bluuebunny/crossref_metadata_2025 huggingface dataset:
USE OF AN ELECTRONIC DATA WAREHOUSE TO ENHANCE CARDIAC SURGICAL SITE SURVEILLANCE AT A LARGE CANADIAN CENTRE
Authors: Rose G W , Roth V R , Suh K N , Taljaard M , Van Walraven C , Forster A J
Published: May 2017

Background/Purpose: Surgical site infection surveillance to determineincidence is a key infection control activity. Case detection is labour-intensive, therefore most infection control programs use manual or simple electronic mechanisms to “trigger” chart review. However, such “trigger” mechanisms are also labour-intensive, and often of poor specificity. Our objective is to develop a complex trigger mechanism using data from an electronic data warehouse, to improve specificity of surveillance of surgical site infection compared to current trigger mechanisms.

Methods: We will derive an electronic trigger tool for cardiac surgical site infection surveillance using a nested case-control design, among a cohort of all patients undergoing coronary artery bypass grafting, cardiac valve repairor replacement, or heart transplant at the University of Ottawa Heart Institute, from July 1 2004 to June 30 2007.

We will perform a systematic literature review to identify potential trigger factors to include in the model, then construct the trigger tool by backwards stepwise logistic regression. The best-fit model will be used to calculate the probability of surgical site infection. We will select the threshold probability to use in surveillance by visual inspection of receiver-operator-characteristic curves. The accuracy of this electronic trigger mechanism will be compared to pre-existing manual and simple electronic mechanisms using relative true positive ratios and relative false positive ratios.

Results/Conclusions: We have selected 200 cases of surgical site infection and 541 controls from among 3744 procedures performed during the study period. As of the date ofthis abstract we are still undertaking the systematic review.
RENAL OUTCOMES FOLLOWING HYDROXYETHYL STARCH RESUSCITATION: A META-ANALYSIS OF RANDOMISED TRIALS
Authors: Zarychanski Ryan , Turgeon Alexis F , Fergusson Dean A , Cook Deborah J , Hébert Paul , Bagshaw Sean M , Monsour Danny , McIntyre Lauralyn
Published: May 2017

Objectives: To evaluate the impact of HES solutions on adverse renal outcomes and mortality in critically ill patients requiring acute volume resuscitation.

Design: Systematic review and meta-analysis of randomized controlled trials.

Data Sources: We searched electronic databases from 1950 to 2007 (MEDLINE, EMBASE, the Cochrane Central Registry of Controlled Trials, and the SCOPUS database). Conference proceedings and grey literature sources were also searched from 2002-2007.

Review Methods: We included all randomised controlled trials of patients requiring acute volume resuscitation who received HES compared to an alternative resuscitation fluid. No restrictions were considered regarding language or publication type. Data were independently extracted in duplicate.

Results:Of 2381 citations reviewed, we included 22 trials (n=1866) in the analysis. Patients receiving HES were more likely to receive renal replacement therapy [odds ratio [OR] 1.91 (95% confidence interval [CI] 1.22-2.99, I^210.5%)]. This was also true for patients with severe sepsis or septic shock [OR 1.82 (95% CI 1.27-2.62, I^20%)]. In high quality trials, multicentre trials, and in reports indicating adequate allocation concealment, there was a trend toward increased risk of death associated with HES. Other adverse events were not systematically evaluated and were poorly reported.

Limitations: Considerable clinical and methodologic heterogeneity exists among these trials.

Conclusions: The use of HES for volume resuscitation in critically ill patients is associated with increased use of renal replacement therapy and may result in increased mortality. We caution against the routine use of HES for volume resuscitation in critically ill patients.
Impact of US state government regulation on patient access to elective surgical care
Authors: Fric-Shamji Elana C , Shamji Mohammed F
Published: May 2017

Purpose. Rising health care costs in the United States have led to government regulation of services via a Certificate of Need (CON) law in many states. Such regulation may decrease access to elective surgical procedures. This study describes the impact of CON laws on elective surgical care.

Methods. This retrospective cohort trial used data from the Health Care Utilization Project, a publicly available, inpatient database. Rates of six elective procedures were compared between 21 CON states and 5 non-CON states (2004-2005). Further, facility type (non-profit versus for-profit), facility teaching status, and median charges were also compared as a function of CON status. Statistical analysis was performed by Student’s t-tests (?=0.05).

Results. CON laws did not affect procedure rates (P = 0.11-0.97), but lower charges were found for lumbar discectomy ($16,819 versus $13,493 p=0.04), acoustic neuroma resection ($60,993 versus $46,353, P < 0.001), and microvascular decompression (MVD) for trigeminal neuralgia ($37,741 versus $27,729, P < 0.001) in CON states. Various procedures exhibited a shift from for-profit to non-profit facilities including lumbar disectomy (20% versus 9%, P=0.01), acoustic neuroma resection (5.5% versus 0.2%, P=0.03), MVD (20% versus 3%, P=0.02), and rotator cuff repair (23% versus 10%, P=0.01). CON status had no effect on proportion of cases occurring at teaching facilities.

Conclusions. CON laws appear to maintain patient access to elective surgical care while successfully reducing hospital charges. The location of surgery may shift to non-profit centers suggesting preferential certificate distribution, though this only partly explains the decreased charges in states with CON regulation.
Protective effects of caffeic acid phenethyl ester on radiation induced lung injury in rats
Authors: Yildiz Oguz Galip , Soyuer Serdar , Saraymen Recep , Eroglu Celalettin
Published: May 2017

Purpose: The prevention of radiation-induced pulmonary toxicity may help to improve radiation therapy in the cancer patient. The aim of this study was to investigate the pulmonary protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant, on radiation-induced lung injury in rats.

