were 8.33% (3/36) and 96.43% (27/28) for those with scores from 7 to 15, respectively.

Conclusion: A six-indices scoring system is an objective, pertinent, and sensitive system, and may be useful for the prognostic evaluation of ACLFB.