bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxicity of natural extract from Tegillarca granosa on ovarian cancer cells is mediated by multiple molecules
Authors: Gao Ming-Qing , Han Yan-Tao , Zhu Li , Chen Shou-Guo , Hong Zhen-Yu , Wang Chun-Bo
Published: May 2017

Purpose: To determine the cellular and molecular mechanism of cytotoxicity induced by Haishengsu (HSS), nature extract from Tegillarca granosa, toward human ovarian cancer cell lines SKOV-3 and OVCAR-3.

Methods: The cytotoxic effects of HSS on two ovarian cancer cell lines were tested by XTT assay. Cell apoptosis and cell cycle arrest induced by HSS were demonstrated by DNA ladder assay and flow cytometric analysis, respectively. RT-PCR or flow cytometric analysis was used to investigate the expression of bcl-2, caspase-3, p53, ?-catenin, E-cadherin, CD24, and CD44.

Results: Continuous exposure to HSS for 48 h produced cytotoxic effects on both cell lines in a concentration dependent manner, which was accompanied by apoptosis and cell cycle arrest. Apoptosis associated gene bcl-2 and caspase-3, tumor metastasis associated gene ?-catenin, but not E-cadherin, and CD24, but not CD44, were involved in the effect of growth inhibition induced by HSS. Although p53 mediated apoptosis induced by HSS in OVCAR-3 cells, it was not required in SKOV-3 cells.

Conclusion: HSS has a potential cytotoxic effect on human ovarian cancer cells, which was mediated by multiple signal molecules including bcl-2, caspase-3, ?-catenin, and CD24. These findings will provide a theoretical basis for HSS’s potential clinical application as a novel marine anti-cancer agent.
Liver X Receptors as potential therapeutic targets in atherosclerosis
Authors: Zhu Yanfei , Li Yousheng
Published: May 2017

Purpose: Atherosclerosis is the primary independent risk factor of cardiovascular disease, and Liver X Receptors (LXR? and LXR?) activation may play an anti-atherosclerosis effect. In this article, we summarize the current state of knowledge of roles of LXRs in physiology and homeostasis as well as the links between LXR action and atherosclerosis, and discuss the potential therapeutic effects of LXR agonists.

Source: A MEDLINE database search was performed to identify relevant articles using the keywords “liver X receptors”, “LXRs”, and “atherosclerosis”. Additional papers were identified by a manual research of the references from the key articles.

Principle findings: Both LXR isoforms promote reverse cholesterol transport (RCT) and have anti-inflammatory activity. LXR? is the predominant receptor in the liver regulating triglyceride synthesis. The antiatherosclerotic ability of LXRs makes them attractive targets for drugs for the treatment of cardiovascular disease. However, LXR activation induces lipogenesis and hypertriglyceridemia. The first-generation synthetic ligands of LXR increase hepatic lipogenesis and plasma triglyceride levels. New LXR ligands need to be designed without undesirable side effects.

Conclusion: LXR ?-selective agonists and LXR modulators, which act as agonists in macrophages and induce cholesterol efflux while as antagonists of lipogenesis in the liver, are two critical and attractive approaches to treat atherosclerosis and cardiovascular diseases.
CSCI/RCPSC HENRY FRIESEN LECTURE: Clinical research in Canada: the dawn of a new era?
Authors: Rouleau Jean L
Published: May 2017

In response to the growing gap between discovery and the optimal application of medical advancements to health care delivery, countries the world over have developed large and well funded programs to reduce these gaps. Although these programs vary in nature, they have generally largely focused more on reducing the gap in bench to bedside research. Canada’s strong biomedical and patient oriented research (POR) community has a strong base from which to build, but requires support in order to fill the missing elements needed to take full advantage of the important unmet needs in health related research. In Canada, a coalition of funders of medical research, led by the Canadian Institutes for Health Research (CIHR) is developing a large and comprehensive program to build a Canadian infrastructure that will provide these missing elements, and further strengthen POR in Canada. This coalition proposes to put particular emphasis on bedside to community POR, including phase 3 clinical trials, to take advantage of and improve the sustainability of Canada’s unique universal health care system. The major initiatives in POR developed by so many countries, including Canada clearly heralds a new era in clinical research, one that the Canadian research community needs to take full advantage of.
CIM: Beyond a new start
Authors: Gan Bing Siang
Published: May 2017

This issue marks the last edition of Clinical and Investigative Medicine under the leadership of Dr. David Bevan. Dr. Bevan has been the Editor-in-Chief of CIM for the past six years. During this time, CIM, as the official journal of the Canadian Society for Clinical Investigation, underwent several major changes. First, CIM was bought from the CMA and is now independently produced. Second, CIM went from a hard copy journal to an on-line journal with open access six months after publication of each issue. Third, the journal now levies publication page charges from its authors with members of CSCI exempted from these charges. Dr. Bevan succeeded in not only maintaining CIM as a MedLine and PubMed referenced journal, but also in increasing its prominence as an open access type on-line journal, while at the same time turning around its finances. The number of submissions to CIM has more than doubled since CIM instituted these changes, and CIM went from a deficit journal to making a small profit: a true great beginning of a new era for CIM. We thank Dr. Bevan for his important contributions.

