bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteoglycans in health and disease: novel roles for proteoglycans in malignancy and their pharmacological targeting
Authors: Theocharis Achilleas D. , Skandalis Spyridon S. , Tzanakakis George N. , Karamanos Nikos K.
Published: August 2010

The expression of proteoglycans (PGs), essential macromolecules of the tumor microenvironment, is markedly altered during malignant transformation and tumor progression. Synthesis of stromal PGs is affected by factors secreted by cancer cells and the unique tumor‐modified extracellular matrix may either facilitate or counteract the growth of solid tumors. The emerging theme is that this dual activity has intrinsic tissue specificity. Matrix‐accumulated PGs, such as versican, perlecan and small leucine‐rich PGs, affect cancer cell signaling, growth and survival, cell adhesion, migration and angiogenesis. Furthermore, expression of cell‐surface‐associated PGs, such as syndecans and glypicans, is also modulated in both tumor and stromal cells. Cell‐surface‐associated PGs bind various factors that are involved in cell signaling, thereby affecting cell proliferation, adhesion and motility. An important mechanism of action is offered by a proteolytic processing of cell‐surface PGs known as ectodomain shedding of syndecans; this facilitates cancer and endothelial cell motility, protects matrix proteases and provides a chemotactic gradient of mitogens. However, syndecans on stromal cells may be important for stromal cell/cancer cell interplay and may promote stromal cell proliferation, migration and angiogenesis. Finally, abnormal PG expression in cancer and stromal cells may serve as a biomarker for tumor progression and patient survival. Enhanced understanding of the regulation of PG metabolism and the involvement of PGs in cancer may offer a novel approach to cancer therapy by targeting the tumor microenvironment. In this minireview, the implication of PGs in cancer development and progression, as well as their pharmacological targeting in malignancy, are presented and discussed.
Evidence for the slow reaction of hypoxia‐inducible factor prolyl hydroxylase 2 with oxygen
Authors: Flashman Emily , Hoffart Lee M. , Hamed Refaat B. , Bollinger Jr J. Martin , Krebs Carsten , Schofield Christopher J.
Published: August 2010

The response of animals to hypoxia is mediated by the hypoxia‐inducible transcription factor. Human hypoxia‐inducible factor is regulated by four Fe(II)‐ and 2‐oxoglutarate‐dependent oxygenases: prolyl hydroxylase domain enzymes 1–3 catalyse hydroxylation of two prolyl‐residues in hypoxia‐inducible factor, triggering its degradation by the proteasome. Factor inhibiting hypoxia‐inducible factor catalyses the hydroxylation of an asparagine‐residue in hypoxia‐inducible factor, inhibiting its transcriptional activity. Collectively, the hypoxia‐inducible factor hydroxylases negatively regulate hypoxia‐inducible factor in response to increasing oxygen concentration. Prolyl hydroxylase domain 2 is the most important oxygen sensor in human cells; however, the underlying kinetic basis of the oxygen‐sensing function of prolyl hydroxylase domain 2 is unclear. We report analyses of the reaction of prolyl hydroxylase domain 2 with oxygen. Chemical quench/MS experiments demonstrate that reaction of a complex of prolyl hydroxylase domain 2, Fe(II), 2‐oxoglutarate and the C‐terminal oxygen‐dependent degradation domain of hypoxia‐inducible factor‐α with oxygen to form hydroxylated C‐terminal oxygen‐dependent degradation domain and succinate is much slower (approximately 100‐fold) than for other similarly studied 2‐oxoglutarate oxygenases. Stopped flow/UV‐visible spectroscopy experiments demonstrate that the reaction produces a relatively stable species absorbing at 320 nm; Mössbauer spectroscopic experiments indicate that this species is likely not a Fe(IV)=O intermediate, as observed for other 2‐oxoglutarate oxygenases. Overall, the results obtained suggest that, at least compared to other studied 2‐oxoglutarate oxygenases, prolyl hydroxylase domain 2 reacts relatively slowly with oxygen, a property that may be associated with its function as an oxygen sensor.

Structured digital abstract

 MINT‐7987711: PHD2 (uniprotkb:Q9GZT9) enzymaticly reacts (MI:0414) CODD (uniprotkb:Q16665) by enzymatic study (MI:0415)
Poly(ADP-Ribose) Polymerase Inhibition Improves Erectile Function in Diabetic Rats
Authors: Wan Zhihua H. , Li Wenzhou Z. , Li Yunzhu Z. , Chen Lin , Li Guohao H. , Hu Weifeng F. , Peng Song , Yu Jiajun J. , Guo Feng
Published: August 2010

Introduction

Erectile dysfunction (ED) is a common and hard-to-treat complication of diabetes mellitus (DM). Multiple lines of evidence have shown that poly(ADP-ribose) polymerase (PARP) activation plays an important role in neurovascular dysfunction in diabetes, which is the crucial mechanism for diabetic ED.

Aim

To investigate the preventive benefit of a PARP inhibitor in a rat model of ED induced by diabetes.

Methods

Established streptozotocin-diabetic male Sprague-Dawley rats were given PJ-34, a selective PARP inhibitor, by oral gavage at a dose of 10 mg/kg twice daily for 8 weeks. Erectile responses under electrical stimulation of the cavernous nerve, PARP activity and reactive oxygen species (ROS) production were measured. Nitric oxide synthase (NOS) isoforms were evaluated by Western blot and real-time quantitative PCR. Nuclear factor-kappa B activition and apoptosis in corpus cavernosa (CC) were also investigated.

Main Outcome Measures

The effects of PARP inhibition on the development of diabetic ED were determined.

