bluuebunny/crossref_metadata_2025 huggingface dataset:
Atrial Electromechanical Delay and Diastolic Dysfunction in Primary Sjögren Syndrome
Authors: Akyel Ahmet , Tavil Yusuf , Tufan Abdurrahman , Yayla Cagri , Kaya Arif , Tezcan Mehme Engin , Ozturk Mehmet Akif , Boyaci Bulent
Published: May 2017

Purpose: In this study we aimed to investigate myocardial function and atrial electromechanical properties by conventional and tissue doppler echocardiography in patients with primary Sjögren syndrome.

Methods: Forty patients with Sjögren syndrome (SS) and 25 age- and sex-matched healthy volunteers were enrolled in the study. Using transthoracic echocardiography, myocardial performance index and atrial electromechanical properties were measured.

Results: Basal characteristics were similar between two groups. Myocardial performance index values were disturbed in patients with Sjögren syndrome (0.41 vs. 0.32, p < 0.01). There was significant intraatrial (16.4±6.4, 5.0±4.5, p < 0.01) and interatrial (30.6±10.1, 15.4±5.9, p < 0.01) electromechanical delay in this patient group.

Conclusion: Myocardial function is disturbed and there is significant atrial electromechanical delay in patients with primary SS. This study is the first to show altered myocardial function and atrial electromechanical properties in primary SS.
Immune Status and the Development of Listeria monocytogenes Infection in Aged and Young Guinea Pigs
Authors: Wu Wen-Hsuan , Pang Hoan-Jen E. , Matthews Karl R.
Published: May 2017

Purpose: Consuming even low numbers of the foodborne pathogen, Listeria monocytogenes, places the elderly at risk for severe illness. The impact of immunomodulation on the development of listerial infection within a young and aged population after low dose challenge with L. monocytogenes was investigated.

Methods: Animals received daily supplementation of vitamin E for a period of 21 days to promote immunomodulation, and were then orally challenged with 100 CFU of L. monocytogenes. Levels of CD8+, CD4+ and CD3+ T cells were used as markers to determine the influence of daily supplementation with vitamin E on immune response; the spleen and liver were harvested for microbiological analysis.

Results: Higher numbers of animals became infected in control groups than in vitamin E-treated group. During the post-challenge period, vitamin E-treated aged animals showed faster CD8+ T cell proliferation than control aged animals.

Conclusion: Daily supplementation with vitamin E was more beneficial in young compared with aged animals in mitigating listerial infection. Results suggest exposure to even low numbers of L. monocytogenes can result in infection in both healthy young and aged populations.
Genome-Wide Association Studies-derived susceptibility loci in Type 2 Diabetes: confirmation in a Chinese population
Authors: Lu Shuangyan , Xie Yan , Lin Kun , Li Siwei , Zhou Yidan , Ma Pei , Lv Zhihua , Zhou Xin
Published: May 2017

Purpose: Several novel genetic variants for type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWAS). A case-controll study was performed to investigate the association of five new European or South Asian GWAS-derived susceptibility loci with T2DM in a Chinese population.

Methods: Five single nucleotide polymorphisms (SNPs) were genotyped: rs3923113 near GRB14, rs16861329 in ST6GAL1, rs1802295 in VPS26A, rs7178572 in HMG20A, and rs231362 near KCNQ1, by high-resolution melting (HRM) of small amplicons. The association between T2DM and related quantitative traits in a total of 900 Chinese individuals, including 498 type 2 diabetic patients and 402 ethnically matched control subjects, were examined.

Results: After adjusting for age and gender, rs1802295 (OR 5.724, P=0.03) and rs231362 (OR=5.683, P=0.016) were found to be associated with T2DM. Triglyceride levels were higher in TT and CT carriers for rs16861329 (1.05 (0.8-1.34) mmol/l) than in CC carriers (0.91 (0.73-1.23) mmol/l) with P=0.008 and that high-density lipoprotein cholesterol (HDL-C) was lower in TT and CT carriers (1.17 (1.02-1.33) mmol/l) than in CC carriers (1.21 (1.05-1.41) mmol/l), with P=0.034. For rs3923113, the HDL-C levels were lower in the GG carriers (1.08 (0.90-1.18) mmol/l) than in the GT+TT carriers (1.21 (1.04-1.38) mmol/l), with P=0.018. Ours is the first report of this association.

Conclusion: rs231362-KCNQ1 and rs1802295-VPS26A are associated with T2DM in the Chinese population. The remaining three SNPs are associated with other aspects of lipid metabolism.
Relationship Between Duke Treadmill Score and Coronary Artery Lesion Complexity
Authors: Acar Zeydin , Korkmaz Levent , Agac Mustafa T , Erkan Hakan , Dursun Ihsan , Kalaycioglu Ezgi , Kiris Gulhanim , Celik Sukru
Published: May 2017

Purpose: The purpose of this study was to investigate the relationship between the Duke Treadmil Score (DTS) and coronary artery disease (CAD) complexity in patients with suspected coronary artery disease (CAD).

Methods: Sixty five patients who had positive exercise testing for CAD were enrolled. Coronary angiography was performed and Syntax score (SxScore), a marker of CAD complexity, was determined. The relationship between DTC and SxScore then evaluated.

Results: There was a strong negative correlation between DTS and SxScore (r= - 0.91, p < 0.001). In addition, patients with higher and intermediate risk as evaluated by DTS had increased SxScore compare to those that were low risk (23 ± 6, 6 ± 5 and 0 ± 0 respectively).

