bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased oxidized-LDL levels and arylesterase activity/HDL ratio in ESRD patients treated with hemodialysis
Authors: Mahrooz Abdolkarim , Zargari Mehryar , Sedighi Omid , Shaygani Hamed , Gohari Ghorban
Published: May 2017

Purpose: Investigations, in which oxidized-low density lipoprotein (ox-LDL), serum paraoxonase (PON1) and homocysteine (Hcy) are considered together as important agents involved in the development of oxidative and atherogenic events in non-diabetic hemodialysis (HD) population, are limited. This case-control study was designed to evaluate these parameters in the patients and control subjects and to determine the correlations among the factors.

Methods: Forty-nine age- and sex- matched subjects, including 28 non-diabetic HD patients (paired pre-and post-dialysis samples) and 21 control subjects, were enrolled. Ox-LDL and Hcy levels were measured with ELISA and EIA methods, respectively. Arylesterase activity of PON1 was measured by spectrophotometric assay.

Results: Compared with the control group, ox-LDL levels were significantly increased both before (p=0.001) and after HD (p=0.036). Arylesterase activity-to-HDL ratio in HD patients was significantly higher than control subjects (p=0.003). Homocysteine levels in the ESRD patients were higher than control subjects both in pre-dialysis and post-dialysis. There was a significant positive correlation (r= 0.25, p= 0.026) between ox-LDL and homocysteine in samples obtained before HD. Logistic regression analysis revealed ox-LDL levels (OR=3.02, p < 0.001) and arylesterase activity/HDL ratio (OR=2.43, p=0.01) to be associated with the increased risk of ESRD.

Conclusions: Ox-LDL levels and arylesterase activity/HDL ratio indicated the strongest association with ESRD risk. These factors, especially ox-LDL as an indicator of oxidative stress, may be biomarkers in evaluating the status of non-diabetic ESRD patients. Because of the pathogenic relationship between ox-LDL and homocysteine as nontraditional risk factors of atherosclerosis, therapeutic strategies adopted to reduce them may be useful in decrease of high prevalence of cardiovascular mortality in dialysis patients. In addition, measurement of PON1 activity to HDL ratio is possibly a more valuable biomarker than arylesterase activity alone in non-diabetic ESRD.
Effects of long-term low-level solvent exposure on cognitive function
Authors: Saygun Meral , Ekici Aydanur , Muluk Nuray Bayar , Çakmak Aytül , Pinar Tevfik , Dağ Ersel , Ekici Mehmet
Published: May 2017

Purpose: The effects of long-term low-level exposures to solvents on cognitive function were investigated.

Methods: A total of 389 workers at a gun factory, those exposed to solvents (n=193) and those that were not exposed to solvents during work (n=196), were included. All the workers were given a questionnaire. Cognitive function was evaluated by Mini-mental Status Examination (MMSE) and psychological status was assessed by Hospital Anxiety and Depression (HAD) Scale.

Results: No differences were found in the MMSE and HAD scores between solvent-exposed workers and control workers (p > 0.05). In the workers who had used a mask for a longer time, orientation scores were lower. Daytime sleepiness was related to lower recall scores. Left-handed workers had higher total HAD scores than right-handed workers.

Conclusions: Long-term low-level exposure to solvents did not affect cognitive function in the workers, according to their MMSE scores. Duration of solvent exposure was also not related to MMSE Scores. Short sleep duration and daytime sleepiness may negatively affect cognitive function.
The relation of fragmented QRS with tissue Doppler derived parameters in patients with b-thalassaemia major
Authors: Buyukkaya Eyup , Karakas Mehmet Fatih , Kurt Mustafa , Bilen Perihan , Yalcın Fatih , Celik Murat , Helvacı Rami , Kaya Hasan , Ertekin Filiz , Sökmen Erdogan , Sen Nihat , Akcay Adnan Burak
Published: May 2017

Purpose: The most important complication encountered in patients with b-thalassaemia major is degenerative fibrosis developing as a result of iron accumulation in myocardial tissue. Dysfunction pursues this accumulation. Recently, presence of fragmented QRS (fQRS) in ECG has been regarded as a predictor of myocardial fibrosis. We aimed in our study to investigate the frequency with which fQRS develops in patients with b-thalassaemia major and to disclose the correlation between fQRS frequency and Doppler-derived indices.

Methods: The patients with b-thalassaemia major (n=66; mean age: 23±6 years) and healthy controls (n=30; mean age: 23±4 years) were included. fQRS pattern was described as presence of RSR’ manifested as existence of additional R wave and notching in either R or S waves in ECG recordings. 2D, M-mode, conventional Doppler, tissue Doppler echocardiography parameters were assessed. Mean serum ferritin levels over past 5 years were also calculated.

Results: When compared to those in control group, fQRS was more frequent in b-thalassaemia major group, indicating statistical significance (p = 0.001). While E/Em and ferritin level exhibited statistically significant increase in thalassaemia patients with fQRS (p < 0.05), the mean Em and Sm values were found to be significantly low (p < 0.05).

