bluuebunny/crossref_metadata_2025 huggingface dataset:
Old Cryptococcus neoformans Cells Contribute to Virulence in Chronic Cryptococcosis
Authors: Bouklas Tejas , Pechuan Ximo , Goldman David L. , Edelman Batya , Bergman Aviv , Fries Bettina C.
Published: August 2013

Does cell age matter in virulence? The emergence of persister cells during chronic infections is critical for persistence of infection, but little is known how this occurs. Here, we demonstrate for the first time that the replicative age of the fungal pathogen
Cryptococcus neoformans
contributes to persistence during chronic meningoencephalitis. Generationally older
C. neoformans
cells are more resistant to hydrogen peroxide stress, macrophage intracellular killing, and antifungal agents. Older cells accumulate in both experimental rat infection and in human cryptococcosis. Mathematical modeling supports the concept that the presence of older
C. neoformans
cells emerges from
in vivo
selection pressures. We propose that advanced replicative aging is a new unanticipated virulence trait that emerges during chronic fungal infection and facilitates persistence. Therapeutic interventions that target old cells could help in the clearance of chronic infections.

IMPORTANCE
Our findings that the generational age of
Cryptococcus neoformans
cells matters in pathogenesis introduces a novel concept to eukaryotic pathogenesis research. We propose that emerging properties of aging
C. neoformans
cells and possibly also other fungal pathogens contribute to persistence and virulence. Whereas the replicative life span of strains may not matter for virulence
per se
, age-related resilience and thus the generational age of individual
C. neoformans
cells within a pathogen population could greatly affect persistence of the pathogen population and therefore impact outcome.
Severe Acute Respiratory Syndrome Coronavirus Nonstructural Proteins 3, 4, and 6 Induce Double-Membrane Vesicles
Authors: Angelini Megan M. , Akhlaghpour Marzieh , Neuman Benjamin W. , Buchmeier Michael J.
Published: August 2013

Coronaviruses (CoV), like other positive-stranded RNA viruses, redirect and rearrange host cell membranes for use as part of the viral genome replication and transcription machinery. Specifically, coronaviruses induce the formation of double-membrane vesicles in infected cells. Although these double-membrane vesicles have been well characterized, the mechanism behind their formation remains unclear, including which viral proteins are responsible. Here, we use transfection of plasmid constructs encoding full-length versions of the three transmembrane-containing nonstructural proteins (nsps) of the severe acute respiratory syndrome (SARS) coronavirus to examine the ability of each to induce double-membrane vesicles in tissue culture. nsp3 has membrane disordering and proliferation ability, both in its full-length form and in a C-terminal-truncated form. nsp3 and nsp4 working together have the ability to pair membranes. nsp6 has membrane proliferation ability as well, inducing perinuclear vesicles localized around the microtubule organizing center. Together, nsp3, nsp4, and nsp6 have the ability to induce double-membrane vesicles that are similar to those observed in SARS coronavirus-infected cells. This activity appears to require the full-length form of nsp3 for action, as double-membrane vesicles were not seen in cells coexpressing the C-terminal truncation nsp3 with nsp4 and nsp6.

IMPORTANCE
Although the majority of infections caused by coronaviruses in humans are relatively mild, the SARS outbreak of 2002 to 2003 and the emergence of the human coronavirus Middle Eastern respiratory syndrome (MERS-CoV) in 2012 highlight the ability of these viruses to cause severe pathology and fatality. Insight into the molecular biology of how coronaviruses take over the host cell is critical for a full understanding of any known and possible future outbreaks caused by these viruses. Additionally, since membrane rearrangement is a tactic used by all known positive-sense single-stranded RNA viruses, this work adds to that body of knowledge and may prove beneficial in the development of future therapies not only for human coronavirus infections but for other pathogens as well.
Spindle cell lipoma
Authors: Pardhe Nilesh , Singh Neeraj , Bharadwaj Gaurav , Nayak Prathibha Anand
Published: August 2013

Spindle cell lipomas (SCLs) are a group of benign lipogenic tumours, typically arising in the posterior neck, upper back and shoulder of elderly male patients. Approximately 80% of these tumours arise in characteristic location, but 20% arise in unusual locations, thereby making these cases more difficult to diagnose. We present a case of SCL occurring in the right periorbital region of a 14-year-old boy. The MRI was suggestive of possible malignancy. Diagnosis of neurofibroma was made on incisional biopsy. However, the histopathological and immunohistochemical analyses of the excised lesion confirmed the diagnosis of SCL.
Antepartum fetal bladder rupture leading to urinary ascitis: attempt to rescue by placement of peritoneo-amniotic shunt
Authors: Singh Nilanchali , Tripathi Reva , Tyagi Shakun , Batra Atul
Published: August 2013

Fetal bladder rupture is a rare complication occurring due to bladder outlet obstruction, mostly posterior urethral valves. A 26-year-old primigravida presented to us at 27 weeks gestation with an ultrasound report showing gross fetal ascitis and mild oligohydramnios. A repeat scan was performed which showed fetal bladder rupture and urinary ascitis. In conjunction with paediatric surgeon, we performed ultrasound-guided placement of double-ended pigtail catheter connecting the fetal peritoneal cavity with the amniotic cavity at 28 weeks gestation. Ultrasound performed 3 days after the placement of the catheter showed its correct placement. Unfortunately, 1 week after the procedure at 29 weeks gestation, the patient had premature rupture of membranes and later went into labour and delivered vaginally. The neonate could not be revived and expired after few hours of birth due to prematurity-related complications. The placement of the shunt could have probably precipitated preterm rupture of membranes.
Chronic empyema: importance of preventing complications in the management of pleural effusions
Authors: Molander Viktor , Diakopoulou Maria , Orre Lotta , Ferrara Giovanni
Published: August 2013