Conclusions: A strong negative correlation was seen between DTS and coronary lesion complexity. By assessing DTS important information about coronary artery lesion complexity can be obtained before invasive coronary angiography.
2012 CSCI/CITAC Young Investigators Forum Abstracts
Authors: CSCI CITAC
Published: May 2017

CSCI/CITAC young investigators forum

for

CLINICAL SCIENTISTS IN TRAINING
CIP and MD/PhD STUDENTS

TRIBUNE DES JEUNES CHERCHEURS

pour

CHERCHEURS CLINICIENS EN FORMATION
ÉTUDIANTS INSCRITS AU PROGRAMMES
PFCC ET MD/PHD

Thursday, September 20, 2012
Jeudi, le 20 septembre 2012

The National Art Centre, Ottawa.
Ottawa, Ontario
Effects of Ozone Therapy on Cyclophosphamide-induced Urinary Bladder Toxicity in Rats
Authors: Tasdemir Seda , Tasdemir Cemal , Vardi Nigar , Ates Burhan , Taslidere Elif , Karaaslan Merve G , Sapmaz Hilal I , Sagir Mustafa , Kurt Ahmet , Baser Canan A
Published: May 2017

Purpose: This study investigated the efficacy of ozone therapy (OT) in a rat model of cyclophosphamide-induced hemorrhagic cystitis (HC).

Methods: Forty Wistar Albino male rats were divided into five groups: sham, OT, cyclophosphamide (CP), OT+CP and CP+OT. Hemorrhagic cystitis (HC) was induced by intraperitoneal (i.p) administration a single dose of 100 mg/kg CP. OT was performed once daily for three days. The CP+OT group received OT (0.2 mg/kg) i.p 24 h after CP administration. CP was injected to the OT+CP group the day after the third course of OT. All animals were killed four days after CP administration. Bladder injury and oxidative stress parameters were determined from tissue samples.

Results: We found small, but non-statistically significant biochemical and histological changes in the animals treated with OT alone. CP administration induced cystitis, as manifested by a marked loss of urothelial cells, as well as hemorrhaging and edema in the bladder as determined by histopathological examination. It also caused a significant decrease in the endogenous antioxidant compound glutathione (GSH) and elevation of lipid peroxidation, and nitric oxide (NO) and myeloperoxidase (MPO) levels in the rats’ urinary bladder tissue. OT was able to ameliorate these changes; however these effects were prominent in the CP+OT group when compared with the OT+CP group.: For example, the NO level in the CP+OT group was 68% of the OT+CP group (p < 0.05).

Conclusion: OT prevented CP-induced urothelial damage by diminishing bladder oxidative stress, inflammation and NO levels. OT may help to ameliorate bladder damage induced by CP in the clinical setting.
Association of monocyte CCR2 expression with obesity and insulin resistance in postmenopausal women
Authors: Pandzic Jaksic Vlatka , Gizdic Branimir , Miletic Zorana , Trutin-Ostovic Karmen , Jaksic Ozren
Published: May 2017

Purpose: Monocytes actively participate in inflammatory mechanisms that contribute to the development of adipose tissue dysfunction and atherogenesis. The aim of this study was to evaluate the association of monocyte CCR2 chemokine receptor expression and intracellular oxidative burst with the metabolic and inflammatory factors related to body weight.

Methods: The study was performed in 67 postmenopausal women with normal, overweight and obese body mass index. Monocyte CCR2 surface expression and intracellular oxidative burst activity (determined using 2', 7'-dichlorofluorescin diacetate) were analyzed by flow cytometry. Serum levels of HMW adoponectin, monocyte chemoattractant protein-1 (MCP-1), insulin, glucose, lipids and C-reactive protein were determined.

Results: Subjects with homeostasis model assessment-estimated insulin resistance (HOMA-IR) above the median had significantly higher proportion of CCR2+ monocytes and higher mean fluorescence intensity (MFI) of CCR2 and oxidative burst. The proportion of CCR2+ monocytes and CCR2 MFI were correlated with body weight, body mass index, fat mass, insulin and HOMA-IR. Oxidative burst also correlated with anthropometric measures, fat mass and expression of CCR2. No correlations were found between these markers of monocyte activation and HMW adiponectin or monocyte chemoattractant protein-1. The absolute number of monocytes was associated with insulin and this association remained significant after adjusting for C-reactive protein. In the multiple regression model the monocyte number was determined to be an independent predictor of insulin level.

Conclusion: These results provide support for significant associations of monocyte number and markers involved in monocyte activation with obesity and insulin resistance.
HDAC inhibitor trichostatin A suppresses esophageal squamous cell carcinoma metastasis through HADC2 reduced MMP-2/9
Authors: Wang Feng , Qi Yu , Li Xin , He Wei , Fan Qing-Xia , Zong Hong
Published: May 2017

Purpose: The histone deacetylase (HDAC) inhibitor trichostatin A (TSA) has been shown to act as an anti-tumor agent; however, the effect and mechanism of TSA on the invasion of esophageal squamous cell carcinoma (ESCC) remains unknown.

Methods: To determine whether TSA suppresses the invasiveness of ESCC cell via HDAC2, the expression of HDAC2 in ESCC tissues and adjacent non-tumor tissues were compared using Western blot and immunohistochemistry. Cells were transfected with HDAC2 siRNAs and non-targeting control siRNA using Lipofectamine TM 2000. Cell invasion was investigated using a transwell assay. The protein levels of matrix metalloproteinase-2/9 (MMP-2/9) were examined by Western blot analysis.