Results

Diabetes markedly attenuated the erectile responses (intracavernosal pressure/mean systemic arterial blood pressure) and these were partially prevented by PJ-34 treatment. Promoted oxidative stress associated PARP activation was found in CC from vehicle-treated diabetic rats. PJ-34 blocked PARP activity and the diabetes-associated ROS generation. Decreased expression and activity of constitutive NOS (cNOS), including endothelial NOS (eNOS) and neuronal NOS (nNOS), associated with enhanced inducible NOS (iNOS) expression and activity were observed in vehicle-treated diabetic rats. Although PJ-34 had no effect on eNOS expression, it significantly prevented the decrease in nNOS expression and cNOS activity, and inhibited iNOS expression and activity in diabetic rats. PARP blockade by PJ-34 to some extent prevented diabetes-associated apoptosis and NF-κB activation.

Conclusions

Our results indicate that PARP activation plays an important role in the pathogenesis of diabetic ED and PARP inhibition may be a promising strategy to prevent development of diabetic ED.
p38 Mitogen-Activated Protein Kinase (MAPK) Increases Arginase Activity and Contributes to Endothelial Dysfunction in Corpora Cavernosa from Angiotensin-II-Treated Mice
Authors: Toque Haroldo A. , Romero Maritza J. , Tostes Rita C. , Shatanawi Alia , Chandra Surabhi , Carneiro Zidonia N. , Inscho Edward W. , Webb Robert Clinton , Caldwell Ruth B. , Caldwell Robert William
Published: August 2010

Introduction

Angiotensin II (AngII) activates p38 mitogen-activated protein kinase (MAPK) and elevates arginase activity in endothelial cells. Upregulation of arginase activity has been implicated in endothelial dysfunction by reducing nitric oxide (NO) bioavailability. However, signaling pathways activated by AngII in the penis are largely unknown.

Aim

We hypothesized that activation of p38 MAPK increases arginase activity and thus impairs penile vascular function in AngII-treated mice.

Methods

Male C57BL/6 mice were implanted with osmotic minipumps containing saline or AngII (42 µg/kg/h) for 14 days and cotreated with p38 MAPK inhibitor, SB 203580 (5 µg/kg/day), beginning 2 days before minipump implantation. Systolic blood pressure (SBP) was measured. Corpus cavernosum (CC) tissue was used for vascular functional studies and protein expression levels of p38 MAPK, arginase and constitutive NO synthase (NOS), and arginase activity.

Main Outcome Measures

Arginase expression and activity; expression of phospho-p38 MAPK, endothelial NOS (eNOS) and neuronal NOS proteins; endothelium-dependent and nitrergic nerve-mediated relaxations were determined in CC from control and AngII-infused mice.

Results

AngII increased SBP (22%) and increased CC arginase activity and expression (∼twofold), and phosphorylated P38 MAPK levels (30%) over control. Treatment with SB 203580 prevented these effects. Endothelium-dependent NO-mediated relaxation to acetylcholine was significantly reduced by AngII and this effect was prevented by SB 203580 (P <0.01). AngII (2 weeks) did not alter nitrergic function. However, SB 203580 significantly increased nitrergic relaxation in both control and AngII tissue at lower frequencies. Maximum contractile responses for phenylephrine and electrical field stimulation were increased by AngII (56% and 171%, respectively) and attenuated by SB 203580 treatment. AngII treatment also decreased eNOS phosphorylation at Ser-1177 compared to control. Treatment with SB 203580 prevented all these changes.

Conclusion

p38 MAPK inhibition corrects penile arginase activity and protects against erectile dysfunction caused by AngII.
The Development of a Sensory Substitution System for the Sexual Rehabilitation of Men with Chronic Spinal Cord Injury
Authors: Borisoff Jaimie F. , Elliott Stacy L. , Hocaloski Shea , Birch Gary E.
Published: August 2010

Introduction

Sexual health is often severely impacted after spinal cord injury (SCI). Current research has primarily addressed male erection and fertility, when in fact pleasure and orgasm are top priorities for functional recovery. Sensory substitution technology operates by communicating input from a lost sensory pathway to another intact sensory modality. It was hypothesized that through training and neuroplasticity, mapped tongue sensations would be interpreted as sensory perceptions arising from insensate genitalia, and improve the sexual experience.

Aim

To report the development of a sensory substitution system for the sexual rehabilitation of men with chronic SCI.

Methods

Subjects performed sexual self-stimulation while using a novel sensory substitution device that mapped the stroking motion of the hand to a congruous flow of electrocutaneous sensations on the tongue.

Main Outcome Measures

Three questionnaires, along with structured interviews, were used to rate the perceived sexual sensations following each training session.

Results

Subjects completed 20 sessions over approximately 8 weeks of training. Each subject reported an increased level of sexual pleasure soon after training with the device. Each subject also reported specific perceptions of cutaneous-like sensations below their lesion that matched their hand motion. Later sessions, while remaining pleasurable and interesting, were inconsistent, and no subject reported an orgasmic feeling during a session. The subjects were all interested in continuing training with the device at home, if possible, in the future.

Conclusions

This study is the first to show that sensory substitution is a possible therapeutic avenue for sexual rehabilitation in people lacking normal genital sexual sensations. However more research, for instance on frequency and duration of training, is needed in order to induce functional lasting neuroplasticity. In the near term, SCI rehabilitation should more fully address sexuality and the role of neuroplasticity for promoting the maximal potential for sexual pleasure and orgasm.
A New Female Rat Animal Model for Hypoactive Sexual Desire Disorder; Behavioral and Pharmacological Evidence
Authors: Snoeren Eelke M.S. , Chan Johnny S.W. , De Jong Trynke R. , Waldinger Marcel D. , Olivier Berend , Oosting Ronald S.
Published: August 2010

Introduction

Female sexual dysfunction (FSD) affects 33–48% of women. Female rats with low sexual activity might model FSD.