We report a case of chronic empyema in a 63-year-old man with a history of asbestos exposure and alcohol overconsumption. In 2009, he presented with dyspnoea, exudative pleurisy on the right side with no symptoms of infection or malignancy. In 2013, the patient presented with increased dyspnoea and a massive chronic empyema had evolved. Culture of the pleural fluid was positive forEscherichia coliand anaerobic bacteria, and he was treated with antibiotics, chest drainage as well as surgical evacuation. After surgery, as the lung failed to expand, growth of opportunistic bacteria and rising C reactive protein obliged long-time treatment with broad-spectrum antibiotics as well as chest drainage with daily saline flushes. The patient still suffers from fatigue, poor nutritional status and anaemia, and further treatment with chest drainage and antibiotics is planned. Advanced chronic empyema is a difficult condition with poor response to treatment, and diagnostic delay is the main cause of complications.
Giant intrascrotal lipoma
Authors: Kaplanoglu Veysel , Kaplanoglu Hatice , Parlak Izzet Selçuk , Tatar Idil Güneş
Published: August 2013

Intrascrotal lipomas are rarely seen. Scrotal lipomas originate from the spermatic cord. We present a 64-year-old male patient, in the light of the literature, with painless swelling on the left half of the scrotum, histopathologically diagnosed with scrotal lipoma.
Endogenous testosterone level and testosterone supplementation therapy in chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis
Authors: Atlantis Evan , Fahey Paul , Cochrane Belinda , Wittert Gary , Smith Sheree
Published: August 2013

Objective

Low testosterone level may be a reversible risk factor for functional disability and deterioration in patients with chronic obstructive pulmonary disease (COPD). We sought to systematically assess the endogenous testosterone levels and effect of testosterone therapy on exercise capacity and health-related quality of life (HRQoL) outcomes in COPD patients, as well as to inform guidelines and practice.

Design

Systematic review and meta-analysis.

Data sources

We searched PubMed, Scopus, Cochrane Library, CINAHL, Health Source Nursing and PsychINFO and the reference lists of retrieved articles published before May 2012.

Inclusion criteria

Observational studies on endogenous testosterone levels in people with chronic lung disease compared with controls, or randomised controlled trials (RCTs) on testosterone therapy for exercise capacity and/or HRQoL outcomes in COPD patients were eligible.

Data extraction and analysis

Data on the mean difference in endogenous total testosterone (TT) values, and the mean difference in exercise capacity and HRQoL values were extracted and pooled using random effects meta-analysis.

Results

Nine observational studies in 2918 men with COPD reported consistently lower levels of TT compared with controls (weighted mean difference was –3.21 nmol/L (95% CI −5.18 to −1.23)). Six RCTs in 287 participants yielded five studies on peak muscle strength and peak cardiorespiratory fitness outcomes (peak oxygen uptake (VO2) and workload) and three studies on HRQoL outcomes. Testosterone therapies significantly improved peak muscle strength (standardised mean difference (SMD) was 0.31 (95% CI 0.05 to 0.56)) and peak workload (SMD was 0.27 (95% CI 0.01 to 0.52)) compared with control conditions (all but one used placebo), but not peak VO2(SMD was 0.21 (95% CI −0.15 to 0.56)) or HRQoL (SMD was –0.03 (95% CI −0.32 to 0.25)).

Conclusions

Men with COPD have clinically relevant lower than normal TT levels. Insufficient evidence from short-term studies in predominately male COPD patients suggests that testosterone therapy improves exercise capacity outcomes, namely peak muscle strength and peak workload.
Urinary albumin excretion as a marker of endothelial dysfunction in migraine sufferers: the HUNT study, Norway
Authors: Jacobsen Line M , Winsvold Bendik S , Romundstad Solfrid , Pripp Are H , Holmen Jostein , Zwart John-Anker
Published: August 2013

Objective

To investigate urine albumin leakage as a marker of endothelial dysfunction in migraine patients.

Design

A population-based health study.

Participants

303 patients with migraine, 1009 patients with non-migraine headache and 5287 headache-free controls.

Outcomes

The association between urine albumin- to-creatine ratio (ACR) and headache status was investigated in the Nord-Trøndelag Health Study (HUNT-2). Patients were selected in two strata, based on either (1) self-reported hypertension/diabetes (morbid sample) or (2) a random sample. Analyses were performed using analysis of covariance.

Results

There was no association between headache status and ACR in the study population (p=0.23, mean ACR for migraine 1.66, 95% CI 1.31 to 2.01, for non-migraine headache 1.90, 95% CI 1.71 to 2.09 and for no headache 1.73, 95% CI 1.64 to 1.81) after relevant adjustments. Similarly, no association between headache status and ACR was seen when the analysis was stratified for morbid and random samples, or for migraine with and without aura.

Conclusions

We found no evidence of increased urine albumin leakage in migraine sufferers when compared with headache-free controls. This could indicate that systemic endothelial dysfunction is not a prominent feature of migraine.
Statin use and asthma control in patients with severe asthma
Authors: Zeki Amir A , Oldham Justin , Wilson Machelle , Fortenko Olga , Goyal Vishal , Last Michael , Last Andrew , Patel Ayan , Last Jerold A , Kenyon Nicholas J
Published: August 2013

Objectives

We hypothesised that severe asthmatics taking a statin drug, in addition to inhaled corticosteroids/long-acting β-agonist inhaler therapy, would have better asthma symptom control and improved lung function compared to their controls.