Conclusions: fQRS was frequently observed in the patients with b-thalassaemia major, which was of statistical significance. Tissue Doppler-derived diastolic and systolic indices in thalassaemia cases with fQRS showed statistically significant impairment compared to those without fQRS. In conclusion, fQRS may represent a novel noninvasive marker for cardiac involvement in patients with b-thalassaemia major.
Vascular endothelial growth factor production is induced by histone deacetylase 1 and suppressed by von Hippel-Lindau protein in HaCaT cells
Authors: Reynoso-Roldán Angélica , Roldán Maria L , Cancino-Diaz Juan C , Rodríguez-Martínez Sandra , Cancino-Diaz Mario E
Published: May 2017

Purpose: In hypoxic tumoral tissues, vascular endothelial growth factor (VEGF) expression is positively regulated by histone deacetylase 1 (HDAC1) and negatively regulated by the tumour suppressor protein von Hippel-Lindau (VHL) via transforming growth factor-alpha (HIF-1alpha). It has been reported that VEGF, HDAC1 and LL-37, but not VHL, are over-expressed in psoriatic skin. Although HIF-1alpha is constitutively expressed in normal keratinocytes, it is not known if HDAC1 and VHL can regulate VEGF production in these cells.

Methods: The participation of HDAC1 and VHL in the regulation of VEGF expression in HDAC-, VHL- and LL-37-transfected HaCaT cells, and in HaCaT cells treated with HDAC1 inhibitors, was studied.

Results: The production of VEGF was increased in HDAC1- and LL-37-transfected HaCaT cells and maintained in VHL-transfected cells under hypoxic conditions; meanwhile, VEGF production decreased in HaCaT cells treated with TSA, in cells transfected with HDAC1-siRNA, in cells co-transfected with HIF-1alpha-siRNA and pHDAC-1 and in VHL-transfected HaCaT cells. The levels of cytoplasmic HIF-1alpha were high in pLL37-transfected cells and low in pVHL- and pHDAC1-transfected cells; however, HIF-1alpha was detected in the nucleus of the HDAC1-transfected cells. The expression of VEGF was high in cells co-transfected with pHDAC1- and pLL-37, and the expression decreased when pVHL was present.

Conclusions: These data demonstrate that HDAC1, LL-37 and VHL can modulate the production of VEGF via HIF-1alpha in HaCaT cells.
Precision of Histological Bone Marrow Staging in Follicular Lymphoma and Diffuse Large B-cell Lymphoma
Authors: Chen Titi , McDonald Anne , Shadbolt Bruce , Talaulikar Dipti
Published: May 2017

Introduction: In Non-Hodgkin Lymphoma (NHL), bone marrow histology is the gold standard against which ancillary investigations such as immunophenotyping and gene rearrangement studies are interpreted. There is currently no data on the reproducibility of histological findings. This study was conducted to determine the rates of inter- and intra-observer agreement in histological detection of bone marrow involvement in the two major subtypes of NHL, Diffuse Large B-cell Lymphoma (DLBCL), and Follicular Lymphoma (FL).

Methods: The bone marrow slides of randomly selected DLBCL and FL cases were independently examined by two hematologists using standardized reporting criteria on two occasions at least two weeks apart. Samples included both aspirate and trephine biopsy slides. Weighted kappa statistics were used to examine agreement for the discrete measures.

Results: Weighted kappa analyses showed variable inter-observer agreement in 38 DLBCL cases [aspirate=0.52; trephine= 0.77] and 38 FL cases [aspirate=0.48; trephine=0.77].

Conclusion: Overall, higher agreement rates were noted with trephine biopsies than with aspirates. Except for the high intra-observer agreement on trephine biopsy assessment in FL, there is poor agreement in histological staging of both FL and DLBCL which demonstrates the limitations of histological diagnosis and the futility of interpreting ancillary tests against histology.
Pancreatic islet cell autophagy during aging in rats
Authors: Wang Shuang , Sun Qian-qian , Xiang Bing , Li Xiu-Jun
Published: May 2017

Purpose: Autophagy induces pancreatic β cell death. The purpose of the present study was to examine the hypothesis that the extent of pancreatic autophagy is associated with aging and age-related diabetes.

Methods: Pancreatic tissue and blood samples were collected from Sprague Dawley rats receiving a normal diet at 2 (the young group), 6 (the adult group), 12 (the middle-age group) and 20-24 (the aged group) months of age. Body weight and fasting blood glucose, serum lipid levels and serum insulin levels were determined. Pancreatic cell structure and autophagy were determined using transmission electron microscopy of rats at 6, 12 and 24 months of age. Lamp2 and LC3b protein expression levels were determined by both immunohistochemistry and Western blot analyses, and islet cell apoptosis was assessed using the TUNEL assay.

Results: Fasting blood glucose, triglyceride and FFA levels increased significantly with age (p < 0.05). Compared with levels seen in two-month-old rats, insulin secretion of islet cells in vitro was significantly reduced at 6, 12, and 20 months of age (p < 0.05). Autophagosomes were only observed in islet cells of 24 month-old rats. Increased expression of the autophagic markers, Lamp2 and LC3b, was observed with age. A significant increase in apoptotic index was observed between young rats (two-months-old) and older rats (six-, 12- and 24-months-old), but no differences were observed between rats six, 12 and 24 months of age.