Aim

In this study, we have investigated whether in a population of normal female rats, subpopulations of rats exist with different levels of sexual behavior.

Methods

Sexually experienced, intact, estradiol-primed female rats were placed in an empty compartment adjacent to a compartment with a male. The females were allowed, during 30 minutes, to switch between the compartments via a hole through which only the females could pass (paced mating). Next, we investigated the acute effects on female sexual behavior of apomorphine, a D1- and D2-type dopamine receptor agonist, (+/–)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (±8-OH-DPAT), a 5-HT1A receptor agonist, and paroxetine, a selective serotonin reuptake inhibitor.

Main Outcome Measures

Time spent in compartments, proceptive behaviors, contact–return latencies, and percentages of exits were quantified.

Results

Based on their behavior in the paced mating sex test, estradiol-primed, intact female rats can be divided into three groups: those that mostly avoid the male, a large middle group, and those that mostly approach the male. The avoiders also showed significantly less proceptive behavior than the male approachers. The sexual behavior of the females was relatively stable over time, suggesting the existence of different endophenotypes in female rats. Apomorphine and ±8-OH-DPAT had an inhibiting effect on sexual behavior, but only females dosed with apomorphine showed a different response in avoiders and approachers, more inhibiting effect in avoiders than approachers. Paroxetine had no effect on proceptive behavior.

Discussion

The stable, male-avoiding behavior of some females might correspond to the characteristics of women with FSD. Therefore, these avoiders are a promising new model for FSD, specifically for sexual desire and/or arousal disorders. Furthermore, the apomorphine data suggest that differences in the dopamine system may (partly) underlie the differences in sexual behaviors between avoiders and approachers.
Neuroimaging of Love: fMRI Meta-Analysis Evidence toward New Perspectives in Sexual Medicine
Authors: Ortigue Stephanie , Bianchi-Demicheli Francesco , Patel Nisa , Frum Chris , Lewis James W.
Published: August 2010

Introduction

Brain imaging is becoming a powerful tool in the study of human cerebral functions related to close personal relationships. Outside of subcortical structures traditionally thought to be involved in reward-related systems, a wide range of neuroimaging studies in relationship science indicate a prominent role for different cortical networks and cognitive factors. Thus, the field needs a better anatomical/network/whole-brain model to help translate scientific knowledge from lab bench to clinical models and ultimately to the patients suffering from disorders associated with love and couple relationships.

Aim

The aim of the present review is to provide a review across wide range of functional magnetic resonance imaging (fMRI) studies to critically identify the cortical networks associated with passionate love, and to compare and contrast it with other types of love (such as maternal love and unconditional love for persons with intellectual disabilities).

Methods

Retrospective review of pertinent neuroimaging literature.

Main Outcome Measures

Review of published literature on fMRI studies of love illustrating brain regions associated with different forms of love.

Results

Although all fMRI studies of love point to the subcortical dopaminergic reward-related brain systems (involving dopamine and oxytocin receptors) for motivating individuals in pair-bonding, the present meta-analysis newly demonstrated that different types of love involve distinct cerebral networks, including those for higher cognitive functions such as social cognition and bodily self-representation.

Conclusions

These metaresults provide the first stages of a global neuroanatomical model of cortical networks involved in emotions related to different aspects of love. Developing this model in future studies should be helpful for advancing clinical approaches helpful in sexual medicine and couple therapy.
Erectile Dysfunction in Young Non-Obese Type II Diabetic Goto-Kakizaki Rats is Associated with Decreased eNOS Phosphorylation at Ser1177
Authors: Carneiro Fernando S. , Giachini Fernanda R.C. , Carneiro Zidonia N. , Lima Victor V. , Ergul Adviye , Webb R. Clinton , Tostes Rita C.
Published: August 2010

Introduction

Diabetes mellitus (DM) is a risk factor for erectile dysfunction (ED). Although type 2 DM is responsible for 90–95% diabetes cases, type 1 DM experimental models are commonly used to study diabetes-associated ED.

Aim

Goto-Kakizaki (GK) rat model is relevant to ED studies since the great majority of patients with type 2 diabetes display mild deficits in glucose-stimulated insulin secretion, insulin resistance, and hyperglycemia. We hypothesized that GK rats display ED which is associated with decreased nitric oxide (NO) bioavailability.

Methods

Wistar and GK rats were used at 10 and 18 weeks of age. Changes in the ratio of intracavernosal pressure/mean arterial pressure (ICP/MAP) after electrical stimulation of cavernosal nerve were determined in vivo. Cavernosal contractility was induced by electrical field stimulation (EFS) and phenylephrine (PE). In addition, nonadrenergic-noncholinergic (NANC)- and sodium nitroprusside (SNP)-induced relaxation were determined. Cavernosal neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) mRNA and protein expression were also measured.

Main Outcome Measure

GK diabetic rats display ED associated with decreased cavernosal expression of eNOS protein.

Results

GK rats at 10 and 18 weeks demonstrated impaired erectile function represented by decreased ICP/MAP responses. Ten-week-old GK animals displayed increased PE responses and no changes in EFS-induced contraction. Conversely, contractile responses to EFS and PE were decreased in cavernosal tissue from GK rats at 18 weeks of age. Moreover, GK rats at 18 weeks of age displayed increased NANC-mediated relaxation, but not to SNP. In addition, ED was associated with decreased eNOS protein expression at both ages.

