bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonerythropoietic Properties of Erythropoietin: Implication for Tissue Protection
Authors: Rathod Dhanesh B. , Salahudeen Abdulla K.
Published: May 2016

Erythropoietin (EPO) is used at present in clinical practice to stimulate red cell production. However, a number of reports have emerged suggesting the presence of nonerythropoietic properties for EPO. Chief among them is its ability to confer protection against acute tissue injury. In this report, we briefly review the role of EPO in tissue protection and provide examples of tissue protection using cisplatin-induced kidney injury model. Also provided is a brief description of potential pathways through which EPO may be mediating this effect.
ANKK1/DRD2 Locus Variants are Associated with Rimonabant Efficacy in Aiding Smoking Cessation
Authors: Wilcox Charles S. , Noble Ernest P. , Oskooilar Nader
Published: May 2016

Background

Polymorphism of the DRD2 gene (rs1800497), previously termed Taq1A, includes the A1 and A2 alleles. The A1+ genotype (A1/A1, A1/A2) has been associated with smoking dependence. The present study determined which polymorphism of the DRD2 gene had a salutary outcome in administration of rimonabant, a drug used in smoking cessation and obesity studies.

Methods

Seventy-six (76) smokers enrolled into a double-blind, placebo-versus-rimonabant, 10-week smoking cessation drug trial. Subjects provided a blood sample to determine whether they had the DRD2 A1+ genotype (A1/A1, A1/A2) or the DRD2 A1− genotype (A2/A2). Smoking cessation (or continuation) was monitored on a weekly basis with on-site carbon monoxide (CO) monitoring.

Results

Smokers in the rimonabant A1− group were significantly more successful in completely stopping smoking compared to subjects in the placebo A1− group ( P < 0.05). However, there was no difference in smoking cessation when the rimonabant A1+ group was compared to the placebo A1+ group. With respect to quantified verifiable/objective smoking cessation outcomes, exhaled CO (parts per million) was monitored during each week of the study. The rimonabant A1− group compared to the placebo A1− group was quantifiably smoking less at weeks 5, 6, and 7 ( P < 0.05), at week 8 ( P < 0.01), and at weeks 9 and 10 ( P < 0.001). No significant difference was found in exhaled CO levels between rimonabant A1+ group and the placebo A1+ group in any of the weeks studied.

Conclusions

These findings further support the rationale for incorporating genotyping into clinical trials, particularly smoking cessation trials. Rimonabant demonstrated early and sustained smoking cessation efficacy only in noncarriers of the A1 allele. These results also underscore the risks of heterogeneity contributing to type 2 errors, when analyzing (phase 2 or 3) data. The potential clinical, regulatory, and commercial benefits associated with expediting and enhancing drug development, vis-à-vis the integration of biomarkers in clinical research, is supported by our findings.
Protein Kinase C-Beta Inhibition Induces Apoptosis and Inhibits Cell Cycle Progression in Acquired Immunodeficiency Syndrome–Related Non-Hodgkin Lymphoma Cells
Authors: Saba Nakhle S. , Levy Laura S.
Published: May 2016

Introduction

Acquired immunodeficiency syndrome (AIDS)-related non-Hodgkin lymphoma (NHL) constitutes an aggressive variety of lymphomas characterized by increased extranodal involvement, relapse rate, and resistance to chemotherapy. Protein kinase C-beta (PKCβ) targeting showed promising results in preclinical and clinical studies involving a wide variety of cancers, but studies describing the role of PKCβ in AIDS-NHL are primitive if not lacking.

Methods

In the present study, 3 AIDS-NHL cell lines were examined: 2F7 (AIDS–Burkitt lymphoma), BCBL-1 (AIDS–primary effusion lymphoma), and UMCL01-101 (AIDS–diffuse large B-cell lymphoma).

Results

Immunoblot analysis demonstrated expression of PKCβ1 and PKCβ2 in 2F7 and UMCL01-101 cells, and PKCβ1 alone in BCBL-1 cells. The viability of 2F7 and BCBL-1 cells decreased significantly in the presence of PKCβ-selective inhibitor at half-maximal inhibitory concentration of 14 and 15 μmol/L, respectively, as measured by tetrazolium dye reduction assay. In contrast, UMCL01-101 cells were relatively resistant. As determined using flow cytometric deoxynucleotidyl transferase dUTP nick-end labeling assay with propidium iodide staining, the responsiveness of sensitive cells was associated with apoptotic induction and cell cycle inhibition. Protein kinase C-beta–selective inhibition was observed not to affect AKT phosphorylation but to induce a rapid and sustained reduction in the phosphorylation of glycogen synthase kinase-3 beta, ribosomal protein S6, and mammalian target of rapamycin in sensitive cell lines.

Conclusions

The results indicate that PKCβ plays an important role in AIDS-related NHL survival and suggest that PKCβ targeting should be considered in a broader spectrum of NHL. The observations in BCBL-1 were unexpected in the absence of PKCβ2 expression and implicate PKCβ1 as a regulator in those cells.
Evaluation of Serum Level of Tumor Necrosis Factor Receptor II in Hepatitis C Virus (Genotype 4)-Infected Middle-Aged Men with and without Diabetes and Its Complications in Egypt: A Pilot Study
Authors: Sobhy Said Elham , El Husseiny Noha Mohamed , Mosaad Nehad A.
Published: May 2016

Background

Tumor necrosis factor α (TNF-α) is a type of cytokine produced by macrophages and other cell types in response to various stimuli. Many studies have shown that TNF-α is involved in the development of diabetes. It also has a pivotal role in the inflammatory process of chronic hepatitis C.

Objectives

This study aimed to examine the hypothesis that TNF is increased in patients infected with hepatitis C virus (HCV) and with diabetes rather than in patients infected with HCV or with diabetes alone.

