bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a new microRNA expression profile as a potential cancer screening tool
Authors: Roa Wilson , Brunet Bryan , Guo Linghong , Amanie John , Fairchild Alysa , Gabos Zsolt , Nijjar Tirath , Scrimger Rufus , Yee Don , Xing James
Published: May 2017

Purpose: Small non-coding microRNAs (miRNAs) are key components of cancer development and are considered as potential biomarkers for cancer diagnosis and treatment monitoring. This study investigated miRNA expression profiles of human cancer cells in order to develop a screening method for lung cancer.

Methods: A series of lung cancer related miRNAs (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, let-7a) were selected as candidates for miRNA expression profiles of human lung cancer cell lines (A549, SK-mes-1). MicroRNA u6 was the endogenous control. Cancer cell lines for positive controls; breast MCF-7, prostate Du-145, and glioblastoma U118. The negative control was normal lung fibroblast cell line MRC-5. RT-PCR was performed on StepOnePlus (Applied Biosystem, USA). MiRNA expressions of malignant cells were compared with normal fibroblast cells as well as endogenous control (u6) using the thermal cycle at threshold. Assessment of miRNA expression profiles were then performed using agglomerative hierarchical cluster analysis software (SPSS13, USA).

Results: We demonstrated that miR-21, miR-182 and let7-5a were over-expressed, and miR-145 and miR-155 were under-expressed in all cancer cell lines. Combined with the cluster analysis we were able to clearly distinguish cell lines for normal fibroblasts, breast cancer, prostate cancer, glioblastoma, and lung cancer.

Conclusion: There is potential utility of screening for lung cancer with miRNA expression profiles. Future work will focus on the sensitivity of such miRNA expression profiles in screening sputum for lung cancer, which can be performed in real time.
Statistical significance in genetic association studies
Authors: Qu Hui-Qi , Tien Matthew , Polychronakos Constantin
Published: May 2017

Clinical & Investigative Medicine (CIM) is receiving an increasing number of reports of candidate-based association studies. The track record of such studies in the past has been poor: numerous genetic associations reported from candidate gene studies have not been replicated in later studies. The rise of the genome-wide association study (GWAS) is changing this situation. A well-designed GWAS may identify a number of candidate loci without bias by screening the whole human genome. Validating and fine-mapping the candidate loci from GWAS are required to clarify the genetic mechanisms. Thus, a candidate-based association study has become a well-directed effort, instead of searching for a needle in a haystack. In the post-GWAS era, exponential growth of candidate-based genetic association studies is expected. A pressing issue accompanying this new trend is the assessment of the validity of an association study. In this editorial, we illustrate the major cause of false positive association from random sampling bias by an empirical example, and emphasize the application of the probability theory in assessing the validity of a genetic association study.
Immunological and hematological changes in patients with hyperthyroidism or hypothyroidism
Authors: Jafarzadeh Abdollah , Poorgholami Masoud , Izadi Nazanin , Nemati Maryam , Rezayati Mohammad
Published: May 2017

Aims: Thyroid hormones have been shown to influence the immune system and haematopoiesis. The aim of this study was to evaluate some immunological and hematological parameters in peripheral blood of hypo- or hyperthyroid women.

Materials and Methods: Blood samples were collected from 50 women with hypothyroid disease, 50 women with hyperthyroid disease and a control group consisting of 50 sex - and age - matched euthyroid subjects. Thyroid function assesed according to measurent of T3, T4 and TSH levels. The complete blood count (CBC), total and differential counts of white blood cells (WBC), serum levels of immunoglobulins (IgG, IgA, IgM and IgE) and C3 and C4 complement components determined in three groups by using standard immunological and hematological methods.

Results: In hyperthyroid women the mean serum concentrations of IgG (2312.4±584 mg/dl), IgA (296± 87 mg/dl) and IgE ( 301± 264 IU/ml) were significantly higher than those found in the control group (1539± 974 mg/dl, P < 0.0003; 234± 116 mg/dl, P < 0.01; 109.8±115 IU/ml, P < 0.0001, respectively) and the mean MCV was significantly lower in comparison with the euthyroid group (P < 0.05). Hypothyroid patients had higher serum IgE concentrations in comparison with the euthyroid group (179.8± 218 IU/ml vs. 109.8± 115 IU/ml; P < 0.047). The mean serum C3 concentration in hypothyroid patients was also significantly higher in comparison with the euthyroid group (138.7± 36.6 mg/ml vs. 117.8± 32.1 mg/dl; P < 0.01). In the hypothyroid group the mean eosinophil count was markedly higher in comparison with the hyperthyroid group (P < 0.06) and the mean count of RBC and the levels of some RBC-related indices, such as hematocrit and hemoglobin, were significantly lower in comparison with the euthyroid group (P < 0.05).

Conclusion: These results indicate hypergammablobulinemia and lower MVC in hyperythyroid patients, and higher IgE levels, C3 levels and eosinophil count as well as anemia in hypothyroid patients.
Effect of ex vivo-expanded γδ-T cells combined with galectin-1 antibody on the growth of human cervical cancer xenografts in SCID mice
Authors: Li Hua , Wang Yubin , Zhou FuXiang
Published: May 2017

Objective: To investigate the antitumor activity of ex vivo-expanded γδ-T cells derived from tumor-infiltrating lymphocytes(γδTILs) from cervical cancer patients when combined with galectin-1 antibody and studied both in vitro and in vivo.

