bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of pioglitazone on weight, lipid profile and liver enzymes in type 2 diabetic patients
Authors: Aghamohammadzadeh Nasser , Niafar Mitra , Dalir Abdolahinia Elham , Najafipour Farzad , Mohamadzadeh Gharebaghi Saeed , Adabi Khadijeh , Dalir Abdolahinia Elaheh , Ahadi Hamidreza 
Published: March 2015

Background: Pioglitazone is one of the antidiabetic agents used in the management of type 2 diabetes mellitus (DM). The effect of pioglitazone on blood glucose, lipid profile, liver enzymes and weight has been shown with conflicting results. In this study we aim to evaluate the effect of pioglitazone on the weight, lipid profile and liver enzymes in patients with DM. Methods: In this single-arm clinical trial, 110 poorly controlled diabetic type 2 patients (63.6% female with mean age of 54.26 ± 8.96 years) who were on maximal dosage of metformin and glibenclamide were enrolled. Patients were treated with pioglitazone for 3 months and laboratory. Fasting blood sugar (FBS), haemoglobin A1C (HbA1C), cholesterol, triglyceride, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), alkaline phosphatase (ALK-P), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and weight changes were measured before and at the end of the study. Results: The levels of FBS ( p < 0.001), HbA1c ( p < 0.001), triglyceride ( p = 0.001), ALT ( p = 0.005) and ALK-P ( p = 0.001) were significantly decreased, but weight was significantly increased ( p < 0.001) after the intervention. There were no significant difference in cholesterol, LDL and HDL values before and after study. Conclusion: Although pioglitazone causes a significant decrease in FBS, HbA1C and triglyceride levels, it is associated with weight gain, which would limit its utility. IRCT registration code: IRCT201209276712N2
Peripherally Increased Artemin is a Key Regulator of TRPA1/V1 Expression in Primary Afferent Neurons
Authors: Ikeda-Miyagawa Yasuko , Kobayashi Kimiko , Yamanaka Hiroki , Okubo Masamichi , Wang Shenglan , Dai Yi , Yagi Hideshi , Hirose Munetaka , Noguchi Koichi 
Published: March 2015

Background Artemin, a member of the glial cell line-derived neurotrophic factor family, is known to have a variety of neuronal functions, and has been the subject of attention because it has interesting effects, including bi-directional results in modulation in neuropathic and inflammatory pain. It has been shown that the overexpression of artemin is associated with an increase in the expression of TRP family channels in primary afferents and subsequent hyperalgesia, and an increase in neuronal activity. The purpose of this study was to examine the peripheral synthesis of artemin in inflammatory and neuropathic pain models, and to demonstrate the effects of long-term or repeated application of artemin in vivo on pain behaviors and on the expression of TRP family channels. Further, the regulatory mechanisms of artemin on TRPV1/A1 were examined using cultured DRG neurons. Results We have demonstrated that artemin is locally elevated in skin over long periods of time, that artemin signals significantly increase in deep layers of the epidermis, and also that it is distributed over a broad area of the dermis. In contrast, NGF showed transient increases after peripheral inflammation. It was confirmed that the co-localization of TRPV1/A1 and GFRc3 was higher than that between TRPV1/A1 and TrkA. In the peripheral sciatic nerve trunk, the synthesis of artemin was found by RT-PCR and in situ hybridization to increase at a site distal to a nerve injury. We demonstrated that in vivo repeated artemin injections into the periphery changed the gene expression of TRPV1/A1 in DRG neurons without affecting GFRc3 expression. Repeated artemin injections also induced mechanical and heat hyperalgesia. Using primary cultured DRG neurons, we found that artemin application significantly increased TRPV1/A1 expression and Ca2+ influx. Artemin-induced p38 MAPK pathway regulated the TRPV1 channel expression, however TRPA1 upregulation by artemin is not mediated through p38 MAPK. Conclusions These data indicate the important roles of peripherally-derived artemin on the regulation of TRPV1/A1 in DRG neurons in pathological conditions such as inflammatory and neuropathic pain.
A [14C]iodoantipyrine Study of Inter-Regional Correlations of Neural Substrates Following Central Post-Stroke Pain in Rats
Authors: Lu Hsiang-Chin , Chang Wei-Jen , Kuan Yung-Hui , Huang Andrew Chih-Wei , Shyu Bai Chuang 
Published: March 2015

