bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Ranolazine on Noninvasive Coronary Flow Reserve in Patients with Myocardial Ischemia But without Obstructive Coronary Artery Disease
Authors: Tagliamonte Ercole , Rigo Fausto , Cirillo Teresa , Astarita Costantino , Quaranta Gaetano , Marinelli Umberto , Caruso Archimede , Romano Carlo , Capuano Nicola
Published: July 2014

Introduction

Ranolazine reduces the Na‐dependent calcium overload via inhibition of the late sodium current, improving diastolic tone and oxygen handling during myocardial ischemia. In patients with angina, evidence of myocardial ischemia, but no obstructive coronary artery disease (CAD), abnormal coronary autoregulation plays a key role. Transthoracic Doppler–derived coronary flow reserve (CFR) is an index of coronary arterial reactivity and decreases in both microvascular dysfunction and coronary artery stenosis. The aim of this study was to assess the effect of ranolazine on CFR in this group of patient.

Methods

Fifty‐eight (39M, 19F) patients with angina and evidence of myocardial ischemia, but no obstructive CAD, were enrolled in a double‐blind, placebo‐controlled trial. Participants were assigned to ranolazine (29) or placebo (29) for 8 weeks (up to 500 mg twice a day). CFR was determined as the ratio of hyperemic, induced by intravenous dypiridamole administration, to baseline diastolic coronary flow velocity. CFR was assessed before and after 8‐week therapy.

Results

CFR was successfully performed in all patients. There were no significant differences in baseline characteristics and CFR between ranolazine and placebo group. After 8 weeks CFR significantly increased in ranolazine group (2.54 ± 0.44 vs. 1.91 ± 0.31; P = 0.005) but not in placebo group (1.99 ± 0.32 vs. 1.94 ± 0.29; P = ns). No patient dropped out during 8 weeks therapy. Side effects were similar in both groups.

Conclusions

Ranolazine is able to improve CFR in these patients. This is probably due to improvement in abnormal coronary autoregulation, both reducing baseline diastolic coronary flow velocity and increasing hyperemic diastolic coronary flow velocity.
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae
Authors: de Laat M. A. , Clement C. K. , Sillence M. N. , McGowan C. M. , Pollitt C. C. , Lacombe V. A.
Published: July 2014

Reasons for performing study

An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance. Laminitis, failure of the weightbearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs), responsible for glucose uptake, is central to the dysregulation of glucose metabolism and may play a role in the pathophysiology of laminitis.

Objectives

We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin‐sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during marked and moderate hyperinsulinaemia.

Study design

Randomised, controlled study.

Methods

Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged euglycaemic–hyperinsulinaemic clamp or a prolonged glucose infusion, and results were compared with those of electrolyte‐treated control animals. Protein expression of GLUTs was examined with immunoblotting.

Results

Lamellar tissue contained more GLUT1 protein than skeletal muscle (P = 0.002) and less GLUT4 than the heart (P = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the prolonged euglycaemic–hyperinsulinaemic clamp), GLUT1 protein expression was decreased in skeletal muscle (P = 0.029) but unchanged in the lamellae, while novel GLUTs (8 and 12) were increased in the lamellae (P = 0.03) but not in skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the prolonged glucose infusion) did not cause differential GLUT protein expression in the lamellae compared with control horses.

Conclusions

The results suggest that lamellar tissue functions independently of insulin and that insulin resistance may not be an essential component of the aetiology of laminitis. Marked differences in GLUT expression exist between insulin‐sensitive and insulin‐independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation.
Sestrin2 promotes Unc‐51‐like kinase 1 mediated phosphorylation of p62/sequestosome‐1
Authors: Ro Seung‐Hyun , Semple Ian A. , Park Haewon , Park Haeli , Park Hwan‐Woo , Kim Myungjin , Kim Jeong Sig , Lee Jun Hee
Published: July 2014

Autophagy is a homeostatic process that is important for degrading protein aggregates, nutrient deposits, dysfunctional organelles and several signaling molecules. p62/sequestosome‐1 is a protein that binds to several autophagy substrates, such as ubiquitinated proteins, damaged mitochondria and signaling molecules such as an Nrf2 inhibitor Keap1, promoting their autophagic degradation. Sestrin2, a stress‐inducible protein, has recently been shown to bind to p62 and promote autophagic degradation of such p62 targets. Because Sestrin2 is a metabolic regulator that suppresses diverse age‐ and obesity‐associated pathologies, the autophagy‐controlling function of Sestrin2 may be important for its other physiological functions. However, the molecular mechanism of how Sestrin2 can promote clearance of p62‐associated proteins has been unclear. Here we show that Sestrin2 physically associates with Unc‐51‐like protein kinase 1 (ULK1) and p62 to form a complex in which both Sestrin2 and p62 become phosphorylated by ULK1 at multiple sites. Ser403 of p62, whose phosphorylation is known to promote autophagic degradation of p62 and its targets, is among the sites phosphorylated by ULK1. ULK1‐mediated p62 phosphorylation was facilitated by Sestrin2 in cells as well as in in vitro kinase assays. Consistent with this finding, oligomycin‐induced energy deprivation, which strongly activates ULK1, provoked a robust Ser403 phosphorylation of p62 in wild‐type mouse embryonic fibroblasts. However, in ULK1/2‐ and Sestrin2‐deficient mouse embryonic fibroblasts, oligomycin‐induced p62 phosphorylation was dramatically attenuated, suggesting that endogenous Sestrin2‐ULK1/2 mainly mediates p62 phosphorylation in response to energetic stress. Taken together, this study identifies ULK1 as a new p62 Ser403 kinase and establishes Sestrin2 as a promoter of ULK1‐mediated p62 phosphorylation.