Methods: The presence of γδTILs in cervical cancer specimens was detected by immunohistochemistry and γδTILs were expanded using the solid-phase antibody method. The expression of galectin-1 by the human cervical cancer cell line, SiHa, was measured by Western blot and ELISA. In vitro cytotoxic activities of expanded γδTILs, with or without galectin-1 inhibitor, were determined using the LDH-release test. In vivo antitumor activity of γδTILs, combined with galectin-1 antibody, was evaluated using the SCID mouse model.

Results: γδTILs existed in the cervical cancer and the percentage of TCRγδ+ cells in γδTILs after ex vivo expansion was 91.2±1.2% detected by flow cytometry. SiHa cell expressed and secreted galectin-1 as measured by Western blot and ELISA. Expanded γδTILs from human cervical cancer demonstrated marked cytotoxicity to SiHa or Hela cells. In comparison with non-treated group, the cytotoxicity of γδ TILs towards SiHa or Hela cell was significantly increased when effector and target cells were incubated with either lactose or galectin-1 antibody at E/T ratio of 1:1 (p < 0.05). γδTILs, in combination with galectin-1 antibody treatment, significantly suppressed the growth of xenografts in SCID mice, in comparison with all other groups (p < 0.05). γδTILs alone also showed the ability to inhibit tumour growth in vivo, but were more efficient when combined with specific antibody (p < 0.05).

Conclusion: Taken together, our results suggest that γδ-T cells, combined with galectin-1 antibody treatment, could be a more effective adoptive immunotherapy for patients with cervical cancer than traditional adoptive immunotherapy methods.
Comparison of total oxidant/antioxidant status in unconjugated hyperbilirubinemia of newborn before and after conventional and LED phototherapy: A prospective randomized controlled trial
Authors: Demirel Gamze , Uras Nurdan , Celik Istemi H , Aksoy Hatice T , Oguz Serife S , Erdeve Omer , Erel Ozcan , Dilmen Ugur
Published: May 2017

Purpose: We evaluated and compared the oxidant and antioxidant status of hyperbilirubinemic infants before and after the two forms of phototherapy: conventional and LED phototherapy, in order to identify the optimal treatment method.

Method: Thirty newborns exposed to conventional (Group I) phototherapy and 30 infants exposed to LED phototherapy (Group II) were studied. The serum total antioxidant capacity (TAC) and the total oxidant status (TOS) were assessed by EREL's method.

Results: There were no statistically significant differences in TAC or TOS levels between Group I and Group II prior to phototherapy, and no statistically significant difference in TAC levels between the two groups after phototherapy; however, TOS levels were significantly lower in Group II compared to Group I after phototherapy. Oxidative stress index (OSI) increased after conventional phototherapy (p < 0.05)

Conclusion: The increase in TOS following conventional phototherapy was not not observed following LED phototherapy. This difference should be considered when using phototherapy.
Sources of bias in signals of pharmaceutical safety in pregnancy
Authors: Koren Gideon , Nickel Sheri
Published: May 2017

Every year scores of new pharmaceuticals enter the market, almost never with human fetal safety data. Such data typically accumulate during the first years of clinical use, in the form of case reports, case series, prospective and retrospective cohorts and case control studies. All of these methods suffer from serious sources of bias, often leading to alarming signals of teratogenicity that are later found to be false. This review highlights major sources of bias, including the bias against the null hypothesis in its different forms, ascertainment and recall bias, in fetal exposure to pharmaceutical molecules.
The relationship between lipoprotein(a) and coronary artery disease, as well as its variable nature following myocardial infarction
Authors: Ornek Ender , Murat Sani , Duran Mustafa , Turfan Murat , Kurtul Alparslan , Demircelik Muhammed B , Vatankulu Mehmet A , Ocek Hakan , Akdemir Ramazan
Published: May 2017

Purpose: The present study aimed to investigate the relationship between the severity of coronary artery disease (CAD) and level of Lipoprotein (LP)(a).

Methods: The study included 52 CAD patients and a control group consisting of 38 individuals. The patients were classified into three groups based on the clinical form of CAD (stable angina pectoris, SAP, unstable angina pectoris,UAP, and myocardial infarction,MI), and were further divided into three groups based on CAD severity (1-, 2- and 3-vessel). Serum Lp(a) levels were monitored 4, 8, and 24 h, 10 and 30 days following acute MI in 18 patients.

Results: Based on regression analysis, Lp(a) was not correlated with other lipoproteins or with risk factors of CAD, such as body mass index, smoking, family history, diabetes, age, gender, and hypertension (r = 0.08-0.22). 72% of the patients in the CAD group and 24% of the control group had an Lp(a) level > 30 mg dL–1 (P = 0.004), and Lp(a) levels were higher in 3-vessel patients than in 2-vessel and 1-vessel CAD patients (86% vs. 68%, P = 0.02 and 86% vs. 62%, P=0.01, respectively). Serum Lp(a) levels were higher in the UAP and MI groups than in the SAP group (48 ± 44.7 mg dL–1, 49 ± 36.1 mg dL–1 and 31.2 ± 22.3 mg dL–1 , respectively,P=0.02). Lp(a) levels increased after acute MI, and reached peak levels 10 days post-MI (41% increase, P=0.001) and remained considerably elevated (18%) 30 days post-MI (P=0.01).

