bluuebunny/crossref_metadata_2025 huggingface dataset:
Motion perception in children with foetal alcohol syndrome
Authors: Gummel Kristina , Ygge Jan , Benassi Mariagrazia , Bolzani Roberto
Published: April 2012

Aim:  To evaluate the visual magnocellular pathway by a coherent motion perception test in children with foetal alcohol syndrome (FAS).

Methods:  Eighty‐nine children (49 with verified FAS and 40 without FAS) aged from 10 to 16 years were included into the study. Both the study and the control group were children living in orphanages. A coherent motion perception test was used. The test consisted of 150 white moving dots on a black background presented in different signal‐to‐noise ratio conditions. The task was direction detection of the coherently moving dots whose percentage decreased at each step.

Results:  A significant difference between the two groups was found (p = 0.018). Children with FAS had lower coherent motion perception ability in all the signal‐to‐noise ratio conditions. A significant difference between difficulty levels (p < 0.001) was found for all subjects in both groups – decreasing the stimulus signal‐to‐noise level decreased the motion perception score. In both groups, the motion perception score differed for vertical and horizontal stimuli (p = 0.003) with better performance with vertical stimuli.

Conclusion:  Impaired motion perception in FAS children could be indicative of a dorsal stream developmental dysfunction resulting from alcohol brain damage.
The effect of sex on outcome of preterm infants – a population‐based survey
Authors: Neubauer Vera , Griesmaier Elke , Ralser Elisabeth , Kiechl‐Kohlendorfer Ursula
Published: April 2012

Aim:  To provide comprehensive data on potential sex differences in maternal and neonatal characteristics, short‐term morbidity and neurodevelopmental outcome within an entire geographically determined collective of infants born at a gestational age <32 weeks.

Methods:  Between 2003 and 2008, we prospectively enrolled all infants born in Tyrol at <32 weeks of gestation; the association between sex, and a wide set of pre‐ and postnatal factors, post‐discharge morbidity and neurodevelopmental outcome was analysed.

Results:  Girls less frequently suffered from early‐onset sepsis than boys (p = 0.030). After adjustment for multiple corrections (Bonferroni’s p = 0.003), no sex differences were seen within any maternal or neonatal parameter. Analysis of morbidity revealed a higher readmission rate in boys (p < 0.0001), which was primarily caused by a greater incidence of respiratory problems (p = 0.003). Boys did not show a greater adverse neurodevelopmental outcome at the age of 12 or 24 months.

Conclusion:  Parents of boys should be prepared for a potentially higher frequency of readmission after initial discharge, but our data currently give no reason for parents of boys to be disproportionately anxious about their neurodevelopmental outcome. Whether boys also enjoy a rosy prognosis for developmental outcome at school age remains to be elucidated.
EFFECT OF BREED, AGE, WEIGHT AND GENDER ON RADIOGRAPHIC RENAL SIZE IN THE DOG
Authors: Lobacz Monika Anna , Sullivan Martin , Mellor Dominic , Hammond Gawain , Labruyère Julien , Dennis Ruth
Published: April 2012

In the adult dog, kidney length has been reported as 2.98 ± 0.44 times the length of L2 on ventrodorsal views and 2.79 ± 0.46 times the length of L2 on lateral radiographs. Our aim was to test the hypothesis that the suggested maximum normal left kidney size is too high, and to evaluate the effect of breed type, gender, weight and age of the dog on kidney size. Abdominal radiographs of 200 dogs with no evidence of concurrent disease that might have an effect on renal size were included in the study. The mean ratio of kidney length to the second lumbar vertebra length was similar to previous reports. For the right lateral view it measured 2.98 ± 0.60 and for the ventrodorsal view 3.02 ± 0.66. Significant differences of this ratio between skull type were present, especially between brachycephalic and dolichocephalic dogs. On the right lateral view brachycephalic dogs had the highest median LK/L2 ratio of 3.1 (3.20 ± 0.40), whereas for dolichocephalic dogs it was 2.8 (2.82 ± 0.50), and for mesaticephalic dogs it was 2.97 (3.01 ± 0.6). A ratio >3.5 was found only in mesaticephalic dogs on the ventrodorsal view. There was a significant difference in the LK/L2 ratio between small (≤10kg) and large breed dogs (>30kg) where small dogs had a significantly higher LK/L2 ratio. There was no statistically significant relation between this ratio and age or gender. The previously reported ratios for kidney size seem valid, but because skull type has an impact on the LK/L2 ratio, a single normal ratio should not be used for all dogs.
Laser‐flash photolysis indicates that internal electron transfer is triggered by proton uptake by Alcaligenes xylosoxidans copper‐dependent nitrite reductase
Authors: Leferink Nicole G. H. , Eady Robert R. , Hasnain S. Samar , Scrutton Nigel S.
Published: April 2012