Structured digital abstract

ULK1 physically interacts with Sestrin2 by pull down (View interaction)

p62 physically interacts with Sestrin2 by anti tag coimmunoprecipitation (1, 2)

p62 physically interacts with ULK1 by anti tag coimmunoprecipitation (View interaction)

Sestrin2 physically interacts with p62 and ULK1 by anti bait coip (View interaction)

Sestrin2 physically interacts with ULK1, FIP200 and Atg13 by anti tag coimmunoprecipitation (View interaction)

p62 physically interacts with ULK1 and Sestrin2 by anti tag coimmunoprecipitation (View interaction)

ULK1 physically interacts with Sestrin2 by anti tag coimmunoprecipitation (1, 2, 3)

p62 physically interacts with Sestrin2 by pull down (View interaction)

p62 physically interacts with Sestrin2 by anti tag coimmunoprecipitation (View interaction)
Dynamics of genomic 5‐hydroxymethylcytosine during mouse oocyte growth
Authors: Sakashita Akihiko , Kobayashi Hisato , Wakai Takuya , Sotomaru Yusuke , Hata Kenichiro , Kono Tomohiro
Published: July 2014

Recent studies of the demethylation process in murine zygotes have shown that 5‐methylcytosine (5mC) is first converted into 5‐hydroxymethylcytosine (5hmC) or further‐oxidized cytosines in the paternal genome by the maternal ten–eleven translocation 3 (TET3) enzyme. This process is crucial for normal embryogenesis, and our aim was to elucidate the effect of Tet3 on the maternal genome during female germ‐line development. Immunofluorescence analysis showed that 5hmC was clearly present in fully grown oocytes but not in nongrowing and early growth‐stage oocytes. The 5hmC in the maternal genome was clearly detectable in DNA methyltransferase 3‐like enzyme (Dnmt3L)‐null oocytes and their fertilized zygotes, although Dnmt3L is essential for DNA methylation in oocytes. An analysis using an enzyme digestion‐based method showed that 5hmC was present in LTR retrotransposons from the late growth period of oocytes. Quantitative RT‐PCR analysis showed that Tet3 expression was enhanced during oocyte growth and exhibited an approximately 40‐fold increase between nongrowing and fully grown oocytes. Our results show that 5hmC is generated since the oocyte growth stage, accompanied by up‐regulation of Tet3; 5hmC is located mainly in LTR retrotransposons, indicating that 5hmC generated in growth‐stage oocytes is responsible for genomewide demethylation after fertilization.
Radioisotope Cisternography in Spontaneous CSF Leaks: Interpretations and Misinterpretations
Authors: Mokri Bahram
Published: July 2014

A broadening of the clinical and imaging features of the spontaneous cerebrospinal fluid (CSF) leaks is now well recognized, far beyond what was thought only two decades ago. This has resulted in increasing number of patients with atypical and unusual features who, not unexpectedly, are directed to headache specialists and tertiary referral centers. In many cases, obviously the fundamental question of presence or absence of CSF leak will need to be addressed prior to proceeding with further and often more involved, more invasive, and more costly diagnostic and therapeutic considerations. Radioisotope cisternography often proves to be very helpful in these situations by demonstrating reliable, although indirect, evidences of CSF leak while it is less helpful in directly identifying the exact site of the CSF leakage. In this overview article, the expectations from and the limitations of this diagnostic method are described along with some personal observations in the past 25 years.
IgE/antigen‐mediated enhancement of IgE production is a mechanism underlying the exacerbation of airway inflammation and remodelling in mice
Authors: Mizutani Nobuaki , Nabe Takeshi , Yoshino Shin
Published: July 2014

IgE is known to enhance some antibody responses to specific antigens, but whether this contributes to allergic asthma remains unclear. We have previously found that repeated antigen challenges in mice sensitized with antigen‐specific IgE monoclonal antibody (mAb) exacerbated airway inflammation and remodelling accompanied by increased levels of endogenous antigen‐specific IgE and IgG1. Here, we investigated whether IgE/antigen‐mediated enhancement of endogenous IgE production contributes to the exacerbation of airway inflammation and remodelling. BALB/c mice passively sensitized with ovalbumin (OVA) ‐specific IgE mAb were challenged with OVA intratracheally seven times; anti‐IgE mAb was intraperitoneally administered 1 day before the fourth challenge. Treatment with anti‐IgE mAb inhibited the increased level of endogenous OVA‐specific IgE in serum, but not OVA‐specific IgG1, and a biphasic increase in airway resistance at the fourth challenge. Furthermore, a biphasic increase in airway resistance, airway hyper‐responsiveness to methacholine, OVA‐specific IgE and IgG1 production, and infiltrations by neutrophils and eosinophils in the lungs at the seventh challenge were suppressed by treatment; airway remodelling, such as goblet cell hyperplasia and sub‐epithelial fibrosis, was also reduced. In addition, the production of interleukin‐17A, interleukin‐33 and CXCL1 in the lungs related to these IgE‐mediated responses was decreased by treatment. Collectively, we found that the mechanism leading to the exacerbation of allergic asthma is closely related to IgE/antigen‐mediated enhancement of IgE production, suggesting that this may create a vicious circle leading to the chronic status in asthmatic patients having levels of antigen‐specific IgE ready to form complexes with antigen.
Self‐Generating High‐Temperature Oxidation‐Resistant Glass‐Ceramic Coatings for C–C Composites Using UHTCs
Authors: Walker Luke S. , Corral Erica L.
Published: July 2014