Conclusion: Serum Lp(a) was higher in the UAP and MI patients in comparison with the SAP patients, and was higher in 3-vessel CAD in comparison with 1- and 2-vessel CAD patients.
LYVE-1 enhances the adhesion of HS-578T cells to COS-7 cells via hyaluronan
Authors: Du Yan , Liu Yiwen , Wang Yingzhi , He Yiqing , Yang Cuixia , Gao Feng
Published: May 2017

Purpose: Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), a specific molecular marker for lymph systems, has only one known ligand, hyaluronan (HA). Many studies have reported that HA, on the surface of tumor cells, is associated with the metastatic behavior of cancer cells. The interaction of LYVE-1 with HA may facilitate tumor cell attachment and enhance dissemination of tumor cells to lymph nodes. The aim of this study was to explore the biological function of LYVE-1 and to determine whether the interaction between LYVE-1 and HA was directly involved in the adhesion of tumor cells to lymphatic vessels.

Methods: COS-7 cells were transfected with cDNA encoding LYVE-1 and expressed LYVE-1 assembled exogenously added HA. A high HA-expressing breast cancer cell line, HS-578T, was chosen to be the upper layer of cells that adhered to a lower layer of COS-7LYVE-1(+), COS-7pegfp-N1, or COS-7 cells for the adhesion analyses. The mechanism of adhesion was investigated by an experiment in which the HA on the surface of HS-578T cells was digested by Streptomyces hyaluronidase before the HS-578T cells were allowed to adhere to COS-7LYVE-1(+) cells.

Results: Results showed that more adhesion was observed between HS-578T and COS-7LYVE-1(+) cells, while less adhesion was observed between HS-578T cells and either COS-7pegfp-N1 or COS-7 cells (p < 0.01). Decreased HA on the HS-578T cell surface could reduce the adhesion of HA-578T cells to COS-7LYVE-1(+) cells.suggesting that this adhesion might be mediated through HA.

Conclusion: Our results suggest that LYVE-1 allows the adhesion of tumor cells through the interaction of HA on the tumor cell membrane with LYVE-1.
Increased NPC1L1 and serum cholesterol in a chronic rejection rat
Authors: Zhu Yanfei , Zhou Jing
Published: May 2017

Purpose: To measure serum cholesterol and triglyceride levels and NPC1L1 mRNA and protein as an index of cholesterol absorption during the development of chronic rejection (CR) in a rat model of intestinal transplantation.

Methods: Rats were randomly divided into two groups: Group 1 (n=20) underwent syngenic Lewis-to-Lewis transplantation and Group 2 (n=20) underwent allogenic F344-to-Lewis transplantation as well as treatment with FK506. Blood samples and intestinal tissue were procured on the 190th day after operation. Histological changes were analyzed and the semiquantitative scores of histological parameters were compared. The serum levels of cholesterol and triglyceride were determined. The expression of Niemann-Pick C1 Like 1(NPC1L1) mRNA and protein were analyzed by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) and immunohistochemistry, respectively.

Results: All the animals survived for the 190 days. The appearance and histology of isografts were almost normal whereas the allografts displayed thickened bowel wall and mesenteric fibrosis, concentric intimal thickening and interstitial fibrosis and inflammatory infiltration. The histology scores displayed a significant difference between the allografts and isografts (P < 0.001). No differences were observed for triglycerides for the two groups. The serum cholesterol levels increased significantly in the allogenic group in comparison with the syngenic group (P=0.034), while no difference was observed for triglyceride levels between groups. RT-PCR showed that the expression of NPC1L1 of allografts increased significantly (P=0.004). Immunohistochemistry confirmed RT-PCR findings.

Conclusions: Neointima formation and mesenteric fibrosis were the dominant pathological features. The increased expression of NPC1L1 might contribute to hypercholesterolemia, which may be involved in the pathogenesis of transplant arteriosclerosis.
Reduced expression of ΔΝp63α in cervical squamous cell carcinoma
Authors: Zhou Ying , Xu Qianqian , Ling Bin , Xiao Weihua , Liu Peishu
Published: May 2017

Purpose: As a member of the p53 family, p63 is considered to be an important differentiation regulation transcriptional factor, but the roles of p63 in many epithelial tumourigenesis and metastasis processes are still not clear. This study was designed to investigate the expression of p63 and its isoform in normal tissues and squamous cell cancer tissues of uterine cervix, and its significance in cancer cell differentiation.

Methods: The expression of p63 was assessed in cervical tissue and cell lines by immunohistochemistry, RT-PCR and Western Blotting. The relationships between p63 protein, various clinico-pathological features, and the differentiation marker involucrin were analyzed.

Results: ΔΝp63α is the predominant isoform expressed in cervical epithelial tissues, and it is decreased in moderately or poorly differentiated cervical squamous carcinoma, as well as in the HeLa, SiHa and C33A cervical cancer cell lines. The expression level of ΔΝp63α was positively correlated with that of involucrin in cervical squamous cancer tissue, and the expression of ΔΝp63α is decreased with the degree of tumour invasion.

Conclusion: The decrease of ΔΝp63α in cervical squamous cell cancer appears to be associated with the tumour progression, and ΔΝp63α may be a sensitive marker for cervical squamous cancer differentiation.
Nausea and vomiting of pregnancy (NVP) and depression: cause or effect?
Authors: Bozzo Pina , Einarson Thomas R , Koren Gideon , Einarson Adrienne
Published: May 2017

Background: Both nausea and vomiting and depression are common conditions affecting women during pregnancy. Several studies have linked depression with nausea and vomiting of pregnancy (NVP); however, researchers were unable to determine whether depression was caused by NVP or by a pre-existing condition.

Objective: To determine whether NVP is associated with depression in women with no history of depression prior to pregnancy.

Study design and methods: This was a prospective, observational, longitudinal study. Women with no diagnosis of depression who contacted The Motherisk Program prior to becoming pregnant or were at < 6 weeks gestation were enrolled in the study. Each woman was interviewed at 8, 11, 18, 30 weeks gestation and at 6-18 weeks post-partum. At each interview, we administered the EDPS, Wellbeing and PUQE questionnaires and analyzed the data for correlation between depression and NVP.

