bluuebunny/crossref_metadata_2025 huggingface dataset:
Italian consensus conference for colonic diverticulosis and diverticular disease
Authors: Cuomo Rosario , Barbara Giovanni , Pace Fabio , Annese Vito , Bassotti Gabrio , Binda Gian Andrea , Casetti Tino , Colecchia Antonio , Festi Davide , Fiocca Roberto , Laghi Andrea , Maconi Giovanni , Nascimbeni Riccardo , Scarpignato Carmelo , Villanacci Vincenzo , Annibale Bruno
Published: August 2014

The statements produced by the Consensus Conference on Diverticular Disease promoted by GRIMAD (Gruppo Italiano Malattia Diverticolare, Italian Group on Diverticular Diseases) are reported. Topics such as epidemiology, risk factors, diagnosis, medical and surgical treatment of diverticular disease (DD) in patients with uncomplicated and complicated DD were reviewed by a scientific board of experts who proposed 55 statements graded according to level of evidence and strength of recommendation, and approved by an independent jury. Each topic was explored focusing on the more relevant clinical questions. Comparison and discussion of expert opinions, pertinent statements and replies to specific questions, were presented and approved based on a systematic literature search of the available evidence. Comments were added explaining the basis for grading the evidence, particularly for controversial areas.
Security of Attachment to Spouses in Late Life
Authors: Waldinger Robert J. , Cohen Shiri , Schulz Marc S. , Crowell Judith A.
Published: August 2014

Social ties are powerful predictors of late-life health and well-being. Although many adults maintain intimate partnerships into late life, little is known about mental models of attachment to spouses and how they influence aging. A total of 81 elderly heterosexual couples (162 individuals) were interviewed to examine the structure of attachment security to their partners; respondents also completed measures of cognition and well-being concurrently and 2.5 years later. Factor analysis revealed a single factor for security of attachment. Higher security was linked concurrently with greater marital satisfaction, fewer depressive symptoms, better mood, and less frequent marital conflicts. Greater security predicted lower levels of negative affect, less depression, and greater life satisfaction 2.5 years later. For women, greater security predicted better memory 2.5 years later and attenuated the link between frequency of marital conflict and memory deficits. Late in life, mental models of attachment to partners are linked to well-being concurrently and over time.
Threat of Death and Autobiographical Memory
Authors: McKinnon Margaret C. , Palombo Daniela J. , Nazarov Anthony , Kumar Namita , Khuu Wayne , Levine Brian
Published: August 2014

We investigated autobiographical memory in a group of passengers onboard a transatlantic flight that nearly ditched at sea. The consistency of traumatic exposure across passengers, some of whom developed posttraumatic stress disorder (PTSD), provided a unique opportunity to assess verified memory for life-threatening trauma. Using the Autobiographical Interview, which separates episodic from nonepisodic details, passengers and healthy controls (HCs) recalled three events: the airline disaster (or a highly negative event for HCs), the September 11, 2001, attacks, and a nonemotional event. All passengers showed robust mnemonic enhancement for episodic details of the airline disaster. Although neither richness nor accuracy of traumatic recollection was related to PTSD, production of nonepisodic details for traumatic and nontraumatic events was elevated in PTSD passengers. These findings indicate a robust mnemonic enhancement for trauma that is not specific to PTSD. Rather, PTSD is associated with altered cognitive control operations that affect autobiographical memory in general.
Response Time to Craving-Item Ratings as an Implicit Measure of Craving-Related Processes
Authors: Germeroth Lisa J. , Wray Jennifer M. , Tiffany Stephen T.
Published: August 2014

Drug craving is typically measured through explicit ratings of craving levels. We examined response time to craving ratings as an implicit measure of craving processes in cigarette smokers. Response time and interitem variability were investigated as potential indices of certainty in craving ratings. Cigarette smokers, categorized as tobacco dependent or nondependent, completed multiple cue-reactivity sessions with smoking and neutral cues. After each cue presentation, craving level and response time were assessed. Significant inverted-U relationships emerged between craving level and both response time and interitem variability across conditions, sessions, and groups. Faster response times and less interitem variability emerged after neutral cues relative to smoking cues for nondependent smokers and after smoking cues relative to neutral cues for dependent smokers. Response time provided incremental validity beyond craving level in predicting dependence. Results support use of response time as an implicit measure of craving processes and further distinguish craving experiences between dependent and nondependent smokers.
Impacts of Parcel-based Second Level Landholding Certificates on Soil Conservation Investment in Tigrai, Northern Ethiopia
Authors: Gerezihar Kahsay , Tilahun Mesfin
Published: August 2014

The question of whether the rural land registration and certification has an impact on farm level investment or not, remains an important policy question. It is also a deeply sensitive political issue in present day of Ethiopia. Using household level data collected from 279 household, this article investigates the impacts of rural land certificates on investment and its implication on fostering land productivity. Farmers’ reasons for adopting soil conservation measures vary sharply between stone terraces and soil bunds. The likelihood ratio test of model appropriates rejects the Tobit model in favour of the double hurdle model. This encourages the researcher to separately estimate the impacts of certificate on adoption decision and intensity of adoption. Results from the double hurdle model shows certificate have positively and significantly correlated with decision to invest but negatively correlated with intensity of investment.
Regional Backwardness and Public Spending on Development of Rural Physical and Social Infrastructure in Karnataka
Authors: H.M. Siddaram
Published: August 2014

The word infrastructure has been derived from the different two independent words ‘Infra’ means which lies beneath or comes before and similarly ‘Structure’ which means well planned or organised. Infrastructure could serve as a true engine of growth and can provide the much needed momentum to the economic in the time of economic slowdown. The Indian economy has grown at an average 8 per cent in the recent past years, and a 10 per cent annual GDP growth is difficult to achieve unless the county improves its rural infrastructure. If India is to sustain its high growth much of the required investment is of a public goods nature and thus most of the infrastructure investments must come from public sources.