Conclusion: Appearance of autophagosomes and increased Lamp2 and LC3b expression in pancreatic islet cells coincided with a significant decrease in insulin secretion and elevation of fasting blood glucose in aged rats.
End of Life Care in Canada: A Report from the Canadian Academy of Health Sciences Forum
Authors: Cook Deborah , Rocker Graeme
Published: May 2017

In Ottawa on September 20, 2012, the Canadian Academy of Health Sciences held a forum entitled, ‘End of Life Care: the Last 100 Days’.  Following an opening plenary by Dr. Daren Heyland, presentations and discussions ensued, highlighting recent research, current controversies, and future directions to improve end-of-life care in Canada [1]. Three articles in this issue of Clinical Investigative Medicine build on presentations from that day.
'INSPIRED' Approaches to Better Care for Patients with Advanced COPD
Authors: Rocker Graeme M , Cook Deborah
Published: May 2017

Chronic Obstructive Pulmonary Disease (COPD) is the most common cause of admission to acute care facilities in Canada. The burden of illness for patients, caregivers and the health care system is profound. Dyspnea in advanced COPD pervades all aspects of patients’ lives. When increasing symptom burden limits patients to their homes, crucial primary care services become less accessible, and care of end-stage COPD becomes increasingly fragmented and reactive. Given the considerable physical and psychosocial consequences of advanced COPD, this phase can be devastating for patients and families. In this article we outline the need for clinical interventions and re-organized models of care designed for better continuity to achieve more favorable outcomes for these patients and their families. Outreach programs and use of personalized action plans that include advice on careful use of opioids can be remarkably effective. The move toward an integrated approach to COPD management with more effective advance care planning will help patients and their families make informed decisions throughout the illness trajectory. Intensive medical treatment focused on increasing survival can coexist with both holistic and palliative approaches to improve the quality of life of patients with severe end-stage COPD.
Coronary artery calcification score is increased in patients with isolated coronary artery ectasia
Authors: Erkan Hakan , Ağaç Mustafa T , Akyol Seda , Korkmaz Levent , Kiriş Abdulkadir , Erkan Merve , Acar Zeydin , Vatan Bulent , Erkuş Emre , Akyüz Ali R , Çelik Şükrü
Published: May 2017

Purpose: Coronary artery calcification (CAC) is an indicator of coronary atherosclerosis and is associated with future adverse cardiac events. Isolated coronary artery ectasia (CAE) is defined as localized or diffuse dilation of the coronary arteries without coronary stenosis. The aim of this study was to assess the relationship between CAC and isolated CAE.

Methods: Thirty-four patients with isolated CAE and 50 controls subjects, with normal coronary arteries, were enrolled in the study. Baseline demographic features and atherosclerosis risk factors were similar in both groups.

Results: Patients with CAE had higher total CAC than control subjects (84±111 vs. 33.5 ± 103.5; p < 0.001). There was also a significant correlation between per-segment CAC and ectatic segment length (r=0.32; p=0.01) but no correlation with diameter (r=0.09; p=0.5).

Conclusion: Patients with isolated CAE had higher CAC than control subjects, suggesting that atherosclerosis may be involved in the pathogenesis of isolated CAE. Patients with isolated CAE may have increased cardiovascular risk and should receive appropriate risk stratification and relevant medical treatment.
The Limited Effectiveness of a Home-Based Eccentric Training for Treatment of Achilles Tendinopathy
Authors: Ram Rithesh , Meeuwisse Willem , Patel Chirag , Wiseman David A , Wiley J Preston
Published: May 2017

Purpose: Objective was to evaluate the outcome of a standardized heavy load eccentric training program in adults with chronic painful Achilles tendinopathy, and the presence of increased Colour Doppler activity in diseased and non-diseased adults. The hypothesis was that patient satisfaction would fall within the range of average satisfaction present in the literature (60 to 90%).

Methods: Twenty patients were instructed on a training program based on the Alfredson protocol of straight leg followed by bent knee heel drops and raises. Patient satisfaction was recorded as the primary outcome. Secondary outcomes included the VISA-A and Tegner scales. Twenty one subjects without present or history of lower extremity pain and seven patients presenting at the clinic but without Achilles tendinopathy were included as controls.

Results: Patient satisfaction was significantly lower when compared to the literature as two patients reported that they were satisfied with the treatment while the remaining 15 reported that they were unsatisfied. Three patients were excluded from the analysis as they were unable to complete the exercises. Increased Colour Doppler activity was present in only one participant without the disease and in all patients with the disease at the end of the study (increased Colour Doppler activity was present in 40% of patients with the disease at the beginning of the study).

Conclusion: Although some patients’ symptoms improved over time, eccentric training did not satisfy patient expectations of improvement following treatment despite compliance with the home based program. Although it is a mainstay of treatment, other options, which are both efficacious and effective, need to be provided for patients who prefer a conservative and relatively non-invasive treatment option from the start.
Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats
Authors: Bozkurt Mehtap , Em Serda , Oktayoglu Pelin , Turkcu Gul , Yuksel Hatice , Sarıyıldız Mustafa A , Caglayan Mehmet , Batmaz İbrahim , Nas Kemal , Bozkurt Yasar , Kuyumcu Mahir
Published: May 2017

Purpose: The purpose of this study was to investigate the effect of carvacrol (CAR) on methotrexate (MTX)-induced renal damage in rats.

Methods: Twenty-four male rats were equally divided into three groups: group I, control treatment; group II, MTX-treated; and group III, MTX+CAR-treated. A single dose of CAR (73 mg/kg) was administered intraperitoneally to group III on the first day of the experiment and a single dose of MTX (20 mg/kg) was administered intraperitoneally to groups II and III on the second day of the experiment. Blood samples and kidney tissue were obtained from each animal on day 8 for the measurement of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). Light microscopy was used for histopathological examination of kidney specimens.

