bluuebunny/crossref_metadata_2025 huggingface dataset:
PPARγ Antagonist Gleevec Improves Insulin Sensitivity and Promotes the Browning of White Adipose Tissue
Authors: Choi Sun-Sil , Kim Eun-Sun , Jung Ji-Eun , Marciano David P. , Jo Ala , Koo Ja Young , Choi Soo Youn , Yang Yong Ryoul , Jang Hyun-Jun , Kim Eung-Kyun , Park Jiyoung , Kwon Hyug Moo , Lee In Hee , Park Seung Bum , Myung Kyung-Jae , Suh Pann-Ghill , Griffin Patrick R. , Choi Jang Hyun
Published: January 2016

Blocking phosphorylation of peroxisome proliferator–activated receptor (PPAR)γ at Ser273 is one of the key mechanisms for antidiabetes drugs to target PPARγ. Using high-throughput phosphorylation screening, we here describe that Gleevec blocks cyclin-dependent kinase 5–mediated PPARγ phosphorylation devoid of classical agonism as a PPARγ antagonist ligand. In high fat–fed mice, Gleevec improved insulin sensitivity without causing severe side effects associated with other PPARγ-targeting drugs. Furthermore, Gleevec reduces lipogenic and gluconeogenic gene expression in liver and ameliorates inflammation in adipose tissues. Interestingly, Gleevec increases browning of white adipose tissue and energy expenditure. Taken together, the results indicate that Gleevec exhibits greater beneficial effects on both glucose/lipid metabolism and energy homeostasis by blocking PPARγ phosphorylation. These data illustrate that Gleevec could be a novel therapeutic agent for use in insulin resistance and type 2 diabetes.
Hypothyroidism Impairs Human Stem Cell–Derived Pancreatic Progenitor Cell Maturation in Mice
Authors: Bruin Jennifer E. , Saber Nelly , O’Dwyer Shannon , Fox Jessica K. , Mojibian Majid , Arora Payal , Rezania Alireza , Kieffer Timothy J.
Published: January 2016

Pancreatic progenitors derived from human embryonic stem cells (hESCs) are a potential source of transplantable cells for treating diabetes and are currently being tested in clinical trials. Yet, how the milieu of pancreatic progenitor cells, including exposure to different factors after transplant, may influence their maturation remains unclear. Here, we examined the effect of thyroid dysregulation on the development of hESC-derived progenitor cells in vivo. Hypothyroidism was generated in SCID-beige mice using an iodine-deficient diet containing 0.15% propyl-2-thiouracil, and hyperthyroidism was generated by addition of L-thyroxine (T4) to drinking water. All mice received macroencapsulated hESC-derived progenitor cells, and thyroid dysfunction was maintained for the duration of the study (“chronic”) or for 4 weeks posttransplant (“acute”). Acute hyperthyroidism did not affect graft function, but acute hypothyroidism transiently impaired human C-peptide secretion at 16 weeks posttransplant. Chronic hypothyroidism resulted in severely blunted basal human C-peptide secretion, impaired glucose-stimulated insulin secretion, and elevated plasma glucagon levels. Grafts from chronic hypothyroid mice contained fewer β-cells, heterogenous MAFA expression, and increased glucagon+ and ghrelin+ cells compared to grafts from euthyroid mice. Taken together, these data suggest that long-term thyroid hormone deficiency may drive the differentiation of human pancreatic progenitor cells toward α- and ε-cell lineages at the expense of β-cell formation.
Association Between Hospitalization for Heart Failure and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes: An Observational Study
Authors: Fu Alex Z. , Johnston Stephen S. , Ghannam Ameen , Tsai Katherine , Cappell Katherine , Fowler Robert , Riehle Ellen , Cole Ashley L. , Kalsekar Iftekhar , Sheehan John
Published: January 2016

OBJECTIVE

To examine, among patients with type 2 diabetes, the association between hospitalization for heart failure (hHF) and treatment with dipeptidyl peptidase 4 inhibitors (DPP-4is) versus sulfonylureas (SUs), and treatment with saxagliptin versus sitagliptin.

RESEARCH DESIGN AND METHODS

This was a retrospective, observational study using a U.S. insurance claims database. Patients initiated treatment between 1 August 2010 and 30 August 2013, and had no use of the comparator treatments in the prior 12 months (baseline). Each comparison consisted of patients matched 1:1 on a propensity score. Time to each outcome was compared between matched groups using Cox models. Analyses were stratified by the presence of baseline cardiovascular disease (CVD). Secondary analyses examined associations between comparator treatments and other selected cardiovascular events.

RESULTS

After matching, the study included 218,556 patients in comparisons of DPP-4i and SU, and 112,888 in comparisons of saxagliptin and sitagliptin. The hazard ratios (HRs) of hHF were as follows: DPP-4i versus SU (reference): HR 0.95 (95% CI 0.78–1.15), P = 0.580 for patients with baseline CVD; HR 0.59 (95% CI 0.38–0.89), P = 0.013 for patients without baseline CVD; saxagliptin versus sitagliptin (reference): HR 0.95 (95% CI 0.70–1.28), P = 0.712 for patients with baseline CVD; HR 0.99 (95% CI 0.56–1.75), P = 0.972 for patients without baseline CVD. Comparisons of the individual secondary and composite cardiovascular outcomes followed a similar pattern.