Enzyme‐catalysed electron transfer reactions are often controlled by protein motions and coupled to chemical change such as proton transfer. We have investigated the nature of this control in the blue copper‐dependent nitrite reductase from Alcaligenes xylosoxidans (AxNiR). Inter‐Cu electron transfer from the T1Cu site to the T2Cu catalytic site in AxNiR occurs via a proton‐coupled electron transfer mechanism. Here we have studied the kinetics of both electron and proton transfer independently using laser‐flash photolysis for native AxNiR and its proton‐channel mutant N90S. In native AxNiR, both inter‐Cu electron transfer and proton transfer exhibit similar rates, and show an unusual dependence on the nitrite concentration. An initial decrease in the observed rates at low nitrite concentrations is followed by an increase in the observed rates at high nitrite concentrations (> 5 mm). In N90S, in which the T1Cu reduction potential is elevated by 60 mV, no inter‐Cu electron transfer or proton transfer was observed in the absence of nitrite. Only in the presence of nitrite were both processes detected, with similar [nitrite] dependence, but the nitrite dependence was different compared with native enzyme. The substrate dependence in N90S was similar to that observed in steady‐state assays, suggesting that this substitution resulted in proton‐coupled electron transfer becoming rate‐limiting. A pH perturbation experiment with native AxNiR revealed that protonation triggers inter‐Cu electron transfer and generation of NO. Our results show a strong coupling of inter‐Cu electron transfer and proton transfer for both native AxNiR and N90S, and provide novel insights into the controlled delivery of electrons and protons to the substrate‐utilization T2Cu active site of AxNiR.
Characterization of the protein ubiquitination response induced by Doxorubicin
Authors: Mandili Giorgia , Khadjavi Amina , Gallo Valentina , Minero Valerio G. , Bessone Luca , Carta Franco , Giribaldi Giuliana , Turrini Francesco
Published: April 2012

Doxorubicin is commonly considered to exert its anti‐tumor activity by triggering apoptosis of cancer cells through DNA damage. Recent reports have shown that Doxorubicin elicits a marked heat shock response, and that either inhibition or silencing of heat shock proteins enhance the Doxorubicin apoptotic effect in neuroblastoma cells. In order to investigate whether Doxorubicin may also act through protein modification, we performed a proteomic analysis of ubiquitinated proteins. Here we show that nanomolar Doxorubicin treatment of neuroblastoma cells caused: (a) dose‐dependent over‐ubiquitination of a specific set of proteins in the absence of measurable inhibition of proteasome, (b) protein ubiquination patterns similar to those with Bortezomib, a proteasome inhibitor, (c) depletion and loss of activity of ubiquitinated enzymes such as lactate dehydrogenase and α‐enolase, and (d) a decrease in HSP27 solubility, probably a consequence of its binding to denatured proteins. These data strongly reinforce the hypothesis that Doxorubicin may also exert its effect by damaging proteins.
PROSO II – a new method for protein solubility prediction
Authors: Smialowski Pawel , Doose Gero , Torkler Phillipp , Kaufmann Stefanie , Frishman Dmitrij
Published: April 2012

Many fields of science and industry depend on efficient production of active protein using heterologous expression in Escherichia coli. The solubility of proteins upon expression is dependent on their amino acid sequence. Prediction of solubility from sequence is therefore highly valuable. We present a novel machine‐learning‐based model called PROSO II which makes use of new classification methods and growth in experimental data to improve coverage and accuracy of solubility predictions. The classification algorithm is organized as a two‐layered structure in which the output of a primary Parzen window model for sequence similarity and a logistic regression classifier of amino acid k‐mer composition serve as input for a second‐level logistic regression classifier. Compared with previously published research our model is trained on five times more data than used by any other method before (82 000 proteins). When tested on a separate holdout set not used at any point of method development our server attained the best results in comparison with other currently available methods: accuracy 75.4%, Matthew’s correlation coefficient 0.39, sensitivity 0.731, specificity 0.759, gain (soluble) 2.263. In summary, due to utilization of cutting edge machine learning technologies combined with the largest currently available experimental data set the PROSO II server constitutes a substantial improvement in protein solubility predictions. PROSO II is available at http://mips.helmholtz‐muenchen.de/prosoII.
Distinct sulfonation activities in resveratrol‐sensitive and resveratrol‐insensitive human glioblastoma cells
Authors: Sun Zheng , Li Hong , Shu Xiao‐Hong , Shi Hui , Chen Xiao‐Yan , Kong Qing‐You , Wu Mo‐Li , Liu Jia
Published: April 2012

Glioblastoma multiforme (GBM) cells show different responses to resveratrol, for unknown reasons. Our data from human medulloblastoma cells and primary cultures of rat brain cells revealed an inverse correlation of sulfonation activity with resveratrol sensitivities, providing a clue to the underlying mechanisms of the variable sensitivities of GBM cells to resveratrol. In this study, we found that U251 cells were sensitive and LN229 cells were insensitive to resveratrol. Thus, these two cell lines were taken as comparable models for elucidating the influence of sulfonation activities on resveratrol sensitivity. HPLC showed identical resveratrol metabolic patterns in both cell lines. LC/MS and high‐resolution mass MS analyses further demonstrated that resveratrol monosulfate generated by sulfotransferases (SULTs) was the major metabolite of human GBM cells. The levels of brain‐associated SULT (SULT1A1, SULT1C2, and SULT4A1) expression in U251 cells were lower than those in LN229 cells, suggesting the inverse relationship of SULT‐mediated sulfonation activity with high intracellular resveratrol bioavailability and resveratrol sensitivity of human GBM cells. Furthermore, immunohistochemical staining revealed reductions in expression of the three brain‐associated SULTs in 72.8%, 47.5% and 66.3% of astrocytomas, respectively. Therefore, the levels of brain‐associated SULTs and sulfonation activity mediated by them could be important parameters for evaluating the potential response of human GBM cells to resveratrol, and may have value in the personalized treatment of GBMs with resveratrol.

Database
 Nucleotide sequence data for SULT1A1, SULT1C2 and SULT4A1 are available in the GenBank database under the accession numbers BC110887, BC005353, and BC028171.
Occupational therapy for inpatients with chronic schizophrenia: A pilot randomized controlled trial
Authors: FORUZANDEH Nasrin , PARVIN Neda
Published: April 2012

Aim:  People with schizophrenia tend to experience difficulties in social and cognitive function, self‐care, residual negative symptoms, high rates of unemployment, and social exclusion. Occupational therapy has contributed to the treatment and rehabilitation of people with severe mental health problems. Therefore, this study investigated the effects of occupational therapy on symptoms of patients with schizophrenia.