Study design

A retrospective, cross-sectional study of 165 patients with severe asthma seen from 2001–2008. Hierarchical linear and logistic regression models were used for modelling fitting.

Setting

University of California, Davis Medical Center (Sacramento, California, USA). Academic, single-centre, severe asthma subspecialty clinic.

Participants

612 screened, 223 eligible and 165 adult patients were included in the final study (N=165; 31 statin users and 134 non-users).

Primary and secondary outcome measures

The primary endpoint was asthma control as measured by the Asthma Control Test (ACT). The secondary endpoints included lung function, symptoms and the need for corticosteroid burst and peripheral eosinophil count.

Results

At baseline, statin users compared to non-users were older, had lower lung function (FEV1% predicted, FEV1, forced vital capacity and FEF25–75%) and had a higher prevalence of comorbid conditions. Statin use was associated with more aspirin and ipratropium inhaler use than in non-users. Patients in both groups were obese (body mass index ≥ 30). Statin users had better asthma symptom control compared to non-users (higher adjusted mean ACT score by 2.2±0.94 points, p<0.02). Median statin use was for 1 year. There were no statistically significant differences in lung function, corticosteroid or rescue bronchodilator use or peripheral eosinophilia between the two groups.

Conclusions

In our severe asthma referral population, statin users already taking inhaled controller therapy achieved better asthma control compared to non-users. The implications of this study is that patients with severe asthma could potentially benefit from added statin treatment. Because our study population was on average obese, the obese severe asthmatic may be a viable asthma subphenotype for further studies. Prospective randomised clinical trials evaluating the safety and efficacy of statins in severe asthma are warranted.
Assessing remedies for missing weekly individual exposure in sport injury studies
Authors: Kang Jian , Yuan Yan , Emery Carolyn
Published: August 2013

Background

In sport injury epidemiology research, the injury incidence rate (IR) is defined as the number of injuries over a given length of participation time (exposure, eg, game hours). However, it is common that individual weekly exposure is missing due to requirements of personnel at every game to record exposure information. Ignoring this issue will lead to an inflated injury rate because the total exposure serves as the denominator of IR, where the number of injury cases were captured accurately.

Purpose

This paper used data collected from a large community cohort study in youth ice hockey as an example, and compared six methods to handle missing weekly exposure of individual players.

Methods

The six methods to handle missing weekly exposures include available case analysis, last observation carried forward, mean imputation, multiple imputation, bootstrapping and best/worst case analysis. To estimate injury rate ratios (IRRs) between Alberta and Quebec, as in the original study, three statistical models were applied to the imputed datasets: Poisson, zero-inflated Poisson and negative binomial regression models.

Results

The final sample for imputation included 2098 players for whom 12.5% of weekly game hours were missing. Estimated IRs and IRRs with CIs from different imputation methods were similar when the proportion of missing was small. Simulations showed that mean and multiple imputations provide the least biased estimates of IRR when the proportion of missing was large.

Conclusions

Complicated methods, like multiple imputation or bootstrap, are not superior over the mean imputation, a much simpler method, in handling missing weekly exposure of injury data where exposures were missing at random.
Intermittent balloon occlusion to favor nidal penetration during embolization of arteriovenous malformations: a technique modification
Authors: Bank William O , Stemer Andrew B , Armonda Rocco A , Bell Randy S
Published: August 2013

Endovascular embolization of brain arteriovenous malformations (AVMs) has improved with liquid occlusive agents, but flow-related and anatomic restrictions limit endovascular capabilities. AVM compartments supplied by leptomeningeal networks and feeding arteries too small and/or tortuous for safe catheterization are rarely penetrated by liquid occlusive agents. A case with both impediments prompted a novel solution. A balloon was inflated across the supply to a lenticulostriate feeder, thereby favoring penetration of the liquid occlusive agent, injected from a different feeding territory, back into the AVM compartment supplied by the temporarily occluded feeder. This technique may reduce the number of embolization stages in large high-flow AVMs and increase the likelihood of achieving complete occlusion. This technique is highly complex and requires meticulous monitoring of multiple events.
Modified murine intracranial aneurysm model: aneurysm formation and rupture by elastase and hypertension
Authors: Hosaka Koji , Downes Daniel P , Nowicki Kamil W , Hoh Brian L
Published: August 2013

Introduction

Cerebral aneurysms occur in up to 5% of the population. There are several murine models of aneurysms; however, all have limitations and none reproducibly model aneurysm rupture. To fulfill this need, we modified two current rodent aneurysm models to create a murine model which reproducibly produces intracranial aneurysms and rupture.

Methods

The left common carotid arteries and the right renal arteries were ligated in C57BL/6 female mice with a hypertensive diet. One week later, small burr holes were created with a stereotactic frame using the following stereotactic measurements: 1.2 mm rostral and 0.7 mm lateral to the right of the bregma. A 26 G needle was gradually advanced via the burr hole until contact with the skull base, upon which the needle was pulled back 0.3 mm. Five, 10 and 20 μL of 10 U/mL elastase solution and 10 μL of 1 U/mL elastase solution were stereotactically injected into the basal cisterns. Angiotensin II was then continually infused at a dose of 1000 ng/kg/min via an osmotic pump placed subcutaneously. In the control mice, 20 μL bromophenol blue solution was injected. Three weeks later, or earlier if mice expired prior to 3 weeks, the circle of Willis was inspected by microscopy for aneurysm formation and/or signs of rupture. Histological analyses were then performed to evaluate elastic lamina destruction, inflammatory cell and macrophage infiltration, absence of intimal endothelial cells and thickening of the smooth muscle layer within the aneurysm wall. To compare with human aneurysms, human aneurysm specimens (n=35; 34 unruptured and 1 ruptured) and normal control superficial temporal arteries (STAs) (n=9) were examined.