CONCLUSIONS

In patients with type 2 diabetes, there was no association between hHF, or other selected cardiovascular outcomes, and treatment with a DPP-4i relative to SU or treatment with saxagliptin relative to sitagliptin.
Reduced Lower-Limb Muscle Strength and Volume in Patients With Type 2 Diabetes in Relation to Neuropathy, Intramuscular Fat, and Vitamin D Levels
Authors: Almurdhi Monirah M. , Reeves Neil D. , Bowling Frank L. , Boulton Andrew J.M. , Jeziorska Maria , Malik Rayaz A.
Published: January 2016

OBJECTIVE

Muscle weakness and atrophy of the lower limbs may develop in patients with diabetes, increasing their risk of falls. The underlying basis of these abnormalities has not been fully explained. The aim of this study was to objectively quantify muscle strength and size in patients with type 2 diabetes mellitus (T2DM) in relation to the severity of neuropathy, intramuscular noncontractile tissue (IMNCT), and vitamin D deficiency.

RESEARCH DESIGN AND METHODS

Twenty patients with T2DM and 20 healthy control subjects were matched by age, sex, and BMI. Strength and size of knee extensor, flexor, and ankle plantar and dorsiflexor muscles were assessed in relation to the severity of diabetic sensorimotor polyneuropathy (DSPN), amount of IMNCT, and serum 25-hydroxyvitamin D (25OHD) levels.

RESULTS

Compared with control subjects, patients with T2DM had significantly reduced knee extensor strength (P = 0.003) and reduced muscle volume of both knee extensors (P = 0.045) and flexors (P = 0.019). Ankle plantar flexor strength was also significantly reduced (P = 0.001) but without a reduction in ankle plantar flexor (P = 0.23) and dorsiflexor (P = 0.45) muscle volumes. IMNCT was significantly increased in the ankle plantar (P = 0.006) and dorsiflexors (P = 0.005). Patients with DSPN had significantly less knee extensor strength than those without (P = 0.02) but showed no difference in knee extensor volume (P = 0.38) and ankle plantar flexor strength (P = 0.21) or volume (P = 0.96). In patients with <25 nmol/L versus >25 nmol/L 25OHD, no significant differences were found for knee extensor strength and volume (P = 0.32 vs. 0.18) and ankle plantar flexors (P = 0.58 vs. 0.12).

CONCLUSIONS

Patients with T2DM have a significant reduction in proximal and distal leg muscle strength and a proximal but not distal reduction in muscle volume possibly due to greater intramuscular fat accumulation in distal muscles. Proximal but not distal muscle strength is related to the severity of peripheral neuropathy but not IMNCT or 25OHD level.
Adherence to Oral Glucose-Lowering Therapies and Associations With 1-Year HbA1c: A Retrospective Cohort Analysis in a Large Primary Care Database
Authors: Farmer Andrew J. , Rodgers Lauren R. , Lonergan Mike , Shields Beverley , Weedon Michael N. , Donnelly Louise , Holman Rury R. , Pearson Ewan R. , Hattersley Andrew T.
Published: January 2016

OBJECTIVE

The impact of taking oral glucose-lowering medicines intermittently, rather than as recommended, is unclear. We conducted a retrospective cohort study using community-acquired U.K. clinical data (Clinical Practice Research Database [CPRD] and GoDARTS database) to examine the prevalence of nonadherence to treatment for type 2 diabetes and investigate its potential impact on HbA1c reduction stratified by type of glucose-lowering medication.

RESEARCH DESIGN AND METHODS

Data were extracted for patients treated between 2004 and 2014 who were newly prescribed metformin, sulfonylurea, thiazolidinedione, or dipeptidyl peptidase 4 inhibitors and who continued to obtain prescriptions over 1 year. Cohorts were defined by prescribed medication type, and good adherence was defined as a medication possession ratio ≥0.8. Linear regression was used to determine potential associations between adherence and 1-year baseline-adjusted HbA1c reduction.

RESULTS

In CPRD and GoDARTS, 13% and 15% of patients, respectively, were nonadherent. Proportions of nonadherent patients varied by the oral glucose-lowering treatment prescribed (range 8.6% [thiazolidinedione] to 18.8% [metformin]). Nonadherent, compared with adherent, patients had a smaller HbA1c reduction (0.4% [4.4 mmol/mol] and 0.46% [5.0 mmol/mol] for CPRD and GoDARTs, respectively). Difference in HbA1c response for adherent compared with nonadherent patients varied by drug (range 0.38% [4.1 mmol/mol] to 0.75% [8.2 mmol/mol] lower in adherent group). Decreasing levels of adherence were consistently associated with a smaller reduction in HbA1c.

CONCLUSIONS

Reduced medication adherence for commonly used glucose-lowering therapies among patients persisting with treatment is associated with smaller HbA1c reductions compared with those taking treatment as recommended. Differences observed in HbA1c responses to glucose-lowering treatments may be explained in part by their intermittent use.
Prevalence of Diabetes and Diabetic Nephropathy in a Large U.S. Commercially Insured Pediatric Population, 2002–2013
Authors: Li Lin , Jick Susan , Breitenstein Stefanie , Michel Alexander
Published: January 2016

OBJECTIVE

To estimate the prevalence of diabetes and diabetic nephropathy in a large population of U.S. commercially insured patients aged <18 years from 2002 to 2013.

