bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mouse Models of Fragile X-Associated Tremor Ataxia
Authors: Berman Robert F. , Willemsen Rob 
Published: May 2016

Objective To describe the development of mouse models of fragile X-associated tremor/ataxia (FXTAS) and the behavioral, histological and molecular characteristics of these mice. Method This paper compares the pathophysiology and neuropsychological features of FXTAS in humans to the major mouse models of FXTAS. Specifically, the development of a transgenic mouse line carrying an expanded CGG trinucleotide repeat in the 5′-untranslated region (5′-UTR) of the Fmr1 gene is described along with a description of the characteristic intranuclear ubiquitin-positive inclusions and the behavioral sequella observed in these mice. Results CGG KI mice model many of the important features of FXTAS, although some aspects are not well modeled in mice. Aspects of FXTAS that are modeled well include elevated levels of Fmr1 mRNA, reduced levels of Fmrp, the presence of intranuclear inclusions that develop with age and show similar distributions within neurons, and neuropsychological and cognitive deficits, including poor motor function, impaired memory and evidence of increased anxiety. Features of FXTAS that are not well modeled in these mice include intentional tremors that are observed in some FXTAS patients but have not been reported in CGG KI mice. In addition, although intranuclear inclusions in astrocytes are very prominent in FXTAS, there are relatively few observed in CGG KI mice. A number of additional features of FXTAS have not been systematically examined in mouse models yet, including white matter disease, hyperintensities in T2-weighted magnetic resonance imaging, and brain atrophy, although these are currently under investigation in our laboratories. Conclusions The available mouse model has provided valuable insights into the molecular biology and pathophysiology of FXTAS and will be particularly useful for developing and testing new therapeutic treatments in the future.
Procalcitonin, C-Reactive Protein, and Cell Counts in the Diagnosis of Parapneumonic Pleural Effusions
Authors: San José M. Esther , Valdés Luis , Vizcaíno Luis H. , Mora Teresa , Pose Antonio , Soneira Esther , Crecente Carmen , González-Barcala Francisco J. 
Published: May 2016

Background and Objective Pleural effusion is relatively common in pneumonia. Because traditional methods for its diagnosis are not always effective, there is a need for new biomarkers to make its differential diagnosis easier. Methods A total of 233 patients with pleural effusion were admitted to our hospital between 2005 and 2008. Total and differential leukocyte counts, along with blood and pleural fluid procalcitonin and C-reactive protein (CRP) were performed on all of them. The patients were classified into 5 groups depending on the cause of their effusion: (1) parapneumonic, n = 28; (2) tuberculous, n = 49; (3) neoplastic, n = 57; (4) miscellaneous, n = 46; and (5) transudates, n = 53. Results Procalcitonin levels were higher in the pleural fluid of the parapneumonic group (PAR, 0.15 ng/mL) compared with those of the rest of the groups, but statistically significant differences were only observed with the miscellaneous and tuberculous groups ( P < 0.001). Levels of CRP were also higher in the PAR (0.67 mg/L) compared with those of the rest of the groups, with statistically significant differences observed ( P < 0.001-0.004) in all of them. The parameter with the largest area under the receiver operator characteristics curve was the product of the total neutrophil count and the CRP in the pleural fluid, in which an area of 0.836 had a sensitivity of 64.3% and a specificity of 93.4%. Conclusions Determination of procalcitonin and CRP, in the pleural fluid and blood, does not seem to provide great value to the diagnosis of PAR. However, calculating the product of the total neutrophil count and the CRP may be useful in the diagnosis of these effusions because increased values have a high specificity and predictive values.
Chromosome 9p21 Genetic Variants are Associated with Myocardial Infarction but Not with Ischemic Stroke in a Taiwanese Population
Authors: Lin Hsiu-Fen , Tsai Pei-Chien , Liao Yi-Chu , Lin Tsung-Hsien , Tai Chih-Ta , Juo Suh-Hang Hank , Lin Ruey-Tay 
Published: May 2016