Results

All mice given 5, 10 and 20 μL of 10 U/mL elastase solution developed intracranial aneurysms within the circle of Willis; 40%, 60% and 50% of mice had ruptured aneurysms, respectively. In mice given 10 μL of 1.0 U/mL elastase solution, 90% developed intracranial aneurysms and 20% had ruptured aneurysms. Aneurysms were confirmed by examining the destruction of the elastic lamina. Aneurysms consistently demonstrated CD45 positive inflammatory cell and F4/80 positive macrophage infiltration within the aneurysm wall which was not present in the circle of Willis of normal sham-operated mice. These results were similar to those in human aneurysms and STA control arteries.

Conclusions

We modified two current rodent aneurysm models to create a murine model that produces consistent aneurysms and rupture and can be used for studying cerebral aneurysm formation, rupture and treatment.
STUDY OF FLAPPING FLIGHT USING DISCRETE VORTEX METHOD BASED SIMULATIONS
Authors: DEVRANJAN S. , JALIKOP SHREYAS V. , SREENIVAS K. R.
Published: August 2013

In recent times, research in the area of flapping flight has attracted renewed interest with an endeavor to use this mechanism in Micro Air vehicles (MAVs). For a sustained and high-endurance flight, having larger payload carrying capacity we need to identify a simple and efficient flapping-kinematics. In this paper, we have used flow visualizations and Discrete Vortex Method (DVM) based simulations for the study of flapping flight. Our results highlight that simple flapping kinematics with down-stroke period (tD) shorter than the upstroke period (tU) would produce a sustained lift. We have identified optimal asymmetry ratio (Ar = tD/tU), for which flapping-wings will produce maximum lift and find that introducing optimal wing flexibility will further enhances the lift.
IOCD: INTENSITY ORDER CURVE DESCRIPTOR
Authors: LIU HONGMIN , ZHI SHANSHAN , WANG ZHIHENG
Published: August 2013

Curve matching plays an important role in pattern recognition, computer vision and image understanding. In several past years, this problem has been studied mainly based on the curve contour, while only little progress has been made using the texture feature of the curve's neighborhood. This paper develops a novel texture-based curve matching method called IOCD, which consists of three steps: (1) Curve support region (CSR) without assigning a dominant orientation is first determined; (2) CSR is equally partitioned into several order bins according to the overall intensity order; (3) The feature vector is computed based on the local intensity order mapping. Experiments prove that the proposed IOCD performs robust to image rotation, viewpoint change, illumination change, blur, noise and JPEG compress. The application of image mosaic further identifies IOCD can achieve good matching performance.
EXPERIMENTAL AND QUANTUM STUDIES ON ADSORPTION AND CORROSION INHIBITION EFFECT OF IMIDAZOLE DERIVATIVES ON N80 STEEL IN HYDROCHLORIC ACID
Authors: YADAV M. , KUMAR SUMIT , SHARMA DIPTI , YADAV P. N.
Published: August 2013

The inhibition effect of synthesized N ′-(phenylmethylidene)-2-(2-methyl-1 H -benzimidazol-1-yl)acetohydrazides, N ′-(4-methylphenylmethylidene)-2-(2-methyl-1 H -benzimidazol-1-yl)acetohydrazides, and N ′-(4-methoxyphenylmethylidene)-2-(2-methyl-1 H -benzimidazol-1-yl)acetohydrazides on the corrosion behaviour of N 80 steel in 15% hydrochloric acid solution was investigated using weight loss, potentiostatic polarization and electrochemical impedance spectroscopy methods. The inhibition efficiency increased as the concentration of the inhibitors was increased. The effect of temperature on corrosion inhibition was investigated by weight loss method and thermodynamic parameters were calculated. Potentiodynamic polarization measurements show that all the three studied inhibitors act as mixed inhibitor. The adsorption of inhibitors on N 80 steel surface obeys Langmuir adsorption isotherm. The structure of inhibitors was optimized using semiemperical AM1 method. Theoretical parameters such as the highest occupied molecular orbital (E HOMO ), lowest unoccupied molecular orbital (E LUMO ) energy levels, energy gap (ΔE = E LUMO - E HOMO ), dipole moment (μ), global hardness (γ), softness (σ), binding energy, molecular surface area and the fraction of electrons transferred (ΔN) were calculated and the adsorption mechanism was discussed. Scanning electron microscopy was used to characterize the surface marphology of the N 80 steel.
Skeletal muscle denervation causes skeletal muscle atrophy through a pathway that involves both Gadd45a and HDAC4
Authors: Bongers Kale S. , Fox Daniel K. , Ebert Scott M. , Kunkel Steven D. , Dyle Michael C. , Bullard Steven A. , Dierdorff Jason M. , Adams Christopher M.
Published: August 2013