Methods:  This survey was an experimental study in which positive and negative symptoms of patients with schizophrenia were assessed with a scale for the assessment of positive and negative symptoms (SANS, SAPS, respectively). The study was conducted in Sina Hospital, Shahrekord, Iran. The samples consisted of patients with schizophrenia who were divided randomly into intervention and usual treatment groups (30 patients in each group). The occupational therapy was performed in the intervention group for 18 h/week for 6 months. SANS and SAPS were assessed at the beginning and after 6 months of treatment.

Results:  The groups were homogeneous in demographic variables, SANS and SAPS scores at baseline. The occupational therapy group showed significant improvement in the total score for the SANS and SAPS at 6 months (P < 0.001), but the control group did not show any significant improvement.

Conclusion:  The results of this study indicated that occupational therapy combined with medications can improve the symptoms of schizophrenia.
HLA‐A*11:53 is shown to be identical to the corrected A*11:02:01 allele sequence
Authors: Yang K. L. , Chu C. C. , Marsh S. G. E. , Lin P. Y.
Published: April 2012

According to the IMGT/HLA Database, the DNA sequence of A*11:53 is identical to A*11:02:01 in exons 2, 3, 4 and 5 except at codon 276. A*11:53 was reported as a rare variant of A*11, while A*11:02:01 was understood to be the second most frequently observed variant of A*11 after A*11:01:01 in Taiwanese. We sequenced HLA‐A locus exons 2, 3, 4 and 5 of Taiwanese blood donors (n = 50) previously typed to carry A*11:02:01. We found out all of their sequences are identical to A*11:53 in exons 2, 3, 4 and 5′ part of exon 5 including codon 276.
Optical spectroscopy of the γ-ray bright blazars PKS 0447−439 and PMN J0630−24
Authors: Landt Hermine
Published: April 2012

The large majority of sources detected by the Fermi Gamma-ray Space Telescope are blazars, belonging in particular to the blazar subclass of BL Lacertae objects (BL Lacs). BL Lacs often have featureless optical spectra, which make it difficult and sometimes impossible to determine their redshifts. This presents a severe impediment for the use of BL Lacs to measure the spectrum of the extragalactic background light through its interaction with high-energy γ-ray photons. I present here high-quality optical spectroscopy of two of the brightest γ-ray blazars, namely PKS 0447−439 and PMN J0630−24. The medium-resolution and high signal-to-noise ratio optical spectra show clear absorption lines, which place these BL Lacs at relatively high redshifts of z≥ 1.246 for PKS 0447−439 and z≥ 1.238 for PMN J0630−24.
PHYSICOCHEMICAL PROPERTIES OF FORTIFIED CORN CHIPS WITH BROAD BEAN FLOUR, CHICKPEA FLOUR OR ISOLATED SOY PROTEIN
Authors: RABABAH TAHA M. , BREWER SUSAN , YANG WADE , AL‐MAHASNEH MAJDI , AL‐U'DATT MUHAMMAD , RABABA SHAFEAH , EREIFEJ KHALIL
Published: April 2012

The effectiveness of substituting different concentrations (3, 6 or 9%) of broad bean flour (Bb), chickpea flour (Cp) or isolated soy protein (ISP) on the physiochemical and sensory properties of corn chips was evaluated. Fortification increased (P ≤ 0.05) protein contents from 6.4 to 10.5%. Sensory and instrumental color results indicated that fortification at high levels (9%) increased (P ≤ 0.05) chip redness. Texture profile analysis results (TPA) indicated that, as fortification ratios increased, texture measures of TPA measures decreased (P ≤ 0.05). The raw and cooked corn flavor attributes decreased (P ≤ 0.05) in chips fortified with 9% Bb and Cp, and with 6 and 9% ISP. The descriptive texture indicated that 9% Bb and Cp decreased hardness. The consumer intensity scale results showed that Bb, Cp and ISP at 9% decreased (P ≤ 0.05) crunchiness and hardness. It can be concluded that Bb, Cp or ISP can be added in corn chips.

PRACTICAL APPLICATIONS

As the protein–energy–malnutrition problem continues to expand because of limited protein sources, using inexpensive and readily available sources of protein has become a major research focus in recent years. Fortification of several food products with components such as legume flours was proposed to enhance the nutritional values of products by using these products in schools, feeding programs and in catastrophic situations. Chickpeas and broad beans, rich in food proteins, are widely available and used in different countries as a source of protein. Soybean flour contains 38% protein, also has been used to fortify different types of food to enhance their quality. Corn and tortilla chips account for 80% of the corn‐based snacks consumed worldwide. Corn‐based snacks increased over the last 30 years because of being included to the main meal as well as between‐meal nourishments. For that, this study evaluated fortifications in chips with different high‐legume proteins.
ANTIFUNGAL, AFLATOXIN INHIBITORY AND FREE RADICAL‐SCAVENGING ACTIVITIES OF SOME MEDICINAL PLANTS EXTRACTS
Authors: SHUKLA RAVINDRA , SINGH PRIYANKA , PRAKASH BHANU , ANURADHA  , DUBEY N.K.
Published: April 2012

The antifungal, aflatoxin inhibitory and antioxidant activity of methanol–aqueous extract (2:1) of 62 medicinal plants was explored. Based on the antifungal results, the extracts of 25 plants showed more than 50% antifungal activity and were further investigated for their aflatoxin inhibition and antioxidant properties. Methanol–aqueous extracts of Phyllanthus emblica and Terminalia chebula fruits caused 100% inhibition of aflatoxin production by the toxigenic strain of Aspergillus flavus in semisynthetic medium at 1 mg/mL. In addition, P. emblica (IC50 = 4.1 µg/mL) and T. chebula (IC50 = 6.9 µg/mL) fruits extracts exhibited strong antioxidant activity during the 2,2‐diphenyl‐1‐picrylhydrazyl radical‐scavenging assay in comparison with butylated hydroxytoluene (IC50 = 8.1 µg/mL) and butylated hydroxyanisole (IC50 = 6 µg/mL).