Results: Expression of HDAC2 was significantly higher in ESCC than in adjacent non-tumor tissues. Additionally, the in vitro invasion assay found that both downregulation of HDAC2 expression and TSA treatment inhibited ESCC cell invasion by approximately 75%. Also, an MMP2/9-specific inhibitor sharply suppressed ESCC cell invasion. Furthermore, both downregulation of HDAC2 and treatment with TSA decreased MMP-2 and MMP-9 protein levels in ESCC cells.

Conclusions: These results suggest that the inhibitory effect of TSA on cancer invasion is mediated through the suppression of HDAC2 expression, and that the reduction of MMP-2 and MMP-9 expression induced by HDAC2 may be involved in the anti-invasive effect of TSA.
End-of-Life Care in Canada
Authors: Fowler Robert , Hammer Michael
Published: May 2017

End-of-life care and planning is critically important to the next decades of health care in Canada. In our country, between 2005 and 2036, the number of seniors 65 years and older is projected to increase by up to 25%, and the number of deaths by 65%. The majority of patients are currently admitted to hospital and intensive care units at the end of life; however, up to 70% of elderly patients say they would prefer a less aggressive treatment plan focusing on providing comfort rather than a technologically supported, institutionalized death. Herein we provide a brief overview of the end-of-life care in the Canadian context, and highlight challenges and opportunities for health care system change in the coming decades.
The biodistribution and pharmacokinetic evaluation of choline-bound gold nanoparticles in a human prostate tumor xenograft model
Authors: Razzak Rene , Zhou Joe , Yang XiaoHong , Pervez Nadim , Bédard Eric LR , Moore Ronald B , Shaw Andrew , Amanie John , Roa Wilson H
Published: May 2017

Purpose: Gold nanoparticles (GNPs) have attracted significant attention in the treatment of cancer due to their potential as novel radiation enhancers, particularly when functionalized with various targeting ligands. The aim of this study was to assess the biodistribution and pharmacokinetic characteristics of a novel choline-bound GNP (choline-GNP) stabilized with polyethelenimine (PEI).

Methods: Choline bound to 27 nm diameter GNPs was characterized using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR). Toxicity of choline-GNPs was examined on DU-145 prostate cancer cells using an MTT assay. Using balb/c mice bearing flank DU-145 prostate tumors, choline-GNPs bio-distribution was measured using inductively coupled mass spectroscopy (ICP-MS). Blood, heart, lung, liver, spleen, brain, kidney and tumor gold content were examined at multiple time points over a 24-hour period after tail vein injection.

Results: An MTT assay using DU-145 prostate cancer cells yielded a 95% cell viability 72 hours after choline-GNP administration. The tumor GNP area under the concentration-time curve during the first 4 hours (AUC0-4) was 2.2 µg/ml h, representing 13% of the circulating blood GNP concentration over the same time period. The maximum intra-tumor GNP concentration observed was 1.4% of the injected dose per gram of tumor tissue (%ID/g) one hour post injection.

Conclusions: GNPs functionalized with choline demonstrates a viable future nanoparticle platform with increased intra-tumor uptake as compared to unconjugated GNPs. Decreased intra-hepatic accumulation appears to be the reason for the improved systemic bioavailability. The next logical translational investigation will incorporate external beam radiation with the observed maximum intra-tumor uptake.
A non-tracheal intubation (tubeless) anesthetic technique with spontaneous respiration for upper airway surgery
Authors: Xu Jing , Yao Zheng , Li Shaoqing , Chen Lianhua
Published: May 2017

Background: The most important consideration for administration of anesthesia in upper airway surgery is maintenance of a patient’s airway for optimal surgical exposure, adequate ventilation and sufficient depth of anesthesia. The tubeless anesthetic techniques, including total intravenous anesthesia with a combination of propofol and remifentanil or inhalation anesthesia with the insufflation of anesthetic gas, are considered experimental in many countries.

Methods: Fifteen pediatric (8 to 60 months) and 16 adult (23 to 55 years) patients were included in the study. Anesthesia (gas insufflation) was induced into the pediatric patients by inhalation of 8% sevoflurane in 8 L/min oxygen flow. An endotracheal tube, inserted through the nasal or oral cavity with its tip in the laryngopharynx, was used to maintain anesthesia with 3%-6% sevoflurane in 4 L/min oxygen flow. Total intravenous anesthesia was induced in adult patients by inhalation, 8% sevoflurane in 8 L/min oxygen flow, combined with intravenous injections of propofol (1.5-2 mg/kg) and fentanyl (1.5-2 μg/kg). Assisted ventilation was maintained by use of a face or laryngeal mask. Propofol infusion at 200-300 μg/kg/min, combined with remifentanil infusion at 0.06-0.2 μg/kg/min, was used for maintaining anesthesia.

Results: All patients had surgery under tubeless anesthesia with steady spontaneous respiration. The mean time from induction of anesthesia to unconsciousness was 16±3 s and 36±14 s in pediatric and adult groups, respectively. The average times from induction of anesthesia to the attainment of necessary anesthetic level for surgery while keeping steady spontaneous respiration was 4.17±0.96 min and 8.69±3.17 min in pediatric and adult groups, respectively. The frequency and extent of respiration and heart rate were maintained within the normal range; SpO2 was > 98%. None of the patients developed complications.