RESEARCH DESIGN AND METHODS

Using the U.S. MarketScan Commercial Claims and Encounters Database, we identified 96,171 pediatric patients with diabetes and 3,161 pediatric patients with diabetic nephropathy during 2002–2013. We estimated prevalence of pediatric diabetes overall, by diabetes type, age, and sex, and prevalence of pediatric diabetic nephropathy overall, by age, sex, and diabetes type.

RESULTS

The annual prevalence of diabetes in the whole pediatric population increased from 1.86 to 2.82 per 1,000 during 2002–2013: 1.48 to 2.32 per 1,000 for type 1 diabetes and 0.38 to 0.67 per 1,000 for type 2 diabetes in 2002–2006 and then 0.56 to 0.49 per 1,000 thereafter. The annual prevalence of diabetic nephropathy in pediatric patients with diabetes increased from 1.16 to 3.44% for all cases and 0.83 to 2.32% for probable cases only in 2002–2013. Prevalence of diabetes and diabetic nephropathy was highest in patients aged 12 to <18 years. While prevalence of type 1 diabetes was higher in male than in female youth, prevalence of type 2 diabetes and diabetic nephropathy was higher in female than in male youth. There was no difference in prevalence of diabetic nephropathy by diabetes type.

CONCLUSIONS

The prevalence of diabetes and diabetic nephropathy increased in the U.S. MarketScan commercially insured pediatric population from 2002 to 2013. The prevalence of diabetes and diabetic nephropathy markedly increased starting at age 12 years.
Association of Gestational Diabetes Mellitus With Left Ventricular Structure and Function: The CARDIA Study
Authors: Appiah Duke , Schreiner Pamela J. , Gunderson Erica P. , Konety Suma H. , Jacobs David R. , Nwabuo Chike C. , Ebong Imo A. , Whitham Hilary K. , Goff David C. , Lima Joao A. , Ku Ivy A. , Gidding Samuel S.
Published: January 2016

OBJECTIVE

Gestational diabetes mellitus (GDM) predicts incident cardiovascular disease (CVD). However, mechanisms linking GDM to CVD beyond intervening incident diabetes are not well understood. We examined the relation of GDM with echocardiographic parameters of left ventricular (LV) structure and function, which are important predictors of future CVD risk.

RESEARCH DESIGN AND METHODS

We studied 609 women (43% black) from the Coronary Artery Risk Development in Young Adults (CARDIA) study who delivered one or more births during follow-up and had echocardiograms in 1990–1991 (mean age 28.8 years) and 2010–2011.

RESULTS

During the 20-year follow-up, 965 births were reported, with GDM developing in 64 women (10.5%). In linear regression models adjusted for sociodemographic factors, BMI, physical activity, parity, smoking, use of oral contraceptives, alcohol intake, family history of coronary heart disease, systolic blood pressure, and lipid levels, women with GDM had impaired longitudinal peak strain (−15.0 vs. −15.7%, P = 0.025), circumferential peak strain (−14.8 vs. −15.6%, P = 0.028), lateral e′ wave velocity (11.0 vs. 11.8 cm/s, P = 0.012), and septal e′ wave velocity (8.6 vs. 9.3 cm/s, P = 0.015) in 2010–2011 and a greater 20-year increase in LV mass indexed to body surface area (14.3 vs. 6.0 g/m2, P = 0.006) compared with women with non-GDM pregnancies. Further adjustment for incident type 2 diabetes after pregnancy did not attenuate these associations.

CONCLUSIONS

Pregnancy complicated by GDM is independently associated with increased LV mass and impaired LV relaxation and systolic function. Implementation of postpartum cardiovascular health interventions in women with a history of GDM may offer an additional opportunity to reduce future CVD risk.
Health Care Transition in Young Adults With Type 1 Diabetes: Perspectives of Adult Endocrinologists in the U.S.
Authors: Garvey Katharine C. , Telo Gabriela H. , Needleman Joseph S. , Forbes Peter , Finkelstein Jonathan A. , Laffel Lori M.
Published: January 2016

OBJECTIVE

Young adults with type 1 diabetes transitioning from pediatric to adult care are at risk for adverse outcomes. Our objective was to describe experiences, resources, and barriers reported by a national sample of adult endocrinologists receiving and caring for young adults with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We fielded an electronic survey to adult endocrinologists with a valid e-mail address identified through the American Medical Association Physician Masterfile.

RESULTS

We received responses from 536 of 4,214 endocrinologists (response rate 13%); 418 surveys met the eligibility criteria. Respondents (57% male, 79% Caucasian) represented 47 states; 64% had been practicing >10 years and 42% worked at an academic center. Only 36% of respondents reported often/always reviewing pediatric records and 11% reported receiving summaries for transitioning young adults with type 1 diabetes, although >70% felt that these activities were important for patient care. While most respondents reported easy access to diabetes educators (94%) and dietitians (95%), fewer (42%) reported access to mental health professionals, especially in nonacademic settings. Controlling for practice setting and experience, endocrinologists without easy access to mental health professionals were more likely to report barriers to diabetes management for young adults with depression (odds ratio [OR] 5.3; 95% CI 3.4, 8.2), substance abuse (OR 3.5; 95% CI 2.2, 5.6), and eating disorders (OR 2.5; 95% CI 1.6, 3.8).