Results: MDA, TOS and OSI levels were significantly greater in the group receiving MTX alone relative to the control animals, while the TAS level was significantly reduced in the MTX group compared with the control group. The administration of CAR was associated with significantly decreased MDA, TOS, and OSI levels and increased TAS levels relative to the rats treated with MTX alone. Animals treated with CAR exhibited decreased tubular degeneration and architectural impairment relative to animals treated with MTX alone; however, the difference in histological scores did not meet the threshold of statistical significance.

Conclusions: MTX treatment results in oxidative damage to the rat kidney; damage which is partially abrogated by the administration of CAR.
Noninvasive prediction of large esophageal varices in liver cirrhosis patients
Authors: Wang Lijing , Hu JunWei , Dong Shuang , Jian Yi Cheng , Hu Lijuan , Yang Genmei , Wang Jinjun , Xiong Wujun
Published: May 2017

Purpose: Esophageal varices are a dangerous complication of liver cirrhosis. The development of cost effective, noninvasive means for prediction of large esophageal varices could reduce the use of upper gastrointestinal endoscopy in variceal screening and also provide an alternative way to confirm the results of conventional endoscopic diagnosis. Previously proposed predictive models are neither sensitive nor specific.

Methods: A retrospective study based on a group of 104 liver cirrhosis patients was performed. Multiple statistical approaches were used to evaluate the association of large esophageal varices with 20 individual and six compound clinical laboratory variables. A new predictive model was developed.

Results: Univariate analysis suggested that eight out of 26 variables were significantly associated with large esophageal varices. Further stepwise logistic regression eventually identified three variables (hemoglobin level, portal vein diameter and the ratio of platelet count/spleen diameter) that contributed significantly to the final regression model. Receiver operating characteristic (ROC) curve analysis showed that this new regression model achieved 77.8% and 72% of diagnostic sensitivity and specificity, respectively, for the prediction of large esophageal varices. In our study group, its diagnostic accuracy (AUROC=0.814) was found to be significantly higher than six predictive models previously published.

Conclusions: No single variable offers self-sufficient predictive function for large esophageal varices. A comprehensive model using multiple variables significantly improves the predictive accuracy in screening the most at risk patients with potential variceal hemorrhage.
How to Succeed in Research During Medical Training: A Qualitative Study
Authors: Alak Aiman , Jerzak Katarzyna J , Quirt Jaclyn A , Lane Shannon J , Miller Patricia A , Haider Shariq , Arnold Donald M
Published: May 2017

Purpose: The objective of this study was to examine the characteristics of the medical trainee (resident), the supervisor and the project that contribute to successful completion of resident-led research and publication in a peer-reviewed scientific journal.

Methods: Qualitative, interview-based study of Internal Medicine trainees and their supervisors. All interviewed trainees published at least one first-author research paper based on a project they completed during residency. Thematic analysis was used to explore key themes from interview transcripts. An iterative, team-based approach was used to develop a coding framework, which was then applied to the data and summarized. Six investigators independently reviewed and coded transcripts, discussed the data collectively and developed key themes by consensus.

Results: Thirty participants (15 residents and 15 supervisors) were interviewed. Three major themes for successful resident research projects emerged: 1) the resident is the project champion; 2) supervisors ensure feasibility and timeliness of the project; and, 3) limited time is a challenge that can be overcome. Residents were motivated by fellowship aspirations, prioritized the project and were genuinely interested in the content area. Supervisors were responsible for setting deadlines, limiting the scope of the project and ensuring feasibility of the study design. Existing research funds and infrastructure from other projects were frequently used by supervisors to support research done by trainees.

Conclusions: Successful resident-led research projects require leadership and motivation by the resident and engagement, reality-checking and deadline-setting by the supervisor. Responsibilities and expectations in the resident-supervisor relationship should be set early and adequate program resources and funding are required.
MicroRNA-222 promotes the proliferation and migration of cervical cancer cells
Authors: Sun Yi , Zhang Bo , Cheng Jiajing , Wu Yi , Xing Fing , Wang Yingyi , Wang Qingying , Qiu Jin
Published: May 2017

Purpose: This study aimed to investigate the role of small non-coding RNA-222 (microRNA-222; miR-222) in the development of cervical cancer (CC).

Methods: Normal and CC specimens were obtained from 18 patients. HeLa and SiHa cells were grown in Dulbecco’s modified Eagle’s medium. RT–PCR, Western blot, migration assay, flow cytometry and immunofluorescence microscopy were used for analyses.

Results: When compared with normal cervical tissues, miR-222 was upregulated in human CC, and the extent of up-regulation was associated with the extent and depth of CC invasion. Expression of miR-222 was inversely related to the expression of phosphatase and tensin homolog (PTEN) and p27. The reduced the expression of PTEN and p27 by miR-222 in HeLa cells and SiHa cells was associated with increased proliferation and migration of CC cells. The expression of proteins (E-cadherin and paxillin) related to the proliferation and migration was also elevated.

Conclusion: MiR-222 plays an important role in the tumorigenesis of CC, possibly by specifically down-regulating p27Kip1 and PTEN. Our findings suggest that miR-222 may serve as a new therapeutic target in CC.
Prevalent hypovitaminosis D in Crohn´s disease correlates highly with mediators of osteoimmunology
Authors: Turk Nikša , Turk Zdenka
Published: May 2017

Purpose: In the context of osteoimmunology in Crohn's disease, an association was hypothesized among vitamin D and members of the TNF-α family, known as the RANK (receptor-activator of nuclear factor- κB)-RANK ligand-osteoprotegerin pathway.