Methods

Patients were divided into 5 groups: patients with diabetes without complications and without HCV infection (group 1), patients with diabetes and complications but without HCV infection (group 2), patients without diabetes but with HCV infection (group 3), patients with diabetes without complications but with HCV infection (group 4), and patients with diabetes and complications and with HCV infection (group 5).

Results

Results revealed an activation of the TNF axis in all tested patients when compared with the level of healthy Egyptians done in previous studies. However, although there was a gradual escalation in the activation of the TNF axis in these groups, the increase did not amount to a statistical difference between them ( P > 0.05). However, the trend was toward the higher values in HCV infection with diabetes and its complications. The number of studied patients may be a limitation of this research. There was no correlation between the level of TNF receptor II and the levels of transaminases, albumin, and creatinine in the different groups or the degree of microalbuminuria in the groups of patients with diabetic complications. Also, there was no relation between the hepatic or splenic size and the level of TNF receptor II.

Conclusions

The presence of diabetes and its complications in patients with HCV infection could not be attributed only to the activation of the TNF system at least in Egyptian patients.
Dose-Dependent Acute Effects of Passive Smoking on Left Ventricular Cardiac Functions in Healthy Volunteers
Authors: Yarlioglues Mikail , Kaya Mehmet Gungor , Ardic Idris , Dogdu Orhan , Yarlioglues Hatice , Zencir Cemil , Ozdogru Mehtap , Akpek Mahmut , Kasapkara Haci Ahmet , Sarli Bahadir , Duran Mustafa , Dogan Ali , Ozdogru Ibrahim , Oguzhan Abdurrahman
Published: May 2016

Objective

We have previously shown that acute passive smoking impaired left ventricular diastolic function in healthy volunteers. The aim of this study was to determine whether length of exposure and/or ambient smoke concentration is the key determinant of this outcome.

Methods

We measured blood carboxyhemoglobin (COHb)and lactate level to investigate the acute effects of passive smoking on tissue oxygenation. A total of 90 healthy nonsmoker volunteers were prospectively enrolled into the study. Each of 30 subjects were exposed to carbon monoxide (CO) less than 5.0 ppm smoke in group A for 30 minutes, to CO 5 to 10 ppm smoke in group B for 30 minutes, and to CO less than 5.0 ppm smoke in group C for 60 minutes. Hemodynamic parameters were obtained, blood samples for measuring COHb and lactate levels were taken and echocardiographic examinations were performed at baseline and after exposure to passive smoking.

Results

Mean ± SD CO levels in groups A, B, and C were 4.2 ± 0.5 ppm, 9.2 ± 0.3 ppm, and 4.1 ± 0.8 ppm, respectively. There was no change in left ventricular systolic functions in all groups. Left ventricular diastolic functions were impaired in groups B and C, whereas no change was observed in group A. Carboxyhemoglobin and lactate levels increased after passive smoking in groups B and C. However, group B had significantly higher COHb and lactate levels compared to group C ( P < 0.001).

Conclusions

Our results suggested that passive smoking at a certain dose in relation with length of exposure and ambient smoke concentration seems to cause relative left ventricular diastolic dysfunction.
Developing Your Career in an Age of Team Science
Authors: Zucker Deborah
Published: May 2016

Academic institutions and researchers are becoming increasingly involved in translational research to spur innovation in addressing many complex biomedical and societal problems and in response to the focus of the National Institutes of Health and other funders. One approach to translational research is to develop interdisciplinary research teams. By bringing together collaborators with diverse research backgrounds and perspectives, these teams seek to blend their science and the workings of the scientists to push beyond the limits of current research.

While team science promises individual and team benefits in creating and implementing innovations, its increased complexity poses challenges. In particular, because academic career advancement commonly focuses on individual achievement, team science might differentially impact early stage researchers. The need to be recognized for individual accomplishments to move forward in an academic career may give rise to research team conflicts. Raising awareness to career-related aspects of team science will help individuals (particularly trainees and junior faculty) take steps to align their excitement and participation with the success of both the team and their personal career advancement.
Identification of Two Novel Mutations in TRPS1 Gene in Families with Tricho-Rhino-Phalangeal Type I Syndrome
Authors: Flores-Cuevas Arturo , Mutchinick Oswaldo , Morales-Suárez Jose J. , González-Huerta Luz Maria , Cuevas-Covarrubias Sergio A.
Published: May 2016

Background

Autosomal dominant tricho-rhino-phalangeal syndrome I (TRPS I) is due to mutations in the TRPS1 gene. Tricho-rhino-phalangeal syndrome I is characterized by peculiar face and skeletal anomalies. Cone-shaped epiphyses are the characteristic radiographic findings.

Objective

To describe 2 families with TRPS I and 2 novel mutations in the TRPS1 gene.

Patients

The study included 2 nonrelated families with TRPS I. All exons of the TRPS1 gene were analyzed from genomic DNA.

Results

The TRPS1 gene mutation analysis showed in family 1 the c.978C>A nonsense mutation within exon 4 and in family 2 the c.164A>C missense mutation within exon 3.