Results: Data were analyzed obtained from 57 women. There were five EPDS scores ≥13 (one at baseline and two each at weeks 8 and 11) considered indicative of depression and 11 cases with PUQE scores ≥7, indicative of moderate-high severity of NVP. We did not find an association between high PUQE scores and high EPDS scores and conversely, there was no relationship between high EPDS scores and high PUQE scores.

Conclusion: No association between depressive symptoms and NVP was observed; however, our sample size was very small and further studies could be done with a larger population of pregnant women.
Relationship between white blood cell count at admission and short term outcome in patients with acute cerebral infarction
Authors: Peng Yanbo , Wang Dali , Zhang Jiang , Xue Xinhong , Wang Zhuo , Tong Weijun , Xu Tan , Zhang Yonghong
Published: May 2017

Purpose: We studied the association between admission white blood cell (WBC) count and short term outcome in patients with acute cerebral infarction.

Methods: 2808 patients with acute cerebral infarction were included in the study. WBC count and other variables were collected within the first 24 hours of admission. Clinical outcomes (death or dependency) were evaluated by neurologists during hospitalization. The associations between WBC count and in-hospital death or dependency at discharge were analyzed using a multiple logistic model.

Result: Multivariate-adjusted odds ratio (95% confidence intervals) of dependency associated with patients with WBC of 10.0-10.9×109/L, 11.0-11.9×109/L, ≥12.0×109/L were 1.46(0. 87-2. 45), 6.21(3. 70-10. 42) and 7.01(4. 53-10. 87), respectively, when compared with patients with admission WBC counts < 10.0x109/L. Multivariate-adjusted odds ratio (95% confidence intervals) of death associated with WBC 10.0-10.9×109/L, 11.0-11.9×109/L and ≥12.0×109/L were 2.098(0. 96-4. 58), 4.79(2. 24-10. 22) and 5.59(3. 14-9. 98), respectively.

Conclusion: Increased WBC count at admission was significantly and positively associated with in-hospital death or dependency at discharge among patients with acute cerebral infarction.
Adiponectin/leptin ratio and Metabolic Syndrome in a Mexican American population
Authors: Mirza Shaper , Qu Hui-Qi , Li Quan , Martinez Perla J , Rentfro Anne R , McCormick Joseph B , Fisher-Hoch Susan P
Published: May 2017

Objective: Adiponectin and leptin play critical roles in the development of Metabolic Syndrome (MetS). This study was designed to assess the feasibility of using circulating levels of adiponectin and leptin for the early diagnosis of MetS.

Methods: A cross-sectional study was performed using data from 367 participants randomly selected from a well-characterized cohort of Mexican-Americans living at the US-Mexico border.

Results: Significant differences in circulating levels of adiponectin and leptin were observed between males and females. Adiponectin/leptin correlated significantly with MetS in this population. A receiver-operator characteristic (ROC) analysis demonstrated that adiponectin/leptin showed a high sensitivity (70.9% for males, 78.9% for females) and specificity (90.2% for males and 69.8% for females) for the diagnosis of MetS, independent of BMI measurements.

Conclusion: These data support the central role of adiponectin and leptin in MetS, and demonstrated that adiponectin/leptin can be used as a highly sensitive and specific biomarker for MetS.
Anti-inflammatory and anti-fibrotic effects of sirolimus on bleomycin-induced pulmonary fibrosis in rats
Authors: Tulek Baykal , Kiyan Esen , Toy Hatice , Kiyici Aysel , Narin Cuneyt , Suerdem Mecit
Published: May 2017

Purpose: Pulmonary fibrosis is a devastating disease with a poor prognosis. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. The aim of this study was to evaluate the anti-inflammatory and anti-fibrotic effects of sirolimus (SRL), which is a potential anti-fibrotic agent, by using bleomycin (BLM)-induced pulmonary fibrosis model in rats.

Methods: A single intra-tracheal injection of BLM (2.5 U/kg) was administered and sirolimus (2.5 mg/kg/day) was given orally, beginning either one day before (early SRL) or nine days after (late SRL) the BLM administration. The effect of SRL on fibrosis was studied by analysis of cytokine levels in BAL fluid, measurement of lung tissue hydroxyproline (HPL) content and histopathological examination.

Results: Both early and late SRL administrations caused a decrease in the levels of IL-13, PDGF-A and TGF-β1 (p=0.001) and an increase in IFN-γ levels (p=0.001) in BAL fluid. Early and late SRL also caused a decrease in HPL content (p=0.001). Early sirolimus caused a significant decrease in fibrosis score (p=0.001), while late SRL did not.

Conclusion: Sirolimus was effective in BLM-induced pulmonary fibrosis model, especially in the early phases of the disease.
Association of Interleukin-10 gene polymorphisms with ankylosing spondylitis
Authors: Lv Chengyu , Wang Yingzheng , Wang Jinqin , Zhang Haining , Xu Hao , Zhang Dianliang
Published: May 2017

Objective: Genetic polymorphisms of the Interleukin-10 (IL-10) promoter have been implicated in several autoimmune diseases, including seronegative spondyloarthropathies. This study investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of IL-10 are associated with ankylosing spondylitis (AS), a common subtype of spondyloarthritis (SpA).