Methods:30 Wistar albino rats were divided into three groups and treated with saline, Radiation (RT) and RT + CAPE respectively. All rats were treated with CAPE (50 ?mol/kg i.p.) or saline. The first dose of CAPE was injected 24 h before radiation and application continued daily, with radiation in second day and 2 days more after the radiation treatment. Radiation dose was 800 cGy for total body. At 72 hr after the last radiation application, under general anesthesia using ip ketamine, the lungs were removed immediately after decapitation. After sacrification, antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) activities and malondiadehyde (MDA) levels were evaluated in lung tissue.

Results: The level of malondialdehyde (MDA) was higher in the RT group (233.4±1.5 nmol/g protein) than in both the control (131.8±0.92) and the RT + CAPE (151.4±1.8) groups (P < 0.001). However, CAT activity was decreased in the RT group (7.26±0.27 Umg protein) compared with control (8.49±0.51) and increased again in the RT + CAPE group (8.31±0.56; P < 0.001). In accord with CAT activity, SOD activity in the RT group (0.42±0.07 nmolMDA/g wet tissue) was different from the control (0.78±0.02) and RT + CAPE (0.86±0.06) groups (P < 0.001).

Conclusion: CAPE aplication with radiation therapy attenuated radiation induced pulmonary injury in vivo, possibly by its antioxidant effect.
JOE DOUPE LECTURE: Chemical biology – understanding biology and advancing therapy
Authors: Schimmer Aaron D
Published: May 2017

Chemical biology is a new academic discipline whose goals are to understand biological systems using chemistry and chemical compounds. In addition to serving as important biological probes, some of these small molecules could be useful therapeutically. This review will discuss how advances in chemical biology by academics can aid in the discovery of new anti-cancer agents. Specifically, novel molecules can be useful tools to validate a potential target in a disease site and help provide the rationale for a clinical trial with a related molecule developed by industry. These novel molecules can also be developed for clinical use, although obstacles to this approach are recognized. Finally, this review discusses the opportunities to identify off-patent drugs with previously unrecognized anti-cancer activity and how the prior data on the drug would permit it to be rapidly repurposed.
Differential heat shock protein responses to strenuous standardized exercise in chronic fatigue syndrome patients and matched healthy controls
Authors: Thambirajah Anita A , Sleigh Kenna , Stiver H. Grant , Chow Anthony W
Published: May 2017

Purpose: Since physical exertion is known to exacerbate the symptoms of chronic fatigue syndrome (CFS) and metabolic changes and including oxidative stress can modulate heat shock protein (HSP) expression responses, we sought to determine whether HSP expression is altered in CFS patients before and after exercise. Heat shock proteins (HSPs) in peripheral blood mononuclear cells (PBMC) were examined from 6 chronic fatigue syndrome (CFS) patients and 7 controls before and after a standardized treadmill exercise. Basal hsp27 was significantly higher among CFS patients compared to controls, and decreased immediately post-exercise, remaining below basal levels even at 7 days. A similar pattern was observed for HSP60, which gradually decreased in CFS patients but increased in controls post-exercise. These findings suggest an abnormal adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.

Methods: HSP27, HSP60, HSP70 and HSP90 expression from 6 CFS patients and 7 age- and sex-matched controls were examined by western blot analysis of peripheral blood mononuclear cells immediately before, after, and at 1 day and 7 days following a standardized treadmill exercise.

Results: Basal HSP27 was higher among CFS patients than in controls (0.54 ± 0.13 vs. 0.19 ± 0.06, mean ± SEM; P < 0.01). In addition, these levels in CFS patients decreased immediately post-exercise (0.25 ± 0.09; P < 0.05) and remained below basal levels at day 1 post-exercises (0.18 ± 0.05; P < 0.05). P < 0.05). This declining expression of HSP27 during the post-exercise period among CFS patients was confirmed by one-way ANOVA analysis with repeated measures (P < 0.05). In contrast, HSP27 levels remained relatively constant following exercise among control subjects. Similar patterns of declining HSP levels in CFS patients were also observed for HSP60 (0.94 ± 0.40 vs. 1.32 ± 0.46; P < 0.05), and for HSP90 (0.34 ± 0.09 vs. 0.49 ± 0.10; P < 0.05) at day 7 post-exercise compared with basal levels, respectively. In contrast, HSP60 levels in control subjects increased at day 1 (1.09 ± 0.27) and day 7 (1.24 ± 0.50) post-exercise compared to corresponding levels immediately post-exercise (0.55 ± 0.06) (P < 0.05, respectively).

Conclusion: These preliminary findings suggest an abnormal or defective adaptive response to oxidative stress in CFS, and raise the possibility that HSP profiling may provide a more objective biologic marker for this illness.
Allogeneic diabetic mesenchymal stem cells transplantation in streptozotocin-induced diabetic rat
Authors: Dong Qing-Yu , Chen Li , Gao Guan-Qi , Wang Lei , Song Jun , Chen Bo , Xu Yu-Xin , Sun Lei
Published: May 2017

Background: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stroma cells which can provide a potential therapy for diabetes mellitus. But the mechanism is still controversial. Also, the status of BM-MSCs under hyperglycemia is not known. In the present study, we investigated the status of BM-MSCs in experimental-diabetic rat and demonstrated the rescue of experimental diabetes by diabetic MSCs transplantation.