With the retirement of Dr. Bevan, CSCI is happy to announce that Dr. Jonathan Angel from Ottawa will take over from Dr. Bevan as Editor-in-Chief from January 1, 2010. Dr. Angel is a Professor of Medicine at the University of Ottawa and a recognized expert in infectious diseases. He is widely published and brings a wealth of expertise to CIM. Under the stewardship of Dr. Angel, CIM will build on the foundation laid by Dr. Bevan and will continue to publish high quality original research related to any aspect of clinical investigation. At CSCI, we are all looking forward to working with Dr. Angel to increase CIM’s scope and impact factor. We are convinced that Dr. Angel will have a successful tenure at CIM and look forward to seeing the Journal grow further.
Exercise capacity of children with pediatric lung disease
Authors: Zavorsky G S , Kryder J R , Jacob S V , Coates A L , Davis G M , Lands L C
Published: May 2017

Background: Pulmonary function of children with cystic fibrosis (CF) and bronchopulmonary dysplasia (BPD) is similar at rest even though the mechanisms of injury differ. We sought to compare the peak exercise responses in children with BPD versus CF while controlling for pulmonary impairment, nutritional status, gender, age, height, and predicted forced expired volume in 1 second (~73% of predicted).

Methods: Nine BPD children and 9 CF children underwent spirometry and a progressive exercise test to maximum on a cycle ergometer.

Results: There was no difference between groups in body mass percentile (CF:97 ± 13%, BPD: 98 ± 11%), peak power output (Wpeak) (CF:67 ± 19 W, BPD:73 ± 28 W), % predicted Wpeak (CF:83 ± 28%, BPD:88 ± 15%), peak oxygen uptake (VO2peak, CF: 38 ± 7 ml/kg/min, BPD: 39 ±6 ml/kg/min), or % predicted VO2peak (CF:99 ± 16 %, BPD:96 ± 27%).

Conclusions: Children with mild pulmonary impairments are able to achieve a near normal peak power output and a normal VO2peak. Neither the aetiology nor the developmental onset of the process appears to be important influences on VO2peak or Wpeak.
Prognostic value of CRM1in pancreas cancer
Authors: Huang Wei-yi , Yue Lu , Qiu Wen-shen , Wang Li-wei , Zhou Xiao-han , Sun Yuan-jue
Published: May 2017

Purpose: Pancreatic cancer is a highly aggressive malignant tumour with poor prognosis. The median survival is only 6 months. This study investigated the prognostic value of nuclear export protein chromosomal region maintenance/exportin 1/Xpo1 (CRM1) expression in pancreas cancer.

Methods: CRM1 expression was detected, by Western blot, in pancreatic tissue from 69 cancer patients and 10 normal subjects.

Results: CRM1 showed increased expression in pancreatic cancer tissue (P = 0.007). The high expression of CRM1 was associated with increased serum levels of CEA (P = 0.002) and CA19-9 (P = 0.005). There was an association between CRM1 expression and tumour size (P = 0.01), lymphadenopathy (P = 0.004) and liver metastasis (P = 0.003). High CRM1 expression was not correlated with the other clinicopathological parameters. High CRM1 expression was a prognostic indicator for progression-free survival (PFS) (P = 0.006) as well as overall survival (OS) (P = 0.001). Expression of CRM1 was an independent prognostic parameter for poorer PFS and OS (95% CI, 1.27–5.39).

Conclusions: CRM1 expression demonstrated prognostic value in pancreatic cancer. Prospective studies are required to determine the prognostic role of high expression of CRM1 in pancreatic cancer.
CETP IN RARE DYSLIPIDEMIAS
Authors: Al-Sarraf A , Sachs-Barrable K , Hill J , Wasan K , Frohlich J
Published: May 2017

Objective: To determines CETP mass and activity in rare disorders of HDL metabolism.

Methods: Patients: Fasting plasma samples were obtained from two individuals with TD and from patients with LCAT deficiency, analphalipoproteinemia, Hepatic lipase deficiency (HL), vasculitis, and hypoalphalipoprteinemia. Their clinical and laboratory findings have been previously reported.

Assay: CETP activity was measured using commercial CETP Fluorescence kit (Roar Biomedical Inc., New York, NY). The kit includes donor (without apoA-I) and acceptor lipoprotein particles. Incubation of donor and acceptor with a CETP source results in the CETP mediated transfer of fluorescent neutral lipid from donor to acceptor, rate of which is determined by the increase in fluorescence intensity as the fluorescent neutral lipid is removed from the donor to the acceptor. The amount of fluorescent substrate transferred was expressed as pmoles of fluorescent substrate transferred within 3 hours. CETP concentration was measured by ELISA using specific rabbit antibody against human CETP.

Results: While CETP mass correlated with serum HDL-C levels, the activity decreased in patients with LCAT deficiency, FED, HL deficiency and vascultis, but increased in TD. We speculate that the composition of HDL particles in these disorders differs and results in the different CE transfer rates.

Conclusion: CETP mass correlates with the HDL-C concentration but the activity differ widely among the patients with rare disorders of HDL metabolism, probably due to the changes in HDL quality.
CHARACTERIZATION OF A NEW LCAT MUTATION CAUSING FAMILIAL LCAT DEFICIENCY (FLD) AND THE ROLE OF APOE AS A MODIFIER GENE OF THE FLD PHENOTYPE
Authors: Baass A , Wassef H , Tremblay M , Bernier L , Dufour R , Davignon J
Published: May 2017

Introduction: LCAT (lecithin:cholesterol acyltransferase ) is an enzyme which plays an essential role in cholesterol esterification and reverse cholesterol transport. Familial LCAT deficiency (FLD) is a disease characterized by a defect in LCAT resulting in extremely low HDL-C, premature corneal opacities, anemia as well as proteinuria and renal failure.