Background Central pain syndrome is characterized by a combination of abnormal pain sensations, and pain medications often provide little or no relief. Accumulating animal and clinical studies have shown that impairments of the spinothalamic tract (STT) and thalamocingulate pathway causes somatosensory dysfunction in central post-stroke pain (CPSP), but the involvement of other neuronal circuitries in CPSP has not yet been systematically examined. The aim of the present study was to evaluate changes in brain activity and neuronal circuitry using [14C]iodoantipyrine (IAP) in an animal model of CPSP. Results Rats were subjected to lateral thalamic hemorrhage to investigate the characteristics of CPSP. Thermal and mechanical hyperalgesia developed in rats that were subjected to thalamic hemorrhagic lesion. The medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), striatum, thalamus, hypothalamus, and amygdala were more active in the CPSP group compared with rats that were not subjected to lateral thalamic hemorrhage. The inter-regional correlation analysis showed that regional cerebral blood flow in the mPFC was highly correlated with the amygdala in the right brain, and the right brain showed complex connections among subregions of the ACC. Rats with CPSP exhibited strong activation of the thalamocingulate and mPFC-amygdala pathways. Conclusions These results corroborate previous findings that the STT and thalamocingulate pathway are involved in the pathophysiological mechanisms of CPSP symptoms. The mPFC, amygdala, and periaqueductal gray emerged as having important correlations in pain processing in CPSP. The present data provide a basis for a neural correlation hypothesis of CPSP, with implications for CPSP treatment.
Unsteady turbulent boundary layers in swimming rainbow trout
Authors: Yanase Kazutaka , Saarenrinne Pentti 
Published: March 2015

The boundary layers of rainbow trout, Oncorhynchus myskiss, swimming at 1.02±0.09 L s−1 (mean±s.d., N=4), were measured by the Particle Image Velocimetry (PIV) technique at a Reynolds number of 4×105. The boundary-layer profile showed unsteadiness, oscillating above and beneath the classical logarithmic law of the wall with body motion. Across the entire surface regions that were measured, local Reynolds numbers based on momentum thickness, which is the distance that is perpendicular to the fish surface through which the boundary-layer momentum flows at free-stream velocity, were greater than the critical value of 320 for laminar-to-turbulent transition.
The skin friction was dampened on the convex surface while the surface was moving towards a free-stream flow and increased on the concave surface while retreating. These observations contradict the result of a previous study using different species swimming by different methods. Boundary layer compression accompanied by an increase in local skin-friction was not observed. Thus, the overall results may not support absolutely the Bone-Lighthill boundary-layer thinning hypothesis that the undulatory motions of swimming fish cause a large increase in their friction drag because of the compression of the boundary layer. In some cases, marginal flow separation occurred on the convex surface in the relatively anterior surface region, but the separated flow reattached to the fish surface immediately downstream. Therefore, we believe that a severe impact due to induced drag components (i.e. pressure drag) on the swimming performance, an inevitable consequence of flow separation, was avoided.
Disruption of Src Is Associated with Phenotypes Related to Williams-Beuren Syndrome and Altered Cellular Localization of TFII-I
Authors: Sinai Laleh , Ivakine Evgueni A. , Lam Emily , Deurloo Marielle , Dida Joana , Zirngibl Ralph A. , Jung Cynthia , Aubin Jane E. , Feng Zhong-Ping , Yeomans John , Roderick R. McInnes , Osborne Lucy R. , Roder John C. 
Published: March 2015