Carbon–carbon (C–C) composites are ideal for use as aerospace vehicle structural materials; however, they lack high‐temperature oxidation resistance requiring environmental barrier coatings for application. Ultra high‐temperature ceramics (UHTCs) form oxides that inhibit oxygen diffusion at high temperature are candidate thermal protection system materials at temperatures >1600°C. Oxidation protection for C–C composites can be achieved by duplicating the self‐generating oxide chemistry of bulk UHTCs formed by a “composite effect” upon oxidation of ZrB2–SiC composite fillers. Dynamic Nonequilibrium Thermogravimetric Analysis (DNE‐TGA) is used to evaluate oxidation in situ mass changes, isothermally at 1600°C. Pure SiC‐based fillers are ineffective at protecting C–C from oxidation, whereas ZrB2–SiC filled C–C composites retain up to 90% initial mass. B2O3 in SiO2 scale reduces initial viscosity of self‐generating coating, allowing oxide layer to spread across C–C surface, forming a protective oxide layer. Formation of a ZrO2–SiO2 glass‐ceramic coating on C–C composite is believed to be responsible for enhanced oxidation protection. The glass‐ceramic coating compares to bulk monolithic ZrB2–SiC ceramic oxide scale formed during DNE‐TGA where a comparable glass‐ceramic chemistry and surface layer forms, limiting oxygen diffusion.
Phase Evolution and Microwave Dielectric Properties of (Bi1−xFex)VO4 (x ≤ 0.40) Ceramics
Authors: Zhou Di , Bin He , Guo Jing , Pang Li‐Xia , Qi Ze‐Ming , Shao Tao , Wang Qiu‐Ping , Yue Zhen‐Xing , Yao Xi
Published: July 2014

In the present work, (Bi1−xFex)VO4 (x ≤ 0.40) ceramics were prepared using the solid‐state reaction method. All the ceramics could be well densified at sintering temperatures below 800°C. X‐ray diffraction (XRD) results showed that monoclinic solid solution was formed within x ≤ 0.08. When x ≥ 0.10, both monoclinic scheelite and FeVO4 phases were detected. The (Bi0.92Fe0.08)VO4 sample sintered at 720°C for 2 h had a permittivity of 57.5 and a Qf value of 15 000 GHz. The IR reflectivity was fitted to study the intrinsic dielectric properties, showing that the majority of the dielectric contribution for this system at microwave region was attributed to the absorptions of structural phonon oscillation in infrared region.
Aramid‐Al2O3 Nano‐Needle Scaffold as Pore Former for Optimal Mechanical and Permeable Properties of Ceramic Matrix
Authors: Chen Xinwei , Tan Yirong , Hong Liang
Published: July 2014

An adroit design of pore‐forming system is required to achieve a porous ceramic matrix with high permeability and adequate mechanical strength. This work developed a hybrid pore‐forming regime constructed in the green body (dense powder packing) of yttria stabilized zirconia (YSZ) through the condensation polymerization to form poly(p‐phenylene terephthalamide) (PPTA) chains and their in‐situ grafting with alumina nano‐needles with pendant–NH2 groups (Sasol®). A PPTA‐Sasol pore‐former scaffold was resulted and distributed uniformly in the green body. It was then subjected to calcination treatment in Ar, through which fibers and ribbons consisting of carbon and alumina needles were derived and penetrated throughout the partially sintered YSZ matrix as the final form of pore‐former. This work further investigates the impacts of the PPTA‐Sasol pore‐former, including the morphologies and loadings, on the Darcy's permeability, pore‐size distribution and flexural strength, displayed by the porous YSZ matrices ultimately attained. It is showed that the vital role of Sasol needles in the present pore‐forming regime lies in significant enhancement on mechanical strength accompanying an improved permeability contrary to the best result achieved without them.
Polarization Response and Thermally Stimulated Depolarization Current of BaTiO3‐based Y5V Ceramic Multilayer Capacitors
Authors: Zhang Xiaohua , Yue Zhenxing , Peng Bin , Xie Zhenkun , Yuan Lixin , Zhang Jie , Li Longtu
Published: July 2014

Polarization response and thermally stimulated depolarization current (TSDC) of BaTiO3‐based ceramic multilayer capacitors with Y5V specification were studied. The temperature dependence of dielectric behavior shows that as the dc electric field increases, the polarization response in the whole measurement range (from −125°C to +350°C) is suppressed. As the temperature rises to about 250°C, dielectric loss significantly increases and has a dependence on dc electric field, due to the leakage behavior at high temperature. According to the hysteresis loops, the calculated electrostatic energy density and energy efficiency are also closely related to polarization‐electric field. Utilizing a fixed measuring polarization condition, two TSDC relaxation peaks are observed and both are associated with oxygen vacancies. It is demonstrated that the weak peak originates from the in‐grain migration of oxygen vacancies and the strong peak with high relaxation temperature is caused by the across grain‐boundary oxygen vacancies. The activation energy estimated for the relaxation of oxygen vacancies across grain boundaries is about 0.78 eV. The main contribution for the leakage behavior is from the across grain‐boundary relaxation of oxygen vacancies. With increasing of temperature and electric field stress, the extrinsic oxygen vacancy defects show more fluent migration, which eventually leads to the resistance degradation and breakdown.
Silicon Carbonitride Hollow Nanospheres from a Block‐Copolymer Precursor
Authors: Yang Xueping , Chen Yaohan , Cao Yejie , An Linan
Published: July 2014