Methods:This was a cross-sectional study of 95 patients with Crohn’s disease (80 with long-standing disease and 15 newly diagnosed, never treated) and two control groups (healthy volunteers, n=30; and ulcerative colitis patients, n=30). Spine and hip bone mineral density was measured by dual-energy x-ray absorptiometry. Serum 25-hydroxyvitamin-D3, TNF-α, IL-6, sRANKL, osteoprotegerin levels and biochemical markers of bone turnover were analyzed.

Results: The precursor metabolite, 25(OH)D3, was measured in 95 young adult CD patients (47 men, 48 women; median age 30 years). A suboptimal 25(OH)D3 level was observed in 90% of CD patients, of whom 40% had a serious deficiency. There was no significant difference in 25(OH)D3 levels between CD patients and those with ulcerative colitis. Analysis revealed an association between 25(OH)D3 deficiency and the increased biogenesis of osteoclastically-active sRANKL (p=0.014) and the proinflammatory cytokines TNF-α (p=0.015) and IL-6 (p=0.029) . CD patients with low bone mineral density had a mean 25(OH)D3 (35±18 nmol/l) in the range of serious deficiency to insufficiency, whereas mean 25(OH)D3 was higher (49±28 nmol/l) in patients with healthy bone status, although levels were still inadequate (p=0.004). The logistic model reported low levels of 25(OH)D3 to be a significant predictor of bone disease [odds ratio=2.66(6.8), p < 0.009]. In the multivariable analysis, adjusted for several confounding factors, 25(OH)D3, sRANKL, IL-6 and TNF-α were independently associated with a likelihood of bone disease [odds ratio (range): 1.02(2.75); 1.09(3.71); 1.27(6.95) respectively, p=0.001].

Conclusion: The presented findings suggest that a 25(OH)D3 deficiency accompanying an inflammatory state in CD is a high risk condition for metabolic bone disease.
Visceral Fat Reflects Disease Activity in Patients with Ankylosing Spondylitis
Authors: Aydin Mesut , Aydin Fatma , Yuksel Murat , Yildiz Abdulkadir , Polat Nihat , Akil Mehmet A , Bilik Mehmet Z , Akyuz Abdurrahman , Batmaz Ibrahim , Alan Sait
Published: May 2017

Purpose: Response to infliximab treatment diminishes as body mass index (BMI) increases in patients with ankylosing spondylitis (AS). The purpose of the study was to determine if diminished response to infliximab treatment in patients with AS could be associated with increased visceral adipose tissue rather than increased BMI.

Methods: Twenty six AS patients (21 males and five females) who fulfilled the modified New York criteria and who were currently receiving infliximab treatment were enrolled in the study. Pain was measured by the visual analogue scale (VAS). The disease activity and functional status were assessed by the Bath AS Disease Activity Index (BASDAI) and the Bath AS Functional Index (BASFI). The Bath AS Metrology Index (BASMI) was used to evaluate mobility restrictions. Weight and visceral body composition were measured without shoes in light indoor clothes using a bio-impedance meter.

Results: There was a significant correlation between visceral adipose tissue amount and disease activity under infliximab treatment. In correlation analysis, visceral fat showed significant correlations between BASDAI (r=0.545, p=0.004) and VAS (r=0.458, p=0.019). Total body fat also showed a significant correlation with BASDAI (r=0.463, p=0.017).

Conclusion: A significant correlation was found between visceral adipose tissue amount and disease activity in patients with AS.
Comparison of Artecoll, Restylane and silicone for augmentation rhinoplasty in 378 Chinese patients
Authors: Chen Liang , Li Shi-Rong , Yu Pan , Wang Zhen-Xiang
Published: May 2017

Purpose: Dermal fillers have been proven to be safe in soft tissue augmentation; however, their efficacy in modeling the noses of Asian patients has not been demonstrated.

Methods: In this study, 378 patients were included and underwent augmentation rhinoplasty (Artecoll, n=126; Restylane, n=126 and silicone implants, n=126). The subjective and objective outcomes were evaluated on day 1, and months 1, 3, 6, and 12 after injection rhinoplasty.

Results: All patients achieved significant improvement in nasal shape and contour immediately after surgery. Patients treated with Restylane failed to maintain the nasal shape and contour 1 year after surgery, whereas patients undergoing Artecoll rhinoplasty completely maintained the post-treatment nasal shape and contour. More patients with silicone implants experienced adverse events and the severity of these events was greater in the silicone group compared to those in the Restylane and Acetoll groups.

Conclusion: Artecoll rhinoplasty has a low incidence of adverse effects and the shape and contour of the nose are maintained for a prolonged period.
Predictive value of cystic fibrosis transmembrane conductance regulator (CFTR) in the diagnosis of gastric cancer
Authors: Liu Haiyan , Wu Wenyong , Liu Yang , Zhang Changle , Zhou Zheng
Published: May 2017

Purpose: Gastric cancer is associated with poor prognosis. The high mortality rate of gastric cancer is mainly attributed to late detection, so diagnosis and treatment are crucial to decreasing mortality. The purpose of this study was to examine the predictive accuracy and discriminative ability of cystic fibrosis transmembrane conductance regulator (CFTR) in gastric cancer patients, in addition to the classical cancer tumor biomarkers carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA).