PRACTICAL APPLICATIONS

Based on the results of the present study, methanol–aqueous extracts of Phyllanthus emblica and Terminalia chebula, being endowed with strong antifungal, aflatoxin inhibitory and antioxidant activity, may be recommended as plant‐based preservatives for the enhancement of shelf life of food items and their protection from the undesirable harmful effects of molds, aflatoxin and free radical‐mediated damages.
PREVIOUS BACTERIAL INFECTION AFFECTS TEXTURAL QUALITY PARAMETERS OF HEAT‐TREATED FILLETS FROM RAINBOW TROUT (ONCORHYNCHUS MYKISS)
Authors: INGERSLEV H.‐C. , HYLDIG G. , PRZYBYLSKA D. , FROSCH S. , NIELSEN M.E.
Published: April 2012

Sensory quality of fish meat is influenced by many parameters prior to slaughter. In the present study, it was examined if previous infections or damages in the muscle tissue influence product quality parameters in fish. Fillets from rainbow trout (Oncorhynchus mykiss) reared in seawater at a commercial fish farm were sensory evaluated for more than a year after recovery following physical tissue damage or infection by the bacterial pathogens Yersinia ruckeri and Vibrio anguillarum. The effect of vaccination was also included as some fish were vaccinated before bacterial challenge. The fish fillets were sensory examined as heat‐treated and cold‐smoked. Heat‐treated fillets from nonvaccinated fish previously infected by V. anguillarum had changed textural characteristics and were less flaky, had a lower oiliness and a higher toughness and fibrousness in comparison with control fish. This article was the first to describe a correlation between previous infections in fish and changes in sensory‐quality parameters.

PRACTICAL APPLICATIONS

This work contributes with knowledge about sensory‐quality parameters of fish meat after recovery from infections and physical‐tissue damage. Because the results demonstrate an influence on the texture from previous disease, the practical potentials of the results are valuable for the aquaculture industry. In order to minimize the effects of previous diseases on the sensory quality regarding the texture, these fishes should be processed as cold‐smoked instead of being sold as raw meat. The established correlation between disease history stresses the importance of disease prevention in aquaculture production, e.g., vaccination of the fish.
The Agency of Dolphins: Towards Inter‐species Embassies as Sites of Engagement with ‘Significant Otherness’
Authors: TAYLOR C. SCOTT , CARTER JENNIFER
Published: April 2012

Cetacean–human interaction, at sites where free‐ranging dolphins approach humans, is occurring more than ever before. Management policies and strategies, and their underlying research, intended to protect both dolphins and humans during these interactive events, affect the quality and nature of interactivity. The agency of the dolphins, and its representation in management schemes, is analysed using Critical Discourse Analysis of selected texts from the discourse of Dolphin–Human Interaction Management (DHIM). Analysis suggests a prevailing discourse of protectionism but also reveals the possibility for a new kind of management scheme based upon an acceptance of the ‘significant otherness’ of non‐human species. This can be achieved by means of inter‐species etiquette, acknowledging the choices made by non‐humans to interact with humans. An inter‐species etiquette, coupled with multi‐species education (education across species boundaries, designed and delivered so as to enable mutually beneficial interaction), offers those non‐human animals widely referred to as ‘ambassadors’ safe places in which to be encountered. This new form of inter‐species interaction space is named an ‘embassy’.
Metformin, an Antidiabetic Agent Reduces Growth of Cutaneous Squamous Cell Carcinoma by Targeting mTOR Signaling Pathway†
Authors: Chaudhary Sandeep C. , Kurundkar Deepali , Elmets Craig A. , Kopelovich Levy , Athar Mohammad
Published: April 2012

The biguanide metformin is widely used for the treatment of Type‐II diabetes. Its antiproliferative and pro‐apoptotic effects in various tumor cells suggest its potential candidacy for cancer chemoprevention. Herein, we report that metformin significantly inhibited human epidermoid A431 tumor xenograft growth in nu/nu mice, which was associated with a significant reduction in proliferative biomarkers PCNA and cyclins D1/B1. This tumor growth reduction was accompanied by the enhanced apoptotic cell death and an increase in Bax:Bcl2 ratio. The mechanism by which metformin manifests antitumor effects appears to be dependent on the inhibition of nuclear factor kappa B (NFkB) and mTOR signaling pathways. Decreased phosphorylation of NFkB inhibitory protein IKBα together with reduced enhancement of NFkB transcriptional target proteins, iNOS/COX‐2 were observed. In addition, a decrease in the activation of ERK/p38‐driven MAP kinase signaling was seen. Similarly, AKT signaling activation as assessed by the diminished phosphorylation at Ser473 with a concomitant decrease in mTOR signaling pathway was also noted as phosphorylation of mTOR regulatory proteins p70S6K and 4E‐BP‐1 was significantly reduced. Consistently, decreased phosphorylation of GSK3β, which is carried out by AKT kinases was also observed. These results suggest that metformin blocks SCC growth by dampening NFkB and mTOR signaling pathways.
Frequency of VKORC1 (C1173T) and CYP2C9 genetic polymorphisms in Egyptians and their influence on warfarin maintenance dose: proposal for a new dosing regimen
Authors: EL DIN M. S. , AMIN D. G. , RAGAB S. B. , ASHOUR E. E. , MOHAMED M. H. , MOHAMED A. M.
Published: April 2012

Introduction:  Warfarin is one of the most widely used anticoagulants, yet interindividual differences in drug response, a narrow therapeutic range and a high risk of bleeding or stroke complicate its use. We aimed to determine the allele and genotype frequency of VKORC1 1173 C>T, CYP2C9*2 and CYP2C9*3 variant polymorphisms in the Egyptian population and to evaluate their influence on the interindividual differences in warfarin dosage.