Methods: The serum levels of IL-10 were measured with an enzyme-linked immunosorbent assay (ELISA). The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819C/T and -592C/A in the IL-10 gene promoter were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: 110 AS patients and 120 ethnic-matched healthy controls were included in this study. The serum levels of IL-10 were significantly higher in AS patients than healthy controls (Z=-10.9, P < 0.001). Single SNP analysis showed no significant differences in the allelic and genotypic frequencies of -592A/C between the AS patients and healthy controls. No -1082GG genotype was found in this study. An increased frequency of -1082G allele was noted in AS patients (P=0.047). In a logistic regression analysis, the -1082AG genotype was associated with an odds ratio of 1.993 (95%CI, 1.046-3.800, P=0.034) for AS. And the -819CC genotype was associated with an odds ratio of 3.125 (95%CI, 1.246-7.836, P=0.015) for AS. Furthermore, haplotype analysis revealed that GCC haplotype was associated with a significantly increased risk of AS as compared with the ATA haplotype (OR=2.19; 95% CI, 1.13-4.26; P=0.02).

Conclusion: Our results indicate that the gene haplotype of IL-10 can contribute to the susceptibility to AS in a Chinese population.
Characterization of management and outcomes of patients with acromegaly in Vancouver over 30 years
Authors: Almalki Mussa H , Chesover Alexander D , Johnson Michelle D , Wilkins Graeme E , Maguire John A , Ur Ehud
Published: May 2017

Purpose: The purpose of this study was to characterize the management and outcomes of patients with acromegaly seen in single center in Vancouver, British Columbia, Canada over a 30 year period.

Methods: The study involved retrospective data collection from charts of patients diagnosed with acromegaly since 1980: 130 patients (63 male and 67 female) were included in the analysis, with a mean age at diagnosis of 43 years (male) and 47 years (female).

Results: The most common presenting features included acral enlargement, coarse facial features, sweating/oily skin and headache. All cases were caused by pituitary adenomas, of which 58.5% were macroadenomas and of these, 30.8% were invasive. The most common co-morbidities were hypertension 31.5%, arthralgia 28%, diabetes 27.7% and sleep apnea 23.8%. The vast majority (88.5%) of patients was treated surgically and of these patients, 21.5% also received radiotherapy and 66.9% received medical therapy. When stringent cure criteria were applied (based on latest growth hormone (GH) and IGF-1 results) the outcomes were 35.4% cured or controlled, 30% remained active, 15.4 discordant results and 19.2 % with no results reported. Twenty eight percent of patients who underwent surgery and 32% of patients who underwent radiotherapy were not cured but symptoms were moderately well controlled with medical therapy.

Conclusion: Based on the size of population studied, this study showed a prevalence of acromegaly of 29 per million. The cure rate was low following surgery but with adjuvant medical treatment disease control was achieved in most individuals.
Telmisartan-induced eNOS gene expression is partially independent of its PPAR-gamma agonist property
Authors: Ríos Nisa Buset , Esparragón Francisco Rodríguez , Pérez José C Rodríguez
Published: May 2017

Purpose: Telmisartan, an angiotensin II receptor blocker (ARB), also acts as an activator of peroxisome proliferator-activated receptor-gamma (PPAR-gamma; PPAR-γ). Several studies have explored the PPAR-γ-endothelial nitric oxide synthase (eNOS) pathway associated with improvement of endothelial function by telmisartan. The ability of telmisartan to induce gene expression and protein level of eNOS and PPARγ in adipocytes was investigated.

Methods: Expression of aP2, PPARγ, eNOS and iNOS genes were measured using the quantitative real-time polymerase chain reaction. The changes, at the protein level, were explored by Western blot, which evaluated the native and phosphorylated eNOS forms, eNOS-Ser1177 and eNOS-Thr495.

Results: Adipocytes, exposed to telmisartan, exhibited an increase in PPARγ gene expression but a decrease in protein level. Nonetheless, after the exposure to telmisartan, eNOS-Ser1177 phosphorylation, associated with eNOS activity increment, reached its highest value while eNOS-Thr495 phosphorylation, involved in the inhibition of eNOS activity, showed its lowest value.

Conclusion: The results suggest that telmisartan preserves eNOS activity via a mechanism that is partially independent of the PPARγ-eNOS pathway in adipocytes.
Prevalence of atrial fibrillation in patients taking TSH suppression therapy for management of thyroid cancer
Authors: Abonowara Abdulgani , Quraishi Ata , Sapp John L. , Alqambar Mohammed H. , Saric Adi , O'Connell Colleen M. , Rajaraman Murali M. , Hart Robert D. , Imran Syed A.
Published: May 2017

Background: Suppression of thyroid stimulating hormone (TSH) below the normal range with administration of L-thyroxine has been shown to improve survival in patients treated for thyroid cancer (TC). Although most TC patients require long-term TSH suppression therapy, the effect of this treatment on cardiac rhythm remains unknown. A cross-sectional study was conducted to determine the prevalence of atrial fibrillation (AF) in TC patients on TSH suppressive therapy.

Methods: All TC patients seen between June 2009 and March 2010 through a multidisciplinary thyroid oncology clinic, Halifax, Nova Scotia, Canada, for whom TSH suppressive therapy had previously been recommended, were recruited into the study. Each patient underwent an electrocardiogram and filled out a questionnaire relevant to causes, signs/symptoms of AF and/or its complications. The prevalence of AF in this population then was compared against the published prevalence of AF in general populations.