Method: We have identified two brothers presenting characteristics of familial LCAT deficiency. We sequenced the LCAT gene, measured the lipid profile as well as the LCAT activity in 15 members of this kindred. We also characterized the plasma lipoproteins by agarose gel electrophoresis and size exclusion chromatography and sequenced several candidate genes related to dysbetalipoproteinemia in this family.

Results: We have identified the first French Canadian kindred with familial LCAT deficiency. Two brothers affected by FLD, were homozygous for a novel LCAT mutation. This c.102delG mutation occurs at the codon for His35 causing a frameshift that stops transcription at codon 61 abolishing LCAT enzymatic activity both in vivo and in vitro. It has a dramatic effect on the lipoprotein profile, with an important reduction of HDL-C in both heterozygotes (22%) and homozygotes (88%) and a significant decrease in LDL-C in heterozygotes (35%) as well as homozygotes (58%). Furthermore, the lipoprotein profile differed markedly between the two affected brothers who had different APOE genotypes. We propose that APOE could be an important modifier gene explaining heterogeneity in lipoprotein profiles observed among FLD patients. Our results suggest that a LCAT-/- genotype associated with an APOE ?2 allele could be a novel mechanism leading to dysbetalipoproteinemia.
UNE HYPERLIPIDÉMIE SECONDAIRE A NE PAS OMETTRE
Authors: Chouiali Ahlem , Jean Dubé
Published: May 2017

Introduction: Devant une perturbation du bilan lipidique chez un enfant dont l’un des parents est connu pour hypercholestérolémie familiale (HF), le diagnostic repose sur deux arguments : les LDL > 95e percentile et la présence de xanthomes tendineux chez le parent. Toutefois, une hyperlipidémie type IIb peut orienter le diagnostic vers une cause secondaire.

Objectif: Reconnaitre une cause secondaire d’hyperlipidémie mixte dans un contexte d’histoire familiale d’hypercholestérolémie familiale (HF).

Observation: Nous rapportons l’observation de deux frères d’âge respectifs de 8 et 10 ans, d’origine canadienne française, ayant une histoire familiale d’HF. L’enfant de 10 ans asymptomatique, présentait une hyperlipidémie type IIa compatible avec un diagnostic d’HF hétérozygote alors que l’enfant de 8 ans présentait un type IIb. Un bilan sanguin d’extension chez ce dernier orientait le diagnostic vers une cause secondaire. L’absence de mutation du récepteur à LDL renforçait encore plus ce diagnostic. Après traitement étiologique de trois mois, normalisation du bilan lipidique sans que le patient ait recours a une statine. Cette évolution favorable est consolidée depuis trois mois.

Conclusion: Une dyslipidémie de cause secondaire peut mimer une HF chez un patient avec une histoire familiale positive. Le traitement de l’étiologie corrige la dyslipidémie sans recours aux statines.
A NEW CAPILLARY ZONE ELECTROPHORESIS METHOD FOR THE SCREENING OF CONGENITAL DISORDERS OF GLYCOSYLATION (CDG)
Authors: Parente F , Ah Mew N , Jaeken J , Gilfix B M
Published: May 2017

Background: The Congenital Disorders of Glycosylation (CDG) are an expanding group of
metabolic diseases with a broad clinical presentation. We sought to validate a new Capillary Zone Electrophoresis (CZE) method (Sebia CAPILLARYS™ CDT) to screen for CDG.

Methods: We analyzed 119 serum samples from children of varying ages and of both sexes to establish a reference range of transferrin glycoforms including CDT (Carbohydrate Deficient Transferrin). We then studied serums from 8 known CDG patients and compared the CZE results to the isoelectric focusing (IEF) profiles. We also analyzed serums after extraction from spotted Guthrie cards.

Results: The mean (SD) percentage of transferrin glycoforms is 18.5 (4.4), 78.5 (4.2), 2.5 (1.3) and 0.6 (0.3) for penta-, tetra-, trisialotransferrin and CDT, respectively. There is no statistically significant difference between the different age groups analyzed (0-5, 6-11, 12-15, 16-18, and > 18 years) or between sexes. We observed a good correlation between the CZE and IEF profiles with both fresh serum and serum extracted from Guthrie cards.

Conclusions: The Sebia CAPILLARYS™ CDT system is a simple and reliable method to screen for CDG in pediatric and adult patients with an unexplained clinical syndrome, particularly when the nervous system is involved.
CD133+ human pulmonary adenocarcinoma cells induce apoptosis of CD8+T cells by highly expressed galectin-3
Authors: Li Wan , Jian-jun Wang , Xue-Feng Zhou , Feng Zhao
Published: May 2017

Purpose: To investigate the expression and function of Galectin-3 (Gal-3) in CD133+ pulmonary adenocarcinoma.

Methods: CD133+ pulmonary adenocarcinoma cells were separated by MACS from excised pulmonary adenocarcinoma specimens of 11 patients. The percentage of CD133+ cells in different cells population was determined by flow cytometry (FCM). Expression of Gal-3 in cancer cells was detected by Fluorescence Quantitation RT-PCR (FQRT-PCR) and Western blot whereas extracellular expression was detected by ELISA. CD133+ cells were transfected with Gal-3 specific siRNA to explore the affects of Gal-3 inhibition on cancer cell growth and induction of CD8+ T cell apoptosis.