Nonoxide SiCN hollow nanospheres were prepared from a block‐copolymer comprising of a precursor block and a sacrificial block. The copolymer was first synthesized and then self‐assembled into core‐shell structured micelles with the sacrificial block forming the core and the precursor block forming the shell. The micelles were subsequently pyrolyzed at high temperatures to transform the shell into ceramics and to completely decompose the core to form a hole. The technique is probably applicable to other material systems.
In Situ Gamma Radiation‐Induced Attenuation in Sapphire Optical Fibers Heated to 1000°C
Authors: Petrie Christian M. , Wilson Brandon , Blue Thomas E.
Published: July 2014

The purpose of this work was to determine the suitability of using instrumentation utilizing sapphire optical fibers in a high‐temperature gamma radiation environment. In this work, the broadband (500–2200 nm, or 0.56–2.48 eV) optical attenuation of commercially available sapphire optical fibers was monitored in situ during continuous gamma irradiation from room temperature up to 1000°C. The gamma dose rate of the irradiation facility was measured to be 370 rad/h (dose in sapphire). Results show rapid growth of an absorption band centered below 500 nm (the minimum detectable wavelength in this work) and extending as far as ~1000 nm that reached a dynamic equilibrium after approximately 4 h of irradiation at room temperature. Increasing temperature generally reduced the added attenuation, although the added attenuation came to a nonzero equilibrium at temperatures of 1000°C and below. No peaks in the added attenuation were observed above 1000 nm, and the added attenuation at 1300 and 1550 nm remained less than 0.7 dB throughout the entire experiment. Fitting the attenuation spectra to Gaussian functions at each temperature revealed a large absorption band near 3 eV that monotonically decreased both in magnitude and width with increasing temperature. A second smaller band near 1.73 eV monotonically increased in both magnitude and width with increasing temperature, suggesting that some interconversion between defects may be occurring at higher temperatures.
Mid‐term outcome of endoscopic sphincterotomy combined with large balloon dilation
Authors: Itokawa Fumihide , Itoi Takao , Sofuni Atsushi , Kurihara Toshio , Tsuchiya Takayoshi , Ishii Kentaro , Tsuji Shujiro , Ikeuchi Nobuhito , Umeda Junko , Tanaka Reina , Tonozuka Ryosuke , Honjyo Mitsuyoshi , Moriyasu Fuminori , Kasuya Kazuhiko , Tsuchida Akihiko
Published: July 2014

Background and Aim

Endoscopic sphincterotomy (ES) combined with large balloon dilation (ESLBD) can be useful for extracting large and multiple bile duct stones. Although there are many studies on the feasibility and short‐term outcome, there are few reports about mid‐ to long‐term outcome after ESLBD. The aim of our study is to prospectively evaluate the mid‐term outcome of ESLBD.

Methods

One hundred eighty‐three patients who underwent ESLBD between November 2006 and May 2012 were included. The patients were followed up periodically after the procedure until April 2013. Papillary dilation was performed at the time of initial ES or prior ES. Early and late adverse events and stone recurrence were evaluated in this study.

Results

The patients' mean age was 76.6 ± 10.7 years. Surgically altered anatomy was present: Billroth I gastrectomy (2), Billroth II gastrectomy (13), and gastrectomy with Roux‐en Y reconstruction (18). Seventy‐eight (42.6%) patients had periampullary diverticulum. Prior ES had been performed in 40 (21.9%) patients. The mean follow‐up period was 43.5 ± 19.7 months (range 11–78). Eight (4.4%) patients had stone recurrence. There was rare stone recurrence after initial ESLBD treatment and native gastrointestinal anatomy. Univariate and multivariate analyses showed that prior ES and previous history of stone recurrence were predictive of stone recurrence (P < 0.001).

Conclusion

At mid‐term outcome, ESLBD is associated with a low rate of recurrent bile duct stones, although long‐term follow up is needed.
Interspecies comparison of stellate cell‐containing macula flavae and vitaminAstorage in vocal fold mucosa
Authors: Toya Yutaka , Riabroy Napaporn , Davis Christopher R. , Kishimoto Yo , Tanumihardjo Sherry A. , Bless Diane M. , Welham Nathan V.
Published: July 2014

The macula flavae (MF), populated by vitaminA‐storing stellate cells (SCs), are believed to play a fundamental role in development, maintenance and repair of the vocal fold (VF) mucosa; however, to date, they have mostly been examined in observational human cadaver studies. Here, we conducted an interspecies comparison of MF and SC phenotype, as well as vitaminAquantification and localization, in human, pig, dog, rabbit and rat VF mucosae. MF containing vitaminA‐positive SCs were only identified in human and rat specimens. Pig, dog and rabbitVFmucosae contained no discernable MF, but rather exhibited preferential vitaminAlocalization to mucous (pig), serous (dog) or mixed (rabbit) glands. This glandular vitaminAstorage corresponded to exceedingly high concentrations of retinol in pig and dog mucosae, and retinyl ester in dog mucosa. These findings have significant implications for the presumed role of the MF and SCs in VF biology, the nature of vitaminAstorage within the VF mucosa, and the selection of an appropriate animal model for future experimental studies.
Change in affective well‐being on change in perceived job characteristics: The mediating role of hope
Authors: Reis Dorota , Hoppe Annekatrin
Published: July 2014