Methods: BM-MSCs were cultured and the potential of multiple-differentiation was identified through induction into osteoblasts. MSCs of passage 3 were used for the following experiment. The MSCs were labeled with 5-bromo-2?-deoxyuridine (BrdU). Diabetes in rats was induced by STZ injection. The rats were divided into three groups: normal control group (no DM, rats treated with saline through tail vein, n=10); DM control group (DM, no transplantation of MSCs, n=20); experimental group (DM and transplantation of MSCs, n=20). Body weight and blood glucose of the rats were monitored during the experiment after transplantation of MSCs. Paraffin sections of pancreas were obtained from rats of each group. Immuno-histochemistry analysis and double immunofluorescence were used to detect the BM-MSCs in the pancreatic tissue and their differentiating state.

Results: MSCs were 89.5% labeled by BrdU and DAPI, which was green/blue double stained under fluorescent microscopy. Transplantation of diabetic MSCs resulted in a reduction of hyperglycemia on day 45 in experimental diabetic rats compared with control rats (17.7 mM ±3.9 vs 27.8 mM ± 2.1, P < 0.05), There was also a difference between MSC-treated experimental diabetic rats and control rats in body weight (232.7 g ±19.7 vs 133.3g ±13.1, P < 0.05). Histological and morphometric analysis of the pancreas of experimental diabetic rats showed the presence and differentiation of transplanted MSCs into insulin-producing cells which evidenced by double-staining of anti-BrdU and insulin. Also, there were many small islets throughout the sections. Their mean area and diameter analysis revealed that they were smaller thancontrol islets (1835.7 ± 175.8 µm2 vs 13257.2 ± 1457.6 µm2; 43.5 ± 3.7 µm vs 119.9 ± 5.8 µm, respectively, P < 0.05).

Conclusion: Allogeneic MSCs transplantation can reduce blood glucose level in recipient rats. A relatively small quantity of transplanted diabetic MSCs survive and transdifferentiate into insulin-producing cells in the pancreas of recipient rats. Upon transplantation these cells initiate endogenous pancreatic regeneration by neogenesis of islet of recipient origin. The present study demonstrates that diabetic MSCs retains its stemness and potential to induce pancreatic regeneration on transplantation.
Impact of diabetes on maternal-fetal outcomes in Manitoba: Relationship with ethnic and environmental factors
Authors: Aljohani Naji , Rempel Brenda M , Ludwig Sora , Morris Margaret , Cheang Mary , Murray Robert , Bruce Sharon , Shen Garry X
Published: May 2017

Purpose: To examine the impact of gestational diabetes mellitus (GDM) on maternal-fetal outcomes in Manitoba.

Methods: The rates of macrosomia, stillbirth, cesarean section (C/S) and shoulder dystocia (S/D) in 324,605 births in Manitoba during 1985-2004, and their relationships with diabetes and demographical factors were analyzed.

Results: The incidence of macrosomia, stillbirth, C/S and S/D were 15.3%, 0.57%, 16.0%, and 1.2%, respectively. The rates of macrosomia were elevated in mothers with GDM, type 2 DM (T2DM), rural living, First Nations (FN) status, or ?35 years of age. Increased rates of stillbirth were associated with women with T2DM, FN status or ?35 years, but not those with GDM. C/S and S/D were increased in women with GDM or T2DM. FN status in combination with GDM increased the risk of S/D.

Conclusions: GDM, T2DM, advanced maternal age, FN status or rural living affected pregnancy outcomes in Manitoba.
Chronic stable angina: Addressing the needs of patients through risk reduction, education and support
Authors: Berra Kathy , Fletcher Barbara , Miller Nancy Houston
Published: May 2017

Chronic stable angina (CSA) is one of the most common symptoms experienced by persons with heart disease. CSA is defined by the physical symptoms resulting from blockage of blood flow through the coronary arteries. Anginal symptoms generally occur as a result of increased demands for blood flow, such as with physical activity, eating a large meal, emotional upset or exposure to cold weather. Symptoms vary widely and can include discomfort in the chest, arms, back and jaw, shortness of breath and a sense of increased fatigue. Many patients with chronic stable angina do not describe their symptoms as “pain” but have a sense of burning, tightness, pressure or heaviness in the chest and upper body. Chronic stable angina is usually relieved by stopping the activity that precipitated the symptoms, by resting, and by the use of Nitroglycerine. Anginal symptoms are called “chronic and stable” when they occur in a predictable fashion and are in response to “triggers” such as those mentioned above.
Canadian Association of Professors of Medicine Awards
Authors: CAPM Awards _
Published: May 2017

The 2008 Core Medical Residents Research Awards were presented to Dr. Anna Mathew from the University of Western Ontario, Dr. Jeya Nadarajah of McMaster University, and Dr. Sara Stafford and Dr. Tara Sedlak from the University of British Columbia at the Annual Meeting of the Canadian Society for Clinical Investigation. The awards, co-sponsored by the CSCI and the Canadian Association of Professors of Medicine are to recognize outstanding research by core medicine residents and to highlight the importance of research participation as a component of the core medical training experience.
Connecting KCNQ1 mutants with clinical outcome
Authors: Yan Shaomin , Wu Guang
Published: May 2017

Purpose: Mutations in KCNQ1 are linked to long QT and other syndromes. This study reports a method to predict clinical outcome when a mutation at KCNQ1 is found.