Results: Cells expressing CD133 constituted 90% of the CD133+ subpopulation after separation by MACS whereas they made up only 1.2% of the unsorted cell population. Expression of Gal-3 was 1.24 fold, 1.5 fold and 2 fold higher in CD133+ cells than in CD133– cells as detected by FQRT-PCR, Western blot and ELISA respectively (p < 0.05 for each). The supernatants of CD133+ cells induced apoptosis of CD8+ T cells to a greater degree (27.1±2.6%) compared with supernatants from CD133– cells (10.1±2.2%), and could be down-regulated by lactose, anti-galectin-3 polyclonal antibody and Gal-3 siRNA. Downregulation of Gal-3 resulted in significant inhibition of cancer cell growth in vitro.

Conclusion: Gal-3 is expressed at a relatively higher level in CD133+ lung adenocarcinoma cells and could induce CD8+ T cell apoptosis in vitro, both of which could be down-regulated by Gal-3 siRNA. These findings indicate that Gal-3 may play an important role during oncogenesis, implying a potential therapeutic target for pulmonary adenocarcinoma.
Scientific Overview of the CSCI-CITAC 2009 Conference
Authors: Ong Tone Stephan , Dugani Sagar , Marshall Harry , Shamji Mohammed Farid , Murray Jean-Christophe , Bossé Dominick
Published: May 2017

From September 21st-23rd 2009, the Clinical Investigator Trainee Association of Canada – Association des cliniciens-chercheurs en formation du Canada (CITAC-ACCFC) and the Canadian Society for Clinician Investigators (CSCI), held their annual conference in Ottawa. Participants included clinician investigators and trainees from across the country.

The conference featured many excellent guest speakers including this year’s recipient of the Henry G. Friesen International Prize in Health Research, Sir John Bell. There were several forums focusing on professional development, with topics such as “sustaining the clinician investigator in Canada”, “succeeding as a clinician investigator”, and “collaborating internationally with MD+ trainees”, alongside networking opportunities to help establish relationships with potential mentors and collaborators. Further, the CSCI-CITAC annual conference featured some of the cutting edge research that MD+ trainees throughout Canada are engaged in. Trainees presented their research either at the Young Investigators Forum poster session or at the oral plenary.

This scientific overview aims to highlight some of the research presented by trainees at the annual conference. The broad themes of scientific interest included topics from both basic science and clinical research. In this article, we summarize some of the major research questions that are being investigated by clinician-investigator trainees in the following areas: neurological sciences, cell biology, medicine, immunology, obstetrics, gynecology, neonatology, orthopedics, rheumatology, and public health.
Survol du programme scientifique du congrès annuel de la SCRC-ACCFC 2009
Authors: Ong Tone Stephan , Dugani Sagar , Marshall Harry , Shamji Mohammed Farid , Murray Jean-Christophe , Bossé Dominick
Published: May 2017

Du 21 au 23 septembre 2009 a eu lieu à Ottawa le congrès annuel de l’Association des cliniciens-chercheurs en formation du Canada – Clinical Investigator Trainee Association of Canada (ACCFC-CITAC) et de la Société canadienne de recherche clinique (SCRC). Parmi les participants se trouvaient des cliniciens-chercheurs et des étudiants en provenance des quatre coins du pays.

Cette conférence mettait à l’avant-plan des invités de marque, dont le récipiendaire actuel du Prix international de la recherche en santé Henry G. Friesen, Sir John Bell. Plusieurs tables rondes entourant le développement professionnel s’y tenaient, avec des sujets tels que « le support des cliniciens-chercheurs canadiens », « le succès des cliniciens-chercheurs » et « la collaboration internationale des MD+ en formation », tout en donnant l’opportunité d’établir des liens avec des mentors et collaborateurs potentiels. De plus, le congrès annuel de l’ACCFC-CITAC mettait en vedette plusieurs recherches impliquant des MD+ en formation à travers tout le Canada, dans le cadre de la séance de présentation par affiches du Forum des jeunes chercheurs ou lors de la séance plénière.

Ce survol vise à mettre en évidence certaines des recherches présentées par les chercheurs en formation lors de la conférence annuelle, autant sur le plan de la recherche fondamentale que de la recherche clinique. Dans cet article, nous résumons les principales questions de recherche abordées par ces cliniciens-chercheurs en formation dans les disciplines suivantes : neurosciences, biologie cellulaire, médecine, immunologie, obstétrique, gynécologie, néonatalogie, orthopédie, rhumatologie et santé publique.
Association between TNF-α, TGF-β1, IL-10, IL-6 and IFN-γ gene polymorphisms and generalized aggressive periodontitis
Authors: Erciyas Kamile , Pehlivan Sacide , Sever Tugce , Igci Mehri , Arslan Ahmet , Orbak Recep
Published: May 2017

Objective: The aim of this study was to investigate links among cytokine genetic variants and generalized aggressive periodontitis (GAgP).

Methods: Thirty-five patients with generalized aggressive periodontitis and 85 healthy controls without periodontitis were included in the study. Probing depth (PD), clinical attachment loss (CAL), plaque index (PI), and gingival index (GI) were recorded as clinical parameters. Polymorphisms of IL-6, IL-10, IFN-γ, TGF-ß1 and TNF-α gene were analysed using the polymerase chain reaction sequence-specific primer method (PCR-SSP).

Results: No significant differences were observed for IL-6, IL-10, IFN-γ, and TGF-ß1 cytokine polymorphisms, from the genotype distribution and allele frequency, between GAgP and healthy control groups. In contrast, significant differences were observed in the TNF-α gene polymorphism between GAgP and healthy control groups (P = 0.002).