Methods: The study was performed on 78 serum samples from gastric cancer patients and 88 serum samples from healthy adults. Serum levels of CFTR, CA199, CEA and CHN were determined by enzyme-linked immunosorbent assay (ELISA)

Results: Spearman’s coefficient analysis showed that, in some cases, CFTR was strongly correlated with CA199 and that CFTR levels increased with age. Kruskal-Wallis testing indicated concentrations of CFTR and CA199 had statistically significant association with stage. Logistic regression showed that CFTR and CA199 independently predicted gastric cancer. Receiver operating characteristics (ROC) showed that combinations of CFTR, CA199, and CEA yielded the best ROC curve, with an AUC of 0.875.

Conclusions: The results of this study indicate that the serum CFTR has a broad application prospects for detection of GC.
A Prescription that Addresses the Decline of Basic Science Education
in Medical School
Authors: Miller Daniel , Thornton Christina S , Keough Michael B , Roberts Jodie I , Yipp Bryan , Hollenberg Morley , Bau Jason T , Peplowski Michael A , Beck Paul L
Published: May 2017

Over 30 years ago a cry rang out through the proverbial halls of academia; “The clinician scientist is an endangered species.” These prophetic words have been reverberated in the ears of every specialty and every general medical organization in deafening tones. Why is the role of the clinician scientist or clinician investigator so important that this phrase has been repeated subsequently in medical and educational journals? Simply put, the clinician scientist bridges the ravine between the ever-growing mountain of scientific knowledge and the demanding patient centered clinical care. Here, we describe the current educational model established by the University of Calgary, Leaders in Medicine Program. Our program seeks to train future physicians and clinician scientists by incorporating training in basic science, translational and clinical research with clinical and medical education in a longitudinal program to students of traditional MD/PhD, MD/MSc or MD/MBA stream as well as interested Doctor of Medicine students.
Effect of Sleep Quality on Hemodynamic Response to Exercise and Heart Rate Recovery in Apparently Healthy Individuals
Authors: Yuksel Murat , Yildiz Abdulkadir , Demir Melike , Bilik Mehmet Z , Ozaydogdu Necdet , Aktan Adem , Isik Ferhat , Demir Suleyman , Yazgan Umit C , Toprak Nizamettin
Published: May 2017

Purpose: Poor sleep quality has an unfavorable impact on autonomic nervous system activity, especially that of the cardiovascular (CV) system. The heart rate (HR) and blood pressure (BP) at rest and during exercise, along with the heart rate recovery (HRR), were examined in poor sleepers and compared with individuals with good sleep quality.

Methods: A total of 113 healthy individuals were enrolled to the study. All participants performed treadmill stress testing. Sleep quality of participants was assessed by using the Pittsburgh Sleep Quality Index (PSQI) questionnaire: 48 subjects were categorized as ‘poor sleepers’ (PSQI score > 6 points), and the rest were grouped as ‘good sleepers’.

Results: The poor sleepers showed higher resting HR (p
Evaluation of the Urinary Kidney Injury Molecule-1 Levels in Patients With Diabetic Nephropathy
Authors: Kin Tekce Buket , Tekce Hikmet , Aktas Gulali , Sit Mustafa
Published: May 2017

Purpose: Kidney Injury Molecule-1 is a protein that increases in urine following tubular damage. Kidney Injury Molecule-1 levels were correlated with the level of chronic kidney disease secondary to diabetic nephropathy in patients with type 2 Diabetes Mellitus.

Methods: Clinical and laboratory findings of 142 patients with diabetic nephropathy and 34 control subjects were analysed. Creatinine and HbA1c levels in blood samples and albumin, creatinine and Kidney Injury Molecule-1 levels in urine samples were assessed.

Results: Urinary Kidney Injury Molecule-1 levels were significantly increased both in subgroups of diabetic nephropathy (normo-/micro-/macro-albuminuria) and in chronic kidney disease (stage 2-4) compared with controls. Urinary Kidney Injury Molecule-1 levels in stage 2 chronic kidney disease patients were significantly higher than those of the patients with stage 3-4 chronic kidney disease. Urinary Kidney Injury Molecule-1 levels, along with urinary albumin excretion and the duration of diabetes, were found to be independent risk factors associated with low glomerular filtration rates.

Conclusion: Urinary Kidney Injury Molecule-1 levels seems to predict renal injury secondary to diabetic nephropathy in early period independent of albuminuria, because urinary Kidney Injury Molecule-1 was elevated despite normal urinary albumin excretion in the normoalbuminuric subgroup. Urinary Kidney Injury Molecule-1 levels, which are elevated in primarily in stage 2, shows a gradual decrease in patients with chronic kidney disease stages 3 and 4; thus, urinary Kidney Injury Molecule-1 levels may be useful in tracking the progression of kidney disease.
A new rapamycin-abluminally coated chitosan/heparin stent system accelerates early re-endothelialisation and improves anti-coagulant properties in porcine coronary artery models
Authors: Gao Junqing Q , Zheng Jianpu P , Jin Huigen G , Zhang Wenquan Q , Yan Pengyong Y , Chen Tao , Liu Zongjun J
Published: May 2017

Purpose: Drug-eluting stents (DES) in percutaneous coronary intervention are more effective in preventing in-stent restenosis compared with bare metal stents (BMS); however, DES may cause late stent thrombosis, which has limited its use. In this study, the functional properties of a newly developed DES (RAP/CS/HEP), in which rapamycin was abluminally-loaded onto a chitosan/heparin coating stent (CS/HEP), were investigated in large animal artery injury models.