Methods: We used amino-acid distribution probability to measure KCNQ1 mutants, and cross-impact analysis to couple KCNQ1 mutants with clinical outcome. Then, Bayesian equation was used to calculate the probability of occurrence of long-QT syndrome in the presence of a mutation.

Results: Seventy-six mutations were classified into two groups according to whether a mutation increased or decreased amino-acid distribution probability. Cross-impact analysis showed that a mutation that increases the distribution probability has a greater chance of causing long-QT syndrome than a mutation that decreases the distribution probability. Bayesian calculation suggested that a patient would have a 90% chance of developing long-QT syndrome when a mutation is found at KCNQ1.

Conclusion: This study details the process of building a quantitative relationship between KCNQ1 mutations and clinical outcome and provides the probability of LQT1 in the presence of a mutation.
Haemodialysis through a cellulose membrane induces dephosphorylation of CD11b and promotes leukocyte adhesion to endothelial cells
Authors: Hernandez E Rosa , Fuste Berta , Cases Aleix , Tonda Raul , Escolar Gines , Ordinas Antonio , Diaz-Ricart Maribel
Published: May 2017

Purpose: To explore modifications in signal mechanisms involving CD11b and leukocyte adhesion in patients under haemodialysis (HD).

Methods: Samples were obtained from uremic patients at baseline, 15 and 120 min of HD from both arterial and venous lines. CD11b expression was studied by flow cytometry. To study signalling mechanisms, CD11b was immunoprecipitated using a specific antibody. Immunoprecipitates were resolved by 8% SDS-PAGE to measure phosphorylation in immunoblots. Leukocyte adhesion was measured after blood perfusion using endothelial cells (EC) as adhesive substrate. Parallel studies were performed with blood from healthy donors.

Results: The percentage of CD11b+ cells increased during HD with a cellulose membrane in the venous line at 15 and 120 min (6.2±2.9% and 11.0±7.1%) and in the arterial line at 120 min (11.5±8.5 vs. 3.1±1.0% in control P < 0.05). After 120 min HD, CD11b phosphorylation decreased in leukocytes from both arterial (72.6±2.9) and venous lines (51.8±6.5) vs. basal samples (119.5±15.5 P < 0.005). Control leukocytes showed enhanced adhesion to uremic EC compared with control EC (3.0±0.3 vs. 2.3±1.0 leukocytes x100 EC-1 P < 0.05). Uremic leukocyte adhesion was enhanced after HD compared with basal samples 4.2±0.2 leukocytes/100 EC in the arterial and 4.4±0.3 in the venous line; after 120 min vs 2.3±1.0 (P < 0.005).

Conclusion: Leukocyte activation during HD through a cellulose membrane occurs with decreases in CD11b phosphorylation. Activation also induces increases in CD11b expression associated with enhanced leukocyte adhesion to uremic endothelial cells.
Comparison of mechanical motion profiles following instrumented fusion and non-instrumented fusion at the L4-5 segment
Authors: Kim Ho-Joong , Moon Seong-Hwan , Chun Heoung-Jae , Kang Kyoung-Tak , Kim Hak-Sun , Moon Eun-Su , Park Jin-Oh , Hwang Byung-Yoon , Lee Hwan-Mo
Published: May 2017

Purpose: To investigate the difference in motion profiles between instrumented and non-instrumented fusion of the lumbar spine..

Method: In vivo retrospective radiological analysis of dynamic (flexion-extension) lateral plain films was performed in different lumbar spine fusion types. Twenty-eight patients underwent lumbar fusion surgery at the L4/5 level. Fourteen patients underwent anterior fusion surgery without implantation, and the others underwent posterior instrumented fusion. Segmental angular motion was measured at the fused and adjacent levels using dynamic plain lateral film 2 years after operation.

Results: The anterior uninstrumented fusion group showed mean 2.0° of segmental angular motion at the fused level compared with mean of 0.8° in the posterior instrumented fusion group (P < 0.05). In contrast, at the proximal adjacent level, decreased angular motion (mean 7.7°) was noted in the anterior uninstrumented fusion group compared with mean 11.6° in the posterior instrumented fusion group (P < 0.05).

Conclusion: This study suggests that differing stiffness of fusion segments could cause different mechanical motion profiles at adjacent segments.
Pulmonary cryptococcosis in non-AIDS patients
Authors: Wu Benquan , Liu Hui , Huang Jing , Zhang Wenxian , Zhang Tiantuo
Published: May 2017

Purpose: To clarify the clinical features and imaging characteristics of non-AIDS patients with pulmonary cryptococcosis.

Methods: We retrospectively collected 15 HIV-negative patients with pathology-proved pulmonary cryptococcosis from Sep1992 to Jan 2008. Their medical records and radiological data were reviewed and analyzed.

Results: Only one patient was asymptomatic.Thirteen patients were immunocompetent and two were immunosuppressed. Three patients had associated cryptococcosis meningitis. The most common radiographic abnormalities were multiple pulmonary nodules or masses, seen in 8 and 5 cases of patients respectively. 14 patients received specific therapy for Cryptococcus neoformans. Two patients died. In the 11 patients with isolated pulmonary cryptococcosis, treatment consisted of fluconazole alone (n=7), in combination with amphotericin B (n=2), and both 5-flucytosine and amphotericin B (n=2). For the other 2 patients with cryptococcosis meningitis, one was treated with amphotericin B alone and the other with fluconazole combined with amphotericin B and 5-flucytosine.