Conclusion: Our data suggest that TNF-α (-308) may be associated with the development of generalized aggressive periodontitis. These results should be replicated in a larger and more diverse population of patients diagnosed with generalized aggressive periodontitis to determine of these findings are generalizable.
Peak expiratory flow values are higher in older and taller healthy male children: An observational study
Authors: Radziavicius Fernanda R , Martins Lourdes C , Radziavicius Camilla C , Valenti Vitor E , Siqueira Arnaldo AF , De Souza Cíntia G , De Abreu Luiz C
Published: May 2017

Purpose: Peak expiratory flow (PEF) was measured in healthy children aged five to ten years in order to provide baseline values and to determine correlations between PEF and factors such as gender, age and type of school.

Methods: After the Ethical Committee of Research in Human of the School of Medicine of ABC – FMABC approval, PEF and height were measured in 1942 children between five and ten years old from nine public schools and nine private schools throughout São Bernardo do Campo City. PEF was measured using the Mini-Wright Peak Flow Meter (Clement Clarke International Ltd.) and. height was measured using a Sanny professional stadiometer .

Results: Significant differences were found in values for PEF: higher values were seen in older students in comparison with younger students, in males in comparison with females and in students from private schools in comparison with public schools, with average values ranging from 206 L/min to 248 L/min,. Linear correlations were seen for PEF values with both height and age (Spearman Coefficient).

Conclusions: Differences were seen for PEF between genders and between types of school, and a linear correlation was seen for PEF with both age and height in healthy children from five to ten years old.
Primary care management for isolated limb injury: Referral to orthopedic surgery in a trauma center
Authors: Rouleau Dominique M , Parent Stefan , Feldman Debbie Ehrmann
Published: May 2017

Introduction: Musculoskeletal injuries affect up to 13% of adults annually. Despite this high incidence, quality of primary care, including analgesia, may be sub-optimal. The goal of this study is to describe the quality of primary care for ambulatory patients with isolated limb injury and to identify related factors.

Methods: A cross sectional study was undertaken prospectively on 166 consecutive ambulatory adult patients with isolated limb injury who presented to orthopedics service in a Level one Trauma Centre. Quality of care was assessed by evaluating analgesia, walking aids, immobilization, and quality of referral diagnosis according to actual expert recommendations.

Results: This study revealed low quality of primary care for 82 (53.2%) of injured patients. Seventy-three patients (50.3%) had pain level over 5/10 and 45 cases (28.5%) had insufficient/absent analgesia prescriptions. Fifty-one (32.3%) had unacceptable immobilization and 21/59 (35.6%) patients with a lower limb injury did not receive a walking aid prescription. A total of 61 patients (36.7%) had an absent or inadequate referral diagnosis. Factors associated with lower quality depended on the specific quality indicator and included: living further away from the hospital, younger age, initially consulting at another health care center, having a fracture, and being a smoker.

Conclusion: The high frequency of low quality of care underlines the necessity for orthopedic surgeons to be involved in primary care education. Identifying factors associated with lower quality of care will orient efforts to improve medical care of patients with isolated traumatic injury.
Comparison of the usefulness of plasma levels of oxidatively modified forms of albumin in estimating kidney dysfunction in diabetic patients
Authors: Piwowar Agnieszka , Knapik-Kordecka Maria , Warwas Maria
Published: May 2017

Purpose: Advanced oxidation protein products (AOPP) and ischemia-modified albumin (IMA) are forms of oxidatidatively modified albumin and have recently been investigated as indicators of oxidative stress. They are increased in different disorders, including diabetes mellitus, as a result of hyperglycaemia, oxidative stress and hypoxia. The usefulness of the plasma levels of these two parameters in estimating kidney dysfunction in type 2 diabetic patients (T2DM) was compared in this study.

Methods: Plasma levels of AOPP and IMA were determined spectrophotometrically in 218 individuals, 153 patients with T2DM and 65 healthy people.. The urinary albumin/creatinine ratio (UACR) was used as the reference to define the stage of kidney dysfunction by the assessment of the degree of albuminuria.

Results: Receiver Operating Characteristic (ROC) curve analysis, likelihood ratio (LR), and Youden’s index (J) revealed that AOPP and IMA had acceptable sensitivities and specificities in individuals with different degrees of albuminuria; however, AOPP had higher values of the area under the curve (AUC: 0.934) than IMA, as well as 100% sensitivity and 77.01% specificity for distinguishing patients with micro- and macroalbuminuria.

Conclusions: Both AOPP and IMA may be helpful clinical markers for estimating kidney dysfunction, but AOPP is better able to identify diabetic patients with nephropathy. We suggest that AOPP is almost ideal for discriminating between T2DM patients with micro- and macroalbuminuria.
Expression patterns of ClC-3 mRNA and protein in aortic smooth muscle, kidney and brain in diabetic rats
Authors: Fu Jianfang , Fu Jufang , Gao Bing , Wang Li , Zhang Nanyan , Li Xiaomiao , Ji Qiuhe
Published: May 2017