Conclusion

Although GK rats display ED, they exhibit changes in cavernosal reactivity that would facilitate erectile responses. These results are in contrast to those described in other experimental diabetes models. This may be due to compensatory mechanisms in cavernosal tissue to overcome restricted pre-penile arterial blood supply or impaired veno-occlusive mechanisms. Carneiro FS, Giachini FRC, Carneiro ZN, Lima VV, Ergul A, Webb RC, and Tostes RC. Erectile dysfunction in young non-obese type II diabetic Goto-Kakizaki rats is associated with decreased eNOS phosphorylation at Ser1177.
The Role of the Dopamine Transporter in Dopamine‐Induced DNA Damage
Authors: Fazeli Gholamreza , Oli Rajaraman Gnana , Schupp Nicole , Stopper Helga
Published: August 2010

The neurotransmitter dopamine causes DNA damage, oxidative stress and is involved in the pathology of neurological diseases. To elucidate this potential link we investigated the mechanism of dopamine‐induced DNA damage. We studied the role of the dopamine transporter (DAT) in MDCK and MDCK‐DAT cells, containing the human DAT gene. After treatment with dopamine, only MDCK‐DAT cells showed elevated chromosomal damage and dopamine uptake. Although stimulation of dopamine type 2 receptor (D2R) with quinpirole in the absence of dopamine did not induce genotoxicity in rat neuronal PC12 cells, interference with D2R signaling by inhibition of G‐proteins, phosphoinositide 3 kinase and extracellular signal‐regulated kinases reduced dopamine‐induced genotoxicity and affected the ability of DAT to take up dopamine. Furthermore, the D2R antagonist sulpiride inhibited the dopamine‐induced migration of DAT from cytosol to cell membrane. To determine whether oxidation of dopamine by monoamine oxidase (MAO) is relevant in its genotoxicity, we inhibited MAO, which reduced the formation of micronuclei and of the oxidative DNA adduct 8‐oxodG. Overall, dopamine exerted its genotoxicityin vitroupon transport into the cells and oxidation by MAO. D2R signaling was involved in the genotoxicity of dopamine by affecting activation and cell surface expression of DAT and hence modulating dopamine uptake.
Mutation Analysis of CCM1, CCM2 and CCM3 Genes in a Cohort of Italian Patients with Cerebral Cavernous Malformation
Authors: D'Angelo Rosalia , Marini Valeria , Rinaldi Carmela , Origone Paola , Dorcaratto Alessandra , Avolio Maria , Goitre Luca , Forni Marco , Capra Valeria , Alafaci Concetta , Mareni Cristina , Garrè Cecilia , Bramanti Placido , Sidoti Antonina , Retta Saverio Francesco , Amato Aldo
Published: August 2010

Cerebral cavernous malformations (CCMs) are vascular lesions of the CNS characterized by abnormally enlarged capillary cavities. CCMs can occur as sporadic or familial autosomal dominant form. Familial cases are associated with mutations in CCM1[K‐Rev interaction trapped 1 (KRIT1)], CCM2 (MGC4607) and CCM3 (PDCD10) genes. In this study, a three‐gene mutation screening was performed by direct exon sequencing, in a cohort of 95 Italian patients either sporadic or familial, as well as on their at‐risk relatives. Sixteen mutations in 16 unrelated CCM patients were identified, nine mutations are novel: c.413T > C; c.601C > T; c.846 + 2T > G; c.1254delA; c.1255‐4delGTA; c.1681‐1682delTA in CCM1; c.48A > G; c.82‐83insAG in CCM2; and c.396G > A in CCM3 genes. The samples, negative to direct exon sequencing, were investigated by MLPA to search for intragenic deletions or duplications. One deletion in CCM1 exon 18 was detected in a sporadic patient. Among familial cases 67% had a mutation in CCM1, 5.5% in CCM2, and 5.5% in CCM3, whereas in the remaining 22% no mutations were detected, suggesting the existence of either undetectable mutations or other CCM genes. This study represents the first extensive research program for a comprehensive molecular screening of the three known genes in an Italian cohort of CCM patients and their at‐risk relatives.
Development of an ErbB‐overexpressing A‐431 Optical Reporting Tumor Xenograft Model to Assess Targeted Photodynamic Therapy Regimens
Authors: Savellano Mark D. , Owusu‐Brackett Nicci , Son Ji , Callier Thierri , Savellano Dagmar Högemann
Published: August 2010

To better assess the efficacy of erbB‐targeted therapies, it would help to have optical reporting human tumor xenograft models that abundantly express erbB receptors. A‐431 cells have frequently been used in erbB1‐targeting studies, but a well‐characterized optical reporting version of the cell line has not been readily available. In this study, optical reporting A‐431 clones were developed that express both a fluorescent protein reporter (green, GFP; or red, RFP) and a bioluminescent reporter, firefly luciferase. Reporter genes were transduced into cells using commercial lentiviral vectors, and clonal selection was carried out using a series of procedures. A number of clones were isolated for further characterization. A GFP/luciferase clone, A‐431/D4, and an RFP/luciferase clone, A‐431/G4, were obtained that exhibit erbB1 expression levels and tumor growth kinetics similar to the parental cells. To demonstrate the utility of the optical reporting clones, A‐431/G4 tumors were grown subcutaneously in nude mice and treated with vascular‐targeted photodynamic therapy (PDT), which targets the angiogenic consequences of erbB signaling. The A‐431/G4 tumor model permitted highly sensitive longitudinal monitoring of PDT treatment response using optical imaging. A‐431/D4 and A‐431/G4 optical reporting tumor models should also prove useful for assessing therapies that directly target the erbB1 receptor.
Inhibition of Histidine Ammonia Lyase by 8‐Methoxypsoralen and Psoralen‐oxidized Photoproducts
Authors: Reilly John T. , Troester Kyle A. , Tyner Trista T. , Vitale Dominick A. , Risher Tiffiany R.
Published: August 2010