Skeletal muscle denervation causes muscle atrophy via complex molecular mechanisms that are not well understood. To better understand these mechanisms, we investigated how muscle denervation increases growth arrest and DNA damage-inducible 45α ( Gadd45a) mRNA in skeletal muscle. Previous studies established that muscle denervation strongly induces Gadd45a mRNA, which increases Gadd45a, a small myonuclear protein that is required for denervation-induced muscle fiber atrophy. However, the mechanism by which denervation increases Gadd45a mRNA remained unknown. Here, we demonstrate that histone deacetylase 4 (HDAC4) mediates induction of Gadd45a mRNA in denervated muscle. Using mouse models, we show that HDAC4 is required for induction of Gadd45a mRNA during muscle denervation. Conversely, forced expression of HDAC4 is sufficient to increase skeletal muscle Gadd45a mRNA in the absence of muscle denervation. Moreover, Gadd45a mediates several downstream effects of HDAC4, including induction of myogenin mRNA, induction of mRNAs encoding the embryonic nicotinic acetylcholine receptor, and, most importantly, skeletal muscle fiber atrophy. Because Gadd45a induction is also a key event in fasting-induced muscle atrophy, we tested whether HDAC4 might also contribute to Gadd45a induction during fasting. Interestingly, however, HDAC4 is not required for fasting-induced Gadd45a expression or muscle atrophy. Furthermore, activating transcription factor 4 (ATF4), which contributes to fasting-induced Gadd45a expression, is not required for denervation-induced Gadd45a expression or muscle atrophy. Collectively, these results identify HDAC4 as an important regulator of Gadd45a in denervation-induced muscle atrophy and elucidate Gadd45a as a convergence point for distinct upstream regulators during muscle denervation and fasting.
A form of mitofusin 2 (Mfn2) lacking the transmembrane domains and the COOH-terminal end stimulates metabolism in muscle and liver cells
Authors: Segalés Jessica , Paz José C. , Hernández-Alvarez María Isabel , Sala David , Muñoz Juan Pablo , Noguera Eduard , Pich Sara , Palacín Manuel , Enríquez José Antonio , Zorzano Antonio
Published: August 2013

Mitofusin 2 (Mfn2), a protein that participates in mitochondrial fusion, is required to maintain normal mitochondrial metabolism in skeletal muscle and liver. Given that muscle Mfn2 is repressed in obese or type 2 diabetic subjects, this protein may have a potential pathophysiological role in these conditions. To evaluate whether the metabolic effects of Mfn2 can be dissociated from its function in mitochondrial dynamics, we studied a form of human Mfn2, lacking the two transmembrane domains and the COOH-terminal coiled coil (ΔMfn2). This form localized in mitochondria but did not alter mitochondrial morphology in cells or in skeletal muscle fibers. The expression of ΔMfn2 in mouse skeletal muscle stimulated glucose oxidation and enhanced respiratory control ratio, which occurred in the absence of changes in mitochondrial mass. ΔMfn2 did not stimulate mitochondrial respiration in Mfn2-deficient muscle cells. The expression of ΔMfn2 in mouse liver or in hepatoma cells stimulated gluconeogenesis. In addition, ΔMfn2 activated basal and maximal respiration both in muscle and liver cells. In all, we show that a form of Mfn2 lacking mitochondrial fusion activity stimulates mitochondrial function and enhances glucose metabolism in muscle and liver tissues. This study suggests that Mfn2 regulates metabolism independently of changes in mitochondrial morphology.
Low-Dose-Area-Constrained Helical TomoTherapy-Based Whole Breast Radiotherapy and Dosimetric Comparison with Tangential Field-in-Field IMRT
Authors: Qiu Jie , Liu Zhikai , Yang Bo , Hou Xiaorong , Zhang Fuquan
Published: August 2013

Background and Purpose.To present a novel helical TomoTherapy-based method for whole breast radiotherapy that has better dosimetry and also has acceptable low-dose regions for lungs, heart, and contralateral breast compared with tangential field-in-field IMRT (FIF-IMRT).Material and Methods.Ten patients with left-side breast cancer were planned with low-dose-area-constrained helical TomoTherapy (LDC-HT) and FIF-IMRT. Dosimetry was compared for all techniques.Results.Coverage of the whole breast was adequate with both techniques. Homogeneity index (HI) and conformity index (CI) were better with LDC-HT. LDC-HT showed dosimetry advantages over FIF-IMRT for ipsilateral lung and heart in not only high-dose levels but also in low-dose levels such asV10 GyandV5 Gy. For contralateral lung, both techniques can provide good protection, although the mean dose of LDC-HT is higher than that of FIF-IMRT.Conclusions.With LDC-HT, we obtained adequate target coverage, better HI and CI of target volume, better sparing of organs at risk, and acceptably low-dose areas compared with FIF-IMRT. LDC-HT could be a feasible method in whole breast radiotherapy. Clinical benefits of LDC-HT need further investigation.
Identification of Lethal microRNAs Specific for Head and Neck Cancer
Authors: Lindenbergh-van der Plas Marlon , Martens-de Kemp Sanne R. , de Maaker Michiel , van Wieringen Wessel N. , Ylstra Bauke , Agami Reuven , Cerisoli Francesco , Leemans C. René , Braakhuis Boudewijn J.M. , Brakenhoff Ruud H.
Published: August 2013

Purpose: The prognosis of head and neck squamous cell carcinomas (HNSCC) remains disappointing and the development of novel anti-cancer agents is urgently awaited. We identified by a functional genetic screen microRNAs that are selectively lethal for head and neck cancer cells but not for normal cells. We further investigated the genes targeted by these microRNAs.

Experimental Design: A retroviral expression library of human microRNAs was introduced in HNSCC cell lines and normal oropharyngeal keratinocytes to identify tumor-selective lethal microRNAs. Potential downstream gene targets of these microRNAs were identified by gene expression profiling and validated by functional assays.