Conclusions: Non-AIDS patients might also susceptible to cryptococcosis infection. Histological examination is the principal method of diagnosis. The most common CT findings are solitary or multiple nodules with or without cavitation in the subpleural areas of the lung.
An alternative kinase activity assay for primary cultures derived from clinical isolates
Authors: McLean Kristopher , Wu Yan , Gan Bing Siang , O'Gorman David B
Published: May 2017

Purpose: The measurement of protein kinase activity is central to understanding the signaling pathways that regulate cellular proliferation and apoptosis in virtually all disease processes. These measurements typically involve either indirect, time consuming assessment methods that require large amounts of sample, such as western immunoblotting, or the use of high maintenance, specialized equipment not typically available to a small clinical research facility. The purpose of this project was to determine if a benchtop Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) unit could be used to detect and directly assess kinase activity of the serine/threonine kinase Akt.

Method: Biotinylated substrate peptides, predicted to be recognized and phosphorylated by Akt to varying extents, were incubated in crude lysates of primary cells derived directly from clinical isolates. Streptavidin-coated chips were then used to isolate the substrate peptides from the lysates after incubation. Finally SELDI-TOF-MS was used to detect the peptide substrates and identify any changes in mass resulting from phosphorylation.

Results: The biotinylated peptide substrates were readily detected and a simple, rapid procedure that allows direct measurement of Akt activity in less than 1 µg of cell lysate in a 2µL volume was developed. Further, a linear correlation between native to phospho-peptide ratios and SELDI-TOF-MS output demonstrated that this approach is semi-quantitative.

Conclusion: This assay avoids many of the pitfalls associated with the currently available kinase protocols as well as labour-intensive mass-spectrometry analysis by specialist laboratories. We propose that this approach may be a viable alternative for clinical research laboratories aiming to measure the activity of kinases in clinical isolates.
Effects of estrogens on oxidative protein damage in plasma and tissues in ovariectomised rats
Authors: Topçuoglu A , Uzun H , Balci H , Karakus M , Çoban I , Altug T , Aydin S , Topçuoglu D , Çakatay U
Published: May 2017

Purpose: To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats

Methods: Twelve-week-old, sexually mature female Sprague–Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17?-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH).

Results: Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05)

Conclusions: The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.
The prevalence of Th17 cells in patients with dilated cardiomyopathy
Authors: Yi An , Jian Li , Xiaojing Hu , Hui Xin
Published: May 2017

Purpose: Dilated cardiomyopathy (DCM) is a chronic disease characterized by autoimmunity. Th17 cells are a distinct subset from Th1 and Th2 cells and play crucial regulatory functions in inflammatory and autoimmune processes. The current study was designed to investigate the possible involvement of Th17 cells in DCM.

Methods: Th17 cells were detected in blood from DCM subjects and healthy blood donors using several methods including Th17 frequencies by flow cytometric analysis, cytokine (IL-17, IL-6 and IL-23) secretion by enzyme-linked immunosorbent assay and key transcription factor (ROR?t) by real time-PCR.

Results: Patients with DCM demonstrated increased peripheral Th17 cells (2.2±1.2% vs 0.4±0.3%,P < 0.01), Th17 related cytokines (IL-17: 62.7±22.8 vs 15.6±8.6pg/ml, IL-6: 40.7±16.6 vs 10.9±5.3pg/ml, IL-23: 210.7±89.9 vs 90.6±38.8pg/ml, P < 0.01) and ROR?t (24.6±6.5 vs 3.2±1.1,P < 0.01) compared with healthy blood donors (HBD). Furthermore, there was a consistent differential sex-defined cytokine profile. Males showed higher frequencies of IL-17, IL-6 and IL-23 than females (IL-17: 70.7±20.7 vs 54.7±22.2pg/ml, P < 0.01; IL-6: 46.0±18.2 vs 35.4±13.0pg/ml, P < 0.05; IL-23: 238.1±106.2 vs 183.4±60.2pg/ml, P < 0.05) in patients with DCM .

Conclusion: Th17 function is increased in patients with DCM, suggesting a role for Th17 cells in the pathogenesis of DCM.
Handbook for Clinician Scientists: Tools for a Successful Academic Career (edited by Robert Bortolussi)
Authors: Young Fiona BJ
Published: May 2017

The “Handbook for Clinician Scientists,” edited by Dr. Robert Bortolussi with contributors from a variety of fields, is a recently released useful tool for the aspiring Clinician-Investigator trainee. It can also serve as a useful refresher for more established investigators looking to take on new dimensions in their research. Topics are sorted into four general categories or skill sets that will typically be required of a young clinician investigator at some point in their career.
Peptidic sequence “HSEAETGPP” is recognized by the sera of pars planitis patients
Authors: Castañeda-Sánchez Jorge I , Curiel-Quesada Everardo , Pedrosa-Seres Miguel , Cancino-Diaz Mario E , Rodríguez-Martínez Sandra , Cancino-Diaz Juan C
Published: May 2017

Purpose: HLA class II, p-36 protein, heat shock protein and retinal antigens have been associated with pars planitis (PP), but their participation in the development of the disease are unknown. A search for new molecules related to PP is necessary. This work focused on the identification of peptides recognized by PP patient sera using the phage display method.

Methods: Sera of PP patients were used to isolate peptides fused to M13-phage pIII protein. The response of PP and healthy sera to peptides was determined by ELISA. PCR amplification and sequencing of peptide-encoding fragments from clones with high recognition by PP sera were used to characterize displayed peptides.