The effect of 8‐methoxypsoralen‐UVA therapy on the catalysis of histidine to trans‐urocanic acid by histidine ammonia lyase (HAL, EC 4.3.1.3) was examined using an enzymatic assay from Sigma‐Aldrich where the growth of the trans‐urocanic acid peak at 277 nm was monitored. A Rayonet Photochemical Mini Reactor (Model RMR‐600) equipped with eight, 3500 Å light sources and a custom UVA filter (Model S‐BAL3 2.9 mm), from the Solar Light Company, were used to expose various reaction mixtures to broadband UVA light and UVA/UVB light. A UV‐Vis spectrophotometer (Model Shimadzu UV 2540) with a temperature‐controlled cell holder (Model TCC240) was used to monitor the growth of the trans‐urocanic peak. Results of dark‐binding experiments of 8‐methoxypsoralen in denatured ethanol indicate no inhibition of enzyme activity due to ethanol but noncompetitive inhibition due to 8‐methoxypsoralen. The effects of preirradiated 8‐methoxypsoralen, with both broadband UVA and UVA/UVB, indicate that inhibition was due to psoralen‐oxidized photoproducts. Inhibition of HAL was found when exposed to broadband UVA/UVB and to a lesser extent when exposed to broadband UVA.
Prevalence of the Metabolic Syndrome in Patients With Acute Coronary Syndrome in Six Middle Eastern Countries
Authors: Al Suwaidi Jassim , Zubaid Mohammad , El‐Menyar Ayman A. , Singh Rajvir , Rashed Wafa , Ridha Mustafa , Shehab Abdulla , Al‐Lawati Jawad , Amin Haitham , Al‐Mottareb Ahmed
Published: August 2010

J Clin Hypertens (Greenwich).

The objective of this study was to evaluate the prevalence and effect of the metabolic syndrome (MetS) on patients with acute coronary syndrome (ACS) in six Middle Eastern countries using the new definition of MetS. Analysis of the Gulf Registry of Acute Coronary Events (Gulf RACE), which included 8716 consecutive patients hospitalized with ACS, was conducted and patients were divided into two groups: patients with and patients without the MetS. Overall, 46% of patients had MetS. Patients with MetS were more likely to be female and less likely to be smokers. In‐hospital mortality and cardiogenic shock were comparable between the two groups, although MetS patients were more likely to have congestive heart failure and recurrent ischemia. In ST‐elevation myocardial infarction, MetS was also associated with increased risk of recurrent myocardial infarction and stroke. Using the recent MetS definition, MetS is highly prevalent among Middle Eastern patients presenting with ACS. MetS is associated with higher‐risk profile characteristics and increased risk for development of heart failure and recurrent myocardial ischemia without an increase in hospital mortality. J Clin Hypertens (Greenwich). 2010;12:890–899.
Distance‐based population classification software using mean‐field annealing
Authors: CANDY JOHN R. , WALLACE COLIN G. , BEACHAM TERRY D.
Published: August 2010

We describe a distance‐based clustering method using a proximity matrix of genetic distances to partition populations into genetically similar groupings. The optimization heuristic mean‐field annealing (MFA) was used to find locally optimal solutions where exhaustive search was not possible. To illustrate this method, we analysed both simulated and real data sets. Simulated data indicated that MFA successfully differentiated population groups, even with smallFSTvalues, as long as there was separation of within and between group distances. Reanalysis of microsatellite data from various human populations using mean‐fields found similar ethnic groups corresponding to major geographic regions reported byRosenberget al.(2002)who used the model‐based computer program Structure. However, with MFA, the Kalash population was found to group with other Central/South Asian populations instead of being the only member of its own genetic cluster. Europe/Middle East populations formed a separate group from Central/South Asian populations instead of being a single group in the Structure analysis. The MFA analysis determined the greatest genetic distances (largest mean intracluster distance) occurred in native American populations, identifying three groups instead of only one found with Structure. For conservation purposes, it is not only important to identify genetically similar groupings but also to determine the relative level of genetic differentiation captured within these groups. To illustrate this, we compare two separate MFA analyses of Chinook salmon (Oncorhynchus tshawytscha) populations from British Columbia, Canada. The software called PORGS‐MFA used in this article can be downloaded fromhttp://www.pac.dfo‐mpo.gc.ca/science/facilities‐installations/pbs‐sbp/mgl‐lgm/apps/porgs/index‐eng.htm.
Local retinal sensitivity in relation to specific retinopathy lesions in diabetic macular oedema
Authors: Soliman Wael , Hasler Pascal , Sander Birgit , Larsen Michael
Published: August 2010

Purpose:  To study microperimetric macular sensitivity in diabetic macular oedema (DMO) in relation to lesion characteristics obtained by optical coherence tomography (OCT), colour fundus photography, and fluorescein angiography (FA).

Methods:  The study comprised 20 eyes in 15 patients with nonproliferative diabetic retinopathy and recently diagnosed untreated DMO. Investigations included microperimetry, fluorescein angiography, colour fundus photography, and OCT. All measures and gradings were made for each of the nine fields of an early treatment diabetic retinopathy study macula template. Statistical analysis was made using Spearman’s nonparametric test including field and mean values within fields. Comparisons were made within the study population and with a normative microperimetry database.