ClC-3, a member of the ClC family of voltage-gated chloride channels, regulates cell proliferation of cultured rat aortic vascular smooth muscle cells, pathogenesis of allergic rhinitis and tumor cell migration. However, its role in diabetic animals is still unknown. To address this issue, we investigated the expression patterns of ClC-3 in diabetic rats. Five-week-old Sprague-Dawley rats were divided into two groups, 50 non-diabetic control rats (non-DM) and 50 diabetic model rats (DM). ClC-3 mRNA and protein expression in aortic smooth muscle, kidney and brain tissues were examined by fluorimeter-based quantitive RT-PCR assay and Western blot analysis, respectively. ClC-3 mRNA and protein were endogenously expressed in aortic smooth muscle, kidney (cortex and medulla) and brain tissues of both control and streptozotocin-induced diabetic rats. ClC-3 mRNA and protein expression levels were significantly higher in aortic smooth muscle and brain tissues of diabetic rats, but significantly decreased in kidney medulla tissue, relative to non-DM controls..There were no significant differences in ClC-3 mRNA and protein expression in kidney cortex between non-diabetic control and diabetic rats. Furthermore, the altered ClC-3 expression patterns in diabetic rat aortic smooth muscle, brain, and kidney medulla tissues all correlated with the changes in blood glucose levels (p < 0.05). In conclusion, our data show for the first time that diabetes alters both the gene and protein expression of ClC-3 channels. These changes may contribute to the impaired vascular, brain and kidney functions observed in diabetes.
Protective effects of combined Mycobacterium bovis BCG and interleukin-12 vaccination on airway inflammation in a murine model of allergic asthma
Authors: Ke Xia , Huang Jiangju , Chen Quan , Hong Suling , Zhu Daoyin
Published: May 2017

Purpose. Allergic asthma is characterized by chronic airway inflammation and airway hyperresponsiveness driven by allergen-specific T helper (Th)2 cells. Mycobacterium bovis bacillus Calmette-Guérin (BCG) vaccination has been documented to suppress Th2 responses and allergic airway inflammation in animal models. Since interleukin (IL)-12 is capable of inhibiting Th2 responses, we sought to investigate whether IL-12 could function as an adjuvant to increase the efficacy of BCG vaccination against allergic asthma.

Methods. BALB/c neonatal mice (24 mice, 48-72 h old) were randomly divided into 3 subgroups (n = 8 for each group) to be immunized with PBS (control) or BCG with or without DNA plasmid-expressing IL-12. All of the mice were then sensitized and provoked with ovalbumin (OVA) to establish a model of allergic asthma.

Results. Mice vaccinated with BCG alone showed a significant reduction in airway inflammation, percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and serum OVA-specific immunoglobulin E (IgE) levels in comparison with control animals. The suppressive effects of BCG were substantially augmented by the combination with IL-12. Furthermore, a decreased IL-4 and increased interferon-gamma (IFN-γ) production in BAL fluid were observed in animals inoculated with BCG alone or with IL-12 relative to control animals.

Conclusion. Our data indicate that the combined vaccination with BCG and IL-12 yields a favorable outcome in prevention of experimental allergic airway inflammation, which is likely mediated through triggering a shift from a Th2 response to a Th1 response.
Hypersecretion of the α-subunit in clinically non-functioning pituitary adenomas: Diagnostic accuracy is improved by adding α-subunit/gonadotropin ratio to levels of α-subunit
Authors: Andersen Marianne , Ganc-Petersen Joanna , Jørgensen Jens OL , Mellemkjær Søren , Petersen Per H , Blaabjerg Ole , Hagen Claus
Published: May 2017

Background: In vitro, the majority of clinically non-functioning pituitary adenomas (NFPAs) produce gonadotropins or their α-subunit; however, in vivo, measurements of α-subunit levels may not accurately detect the hypersecretion of the α-subunit.

Aim: We wanted to estimate the reference intervals and decision limits for gonadotropin α-subunit, LH and FSH levels, and aratio (α-subunit/LH+FSH), especially taking into consideration patient gender and menstrual status. Furthermore, we wanted to examine if the diagnostic utility of α-subunit hypersecretion was improved when the α-ratios, rather than simply the α-subunit levels, were measured in patients with NFPAs.

Material and Methods: Reference intervals for gonadotropin α-subunit serum levels and α-ratios were established in 231 healthy adults. The estimated cut-off limits were applied to 37 patients with NFPAs. Gonadotropin α-subunit, LH and FSH levels were measured and α-ratios were calculated.

Results: In healthy adults, the cut-offs for α-subunit levels were significantly different between men and pre- and postmenopausal women: the cut-offs were 1.10, 0.48 and 3.76 IU/l, respectively. Using these estimated cut-offs, increased α-subunit levels were identified in 10 out of 37 (27%) patients with NFPAs. By adding α-ratio, in combination with α-subunit levels, 23 patients out of 37 (62%) were identified as having elevated α-subunit hypersecretion, and 22 out of these 23 patients (96%) had increased α-ratios. One premenopausal patient out of 23 had elevated α-subunit level but a normal α-ratio.

Conclusion: Our data suggest that adding the simple calculation of α-ratio improves the ability of detecting gonadotropin α-subunit hypersecretion and thereby indentifying patients with NFPAs.
Resolving disagreement during end of life care in the critical care unit: The case for communication not arbitration
Authors: Hartwick Michael , Jones Gwynne
Published: May 2017

Clinical medicine tries to resolve the uncertainties of diagnosis and prognosis. The natural history of the illness is repeatedly examined using both our own knowledge base and that of our colleagues. This is an iterative hypothesis testing process that starts with the history and physical examination and progresses with increasingly complex tests. Thus, the uncertainty of diagnosis and prognosis is diminished but never absolutely eliminated because of the limits of both our knowledge and our tests. Our scientific hypothesis testing, using the reductionist process, by which the whole can be deduced from the sum of its parts, has some human limitations. Science deals with generalities that strive to be objective and value free. In contradistinction, the patient is a unique individual, with deeply embedded personal values, whose wholeness is greater than the sum of his/her parts. For example, the patient may have qualities with descriptors such as insightful, tender, suffering or anxious. Thus, there is often a tension between medicine and science as well as a tension between the wishes of the patient, or Substitute Decision Maker (SDMs), and those of the health care team.
Translational applications of microRNA genes in medulloblastomas
Authors: Ajeawung Norbert F , Li Bin , Kamnasaran Deepak
Published: May 2017

Purpose: To provide a critical assessment of the clinical translational applications of microRNA (miRNA) genes in medulloblastomas.