Research on occupational health has consistently shown that job characteristics and personal resources predict employee well‐being. Building on the associative network theory, we claim that – vice versa – well‐being is likely to affect the perception of job characteristics and personal resources. The aim of this study was to expand the literature on job characteristics, personal resources, and employee well‐being (1) by taking a reversed causation perspective and (2) by investigating the dynamic nature of these relations in a latent change model. More specifically, we hypothesized that baseline levels and change in affective well‐being are related to change in emotional demands and autonomy, two core job characteristics for our sample of psychotherapists. In addition, we explored the mediating role of hope as a personal resource in this process. A total of 326 psychotherapists participated in a two‐wave online survey with a 5‐month time lag. Results revealed that baseline levels of and change in affective well‐being were associated with change in emotional demands. Furthermore, change in hope mediated the effect of change in affective well‐being on change in autonomy. In conclusion, the results show that affective well‐being can mark a starting point for building personal resources and changing employees' perceptions of their job characteristics.

Practitioner points

Employees with high levels of affective well‐being perceive fewer emotional demands at work over time.

An increase in affective well‐being over a period of 5 months further decreases their experience of emotional demands at work.

Employees whose affective well‐being increases over time build hope at work. This, in turn, goes along with a more positive perception of their autonomy at work.
Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to Radical Prostatectomies: Results from a Cross-Sectional Questionnaire-Based Study
Authors: Frey Anders , Sønksen Jens , Jakobsen Henrik , Fode Mikkel
Published: July 2014

Introduction

Altered perception of orgasm, orgasm-associated pain, penile sensory changes, urinary incontinence (UI) during sexual activity, penile shortening (PS), and penile deformity following radical prostatectomy (RP) have received increasing attention from researchers.

Aim

The aim of this study is to describe the prevalence and predictors of the above-mentioned side effects.

Methods

This was a cross-sectional questionnaire-based study among men who had undergone RP between 3 and 36 months prior to study inclusion. Predicting factors were identified through logistic regression analyses.

Main Outcome Measures

The primary outcome measures were prevalence rates of the above-mentioned side effects.

Results

Overall, 316 questionnaires were available for analyses. Of the sexually active patients (n = 256), 12 (5%) reported anorgasmia, whereas 153 (60%) reported decreased orgasm intensity. Delayed orgasms were reported by 146 (57%). Twenty-three patients (10%) had experienced pain during orgasm. UI during sexual activity were reported by 99 patients (38%). Out of the whole population, 77 patients (25%) reported sensory changes in the penis. A total of 143 patients (47%) reported a subjective loss of penile length of >1 cm. An altered curvature of the penis was reported by 30 patients (10%). Patients had increasing risk of UI during sexual activity (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.10–1.25) and orgasmic dysfunction (OR 1.09; 95% CI 1.01–1.16) with increasing International Consultation on Incontinence Questionnaire scores. Erectile dysfunction (OR 1.81; 95% CI 1.07–3.10) and a high body mass index (OR 1.10; 95% CI 1.02–1.19) increased the risk of PS after RP. Nerve-sparing (OR 0.32; 95% CI 0.16–0.95) reduced the risk of PS.

Conclusions

Orgasm-associated problems, UI during sexual activity, penile sensory changes, PS, and penile deformity are common side effects to RP. Daytime UI, erectile dysfunction, and nerve-sparing status can help identify patients at risk.
Association of PCOS and Its Clinical Signs with Sexual Function among Iranian Women Affected by PCOS
Authors: Hashemi Somayeh , Ramezani Tehrani Fahimeh , Farahmand Maryam , Bahri Khomami Mahnaz
Published: July 2014

Introduction

Polycystic ovary syndrome (PCOS) and its physiological and psychological changes influence the sexual function of women affected.

Aim

In the present study, we aimed to investigate the association of PCOS and its clinical signs with sexual function among a population of married Iranian women affected by PCOS.

Main Outcome Measure

The impact of clinical signs of PCOS on sexual function of affected women was the main outcome measure in the present study.

Methods

This cross-sectional study was carried out on 591 married women with PCOS, aged 18–45 years. Data were collected using a questionnaire including information on demographic and reproductive status and the Female Sexual Function Index. Data were analyzed using chi-square test, Mann–Whitney test, and logistic regression analysis.

Results

The participants' mean age was 30.6 years. Among associated manifestations of PCOS, infertility and hair loss have significant adverse effects on female sexual function. Logistic regression analysis showed that PCOS women with infertility have a significantly lower sexual function score compared with those who are fertile. Subgroup analysis demonstrated that compared with their fertile counterparts, PCOS women with infertility had significant sexual dysfunction in all aspects except desire and pain.

Conclusion

Among various manifestations of PCOS, infertility mainly disrupts the sexual function of affected women.
Possibility of the Production of Functional Low‐Fat Food Spread of Hull‐Less Pumpkin Seed Flour from Rheological and Textural Aspect
Authors: Nikolić Ivana , Dokić Ljubica , Krstonošić Veljko , Šereš Zita , Šoronja–Simović Dragana
Published: July 2014

A new kind of functional low‐fat spread with hull‐less pumpkin seed flour and fat replacer, in gel form, was defined in this work from a rheological and textural aspect. Observed spreads were systems with thixotropic flow behavior. All determined rheological parameters, except of yield stress, were affected by gel concentration and amount of gel. Increase in gel concentration caused increase in consistency of the spreads, their possibility to recover and contribution of elastic components in the structure of the spread. Increase in the amount of gel influenced the balancing factor and reduced influence in gel concentration. Statistically, this was confirmed as interaction of observed factors (P < 0.05). Textural parameters confirmed that more gel provided softer consistency and increased the spreadability that could be optimized by concentration of applied gel. Optimal observed properties exhibited the spreads with low concentrated gel ranging from 0.5 to 1% and with a 70% gel amount.