Methods:  A total of 154 unrelated healthy adult patients and 46 warfarin‐treated patients were included. SYBR Green‐based real‐time polymerase chain reaction (PCR) assay was used for studying VKORC1 (C1173T) and CYP2C9*3 polymorphisms. Mutagenically separated PCR assay was used to detect the CYP2C9*2 allele.

Results:  VKORC1 genotype frequencies were 11%, 24% and 65% for CC, CT and TT, respectively. The prevalence of CYP2C9 haplotypes was 81% (*1\*1), 3.3% (*1\*2), 9.7% (*1\*3), 4.5% (*2\*2) and 0.65% (2\*3 and *3\*3). VKORC1 TT and CYP2C9*2\*2 were associated with a significantly lower warfarin dose. VKORC1 and CYP2C9 accounted for 31.7% and 15.6% of warfarin dose variability, respectively, and together with clinical factors explained 61.3% of total variability.

Conclusion:  VKORC1‐TT and CYP2C9 *1/*1 are the most prevalent genotypes among Egyptians. Patients with VKORC1‐TT genotype required a lower warfarin dose.
Exercise Training in Heart Failure With Preserved Systolic Function: A Randomized Controlled Trial of the Effects on Cardiac Function and Functional Capacity
Authors: Smart Neil A. , Haluska Brian , Jeffriess Leanne , Leung Dominic
Published: April 2012

©2012 Wiley Periodicals Inc.

Exercise training improves functional capacity in patients with exercise limitation attributed to systolic dysfunction (SD), but exercise training effects in patients with diastolic dysfunction is unclear. The authors determined the functional capacity, quality of life, and echocardiography responses of heart failure with preserved ejection fraction (HFpEF) patients to 16 weeks exercise training. Thirty patients with HFpEF were randomized to an exercise training or non‐exercising control group. The patients had a baseline mean age of 64±8 years, left ventricular ejection fraction 57%±10%, and peak oxygen consumption (peak VO2) of 13.3±3.8 mL O2/kg/min. Minnesota Living With Heart Failure and Hare‐Davis scores and echocardiographic measures (ejection fraction, systolic and diastolic tissue velocity and filling pressure [E/E′]) were performed at baseline and after 16 weeks of exercise training. The exercise training and non‐exercising control groups showed similar baseline VO2 (12.2±3.6 mL/kg/min vs 14.1±4.1 mL/kg/min), ejection fraction (58%±13% vs 57%±8%), and systolic and diastolic function. After exercise training the increment in peak VO2 in the exercise training group was (24.6%, P=.02), and the non‐exercising control group (5.1%, P=.19). VE/VCO2 slope was reduced by 12.7% in the exercise training group (P=.02) but was unchanged in the non‐exercising control group (P=.03). No significant changes in diastolic or systolic function were noted in either group. Quality‐of‐life and depression scores were unchanged with exercise training. Changes in peak VO2 and VE/VCO2 slope were unrelated to measures of diastolic and systolic function. In patients with exercise limitation attributed to HFpEF, the improvement in peak VO2 with exercise training was not clearly related to changes in cardiac function. Congest Heart Fail.
Clinical Picture and Social Characteristics of Super‐Elderly Patients With Heart Failure in Japan
Authors: Kawai Yu , Inoue Nobutaka , Onishi Kazuo
Published: April 2012

©2012 Wiley Periodicals Inc.

The number of super‐elderly patients older than 80 years with chronic heart failure (HF) is dramatically increased in Japan; however, therapeutic strategies for patients 80 years or older remains to be established. The present investigation was undertaken to clarify the clinical picture and socioeconomic characteristics of super‐elderly HF patients. A total of 380 consecutive patients with acute HF or acutely worsening chronic HF were divided into three groups according to age: patients younger than 60 years, those 60 to 80 years, and those 80 years or older (super‐elderly group). HF patients in the super‐elderly group initially presented with more atypical symptoms at admission compared with those in the younger age group. The prevalence of HF with preserved ejection fraction was more pronounced compared with the patients in the younger age group. Furthermore, the social background was quite different for the 3 groups in several respects: recurrent hospitalization, the prevalence of dementia, and the number of patients living alone all increased with age. The lack of social support in patients with HF is a problem that needs to be resolved in the “super‐graying” societies such as Japan.
Schwartz–Jampel syndrome: a review of the literature and case report
Authors: Mallineni Sreekanth K. , Yiu Cynthia K. Y. , King Nigel M.
Published: April 2012

ABSTRACT  Schwartz–Jampel syndrome (SJS) is a rare autosomal recessive skeletal dysplasia associated with myotonia. The manifestations of SJS include short stature, blepharophimosis, and skeletal anomalies. The combination of skeletal and muscular abnormalities may result in oro‐dental manifestations such as atypical facies, with micrognathia, microstomia, pursed lips, crossbite, cleft palate, as well as mandibular hypoplasia, the risk of dentigerous cysts, and impacted teeth. The use of general anesthesia in patients with SJS is dangerous, as there is a risk of malignant hyperthermia. The purpose of this paper is to describe a 3‐year‐old Chinese boy diagnosed with SJS at birth. His intra‐oral examination revealed significant dental findings such as dentin defects with generalized attrition and hypodontia of the permanent dentition. Comprehensive dental treatment was provided at the same time as lower right limb surgery to reduce the potential complications with general anesthesia.
A prognostic signature of defective p53‐dependent G1 checkpoint function in melanoma cell lines
Authors: Carson Craig , Omolo Bernard , Chu Haitao , Zhou Yingchun , Sambade Maria J. , Peters Eldon C. , Tompkins Patrick , Simpson Dennis A. , Thomas Nancy E. , Fan Cheng , Sarasin Alain , Dessen Philippe , Shields Janiel M. , Ibrahim Joseph G. , Kaufmann William K.
Published: April 2012