AbstractSrc is a nonreceptor protein tyrosine kinase that is expressed widely throughout the central nervous system and is involved in diverse biological functions. Mice homozygous for a spontaneous mutation inSrc(Srcthl/thl) exhibited hypersociability and hyperactivity along with impairments in visuospatial, amygdala-dependent, and motor learning as well as an increased startle response to loud tones. The phenotype ofSrcthl/thlmice showed significant overlap with Williams-Beuren syndrome (WBS), a disorder caused by the deletion of several genes, including General Transcription Factor 2-I (GTF2I). Src phosphorylation regulates the movement of GTF2I protein (TFII-I) between the nucleus, where it is a transcriptional activator, and the cytoplasm, where it regulates trafficking of transient receptor potential cation channel, subfamily C, member 3 (TRPC3) subunits to the plasma membrane. Here, we demonstrate altered cellular localization of both TFII-I and TRPC3 in theSrcmutants, suggesting that disruption of Src can phenocopy behavioral phenotypes observed in WBS through its regulation of TFII-I.
Gender difference in adrenal sensitivity to ACTH is abolished in type 2 diabetes
Authors: Arnetz Lisa , Rajamand Ekberg Neda , Brismar Kerstin , Alvarsson Michael 
Published: March 2015

ObjectiveDysfunction of the hypothalamus–pituitary–adrenal (HPA) axis has been implicated in type 2 diabetes (T2D). The aim of this study was to investigate the impact of T2D and gender on the HPA axis.MethodsSynthetic ACTH (1 μg) was administered to 21 subjects with T2D (age 62 (54–70) years, 11 men/ten women, HbA1c 49±2 mmol/mol, treated with diet or oral antidiabetic drugs) and 38 controls (age 58 (41–67) years, 20 men/18 women). Fasting basal B-glucose, serum cortisol, insulin, IGF1 and IGFBP1 concentrations were measured, and sampling for all but IGF1 was repeated 30, 60, and 90 min after ACTH injection. Patients took 0.25 mg dexamethasone at 2200–2300 h and returned the next morning for the measurement of serum cortisol concentration.DesignCross-sectional study.ResultsPatients with T2D had similar fasting serum cortisol, IGF1 and IGFBP1 concentrations; however, serum cortisol concentration after administration of dexamethasone did not differ between the groups. Healthy women exhibited higher peak cortisol levels compared with healthy men (675±26 vs 582±21 nmol/l, P=0.014), while the peak levels were equally high in men and women with T2D, resulting in a higher peak level in men with T2D compared with healthy men (691±42 vs 582±21 nmol/l, P=0.024). Serum cortisol concentration after administration of dexamethasone did not differ between the groups, nor did IGF1 and IGFBP1.Novelty of the findingsSome studies have previously indicated disturbed regulation of the hypothalamus–pituitary–adrenal (HPA) axis in subjects with type 2 diabetes (T2D); however, much remains unknown in this area. To the best of our knowledge, this is the first study to show that the gender difference in the adrenal response to ACTH (with greater reactivity in women) is abolished in T2D. While the clinical implications cannot be determined by this paper, it is known that gender differences exist in the pathogenesis and complications of T2D. Thus, our findings suggest that further research into gender differences in the HPA axis is warranted.ConclusionsGender differences in adrenal response to ACTH were abolished in T2D. Men with T2D had a higher peak cortisol compared with controls. Further studies are needed to elucidate the clinical implications.
PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study of 60 cases
Authors: Thiel Anne , Reis Anna-Carinna , Haase Matthias , Goh Gerald , Schott Matthias , Willenberg Holger S , Scholl Ute I 
Published: March 2015