Methods: Data were obtained from MEDLINE using Boolean-formatted keyword queries. Top articles were selected for critical analyses - depending on the novelty of findings, qualitative assessment of the citation index and relevance to the diagnosis, prognosis and therapeutic targeting of medulloblastomas.

Results: MiRNAs, non-protein-coding RNA molecules, negatively regulate gene expression in a sequence–specific manner during biological processes. In the past few years, miRNA genes have emerged as key regulators of not only molecular events involved in normal brain development and function but also in the molecular pathogenesis of medulloblastomas. In this manner, microRNA genes are identified with functional roles as oncogenes and tumor suppressor genes. At least four miRNAs have proven useful in improving the molecular classification of medulloblastomas, and eight others have shown potential in predicting patients’ overall prognosis. Moreover, more than 10 miRNA genes can be potentially utilized in therapies against medulloblastomas, using nine recent methods of targetting miRNAs.

Conclusion: The quest to identify miRNA genes that are of biological significance in medulloblastomas is on an ongoing venture. Most importantly, these miRNAs have been shown to be of clinical importance for improving the accuracy of diagnosis and prognosis and even developing therapies that can significantly improve patients’ overall survival from this deadly disease.
Prevention of postoperative peritoneal adhesions by O-carboxymethyl chitosan in a rat cecal abrasion model
Authors: Wang Dejuan , Mo Jiacong , Pan Shirong , Chen Haofan , Zhen Huanglin
Published: May 2017

Purpose: Post-surgial adhesion formation can result in significant morbidity and mortality. N,O-carboxymethyl chitosan (N,O-CMC) has been previously shown to be effective in the prevention of postsurgical adhesion formation. In this study, we evaluated the ability of O-carboxymethyl chitosan (O-CMC), another chitosan derivative generated by carboxymethylation of chitosan's oxygen centers, to reduce postsurgical adhesion development.

Methods: Twenty male Sprague-Dawley rats (250 ± 20 g) were divided into two equal groups: O-CMC group and saline (control) group. All rats underwent a midline laparotomy and the cecum was abraded to cause petechial hemorrhages. Following peritoneal injections of either saline or O-CMC, the incisions were closed. Seven days after surgery, the animals were killed and adhesion formation was scored. Tissue samples from the adhesions were examined histochemically.

Results: Adhesion formation was significantly decreased in the O-CMC group (P < .001) in comparison with the control group. Furthermore, significantly less collagen (P < .001) and fewer inflammatory cells and fibroblasts were detected in the O-CMC-treated animals. Additionally, a significantly (P < .05) lower level of TGF-β1 expression was found in the O-CMC group.

Conclusion: O-CMC appears to be effective in the prevention of postoperative peritoneal adhesion formation, which may be attributed to decreased accumulation of inflammatory cells and fibroblasts and reduced collagen synthesis.
A questionnaire assessment of physical function in hyperlipidemic patients
Authors: Taylor-Gjevre Regina M , Wassef Anthony , Nair Bindu , Gjevre John A , Wilson Thomas
Published: May 2017

Background: A spectrum of myopathic manifestations has been recognized as associated with lipid lowering drug therapy (LLT), but their effect on quality of life and physical functioning is uncertain. We conducted a prospective cohort study in which physical functioning was the dependent variable, in patients with and without exposure to LLT.

Methods: Consecutive patients attending a risk reduction clinic were invited to participate in a questionnaire study which included demographic data, muscular symptoms, the SF-36 Physical Function Score (PF), and the modified Health Assessment Questionnaire (mHAQ). Laboratory and co-morbidity data was recorded.

Results: Of 117 consecutive patients invited to participate, 112 consented. Of these, 81 were receiving statins and/or fibrates as LLT and 31 were participating in a non-pharmacologic therapeutic program (NPT) of diet and exercise therapy. The mean age for the total population was 56.7 years (20-78): the LLT group 58.6 and NPT group 51.9 years. Women comprised 53% of the LLT group and 58% of the NPT. No significant differences in baseline lipid profiles, CK level, BMI, waist measurement, gender, cigarette smoking, alcohol consumption, non-steroidal anti-inflammatory drugs or acetaminophen use, frequency of myalgias, SF-36 PF or mHAQ scores were observed between groups. On comparison of gender groups, we observed that men receiving LLT had significantly better SF- 36 PF (p = 0.037) than men on NPT. There were no differences in SF-36 PF or mHAQ scores between groups for females.

Conclusion: We found no adverse effects of LLT on physical functioning or quality of life. Indeed, men treated with LLT had significantly better SF-36 PF scores than men treated non-pharmacologically.
Discovery research to clinical trial: A ten year journey
Authors: Nielsen Torsten O
Published: May 2017

Clinician-scientists have the training and motivation to translate basic science into tools for improved clinical care, but the road to achieve this is hardly straight forward, particularly for large scale genomic datasets. This year’s Joe Doupe Young Investigator award winner, Dr. Torsten Nielsen, details successful examples of new scientific insights, diagnostics and clinical trials that have resulted from microarray-based gene expression profiling of sarcomas: TLE1 as a biomarker for synovial sarcoma, histone deacetylase inhibitor therapy for translocation-associated sarcomas of young adults, and CSF1 pathway inhibitors for tenosynovial giant cell tumors. Results from exciting, emerging next generation sequencing technologies will need to undergo similar validation and preclinical studies before they can be expected to impact patient care.
The KRESCENT Program: An initiative to match supply and demand for kidney research in Canada
Authors: Burns Kevin D , Wolfs Wim , Bélanger Paul , McLaughlin Kevin , Levin Adeera
Published: May 2017

Background: The prevalence of kidney disease is rising in Canada, and new approaches to prevention, diagnosis, and treatment are required. A kidney research training strategy, which enhances capacity while fostering collaboration and knowledge translation, may help to address this health care problem.