Results: A total of 351 patients were seen in the thyroid clinic of which 136 patients met the inclusion criteria for the study. The mean age was 52 years, 85% were female, and mean follow-up duration prior to recruitment was 11 years. The mean TSH was 0.17 mIU/L (Normal: 0.35 – 5.5 mIU/L). There were 14 patients found to have AF (two patients had long-standing persistent AF and 12 patients had paroxysmal AF). The mean ages of patients with and without AF were 61.6 years and 51.4 years, respectively (P = 0.01). Prevalence of AF in the study group was 10.3%; the rate of AF in the TC patients aged 60 years and over (17.5%) was higher than the rate of AF in published data in people 60 years and over (P < 0.001). AF was diagnosed after the initiation of the TSH suppression therapy in all except one patient.

Conclusion: TSH suppression in thyroid cancer is associated with a high prevalence of AF, particularly in older individuals.
A practical pressure measuring method for the upper urinary tract during ureteroscopy
Authors: Cai Yi , Li Xiaojuan , Zhu Baoyi , Chen Ruihan , Ye Chunwei , Wang Yu , Wang Yu , Tao Yiran , Sun Qipeng , Wen Xingqiao
Published: May 2017

Purpose: The purpose of this study was to develop and test a method for measuring pressure in the upper urinary tract during ureteroscopic operations and to evaluate its efficacy and clinical significance.

Methods: A total of 44 patients, each with a ureteral calculus in the proximal ureteral segment, were enrolled in the study group: 21 patients with an acute and 23 with a chronic obstruction. The ureteroscope was passed forward to the upper segment of the obstructed ureter immediately after the calculus was broken and the intraluminal ureteral pressure was then transmitted along with the irrigant flow (0.9% sodium chloride).

Results: The mean ureteral pressures of the acute obstruction subgroup, the chronic obstruction subgroup and the control group were 74.5 mmHg (22-180 mmHg), 32.5 mmHg (9-53 mmHg) and 10.2 mmHg (8-13 mmHg), respectively. A significant correlation was found between ureteral pressure and the following indexes: the duration of the obstruction (r=0.985), the diameter of the ureter above the calculus (r=0.878) and the depth of the hydronephrosis of the renal pelvis (r=0.862). No associations were observed between the pressure and the serum creatinine level (r=0.214) or the urinary leukocyte count (r=0.047). The intraluminal pressure correlated with the glomerular flow rate (GFR) of the affected kidney (r =0.975, P =0.001).

Conclusions: This new method is non-invasive, practical and reproducible. Measuring the intraluminal pressure of the ureter can provide a valuable index to quantify the severity of the obstruction of the upper urinary tract, which is helpful for the prediction of the affected renal function prognosis.
Melatonin ameliorates oxidative damage in hyperglycemia-induced liver injury
Authors: Korkmaz Gulcan G , Uzun Hafize , Cakatay Ufuk , Aydin Seval
Published: May 2017

Purpose: Melatonin (N-acetyl-5-methoxy-tryptamine) is synthesized mainly by the pineal gland and its antioxidant properties have been demonstrated both in short and long term studies. Our aim was to clarify the effects of hyperglycemia and to administer melatonin on lipid peroxidation, protein oxidation and oxidative DNA damage in rat.

Methods: Malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels were determined in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma and liver. Thirty-eight male Wistar rats were divided into four groups: 1 - injected with saline (n = 8), 2 - injected with melatonin (n = 10), 3 - injected with STZ (65 mg/kg, i.p.) (diabetic group) (n = 10) and 4 - injected with melatonin (10 mg/kg/day, i.p.) and STZ (65 mg/kg, i.p.) (n = 10) for 8 weeks (diabetic+ melatonin group). Colorimetric methods were used to determine the level of the oxidative stress markers. 8-OhdGwas measured using ELISA.

Results: MDA, PCO and 8-OHdG levels in the plasma and the liver homogenates of diabetic rats were higher than controls and were significantly reduced after melatonin treatment. T-SH and GSH levels in samples were markedly reduced in untreated diabetic rats compared with control rats; however, these parameters were increased in diabetic rats following melatonin treatment.

Conclusion: Our findings showed that melatonin administration partially ameliorated oxidative damage in liver injury in STZ-induced diabetic rats. The present study suggests that melatonin functions as a potent antioxidant agent in diabetes. Melatonin, a nutritional supplement, may be a good therapeutic option for diabetic patients.
Protein Oxidation in Metabolic Syndrome
Authors: Hopps Eugenia , Caimi Gregorio
Published: May 2017

Purpose: Oxidative stress plays a pivotal role in the pathogenesis of the metabolic syndrome and in the progression of its complications. Carbonylated proteins are a stable marker of severe oxidative stress because damage to the protein structure is irreversible and may cause an inhibition of their enzymatic activity or an increased susceptibility to proteolysis. There are few data regarding protein oxidation in metabolic syndrome, although elevated levels of carbonyl groups are often detected in subjects with obesity, diabetes mellitus, hypertension or dyslipidemia, well-known components of the metaboic syndrome. In particular, obesity, insulin resistance and diabetes mellitus are frequently associated with increased protein carbonylation. A relationship between insulin resistance, protein oxidative stress and inflammation has also been suggested as well as protein oxidation products are correlated with overexpression of resistin, TNF-α and IL-6.

Conclusion: Therapeutic interventions based on lifestyle modifications and pharmacological agents in order to correct all the main risk factors influence oxidative stress and protein carbonylation.
Dismantling Sociocultural Barriers to Eye Care with Tele-Ophthalmology: Lessons from an Alberta Cree Community
Authors: Arora Sourabh , Kurji Ayaz K , Tennant Matthew TS
Published: May 2017

Purpose: There are significant disparities in access to health care amongst Aboriginal Canadians. The purpose of this study was to determine whether tele-ophthalmology services, provided to Aboriginal Canadians in a culturally-sensitive community-based clinic, could overcome social and cultural barriers in ways that would be difficult in the traditional hospital-based setting.