ObjectiveCortisol excess due to adrenal adenomas or hyperplasia causes Cushing's syndrome. Recent genetic studies have identified a somaticPRKACAL206Rmutation as a cause of cortisol-producing adenomas. We aimed to compare the clinical features ofPRKACA-mutant lesions with those ofCTNNB1mutations, and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone.Design, patients, and methodsIn this study, 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. A total of 36 patients had overt Cushing's syndrome, the remainder were subclinical: 59 cases were adenomas (three bilateral) and one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone.ResultsAmong cortisol-secreting unilateral lesions without evidence of co-secretion (n=52), we identified somatic mutations inPRKACA(L206R) in 23.1%,CTNNB1(S45P, S45F) in 23.1%,GNAS(R201C) in 5.8%, andCTNNB1+GNAS(S45P, R201H) in 1.9%.PRKACAandGNASmutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations inKCNJ5(G151R and L168R). The hyperplastic gland showed aPRKACAL206Rmutation, while patients with bilateral adenomas did not have known somatic mutations.PRKACA-mutant lesions were associated with younger age, overt Cushing's syndrome, and higher cortisol levels vs non-PRKACA-mutant orCTNNB1-mutant lesions.CTNNB1mutations were more significantly associated with right than left lesions.ConclusionsPRKACAL206Ris present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.
Estimating Effective Population Size from Temporally Spaced Samples with a Novel, Efficient Maximum-Likelihood Algorithm
Authors: Hui Tin-Yu J , Burt Austin 
Published: March 2015

Abstract
The effective population size Ne is a key parameter in population genetics and evolutionary biology, as it quantifies the expected distribution of changes in allele frequency due to genetic drift. Several methods of estimating Ne have been described, the most direct of which uses allele frequencies measured at two or more time points. A new likelihood-based estimator NB^ for contemporary effective population size using temporal data is developed in this article. The existing likelihood methods are computationally intensive and unable to handle the case when the underlying Ne is large. This article tries to work around this problem by using a hidden Markov algorithm and applying continuous approximations to allele frequencies and transition probabilities. Extensive simulations are run to evaluate the performance of the proposed estimator NB^, and the results show that it is more accurate and has lower variance than previous methods. The new estimator also reduces the computational time by at least 1000-fold and relaxes the upper bound of Ne to several million, hence allowing the estimation of larger Ne. Finally, we demonstrate how this algorithm can cope with nonconstant Ne scenarios and be used as a likelihood-ratio test to test for the equality of Ne throughout the sampling horizon. An R package “NB” is now available for download to implement the method described in this article.
A cis-Regulatory Mutation in Troponin-I of Drosophila Reveals the Importance of Proper Stoichiometry of Structural Proteins During Muscle Assembly
Authors: Firdaus Hena , Mohan Jayaram , Naz Sarwat , Arathi Prabhashankar , Ramesh Saraf R , Nongthomba Upendra 
Published: March 2015

Abstract
Rapid and high wing-beat frequencies achieved during insect flight are powered by the indirect flight muscles, the largest group of muscles present in the thorax. Any anomaly during the assembly and/or structural impairment of the indirect flight muscles gives rise to a flightless phenotype. Multiple mutagenesis screens in Drosophila melanogaster for defective flight behavior have led to the isolation and characterization of mutations that have been instrumental in the identification of many proteins and residues that are important for muscle assembly, function, and disease. In this article, we present a molecular-genetic characterization of a flightless mutation, flightless-H (fliH), originally designated as heldup-a (hdp-a). We show that fliH is a cis-regulatory mutation of the wings up A (wupA) gene, which codes for the troponin-I protein, one of the troponin complex proteins, involved in regulation of muscle contraction. The mutation leads to reduced levels of troponin-I transcript and protein. In addition to this, there is also coordinated reduction in transcript and protein levels of other structural protein isoforms that are part of the troponin complex. The altered transcript and protein stoichiometry ultimately culminates in unregulated acto-myosin interactions and a hypercontraction muscle phenotype. Our results shed new insights into the importance of maintaining the stoichiometry of structural proteins during muscle assembly for proper function with implications for the identification of mutations and disease phenotypes in other species, including humans.
New records of social wasps in the state of Paraíba, Brazil
Authors: Elisei Thiago , Albuquerque Fabio , Andena Sergio , Martins Celso 
Published: March 2015