Conclusion: Tubeless anesthesia with spontaneous ventilation induced in patients can provide both an interference-free operative field and continuous observation of airway activity, which may provide an effective approach in excellent surgical conditions for the actual airway operation.
Decreased plasma apolipoprotein A-IV levels in patients with acute coronary syndrome
Authors: Li Jiabei , Song Mingbao , Qian Dehui , Lu Wei , Wang Juan , Jiang Guoyan , Jin Jun , Wu Xiaojing , Huang Lan
Published: May 2017

Purpose: The purpose of this study was to evaluate the relationship between apolipoprotein A-IV (apoA-IV) plasma concentrations and acute coronary syndrome (ACS).

Methods: Plasma apoA-IV concentrations were measured in 115 patients with different types of ACS and in 68 gender- and age-matched control subjects using Enzyme-Linked Immunosorbent Assay (ELISA) kits. The clinical data were collected by an internist, who was blinded to plasma apoA-IV concentrations.

Results: Plasma apoA-IV levels in ACS patients were significantly decreased compared to the levels in control subjects (437.0 ± 157.5 μg/mL vs. 590.2 ± 183.7 μg/mL, P < 0.001). An statistically significant decreasing trend of plasma apoA-IV levels from the control subjects, to patients with unstable angina pectoris (UAP) (457.3 ± 152.9 μg/mL), to patients with acute myocardial infarction (AMI) (311.7 ± 127.8 μg/mL), was observed. Moreover, plasma apoA-IV level was negatively associated with New York Heart Association (NYHA) functional class. NYHA class II (467.2 ± 142.1 μg/mL, P < 0.001) and class III/IV (368.1 ± 170.8 μg/mL, P < 0.001) patients had statistically decreased levels of plasma apoA-IV when compared to the control subjects. A stepwise multivariate regression analysis identified types of ACS, NYHA classes, and plasma fibrinogen levels as the most important determinants of plasma apoA-IV levels in ACS patients.

Conclusions: Low plasma apoA-IV levels are associated with ACS, and plasma apoA-IV levels may be a potential treatment target for ACS patients.
Scientific overview: CSCI – CITAC Annual General Meeting and Young Investigator’s Forum 2012
Authors: Antoun Ghadi , Ram Véronique D , Wang Xin , Wilcox Jared T , Yoon Ju-Yoon
Published: May 2017

In 2012, the Annual General Meeting of the Clinical Investigator Trainee Association of Canada – Association des cliniciens-chercheurs en formation du Canada (CITAC – ACCFC) and the Canadian Society of Clinician Investigators (CSCI) was held 19-21 September in Ottawa. Several globally-renowned scientists, including 2012 Friesen International Prize recipient, Dr. Marc Tessier-Lavigne, the CSCI/Royal College Henry Friesen Award recipient, Dr. Morley Hollenberg, and the recipient of the Joe Doupe Young Investigator Award, Dr. Phillip Awadalla, presented on a range of topics on research in basic and translational science in medicine.

This year’s CITAC Symposium featured presentations by Dr. Alain Beaudet, Dr. Michael Strong and Dr. Vivek Goel on the Role of Physician Scientists in Public Health and Policy, which was followed by a lively discussion on the role of basic science and clinical research in patient-oriented policy development.

This scientific overview highlights the research presented by trainees at both the oral plenary and poster presentation sessions. As at previous meetings, research questions investigated by this year’s trainees span multiple medical disciplines; from basic science to clinical research to medical education. Below is a summary of the presentations showcased at the Young Investigator’s Forum.
Here to stay: Clinician investigator training in a changing environment
Authors: Wang Xin
Published: May 2017

Clinician investigators (CI) are a growing sector within the research community. Given the emphasis on patient-oriented research, the need for more physicians with the aptitude to conduct translational research has never been greater. Despite this, there is limited literature on the current Canadian CI training programs. The Clinician Investigator Trainee Association of Canada (CITAC) has a significant interest in ensuring the training of clinician instigators, at both the undergraduate and residency levels, remains adept at meeting the challenges of today’s health care system. In the August issue of Clinical Investigative Medicine, Appleton et al. published the first document reporting on the data collected by CITAC on the basic demographics of Canadian CI trainees [3]. The authors captured census data from each CI training program. This collaborative and national effort is a first and crucial step in understanding the strengths and potential pitfalls of Canadian CI training programs. The data presented will be used as a reference resource to improve training programs and facilitate future research.
Serum fetuin-A levels following recombinant human thyroid-stimulating hormone stimulation
Authors: Gagnon AnneMarie , Abujrad Hussein , Irobi Clara , Lochnan Heather A , Sorisky Alexander
Published: May 2017

Purpose: Fetuin-A is a hepatokine that is linked to lipid metabolism, obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Elevated thyroid-stimulating hormone (TSH) levels are associated with metabolic and cardiovascular disturbances. Our aim was to determine if TSH can regulate fetuin-A levels.

Methods: Fetuin-A serum levels were examined in 26 subjects (19 women; previous thyroidectomy and radioactive iodine ablation) undergoing recombinant human TSH (rhTSH) stimulation to screen for thyroid cancer recurrence. Their age was 49±10 years, and body mass index (BMI) was 28±6 (both expressed as mean±SD). The patients received two doses of rhTSH (0.9 mg), administered 24 hours apart on days 1 and 2, without discontinuation of ongoing L-thyroxine therapy. Morning blood samples were obtained on days 1 (prior to the first dose of rhTSH), 3 and 5.

Results: The baseline value of fetuin-A (mean±SD) for all participants was 527±186 mg/L. Values of fetuin-A did not change in response to rhTSH administration. The lack of response was not dependent on gender, age, baseline free thyroxine level or BMI.