Results:  Subnormal microperimetric sensitivity was associated with cystoid macular oedema, both in foveal petaloid (r = −0.50, p = 0.02) and extrafoveal honeycomb patterns (r = −0.8, p < 0.0001) and with outer nuclear layer cysts (r = −0. 5, p = 0.024), inner nuclear layer cysts (r = −0.31, p = 0.03), and hard exudate (r = −0.38, p = 0.0026). There was no detectable effect of focal noncystoid oedema (r = −0.16, p = 0. 48), diffuse noncystoid oedema (r = −0.14, p = 0.55), capillary nonperfusion (r = −0.33, p = 0.15), intraretinal haemorrhage (r = −0.15, p = 0.53), or serous retinal detachment (r = −0.11, p = 0.63). Foveal thickening was associated with locally reduced sensitivity (r = −0.54, p = 0.01). Foveal sensitivity was positively correlated to the visual acuity, with a correlation of 0.44 and a borderline significance (p = 0.0509).

Conclusions:  Macular hard exudates and cystoid oedema were associated with locally reduced sensitivity. Thus, the lesions associated with reduced sensitivity for a white‐on‐white stimulus were such lesions that cause light to be blocked or scattered before it reaches the photoreceptors, suggesting that optical effects are a major cause of sensitivity loss.
Comorbidities of dry eye disease: a nationwide population‐based study
Authors: Wang Tsung‐Jen , Wang I‐Jong , Hu Chao‐Chien , Lin Herng‐Ching
Published: August 2010

Purpose:  To investigate the comorbidities of dry eye disease in a nationwide population‐based data in Taiwan.

Methods:  This study features a study group and a comparison group. The study group comprised 12 007 patients who sought ambulatory care for treatment of dry eye in 2005 and 2006. In total, 36 021 randomly selected patients were in the comparison group. Conditional logistic regression analyses conditioned on gender, age, monthly income and level of urbanization of the community in which the patient resided were conducted to calculate the odds ratio (OR) for each of 33 comorbidities among patients with and without dry eye disease.

Results:  The regression analyses revealed that compared to patients without dry eye disease, patients with dry eye disease were more likely to have comorbidities of ischaemic heart disease (OR = 1.36), hyperlipidaemia (OR = 1.68), cardiac arrhythmias (OR = 1.55), peripheral vascular disorders (OR = 1.57), stroke (OR = 1.31), migraines (OR = 1.76), myasthenia gravis (OR = 2.85), RA (OR = 2.86), systemic lupus erythematosus (OR = 3.98), asthma (OR = 1.25), pulmonary circulation disorders (OR = 1.37), diabetes with complications (OR = 1.31), hypothyroidism (OR = 1.94), liver diseases (OR = 1.71), peptic ulcers (OR = 1.76), hepatitis B (OR = 1.64), deficiency anaemias (OR = 1.31), depression (OR = 2.11), psychoses (OR = 1.87) and solid tumours without metastasis (OR = 1.41).

Conclusions:  This study demonstrates significantly higher prevalence of medical comorbidities in patients with dry eye disease in Taiwan.
Retinopathy and visual impairment in diabetes, impaired glucose tolerance and normal glucose tolerance: the Nord‐Trøndelag Health Study (the HUNT study)
Authors: Sundling Vibeke , Platou Carl G. P. , Jansson Ragnhild Wivestad , Bertelsen Geir , Wøllo Erik , Gulbrandsen Pål
Published: August 2010

Purpose:  The aim of the study was to describe the prevalence of visual impairment and retinopathy and to investigate risk factors for retinopathy in persons with diabetes, screen‐detected diabetes, impaired glucose tolerance and normal glucose tolerance in a subpopulation of the HUNT study.

Methods:  We used a sample (n = 163) from a population‐based screening survey of hyperglycaemia, undertaken in 2004–2005 in Verdal, Norway. Baseline information was accessible through the second Nord‐Trøndelag Health Study (HUNT2), 1995–97. Data collection was made in 2005 and included patient history, refraction, visual acuity, cataract assessment and single‐field, nonmydriatic retinal photography. Retinal photographs were graded independently by two graders blinded to patient information. Data were analysed with standard statistical methods, and p < 0.05 was considered significant.

Results:  In all, 126 (77%) persons participated, 55% were women. The mean (SD) age was 59 (±14) years. Four (3%) had correctable visual impairment, and none were visually impaired. Retinal photographs were gradable for both eyes in 109 (87%) participants. The prevalence of retinopathy was 11% in persons with known diabetes, 4% in persons with screen‐detected diabetes, 3% in persons with impaired glucose tolerance and 10% in persons with normal glucose tolerance. Retinopathy was not associated with known history of diabetes or current glycaemic status. Nonfasting plasma glucose (in 1995–97) was an independent risk factor for retinopathy (in 2005), OR (95% CI) 1.5 (1.01, 2.13), p = 0.046.