Karnataka is a pioneer State in the transformation of the ‘Gram Swaraj’ concept into reality and enacting the PRI Act to bring the practice of decentralised administration and development in line with the 73rd Amendment to the Constitution. A three-tier structure was created with the Zilla Panchayath at district, Taluka Panchayath at taluks and Gram Panchayath at the village level. 73rd amendment of constitution gives more power to Gram Panchayath in context to local self governance. A high power committee for the redressal of regional imbalance was constituted by the government in 2000. It identified 35 indicators encompassing agriculture, industry, and social-economic infrastructure and population characteristics to index of development. Gram Swaraj Project implemented in Karnataka State from the year 2006–2007 was based on Prof. Nanjundappa committee to address the issue of regional imbalances in his report. With this background the State Government has intend to strengthening the 1,341 Gram Panchayats comes under ‘most backward taluks’ with the collaboration of World bank aid.
Non-HLA genes PTPN22, CDK6 and PADI4 are associated with specific autoantibodies in HLA-defined subgroups of rheumatoid arthritis
Authors: Snir Omri , Gomez-Cabrero David , Montes Ariana , Perez-Pampin Eva , Gómez-Reino Juan J , Seddighzadeh Maria , Klich Katharina U , Israelsson Lena , Ding Bo , Catrina Anca I , Holmdahl Rikard , Alfredsson Lars , Klareskog Lars , Tegnér Jesper , Gonzalez Antonio , Malmström Vivianne , Padyukov Leonid
Published: August 2014

Introduction

Genetic susceptibility to complex diseases has been intensively studied during the last decade, yet only signals with small effect have been found leaving open the possibility that subgroups within complex traits show stronger association signals. In rheumatoid arthritis (RA), autoantibody production serves as a helpful discriminator in genetic studies and today anti-citrullinated cyclic peptide (anti-CCP) antibody positivity is employed for diagnosis of disease. The HLA-DRB1 locus is known as the most important genetic contributor for the risk of RA, but is not sufficient to drive autoimmunity and additional genetic and environmental factors are involved. Hence, we addressed the association of previously discovered RA loci with disease-specific autoantibody responses in RA patients stratified by HLA-DRB1*04.

Methods

We investigated 2178 patients from three RA cohorts from Sweden and Spain for 41 genetic variants and four autoantibodies, including the generic anti-CCP as well as specific responses towards citrullinated peptides from vimentin, alpha-enolase and type II collagen.

Results

Our data demonstrated different genetic associations of autoantibody-positive disease subgroups in relation to the presence of DRB1*04. Two specific subgroups of autoantibody-positive RA were identified. The SNP in PTPN22 was associated with presence of anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Cochran-Mantel-Haenszel test P = 0.0001, Pcorrected <0.05), whereas SNPs in CDK6 and PADI4 were associated with anti-CCP status in DRB1*04 negative patients (Cochran-Mantel-Haenszel test P = 0.0004, Pcorrected <0.05 for both markers). Additionally we see allelic correlation with autoantibody titers for PTPN22 SNP rs2476601 and anti-citrullinated enolase peptide antibodies in carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02) and between CDK6 SNP rs42041 and anti-CCP in non-carriers of HLA-DRB1*04 (Mann Whitney test P = 0.02).

Conclusion

These data point to alternative pathways for disease development in clinically similar RA subgroups and suggest an approach for study of genetic complexity of disease with strong contribution of HLA.
Weakly periodic boundary conditions for the homogenization of flow in porous media
Authors: Sandstöm Carl , Larsson Fredrik , Runesson Kenneth
Published: August 2014

Background

Seepage in porous media is modeled as a Stokes flow in an open pore system contained in a rigid, impermeable and spatially periodic matrix. By homogenization, the problem is turned into a two-scale problem consisting of a Darcy type problem on the macroscale and a Stokes flow on the subscale.

Methods

The pertinent equations are derived by minimization of a potential and in order to satisfy the Variationally Consistent Macrohomogeneity Condition, Lagrange multipliers are used to impose periodicity on the subscale RVE. Special attention is given to the bounds produced by confining the solutions spaces of the subscale problem.

Results

In the numerical section, we choose to discretize the Lagrange multipliers as global polynomials along the boundary of the computational domain and investigate how the order of the polynomial influence the permeability of the RVE. Furthermore, we investigate how the size of the RVE affect its permeability for two types of domains.

Conclusions

The permeability of the RVE depends highly on the discretization of the Lagrange multipliers. However, the flow quickly converges towards strong periodicity as the multipliers are refined.
Fluid Balance, Change in Serum Creatinine and Urine Output as Markers of Acute Kidney Injury Post Cardiac Surgery: An Observational Study
Authors: Chau Katrina , Schisler Travis , Er Lee , Jaswal Dharmvir , Cheung Christopher , Israel Amanda , Bowering John , Levin Adeera
Published: August 2014

Background:

Acute kidney injury (AKI) is defined as oliguria or rise in serum creatinine but oliguria alone as a diagnostic criterion may over-diagnose AKI.

Objectives:

Given the association between fluid overload and AKI, we aimed to determine if positive fluid balance can complement the known parameters in assessing outcomes of AKI.

Design:

Prospective observational study.

Setting:

Teaching hospital in Vancouver, Canada.