Methods: The Aboriginal Diabetes Wellness Program of Alberta incorporates culturally-sensitive health-related activities and rituals as a component of a diabetic retinopathy tele-ophthalmology screening program. Metrics of program attendance were collected while stakeholders participated in a survey to identify barriers to healthcare delivery.

Results: Aboriginal patients, cultural liaison, nurses and program administrators revealed economic, geographic, social and cultural barriers to healthcare faced by Aboriginal people. It was found that the introduction of culturally-sensitive programs led to increased appointment attendance; from 25% to 85%. Involvement of Aboriginal nurses, inclusion of culturally-sensitive activities and participation in spiritual ceremonies led to qualitative accounts of increased patient satisfaction, trust towards the healthcare team and communication amongst participants.

Conclusions: A culturally-sensitive model of healthcare delivery in a community-based health clinic improved access to tele-ophthalmology services. This was demonstrated by increased attendance at appointments and increased satisfaction amongst patients.
Probing without Irrigation in Children with Congenital Nasolacrimal Duct Obstruction
Authors: Isaza Gloria , Arora Sourabh
Published: May 2017

Purpose: The purpose of this study was to evaluate the results of probing, without fluorescein irrigation, as a primary treatment for epiphora and/or mucous discharge, secondary to congenital nasolacrimal duct obstruction (CNLDO)

Methods: The medical records of nine-two children (127 eyes) with CNLDO who underwent a single probing without the use of fluorescein irrigation between January 2006 and December 2011 were reviewed retrospectively. Inclusion criteria were no prior nasolacrimal surgical procedure, history of epiphora and/or discharge since birth or shortly after birth in one or both eyes and at least one of the following clinical signs: epiphora, muco-purulent discharge and increased tear meniscus height. Children were investigated in two sub-groups based on age at time of probing; group 1 (51 eyes/40 children) included children who underwent probing at age ≤ 2 years and group 2 (76 eyes/52 children) included children who underwent probing at age > 2years.
The primary outcome was the complete disappearance of symptoms and signs in the affected eye(s), assessed at 3 months after surgery.

Results: The success rate for the overall sample was 83.5 % (106/127 eyes), in group 1 was 90.2% (46/51) and in group 2 was 78.9% (60/76). There was no significant difference in success rate between groups (p=0.094). Gender (p=0.292), affected eye (p=0.647) and bilateral cases (p=0.739) were not associated with successful elimination of symptoms.

Conclusion: Probing without fluorescein irrigation for CNLDO beyond 1 year of age is highly successful and comparable to the published efficacy rates of the traditional probing with fluorescein irrigation.
Canadian Clinician Investigator Training in the 21st Century
Authors: Appleton C Thomas , Belrose Jillian , Ward Michael R , Young Fiona B
Published: May 2017

Purpose: Enhancing clinician-investigator (CI) training at Canadian medical schools is urgently needed to bolster the dwindling work force of medical professionals carrying out patient-oriented research in a wide array of medical fields. The purpose of this study is to obtain, from the 15 Canadian medical schools that offer one or more CI training programs, data on the number of trainees, funding levels, attrition rates or other important metrics to evaluate the outcomes of such training efforts.

Methods: All Canadian CI programs were surveyed to collect demographic information for the academic year 2010-2011 and compared this to historical data collected by the Association of Faculties of Medicine of Canada (AFMC) and MD/PhD program funding data from the Canadian Institutes of Health Research (CIHR).

Results: Over the past decade, enrolment in Canadian CI training programs has increased approximately four-fold. Program-specific funding (CIHR) has also increased, but nearly 50% of MD/PhD trainees are still not supported through dedicated CIHR funding.

Conclusion: It is too early to know to what extent this increase in both CI and funding will sustain the workforce of Canadian researchers carrying out patient-oriented research. Monitoring of CI training demographics across Canada, beyond this baseline study, will be essential to measure outcomes from CI training programs and to guide response from funding bodies and policy-makers.
A unifying framework for depression: Bridging the major biological and psychosocial theories through stress
Authors: Roy Amrita , Campbell M Karen
Published: May 2017

Several mechanisms for the development of depression have been proposed, and a comparative examination reveals considerable overlap. This paper begins by summarizing the conclusions drawn in the literature on the major biological theories: HPA-axis hyperactivity, the monoamine theory, the cytokine hypothesis/ macrophage theory, and structural changes to relevant brain regions and neurons. It then discusses the role of psychosocial stress as a bridge between the pathophysiology of depression and its predominantly psychosocial risk factors, touching upon theories offered in psychology and in population health. This paper further proposes a unifying framework which integrates the major theories. The multiple systems involved, and the directional complexity among them, likely help to explain the wide-ranging symptoms associated with depression, and the wide variety of comorbid medical conditions. They may also contribute to challenges in treatment, the diversity in symptoms and treatment outcomes among individuals, and the high rates of symptom persistence and relapse. The apparent bi-directionality of associations may suggest the existence of positive-feedback loops which aggravate symptoms; however, further bench research is required to confirm such phenomena. A better understanding of these interweaving associations is warranted. Additionally, given the significant influence of socioeconomic and psychosocial factors on the aetiology of depression, population-level interventions that address the social determinants of health are required. Current individual-level pharmacologic approaches are designed to treat pathophysiology once it is underway, and current individual-level non-pharmacologic interventions (such as talk therapy) are designed to moderate the relationship between psychosocial stress and pathophysiology. In contrast, a key strategy for primary prevention lies in population-level interventions that address the predominantly social causes of one of depression’s most notable risk factors: chronic psychosocial stress.
The Role of Morning Basal Serum Cortisol in Assessment of Hypothalamic Pituitary-Adrenal Axis
Authors: Yip Churn-Ern , Stewart Samuel A , Imran Fatima , Clarke David B , Mokashi Arati , Kaiser Stephanie M , Imran Syed A
Published: May 2017

Purpose: The use of morning basal serum cortisol levels as an alternative to dynamic testing for assessment of hypothalamic-pituitary-adrenal (HPA) axis has previously been reported. The purpose of this study was to determine the lower and upper cutoff values that would obviate subsequent HPA axis testing.