Conclusions

We found 2 families with TRPS1 caused by 2 novel mutations in the TRPS gene, particularly a missense mutation in exon 3, outside the GATA zinc finger domain, that leads a mild TRPS phenotype. Our data show a higher genotypic spectrum in the TRPS I and demonstrate that mutations in the amino terminus of the transcription factor result in TRPS I syndrome.
RANTES, TNF-α, Oxidative Stress, and Hematological Abnormalities in Hepatitis C Virus Infection
Authors: Tawadrous Gamil Amin , Aziz Amal A. , Amin Dalia G. , Eldemery Ahmed , Mostafa Mostafa Abdel-Aziz
Published: May 2016

Background

Chronic infection with hepatitis C virus (HCV) is associated with failures of T-cell–mediated immune clearance and with abnormal B-cell growth and activation. Hepatitis C virus infection is characterized by a systemic oxidative stress that is most likely caused by a combination of chronic inflammation, iron overload, liver damage, and proteins encoded by HCV. After a viral infection, multiple proinflammatory mediators contribute to recruitment of immune cells to the liver and to the generation of an antiviral immune response. Recent publications mark chemokines and their receptors as key players in leukocyte recirculation through the inflamed liver.

Materials and Methods

The present study involved 75 male subjects, divided into 2 groups: group 1 (n = 30), control group; group 2 (n = 45), patients with chronic HCV. For all subjects, the following investigations were performed: estimation of the levels of bilirubin, albumin, prothrombin concentration, glycosylated hemoglobin, creatinine, α-fetoprotein, HCV RNA, and activities of alanine and aspartate transaminases as well as alkaline phosphatase. In addition, regulated on activation normal T cell expressed and secreted (RANTES), tumor necrosis factor alpha, malondialdehyde (MDA) and nitric oxide (NO) were assessed. Plasma HCV-RNA concentration (viral load) was determined by real-time polymerase chain reaction (PCR) StepOne system using Applied Biosystem. Complete blood picture was assayed using Abbott Cell-Dyn 3700 hematology analyzer.

Results

There were significant increases of the levels of RANTES, tumor necrosis factor alpha, MDA, and NO in HCV-infected patients compared with the control group ( P <0.05); and in these patients, these levels showed significant positive correlation with the HCV RNA viral load. Also, mild leukopenia, thrombocytopenia, neutropenia, and lymphocytosis, with consequent significant increase in the lymphocytes/neutrophils ratio, were detected in these patients.

Conclusion

The data support the concept of chemokines (RANTES) as mediators of liver cell injury in HCV infection. In addition, MDA and NO levels might be used as monitoring markers for oxidative stress in hepatitis C infection.
Prevalence of Helicobacter pylori in Patients with Brucellosis
Authors: Esen Ramazan , Dulger Ahmet Cumhur , Begenik Huseyin , Demirtas Levent , Ebinc Senar , Aytemiz Enver , Sunnetcioglu Mahmut , Aslan Mehmet
Published: May 2016

Background

Helicobacter pylori infection affects approximately 40 million individuals in Turkey. Our prefecture is an endemic area for H. pylori infection and brucellosis. However, there are no data on the H. pylori prevalence among patients with brucellosis.

Objectives

The primary aim of the current study was to investigate the link between H. pylori infection and brucellosis. The secondary aim was to determine the seroprevalence of H. pylori infection in healthy individuals.

Methods

Between May 2010 and May 2011, serum was collected from patients with Brucella infection (n = 111) and healthy individuals (n = 120) and analyzed using an enzyme-linked immunosorbent assay kit. Brucella infection was defined as a positive Wright test or blood culture positivity for Brucella in conjunction with disease symptoms and findings.

Results

Among the 111 patients with brucellosis, 69% (n = 77) had a seropositivity result for H. pylori IgG. The healthy control subjects had an 87% (n = 104) seropositivity for H. pylori IgG. The serum H. pylori IgG antibody seropositivity was significantly lower in the patients with Brucella infection compared with the control subjects ( P < 0.001).

Conclusion

Our results show that the serum prevalence of H. pylori among the patients infected with brucellosis is significantly lower than that in the control population. A negative correlation between H. pylori infection and brucellosis infection might be hypothesized.
Association of CXCL12 Levels in Synovial Fluid with the Radiographic Severity of Knee Osteoarthritis
Authors: Xu Qin , Sun Xue-cheng , Shang Xiao-peng , Jiang Hou-sen
Published: May 2016

Objective

Inflammation is implicated to be involved in the pathogenesis of osteoarthritis (OA). CXCL12, also known as stromal cell-derived factor, is the unique identified natural ligand of the G-protein-coupled receptor CXCR4 and exhibits both homeostatic and proinflammatory functions. This study aims to determine whether CXCL12 levels in serum and synovial fluid (SF) of patients with knee OA are correlated with the disease severity.

Methods

This study consisted of 252 patients with knee OA and 144 healthy controls. The radiological grading of OA in the knee was performed according to the Kellgren-Lawrence grading system. CXCL12 levels in serum and SF were measured by enzyme-linked immunosorbent assay.

Results

Higher levels of serum CXCL12 were found in knee OA patients compared with healthy controls. The CXCL12 levels in SF of knee OA patients with KL grade 4 were significantly elevated compared with those with KL grades 2 and 3. Furthermore, knee OA patients with KL grade 3 had significantly higher SF levels of CXCL12 compared with those with KL grade 2. CXCL12 levels in SF of knee OA patients were significantly correlated with disease severity evaluated by KL grading criteria. However, there were no significant differences in the serum CXCL12 levels between patients with different KL grades.