Patients:

111 consecutive patients undergoing elective cardiac surgery from January to April 2012.

Measurements:

Outcomes of cardiac surgery intensive care unit (CSICU) and hospital length of stay (LOS) in relation to fluid balance, urine output and serum creatinine.

Methods:

All fluid input and output was recorded for 72 hours post-operatively. Positive fluid balance was defined as >6.5 cc/kg. Daily serum creatinine and hourly urine output were recorded and patients were defined as having AKI according to the AKIN criteria.

Results:

Of the patients who were oliguric, those with fluid overload trended towards longer LOS than those without fluid overload [CSICU LOS: 62 and 39 hours (unadjusted p-value 0.02, adjusted p-value 0.58); hospital LOS: 13 and 9 days (unadjusted p-value: 0.05, adjusted p-value: 0.16)]. Patients with oliguria who were fluid overloaded had similar LOS to patients with overt AKI (change in serum creatinine ≥ 26.5 μmol/L), [CSICU LOS: 62 and 69 hours (adjusted p value: 0.32) and hospital LOS: 13 and 14 days (adjusted p value: 0.19)]. Patients with oliguria regardless of fluid balance had longer CSICU LOS (adjusted p value: 0.001) and patients who were fluid overloaded in the absence of AKI had longer hospital LOS (adjusted p value: 0.02).

Limitations:

Single centre, small sample, LOS as outcome.

Conclusions:

Oliguria and positive fluid balance is associated with a trend towards longer LOS as compared to oliguria alone. Fluid balance may therefore be a useful marker of AKI, in addition to urine output and serum creatinine.
Estimation of pressure-saturation changes for unconsolidated reservoir rocks with highVP/VSratio
Authors: Bhakta Tuhin , Landrø Martin
Published: August 2014

We find that conventional time-lapse seismic pressure-saturation discrimination methods become unstable for high [Formula: see text] ratios. Using first-order approximations in the amplitude variation with offset (AVO) gradient and intercept changes and in the rock-physics models increase the inaccuracy in pressure-saturation changes estimates. We propose a new method, based on a stepwise linear approximation to the intercept and gradient reflectivity changes, to estimate pressure and saturation changes. The applicability of the new method is tested on synthetic data over a range of 0%–50% gas saturation and 0–3.5 MPa pore-pressure changes. The new method is more consistent and provides better estimates compared with conventional methods. In the presence of random noise (up to 15%), the estimates are reasonably better for the new method. We use this new method to investigate the feasibility of pressure-saturation discrimination for a shallow unconsolidated sand reservoir in which an underground blowout occurred in 1989. We analyze a sand layer at 490-m depth that was charged by gas due to the blowout. Because of the shallow depth, the [Formula: see text] is expected to be higher than 2 before the blowout. Near- and far-offset time-lapse seismic data sets from 1988 and 1990 are used as input to estimate changes in AVO intercept and gradient and then changes in pressure and saturation. We find that the new method estimates more realistic pressure-saturation changes compared to the conventional one.
Brentuximab Vedotin in the Front-Line Treatment of Patients With CD30+ Peripheral T-Cell Lymphomas: Results of a Phase I Study
Authors: Fanale Michelle A. , Horwitz Steven M. , Forero-Torres Andres , Bartlett Nancy L. , Advani Ranjana H. , Pro Barbara , Chen Robert W. , Davies Andrew , Illidge Tim , Huebner Dirk , Kennedy Dana A. , Shustov Andrei R.
Published: August 2014

Purpose

Front-line treatment of peripheral T-cell lymphomas (PTCL) involves regimens such as cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) and results in a 5-year overall survival (OS) rate of less than 50%. This phase I open-label study evaluated the safety and activity of brentuximab vedotin administered sequentially with CHOP or in combination with CHP (CHOP without vincristine) as front-line treatment in patients with CD30+ PTCL.

Patients and Methods

Patients received sequential treatment (once every 3 weeks) with brentuximab vedotin 1.8 mg/kg (two cycles) followed by CHOP (six cycles) or brentuximab vedotin 1.8 mg/kg plus CHP (BV+CHP) for six cycles (once every 3 weeks). Responders received single-agent brentuximab vedotin for eight to 10 additional cycles (for a total of 16 cycles). The primary objective was assessment of safety; secondary end points included objective response rate, complete remission (CR) rate, progression-free survival rate (PFS), and OS. There were no prespecified comparisons of the two treatment approaches.

Results

After sequential treatment, 11 (85%) of 13 patients achieved an objective response (CR rate, 62%; estimated 1-year PFS rate, 77%). Grade 3/4 adverse events occurred in eight (62%) of 13 patients. At the end of combination treatment, all patients (n = 26) achieved an objective response (CR rate, 88%; estimated 1-year PFS rate, 71%). All seven patients without anaplastic large-cell lymphoma achieved CR. Grade 3/4 adverse events (≥ 10%) in the combination-treatment group were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).

Conclusion

Brentuximab vedotin, administered sequentially with CHOP or in combination with CHP, had a manageable safety profile and exhibited substantial antitumor activity in newly diagnosed patients with CD30+ PTCL. A randomized phase III trial is under way, comparing BV+CHP with CHOP (clinical trial No. NCT01777152).
Radiation Field Design in the ACOSOG Z0011 (Alliance) Trial
Authors: Jagsi Reshma , Chadha Manjeet , Moni Janaki , Ballman Karla , Laurie Fran , Buchholz Thomas A. , Giuliano Armando , Haffty Bruce G.
Published: August 2014

Purpose

ACOSOG Z0011 established that axillary lymph node dissection (ALND) is unnecessary in patients with breast cancer with one to two positive sentinel lymph nodes (SLNs) who undergo lumpectomy, radiotherapy (RT), and systemic therapy. We sought to ascertain RT coverage of the regional nodes in that trial.