Melanoma cell lines and normal human melanocytes (NHM) were assayed for p53‐dependent G1 checkpoint response to ionizing radiation (IR)‐induced DNA damage. Sixty‐six percent of melanoma cell lines displayed a defective G1 checkpoint. Checkpoint function was correlated with sensitivity to IR with checkpoint‐defective lines being radio‐resistant. Microarray analysis identified 316 probes whose expression was correlated with G1 checkpoint function in melanoma lines (P ≤ 0.007) including p53 transactivation targets CDKN1A, DDB2, and RRM2B. The 316 probe list predicted G1 checkpoint function of the melanoma lines with 86% accuracy using a binary analysis and 91% accuracy using a continuous analysis. When applied to microarray data from primary melanomas, the 316 probe list was prognostic of 4‐yr distant metastasis‐free survival. Thus, p53 function, radio‐sensitivity, and metastatic spread may be estimated in melanomas from a signature of gene expression.
Combination of Low‐Dose Bupivacaine and Opioids Provides Satisfactory Analgesia with Less Intraoperative Hypotension for Spinal Anesthesia in Cesarean Section
Authors: Qiu Man‐Tang , Lin Fu‐Qing , Fu Shu‐Kun , Zhang Heng‐Bin , Li Hui‐Hua , Zhang Li‐Ming , Li Quan
Published: April 2012

SUMMARY  Aims: This meta‐analysis was undertaken to compare the three most common drug regimens of bupivacaine in spinal anesthesia for cesarean section: high‐dose bupivacaine (≥10 mg, HB), low‐dose bupivacaine (<10 mg, LB) and combination of low‐dose bupivacaine and opioids (LBO). Methods: Databases of MEDLINE, EMBASE, and Cochrane Library were searched (updated on October 30, 2011). Primary endpoints were the incidence of intraoperative hypotension and analgesia efficacy. Pooled risk ratio (RR) or standard mean difference and their 95% confidence intervals (95% CI) were calculated. A RR <1 indicates that LB or LBO regimen is associated with less intraoperative complications and better anesthesia or analgesia efficacy. Results: A total of 11 randomized controlled trials including 605 parturients were analyzed. Results of this meta‐analysis showed that compared with HB regimen, LB regimen decreased the incidence of intraoperative hypotension (RR = 0.64, 95% CI: 0.42–0.96) with less satisfactory analgesia (fixed model, RR = 1.50, 95% CI: 1.14–1.98). LBO regimen significantly reduced the incidence of intraoperative hypotension (RR = 0.52, 95% CI: 0.33–0.82) with reliable analgesia efficacy (RR = 2.56, 95% CI: 0.77–8.48). Conclusion: Compared with conventional HB regimen and LB regimen, LBO regimen not only reduced intraoperative hypotension but also provided reliable analgesia. Therefore, LBO regimen should be considered as the preferred drug combination for spinal anesthesia in cesarean section.
How the Bladder Senses? A Five‐Grade Measure
Authors: TSUNOYAMA Kuniko , SAKAKIBARA Ryuji , TAKAHASHI Osamu , SUGIYAMA Megumi , UCHIYAMA Tomoyuki , TATENO Fuyuki , KISHI Masahiko , TSUYUSAKI Yohei , YAMAMOTO Tatsuya , TANABE Kazunari
Published: April 2012

Objectives: During bladder filling, the bladder starts to sense it and the sensation steadily increases. However, little is known concerning volume‐sensory correlation in normal bladder and pressure‐sensory correlation during detrusor overactivity (DO). We aimed to real‐time assess bladder sensation in normal bladder and DO using a five‐grade measure.

Methods: We enrolled 74 normal individuals and 87 patients with DO (51 terminal, 36 phasic). During slow bladder filling, we instructed individuals to indicate sensation in five grades: 1, first sensation; 2, obviously greater than 1 but less than 3; 3, first desire to void when he or she usually goes to toilet; 4, obviously greater than 3 but less than 5; and 5, strong desire to void. We also instructed individuals to report other sensations, such as pain.

Results: The five‐grade measure is feasible in all participants, showing a volume and pressure‐ sensory correlation. Among the five grades, grade 0 to 1 was the longest, followed by grade 4 to 5, in all participants. Grade 0 to 1 in phasic DO and grade 4 to 5 in terminal and phasic DO were shorter than those in normal bladder (P < 0.05). Eighty‐six percent of patients with DO reported that the rapidly increased sensory grade is akin to urinary urgency in daily life.

Conclusion: The five‐grade measure is feasible to assess a volume and pressure‐sensory correlation. Using this measure the sensory grade rapidly increased during DO compared with normal bladder, and 86% of the patients with DO reported that it is akin to urinary urgency in daily life.
Efficacy of rosuvastatin for the treatment of non‐alcoholic steatohepatitis with dyslipidemia: An open‐label, pilot study
Authors: Nakahara Takashi , Hyogo Hideyuki , Kimura Yuki , Ishitobi Tomokazu , Arihiro Koji , Aikata Hiroshi , Takahashi Shoichi , Chayama Kazuaki
Published: April 2012

Aim:  Statins, an inhibitor of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase, are reported to be useful for the treatment of non‐alcoholic steatohepatitis (NASH). Currently, there is no proven therapy for NASH. In this study, we assessed the efficacy of rosuvastatin in NASH patients with dyslipidemia.