Practical Applications

A press cake is the by‐product of the mechanical process of oil extraction from pumpkin seeds. Hull‐less pumpkin seed cakes are chemically and nutritionally valuable because of its high quantity of crude protein, fatty acids, minerals and energy. It is a very low‐cost by‐product. The exploitation of hull‐less pumpkin seed cakes is poor, usually as animal feed. Possibilities of its application as a new low‐cost biosorbent, for enzymatic protein isolation or as flour‐like supplements are published. A number of low‐fat spreads based on nuts, seeds and fat replacers are covered by published articles or patents. Oil seed cakes are an alternative to manufacturing low‐fat spreads in terms of cost‐effectiveness as well as for increased protein content. The presented results demonstrate the possibility of producing low‐fat functional spread based on hull‐less pumpkin seed flour, and a new form of utilization of this raw material.
eGFR decrease during antiviral C therapy with first generation protease inhibitors: a clinical significance?
Authors: Loustaud‐Ratti Véronique , Rousseau Annick , Carrier Paul , Vong Chanlina , Chambaraud Tristan , Jacques Jérémie , Debette‐Gratien Marilyne , Sautereau Denis , Essig Marie
Published: July 2014

Background & Aims

Renal toxicity of first generation protease inhibitors (PIs) was not a safety signal in phase III clinical trials, but was recently reported in recent studies. It appeared important to determine the clinical significance of these findings.

Methods

We retrospectively analysed 101 HCV patients receiving triple therapy with telaprevir (n = 36) or boceprevir (n = 26) or double therapy (n = 39) with peginterferon and ribavirin and having a close monitoring of eGFR (MDRD formula) during and after treatment. EGFR decline over time was assessed by a linear mixed‐effects model (LMEM) with search for possible explanatory covariates.

Results

Patients treated with telaprevir presented a significant decrease of eGFR with the same kinetics: initial decrease at W (week) 4, nadir at W8 (mean decrease 17.0 ± 18.9 ml/min/1.73 m2) and return to baseline at W16. The W8 eGFR was correlated with the D0 eGFR (R2 = 0.49). The LMEM showed that interindividual variability in the slope of eGFR vs time between D0 and W8 was non‐significant and eGFR nadir could be predicted from eGFR obtained at D0. In multivariate analysis, eGFR intercept (i.e. baseline value) was associated with older age and male sex.

Conclusion

The eGFR significantly varied in telaprevir group only. Our model showed that eGFR nadir mainly depended on initial eGFR. As telaprevir has been shown to inhibit mostly the drug transporter OCT2 which interacts with creatinine transport, the early decrease of eGFR observed could be a benign phenomenon. However, as unpredictable true renal toxicity may occur during therapy, we recommend a thorough follow‐up of eGFR.
Increasing access to kidney transplantation in countries with limited resources: The Indian experience with Kidney Paired Donation
Authors: Kute Vivek B , Vanikar Aruna V , Shah Pankaj R , Gumber Manoj R , Patel Himanshu V , Engineer Divyesh P , Modi Pranjal R , Shah Veena R , Trivedi Hargovind L
Published: July 2014

According to the Indian chronic kidney disease registry, in 2010 only 2% of end stage kidney disease patients were managed with kidney transplantation, 37% were managed with dialysis and 61% were treated conservatively without renal replacement therapy. In countries like India, where a well‐organized deceased donor kidney transplantation program is not available, living donor kidney transplantation is the major source of organs for kidney transplantation. The most common reason to decline a donor for directed living donation is ABO incompatibility, which eliminates up to one third of the potential living donor pool. Because access to transplantation with human leukocyte antigen (HLA)‐desensitization protocols and ABO incompatible transplantation is very limited due to high costs and increased risk of infections from more intense immunosuppression, kidney paired donation (KPD) promises hope to a growing number of end stage kidney disease patients. KPD is a rapidly growing and cost‐effective living donor kidney transplantation strategy for patients who are incompatible with their healthy, willing living donor. In principle, KPD is feasible for any centre that performs living donor kidney transplantation. In transplant centres with a large living donor kidney transplantation program KPD does not require extra infrastructure, decreases waiting time, avoids transplant tourism and prevents commercial trafficking. Although KPD is still underutilized in India, it has been performed more frequently in recent times. To substantially increase donor pool and transplant rates, transplant centres should work together towards a national KPD program and frame a uniform acceptable allocation policy.
Effects of endothelial nitric oxide synthase gene on end stage renal disease progression in autosomal dominant polycystic kidney disease
Authors: Xue Cheng , Zhou Chen‐chen , Sun Li‐jun , He Liang‐liang , Xu Cheng‐gang , Dai Bing , Mei Chang‐lin
Published: July 2014

Aim

To investigate whether endothelial nitric oxide synthase (eNOS) gene associate with the progression of autosomal dominant polycystic kidney disease (ADPKD).