Methods

We evaluated case report forms completed 18 months after enrollment. From 2012 to 2013, we collected all available detailed RT records for central review.

Results

Among 605 patients with completed case report forms, 89% received whole-breast RT. Of these, 89 (15%) were recorded as also receiving treatment to the supraclavicular region. Detailed RT records were obtained for 228 patients, of whom 185 (81.1%) received tangent-only treatment. Among 142 with sufficient records to evaluate tangent height, high tangents (cranial tangent border ≤ 2 cm from humeral head) were used in 50% of patients (33 of 66) randomly assigned to ALND and 52.6% (40 of 76) randomly assigned to SLND. Of the 228 patients with records reviewed, 43 (18.9%) received directed regional nodal RT using ≥ three fields: 22 in the ALND arm and 21 in the SLND arm. Those receiving directed nodal RT had greater nodal involvement (P < .001) than those who did not. Overall, there was no significant difference between treatment arms in the use of protocol-prohibited nodal fields.

Conclusion

Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.
Somatotropinomas, But Not Nonfunctioning Pituitary Adenomas, Maintain a Functional Apoptotic RET/Pit1/ARF/p53 Pathway That Is Blocked by Excess GDNF
Authors: Diaz-Rodriguez Esther , Garcia-Rendueles Angela R. , Ibáñez-Costa Alejandro , Gutierrez-Pascual Ester , Garcia-Lavandeira Montserrat , Leal Alfonso , Japon Miguel A. , Soto Alfonso , Venegas Eva , Tinahones Francisco J. , Garcia-Arnes Juan A. , Benito Pedro , Angeles Galvez Maria , Jimenez-Reina Luis , Bernabeu Ignacio , Dieguez Carlos , Luque Raul M. , Castaño Justo P. , Alvarez Clara V.
Published: August 2014

Acromegaly is caused by somatotroph cell adenomas (somatotropinomas [ACROs]), which secrete GH. Human and rodent somatotroph cells express the RET receptor. In rodents, when normal somatotrophs are deprived of the RET ligand, GDNF (Glial Cell Derived Neurotrophic Factor), RET is processed intracellularly to induce overexpression of Pit1 [Transcription factor (gene : POUF1) essential for transcription of Pituitary hormones GH, PRL and TSHb], which in turn leads to p19Arf/p53-dependent apoptosis. Our purpose was to ascertain whether human ACROs maintain the RET/Pit1/p14ARF/p53/apoptosis pathway, relative to nonfunctioning pituitary adenomas (NFPAs). Apoptosis in the absence and presence of GDNF was studied in primary cultures of 8 ACROs and 3 NFPAs. Parallel protein extracts were analyzed for expression of RET, Pit1, p19Arf, p53, and phospho-Akt. When GDNF deprived, ACRO cells, but not NFPAs, presented marked level of apoptosis that was prevented in the presence of GDNF. Apoptosis was accompanied by RET processing, Pit1 accumulation, and p14ARF and p53 induction. GDNF prevented all these effects via activation of phospho-AKT. Overexpression of human Pit1 (hPit1) directly induced p19Arf/p53 and apoptosis in a pituitary cell line. Using in silico studies, 2 CCAAT/enhancer binding protein alpha (cEBPα) consensus-binding sites were found to be 100% conserved in mouse, rat, and hPit1 promoters. Deletion of 1 cEBPα site prevented the RET-induced increase in hPit1 promoter expression. TaqMan qRT-PCR (real time RT-PCR) for RET, Pit1, Arf, TP53, GDNF, steroidogenic factor 1, and GH was performed in RNA from whole ACRO and NFPA tumors. ACRO but not NFPA adenomas express RET and Pit1. GDNF expression in the tumors was positively correlated with RET and negatively correlated with p53. In conclusion, ACROs maintain an active RET/Pit1/p14Arf/p53/apoptosis pathway that is inhibited by GDNF. Disruption of GDNF's survival function might constitute a new therapeutic route in acromegaly.
Role of Melanocortin Signaling in Neuroendocrine and Metabolic Actions of Leptin in Male Rats With Uncontrolled Diabetes
Authors: Meek Thomas H. , Matsen Miles E. , Damian Vincent , Cubelo Alex , Chua Streamson C. , Morton Gregory J.
Published: August 2014