Conclusion: Fetuin-A has been implicated in metabolic and inflammatory conditions, but there have been no reports on whether fetuin-A is influenced by TSH. Within the context of rhTSH administration for surveillance of thyroid cancer recurrence, there was no effect on serum levels of fetuin-A.
It begins with the right supervisor: Importance of mentorship and clinician-investigator trainee satisfaction levels in Canada
Authors: Yoon Ju-Yoon , Appleton Tom , Cecchini Matthew J , Correa Rohann J , Ram Veronique D , Wang Xin , Ng Enoch , Speechley Mark , Wilcox Jared T
Published: May 2017

Purpose: Clinician Investigator Trainee Association of Canada/ Association des cliniciens-chercheurs en formation du Canada (CITAC/ACCFC) represents the interests of clinician-investigator (CI) trainees across Canada. To better advocate for the successful training of CI trainees in Canada, CITAC/ACCFC conducted a survey to assess satisfaction with their training and to find what factors were most associated with satisfaction level.

Methods: A nominal scale-based psychometric survey was conducted online in 2009 on CI trainees in Canada (including MD/MSc, MD/PhD, or CIP/SSP). One hundred fifteen out of a target population of approximately 350-400 responded. Survey respondents were asked to rate their level of satisfaction in four areas: 1) quality of training, 2) financial support, 3) mentorship satisfaction and 4) program structure. Ratings in these four areas were also combined to produce a measure of overall satisfaction.

Results: At least half of the respondents were ‘completely satisfied’ in each of the four categories other than mentorship. While 98% of respondents considered mentorship as important to their success, 62% expressed some level of dissatisfaction with the level of mentorship received. Moreover, increased levels of mentorship were strongly associated with increased levels of overall satisfaction.

Conclusion: The discrepancy between CI trainees’ perceived importance of mentorship and the level of satisfaction in mentorship received reveals a strategic area where CI training should be improved. Recognizing that good mentorship in a CI training program often begins with one’s research supervisor, the CITAC/ACCFC has compiled six specific recommendations for finding a good supervisor.
PI3K-Akt/eNOS in remote postconditioning induced by brief pulmonary ischemia
Authors: Tang Yan-hua , Yang Jue-shen , Xiang Hai-yan , Xu Jia-jun
Published: May 2017

Purpose: Postconditioning, a series of brief ischemia-reperfusion sequences given before an ischemic heart undergoes sustained reperfusion, has been shown to lessen ischemia/reperfusion injury. The current study establishes a rabbit model of myocardial ischemia-reperfusion and studied the effects of pulmonary remote postconditioning in this model.

Methods: Serum levels of creatine kinase (CK), superoxide dismutase (SOD), and malondialdehyde (MDA), protein expression of endothelial nitric oxide synthase (eNOS), Rho kinase (ROCK- 2), and protein kinase B (Akt) in myocardial cells and the apoptosis index of myocardial cells were examined.

Results: Pulmonary remote postconditioning decreased CK, significantly decreased MDA, and increased SOD. Postconditioning significantly increased eNOS protein expression. Administration of eNOS inhibitor, L-NAME, dramatically suppressed the postconditioning-induced eNOS protein expression and serum SOD level, but significantly increased MDA level. The two longer sessions of postconditioning increased Akt, although this increase was not accompanied by changes in levels of the Akt inhibitor, ROCK-2. Blocking eNOS activity with L-NAME had no visible effect on either Akt or ROCK-2.

Conclusion: Our results suggest a role for Akt in remote postconditioning-induced myocardial protection, but do not support an involvement of eNOS in Akt-mediated action.
High prevalence of abnormal gastrointestinal permeability in moderate-severe asthma
Authors: Walker John , Dieleman Levinus , Mah Dennell , Park Kyungran , Meddings Jon , Vethanayagam Dilini
Published: May 2017

Purpose: Abnormal gastrointestinal permeability (GIP) has been implicated in a number of diseases, including chronic intestinal inflammatory disorders such as Crohn’s as well as non-intestinal immunologic diseases such as diabetes and multiple sclerosis. Although evidence in the literature demonstrates mucosal abnormalities of the digestive barrier in asthma, previous studies have assessed only colonic permeability, while ignoring the mucosal-associated lymphoid tissue (MALT) rich areas of the small intestine. Alterations in GIP may lead to increased entry of allergenic proteins from the gut lumen into the systemic circulation, thus priming and activating the adaptive immune system and leading to inappropriate allergen sensitization and/or deregulated extra-intestinal inflammation. This study examines GIP in adults with moderate to severe asthma.

Methods: Patients ingested a mixed-sugar solution and urine was collected. GIP was assayed using high-performance liquid chromatography. Demographics, atopy (assessed by allergen skin testing) and sputum cell counts were also assessed.

Results: Fourteen patients with moderate to severe asthma were studied, half of whom were found to have abnormal GIP. Abnormal GIP did not correlate with sputum cell counts and there was no apparent association between atopy and intestinal permeability.

Conclusion: This study demonstrated our ability to identify abnormal GIP in the MALT-rich, immunogenic small intestine of patients with asthma. The absence of a correlation between airway inflammation and increased GIP suggests that these two parameters are not causally linked, but rather define distinct entities that could separately or sequentially be involved with the development and propagation of asthma over time.
Sepsis, mitochondrial failure and multiple organ dysfunction
Authors: Duran-Bedolla Josefina , Montes de Oca-Sandoval Marco A , Saldaña-Navor Vianey , Villalobos-Silva José A , Rodriguez Maria Carmen , Rivas-Arancibia Selva
Published: May 2017

Purpose: The purpose of this review is to consider the state of oxidative stress, failure of the antioxidant systems and mitochondrial failure as the main physiopathological mechanisms leading to multiple organ dysfunction during sepsis.