CONCLUSIONS

Our findings underscore the need for enhanced information transfer between pediatric and adult providers and increased mental health referral access for young adults with diabetes post-transition.
Hyperbaric Oxygen Therapy Does Not Reduce Indications for Amputation in Patients With Diabetes With Nonhealing Ulcers of the Lower Limb: A Prospective, Double-Blind, Randomized Controlled Clinical Trial
Authors: Fedorko Ludwik , Bowen James M. , Jones Wilhelmine , Oreopoulos George , Goeree Ron , Hopkins Robert B. , O’Reilly Daria J.
Published: January 2016

OBJECTIVE

Hyperbaric oxygen therapy (HBOT) is used for the treatment of chronic diabetic foot ulcers (DFUs). The controlled evidence for the efficacy of this treatment is limited. The goal of this study was to assess the efficacy of HBOT in reducing the need for major amputation and improving wound healing in patients with diabetes and chronic DFUs.

RESEARCH DESIGN AND METHODS

Patients with diabetes and foot lesions (Wagner grade 2–4) of at least 4 weeks' duration participated in this study. In addition to comprehensive wound care, participants were randomly assigned to receive 30 daily sessions of 90 min of HBOT (breathing oxygen at 244 kPa) or sham (breathing air at 125 kPa). Patients, physicians, and researchers were blinded to group assignment. At 12 weeks postrandomization, the primary outcome was freedom from meeting the criteria for amputation as assessed by a vascular surgeon. Secondary outcomes were measures of wound healing.

RESULTS

One hundred fifty-seven patients were assessed for eligibility, with 107 randomly assigned and 103 available for end point adjudication. Criteria for major amputation were met in 13 of 54 patients in the sham group and 11 of 49 in the HBOT group (odds ratio 0.91 [95% CI 0.37, 2.28], P = 0.846). Twelve (22%) patients in the sham group and 10 (20%) in the HBOT group were healed (0.90 [0.35, 2.31], P = 0.823). All other indices of wound healing were also not statistically significantly different between groups.

CONCLUSIONS

HBOT does not offer an additional advantage to comprehensive wound care in reducing the indication for amputation or facilitating wound healing in patients with chronic DFUs.
Day-and-Night Hybrid Closed-Loop Insulin Delivery in Adolescents With Type 1 Diabetes: A Free-Living, Randomized Clinical Trial
Authors: Tauschmann Martin , Allen Janet M. , Wilinska Malgorzata E. , Thabit Hood , Stewart Zoë , Cheng Peiyao , Kollman Craig , Acerini Carlo L. , Dunger David B. , Hovorka Roman
Published: January 2016

OBJECTIVE

To evaluate feasibility, safety, and efficacy of day-and-night hybrid closed-loop insulin delivery in adolescents with type 1 diabetes under free-living conditions without remote monitoring or supervision.

RESEARCH DESIGN AND METHODS

In an open-label, randomized, free-living, crossover study design, 12 adolescents receiving insulin pump therapy (mean [±SD] age 15.4 ± 2.6 years; HbA1c 8.3 ± 0.9%; duration of diabetes 8.2 ± 3.4 years) underwent two 7-day periods of sensor-augmented insulin pump therapy or hybrid closed-loop insulin delivery without supervision or remote monitoring. During the closed-loop insulin delivery, a model predictive algorithm automatically directed insulin delivery between meals and overnight; prandial boluses were administered by participants using a bolus calculator.

RESULTS

The proportion of time when the sensor glucose level was in the target range (3.9–10 mmol/L) was increased during closed-loop insulin delivery compared with sensor-augmented pump therapy (72 vs. 53%, P < 0.001; primary end point), the mean glucose concentration was lowered (8.7 vs. 10.1 mmol/L, P = 0.028), and the time spent above the target level was reduced (P = 0.005) without changing the total daily insulin amount (P = 0.55). The time spent in the hypoglycemic range was low and comparable between interventions.

CONCLUSIONS

Unsupervised day-and-night hybrid closed-loop insulin delivery at home is feasible and safe in young people with type 1 diabetes. Compared with sensor-augmented insulin pump therapy, closed-loop insulin delivery may improve glucose control without increasing the risk of hypoglycemia in adolescents with suboptimally controlled type 1 diabetes.
Effects of post-curing on the thermo-mechanical behavior and the chemical structure of highly filled phenolic molding compounds
Authors: Scheffler Thomas , Englich Sascha , Heyne Ulrich , Gehde Michael
Published: January 2016

Due to their excellent thermomechanical properties, as well as their good media resistance, phenolic molding compounds are outstanding materials for high temperature applications, such as components for the engine compartment. An additional post-curing process, after injection molding, shifts the glass transition temperature towards high temperatures up to 300 °C. The objective of this work is to analyze the influence of the post-curing process on the chemical structure of the material. This structure is responsible for the mechanical and thermal properties of the material. Therefore tensile test bars were molded with a highly filled phenolic molding compound and different post-curing cycles under different atmospheres were done. The tensile properties and the glass transition temperatures (TMA) were measured. To get detailed information of the chemical structure ATR-FTIR and NMR analyses were done. The mechanical properties decreased up to 25 % with higher post-curing temperature (under air atmosphere) although the glass transition temperatures (TMA) and the grades of curing (NMR) increased. Furthermore, in the ATR-FTIR measurements, oxidation products were detected on the surface of the sample which were post-cured under air atmosphere. In comparison, no oxidation products could be detected on the samples post-cured under nitrogen atmosphere and the mechanical properties just decreased about 4 %. Oxidation processes could be provided by post-curing under nitrogen atmosphere which led to higher mechanical properties, in connection with a high grade of cure and a higher glass transition temperature in comparison with post-curing under air atmosphere.
Effect of drawing with shear on structure and properties of low-carbon steel
Authors: Pashinskaya Elena , Zavdoveev Anatoly , Mironov Sergey , Varyukhin Victor , Maksakova Anna
Published: January 2016