Although the antidiabetic effects of leptin require intact neuronal melanocortin signaling in rodents with uncontrolled diabetes (uDM), increased melanocortin signaling is not sufficient to mimic leptin's glucose-lowering effects. The current studies were undertaken to clarify the role of melanocortin signaling in leptin's ability to correct metabolic and neuroendocrine disturbances associated with uDM. To accomplish this, bilateral cannulae were implanted in the lateral ventricle of rats with streptozotocin-induced diabetes, and leptin was coinfused with varying doses of the melanocortin 3/4 receptor (MC3/4R) antagonist, SHU9119. An additional cohort of streptozotocin-induced diabetes rats received intracerebroventricular administration of either the MC3/4R agonist, melanotan-II, or its vehicle. Consistent with previous findings, leptin's glucose-lowering effects were blocked by intracerebroventricular SHU9119. In contrast, leptin-mediated suppression of hyperglucagonemia involves both melanocortin dependent and independent mechanisms, and the degree of glucagon inhibition was associated with reduced plasma ketone body levels. Increased central nervous system melanocortin signaling alone fails to mimic leptin's ability to correct any of the metabolic or neuroendocrine disturbances associated with uDM. Moreover, the inability of increased melanocortin signaling to lower diabetic hyperglycemia does not appear to be secondary to release of the endogenous MC3/4R inverse agonist, Agouti-related peptide (AgRP), because AgRP knockout mice did not show increased susceptibility to the antidiabetic effects of increased MC3/4R signaling. Overall, these data suggest that 1) AgRP is not a major driver of diabetic hyperglycemia, 2) mechanisms independent of melanocortin signaling contribute to leptin's antidiabetic effects, and 3) melanocortin receptor blockade dissociates leptin's glucose-lowering effect from its action on other features of uDM, including reversal of hyperglucagonemia and ketosis, suggesting that brain control of ketosis, but not blood glucose levels, is glucagon dependent.
Genetic Risk Score for Prediction of Newborn Adiposity and Large-for-Gestational-Age Birth
Authors: Chawla Reeti , Badon Sylvia E. , Rangarajan Janani , Reisetter Anna C. , Armstrong Loren L. , Lowe Lynn P. , Urbanek Margrit , Metzger Boyd E. , Hayes M. Geoffrey , Scholtens Denise M. , Lowe William L.
Published: August 2014

Context:

Macrosomic infants are at increased risk for adverse metabolic outcomes. Improving prediction of large-for-gestational-age (LGA) birth may help prevent these outcomes.

Objective:

This study sought to determine whether genes associated with obesity-related traits in adults are associated with newborn size, and whether a genetic risk score (GRS) predicts LGA birth.

Setting and Design:

Single nucleotide polymorphisms (SNPs) in 40 regions associated with adult obesity-related traits were tested for association with newborn size. GRS's for birth weight and sum of skinfolds (SSF) specific to ancestry were calculated using the most highly associated SNP for each ancestry in genomic regions with one or more SNPs associated with birth weight and/or SSF in at least one ancestry group or meta-analyses.

Participants:

Newborns from the Hyperglycemia Adverse Pregnancy Outcomes Study were studied (942 Afro-Caribbean, 1294 Northern European, 573 Mexican-American, and 1182 Thai).

Outcome Measures:

Birth weight >90th percentile (LGA) and newborn SSF >90th percentile were primary outcomes.

Results:

After adjustment for ancestry, sex, gestational age at delivery, parity, maternal genotype, maternal smoking/alcohol intake, age, body mass index, height, blood pressure and glucose, 25 and 23 SNPs were associated (P < .001) with birth weight and newborn SSF, respectively. The GRS was highly associated with both phenotypes as continuous variables across all ancestries (P ≤ 1.6 × 10−19) and improved prediction of birth weight and SSF >90th percentile when added to a baseline model incorporating the covariates listed above.

Conclusions:

A GRS comprised of SNPs associated with adult obesity-related traits may provide an approach for predicting LGA birth and newborn adiposity beyond established risk factors.
No Improvement of High-Density Lipoprotein (HDL) Vasorelaxant Effect Despite Increase in HDL Cholesterol Concentration in Type 2 Diabetic Patients Treated With Glitazones
Authors: Perségol Laurence , Duvillard Laurence , Monier Serge , Brindisi Marie-Claude , Bouillet Benjamin , Petit Jean-Michel , Vergès Bruno
Published: August 2014

Context:

High-density lipoproteins (HDLs) from type 2 diabetic patients are unable to counteract the inhibitory effect of oxidized low-density lipoproteins (ox-LDLs) on vasorelaxation. We hypothesized that glitazones, which improve glycemic control and dyslipidemia, could correct this abnormality.

Objectives and Design:

We compared the ability of HDL from controls (n = 12) and from type 2 diabetic patients before and after 6 months of treatment with either rosiglitazone (n = 11) or pioglitazone (n = 8) to counteract the inhibitory effect of ox-LDL on vasodilatation of rabbit aorta rings.

Results:

Rosiglitazone induced a decrease in hemoglobin A1c (7.7% ± 1.1% vs 9.8% ± 1.0%, P = .003) and an increase in HDL cholesterol (1.14 ± 0.32 vs 0.98 ± 0.24 mmol/L, P = .033). Pioglitazone induced a decrease in hemoglobin A1c (8.3% ± 2.5% vs 9.5% ± 3.2%, P = .068) and serum triglycerides (1.58 ± 0.89 vs 2.03 ± 0.70 mmol/L, P = .069) and an increase in HDL cholesterol (1.39 ± 0.22 vs 1.14 ± 0.22 mmol/L, P = .018). The triglyceride content of HDL was unchanged by rosiglitazone and was decreased by 25% (P = .068) by pioglitazone. HDL from controls counteracted the inhibitory effect of ox-LDL on vasodilatation (maximal relaxation [Emax] = 74.4% ± 3.5% vs 51.9% ± 3.3%, P = .0029), whereas HDL from type 2 diabetic patients did not (Emax = 51.7% ± 5.8% vs 52.3% ± 4.6% [P = .66] and 52.7% ± 5.5% vs 51.9% ± 4.5% [P = .78] for the rosiglitazone and pioglitazone group, respectively). Rosiglitazone or pioglitazone did not improve Emax (58.6% ± 5.9% vs 52.3% ± 4.6% [P = .15] and 49.3% ± 6.5% vs 51.9% ± 4.5% [P = .48], respectively).