Conclusion

CXCL12 levels in SF were closely related to the radiographic severity of OA. CXCL12 levels in SF may be an alternative biomarker for the progression of OA.
IL-33: A Potential Therapeutic Target in Autoimmune Diseases
Authors: Wang Song , Ding Lei , Liu Shan-Shan , Wang Chao , Leng Rui-Xue , Chen Gui-Mei , Fan Yin-Guang , Pan Hai-Feng , Ye Dong-Qing
Published: May 2016

Interleukin 33 (IL-33) is a newly described member of the IL-1 superfamily of cytokines. Through activation of the ST2 receptor, which is widely expressed particularly by helper T 2 cells and mast cells, IL-33 is involved in T-cell–mediated immune responses. Many previous studies have demonstrated that IL-33 may have a pleiotropic function in different diseases, and it could represent a novel target for the treatment of a range of diseases. Recent works have explored the role of IL-33 in chronic autoimmune diseases, such as systemic sclerosis, inflammatory bowel disease, rheumatoid arthritis, and systemic lupus erythematosus. These results indicate that IL-33 may contribute to the pathogenesis of chronic autoimmune diseases. Hence, in this review, we discuss the biological features of IL-33 and summarize recent advances on the role of IL-33 in the pathogenesis and treatment of autoimmune diseases.
Fasting Glucose, Obesity, and Metabolic Syndrome as Predictors of Type 2 Diabetes: The Cooper Center Longitudinal Study
Authors: DeFina Laura F. , Vega Gloria Lena , Leonard David , Grundy Scott M.
Published: May 2016

Background

To determine risk for type 2 diabetes in subjects with fasting glucose levels in the ranges of normoglycemia, mild hyperglycemia, and intermediate hyperglycemia and to assess the effect of obesity and metabolic syndrome on this risk.

Subjects and Methods

Incidence of type 2 diabetes mellitus was evaluated in 28,209 relatively healthy subjects participating in the Cooper Center Longitudinal Study. They were included in the study if they had more than 1 fasting plasma glucose measurement, anthropometry, and other parameters of interest. Three subgroups were identified: normoglycemic (<5.6 mmol/L), mild hyperglycemia (5.6–6.0 mmol/L), and intermediate hyperglycemia (6.1–7.0 mmol/L). Diabetes incidence was calculated in categories of sex, age, obesity, and metabolic syndrome status. Incident diabetes was assessed at the earliest clinic visit at which the individual exhibited a blood glucose level of more than 7.0 mmol/L or reported a diagnosis of diabetes.

Results

Thirty-one percent of men and 15.9% of women had mild hyperglycemia and 11.9% of men and 3.6% of women had intermediate hyperglycemia. Yearly conversion rates to diabetes were low in individuals with normoglycemia and mild hyperglycemia but were strikingly higher in those with intermediate hyperglycemia. In subjects with intermediate hyperglycemia, presence of obesity and/or metabolic syndrome doubled conversion rates to diabetes.

Conclusions

This study showed a marked difference in outcomes in subjects with mild and intermediate hyperglycemia. Moreover, obesity and metabolic syndrome were associated with strikingly elevated risk for diabetes in subjects with intermediate hyperglycemia. Thus intermediate hyperglycemia plus obesity/metabolic syndrome seemingly justifies intensive clinical intervention for prevention of both diabetes and cardiovascular disease.
Physiology and Pathophysiology of the Blood-Brain Barrier: P-Glycoprotein and Occludin Trafficking as Therapeutic Targets to Optimize Central Nervous System Drug Delivery
Authors: McCaffrey Gwen , Davis Thomas P.
Published: May 2016

The blood-brain barrier (BBB) is a physical and metabolic barrier that separates the central nervous system from the peripheral circulation. Central nervous system drug delivery across the BBB is challenging, primarily because of the physical restriction of paracellular diffusion between the endothelial cells that comprise the microvessels of the BBB and the activity of efflux transporters that quickly expel back into the capillary lumen a wide variety of xenobiotics. Therapeutic manipulation of protein trafficking is emerging as a novel means of modulating protein function, and in this minireview, the targeting of the trafficking of 2 key BBB proteins, P-glycoprotein and occludin, is presented as a novel, reversible means of optimizing central nervous system drug delivery.
The Association between Fracture Rates and Neighborhood Characteristics in Washington, DC, Children
Authors: Ryan Leticia Manning , Guagliardo Mark , Teach Stephen J. , Wang Jichuan , Marsh Jennifer E. , Singer Steven A. , Wright Joseph L. , Chamberlain James M.
Published: May 2016

Background

Effects of neighborhood contextual features have been found for many diseases, including bone fractures in adults. Our study objective was to evaluate the association between neighborhood characteristics and pediatric bone fracture rates. We hypothesized that neighborhood indices of deprivation would be associated with higher fracture rates.

Materials and Methods

Pediatric bone fracture cases treated at a tertiary, academic, urban pediatric emergency department between 2003 and 2006 were mapped to census block groups using geographical information systems software. Fracture rates were calculated as fractures per 1000 children in each census block. Exploratory factor analysis of socioeconomic indicators was performed using 2000 census block data. Factor scores were used to predict odds of bone fracture at the individual level while adjusting for mean age, sex composition, and race/ethnicity composition at census block level using our sample data.

Results

We analyzed 3764 fracture visits in 3557 patients representing 349 distinct census blocks groups. Fracture rates among census blocks ranged from 0 to 207 per 1000 children/study period. Logistic regression modeling identified 2 factors (race/education and large families) associated with increased fracture risk. Census variables reflecting African American race, laborer/service industry employment, long-term block group residence, and lower education levels strongly loaded on the race/education factor. The large families factor indicated the children-to-families ratio within the block group. The poverty factor was not independently associated with fracture risk.

Conclusions

Thus, neighborhood characteristics are associated with risk for fractures in children. These results can help inform translational efforts to develop targeted strategies for bone fracture prevention in children.
Usefulness of Hemoglobin A1c as a Criterion to Define Metabolic Syndrome in Nondiabetic Chinese Adolescents
Authors: Li Ping , Jiang Ranhua , Li Ling , Li Xue , Liu Cong , Xu Wanfeng , Xu Duo
Published: May 2016

Aims

To examine whether hemoglobin A1c (HbA1c) can be used instead of fasting plasma glucose (FPG) to identify nondiabetic Chinese adolescents with metabolic syndrome (MS).