Conclusion:  The prevalence of diabetic retinopathy in persons with diabetes in this study was low. Appropriate optical correction and regular eye examination can prevent unnecessary visual impairment in both persons with and without diabetes.
Managing Outsourced Software Projects: An Analysis of Project Performance and Customer Satisfaction
Authors: Narayanan Sriram , Balasubramanian Sridhar , Swaminathan Jayashankar M.
Published: August 2010

We examine the drivers of project performance and customer satisfaction in outsourced software projects using a proprietary panel dataset. The data cover 822 customer observations related to 182 unique projects executed by an India‐based software services vendor. Adopting a multidisciplinary perspective, we investigate how project planning, team stability, and communication effectiveness impact project performance and customer satisfaction. We delineate the direct and interactive influences of the antecedent variables. We also examine how these influences are moderated by two important project contexts: (a) the nature of software work (maintenance and development vs. testing projects) and (b) project maturity (new vs. mature projects). Among other results, we demonstrate that, when project planning capabilities are high, the positive impact of team stability and communication effectiveness on project performance is even higher. In addition, our results suggest that the impact of communication on project performance is muted when team stability is high. Finally, we also demonstrate that the impact of the antecedent variables on project performance varies with the nature of software work. Our findings offer specific and actionable insights to managers that can help them manage outsourced projects better, and open up new research perspectives in the context of outsourced project management.
High-resolution transmission-electron microscope characterization of onionlike carbon transformed from nanodiamond
Authors: Zou Q. , Wang M. Z. , Li Y. G. , Lu B.
Published: August 2010

The onionlike carbon (OLC) was fabricated by annealing nanodiamond synthesized by detonation at the annealing temperatures from 500 to 1400 °C and at the pressure of approximate 2 Pa. A high-resolution transmission-electron microscope was used to characterize the microstructures of the OLC as-fabricated. The results showed that at the annealing temperature of 500 °C, nanodiamond began transforming into amorphous carbon. At the annealing temperature of 800 °C, nanodiamond was transformed into amorphous carbon completely. At the annealing temperature of 900 °C, OLC began appearing and the size of the OLC particles was smaller than 5 nm. At the annealing temperature of 1000–1200 °C, the OLC particle with larger size than 5 nm was fabricated. Moreover, the amorphous carbon untransformed and coexisted in the center of the OLC particle became fewer and fewer with the annealing temperature increase. At the annealing temperature of 1400 °C, all the amorphous carbon was transformed into the OLC. The OLC particles exhibited similarity to the original nanodiamond particles in shape. The formation process of the OLC included formation of amorphous carbon, formation of graphite fragment, connection of graphite fragment, connection and curvature of graphite sheets, and closure of graphite layers.
QA for helical tomotherapy: Report of the AAPM Task Group 148a)
Authors: Langen Katja M. , Papanikolaou Niko , Balog John , Crilly Richard , Followill David , Goddu S. Murty , Grant Walter , Olivera Gustavo , Ramsey Chester R. , Shi Chengyu
Published: August 2010

Helical tomotherapy is a relatively new modality with integrated treatment planning and delivery hardware for radiation therapy treatments. In view of the uniqueness of the hardware design of the helical tomotherapy unit and its implications in routine quality assurance, the Therapy Physics Committee of the American Association of Physicists in Medicine commissioned Task Group 148 to review this modality and make recommendations for quality assurance related methodologies. The specific objectives of this Task Group are: (a) To discuss quality assurance techniques, frequencies, and tolerances and (b) discuss dosimetric verification techniques applicable to this unit. This report summarizes the findings of the Task Group and aims to provide the practicing clinical medical physicist with the insight into the technology that is necessary to establish an independent and comprehensive quality assurance program for a helical tomotherapy unit. The emphasis of the report is to describe the rationale for the proposed QA program and to provide example tests that can be performed, drawing from the collective experience of the task group members and the published literature. It is expected that as technology continues to evolve, so will the test procedures that may be used in the future to perform comprehensive quality assurance for helical tomotherapy units.
Polymer coated fiber Bragg grating thermometry for microwave hyperthermia
Authors: Saxena Indu Fiesler , Hui Kaleo , Astrahan Melvin
Published: August 2010

Purpose:

Measuring tissue temperature distribution during electromagnetically induced hyperthermia (HT) is challenging. High resistance thermistors with nonmetallic leads have been used successfully in commercial HT systems for about three decades. The single 1 mm thick temperature sensing element is mechanically moved to measure tissue temperature distributions. By employing a single thermometry probe containing a fixed linear sensor array temperature, distributions during therapy can be measured with greater ease. While the first attempts to use fiber Bragg grating (FBG) technology to obtain multiple temperature points along a single fiber have been reported, improvement in the detection system's stability were needed for clinical applications. The FBG temperature sensing system described here has a very high temporal stability detection system and an order of magnitude faster readout than commercial systems. It is shown to be suitable for multiple point fiber thermometry during microwave hyperthermia when compared to conventional mechanically scanning probe HT thermometry.

Methods:

A polymer coated fiber Bragg grating (PFBG) technology is described that provides a number of FBG thermometry locations along the length of a single optical fiber. The PFBG probe developed is tested under simulated microwave hyperthermia treatment to a tissue equivalent phantom. Two temperature probes, the multiple PFBG sensor and the Bowman probe, placed symmetrically with respect to a microwave antenna in a tissue phantom are subjected to microwave hyperthermia. Measurements are made at start of HT and 85 min later, when a increase in temperature is registered by both probes, as is typical in clinical HT therapy. The optical fiber multipoint thermometry probe performs highly stable, real‐time thermometry updating each multipoint thermometry scan over a 5 cm length every 2 s. Bowman probe measurements are acquired simultaneously for comparison. In addition, the PFBG sensor's detection system drift over 10 h is measured separately to evaluate system stability for clinical applications.

Results:

The temperature profiles measured by the two probes simultaneously under microwave HT are in good agreement showing mean differences of. The stability of the detection system is better than with response times of the PFBG sensor system of 2 s for each scan over ten points.