Conclusion:

Glitazones increased the concentration of HDL cholesterol without restoring the ability of HDL particles to protect the endothelium from oxidative stress-induced dysfunction, meaning that HDL remained dysfunctional with impaired antiatherogenic properties.
Prospective Study of Surgical Treatment of Acromegaly: Effects on Ghrelin, Weight, Adiposity, and Markers of CV Risk
Authors: Reyes-Vidal Carlos , Fernandez Jean Carlos , Bruce Jeffrey N. , Crisman Celina , Conwell Irene M. , Kostadinov Jane , Geer Eliza B. , Post Kalmon D. , Freda Pamela U.
Published: August 2014

Context:

Although epidemiological studies have found that GH and IGF-1 normalization reduce the excess mortality of active acromegaly to expected rates, cross-sectional data report some cardiovascular (CV) risk markers to be less favorable in remission than active acromegaly.

Objective:

The objective of the study was to test the hypothesis that remission of acromegaly after surgical therapy increases weight and adiposity and some CV risk markers and these changes are paralleled by a rise in ghrelin.

Design:

Forty-two adults with untreated, active acromegaly were studied prospectively. Changes in outcome measures from before to after surgery were assessed in 26 subjects achieving remission (normal IGF-1) and 16 with persistent active acromegaly (elevated IGF-1) after surgery.

Setting:

The study was conducted at tertiary referral centers for pituitary tumors.

Main Outcome Measures:

Endocrine, metabolic, and CV risk parameters, anthropometrics, and body composition by dual-energy X-ray absorptiometry were measured.

Results:

Remission increased total ghrelin, body weight, waist circumference, C-reactive protein, homocysteine, high-density lipoprotein, and leptin and reduced systolic blood pressure, homeostasis model assessment score, triglycerides, and lipoprotein (a) by 6 months and for 32 ± 4 months after surgery. The ghrelin rise correlated with the fall in the levels of GH, IGF-1, and insulin and insulin resistance. Weight, waist circumference, and ghrelin did not increase significantly in the persistent active acromegaly group. Total body fat, trunk fat, and perentage total body fat increased by 1 year after surgery in 15 remission subjects: the increase in body fat correlated with the rise in total ghrelin.

Conclusions:

Although most markers of CV risk improve with acromegaly remission after surgery, some markers and adiposity increase and are paralleled by a rise in total ghrelin, suggesting that these changes may be related. Understanding the mechanisms and long-term implications of the changes that accompany treatment of acromegaly is important to optimizing management because some aspects of the postoperative profile associate with the increased metabolic and CV risk in other populations.
Nephric duct insertion requires EphA4/EphA7 signaling from the pericloacal mesenchyme
Authors: Weiss Anna-Carina , Airik Rannar , Bohnenpoll Tobias , Greulich Franziska , Foik Anna , Trowe Mark-Oliver , Rudat Carsten , Costantini Frank , Adams Ralf H. , Kispert Andreas
Published: August 2014

The vesico-ureteric junction (VUJ) forms through a complex developmental program that connects the primordium of the upper urinary tract [the nephric duct (ND)] with that of the lower urinary tract (the cloaca). The signals that orchestrate the various tissue interactions in this program are poorly understood. Here, we show that two members of the EphA subfamily of receptor tyrosine kinases, EphA4 and EphA7, are specifically expressed in the mesenchyme surrounding the caudal ND and the cloaca, and that Epha4−/−;Epha7+/− and Epha4−/−;Epha7−/− (DKO) mice display distal ureter malformations including ureterocele, blind and ectopically ending ureters with associated hydroureter, megaureter and hydronephrosis. We trace these defects to a late or absent fusion of the ND with the cloaca. In DKO embryos, the ND extends normally and approaches the cloaca but the tip subsequently looses its integrity. Expression of Gata3 and Lhx1 and their downstream target Ret is severely reduced in the caudal ND. Conditional deletion of ephrin B2 from the ND largely phenocopies these changes, suggesting that EphA4/EphA7 from the pericloacal mesenchyme signal via ephrin B2 to mediate ND insertion. Disturbed activity of this signaling module may entail defects of the VUJ, which are frequent in the spectrum of congenital anomalies of the kidney and the urinary tract (CAKUT) in human newborns.
In vivo tmRNA protection by SmpB and pre-ribosome binding conformation in solution
Authors: Ranaei-Siadat Ehsan , Mérigoux Cécile , Seijo Bili , Ponchon Luc , Saliou Jean-Michel , Bernauer Julie , Sanglier-Cianférani Sarah , Dardel Fréderic , Vachette Patrice , Nonin-Lecomte Sylvie
Published: August 2014

TmRNA is an abundant RNA in bacteria with tRNA and mRNA features. It is specialized in trans-translation, a translation rescuing system. We demonstrate that its partner protein SmpB binds the tRNA-like region (TLD) in vivo and chaperones the fold of the TLD-H2 region. We use an original approach combining the observation of tmRNA degradation pathways in a heterologous system, the analysis of the tmRNA digests by MS and NMR, and co-overproduction assays of tmRNA and SmpB. We study the conformation in solution of tmRNA alone or in complex with one SmpB before ribosome binding using SAXS. Our data show that Mg2+ drives compaction of the RNA structure and that, in the absence of Mg2+, SmpB has a similar effect albeit to a lesser extent. Our results show that tmRNA is intrinsically structured in solution with identical topology to that observed on complexes on ribosomes which should facilitate its subsequent recruitment by the 70S ribosome, free or preloaded with one SmpB molecule.
A review of the biologic and pharmacologic role of docosapentaenoic acid n-3
Authors: Yazdi Puya G
Published: August 2014