Methods

This was a cross-sectional study involving 910 adolescents (11–16 years; 46.8% girls) with an HbA1c less than or equal to 6.4% and an FPG less than or equal to 6.9 mmol/L. All participants underwent anthropometric and biochemical examinations. Metabolic syndrome was defined using the definition proposed by the International Diabetes Federation (IDF) and the American Heart Association (AHA). Replacement of an FPG greater than or equal to 5.6 mmol/L with an HbA1c greater than or equal to 5.7% yielded 2 HbA1c definitions (IDF-HbA1c and AHA-HbA1c). The use of an HbA1c greater than or equal to 5.7% or an FPG greater than or equal to 5.6 mmol/L in the definition of the glycemic component of the MS was compared.

Results

The HbA1c definition resulted in an increase in the population prevalence of MS by 2.4% (IDF-HbA1c) and 2.5% (AHA-HbA1c), respectively ( P ≥ 0.05). The degree of concordance (κ index) was as high as 0.900 for the concordance between the IDF and IDF-HbA1c definition, and 0.811 between the AHA and AHA-HbA1c definition. Subjects who were diagnosed as normal based on the FPG definition and met the HbA1c definition for MS had more cardiometabolic risk factors (waist circumference, blood pressure, lipid profiles, uric acid, and homeostasis assessment model of insulin resistance; all P < 0.05), indicating that the HbA1c definition identified more subjects with cardiovascular disease–related risk factors. HbA1c greater than or equal to 5.7% was significantly associated with the presence of MS [adjusted odds ratio, 2.61 (1.13–6.01)].

Conclusions

An HbA1c greater than or equal to 5.7% was associated with the presence of MS and can be considered a surrogate for FPG in the diagnosis of MS in nondiabetic Chinese adolescents.
Telomere Length and Cardiorespiratory Fitness in Marathon Runners
Authors: Mathur Shishir , Ardestani Afrooz , Parker Beth , Cappizzi Jeffery , Polk Donna , Thompson Paul D.
Published: May 2016

Background and Aim

Physical exercise up-regulates telomere-stabilizing proteins in mice, suggesting that physical activity affects telomere length. Several human studies assessing the relationship between physical activity, measured by health or activity surveys, and telomere length have produced conflicting results. The present study sought to explore the association between telomere length and physical fitness measured objectively as maximal oxygen uptake in endurance-trained athletes and sedentary controls.

Methods

Seventeen marathon runners and 15 age- and sex-matched healthy, sedentary control subjects participated in the study. Medical history, demographic information, maximal oxygen uptake (VO2 max), and peripheral blood lymphocyte telomere length were measured in all subjects. Statistical analysis was performed to examine the relationship between telomere length and measured variables.

Results

Athletes and sedentary controls had similar lymphocyte (0.97 ± 0.20 vs 1.01 ± 0.18; P = 0.6) and granulocyte (0.89 ± 0.11 vs 0.89 ± 0.12; P = 0.9) telomere lengths. Linear regression analysis showed age as the only variable significantly associated with telomere length ( P = 0.007). There was no correlation between VO2 max and telomere length.

Conclusion

In a cohort of healthy adult athletes and sedentary controls, there was no association between physical activity measured by VO2 max and peripheral blood lymphocyte and granulocyte telomere length.
Inhibition of Renin-Angiotensin System: Implications for Diabetes Control and Prevention
Authors: Prabhakar Sharma S.
Published: May 2016

Several large-scale clinical studies have consistently demonstrated that use of inhibitors of renin-angiotensin system such as angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was associated with significant reduction of new-onset diabetes in patients with insulin resistance such as primary hypertension. Such observations stimulated major investigations into the interaction of angiotensin and insulin signaling systems, which in turn led to the discovery of a cross talk at several steps between the 2 pathways. Evidence from these clinical trials and from the experimental models of insulin resistance including our findings in ZSF rat and other animal models will be discussed in this review.
Patient Satisfaction with Warfarin- and Non–Warfarin-Containing Thromboprophylaxis Regimens for Atrial Fibrillation
Authors: Coleman Craig I. , Coleman Stacey M. , Vanderpoel Julie , Nelson Winnie , Colby Jennifer A. , Scholle Jennifer M. , Kluger Jeffrey
Published: May 2016

Objective

To compare patient-reported limitations, concerns, and burdens in those receiving and not receiving warfarin for thromboprophylaxis in atrial fibrillation (AF).

Methods

We conducted a cross-sectional survey study of patients with AF receiving thromboprophylaxis for stroke prevention. Patients were administered the validated Anti-Clot Treatment Scale (ACTS). Mean scores of patients receiving and not receiving warfarin were compared for each ACTS item, and for the Burden and Benefit subscales.

Results

From July 2010 to August 2011, 80 patients with AF were administered the survey, with 65 patients receiving a regimen containing warfarin and 15 patients not receiving a regimen containing warfarin. Six of the 17 individual questions depicting patient- perceived limitations in physical activity due to bleeding, limitations on diet, feelings of inconvenience of occasional aspects of thromboprophylaxis therapy, and frustration, and burden had less favorable scores in the warfarin-managed patients compared with the patients not receiving warfarin ( P < 0.05 for all). Mean ACTS Burden scores were more favorable in the no-warfarin group (44.5 ± 6.4) compared with the warfarin group (39.8 ± 8.0; P = 0.003). No difference was seen between the 2 groups on the ACTS Benefits score (11.1 ± 3.4 vs 10.4 ± 3.7; P = 0.38).