Methods: A single-centre, retrospective study from a tertiary care endocrinology clinic was conducted, analyzing data from 106 adult individuals referred for HPA axis testing who had undergone a 0800-0900 morning basal serum cortisol test followed by a standard dose (250 μg) adrenocorticotropin (ACTH) stimulation test. The ability of morning basal serum cortisol values to predict post-ACTH 30 or 60 minute peak cortisol value of > 500 or > 550 nmol/L was investigated.

Results: A morning basal cutoff of < 128 nmol/L is sufficient for predicting a post-ACTH value < 550 nmol/L, and morning basal cutoff levels of > 243 nmol/L and > 266 nmol/L predict peak post-ACTH values of > 500 and > 550 nmol/L respectively, obviating the need for dynamic testing. Regression analysis further demonstrated the log-linear relationship between morning basal and peak levels, while also finding a significant decrease in peak post-ACTH levels for patients diagnosed with secondary hypothyroidism (76 nmol/L lower, p=0.003) or secondary hypogonadism (61 nmol/L lower, p=0.02). These data suggest that the risk of cortisol deficiency is significantly higher in individuals with additional pituitary insufficiencies. The odds ratios for cortisol deficiency in patients with history of isolated secondary hypothyroidism was 3.41 (p=0.015), with isolated secondary hypogonadism was 4.77 (p=0.002) and with both was 7.45 (p=0.0002).

Conclusion: Morning basal serum cortisol levels show promise as an effective screening test for HPA insufficiency for most patients. Clinicians should consider the high probability of HPA insufficiency in patients with one or more pituitary insufficiencies.
Snail family proteins in cervical squamous carcinoma: Expression and significance
Authors: Zhao Weidong , Zhou Ying , Xu Hanjie , Cheng Yong , Kong Beihua
Published: May 2017

Purpose: Epithelial-mesenchymal transition (EMT) is crucial for tumor progression and metastasis. Snail family members, including Snail, Slug and Smuc, are the transcription factors that repress E-cadherin expression and induce epithelial-mesenchymal transition in some tumor tissues. In this study, the expression of snail family proteins in cervical squamous cancers was evaluated.

Methods: A series of 144 samples, comprising 28 cases of normal cervical tissues and 116 cases of squamous cell carcinoma (SCC), were used for analysis. The expression of Snail, Slug, Smuc, E-cadherin and vimentin was assessed in the tissues by immunohistochemistry and was statistically analyzed by SPSS13.0.

Results: The increase in nuclear expression of snail and smuc was associated with down-regulation of E-cadherin and up-regulation of vimentin. The nuclear expression of Snail and Smuc was positively associated with lymph node metastasis of the SCC, and the nuclear expression of Snail was also positively related with histological differentiation. In contrast, tumor size, histological differentiation, lymph node metastasis and stages of the SCC were not associated with the expression of Slug, cytpolasmic Smuc or cytoplasm levels of Snail.

Conclusion: Snail and Smuc proteins, but not Slug, may contribute to the onset of EMT in SCC. Inhibiting the expression of Snail and Smuc might be a potential therapeutic target for the treatment of metastasis and invasion of cervical carcinomas.
Levels of interleukin-33 and interleukin-6 in patients with acute coronary syndrome or stable angina
Authors: Liu Cong-Lin , Shen De-Liang , Zhu Kui , Tang Jun-Nan , Hai Qi-Min , Zhang Jin-Ying
Published: May 2017

Purpose: The purpose of this study was to investigate the levels of interleukin-33 (IL-33) and interleukin-6 (IL-6) in patients with acute coronary syndrome or stable angina.

Methods: Serum IL-33 and IL-6 were measured with Enzyme Linked Immuosorbent Assay (ELISA) in patients with acute coronary syndrome (ACS, n = 40), and stable angina pectoris (SAP, n = 43). IL-33 and IL-6 were also determined in 30 healthy subjects (control group).

Results: The serum level of IL-33 in the ACS group (78.60 ± 44.84 ng/L) was lower than in the SAP (102.58 ± 37.21 ng/L, P < 0.01) or control groups (130.24 ± 10.17 ng/L, P < 0.01). The serum level of IL-6 in the ACS group (39.90 ± 12.64 ng/L) was higher than in the SAP (18.68 ± 11.89 ng/L, P < 0.05) or control groups (6.28 ± 17.72 ng/L, P < 0.05). There were no differences in serum levels of IL-33 and IL-6 among the single-, double- and triple-vessel lesion groups. IL-33 and IL-6 levels were negatively correlated with each other in the ACS (r = -0.871, P < 0.01) and SAP groups (r = -0.788, P < 0.01).

Conclusion: The serum level of IL-33 was lower in patients with ACS or SAP and was negatively correlated with the serum level of IL-6. Thus, IL-33 and IL-6 may be used as biomarkers for evaluating inflammatory response and severity of coronary heart disease in patients with ACS or SAP.