Fish oil contains a complex mixture of omega-3 fatty acids, of which eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) are the three predominant forms. There has been a plethora of previous research on the effects and associations of fish oil supplementation with various clinical manifestations. While the majority of this work was focused on EPA and DHA as the active compounds, emerging research has begun to elucidate the specific role that DPA plays in these physiological processes and its differences with the other omega-3 fatty acids. The purpose of this review is to focus on the new studies undertaken with DPA. This review summarizes the biochemical mechanisms involved in the biosynthesis and metabolism of DPA before focusing on its effects in cardiovascular disease, immune function, and psychiatric and cognitive health. The limited studies point toward a positive role that DPA supplementation can play in these processes and that is separate and distinct from traditional supplementation with DHA and EPA.
Current treatment of early breast cancer: adjuvant and neoadjuvant therapy
Authors: Miller Elizabeth , Lee Hee Jin , Lulla Amriti , Hernandez Liz , Gokare Prashanth , Lim Bora
Published: August 2014

Breast cancer is the most commonly diagnosed cancer in women. The latest world cancer statistics calculated by the International Agency for Research on Cancer (IARC) revealed that 1,677,000 women were diagnosed with breast cancer in 2012 and 577,000 died. The TNM classification of malignant tumor (TNM) is the most commonly used staging system for breast cancer. Breast cancer is a group of very heterogeneous diseases. The molecular subtype of breast cancer carries important predictive and prognostic values, and thus has been incorporated in the basic initial process of breast cancer assessment/diagnosis. Molecular subtypes of breast cancers are divided into human epidermal growth factor receptor 2 positive (HER2 +), hormone receptor positive (estrogen or progesterone +), both positive, and triple negative breast cancer. By virtue of early detection via mammogram, the majority of breast cancers in developed parts of world are diagnosed in the early stage of the disease. Early stage breast cancers can be completely resected by surgery. Over time however, the disease may come back even after complete resection, which has prompted the development of an adjuvant therapy. Surgery followed by adjuvant treatment has been the gold standard for breast cancer treatment for a long time. More recently, neoadjuvant treatment has been recognized as an important strategy in biomarker and target evaluation. It is clinically indicated for patients with large tumor size, high nodal involvement, an inflammatory component, or for those wish to preserve remnant breast tissue. Here we review the most up to date conventional and developing treatments for different subtypes of early stage breast cancer.
The Latin American reconceptualisation movement
Authors: Servio Mariana
Published: August 2014

This article looks at some characteristics of the reconceptualisation movement that took place in the mid-1960s in Latin American social work. It focuses on the social, historical, political and theoretical influences that allowed a turning point in social work, in both academic and professional practice, marked mainly by the ideological-political debate about the role of social workers within the national liberation process and the commitment to people on a low income. The article sets out the changes from the entry of modernisation ideas in the mid-1950s and the emphasis on community development, prolegomena to the questionings of the current social assistance model as well as the teaching that was being developed in schools and institutes. Finally, it pays special attention to the role played by the social work publisher Editorial ECRO in Argentina in the diffusion of these ‘new ideas’ in the Americas.
Franco Basaglia and the radical psychiatry movement in Italy, 1961–78
Authors: Foot John
Published: August 2014

This article provides a short introduction to the life and work of Italian radical psychiatrist and mental health reformer Franco Basaglia. A leading figure in the democratic psychiatry movement, Basaglia is little known and often misunderstood in the English-speaking world. This article will seek to address this by highlighting Basaglia’s significant role in the struggle for both deinstitutionalisation and the human rights of those incarcerated in Italy’s asylums during the 1960s and 1970s.
Integrative Bioinformatics Analysis Reveals New Prognostic Biomarkers of Clear Cell Renal Cell Carcinoma
Authors: Butz Henriett , Szabó Peter M , Nofech-Mozes Roy , Rotondo Fabio , Kovacs Kalman , Mirham Lorna , Girgis Hala , Boles Dina , Patocs Attila , Yousef George M
Published: August 2014

BACKGROUND

The outcome of clear cell renal cell carcinoma (ccRCC) is still unpredictable. Even with new targeted therapies, the average progression-free survival is dismal. Markers for early detection and progression could improve disease outcome.

METHODS

To identify efficient and hitherto unrecognized pathogenic factors of the disease, we performed a uniquely comprehensive pathway analysis and built a gene interaction network based on large publicly available data sets assembled from 28 publications, comprising a 3-prong approach with high-throughput mRNA, microRNA, and protein expression profiles of 593 ccRCC and 389 normal kidney samples. We validated our results on 2 different data sets of 882 ccRCC and 152 normal tissues. Functional analyses were done by proliferation, migration, and invasion assays following siRNA (small interfering RNA) knockdown.

RESULTS

After integration of multilevel data, we identified aryl-hydrocarbon receptor (AHR), grainyhead-like-2 (GRHL2), and KIAA0101 as new pathogenic factors. GRHL2 expression was associated with higher chances for disease relapse and retained prognostic utility after controlling for grade and stage [hazard ratio (HR), 3.47, P = 0.012]. Patients with KIAA0101-positive expression suffered worse disease-free survival (HR, 3.64, P < 0.001), and in multivariate analysis KIAA0101 retained its independent prognostic significance. Survival analysis showed that GRHL2- and KIAA0101-positive patients had significantly lower disease-free survival (P = 0.002 and P < 0.001). We also found that KIAA0101 silencing decreased kidney cancer cell migration and invasion in vitro.