The feasibility of drawing with shear of low-carbon steel for wire production was studied. The new approach was shown to be more effective in producing of homogeneous microstructure with refined grain size, reduced porosity and increased mechanical strength. These effects were attributed to a specific “twist” character of material flow.
Recycled Material Web Map: Connecting Consumers and Producers
Authors: Graettinger Andrew J. , Shake Brittany D. , Smith Randy K. , Bucy Megan Huval
Published: January 2016

An online geographic information system web application that connects producers and consumers of recyclable material was developed to assist engineers and contractors in the beneficial reuse of recycled materials in transportation projects. The Recycled Material Web Map comprises four core layers: producers, stockpiles, specifications, and case studies. Producers of recycled material can locate their facility and enter contact information. The stockpile layer, connected to the producer layer, allows facility managers to add or update information about their recycled material stockpiles that includes material type, application, availability, and cost. Multiple stockpiles can be associated with each producer. The specification layer includes both Department of Transportation specifications and environmental regulations pertaining to the beneficial reuse of nonhazardous recycled material on the basis of specific location, material type, and application. The case study layer locates projects that successfully used recycled materials and has information about the material type, application, volume data, and any additional documentation. As potential consumers of recycled material, engineers and contractors can pinpoint the location of a construction project, search for sources and quantities of recycled material that meets project specifications, and contact material producers. The web map uses search capabilities to locate nearby stockpiles to minimize transportation costs that typically dictate the use of large volumes of materials. The Recycled Material Web Map provides key information that engineers and contractors need to successfully use recycled materials, thereby preserving limited natural resources and benefiting the project and society as a whole.
Learning from Insurance Data: Injuries to Other Road Users in Motorcyclist At-Fault Crashes
Authors: Debnath Ashim Kumar , Haworth Narelle
Published: January 2016

In multivehicle crashes involving motorcycles, the motorcycle rider is less likely to be at fault but more commonly severely injured than the other road user. Not surprisingly, crashes in which motorcycle riders were at fault and, particularly, crashes in which the other road users were injured have not received little research attention. This paper aims to address this gap in the literature by an investigation of the factors influencing the severity of injury to other road users in crashes in which the motorcyclist was at fault. Five years of data from Queensland, Australia, were obtained from a database of claims against the compulsory third party (CTP) injury insurance of the at-fault motorcyclists. Analysis of the data with an ordered profit model showed more severe injuries in crashes involving young (younger than 25) and older (older than 60) at-fault motorcyclists. Of the not-at-fault road users, the young, the old, and males were found to be more severely injured than were others. Injuries to vehicle occupants were less severe than those to motorcycle passengers. Crashes that occurred between vehicles traveling in opposite directions resulted in injuries that were more severe than injuries in crashes involving vehicles traveling in the same direction. While most existing studies have analyzed crash data reported by police, this study used CTP insurance data. Comparison of results indicates that CTP insurance data could be used as an alternative to crash data reported by police for gaining a better understanding of risk factors for motorcycle crashes and injury severity.
Development of a Novel Enzyme-Targeting Radiosensitizer (New KORTUC) Using a Gelatin-Based Hydrogel Instead of a Sodium Hyaluronate
Authors: Morita-Tokuhiro Shiho , Ogawa Yasuhiro , Yokota Norikazu , Tsuzuki Akira , Oda Hideki , Ishida Naoya , Aoyama Nobutaka , Nishioka Akihito
Published: January 2016

We recently developed Kochi Oxydol-Radiation Therapy for Unresectable Carcinomas (KORTUC) as a strategy to increase intratumoral oxygen concentrations and degrade antioxidant enzymes such as peroxidase and catalase. We then developed KORTUC II, which uses sodium hyaluronate containing hydrogen peroxide as a radiosensitizer. KORTUC II requires twice-weekly administration to sustain its effects, but decreasing the frequency of radiosensitizer injections to once-weekly would reduce the burden on the patients and the physicians. The goal of this study was thus to develop a new formulation of KORTUC (New KORTUC) that only requires once-weekly administration. We performed experimental studies using a mouse tumor model and biodegradable hydrogel. C3H/He mice were allocated to control, KORTUC, or hydrogel groups. At 72 h after injection, each tumor was irradiated with a 6 MeV electron beam to a total dose of 30 Gy. During a 62-day observation period, changes in tumor volume and survival rates were assessed in each group. Tumor growth rate was slowest in the hydrogel groups. These data suggest that hydrogel could represent a useful adjunct as a long-acting radiosensitizer in place of sodium hyaluronate. New KORTUC, which contains hydrogen peroxide and hydrogel, exerted a radiosensitizing effect that persisted beyond 72 h following injection of the agent. Use of this new formulation allows radiosensitizer injections to be performed once-weekly with good effect.
Potential Pitfalls on the 99mTc-Mebrofenin Hepatobiliary Scintigraphy in a Patient with Biliary Atresia Splenic Malformation Syndrome
Authors: Maestri Brittain Jane , Borgwardt Lise
Published: January 2016