Results: We identified six microRNAs that selectively inhibit proliferation of head and neck cancer cells. By gene expression profiling and 3′-untranslated region (UTR) luciferase reporter assays, we showed that the ataxia telangiectasia mutated (ATM) gene is a common target for at least two and likely three of these microRNAs. Specific inhibition of ATM resulted in a similar tumor-specific lethal effect, whereas the phenotype was reverted in rescue experiments.

Conclusions: These six microRNAs might be developed as novel anti-cancer agents and highlight ATM as an interesting novel therapeutic target for head and neck cancer. Clin Cancer Res; 19(20); 5647–57. ©2013 AACR.
A New Type of Annular Erythema with Perieccrine Inflammation: Erythema Papulatum Centrifugum
Authors: Ohmori Ryoko , Kikuchi Katsuko , Yamasaki Kenshi , Aiba Setsuya
Published: August 2013

Erythema papulatum centrifugum (EPC) was first described in 1962 by Watanabe [Jpn J Dermatol 1962;72:573] as eczematous lesions extending centrifugally. To date, more than 150 cases have been reported, but only in the Japanese literature. A review of the Japanese literature including our 5 new cases reveals that EPC occurs in middle-aged persons, predominantly in males, as a single lesion on the trunk that is self-limiting but recurs frequently. Although EPC shares several characteristics with the superficial type of erythema annulare centrifugum or asymmetrical periflexural exanthema, EPC differs from erythema annulare centrifugum in clinical manifestation, showing annular rings composed of grouped, tiny papules, and in the histology of perieccrine inflammation, while it differs from asymmetrical periflexural exanthema by male preponderance, onset age, high relapse rate and unique annular configuration. We discuss EPC as compared with other cutaneous disorders showing annular erythema or similar histopathology and suggest that EPC is a distinct clinical entity.
Comparison of Speaking Fundamental Frequency between Premenopausal Women and Postmenopausal Women with and without Hormone Therapy
Authors: D'haeseleer Evelien , Depypere Herman , Van Lierde Kristiane
Published: August 2013

Objective: The purpose of this study was to investigate the speaking fundamental frequency (SFF) in pre- and postmenopausal women with and without hormone therapy (HT) and with low and high body mass index (BMI). Patients and Methods: The SFF of premenopausal women with low BMI (n = 22) was compared with the SFF of premenopausal women with high BMI (n = 13), postmenopausal women with HT and low BMI (n = 35), postmenopausal women with HT and high BMI (n = 19), postmenopausal women without HT and with low BMI (n = 28) and postmenopausal women without HT and with high BMI (n = 12) using ANCOVA and post hoc tests. Results: A significantly lower SFF of the voice was only found in postmenopausal women without HT and with a low BMI. Conclusion: The results of this study suggest that the menopause lowers the voice with approximately 14 Hz and that HT and adipose tissue (high BMI) might counteract the menopausal drop in SFF.
Management of the Treatment Delay in Symptomatic Carotid Artery Stenosis
Authors: Stiehm Markus , Björses Katarina , Kremer Christine
Published: August 2013

Saving time to intervention is crucial in patients with symptomatic carotid artery stenosis (SCAS). We introduced a fast-track protocol (FTP). Time frames from the onset of symptoms to intervention before and after the introduction of an FTP were analyzed. SCAS patients (403 patients/405 procedures) were evaluated according to whether surgery was performed before (group 1) or after (group 2) the introduction of the FTP. Time frames to surgery, causes of delay and frequency of recurrent events are reported. The median time delay decreased from 17 to 12 days (p < 0.001), but time to ultrasound examination remained unchanged. Surgery was within 2 weeks in 41% in group 1 and in 57% in group 2 (p = 0.001). Of 181 (30%) patients treated according to the FTP, 54 were operated within 7 days (median), and 80% had the intervention within 2 weeks. Time to surgery decreased significantly after the introduction of the FTP.
Health Significance of Fat Quality in the Diet
Authors: Nettleton Joyce A. , Villalpando Salvador , Cassani Roberta Soares Lara , Elmadfa Ibrahim
Published: August 2013

This paper summarizes three presentations on the global and Latin American perspectives on the health significance of fat quality in the diet given at the 16th Congress of the Society of Latin American Nutrition in Havana, Cuba, November 11-16, 2012. Dietary fat quality contributes to the risk of the leading chronic diseases and is more important than fat quantity in reducing the risk of chronic disease mortality, especially from cardiovascular disease (CVD). In many countries, the consumption of saturated fats exceeds the recommended limit of 10% energy (%E) and intakes of polyunsaturated fats (PUFAs) are often below the recommended range of 6-11%E. Consumption of long-chain ω-3 PUFAs is especially low. In many Latin American countries, high consumption of carbohydrates, especially sugars, contributes to obesity, diabetes, hypertension and CVD, while intakes of total fat and PUFAs may be low. Thus, dietary fat recommendations must consider the dietary fat patterns of each country. Nutrition counseling can be effective in teaching individuals and families to modify their food intake patterns and control the major risk factors for chronic disease.
Adding Pineapple Juice to a Polyethylene Glycol-Based Bowel Cleansing Regime Improved the Quality of Colon Cleaning
Authors: Altınbas Akif , Aktas Bora , Yılmaz Barıs , Ekiz Fuat , Deveci Murat , Basar Omer , Simsek Zahide , Coban Sahin , Tuna Yasar , Uyar Muhemmet Fatih , Yuksel Osman
Published: August 2013