Methods

Databases of EMBASE, Pubmed, ISI, Ovid Database, Cochrane library and China National Knowledge Infrastructure were all searched. Associated studies about eNOS polymorphisms and ADPKD were analyzed by meta‐analysis.

Results

A total of 11 studies with Glu298Asp and 4b/a polymorphisms were included. A allele of the 4b/a polymorphism increased the risk of end stage renal disease (ESRD) in ADPKD (odds ratio (OR) = 1.85, 95% confidence interval (CI) 1.17–2.94, P = 0.009). However, GG phenotype of Glu298Asp polymorphism neither decreased the ESRD risk (OR = 0.77, 95% CI 0.55–1.08, P = 0.13) nor affected the hypertension risk (OR = 1.04, 95% CI 0.66–1.66, P = 0.86). The GG phenotype carriers had later ESRD age compared with the T allele of Glu298Asp polymorphism (WMD = 2.39; 95% CI 1.32–3.46; P < 0.0001). Significant association was also found in Caucasians (WMD = 2.41; 95% CI 1.18–3.64; P = 0.0001). Subgroup analysis by gender indicated GG genotype carriers had older age of ESRD than T allele carriers in males (WMD = 4.51; 95% CI 3.95–5.08; P = 0.00001), but not in females.

Conclusions

GG genotype of the Glu298Asp variant slowed the ESRD progression in ADPKD, while a allele carriers of the 4b/a variant increased the risk of ESRD. Variants of eNOS gene might play different roles in the ESRD progression in ADPKD.
Effects of a comprehensive cardiac rehabilitation program in patients with coronary heart disease in Korea
Authors: Kim So‐Sun , Lee Sunhee , Kim GiYon , Kang Seok‐Min , Ahn Jeong‐Ah
Published: July 2014

The purpose of this study was to develop a comprehensive cardiac rehabilitation program that considered patients' learning needs and cultural context, and to identify the impact of this program on patients with coronary heart disease in Korea. We employed a quasi‐experimental design to evaluate the effects of the developed program in 61 patients with coronary heart disease. The experimental group received education, counseling, educational materials, and telephone follow‐ups by cardiac nurses for six months. Results showed that participants of the program exhibited reduced body mass index and waist circumference as well as improved left ventricular diastolic function and cardiac disease‐related quality of life. There was no significant difference between the groups with the rate of recurring symptoms or cardiac events. This comprehensive cardiac rehabilitation program safely and effectively improved body composition, cardiac function, and quality of life in patients with coronary heart disease.
The oncogenic role of androgen receptors in promoting the growth of oral squamous cell carcinoma cells
Authors: Wu T‐F , Luo F‐J , Chang Y‐L , Huang C‐M , Chiu W‐J , Weng C‐F , Hsu Y‐K , Yuan T‐C
Published: July 2014

Objectives

The aims of this study were to examine the expression of androgen receptors (AR) in oral squamous cell carcinoma (OSCC) cells and tumors and to determine the role of AR in regulating OSCC cell growth.

Materials and Methods

Four OSCC cell lines were used for analyzing AR expression and transcriptional activity. The effects of AR knockdown on the growth and tumorigenicity of OSCC cells were examined. A series of 11 benign, 22 premalignant, and 21 malignant lesions of the oral cavity were used for analyzing AR expression.

Results

OSCC cells expressed AR proteins with differential activities. Stimulation of AR by dihydrotestosterone in OSCC cells caused an increase in cyclin D1 expression and promoted cell growth, whereas treatment with bicalutamide led to decreased cyclin D1 expression and inhibited cell growth. Knockdown of AR expression in OSCC cells resulted in decreased proliferation, increased apoptosis, and inhibited tumorigenicity. Results from immunohistochemical studies showed that AR immunoreactivity was found in 27% (3/11) of benign lesions, while 68% (15/22) of premalignant and 67% (14/21) of malignant lesions showed positive AR staining.

Conclusion

Our data suggest that OSCC cells express functional AR proteins which are critical for promoting cell growth and causing malignant disease.
Mesophyll conductance decreases in the wild type but not in an ABA‐deficient mutant (aba1) of Nicotiana plumbaginifolia under drought conditions
Authors: MIZOKAMI YUSUKE , NOGUCHI KO , KOJIMA MIKIKO , SAKAKIBARA HITOSHI , TERASHIMA ICHIRO
Published: July 2014

Under drought conditions, leaf photosynthesis is limited by the supply of CO2. Drought induces production of abscisic acid (ABA), and ABA decreases stomatal conductance (gs). Previous papers reported that the drought stress also causes the decrease in mesophyll conductance (gm). However, the relationships between ABA content and gm are unclear. We investigated the responses of gm to the leaf ABA content [(ABA)L] using an ABA‐deficient mutant, aba1, and the wild type (WT) of Nicotiana plumbaginifolia. We also measured leaf water potential (ΨL) because leaf hydraulics may be related to gm. Under drought conditions, gm decreased with the increase in (ABA)L in WT, whereas both (ABA)L and gm were unchanged by the drought treatment in aba1. Exogenously applied ABA decreased gm in both WT and aba1 in a dose‐dependent manner. ΨL in WT was decreased by the drought treatment to −0.7 MPa, whereas ΨL in aba1 was around −0.8 MPa even under the well‐watered conditions and unchanged by the drought treatment. From these results, we conclude that the increase in (ABA)L is crucial for the decrease in gm under drought conditions. We discuss possible relationships between the decrease in gm and changes in the leaf hydraulics.
Glycosyltransferase‐like protein ABI8/ELD1/KOB1 promotes Arabidopsis hypocotyl elongation through regulating cellulose biosynthesis
Authors: WANG XIN , JING YANJUN , ZHANG BAOCAI , ZHOU YIHUA , LIN RONGCHENG
Published: July 2014