Results: One hundred clones were randomly selected from a phage display library after three panning rounds using serum proteins from a PP patient. The immunologic response level of 100 clones selected were determined with a major number of patients, it was found that one clone was recognized stronger in PP patients sera than in healthy sera (PP vs. healthy; P < 0.05). The peptide-encoding region of this clone was sequenced and translated. The peptide sequence corresponded to HSEAETGPP. An identical amino acid sequence to HSEAETGPP is found in the human proline-rich transmembrane protein 2 which has not been related with eye diseases.

Conclusion: These results suggest that the peptide HSEAETGPP is associated with PP.
Quality of life, depression, and cytokine patterns in patients with chronic hepatitis C treated with antiviral therapy
Authors: Falasca Katia , Mancino Paola , Ucciferri Claudio , Dalessandro Margherita , Manzoli Lamberto , Pizzigallo Eligio , Conti Chiara M , Vecchiet Jacopo
Published: May 2017

Purpose: To evaluate the effect of chronic hepatitis C and antiviral therapy on health-related quality of life (HRQoL), depression symptoms and cytokine patterns.

Methods: Twenty HCV+ patients treated with peginterferon plus ribavirin were enrolled in this cohort study and invited to complete SF-12 and BDI questionnaires prior to (T0) and at the end of the treatment (T1). HCV-RNA, serum levels of ALT, AST, haemoglobin, ferritin and IFN-?, TNF-?, IL-2, IL-4, IL-6 and IL-10 were evaluated at T0 and T1. The questionnaire results were correlated to biochemical and cytokine parameters.

Results: Two patients (1%) dropped out and 18 HCV patients composed the final sample (11 males (61.1%); mean age 42.5±11.9 yr; mean disease duration 9.7±6.9 yr). Between T0 and T1 ALT (p=0.02), AST (p=0.052) HCV-RNA (P=0.0002) and haemoglobin levels decreased (p=0.0003), whereas ferritin level increased (P=0.003). Also, at T1 all cytokine levels were augmented. Regarding depression status, at T0 10 patients (55.5%) scored above to the BDI questionnaire (suggesting clinically significant depression), whereas at T1 14 patients scored 10 or above (77.7%). At T1 the mean BDI score increased, but this difference was not significant. Regarding HRQoL, the majority of patients had T0 summary scores ? 50. At T1 HRQoL changed and scores decreased in 66.7% of the patients.

A correlation was observed between the T0 level of ferritin and the amount of change in BDI and SF-12 mental score between T0 and T1 (Spearman rho = -0.56 and +0.61, respectively) and IL-4 level at T0 and the change in BDI and SF-12 mental scores (Spearman rho = -0.49 and +0.45, respectively).

Conclusion: BDI, SF-12, IL-4 and ferritin are good tools to predict the appearance of depressive symptoms and worsening of the quality of life in the HCV+ population.
Protective effect of glycyrrhizin on nephrotic syndrome induced by adriamycin in rats
Authors: Li Yu , Bi XueCheng , Zhu Gang , Han ZhaoDong , Ye YongKang , Liang YuXiang , Zhang Lei , Hao ZhiHong , Zeng GuoHua , He HuiChan , Zhong WeiDe
Published: May 2017

Purpose: To explore the protective effect of glycyrrhizin in rats with nephrotic syndrome (NS) induced by adriamycin (ADR).

Methods: 36 Sprague Dawley (SD) male rats were divided into control, untreated and glycyrrhizin treatment groups. The NS rat model was established by injecting ADR twice in the untreated and in the glycyrrhizin treatment groups. Rats in the glycyrrhizin treatment group were fed glycyrrhizin by intragastric administration for 7 days. Changes in the following indices were observed in the three groups before and 4 weeks after the treatment: 24h urine protein quantitation (UPr), serum cholesterol (Ch), serum albumin (Alb), blood urea nitrogen (BUN), serum creatinine (sCr), laminin (LN), fibronectin (FN), collagen (Col), transforming growth factor ?1 (TGF?1) and connective tissue growth factor (CTGF); histopathology by light and electron microscope. Expression of LN, FN, Col?, TGF?1 and CTGF in the cortex of the kidney were detected by semi-quantitive immunohistochemical analysis. Expression of TGF?1 and CTGF in the cortex of the kidney was detected by Fluorescein Based Quantitive RT-PCR. Macrophage infiltration was evaluated by the immunoperoxidase staining.

Results: Compared with the control group, 24h UPr, Ch, BUN and sCr of rats in the untreated group were increased. Glycyrrhizin reduced 24h Upr, Ch, BUN, sCr, LN, FN, Col, TGF?1, CTGF, and mean arterial blood pressure. Pathological changes in the kidney, the expression of LN, FN, Col, TGF?1 and CTGF in the cortex of the kidney in the glycyrrhizin treatment group were decreased compared with the untreated group. Glycyrrhizin also suppressed macrophage infiltration in the kidneys of NS rat models.

Conclusion: Glycyrrhizin exerts protective effects in rats with NS, reducing the excretion of Upr, Ch, BUN, sCr, and mean arterial blood pressure, and also decreasing expression of LN, FN, Col, TGF?1 and CTGF in the kidney. Renal function is improved and the severity of NS is lessened.
Wait times for surgical and adjuvant radiation treatment of breast cancer in Canada and the United States: Greater socioeconomic inequity in America
Authors: Gorey Kevin M , Luginaah Isaac N , Holowaty Eric J , Fung Karen Y , Hamm Caroline
Published: May 2017

Purpose. The demand for cancer care has increased among aging North American populations as cancer treatment innovations have proliferated. Gaps between supply and demand may be growing. This study examined whether socioeconomic status has a differential effect on waits for surgical and adjuvant radiation treatment (RT) of breast cancer in Canada and the US.