The state of Paraíba is included in the semi-arid region of Northeastern Brazil, called Caatinga, and this region is characterized by low and irregular rainfall, with xerophilous vegetation. Social wasps are an important ecological group, which has been utilized for biological control and as bioindicators of environmental quality. Few studies about the diversity of social wasps were accomplished in the Caatinga and there is no survey of social wasps in the state of Paraiba. This study used data collected from city of Sumé, through field research and analysis of previously deposited material from surveys realized by Brazilian Corporation of Agricultural Research (EMBRAPA). Two species of social wasps, Polistes simillimus and Mischocyttarus cearensis, were recorded for the first time in state of Paraiba.
Cost Structure and Clinical Outcome of a Stem Cell Transplantation Program in a Developing Country: The Experience in Northeast Mexico
Authors: Jaime-Pérez José Carlos , Heredia-Salazar Alberto Carlos , Cantú-Rodríguez Olga G. , Gutiérrez-Aguirre Homero , Villarreal-Villarreal César Daniel , Mancías-Guerra Consuelo , Herrera-Garza José Luís , Gómez-Almaguer David 
Published: March 2015

Abstract

Background and Objective.
Hematopoietic stem cell transplantation (HSCT) in developing countries is cost-limited. Our primary goal was to determine the cost structure for the HSCT program model developed over the last decade at our public university hospital and to assess its clinical outcomes.

Materials and Methods.
Adults and children receiving an allogeneic hematopoietic stem cell transplant from January 2010 to February 2011 at our hematology regional reference center were included. Laboratory tests, medical procedures, chemotherapy drugs, other drugs, and hospitalization costs were scrutinized to calculate the total cost for each patient and the median cost for the procedure. Data regarding clinical evolution were incorporated into the analysis. Physician fees are not charged at the institution and therefore were not included.

Results.
Fifty patients were evaluated over a 1-year period. The total estimated cost for an allogeneic HSCT was $12,504. The two most expensive diseases to allograft were non-Hodgkin lymphoma ($11,760 ± $2,236) for the malignant group and thalassemia ($12,915 ± $5,170) for the nonmalignant group. Acute lymphoblastic leukemia ($11,053 ± 2,817) and acute myeloblastic leukemia ($10,251 ± $1,538) were the most frequent indications for HSCT, with 11 cases each. Median out-of-pocket expenses were $1,605, and 1-year follow-up costs amounted to $1,640, adding up to a total cost of $15,749 for the first year. The most expensive components were drugs and laboratory tests.

Conclusion.
Applying the cost structure described, HSCT is an affordable option for hematological patients living in a developing country.
The Value of Personalizing Medicine: Medical Oncologists’ Views on Gene Expression Profiling in Breast Cancer Treatment
Authors: Bombard Yvonne , Rozmovits Linda , Trudeau Maureen , Leighl Natasha B. , Deal Ken , Marshall Deborah A. 
Published: March 2015

Abstract

Objectives.
Guidelines recommend gene-expression profiling (GEP) tests to identify early-stage breast cancer patients who may benefit from chemotherapy. However, variation exists in oncologists’ use of GEP. We explored medical oncologists’ views of GEP tests and factors impacting its use in clinical practice.

Methods.
We used a qualitative design, comprising telephone interviews with medical oncologists (n = 14; 10 academic, 4 in the community) recruited through oncology clinics, professional advertisements, and referrals. Interviews were analyzed for anticipated and emergent themes using the constant comparative method including searches for disconfirming evidence.

Results.
Some oncologists considered GEP to be a tool that enhanced confidence in their established approach to risk assessments, whereas others described it as “critical” to resolving their uncertainty about whether to recommend chemotherapy. Some community oncologists also valued the test in interpreting what they considered variable practice and accuracy across pathology reports and testing facilities. However, concerns were also raised about GEP's cost, overuse, inappropriate use, and over-reliance on the results within the medical community. In addition, although many oncologists said it was simple to explain the test to patients, paradoxically, they remained uncertain about patients’ understanding of the test results and their treatment implications.

Conclusion.
Oncologists valued the test as a treatment-decision support tool despite their concerns about its cost, over-reliance, overuse, and inappropriate use by other oncologists, as well as patients’ limited understanding of GEP. The results identify a need for decision aids to support patients’ understanding and clinical practice guidelines to facilitate standardized use of the test.