CONCLUSIONS

Using an integrative system biology approach, we identified 3 novel factors as potential biomarkers (AHR, GRHL2 and KIAA0101) involved in ccRCC pathogenesis and not linked to kidney cancer before.
Die Hermeneutik als traditionelle islamische Wissenschaft
Authors: Amirpur Katajun
Published: August 2014

In christlichen Kontexten wird gelegentlich kolportiert, dass der Koran im Islam unhinterfragt als nicht interpretierbares „Wort Gottes“ gilt, das hermeneutische Zugänge verwehrt. Die Autorin zeigt hingegen auf, dass sowohl in der Geschichte des Islam als auch in der gegenwärtigen Beschäftigung mit dem Koran namhafte islamische Denker seine Interpretierbarkeit begründen und entsprechende hermeneutische Konsequenzen ziehen.
Bibelhermeneutik – Von der Diastase zum Diskurs
Authors: Richter Cornelia
Published: August 2014

Der Beitrag benennt aus systematisch-theologischer Perspektive im Gespräch mit Jörg Lauster die Probleme, die sich vor dem Hintergrund der historischen Kritik für das protestantische Schriftprinzip ergeben, führt am Beispiel der Entwürfe von Michael Wolter und Christian Danz zur Christologie vor, wie Exegese und Dogmatik in einen produktiven Diskurs treten können, und plädiert am Ende für eine stärkere Berücksichtigung des Performanzbegriffs bei der Erschließung des Spannungsfelds zwischen Bibel und Systematischer Theologie.
Lebensrelevante Lektüre?
Authors: Pohl-Patalong Uta
Published: August 2014

Exegetische und erfahrungsbezogene Zugänge zur Bibel bilden Alternativen mit unterschiedlichen Akzentsetzungen, jedoch nicht (mehr) im Konflikt. Der Beitrag stellt erfahrungsorientierte Zugänge vor und fragt, welche hermeneutischen Annahmen die erfahrungsbezogenen Ansätze voraussetzen - gemeinsam mit der Exegese oder in Differenz zu ihr. Dies führt zu der Frage, wie die Behauptung einer Aktualität historischer Texte Jahrhunderte später hermeneutisch begründet werden kann: Wie fundiert die Praktische Theologie ihre Überzeugung von der Lebensrelevanz biblischer Texte?
On Two Optimal Control Problems for Magnetic Fields
Authors: Nicaise Serge , Stingelin Simon , Tröltzsch Fredi
Published: August 2014

Two optimal control problems for instationary magnetization
processes are considered in 3D spatial domains that
include electrically conducting and nonconducting regions. The magnetic
fields are generated by induction coils. In the first model, the induction coil
is considered as part of the conducting region and the electrical current is taken
as control. In the second, the coil is viewed as part of the nonconducting region and the
electrical voltage is the control.
Here, an integro-differential equation accounts for the magnetic induction law that couples the given
electrical voltage with the induced electrical current in the induction coil.
We derive first-order necessary optimality conditions for the optimal controls of both problems. Based on them,
numerical methods of gradient type are applied. Moreover, we report on the application
of model reduction by POD that lead to tremendous savings. Numerical tests are
presented for academic 3D geometries but also for a real-world application.
Communication breakdowns and diagnostic errors: a radiology perspective
Authors: Murphy Daniel R. , Singh Hardeep , Berlin Leonard
Published: August 2014

Timely and accurate communication is essential to safe and effective health care. Despite increased awareness over the past decade of the frequency of medical errors and greater efforts directed towards improving patient safety, patient harm due to communication breakdowns remains a significant problem. Communication problems related to diagnostic testing may account for nearly half of all errors made by typical primary care physicians in their medical practices. This article provides an overview of communication breakdowns in the context of radiology related diagnostic errors. In radiology, communication breakdowns between radiologists, referring clinicians, and patients can lead to failure of critical information to be relayed, resulting in delayed or missed diagnosis. New technologies, such electronic health records (EHRs), contribute to the increasing complexity of communication in health care, but if used correctly, they can provide several benefits to safe and effective communication. To address the complexity of communication breakdowns, a multifaceted sociotechnical approach is needed to address both technical and non-technical aspects of health care delivery. The article also provides some future directions in reducing communication breakdowns related to diagnostic testing, including proactive risk assessment of communication practices using recently released SAFER self-assessment guides.
Investigating the influence of temperature on electrospinning of polycaprolactone solutions
Authors: Ramazani Soghra , Karimi Mohammad
Published: August 2014

The present work shows the effect of temperature on successfully obtained uniform electrospun poly-(ε-caprolactone) (PCL) fibers, with specific attention to the molecular orientation and diameter of nanofibers. Experiments were performed at temperatures (T) of 25°, 35°, and 45°C, and at PCL concentrations (w) of 12, 16, and 20 wt.%. Scanning electron microscopy provided the morphology of electrospun fibers and quantified their diameters. Elevated temperature for all PCL concentrations yielded a viscosity that allows for easier stretching of the jet to obtain a smaller diameter for fibers. A minimum size of the fiber diameter (close to 100 nm) was achieved for the set point T=45°C and w=12 and 16 wt.%. Due to the easy stretching of the jet by controlling the elastic property of the solution, a dichroic ratio of 1.62 was accessible for the set point T=35°C and w=12 wt.% from polarized Fourier transform infrared spectra as a factor for the orientation of PCL chains.
Optical Solitons in Magneto-optic Waveguides with Spatio-temporal Dispersion
Authors: Savescu Michelle , Bhrawy A. H. , Hilal E. M. , Alshaery A. A. , Biswas Anjan
Published: August 2014

This paper obtains the exact solution for solitons propagating through magneto-optic waveguides. There are three forms of nonlinear media that are considered. They are Kerr law, power law and log-law nonlinearity. The ansatz approach retrieves bright, dark as well as singular soliton solutions. There are several constraint conditions that needs to be in place for the solitons and Gaussons to exist.