Conclusion

Patients with AF receiving warfarin may have less favorable feelings regarding thromboprophylaxis versus those receiving non-warfarin thromboprophylaxis. Patients report having more limitations and having greater feelings of burden on warfarin.
Carotid Proliferative Plaque Formation in a Canine Model of Chronic Hypertension
Authors: Tian Zuojun , Shen Yuechun , Liao Haixing , Yang Tong , Wang Xiaoming , Han Xiujing , Dong Yaxian , You Tianhui
Published: May 2016

Background

There are few reports describing arterial plaque formation induced by hypertension alone. The aim of this study was to establish a canine model of chronic hypertension and investigate carotid plaque development.

Methods

Ten beagles were studied; 5 underwent bilateral renal artery constriction via a novel vascular clip, and 5 sham-operated animals served as controls. Systolic blood pressure (SBP), diastolic blood pressure (DBP), lipid values, the intima-media thickness, and the carotid artery plaque score were investigated during 1 year after placement of the clips.

Results

The mean SBP and DBP over time were significantly greater in the constriction group ( P < 0.001 for SBP, P < 0.01 for DBP). There were no significant differences in blood lipid levels or other biochemical parameters. Carotid plaques were demonstrated at 4 months postoperation in the constriction group; and in the constriction group, intima-media thickness became significantly greater at 4 months ( P < 0.05), and plaque scores became significantly higher at 8 months ( P = 0.034) after clip placement. Carotid stenosis was proved by digital subtraction angiography 1 year after clip placement, and histological examination revealed that the plaques were mainly comprised of smooth muscle cells, proteoglycans, and collagen fibers, but few macrophages and little lipid.

Conclusions

Carotid proliferative plaques were developed in a canine model of chronic hypertension induced by a novel vascular clip. The plaques were mainly comprised of smooth muscle cells, proteoglycans, and collagen fibers.
Randomized Summer Camp Crossover Trial in 5- to 9-Year-Old Children: Outpatient Wearable Artificial Pancreas Is Feasible and Safe
Authors: Del Favero Simone , Boscari Federico , Messori Mirko , Rabbone Ivana , Bonfanti Riccardo , Sabbion Alberto , Iafusco Dario , Schiaffini Riccardo , Visentin Roberto , Calore Roberta , Moncada Yenny Leal , Galasso Silvia , Galderisi Alfonso , Vallone Valeria , Di Palma Federico , Losiouk Eleonora , Lanzola Giordano , Tinti Davide , Rigamonti Andrea , Marigliano Marco , Zanfardino Angela , Rapini Novella , Avogaro Angelo , Chernavvsky Daniel , Magni Lalo , Cobelli Claudio , Bruttomesso Daniela
Published: May 2016

OBJECTIVE

The Pediatric Artificial Pancreas (PedArPan) project tested a children-specific version of the modular model predictive control (MMPC) algorithm in 5- to 9-year-old children during a camp.

RESEARCH DESIGN AND METHODS

A total of 30 children, 5- to 9-years old, with type 1 diabetes completed an outpatient, open-label, randomized, crossover trial. Three days with an artificial pancreas (AP) were compared with three days of parent-managed sensor-augmented pump (SAP).

RESULTS

Overnight time-in-hypoglycemia was reduced with the AP versus SAP, median (25th–75th percentiles): 0.0% (0.0–2.2) vs. 2.2% (0.0–12.3) (P = 0.002), without a significant change of time-in-target, mean: 56.0% (SD 22.5) vs. 59.7% (21.2) (P = 0.430), but with increased mean glucose 173 mg/dL (36) vs. 150 mg/dL (39) (P = 0.002). Overall, the AP granted a threefold reduction of time-in-hypoglycemia (P < 0.001) at the cost of decreased time-in-target, 56.8% (13.5) vs. 63.1% (11.0) (P = 0.022) and increased mean glucose 169 mg/dL (23) vs. 147 mg/dL (23) (P < 0.001).

CONCLUSIONS

This trial, the first outpatient single-hormone AP trial in a population of this age, shows feasibility and safety of MMPC in young children. Algorithm retuning will be performed to improve efficacy.
“Would they not wish the feast might ever last?”: Strong Spice, Oral History and the Genesis of Globe to Globe
Authors: Quarmby Kevin A.
Published: May 2016

The 2012 Globe to Globe Festival proved a great success. Actors, directors, musicians, dancers, designers and technicians travelled from all over the world to perform on the Globe stage. Visitors to London’s Cultural Olympiad enjoyed six jam-packed weeks of Shakespeare, presented in an array of international languages. The Globe’s Artistic Director, Dominic Dromgoole, and his Festival Director, Tom Bird, had achieved what seemed, to many, the impossible. Nonetheless, filmed interviews with Dromgoole and Bird, conducted during the festival by the American documentary-maker Steve Rowland, offer tantalizing insights into the genesis of the festival venture. These candid interviews confirm the sometimes farcical, often exhausting, but invariably serendipitous truth behind the Globe to Globe Festival’s short, intense history. Although the Globe was “flying completely blind,” it still succeeded in hosting a glorious feast of Shakespearean delights, seasoned with the strong spice of multiculturality.
Thermal and mechanical properties of single-walled and multi-walled carbon nanotube polycarbonate polyurethane composites with a focus on self-healing
Authors: Bass Roger W. , Julien Tamalia C. M. , Rigolo Alyssa , Hong Seongmin , Li Xiao , Harmon Julie P.
Published: May 2016

Single walled and multi walled carbon nanotubes were incorporated into a high molar mass polycarbonate polyurethane via ultrasonication. The polycarbonate polyurethane which is free of any healing additives has the capacity to partially re-heal after rupture. The formation of the polyurethane/carbon nanotube composites has been shown to greatly improve the self-healing characteristics. Moreover, there is an increase in the thermal and mechanical properties of the thermoplastic composites. Herein we investigate the thermal and mechanical properties of the elastomeric material with a focus of the interface of the carbon nanotubes. Additionally, the self-healing polymer is probed using Raman techniques in order to provide an insight into how the self-healing actions are improved upon addition of carbon nanotubes.
Failure Mode Analysis and Dynamic Response of a Coal Mine Refuge Chamber with a Gas Explosion
Authors: Zhang Boyi , Zhai Dongxian , Wang Wei
Published: May 2016