Background/Aims: An unsuccessful colonoscopy procedure is often related to inadequate bowel cleansing. It is difficult for patients to finish the whole 4 liters of polyethylene glycol-electrolyte lavage (PEG-EL) because of its salty taste and the large quantity. Pineapple juice has been shown to be an effective agent in the dissolution of undigested food in the stomach. This study assessed the effectiveness of both 2 and 4 liters of PEG-EL in precolonoscopic bowel cleansing and the quality of colonoscopic cleaning by adding 1 liter of pineapple juice to a reduced-volume PEG-based regime. Methods: The patients were chosen from those undergoing a colonoscopic procedure. A total of 126 patients were randomized into 3 groups receiving 3 different PEG-EL (Golytely®) regimes, i.e. 4 liters of PEG-EL (group 1, n = 44), 2 liters of PEG-EL (group 2, n = 39) or 2 liters of PEG-EL with 1 liter of pineapple juice (Dimes® 100%; group 3, n = 43). Results: Both the 4- and 2-liter PEG-EL regimes resulted in similar bowel cleansing scores in all parts of the colonic segments. However, adding 1 liter of pineapple juice to the reduced-volume PEG-EL regime improved the quality of the cleansing on the right side of the colon and in the transverse colon. Adequate bowel cleansing was achieved in 68.1% of the patients in group 1, 63.9% in group 2 and 80% in group 3 (the lowest score in one of the segments). On the other hand, the tolerability of the regimes was similar in all 3 groups (p = 0.509). Conclusions: Reduced PEG-EL (2 rather than 4 liters) may be sufficient for precolonoscopic bowel cleansing in the Turkish population. Administration of pineapple juice in the reduced-dose preparation regime may improve the quality of the bowel cleaning.
Aortic Regurgitation and Left Ventricular Remodeling After Transcatheter Aortic Valve Implantation
Authors: Merten Constanze , Beurich Hans-Wilko , Zachow Dirk , Mostafa Ahmad E. , Geist Volker , Toelg Ralph , Richardt Gert , Abdel-Wahab Mohamed
Published: August 2013

Background—

Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) has been associated with poor outcomes, but little is known about how it evolves over time. We evaluated left ventricular (LV) function, remodeling, and the occurrence and evolution of AR after TAVI by using cardiac MRI.

Methods and Results—

Forty-three patients treated with transfemoral TAVI underwent cardiac MRI 1 week and 6 months after TAVI. LV volumes and function were assessed by using standard cine MRI sequences. Phase-contrast imaging was performed to quantify the degree of AR. The mean age of the evaluated patients was 80 years, and 65% of patients were women. At baseline MRI, the median LV ejection fraction was 58.1%, which improved significantly at follow-up to 63.4% (
P
<0.0001). A significant reduction of LV end-diastolic volume (149.7±41.4–140.1±43.9 mL;
P
=0.014) and of LV mass (156.3±32.8–142.7±39.3 g;
P
<0.001) was observed. Over time, aortic regurgitant fraction increased slightly but significantly from 5.2% to 7.8% (
P
=0.04). Subgroup analysis revealed that significant changes of LV ejection fraction, volumes, and mass only occurred in patients with no or mild AR at baseline MRI, whereas those parameters remained unchanged in patients with AR more than or equal to grade II.

Conclusions—

By using cardiac MRI in patients with TAVI, a significant improvement of LV function, volume, and mass can be documented. Mild-to-moderate AR is commonly seen, and AR shows a small increase over time. More-than-mild AR seems to prevent LV functional and structural recovery after TAVI.
Triple Antithrombotic Therapy Is the Independent Predictor for the Occurrence of Major Bleeding Complications
Authors: Naruse Yoshihisa , Sato Akira , Hoshi Tomoya , Takeyasu Noriyuki , Kakefuda Yuki , Ishibashi Mayu , Misaki Masako , Abe Daisuke , Aonuma Kazutaka
Published: August 2013

Background—

Triple antithrombotic therapy increases the risk of bleeding events in patients undergoing percutaneous coronary intervention. However, it remains unclear whether good control of percent time in therapeutic range is associated with reduced occurrence of bleeding complications in patients undergoing triple antithrombotic therapy.

Methods and Results—

This study included 2648 patients (70±11 years; 2037 men) who underwent percutaneous coronary intervention with stent in the Ibaraki Cardiovascular Assessment Study registry and received dual antiplatelet therapy with or without warfarin. Clinical end points were defined as the occurrence of major bleeding complications (MBC), major adverse cardiac and cerebrovascular event, and all-cause death. Among these 2648 patients, 182 (7%) patients received warfarin. After a median follow-up period of 25 months (interquartile range, 15–35 months), MBC had occurred in 48 (2%) patients, major adverse cardiac and cerebrovascular event in 484 (18%) patients, and all-cause death in 206 (8%) patients. Multivariable Cox regression analysis revealed that triple antithrombotic therapy was the independent predictor for the occurrence of MBC (hazard ratio, 7.25; 95% confidence interval, 3.05–17.21;
P
<0.001). The time in therapeutic range value did not differ between the patients with and without MBC occurrence (83% [interquartile range, 50%–90%] versus 75% [interquartile range, 58%–87%];
P
=0.7). However, the mean international normalized ratio of prothrombin time at the time of MBC occurrence was 3.3±2.1. Triple antithrombotic therapy did not have a predictive value for the occurrence of all-cause death (
P
=0.1) and stroke (
P
=0.2).