Principal findings: Sepsis is a clinical syndrome caused by a severe infection that triggers an exaggerated inflammatory response. Involved in the pathogenesis of sepsis are the activation of inflammatory, immune, hormonal, metabolic and bioenergetic responses. One of the pivotal factors in these processes is the increase of reactive species accompanied by the failure of the antioxidant systems, leading to a state of irreversible oxidative stress and mitochondrial failure.

In a physiological state, reactive species and antioxidant systems are in redox balance. The loss of this balance during both chronic and infectious diseases leads to a state of oxidative stress, which is considered to be the greatest promoter of a systemic inflammatory response. The loss of the redox balance, together with a systemic inflammatory response during sepsis, can lead to progressive and irreversible mitochondrial failure, energy depletion, hypoxia, septic shock, severe sepsis, multiple organ dysfunction and death of the patient.

Conclusion: Knowledge of the molecular processes associated with the development of oxidative stress should facilitate the development of effective therapies and better prognosis for patients with sepsis and organ dysfunction.
The Effects of Pomegranate and Carvacrol on Methotrexate-Induced Bone Marrow Toxicity in Rats
Authors: Şen Velat , Bozkurt Mehtap , Söker Sevda , Ece Aydın , Güneş Ali , Uluca Ünal , Söker Murat , Yel Servet , Kaplan İbrahim
Published: May 2017

Purpose: The aim of this study was to evaluate the effects of pomegranate (PMG) extract and carvacrol (CARV) on methotrexate (MTX)-induced oxidative stress and bone marrow toxicity.

Methods: Wistar albino rats (32 rats) were divided into four groups (n=8): Group 1 was control; Group 2 was given a single intraperitoneal injection of methotrexate (20 mg/kg); Group 3 was treated with carvacrol (73 mg/kg i.p.) one day before MTX (20 mg/kg i.p.) injection; and, Group 4 received a single dose of MTX (20 mg/kg i.p) while PMG was administered orally for seven days at 225 mg/kg. After animals were euthanized, blood samples were taken to evaluate hematological parameters and oxidative stress. In addition, the femur was cropped and bone marrow was extracted for examination.

Results: White blood cell count, hemoglobin, hematocrit and platelet count were found to be decreased in the MTX group, but these changes were prevented in the groups that received CARV and PMG. Furthermore, decreased bone marrow cellularity was found in the groups treated with MTX, whereas the PMG and CARV groups had cellularity similar to controls. Strikingly, oxidative stress increased in the MTX group, but was ultimately decreased in the rats that received the antioxidants PMG and CARV.

Conclusion: Carvacrol and PMG were found to be protective against methotrexate-induced oxidative bone marrow damage. Use of these antioxidants, in combination with chemotherapeutics, may help to reduce some adverse effects of methotrexate.
The effects of oral isotretinoin (13-Cis retinoic acid) on the inner ear: A prospective clinical study
Authors: Akdag Mehmet , Akkurt Zeynep M , Gul Aylin , Ucmak Derya , Yılmaz Beyhan , Sengul Engin , Topcu Ismail
Published: May 2017

Purpose: The purpose of this study was to investigate the effect of oral isotretinoin, a drug used in the treatment of acne vulgaris, on hearing function determined by serial audiology examinations.

Methods: Forty patients with acne vulgaris were included in this study. Nine patients were excluded from the study because of inconsistent follow-up. The hearing of each participant was tested with pure tone audiometry and transient evoked autoacoustic emissions before and two and four weeks after treatment with isotretinoin (0.3-0.6 mg/kg/day) in the remaining 31 patients (62 ears).

Results: The differences between the mean values of the pre-treatment and post-treatment pure tone hearing thresholds at 1000, 2000, 4000 and 6000 Hz frequencies were statistically significant (p < 0.05), but there was no significant difference between the pre-treatment and post-treatment values at 250 and 500 Hz frequencies (p > 0.05). The difference between the pre-treatment and post-treatment signal–noise ratio values of the transient evoked autoacoustic emissions was not significantly different (p > 0.05).

Conclusion: Our results suggest that the use of isotretinoin may cause bilateral hearing threshold changes. Further animal and human studies are required to investigate and characterize isotretinoin-induced neurophysiological alterations in hearing.
Low-dose ketamine pretreatment reduces oxidative damage and inflammatory response following CO2 pneumoperitoneum in rats
Authors: Xingwei Xu , Xin Gao , Peng Zheng , Tao Feng , Bowen Ding , Xiaoming Kao , Wu Ji , Ning Li , Jieshou Li
Published: May 2017

Purpose: The duration of pneumoperitoneum during laparoscopic procedures may contribute to post-surgical oxidative stress. Previous studies have shown that low-dose ketamine, an anesthetic with anti-inflammatory properties, protects various organs from ischemia-reperfusion injury. This study investigated the effects of low-dose ketamine on the overproduction of oxidants and the tissue damage caused by intra-abdominal pressure during CO2 pneumoperitoneum.

Methods: Male Sprague Dawley rats received a CO2 pneumoperitoneum of 15 mmHg and preceded by either low-dose ketamine (KP1, 5 mg/kg; KP2, 10 mg/kg) or 0.9% saline (PR, 3 ml). General anethesia was provided by pentobarbital and sevoflurane. The control group (CR) received an intraperitoneal saline injection and sham surgery. Three hours after pneumoperitoneum, serum concentrations of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), superoxide dismutase (SOD) and intestinal fatty acid binding protein (iFABP) were measured and liver, kidney, lung, and intestine were evaluated for tissue damage.