A gas and coal dust explosion is potential hazard in majority coal mines. A coal mine mobile refuge chamber is a new class of device for miners those who are unable to escape after an accident which can provide basic survival conditions. In this paper, in order to study the propagation law of an underground methane/air mixture explosive wave, and check the failure mode of a coal mine mobile refuge chamber, a full-sized underground tunnel model and a refuge chamber model have been established in ANSYS/LS-DYNA (LSTC, R7.0.0, Livermore, CA, USA, 2014). The simulation results show that the reflected wave pressure on the front surface of the refuge chamber was about twice as high than the incident wave. The pressure on various locations of the chamber was also analyzed. When the peak pressure of the explosive shockwave reached 0.64 MPa, the maximum displacement and stress occur at the center of the front door and the joint of stiffeners and the front plate, respectively. Most parts of the coal mine mobile refuge chamber were in a plastic failure state and the refuge chamber could be defined as damaged. The front door, the front plate, the connecting flange, and the stiffeners on each side were the primary key components. In the end, suggestions were proposed for the refuge chamber.
Formation of Bragg Band Gaps in Anisotropic Phononic Crystals Analyzed With the Empty Lattice Model
Authors: Wang Yan-Feng , Maznev Alexei , Laude Vincent
Published: May 2016

Bragg band gaps of phononic crystals generally, but not always, open at Brillouin zone boundaries. The commonly accepted explanation stems from the empty lattice model: assuming a small material contrast between the constituents of the unit cell, avoided crossings in the phononic band structure appear at frequencies and wavenumbers corresponding to band intersections; for scalar waves the lowest intersections coincide with boundaries of the first Brillouin zone. However, if a phononic crystal contains elastically anisotropic materials, its overall symmetry is not dictated solely by the lattice symmetry. We construct an empty lattice model for phononic crystals made of isotropic and anisotropic materials, based on their slowness curves. We find that, in the anisotropic case, avoided crossings generally do not appear at the boundaries of traditionally defined Brillouin zones. Furthermore, the Bragg “planes” which give rise to phononic band gaps, are generally not flat planes but curved surfaces. The same is found to be the case for avoided crossings between shear (transverse) and longitudinal bands in the isotropic case.
Influence of Upconversion Processes in the Optically-Induced Inhomogeneous Thermal Behavior of Erbium-Doped Lanthanum Oxysulfide Powders
Authors: Balda Rolindes , Hakmeh Noha , Barredo-Zuriarrain Macarena , Merdrignac-Conanec Odile , García-Revilla Sara , Arriandiaga M. , Fernández Joaquín
Published: May 2016

The efficient infrared-to-visible upconversion emission present in Er-doped lanthanum oxysulfide crystal powders is used as a fine thermal sensor to determine the influence of upconversion processes on the laser-induced thermal load produced by the pump laser and to assess the potentialities of this material in order to obtain anti-Stokes laser-induced cooling. The analysis of the upconversion emission and excitation spectra as well as the decay curves indicates that energy transfer upconversion is the main mechanism responsible for the green (4S3/2) and red (4F9/2) upconversion luminescence. The dependence on temperature of the intensity ratio of upconversion emission from thermally-coupled 2H11/2 and 4S3/2 levels of Er3+ in the 240–300 K temperature range has been used to estimate a relative sensitivity of 1.09 × 10−2 K−1. Thermal measurements performed on the powder samples by using a thermal infrared camera exhibit a very inhomogeneous heat distribution at the sample surface due to the random distribution of the pumping energy inside the sample as well as to the random properties of the thermal field. The analysis of both spectroscopic and thermal measurements show that after a transient heating induced by the background absorption, cooling of discrete regions by means of anti-Stokes processes can be observed.
cDNA and Gene Structure of MytiLec-1, A Bacteriostatic R-Type Lectin from the Mediterranean Mussel (Mytilus galloprovincialis)
Authors: Hasan Imtiaj , Gerdol Marco , Fujii Yuki , Rajia Sultana , Koide Yasuhiro , Yamamoto Daiki , Kawsar Sarkar , Ozeki Yasuhiro
Published: May 2016

MytiLec is an α-d-galactose-binding lectin with a unique primary structure isolated from the Mediterranean mussel (Mytilus galloprovincialis). The lectin adopts a β-trefoil fold that is also found in the B-sub-unit of ricin and other ricin-type (R-type) lectins. We are introducing MytiLec(-1) and its two variants (MytiLec-2 and -3), which both possess an additional pore-forming aerolysin-like domain, as members of a novel multi-genic “mytilectin family” in bivalve mollusks. Based on the full length mRNA sequence (911 bps), it was possible to elucidate the coding sequence of MytiLec-1, which displays an extended open reading frame (ORF) at the 5′ end of the sequence, confirmed both at the mRNA and at the genomic DNA sequence level. While this extension could potentially produce a polypeptide significantly longer than previously reported, this has not been confirmed yet at the protein level. MytiLec-1 was revealed to be encoded by a gene consisting of two exons and a single intron. The first exon comprised the 5′UTR and the initial ATG codon and it was possible to detect a putative promoter region immediately ahead of the transcription start site in the MytiLec-1 genomic locus. The remaining part of the MytiLec-1 coding sequence (including the three sub-domains, the 3′UTR and the poly-A signal) was included in the second exon. The bacteriostatic activity of MytiLec-1 was determined by the agglutination of both Gram-positive and Gram-negative bacteria, which was reversed by the co-presence of α-galactoside. Altogether, these data support the classification of MytiLec-1 as a member of the novel mytilectin family and suggest that this lectin may play an important role as a pattern recognition receptor in the innate immunity of mussels.
Hybrid Integration of Magnetoresistive Sensors with MEMS as a Strategy to Detect Ultra-Low Magnetic Fields
Authors: Valadeiro João , Cardoso Susana , Macedo Rita , Guedes Andre , Gaspar João , Freitas Paulo
Published: May 2016