Conclusions—

Triple antithrombotic therapy predisposes patients to an increased risk of MBC regardless of the time in therapeutic range.
Calibration and Validation of the Integrated Biosphere Simulator (IBIS) for a Brazilian Semiarid Region
Authors: Cunha Ana Paula M. A. , Alvalá Regina C. S. , Sampaio Gilvan , Shimizu Marília Harumi , Costa Marcos Heil
Published: August 2013

The reliability of predictions from climate and weather models is linked to an adequate representation of the land surface processes. To evaluate performance and to improve predictions, land surface models are calibrated against observed data. Despite an extensive literature describing methods of land surface model calibration, few studies have applied a calibration method for semiarid natural vegetation, especially for the semiarid northeast of Brazil, which presents caatinga as its natural vegetation. Caatinga is a highly dynamic ecosystem with the physics at the land surface–atmosphere interface still poorly understood. Therefore, in this study a multiobjective hierarchical method, which provides means to estimate optimal values of the model parameters through calibration, is evaluated. This method is applied to caatinga by using the Integrated Biosphere Simulator (IBIS). Results demonstrated that the calibrated set of vegetation parameters produced a considerably different energy balance from the default parameters. In general, the model was able to simulate the partition of the available energy into sensible and latent heat fluxes when the calibrated parameters were used. The IBIS model was not able to capture short-term, intense changes in latent heat flux from a dry condition to a wetter condition, however, even when the new set of calibrated parameters was used. Therefore, the parameter optimization may not be sufficient if processes are missing or misrepresented. This study is one of the first to understand the physics at the land surface–atmosphere interface in the caatinga ecosystem and to evaluate the ability of the IBIS model to represent the biophysical interactions in this important ecosystem.
Intense Summer Heat in Tokyo and Its Suburban Areas Related with Variation in the Synoptic-Scale Pressure Field: A Statistical Analysis
Authors: Yoshikado Hiroshi
Published: August 2013

Intense summer heat in Tokyo, Japan, and its suburban areas between 1990 and 2010 was statistically analyzed. Sample days were selected from among days with a sea breeze and sufficient sunshine duration, because sea breeze is the dominant summertime meteorological system in the region. Excess in the daily maximum temperature of an inland urban site in Tokyo over a site facing the outer sea where the sea breeze originates was selected as a key index. A comparison of a group of days for which the temperature excess was large with an opposing group of days for which it was small revealed a distinct difference in diurnal wind variations: persistent southwesterly winds overwhelmed the sea breeze in areas facing the outer sea in the former case, whereas in the latter case a diurnal sea-breeze cycle was typically observed in those areas as well as in the inland areas. This difference could furthermore be connected to differences in the pressure gradient in the region, that is, differences in the synoptic-scale pressure field. As a result, slight shifts in the pressure field affect urban heat, suggesting that, in addition to general warming, changes in the pressure field resulting from future climate change can be of great importance.
Arctic Sea Ice Reduction and Extreme Climate Events over the Mediterranean Region
Authors: Grassi Barbara , Redaelli Gianluca , Visconti Guido
Published: August 2013

During the last decade, Arctic sea ice cover has experienced an accelerated decline that has been suggested to drive the increased occurrence of extremely cold winter events over continental Europe. Observations and modeling studies seem to support the idea that Mediterranean climate is also changing. In this work, the authors estimate potential effects on the Mediterranean Basin, during the winter period, of Arctic sea ice reduction. Two sets of simulations have been performed by prescribing different values of sea ice concentrations (50% and 20%) on the Barents–Kara Seas in the NCAR Community Atmosphere Model, version 3 (CAM3), as representative of idealized present and future sea ice conditions. Global model simulations have then been used to run the Abdus Salam International Centre for Theoretical Physics (ICTP) Regional Climate Model, version 4 (RegCM4), over central Europe and the Mediterranean domain. Simulations provide evidence for a large-scale atmospheric circulation response to sea ice reduction, resembling the negative phase of the Arctic Oscillation (AO) and characterized by a wave activity flux from the North Atlantic toward the Mediterranean Basin, during winter months. An increase in the occurrence and intensity of extreme cold events, over continental Europe, and extreme precipitation events, over the entire Mediterranean Basin, was found. In particular, simulations suggest an increased risk of winter flooding in southern Italy, Greece, and the Iberian Peninsula.
Comparison of the Annual Cycles of Moisture Supply over Southwest and Southeast China
Authors: Li Xiuzhen , Zhou Wen , Li Chongyin , Song Jie
Published: August 2013

The variation in regional precipitation over southeast and southwest China depends strongly on externally imported moisture rather than local evaporation. Associated with the different climate over the two regions, great discrepancies appear in the annual cycles of the moisture supply. Stationary moisture transport dominates externally imported moisture to a large extent, with transient transport being much weaker. The stationary moisture sink over southeast China is strong during spring and summer due to strong moisture input via the southern boundary and weak during fall and winter due to the offset between the output via the southern boundary and the net zonal boundary atmospheric flux. Zonal stationary moisture transport dominates the variation in moisture supply over southwest China. Negative net zonal boundary atmospheric flux countervails (collaborates) with positive meridional transport during the dry (wet) season.

Stationary moisture circulations dominate regional atmospheric moisture convergence anomalies over both southeast and southwest China. Weak cold air activity is favorable for a strong moisture sink over southeast China, while the reverse appears over southwest China in spring. The east-to-west location of the abnormal anticyclone determines whether strong moisture converges over southeast China or southwest China in fall. The anticyclonic circulation anomaly over the Philippine Sea, remotely forced by El Niño, is crucial to the strong moisture sink over southeast China from winter to spring, while it does not play a role in the abnormal moisture sink over southwest China.