Background Genetic variants on chromosome 9p21 confer a robust risk for coronary artery disease but inconsistent risk for stroke. This study investigated whether such genetic variants exert differential risks on myocardial infarction (MI) and ischemic stroke in a Taiwanese population. Methods The study recruited 425 MI patients, 687 patients with ischemic stroke, and 1377 healthy controls. Four key single nucleotide polymorphisms (SNPs) on chromosome 9p21 were genotyped. Results Multivariate permutation analyses demonstrated that the risk T allele of rs1333040 and G allele of rs2383207 were associated with MI ( P = 0.045 and 0.002, respectively). Subjects with the rs2383207 GG genotype had a 1.85-fold ( P = 0.021) risk for MI when compared with the subjects with the AA genotype. Further analysis showed that significant results only exist in the young MI group (<65 years) but not in the old MI group (≥65 years). These SNPs were not statistically significant for stroke (adjusted P ranged from 0.097 to 0.540). Haplotype analysis showed global P values of 0.032 for MI and 0.290 for stroke. Conclusions Genetic variations in the 9p21 region are associated with MI but not with stroke in a Taiwanese population. Early-onset MI was more likely to carry the risk genotypes of 9p21 SNPs.
Attrition Rates of Pediatric Emergency Medicine Fellowship Graduates
Authors: Klasner Ann Elizabeth 
Published: May 2016

Objectives To identify the percentage of alumni of one Pediatric Emergency Medicine (PEM) fellowship program who consider themselves to still practice in the field. Methods A brief survey (5 questions) was sent to all physicians who began the PEM fellowship program at the University of Alabama at Birmingham between the years 1986 and 2006. Survey included demographics, length of time out of fellowship, present work location, and whether the respondent considered themselves to be in the field of pediatric emergency medicine. Results Forty-three physicians were identified as beginning fellowship between 1986 and 2006. One physician was excluded as she was deceased. Forty (95%) of the 42 individuals graduated from a PEM fellowship program. Analyzing the 39 responding PEM graduates, 29 (74%) consider themselves practicing pediatric emergency medicine. Six (60%) of those not considered practicing in PEM (n = 10) are women. Four of these 10 individuals are still in academic medicine. Overall attrition rate for this cohort of PEM fellowship-trained physicians is 25.6% (95% confidence interval, 13.0-42.1). Conclusion Overall attrition rates of fellowship-trained PEM physicians seems to mirror that of adult trained counterparts.
Do Serum Angiopoietin-1, Angiopoietin-2, and Their Receptor Tie-2 and 4G/5G Variant of PAI-1 Gene Have a Role in the Pathogenesis of Preeclampsia?
Authors: Kamal Manal , El-Khayat Waleed 
Published: May 2016

Objective To evaluate whether serum angiogenesis markers such as angiopoietins (Ang-1, Ang-2) and their receptor (Tie-2) are altered in women with preeclampsia. We also performed genotyping to determine if the 4G/5G genotypes of −675 PAI-1 gene may play a role in the pathogenesis of preeclampsia. Materials and Methods Sixty-eight pregnant women with preeclampsia were compared to 35 normotensive pregnant women and 24 normotensive nonpregnant women in a cross-sectional study. Using enzyme-linked immunosorbent assay, levels of serum Ang-1 and Ang-2, and Tie-2 were measured. A single base pair insertion/deletion 4G/5G polymorphism of the PAI-1 gene was determined by polymerase chain reaction. Results Serum levels of Ang-1 and Tie-2 were significantly different among the study groups ( P = 0.001 and P = 0.025, respectively) being lower in the preeclamptic group. Positive significant correlation was found between Ang-2 and Tie-2, ( r = 0.26, P = 0.024). The frequency of the genotypes (4G/5G, 4G/4G, and 5G/5G) differed among the groups ( P = 0.001). Also, the mean of systolic and diastolic blood pressures differed significantly according to the PAI-1 genotype being higher in those bearing the 4G allele; P = 0.04 and P = 0.023, respectively. Conclusion Sera Ang-1 and Ang-2, and Tie-2 as well as variants of 4G/5G of PAI-1 polymorphism have positive implications in the pathogenesis of preeclampsia.
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.