Methods:  Nineteen patients with biopsy‐proven NASH with dyslipidemia who agreed to participate in this prospective study were enrolled. The patients were treated for 24 months with 2.5 mg/day rosuvastatin. Clinical and histological alterations were comparatively evaluated before and after treatment. Standard weight‐loss counseling was continued during the treatment period. Follow‐up liver biopsy was performed in nine patients.

Results:  Twenty‐six percent of patients had hyperlipoproteinemia type IIa and 74% had hyperlipoproteinemia type IIb at baseline. Body mass indices were not significantly changed during the treatment. The levels of transaminases were relatively low at the beginning, and were not significantly changed during the treatment. Lipid profiles were significantly improved by the treatment with rosuvastatin for 24 months. While non‐alcoholic fatty liver disease activity score and fibrotic stage did not change significantly in all patients, they were improved in 33.3% and 33.3% individual patients, and stayed stable in 33.3% and 55.6%, respectively.

Conclusion:  NASH‐related metabolic parameters improved with therapy including histology in some patients. However, one of nine patients had progression of fibrosis during the treatment. Our pilot study demonstrated the efficacy of rosuvastatin for the treatment of NASH with dyslipidemia, even if transaminases are not so elevated and controlled trials are needed in the future.
Effect of Tolfenamic Acid on Canine Cancer Cell Proliferation, Specificity Protein (Sp) Transcription Factors, and Sp‐Regulated Proteins in Canine Osteosarcoma, Mammary Carcinoma, and Melanoma Cells
Authors: Wilson H. , Chadalapaka G. , Jutooru I. , Sheppard S. , Pfent C. , Safe S.
Published: April 2012

Background

Tolfenamic acid (TA) is an NSAID currently under investigation as an anticancer agent in humans. TA induces proteosome‐dependent degradation of transcription factors Sp 1, 3, and 4. These proteins are known to be overexpressed in many human cancers.

Hypothesis

To evaluate the protein expression of Sps in canine tissue, and efficacy of TA against several canine tumor cell lines.

Methods

Six canine cell lines (2 osteosarcoma, 2 mammary carcinoma, 2 melanoma) were evaluated. Protein levels of Sp 1–4 and their downstream targets were evaluated using Western Blots. Cell survival and TUNEL assays were performed on cell lines, and Sp1 expression was evaluated on histologic samples from archived canine cases.

Animals

Six immortalized canine cancer cell lines derived from dogs were used. Archived tissue samples were also used.

Results

Sps were highly expressed in all 6 cell lines and variably expressed in histologic tissues. TA decreased expression of Sps 1–4 in all cell lines. All of the downstream targets of Sps were inhibited in the cell lines. Variable Sp1 expression was identified in all histologic samples examined. TA significantly inhibited cell survival in all cell lines in a dose dependant fashion. The number of cells undergoing apoptosis was significantly increased (P < .05) in all cell lines after exposure to TA in a dose‐dependent fashion.

Conclusions, and Clinical Importance

Tolfenamic acid is a potential anticancer NSAID and further investigation is needed to determine its usefulness in a clinical setting.
Anti-tumour effects of elatol, a marine derivative compound obtained from red algae Laurencia microcladia
Authors: Campos Andreza , Souza Christiane Borges , Lhullier Cintia , Falkenberg Miriam , Schenkel Eloir Paulo , Ribeiro-do-Valle Rosa Maria , Siqueira Jarbas Mota
Published: April 2012

Objectives

This paper aims to evaluate the anti-tumour properties of elatol, a compound (sesquiterpene) isolated from algae Laurencia microcladia.

Methods

In-vitro and in-vivo anti-tumour properties of elatol were investigated using: MTT assays to assess the cytotoxic effects; flow cytometry analysis to examine the cell cycle and apoptosis; Western blot analysis for determination of the expression of cell cycle and apoptosis proteins; and study of in-vivo tumour growth in mice (C57Bl6 mice bearing B16F10 cells).

Key findings

Elatol exhibited a cytotoxic effect, at least in part, by inducing cell cycle arrest in the G1 and the sub-G1 phases, leading cells to apoptosis. Western blot analysis demonstrated that elatol reduced the expression of cyclin-D1, cyclin-E, cyclin-dependent kinase (cdk)2 and cdk4. A decrease in bcl-xl and an increase in bak, caspase-9 and p53 expression was also observed. In the in-vivo experiment, treatment with elatol was able to reduce tumour growth in C57Bl6 mice.

Conclusions

Elatol promotes a delay in the cell cycle, probably in the G1/S transition, activating the apoptotic process and this could be responsible, at least in part, for the in-vivo effects observed. Taken together, the in-vitro and in-vivo experiments suggested that elatol has anti-tumour properties. Further studies should be conducted to clarify the mechanism of action.
Investigation into the effect of varying l-leucine concentration on the product characteristics of spray-dried liposome powders
Authors: Chen Kun-Hung , Mueannoom Wunlapa , Gaisford Simon , Kett Vicky L
Published: April 2012

Objectives

Spray-dried formulations offer an attractive delivery system for administration of drug encapsulated into liposomes to the lung, but can suffer from low encapsulation efficiency and poor aerodynamic properties. In this paper the effect of the concentration of the anti-adherent l-leucine was investigated in tandem with the protectants sucrose and trehalose.