Methods. Ontario and California cancer registries provided 929 and 984 breast cancer cases diagnosed between 1998 and 2000 in diverse urban and rural places. Residence-based socioeconomic data were taken from censuses. Cancer care variables were reliably abstracted from health records: stage, receipt of surgery and RT, and waits from diagnosis to initial and initial to adjuvant treatment. Median waits were compared within- and between-country with the non-parametric Mann-Whitney U-test. Categorically long, age-adjusted wait comparisons used the Mantel-Haenszel chi-square test.

Results. There were significant associations between lower socioeconomic status and longer surgical waits, lower access to adjuvant RT and to longer RT waits across diverse places in California. None were observed in Ontario. The two cohorts did not practically differ on access to surgery or on surgical waits. Compared with their counterparts in California, low-income Ontarians, particularly those in small urban places, gained greater access to RT, while high-income Americans had shorter waits for RT.

Conclusions. This historical study contextualized Canada’s “waiting-list problems” with evidence on breast cancer care, where lower income Americans seemed to have waited as long as similar Canadians. Many more low-income Americans seemed to experience the longest wait of all for adjuvant care. They simply did not receive it. In contrast to stark American socioeconomic inequity, this study evidenced remarkable equity in Canadian breast cancer care.
Effect of simvastatin on plasma interleukin-6 in patients with unstable angina
Authors: Ren Hai-Zhou , Ma Long-Le , Wang Le-Xin
Published: May 2017

Purpose: The primary aim of the study was to investigate the effect of sinvastatin on plasma interleukin-6 (IL-6) in patients with unstable angina pectoris (UAP).

Methods: Eighty-six patients with UAP were randomized into simvastatin (40 mg/d for 4 weeks) and the placebo group. Plasma IL-6 was measured by ELISA.

Results: There was a reduction in the plasma total cholesterol and LDL in the simvastatin group (P < 0.01). The simvastatin group also had better angina control than the placebo group (post-treatment angina score, 0.72±0.59 vs 1.07±0.76, P < 0.05). Following treatment, the average left ventricular ejection fraction in the simvastatin group was higher than in the placebo group (0.54±0.06 vs 0.51±0.05, P < 0.05), whereas the plasma BNP levels were lower (16.8±6.6 vs 26.4±1.4, P < 0.01). Before treatment, there was no difference in the plasma levels of IL-6 between the simvastatin and the placebo groups (P > 0.05). Following treatment, the IL-6 levels in the simvastatin group were lower than in the placebo group (0.7±0.4 vs 1.2±0.4 pg/ml, P < 0.05).

Conclusions: Short-term treatment with simvastatin reduces plasma IL-6. The anti-inflammatory effect of simvastatin may contribute to its beneficial effects on the ventricular function and angina control.
Immunological disturbances in Good’s syndrome
Authors: Fijolek Justyna , Wiatr Elzbieta , Demkow Urszula , Orlowsk Tadeusz Maria
Published: May 2017

Background: Immunodeficiency with a thymoma (Good’s syndrome) is a rare condition occurring in patients with adult-onset hypogammaglobulinaemia.

Clinical report: We describe the case of a 38-yr-old woman with an upper mediastinal mass and inflammatory infiltrations in the lungs. After thymectomy, the patient’s condition did not improve. The HRCT scan showed bronchiectasies with parenchymal opacities. As pulmonary infection persisted despite wide spectrum antibiotic therapy, additional tests were performed to diagnose an immunodeficiency. Serum immunoglobulin levels were very low. T cell response to mitogens was normal, but to Staphylococcus aureus Cowan I was impaired. Immunophenotyping of peripheral blood and bone marrow aspirate showed a very low number of B-cell at all the stages of development (CD10+CD19+, CD5+CD20). In peripheral blood 2.5% of CD19+ lymphocytes were found. On the basis of clinical history and immunological analysis, Good’s syndrome was recognized. Treatment with intravenous gammaglobulin and antibiotics improved the patient’s performance.

Conclusion: Measurement of serum immunoglobulin concentration is recommended for all patients suspected of thymoma.
Protective effects of vitamin E on central nervous system in streptozotocin-induced diabetic rats
Authors: Kabay Sibel Canbaz , Ozden Hilmi , Guven Gul , Ustuner M Cengiz , Degirmenci Irfan , Olgun Esra Gurlek , Unal Nedim
Published: May 2017

Objective: To evaluate the histopathological and antioxidant effects of vitamin E (VE) treatment on brain tissue in streptozotocin (STZ)-induced diabetic rats.

Methods: Thirty two male Wistar albino rats were used. The study comprised four groups of 8 rats: Group A - untreated group, group B - diabetic group, group C - VE and group D - diabetic plus VE. In the diabetic groups, diabetes was induced by a single intraperitoneal injection of 65 mg/kg STZ. Vitamin E was given 50 mg/kg/day i.p. for three weeks. Concentrations of glucose, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were detected in the haemolysate.

Results: Glucose concentrations were increased in the blood of the STZ-treated rats compared with those in the diabetic groups (group B and D). The MDA concentrations in the brain from diabetic rats increased, whereas the GPx, SOD, CAT concentrations decreased. Treatment with VE returned concentrations of MDA, GPx, SOD and CAT toward control values. The MDA concentration in the diabetic group (20.65±2.24 nmol/mg Hb) was decreased compared with the VE treated group (15.54±1.32 nmol/mg Hb). There were no pathological differences between untreated and VE treated rats’ brains. Neuronal ischemic damages were determined in STZ-induced diabetic rats. Ischemic neuronal alterations in group B (diabetic) had more damage than group D (diabetic + VE).