Biliary atresia (BA) is an obliterative cholangiopathy affecting 1:10.000–14.000 of newborns. Infants with Biliary Atresia Splenic Malformation syndrome (BASM) are a subgroup of BA patients with additional congenital anomalies. Untreated the disease will result in fatal liver failure within the first years of life. Kasai portoenterostomy restores bile flow and delay the progressive liver damage thereby postponing liver transplantation. An early diagnosis is of most importance to ensure the effectiveness of the operation. The 99mTc-Mebrofenin hepatobiliary scintigraphy is part of the diagnostic strategy when an infant presents jaundice due to conjugated hyperbilirubinemia (>20 µmol/L total bilirubin of which 20% is conjugated) with its high sensitivity of 97%–100% in refuting BA. Rapid extraction of tracer by the liver and no visible tracer in the small bowl after 24 h is indicative of BA. Laparotomy with antegrade cholangiography is then performed giving the final diagnosis when the remains of the obliterated biliary tree are revealed in the case of BA. We present a case demonstrating some of the challenges of interpreting the 99mTc-Mebrofenin hepatobiliary scintigraphy in an infant with BASM and stress the importance that the 99mTc-Mebrofenin hepatobiliary scintigraphy is part of a spectrum of imaging modalities in diagnosing BA.
Self-Aligned Metal Electrodes in Fully Roll-to-Roll Processed Organic Transistors
Authors: Vilkman Marja , Ruotsalainen Teemu , Solehmainen Kimmo , Jansson Elina , Hiitola-Keinänen Johanna
Published: January 2016

We demonstrate the production of organic bottom gate transistors with self-aligned electrodes, using only continuous roll-to-roll (R2R) techniques. The self-alignment allows accurate <5 µm layer-to-layer registration, which is usually a challenge in high-speed R2R environments as the standard registration methods are limited to the millimeter range—or, at best, to tens of µm if online cameras and automatic web control are utilized. The improved registration enables minimizing the overlap between the source/drain electrodes and the gate electrode, which is essential for minimizing the parasitic capacitance. The complete process is a combination of several techniques, including evaporation, reverse gravure, flexography, lift-off, UV exposure and development methods—all transferred to a continuous R2R pilot line. Altogether, approximately 80 meters of devices consisting of thousands of transistors were manufactured in a roll-to-roll fashion. Finally, a cost analysis is presented in order to ascertain the main costs and to predict whether the process would be feasible for the industrial production of organic transistors.
Molecular Level Factors Affecting the Efficiency of Organic Chromophores for p-Type Dye Sensitized Solar Cells
Authors: Karamshuk Svitlana , Caramori Stefano , Manfredi Norberto , Salamone Matteo , Ruffo Riccardo , Carli Stefano , Bignozzi Carlo , Abbotto Alessandro
Published: January 2016

A series of mono- and di-branched donor-π-acceptor charge-separated dyes incorporating triphenylamine as a donor and either Dalton’s or benzothiadiazole group as strong acceptors was synthesized and its fundamental properties relevant to the sensitization of nanocrystalline NiO investigated. The dyes exhibited an intense visible absorption band with a strong charge transfer character favorable to NiO sensitization, shifting the electron density from the donor to the acceptor branches. Nevertheless, the computed exciton binding energy is circa twice that of a common literature standard (P1), suggesting a more difficult charge separation. When tested in p-type dye-sensitized solar cells the dyes successfully sensitized NiO electrodes, with photocurrent densities about half than that of the reference compound. Being recombination kinetics comparable, the larger photocurrent generated by P1 agrees with the superior charge separation capability originating by its smaller exciton binding energy.
Black Layers of Decay and Color Patterns on Heritage Limestone as Markers of Environmental Change
Authors: Perez-Monserrat Elena , Varas-Muriel Maria , Alvarez De Buergo Monica , Fort Rafael
Published: January 2016

Air pollution induces the development of black crusts on the surface of built heritage materials. Black layers on the limestone used on an emblematic Madrilenian building dating from the early twentieth century, mainly built up in the 20 years lapsing between two façade cleaning operations, was studied with POM and SEM-EDS. Particulate matter deposited on surfaces in the same period was analyzed with XRD and IC. Climate change in the environs was also studied and façade coloring patterns were compared. Since black crust and settled dust composition, as well as façade soling intensity, were found to be closely related to the surrounding environment, both are proposed as environment and climate change markers. These are considerations, moreover, that must be addressed when designing conservation strategies. Domestic heating systems and vehicle traffic were identified as the two main sources of pollution throughout the period studied in the target area, where the temperature steadily rose and relative humidity declined. The progressive replacement of coal with gas oil in domestic heating boilers and the proliferation of vehicles with diesel engines have mostly determined the evolution of the pollutants emitted. The color of façade soiling, in turn, has been primarily conditioned by the typology of the particles deposited on the limestone surface, declining humidity and the passage of time.
Identification of Predictors for Weight Reduction in Children and Adolescents with Overweight and Obesity (IDA-Insel Survey)
Authors: Schiel Ralf , Kaps Alexander , Stein Günter , Steveling Antje
Published: January 2016