Conclusions:

The single fixed multipoint fiber thermometry capability compares favorably with the scanning Bowman probe data. This offers an enabling alternative to either scanning or bundled single point temperature probes for distributed thermometry in clinical applications.
Special report: Workshop on 4D‐treatment planning in actively scanned particle therapy—Recommendations, technical challenges, and future research directions
Authors: Knopf Antje , Bert Christoph , Heath Emily , Nill Simeon , Kraus Kim , Richter Daniel , Hug Eugen , Pedroni Eros , Safai Sairos , Albertini Francesca , Zenklusen Silvan , Boye Dirk , Söhn Matthias , Soukup Martin , Sobotta Benjamin , Lomax Antony
Published: August 2010

This article reports on a 4D‐treatment planning workshop (4DTPW), held on 7–8 December 2009 at the Paul Scherrer Institut (PSI) in Villigen, Switzerland. The participants were all members of institutions actively involved in particle therapy delivery and research. The purpose of the 4DTPW was to discuss current approaches, challenges, and future research directions in 4D‐treatment planning in the context of actively scanned particle radiotherapy. Key aspects were addressed in plenary sessions, in which leaders of the field summarized the state‐of‐the‐art. Each plenary session was followed by an extensive discussion. As a result, this article presents a summary of recommendations for the treatment of mobile targets (intrafractional changes) with actively scanned particles and a list of requirements to elaborate and apply these guidelines clinically.
Comparison of GEANT4 very low energy cross section models with experimental data in water
Authors: Incerti S. , Ivanchenko A. , Karamitros M. , Mantero A. , Moretto P. , Tran H. N. , Mascialino B. , Champion C. , Ivanchenko V. N. , Bernal M. A. , Francis Z. , Villagrasa C. , Baldacchino G. , Guèye P. , Capra R. , Nieminen P. , Zacharatou C.
Published: August 2010

Purpose:

TheGEANT4 general‐purpose Monte Carlo simulation toolkit is able to simulate physical interaction processes of electrons, hydrogen and helium atoms with charge states (, ) and (, , ), respectively, in liquid water, the main component of biological systems, down to the electron volt regime and the submicrometer scale, providing GEANT4 users with the so‐called “GEANT4‐DNA” physics models suitable for microdosimetry simulation applications. The corresponding software has been recently re‐engineered in order to provide GEANT4 users with a coherent and unique approach to the simulation of electromagnetic interactions within the GEANT4 toolkit framework (since GEANT4 version 9.3 beta). This work presents a quantitative comparison of these physics models with a collection of experimental data in water collected from the literature.

Methods:

An evaluation of the closeness between the total and differential cross section models available in theGEANT4 toolkit for microdosimetry and experimental reference data is performed using a dedicated statistical toolkit that includes the Kolmogorov–Smirnov statistical test. The authors used experimental data acquired in water vapor as direct measurements in the liquid phase are not yet available in the literature. Comparisons with several recommendations are also presented.

Results:

The authors have assessed the compatibility of experimental data withGEANT4 microdosimetry models by means of quantitative methods. The results show that microdosimetric measurements in liquid water are necessary to assess quantitatively the validity of the software implementation for the liquid water phase. Nevertheless, a comparison with existing experimental data in water vapor provides a qualitative appreciation of the plausibility of the simulation models. The existing reference data themselves should undergo a critical interpretation and selection, as some of the series exhibit significant deviations from each other.

Conclusions:

TheGEANT4‐DNA physics models available in the GEANT4 toolkit have been compared in this article to available experimental data in the water vapor phase as well as to several published recommendations on the mass stopping power. These models represent a first step in the extension of the GEANT4 Monte Carlo toolkit to the simulation of biological effects of ionizing radiation.
Real‐time monitoring and control on deep inspiration breath‐hold for lung cancer radiotherapy—Combination of ABC and external marker tracking
Authors: Wong Victy Y. W. , Tung Stewart Y. , Ng Alice W. Y. , Li Francis A. S. , Leung Joyce O. Y.
Published: August 2010

Purpose:

In this article, the breath‐hold and gating concepts were combined for application of lung cancer radiation treatment. The tumor movement was immobilized based on deep inspiration breath hold (DIBH), in which the breath‐hold consistency and stability were monitored by infrared (IR) tracking and controlled by gating with a predefined threshold. The authors’ goal is to derive the benefits from both techniques, namely, the minimized treatment margin and the known advantages of deep inspiration. The efficacy of the technique in terms of tumor immobility and treatment setup accuracy was evaluated in the study.

Methods:

Fourteen patients who were diagnosed with non small cell lung cancer were included in this study. The control of tumor immobility was investigated interfractionally and intrafractionally. The intrabreath‐hold tumor motion was devised based on the external marker movement, in which the tumor‐marker correlation was studied. The margin of the planning target volume (PTV) was evaluated based on two factors: (1) The treatment setup error accounts for the patient setup and interbreath‐hold variations and (2) the intrabreath‐hold tumor motion in which the residual tumor motion during irradiation was studied.

Results:

As the result of the study, the group systematic error and group random error of treatment setup measured at the isocenter were, , and in the left‐right (LR), anterior‐posterior (AP), and caudal‐cranial (CC) directions, respectively. The Pearson correlation coefficient were 0.81 (LR), 0.76 (AP), and 0.85 (CC) mm and suggest tendency in linear correlation of tumor and marker movement. The intrabreath‐hold tumor was small in all directions. The group PTV margins of 3.8 (LR), 4.6 (AP), and 4.8 (CC) mm were evaluated to account for both setup errors and residual tumor motion during irradiation.

Conclusions:

The study applies the DIBH technique in conjunction with IR positional tracking for tumor immobilization and treatment setup localization. The technique not only proved to be reliable in terms of good tumor immobility and accurate treatment positioning but also to be potentially useful for dose escalation treatment as regarding of the substantially reduced PTV margin and minimizing radiation toxicity from the fully expanded lung volume.