Conclusion: The study revealed neuroprotective effects of VE on ischemic damage in diabetic central neuronal cells, caused by diabetic oxidative stress.
Arrhythmic effects of Ivabradine in patients with coronary artery disease
Authors: Murat Sani N , Orcan Salih , Akdemir Ramazan , Dogan Mehmet , Kara Emel , Balci Mustafa
Published: May 2017

Objectives: Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. The aim of the present study was to investigate the effects of ivabradine therapy on P-wave duration, dispersion and QT duration, dispersion in coronary artery disease patients.

Methods and Results: The study population consisted of 21 patients with CAD who have confirmed by coronary angiography previously. Written informed consent was obtained in all patients. Twelve-lead electrocardiogram was recorded for each subject at a rate of 50mm/s on admission and repeated after 1 month ivabradine therapy. QT duration, QT dispertion, maximum and minimum QT duration calculated. Maximum and minimum P wave and P wave dispersion has been calculated. Heart rate was decreased after ivabradine therapy. (75±15 and 63±10, P=0.02).There was no difference between Pmax, Pmin and Pdis values before and after treatment. QTmax value was prolonged after treatment. (410±43 and 431±14, P=0,005) but there was no difference between cQTmax value.(455±38 and 439±21) There was no difference between QTdis and cQTdis values before and after treatment. (44±18 & 49±14; and 49±22 & 48±15). QTmax was prolonged after ivabradine therapy but cQTmax, Pdis, QTdis and cQTdis were not prolonged.

Conclusion: There is no relationship between ivabradine therapy and increased risk of ventricular and atrial arrhythmia in coronary artery disease patient.
Oxidative status and paraoxonase activity in children with asthma
Authors: Cakmak Alpay , Zeyrek Dost , Atas Ali , Selek Sahabettin , Erel Ozcan
Published: May 2017

Objective: To compare paraoxonase activity and changes in oxidative status in asthmatic children and healthy children by determining serum paraoxonase activity and total oxidative status, total antioxidant capacity and lipid hydroperoxidation.

Methods: Forty two asthmatic children were compared with 32 healthy children of similar age and sex. To evaluate the paraoxonase and oxidative status, total antioxidant capacity and lipid hydroperoxidation were examined. Serum paraoxonase activity was evaluated by measuring the rate of paraoxon hydrolosis. Oxidative status was evaluated by the method developed by Erel. Lipid hydroperoxide was measured by an iodometric method.

Results: In comparison with the healthy control group, the paraoxonase activity of the asthmatic children was found to be low (163.7 ± 73.0 (U/L) and 349.2 ± 153.9 (U/L), P = 0.002) and total oxidant status (9.0 ± 3.5 ?mol H2O2 Eq/L and 13.4 ± 7.0 ?mol H2O2 Eq/L, P =0.002), total antioxidant capacity (5.5 ± 2.5 µmol Trolox Eq/L and 1.0 ± 0.6 µmol Trolox Eq/L, P < 0.001), and lipid hydroperoxidation values (9.9 ± 3.4 ?mol H2O2 Eq/L and 4.4 ± 1.5 ?mol H2O2 Eq/L, P < 0.001) were found to be high. The high density lipoprotein (HDL) concentration of the asthmatic children was lower than that in the control group (40.1 ± 9.2 mg/dl and 54.5 ± 15.9 mg/dl, P < 0.001)

Conclusion: In asthmatic children, when total oxidant status, total antioxidant capacity and lipid hydroperoxidation levels increase, paraoxonase activity decreased.
Susceptibility to apoptosis of lymphocytes from patients with peripheral arterial disease
Authors: Skórkowska-Telichowska Katarzyna , Adamiec Rajmund , Tuchendler Dominika , Gąsiorowski Kazimierz
Published: May 2017

Purpose. To determine, in vitro, the susceptibility to apoptosis of lymphocytes from patients with peripheral arterial disease (PAD) in the presence of a low culture medium serum concentration, and to evaluate the correlation of the degree of apoptosis and the serum lipid levels.

Methods. Lymphocytes were isolated from the venous blood of PAD patients with lower limb ischemia secondary to obliterative atherosclerosis of Fountain stage IIb. None of the patients had received hypo-lipemic therapy. The lymphocytes were incubated for 48 hr in media containing reduced concentrations of fetal calf serum. The study group consisted of 10 patients (7 men and 3 women), with a mean age of 67.0 ± 4.0 yr. The control group consisted of ten healthy volunteers, of the same mean age and sex proportion as the study group.

Results. The percentage of non-apoptotic lymphocytes was lower (by 17%) and the percentage of late apoptotic lymphocytes was higher (by 33%) in the PAD patients than in the healthy donors when comparing the slopes of regression lines describing the relation between frequency of apoptotic lymphocytes in culture media containing reduced concentration of fetal calf serum The percentage of late apoptotic lymphocytes was correlated with the levels of total cholesterol (rs=0.93; P < 0.01) and LDL cholesterol (rs=0.80; P < 0.01) , and negatively correlated with the level of triglycerides (rs=-0.71; P < 0.05).

Conclusion. The results of this study of lymphocyte apoptosis are important in understanding of the disease pathogenesis and should be taken into account in elaboration of treatment strategies.