Results: The highest plasma MDA, TNF-α, IL-6 and iFABP values were observed at T1 (after 3 hours of pneumoperitoneum) in the PR group, followed by the KP1, KP2, and CR groups (P < 0.01). SOD concentrations showed an opposite trend and were highest in the CR group, followed by the KP2, KP1, and PR groups (P < 0.01). TNF-α concentration was significantly lower in the KP2 than the KP1 group (P < 0.05). Histopathologic scoring of organ sections demonstrated the lowest scores in the KP2 group, followed by the KP1 and PR groups, in an increasing order (P < 0.05).

Conclusion: Pretreatment with low-dose ketamine before general anaesthesia protects against potential oxidative damage and inflammatory response caused by CO2 pneumoperitoneum.
Sex/Gender Disparities in Randomized Controlled Trials of Statins: The Impact of Awareness Efforts
Authors: Farahani Pendar
Published: May 2017

Purpose: Studies have demonstrated gender differences in the burden of cardiovascular outcomes for patients with dyslipidemia. Progress in identification of the sex/gender composition in Randomized Controlled Trials (RCTs) is crucial for understanding the distribution of therapeutics effectiveness in the population according to sex/gender.
The purpose of this study was to investigate the evolving pattern of sex/gender disparity in participants of RCTs on statins between 1990 and 2010. A secondary objective was to evaluate changes in the pattern of the average age of participants of RCTs on statins between 1990 and 2010.

Methods: This review focused on RCTs on statins that reported participants’ numbers by sex/gender. Studies were identified from an initial PubMed search using several combinations of MeSH terms. The search was limited to the RCTs on adults in English-language publications. The dates for search were set between January 1, 1990 and December 31, 2010.

Results: In the 1990s, RCTs on statins with an average of more than 500 participants included 18.6% women [95% Confidence Interval (95% C.I.): 16.31%, 21.13%]. By the first decade of the 2000s, women comprised, on average, 31.45% [29.45%, 32.52% (95% C.I.)] of the total cohort of RCTs with more than 500 participants. Regression analysis illustrated a significant increase in the recruitment of women for RCTs of statins (p-value < 0.01). Furthermore, analysis of the average age of participants illustrated a significant trend (p-value = 0.03) towards an increase in the average age of the participants in RCTs on statin between 1990 and 2010: the average age of participants in the 1990s was 58 years [56, 60 (95% C.I.)] and in the 2000s it was 62 years [56, 60 (95% C.I.)].

Conclusion: This study demonstrates significant progress in the inclusion of women in RCTs on statins. This finding reflects the efforts of different agencies and groups to increase the representation of women in clinical trials.
Dipeptidyl peptidase-4 inhibition improves left ventricular function in chronic kidney disease
Authors: Connelly Kim A , Bowskill Bridgit B , Advani Suzanne L , Thai Kerri , Chen Li-Hao , Kabir M Golam , Gilbert Richard E , Advani Andrew
Published: May 2017

Purpose: Heart failure with preserved ejection fraction (HFpEF) is a common comorbidity in people with chronic kidney disease (CKD) for which no evidence-based treatment currently exists. Recently, a group of anti-hyperglycemic agents used in the treatment of Type 2 diabetes, termed incretin-based therapies, have come under scrutiny for their putative glucose-independent effects on cardiac function. In the present study, the actions of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of incretin-based therapy in preventing HFpEF induced by chronic renal impairment were investigated.

Methods: Sham-operated and subtotally-nephrectomized rats were randomized to receive the DPP-4 inhibitors, linagliptin or sitagliptin for seven weeks before assessment of cardiac and renal structure and function.

Results: Analysis of pressure-volume loops revealed that both linagliptin and sitagliptin prevented the development of cardiac diastolic dysfunction, with cardiac collagen I synthesis also being reduced by DPP-4 inhibition. These attenuating cardiac effects occurred without change in renal function or structure where, in the doses administered, neither linagliptin nor sitagliptin affected GFR decline, proteinuria, renal fibrosis or the increased urinary excretion of biomarkers of renal toxicity.

Conclusion: The beneficial cardiac effects of DPP-4 inhibition, in the absence of a concurrent improvement in renal dysfunction, raise the possibility that these agents may confer cardiovascular advantages in the CKD population.
Prior ischemic stroke is not associated with worse clinical outcomes in patients undergoing percutaneous coronary intervention
Authors: Zhang Ming , Guddeti Raviteja R , Wang Shao-ping , Wang Jian , Xin Man-kun , Chen Shu-Juan , Kang Jun-Ping , Lv Qiang , Ma Chang-Sheng , Liu Jing-Hua
Published: May 2017

Purpose: Cerebrovascular accidents (CVAs) frequently coexist with coronary artery disease (CAD) and adversely affect prognosis in patients with CAD; however, fewer studies have investigated the role of prior ischemic stroke on the outcomes of percutaneous coronary intervention (PCI). The aim of this study was to determine the safety and effectiveness of PCI in patients with a prior ischemic stroke.

Methods: A review of patients who underwent PCI between June 2003 and September 2005 (n=3893) at the Beijing Anzhen Hospital of Capital University of Medical Science, identified 295 PCI patients with a prior ischemic stroke (≥3 months) and 3598 patients without a prior stroke. To investigate whether prior history of an ischemic stroke was independently associated with increased risk of adverse PCI outcomes, prognostic parameters were analyzed using univariate analysis and Cox multivariate regression analysis. Propensity score analysis was then used to match the two subgroups of patients based on multiple factors known to impact cardiac outcome.