Methods

Two manufacturing methods were compared in terms of their ability to offer small liposomal size, low polydispersity and high encapsulation of the drug indometacin.

Key findings

Unexpectedly sucrose offered the best protection to the liposomes during the spray drying process, although formulations containing trehalose formed products with the best powder characteristics for pulmonary delivery; high glass transition values, fine powder fraction and yield. It was also found that l-leucine contributed positively to the characteristics of the powders, but that it should be used with care as above the optimum concentration of 0.5% (w/w) the size and polydispersity index increased significantly for both disaccharide formulations.

Conclusions

The method of liposome preparation had no effect on the stability or encapsulation efficiency of spray-dried powders containing optimal protectant and anti-adherent. Using l-leucine at concentrations higher than the optimum level caused instability in the reconstituted liposomes.
Role of Bcl-2 in tumour cell survival and implications for pharmacotherapy
Authors: Tomek Mary , Akiyama Toru , Dass Crispin R
Published: April 2012

Objectives

Bcl-2 is a protein that inhibits apoptosis, leading to cell survival. The Bcl-2 family has six different anti-apoptotic proteins, three pro-apoptotic proteins that are similar in structure, and other integrating proteins that function as promotors or inhibitors in the progression of apoptosis. In this discussion paper, we provide an overview of apoptosis, the role of Bcl-2 in normal cellular and molecular processes, and the role of Bcl-2 in tumour cell survival. It focuses primarily on anti-apoptotic Bcl-2, its activation in cancer, the manner in which it regulates the intrinsic and extrinsic mechanisms of apoptosis, and its broad molecular interactions with other critical proteins in the cell. Certain cancer treatments are reviewed and related directions for the future are presented.

Key findings

Apoptosis is common to all organisms – for eukaryotes it is a normal process of development and regeneration. The rate at which apoptosis occurs is critical to the survival of the organism, as too much can lead to the onset of degenerative diseases such as dementia, and too little may lead to cancer. FKBP-38 is a binding protein that has been discovered to be upregulated in highly aggressive cancers and binds to Bcl-2 rather than the pro-apoptotics to induce a state of hyper-mitosis. A short binding protein (Nur-77) provides new insights into Bcl-2 ‘masking’. Nurr-77 binds to Bcl-2 and exposes the BH3 domain, transforming it from a cancer promoter to an unorthodox cancer inhibitor. This presents in itself an interesting and exciting opportunity – increasing the rate of apoptosis in neoplastic cells that are usually protected by Bcl-2 activity at the mitochondria.

Development of drugs in the form of BH3-only and BH123 mimetic drugs provide a interesting avenue for cancer therapy for the future. Drugs that can either promote, or mimic anti-IAP activity such as Smac/Diablo would certainly be productive, thereby inducing apoptosis. Medicinal usage which can effectively suppress FKBP38 in Bcl-2-dependent cancers would provide further arsenal to combat apoptotic irregularities, particularly a treatment that is more dominant than kinetin riboside. WAVE-1 inhibitors may effectively suppress the phosphorylation of Bcl-2, thereby potentially reducing hyper-mitosis and increasing apoptosis. Recent findings shed molecular light on PDT, namely ER stress, and potential for anti-cancer therapy via either apoptosis or autophagy. A drug that can effectively upregulate Nurr-77, thereby masking the anti-apoptotic properties of Bcl-2, would indeed be life-saving for cancer patients.
The Model of Pathways to Treatment: Conceptualization and integration with existing theory
Authors: Scott S. E. , Walter F. M. , Webster A. , Sutton S. , Emery J.
Published: April 2012

Background. Studying and understanding pathways to diagnosis and treatment is vital for the development of successful interventions to encourage early detection, presentation, and diagnosis. An existing framework posited to describe the decisional and behavioural processes that occur prior to treatment (Andersen et al.'s General Model of Total Patient Delay) does not appear to match the complex and dynamic nature of the pathways into and through the health care system or provide a clear framework for research. Therefore a revised descriptive framework, the Model of Pathways to Treatment, has been proposed.

Purpose. This paper presents the concepts and definitions of the Model of Pathways to Treatment and specifies how the model can encompass existing psychological theory, with particular focus on the Appraisal and Help‐seeking intervals. The potential and direction for future work is also discussed.

Statement of contribution

What is already known on this subject?

The use of theory is often lacking in existing research into delays in presentation, diagnosis and treatment of illness.

What does this study add?

A detailed account of the concepts and definitions of a revised framework: the Model of Pathways to Treatment.

Specification of how the Model of Pathways to Treatment can encompass existing psychological theory such as the Common Sense Model of Illness Self‐regulation and Social Cognitive Theory.
Three-Dimensional Local Yield Maps of Hard Coating Under Sliding Contact
Authors: Zhang P. Y. , Diao D. F. , Wang Z. J.
Published: April 2012

The local yield maps for the identification of the yield initiation positions of hard coating on three-dimensional (3D) elastic half space under sliding contact were developed. In this study, the semi-analytical method (SAM), which is based on the conjugate gradient method (CGM) and the discrete convolution and fast Fourier transform (DC-FFT) technique, was employed to analyze the contact problem. By using this method, the von Mises stress distributions for various combinations of coating thicknesses, friction coefficients, and elastic moduli of the coating and substrate were calculated. Then, the positions of yield initiation were found with the calculated results by comparing the critical maximum contact pressure Pmax,c for von Mises yielding at or in the different positions (surface, coating, interface, and substrate), and the 3D-local yield maps were introduced in relation to the yield strength ratio of the coating to the substrate (Yf/Yb) and the ratio of the coating thickness to the Hertzian contact radius (t/a0). Finally, the effect of critical friction coefficient on the transition of yielding positions was discussed.