Introduction: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods of prevention and therapy for overweight and obesity have remained elusive. It was the aim of the present trial to identify parameters and determinants to guarantee long-term weight reduction. Patients and methods: In total 143/159 children and adolescents (90%) with overweight and obesity completed the prospective, multicenter trial (age 13.9 ± 2.4 years, BMI 31.2 ± 5.4 kg/m2, BMI-SDS 2.51 ± 0.57). During a six-week rehabilitation patients participated in a structured treatment and teaching program (STTP). Following the inpatient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, and standardized questionnaires to assess socio-demographic, socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress-management, social support, and actual body shape). Results: 66% of the children and adolescents showed non-normal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. Mean thickness of carotid intima-media was 0.53 ± 0.09 mm (range, 0.40–0.80); 15% of the patients showed a normal range (<0.45 mm), 40% slightly elevated (0.45–0.50 mm) and 45% an elevated (>0.50 mm) thickness. After an inpatient treatment lasting 40.4 ± 4.1 (range, 28–49) days, children and adolescents reached a mean weight reduction of 5.52 ± 3.94 (0.4–13.3) kg (p < 0.01) accompanied by a reduction of body fat mass. Performing multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square = 0.53): Well-being (β = −0.543), resilience (β = 0.434) and intrafamilial conflicts (β = 0.315). Conclusion: The different parameters (i.e., resilience, intrafamilial conflicts, structured daily schedule) have demonstrated their utility and strategies should be developed allowing an adaption of these into the STTPs and the integration of intervention into the therapeutic setting.
Housing Stakeholder Preferences for the “Soft” Features of Sustainable and Healthy Housing Design in the UK
Authors: Prochorskaite Agne , Couch Chris , Malys Naglis , Maliene Vida
Published: January 2016

It is widely recognised that the quantity and sustainability of new homes in the UK need to increase. However, it is important that sustainable housing is regarded holistically, and not merely in environmental terms, and incorporates elements that enhance the quality of life, health and well-being of its users. This paper focuses on the “soft” features of sustainable housing, that is, the non-technological components of sustainable housing and neighbourhood design that can impact occupants’ health and well-being. Aims of the study are to ascertain the relative level of importance that key housing stakeholders attach to these features and to investigate whether the opinions of housing users and housing providers are aligned with regards to their importance. An online survey was carried out to gauge the level of importance that the key stakeholders, such as housing users, local authorities, housing associations, and developers (n = 235), attach to these features. Results revealed that while suitable indoor space was the feature regarded as most important by all stakeholders, there were also a number of disparities in opinion between housing users and housing providers (and among the different types of providers). This implies a scope for initiatives to achieve a better alignment between housing users and providers.
Tissue-Mimicking Geometrical Constraints Stimulate Tissue-Like Constitution and Activity of Mouse Neonatal and Human-Induced Pluripotent Stem Cell-Derived Cardiac Myocytes
Authors: Pilarczyk Götz , Raulf Alexandra , Gunkel Manuel , Fleischmann Bernd , Lemor Robert , Hausmann Michael
Published: January 2016

The present work addresses the question of to what extent a geometrical support acts as a physiological determining template in the setup of artificial cardiac tissue. Surface patterns with alternating concave to convex transitions of cell size dimensions were used to organize and orientate human-induced pluripotent stem cell (hIPSC)-derived cardiac myocytes and mouse neonatal cardiac myocytes. The shape of the cells, as well as the organization of the contractile apparatus recapitulates the anisotropic line pattern geometry being derived from tissue geometry motives. The intracellular organization of the contractile apparatus and the cell coupling via gap junctions of cell assemblies growing in a random or organized pattern were examined. Cell spatial and temporal coordinated excitation and contraction has been compared on plain and patterned substrates. While the α-actinin cytoskeletal organization is comparable to terminally-developed native ventricular tissue, connexin-43 expression does not recapitulate gap junction distribution of heart muscle tissue. However, coordinated contractions could be observed. The results of tissue-like cell ensemble organization open new insights into geometry-dependent cell organization, the cultivation of artificial heart tissue from stem cells and the anisotropy-dependent activity of therapeutic compounds.
Osseointegration of Titanium Implants in Onlay of Cerament™, a New Ceramic Bone Substitute
Authors: Truedsson Anna , Wang Jian-Sheng , Lindberg Pia , Warfvinge Gunnar
Published: January 2016

The purpose was to investigate whether a new biphasic and injectable ceramic bone substitute Cerament™ that rapidly remodels to bone, may contribute to the retention of titanium implant screws during the healing period, and to analyze the pattern of bone formation around titanium implants.Titanium screws were implanted in rat tibiae and embedded with or without Cerament™ on the cortical surface. Torsional resistance was measured after 1 day, and after 6 and 12 weeks. Implant areas without bone substitute were analyzed histologically for comparison. The torsional resistance increased over time as the screws were osseointegrated. There was no difference in resistance between screws embedded in the bone substitute and control screws. The bone apposition was more pronounced on the proximal side of the screw than on the distal side. Cerament™ is capable of conducting bone growth from a cortical bone surface. The newly formed bone in this application does not significantly add to the osseointegrative strength of the implant screw, as measured by torque resistance, during the first 12 weeks.
Improved Electrochemical Detection of Zinc Ions Using Electrode Modified with Electrochemically Reduced Graphene Oxide
Authors: Kudr Jiri , Richtera Lukas , Nejdl Lukas , Xhaxhiu Kledi , Vitek Petr , Rutkay-Nedecky Branislav , Hynek David , Kopel Pavel , Adam Vojtech , Kizek Rene
Published: January 2016