Purpose: This manuscript describes the Kidney Research Scientist Core Education and National Training (KRESCENT) Program that was launched in 2004 with a major goal to enhance kidney research capacity in Canada.

Features: KRESCENT is an innovative training program, which recruits from a variety of research disciplines, and emphasizes multi-disciplinary research approaches, team-based collaboration and knowledge translation. The program provides salary support for post-doctoral fellows, new investigators and allied health doctoral trainees, and also offers core curriculum and mentorship support. The curriculum involves knowledge acquisition, application and integration and uses workshops and web-based problem modules to enhance research skills. Training in methodological approaches and career development is also included. Initial evaluation of KRESCENT suggests that kidney research capacity in Canada has increased, and trainees have a high success rate in obtaining academic positions (~88%) and peer-review grant support (~50%).

Summary: KRESCENT represents a novel collaborative approach to kidney research training in Canada that may serve as a suitable model for training in other countries, or in other medical disciplines.
Application of an expandable pedicle screw in the severe osteoporotic spine: A preliminary study
Authors: Wu Zi-xiang , Cui Geng , Lei Wei , Fan Yong , Wan Shi-yong , Ma Zhen-sheng , Sang Hong-xun
Published: May 2017

Purpose. To investigate the clinical abstractnd radiographic outcome of multi-axial expandable pedicle screws (MEPS) in patients with osteoporosis.

Methods. One hundred and twenty-five consecutive patients received MEPS from the UPASS spinal fixation system to obtain thorocolumbar or lumbosacral stabilization. All patients underwent bone mineral density (BMD) scans. The indications for use of the MEPS were spinal diseases with severe osteoporosis (degenerative diseases 46 cases, compression fractures 28 cases, lumbar tuberculosis 27 cases and revision spine surgery 24 cases). The pre-operative and three months post-operative functional evaluations were graded with JOA and VAS scoring system. One week, six months and 12 months after surgery, plain film and three-dimensional CT scans were obtained to evaluate the spinal fusion and fixation effectiveness of MEPS.

Results The mean follow-up period was 18 months (ranged from 6 to 33 months). All patients suffered from severely osteoporosis with a decrease of 25.3% in BMD. The pre-operative JOA and VAS scores were 11.3±3.0 and 6.7±1.8 mm, respectively. Three months after operation, the JOA and VAS scores were 25.2±2.0 and 2.3±1.7 mm. The recovery rate was 78.1±11.5％ and the clinical results were satisfying. There were no instances of screw loosening or pullout of the MEPS and the screw-bone interface was excellent. The radiographic results showed that bone healing, both around the screws and inter-vertebral, was achieved.

Conclusion In osteoporosis spine surgery, excellent bone-screw interface and fixation strength can be achieved by using MEPS. MEPS are a novel approach to increase the pedicle screw fixation in osteoporotic and revision spine surgeries.
A survey evaluating surgeons’ peri-operative usage of acetyl-salicylic acid (ASA) and their willingness to enroll their patients in a perioperative ASA randomized controlled trial
Authors: Hiralal Rajesh , Guyatt Gordon , Bhandari Mohit , Cook Deborah , Berwanger Otavio , De Beer Justin , Cina Claudio , Buckley Norm , Villar Juan Carlos , Montori Victor , Marcaccio Michael , Paul James , Whiteacre Laura , Devereaux P J
Published: May 2017

Purpose: Major cardiovascular complications associated with noncardiac surgery represent a substantial population health problem for which there are no established efficacious and safe prophylactic interventions. Acetyl-salicylic acid (ASA) represents a promising intervention. The objective of this study was to determine surgeons’ perioperative usage of ASA, and if they would enrol their patients in a perioperative ASA randomized controlled trial (RCT).

Methods: Cross-sectional survey of all practicing Canadian general, orthopedic, and vascular surgeons. Our mailed, self-administered survey asked surgeons to consider only their patients who were at risk of a major perioperative cardiovascular complication.

Results: The response rate was 906/1854 (49%). For patients taking ASA chronically, there was marked variability regarding ASA continuation prior to surgery amongst the general and orthopedic surgeons, whereas 76% of vascular surgeons continued ASA in 81-100% of their patients. For patients not taking ASA chronically, approaches to starting ASA prior to surgery were variable amongst the vascular surgeons, whereas 70% of general and 82% of orthopaedic surgeons did not start ASA. For patients taking ASA chronically, 73% of general surgeons, 70% of orthopaedic surgeons, and 36% of vascular surgeons would allow at least 40% of their patients to participate in a perioperative RCT comparing stopping versus continuing ASA. For patients not taking ASA chronically, most general (76%), orthopaedic (67%), and vascular (51%) surgeons would allow at least 40% of their patients to participate in a perioperative RCT comparing starting ASA versus placebo.

Conclusion: This national survey demonstrates that perioperative ASA usage as reported by surgeons is variable, identifying the need for, and community interest in, a large perioperative ASA trial.