In this paper, we describe how magnetoresistive sensors can be integrated with microelectromechanical systems (MEMS) devices enabling the mechanical modulation of DC or low frequency external magnetic fields to high frequencies using MEMS structures incorporating magnetic flux guides. In such a hybrid architecture, lower detectivities are expected when compared with those obtained for individual sensors. This particularity results from the change of sensor’s operating point to frequencies above the 1/f noise knee.
Discovery of Potent c-MET Inhibitors with New Scaffold Having Different Quinazoline, Pyridine and Tetrahydro-Pyridothienopyrimidine Headgroups
Authors: Jiang Yingnan , Zhang Ke , Gao Suyu , Wang Guihua , Huang Jian , Wang Jinhui , Chen Lixia
Published: May 2016

Cellular mesenchymal-epithelial transition factor (c-MET) is closely linked to human malignancies, which makes it an important target for treatment of cancer. In this study, a series of 3-methoxy-N-phenylbenzamide derivatives, N-(3-(tert-butyl)-1-phenyl-1H-pyrazol-5-yl) benzamide derivatives and N1-(3-fluoro-4-methoxyphenyl)-N3-(4-fluorophenyl) malonamide derivatives were designed and synthesized, some of them were identified as c-MET inhibitors. Among these compounds with new scaffolds having different quinazoline, pyridine and tetrahydro-pyridothienopyrimidine head groups, compound 11c, 11i, 13b, 13h exhibited both potent inhibitory activities against c-MET and high anticancer activity against tested cancer cell lines in vitro. In addition, kinase selectivity assay further demonstrated that both 13b and 13h are potent and selective c-MET inhibitors. Molecular docking supported that they bound well to c-MET and VEGFR2, which demonstrates that they are potential c-MET RTK inhibitors for cancer therapy.
A Mixed Flavonoid-Fish Oil Supplement Induces Immune-Enhancing and Anti-Inflammatory Transcriptomic Changes in Adult Obese and Overweight Women—A Randomized Controlled Trial
Authors: Cialdella-Kam Lynn , Nieman David , Knab Amy , Shanely R. , Meaney Mary , Jin Fuxia , Sha Wei , Ghosh Sujoy
Published: May 2016

Flavonoids and fish oils have anti-inflammatory and immune-modulating influences. The purpose of this study was to determine if a mixed flavonoid-fish oil supplement (Q-Mix; 1000 mg quercetin, 400 mg isoquercetin, 120 mg epigallocatechin (EGCG) from green tea extract, 400 mg n3-PUFAs (omega-3 polyunsaturated fatty acid) (220 mg eicosapentaenoic acid (EPA) and 180 mg docosahexaenoic acid (DHA)) from fish oil, 1000 mg vitamin C, 40 mg niacinamide, and 800 µg folic acid) would reduce complications associated with obesity; that is, reduce inflammatory and oxidative stress markers and alter genomic profiles in overweight women. Overweight and obese women (n = 48; age = 40–70 years) were assigned to Q-Mix or placebo groups using randomized double-blinded placebo-controlled procedures. Overnight fasted blood samples were collected at 0 and 10 weeks and analyzed for cytokines, C-reactive protein (CRP), F2-isoprostanes, and whole-blood-derived mRNA, which was assessed using Affymetrix HuGene-1_1 ST arrays. Statistical analysis included two-way ANOVA models for blood analytes and gene expression and pathway and network enrichment methods for gene expression. Plasma levels increased with Q-Mix supplementation by 388% for quercetin, 95% for EPA, 18% for DHA, and 20% for docosapentaenoic acid (DPA). Q-Mix did not alter plasma levels for CRP (p = 0.268), F2-isoprostanes (p = 0.273), and cytokines (p > 0.05). Gene set enrichment analysis revealed upregulation of pathways in Q-Mix vs. placebo related to interferon-induced antiviral mechanism (false discovery rate, FDR < 0.001). Overrepresentation analysis further disclosed an inhibition of phagocytosis-related inflammatory pathways in Q-Mix vs. placebo. Thus, a 10-week Q-Mix supplementation elicited a significant rise in plasma quercetin, EPA, DHA, and DPA, as well as stimulated an antiviral and inflammation whole-blood transcriptomic response in overweight women.
Review of Infant Feeding: Key Features of Breast Milk and Infant Formula
Authors: Martin Camilia , Ling Pei-Ra , Blackburn George
Published: May 2016

Mothers’ own milk is the best source of nutrition for nearly all infants. Beyond somatic growth, breast milk as a biologic fluid has a variety of other benefits, including modulation of postnatal intestinal function, immune ontogeny, and brain development. Although breastfeeding is highly recommended, breastfeeding may not always be possible, suitable or solely adequate. Infant formula is an industrially produced substitute for infant consumption. Infant formula attempts to mimic the nutritional composition of breast milk as closely as possible, and is based on cow’s milk or soymilk. A number of alternatives to cow’s milk-based formula also exist. In this article, we review the nutritional information of breast milk and infant formulas for better understanding of the importance of breastfeeding and the uses of infant formula from birth to 12 months of age when a substitute form of nutrition is required.