Methods: The effectiveness of BMS, RAP (the traditional version of rapamycin DES), CS/HEP and RAP/CS/HEP stents in preventing coagulation and promoting re-endothelialisation was examined and compared in the porcine coronary artery models with arteriovenous shunt, high load thrombus and coronary balloon injury at day 7 and 28, respectively, after stent implantation. The re-endothelialisation on these stents was further evaluated in terms of endothelial gene expression using quantitative RT-PCR.

Results: In the porcine coronary artery injury models, both RAP and RAP/CS/HEP stents were potent in reducing neointimal thickness, thus enlarging lumen area efficiently in the stented artery region compared with BMS and CS/HEP. RAP/CS/HEP stents facilitated re-endothelialisation and inhibited thrombosis more efficiently than BMS and RAP. Consistent with this, the expression of endothelial genes, such as CD31, CD34, eNOS and VEGF, was significantly elevated with RAP/CS/HEP stents compared with RAP and BMS stents.

Conclusion: Abluminal coating of rapamycin onto the endothelialisation-accelerated CS/HEP stent and may prove to be an efficient treatment for tackling the late stent thrombosis associated with the traditionally circumferential RAP stent. This new RAP/CS/HEP stent system exhibits considerably improved therapeutic activity.
Hair Cortisol as a Biomarker of Stress in the 2011 Libyan War
Authors: Etwel Fatma , Russell Evan , Rieder Michael J , Van Uum Stan H , Koren Gideon
Published: May 2017

Purpose: There is a substantial body of research that utilizes saliva cortisol levels to examine wartime stress; however, there is a paucity of literature that utilizes hair cortisol levels, which allows for long-term assessment of chronic stress, to investigate the stress of war. The present study aimed to evaluate changes in hair cortisol concentrations before, during, and after the 2011 Libyan war.

Methods: This study examined hair cortisol concentrations of young adult women who were living in Tripoli, Libya during the 2011 war. The participants were recruited at the campus of Tripoli University. Participants needed to have at least 24 cm of hair and to have resided in Tripoli before, during and after the 2011 Libyan war. Hair was sectioned to reflect 3 month windows of cortisol exposure corresponding to periods before, during and after the war. Hair cortisol concentrations were quantified using a modified salivary ELISA test. The women were also asked to complete the Perceived Stress Scale pertaining to the post-war period.

Results: Median hair cortisol concentrations in the post-war period (226.11 ng/g; range 122.95-519.85 ng/g) were significantly higher than both the pre-war (180.07 ng/g; 47.13-937.85 ng/g) and wartime (186.65 ng/g; 62.97-771.79 ng/g) periods (P
JOE DOUPE LECTURE: Emerging Strategies for the Preservation of Pancreatic Beta-cell Function in early Type 2 Diabetes
Authors: Retnakaran Ravi
Published: May 2017

A fundamental problem in the clinical management of type 2 diabetes is the inability to prevent the ongoing deterioration of pancreatic beta-cell function over time that underlies the chronic progressive nature of this condition. Importantly, beta-cell dysfunction has both reversible and irreversible components. Furthermore, the amelioration of reversible beta-cell dysfunction through the early institution of short-term insulin-based therapy has emerged as a strategy that can yield temporary remission of type 2 diabetes. In this context, we have forwarded a novel therapeutic paradigm consisting of initial induction therapy to improve beta-cell function early in the course of diabetes followed by maintenance therapy aimed at preserving this beneficial beta-cell effect. Ultimately, this approach may yield an optimized therapeutic strategy for the durable preservation of beta-cell function and consequent modification of the natural history of type 2 diabetes.
Number Needed To… $ave?
Authors: Rocker Graeme M , Verma Jennifer Y , Demmons Jillian , Mittmann Nicole
Published: May 2017

The ‘Number Needed to Treat’ (NNT) is a useful measure for estimating the number of patients that would need to receive a therapeutic intervention to avoid one of the adverse events that the treatment is designed to prevent. We explored the possibility of an adaption of NNT to estimate the ‘Number Needed to $ave’ (NN$) as a new, conceptual systems metric to estimate potential cost-savings to the health system from implementation of a treatment, or in this case, a program. We used the outcomes of the INSPIRED COPD Outreach ProgramTM to calculate that 26 patients would need to complete the program to avoid healthcare expenditures of $100,000, based on hospital bed days avoided. The NN$ does not translate into 'cost savings' per se, but redirection of resource expenditures for other purposes. We propose that the NN$ metric, if further developed, could help to inform system-level resource allocation decisions in a manner similar to the way that the NNT metric helps to inform individual-level treatment decisions.
Serum Neutrophıl Gelatınase-Assocıated Lıpocalın Levels in Patients with Non-Dipper Hypertension
Authors: Aksan Gökhan , İnci Sinan , Nar Gökay , Siğirci Serhat , Gedikli Ömer , Soylu Korhan , Nar Rukiye , Yüksel Serkan , Şahin Mahmut
Published: May 2017

Purpose: Neutrophil gelatinase-associated lipocalin (NGAL) is a protein belonging to the lipocalin superfamily and plays a role in atherosclerosis, renal injury and inflammation. The present study aimed to investigate serum NGAL concentrations in groups of patients with dipper and non-dipper hypertension (HT) and to characterize the relationship between NGAL concentration and circadian blood pressure in hypertensive patients.

Methods: A total of 41 (22 male, 19 female, mean age: 56.1 ±8.9 years) non-dipper HT patients, 40 (19 male, 21 female, mean age: 54.0 ±10.0 years) dipper HT patients and 42 age- and gender-matched healthy individuals were enrolled in the study. Dipper and non-dipper HT were diagnosed via ambulatory blood pressure monitoring. Serum NGAL concentrations were measured by enzyme-linked immunosorbent assay from blood samples obtained from patients.