Seedling de‐etiolation (photomorphogenesis) is an important light‐regulated developmental process in plants. Here, we showed that disruption of the gene encoding a glycosyltransferase‐like protein, ABA INSENSITIVE 8 (ABI8)/ELONGATION EFFECTIVE 1 (ELD1)/KOBITO1 (KOB1), caused short‐hypocotyl elongation under all light conditions examined and even in darkness. We found that the ABI8 transcript level was down‐regulated by light in a phytochrome A‐dependent manner. Furthermore, light destabilized ABI8 protein via the 26S proteasome degradation pathway. We showed that ABI8 promoted the expression of genes involved in cell elongation and cellulose synthesis. Consistently, the cellulose content was reduced in the abi8 mutants and application of 2, 6‐dichlorobenzonitrile (an inhibitor of cellulose biosynthesis) mimicked the abi8 mutant phenotype. Moreover, we found that phytochrome and cryptochrome photoreceptors negatively, whereas CONSTITUTIVE PHOTOMORPHOGENIC 1 positively, regulated cellulose synthesis. We also showed that ELONGATED HYPOCOTYL 5 directly bound to the promoters of ABI8 and several cellulose synthesis genes and repressed their expression in light conditions. Taken together, our study reveals that ABI8 functions as a negative factor in light inhibition of hypocotyl elongation through modulating cellulose biosynthesis.
Prospects of engineering thermotolerance in crops through modulation of heat stress transcription factor and heat shock protein networks
Authors: FRAGKOSTEFANAKIS SOTIRIOS , RÖTH SASCHA , SCHLEIFF ENRICO , SCHARF KLAUS‐DIETER
Published: July 2014

Cell survival under high temperature conditions involves the activation of heat stress response (HSR), which in principle is highly conserved among different organisms, but shows remarkable complexity and unique features in plant systems. The transcriptional reprogramming at higher temperatures is controlled by the activity of the heat stress transcription factors (Hsfs). Hsfs allow the transcriptional activation of HSR genes, among which heat shock proteins (Hsps) are best characterized. Hsps belong to multigene families encoding for molecular chaperones involved in various processes including maintenance of protein homeostasis as a requisite for optimal development and survival under stress conditions. Hsfs form complex networks to activate downstream responses, but are concomitantly subjected to cell‐type‐dependent feedback regulation through factor‐specific physical and functional interactions with chaperones belonging to Hsp90, Hsp70 and small Hsp families. There is increasing evidence that the originally assumed specialized function of Hsf/chaperone networks in the HSR turns out to be a complex central stress response system that is involved in the regulation of a broad variety of other stress responses and may also have substantial impact on various developmental processes. Understanding in detail the function of such regulatory networks is prerequisite for sustained improvement of thermotolerance in important agricultural crops.
Hormonal dynamics contributes to divergence in seasonal stomatal behaviour in a monsoonal plant community
Authors: MCADAM SCOTT A.M. , BRODRIBB TIMOTHY J.
Published: July 2014

The plant hormone abscisic acid (ABA) is a primary regulator of plant transpiration, but its influence in determining seasonal stomatal behaviour in natural plant communities is poorly understood. We examined distantly related vascular plants growing together in a seasonally dry, monsoonal environment to determine whether ABA dynamics contributed to contrasting water use patterns in this natural setting. Regular sampling of angiosperm, cycad, conifer and fern species revealed characteristic seasonal patterns in ABA production, but these were highly distinct among species. Although no general relationship was observed between ABA levels, plant hydration or stomatal conductance among species, the seasonal dynamics in stomatal behaviour within species were predictable functions of either ABA or leaf water potential. Strong divergence in the seasonal role of ABA among species suggests that modification in ABA–stomatal interactions represents an important evolutionary pathway for adaptation in plant water use.
Protein signatures correspond to survival outcomes of AJCC stage III melanoma patients
Authors: Mactier Swetlana , Kaufman Kimberley L. , Wang Penghao , Crossett Ben , Pupo Gulietta M. , Kohnke Philippa L. , Thompson John F. , Scolyer Richard A. , Yang Jean Y. , Mann Graham J. , Christopherson Richard I.
Published: July 2014

Outcomes for melanoma patients with stage III disease differ widely even within the same subcategory. Molecular signatures that more accurately predict prognosis are needed to stratify patients according to risk. Proteomic analyses were used to identify differentially abundant proteins in extracts of surgically excised samples from patients with stage IIIc melanoma lymph node metastases. Analysis of samples from patients with poor (n = 14, <1 yr) and good (n = 19, >4 yr) survival outcomes identified 84 proteins that were differentially abundant between prognostic groups. Subsequent selected reaction monitoring analysis verified 21 proteins as potential biomarkers for survival. Poor prognosis patients are characterized by increased levels of proteins involved in protein metabolism, nucleic acid metabolism, angiogenesis, deregulation of cellular energetics and methylation processes, and decreased levels of proteins involved in apoptosis and immune response. These proteins are able to classify stage IIIc patients into prognostic subgroups (P < 0.02). This is the first report of potential prognostic markers from stage III melanoma using proteomic analyses. Validation of these protein markers in larger patient cohorts should define protein signatures that enable better stratification of stage III melanoma patients.