Increasing urbanization and industrialization lead to the release of metals into the biosphere, which has become a serious issue for public health. In this paper, the direct electrochemical reduction of zinc ions is studied using electrochemically reduced graphene oxide (ERGO) modified glassy carbon electrode (GCE). The graphene oxide (GO) was fabricated using modified Hummers method and was electrochemically reduced on the surface of GCE by performing cyclic voltammograms from 0 to −1.5 V. The modification was optimized and properties of electrodes were determined using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). The determination of Zn(II) was performed using differential pulse voltammetry technique, platinum wire as a counter electrode, and Ag/AgCl/3 M KCl reference electrode. Compared to the bare GCE the modified GCE/ERGO shows three times better electrocatalytic activity towards zinc ions, with an increase of reduction current along with a negative shift of reduction potential. Using GCE/ERGO detection limit 5 ng·mL−1 was obtained.
Buckling Behavior of Substrate Supported Graphene Sheets
Authors: Yang Kuijian , Chen Yuli , Pan Fei , Wang Shengtao , Ma Yong , Liu Qijun
Published: January 2016

The buckling of graphene sheets on substrates can significantly degrade their performance in materials and devices. Therefore, a systematic investigation on the buckling behavior of monolayer graphene sheet/substrate systems is carried out in this paper by both molecular mechanics simulations and theoretical analysis. From 70 simulation cases of simple-supported graphene sheets with different sizes under uniaxial compression, two different buckling modes are investigated and revealed to be dominated by the graphene size. Especially, for graphene sheets with length larger than 3 nm and width larger than 1.1 nm, the buckling mode depends only on the length/width ratio. Besides, it is revealed that the existence of graphene substrate can increase the critical buckling stress and strain to 4.39 N/m and 1.58%, respectively, which are about 10 times those for free-standing graphene sheets. Moreover, for graphene sheets with common size (longer than 20 nm), both theoretical and simulation results show that the critical buckling stress and strain are dominated only by the adhesive interactions with substrate and independent of the graphene size. Results in this work provide valuable insight and guidelines for the design and application of graphene-derived materials and nano-electromechanical systems.
The Establishment of Surface Roughness as Failure Criterion of Al–Li Alloy Stretch-Forming Process
Authors: Feng Jing-Wen , Zhan Li-Hua , Yang Ying-Ge
Published: January 2016

Taking Al–Li–S4–T8 Al–Li alloy as the study object, based on the stretching and deforming characteristics of sheet metals, this paper proposes a new approach of critical orange peel state characterizations on the basis of the precise measurement of stretch-forming surface roughness and establishes the critical criterion for the occurrence of orange peel surface defects in the stretch-forming process of Al–Li alloy sheet metals. Stretching experiments of different strain paths are conducted on the specimens with different notches so as to establish the Al–Li–S4–T8 Al–Li alloy, forming limit diagram and forming limit curve equation, with the surface roughness of characteristic critical orange peel structure as the stretch-forming failure criterion.
Natural Products for the Prevention and Treatment of Hangover and Alcohol Use Disorder
Authors: Wang Fang , Li Ya , Zhang Yu-Jie , Zhou Yue , Li Sha , Li Hua-Bin
Published: January 2016

Alcoholic beverages such as beer, wine and spirits are widely consumed around the world. However, alcohol and its metabolite acetaldehyde are toxic and harmful to human beings. Chronic alcohol use disorder or occasional binge drinking can cause a wide range of health problems, such as hangover, liver damage and cancer. Some natural products such as traditional herbs, fruits, and vegetables might be potential dietary supplements or medicinal products for the prevention and treatment of the problems caused by excessive alcohol consumption. The aim of this review is to provide an overview of effective natural products for the prevention and treatment of hangover and alcohol use disorder, and special emphasis is paid to the possible functional component(s) and related mechanism(s) of action.
Repair of the Orbital Wall Fractures in Rabbit Animal Model Using Nanostructured Hydroxyapatite-Based Implant
Authors: Gradinaru Sinziana , Popescu Laura , Piticescu Roxana , Zurac Sabina , Ciuluvica Radu , Burlacu Alexandrina , Tutuianu Raluca , Valsan Sorina-Nicoleta , Motoc Adrian , Voinea Liliana
Published: January 2016

Cellular uptake and cytotoxicity of nanostructured hydroxyapatite (nanoHAp) are dependent on its physical parameters. Therefore, an understanding of both surface chemistry and morphology of nanoHAp is needed in order to be able to anticipate its in vivo behavior. The aim of this paper is to characterize an engineered nanoHAp in terms of physico-chemical properties, biocompatibility, and its capability to reconstitute the orbital wall fractures in rabbits. NanoHAp was synthesized using a high pressure hydrothermal method and characterized by physico-chemical, structural, morphological, and optical techniques. X-ray diffraction revealed HAp crystallites of 21 nm, while Scanning Electron Microscopy (SEM) images showed spherical shapes of HAp powder. Mean particle size of HAp measured by DLS technique was 146.3 nm. Biocompatibility was estimated by the effect of HAp powder on the adhesion and proliferation of mesenchymal stem cells (MSC) in culture. The results showed that cell proliferation on powder-coated slides was between 73.4% and 98.3% of control cells (cells grown in normal culture conditions). Computed tomography analysis of the preformed nanoHAp implanted in orbital wall fractures, performed at one and two months postoperative, demonstrated the integration of the implants in the bones. In conclusion, our engineered nanoHAp is stable, biocompatible, and may be safely considered for reconstruction of orbital wall fractures.