Results: Patients with a prior ischemic stroke had more frequent high-risk baseline characteristics (diabetes, hypertension, hyperlipidemia and prior myocardial infarction). No significant differences were found in the major adverse cardiac and cerebrovascular event (MACCEs) rates between the two groups (1.7% in the stroke group vs. 1.4% in the non-stroke group; p=0.06). Diabetes mellitus, triple vessel CAD, number of diseased vessels, chronic total occlusion and previous myocardial infarction were independent predictors of MACCE in patients with prior stroke undergoing PCI.

Conclusions: This study demonstrates that, in daily clinical practice, PCI can be provided safely and with good results to patients with a prior ischemic stroke (≥3 months).
Hypovitaminosis D in Children with Familial Mediterranean Fever
Authors: Yilmaz Resul , Karaaslan Erhan , Ozer Samet , Sonmezgoz Ergun , Kazanci Nafia O , Cakan Nursen , Akbas Ali
Published: May 2017

Purpose: Vitamin D deficiency or insufficiency plays a role in the initiation and perpetuation of certain autoimmune diseases. The purpose of this study was to measure the vitamin D status of children with Familial Mediterranean Fever (FMF) and compare it to their healthy peers.

Methods: A total of 50 FMF patients and 49 healthy children were enrolled in this prospective study. Vitamin D levels were measured via HPLC. Demographic data, FMF symptom severity scores and the levels of other disease activity markers were retrieved from our hospital database.

Results: The mean age and gender balance of patients and controls were similar, being 8.4±3.8 years and 19 male patients, and 9.1±3.0 years and 25 male controls, respectively. The mean 25(-OH) vitamin D3 levels were 15.94±9.66 µg/L in FMF patients and 41.22±21.31 µg/L in controls. Vitamin D levels were normal in 12% of FMF patients, insufficient in 62% and deficient in 26%. No vitamin D deficiency was evident in any control subject; 30% had insufficient and 70% had normal vitamin D levels. Plasma vitamin D3 levels were similar in all patients despite varying FMF symptom severity scores.

Conclusions: Vitamin D deficiency is frequent in children with FMF but is not associated with disease severity score.
Chemical processing and shampooing impact cortisol measured in human hair
Authors: Hoffman M Camille , Karban Laura V , Benitez Patrick , Goodteacher Angela , Laudenslager Mark L
Published: May 2017

Purpose: The assessment of cortisol in hair has gained popularity as a means to measure retrospective hypothalamic-pituitary-adrenal activity in a number of species; however, cortisol levels from human hair subjected to typical chemicals for cosmetic or hygienic purposes may be altered by the chemicals used. The purposed of this study was to determine if exposure of hair to chemical processing or shampooing impacts cortisol values.

Methods: Human hair not exposed to prior chemical processing was cut from the posterior vertex region of the head of 106 human subjects as close to the scalp as possible. The hair sample was divided into 4-6 full-length clusters depending on quantity of hair available. Each hair sample was processed for baseline (native) cortisol and remaining clusters were exposed to five standard chemical hair treatments (Experiment 1) or were shampooed 15 or 30 times (Experiment 2). Hair was ground and cortisol levels were determined by enzyme immunoassay (EIA). Comparisons were made between native hair and processed hair using paired t-tests and Pearson correlation.

Results: Hair cortisol as assessed by EIA was significantly altered by chemical processing but in somewhat different ways. Exposure to bleach (harshest exposure), demi-perm (least exposure) or 15-30 shampoos resulted in a significant decrease in cortisol level while exposure to varying percentages of peroxides increased cortisol measured. There were no differences in cortisol levels associated with sex, age or tobacco use in the native hair for this particular group.

Conclusion: Chemical processing and frequent shampooing affect cortisol levels measured in hair. Chemically processed or excessively shampooed hair should be avoided when recruiting subjects for hair cortisol studies.
Dress and deportment of medical residents: Formal or informal?
Authors: Reid David RJ , Makinde Kehinde A , Wilson Merne P , PausJenssen Anne M , Barton James W , Wilson Thomas W
Published: May 2017

Purpose: Health care workers, including physicians, have adopted more casual dress. The appearance of a physician may influence patients’ opinion of physician knowledge, competence and trustworthiness. We hypothesized that medical inpatients and outpatients would rate these attributes higher in residents who dressed and acted in a more formal manner.

Methods: Prospective cohort included both inpatients and outpatients. One hundred thirty three patients, aged 62.3±16 years, 49% of whom were female, were surveyed. One of two male resident physicians approached each patient, ostensibly to obtain consent to a brief mini-mental status examination. The physician was dressed, and acted, either “formally” (F) or “informally” (I). Patients then completed a six item questionnaire, using a 5 point Likert scale, to assess their confidence in the resident. Total scores could be 6 to 30. Total scores were compared using one-way ANOVA.

Results: Patients’ perceptions were high for both F and I: 25.5±3.1 vs. 24.1±3.0, respectively (p=0.013). This difference was driven by the “labcoat” question: patients generally preferred physicians to wear a labcoat (3.9±1.0 vs. 2.8±1.3, p < 0.0001). Responses to four of the other fivequestions were numerically, but not statistically, higher in F. There was no difference in preference between the tworesidents: 24.6±2.8 vs. 24.9±3.5, p=0.56.

Conclusion: More formal dress and demeanor by residents leads to a modest, but significant, increase in patient perception of the resident’s value. Wearing a white lab coat, in particular, has a positive effect.