Results: Serum NGAL concentrations were found to be significantly higher in the non-dipper and dipper HT patient groups in comparison with the control group (84.9 ±23.0 ng/ml and 62.1 ±17.8 vs. 46.6 ± 13.7 ng/ml, p
Quality of Life Following Treatment of Trochanteric Fractures with Proximal Femoral Nail versus Cementless Bipolar Hemiarthroplasty in Elderly
Authors: Desteli Engin E , İmren Yunus , Erdoğan Murat , Aydagün Özlem
Published: May 2017

Purpose: There is currently no gold standard treatment for unstable intertrochanteric fractures of the elderly. Internal fixation and hemiarthroplasty are two common treatment methods but studies comparing the functional outcomes of these procedures in the elderly are limited. This study evaluates the functional outcomes of hip fracture patients treated either with internal fixation or hemiarthroplasty.

Methods: Eighty-six elderly (>60 years) patients who presented with isolated, unstable intertrochanteric fractures between 2009 and 2013 were included in the study. According to the classification of Association for Osteosynthesis/Orthopaedic Trauma Association; 12 of the patients had a 31A1.3 fracture type, 36 of the patients had 31A2.2 and 19 had 31A2.3 fracture type, 12 had 31A3.1 and seven had 31A3.3 fracture. Forty-two of 86 hip patients (Group 1) were treated with intramedullary nailing and antirotator proximal femoral nail implant (TST, Turkey), and 44 (Group 2) were treated with cementless bipolar hemiarthroplasty. Preoperative social function (Jensen) score, EQ-5D index score and mobility (Palmer/Parker) scores were obtained. Five dimensions of EQ-5D were obtained at every follow-up visit until 24 months postoperative.

Results: There was no statistically significant difference between two groups according to preoperative demographic variables, including mean age and sex and Jensen, Palmer/Parker,EQ-5D index, five dimensions of EQ-5D and American Society of Anesthesiologists scores. At end of 24 months follow-up, health-related quality of life had increased more in Group 1 and they reported better social functioning and mobility scores (p
Mechanisms of remodelling of small arteries, antihypertensive therapy and the immune system in hypertension
Authors: Schiffrin Ernesto L
Published: May 2017

This review summarizes my lecture for the 2015 Distinguished Scientist Award from the Canadian Society of Clinical Investigation, and is based mainly on studies in my laboratory on the mechanisms of remodelling of small arteries in experimental animal and human hypertension and on treatments that lower blood pressure and improve structure and function of resistance vessels. Small resistance arteries undergo either inward eutrophic or hypertrophic remodelling, which raises blood pressure and impairs tissue perfusion. These vascular changes are corrected by some antihypertensive drugs, which may lead to improved outcomes. Vasoconstriction, growth, oxidative stress and inflammation are some of the mechanisms, within the vascular wall, that can be beneficially affected by antihypertensive agents. These antihypertensive-sensitive mechanisms are reviewed in this review, together with the inflammatory and immune mechanisms that may participate in hypertension and associated cardiovascular injury. Molecular studies, based on this research, will hopefully identify novel diagnostic and therapeutic targets, which will improve our ability to prevent and treat hypertension and cardiovascular disease.
Association between obstructive sleep apnea and metabolic syndrome:
a meta-analysis
Authors: Kong De-Lei , Qin Zheng , Wang Wei , Pan Ying , Kang Jian , Pang Jian
Published: May 2017

Purpose: Evidence suggests that obstructive sleep apnea (OSA) is related to metabolic syndrome; however, the relationship among metabolic syndrome parameters (blood pressure, fasting blood glucose (FBG), high density lipoprotein (HDL) and low density lipoprotein (LDL)) and OSA is unclear.

Methods: PRISMA guidelines were followed for this study. Medline, Cochrane, EMBASE and Google Scholar databases were searched until December 23, 2015, using following terms: obstructive sleep apnea, sleep apnea, OSA and metabolic syndrome.

Results: Ten studies were included in the analysis which included 2053 patients. Patients with OSA had higher systolic blood pressure (SBP) (pooled standard mean difference (SMD) = 0.56, 95% CI, 0.40 to 0.71, P
Visualizing A Natural Antibiotic Nanofactory
Authors: Schmeing T. Martin
Published: May 2017

Environmental samples are excellent sources of natural products that possess numerous kinds of therapeutic activities. One important family of natural products is the nonribosomal peptides, which includes penicillin, cyclosporin, viomycin and daptomycin (Cubicin). These peptides are made in bacteria or fungi by large enzymes called nonribosomal peptide synthetases (NRPS). NRPSs are true macromolecular machines or nanofactories, with modular assembly-line logic, a complex catalytic cycle, moving parts and many active sites. Visualization of large fragments of NRPSs at various functional states is required to understand the manner in which NRPSs synthesize their important products. Many excellent structural experiments have been performed to date. Recently, we added to the structural knowledge by visualizing the first module of the NRPS, which makes linear gramicidin, a clinical topical antibiotic, in all its major functional states. These experiments show how the individual domains, including an unusual tailoring domain, function together in assembly-line synthesis. Along with the ever-expanding body of biophysical, biochemical and genetic work, this work brings us closer to a fundamental understanding of these natural antibiotic nanofactories, and perhaps the ability to exploit them to produce novel therapeutics.