bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Melanoma Growth by Small Molecules That Promote the Mitochondrial Localization of ATF2
Authors: Varsano Tal , Lau Eric , Feng Yongmei , Garrido Marine , Milan Loribelle , Heynen-Genel Susanne , Hassig Christian A. , Ronai Ze'ev A.
Published: April 2013

Purpose: Effective therapy for malignant melanoma, the leading cause of death from skin cancer, remains an area of significant unmet need in oncology. The elevated expression of PKCϵ in advanced metastatic melanoma results in the increased phosphorylation of the transcription factor ATF2 on threonine 52, which causes its nuclear localization and confers its oncogenic activities. The nuclear-to-mitochondrial translocation of ATF2 following genotoxic stress promotes apoptosis, a function that is largely lost in melanoma cells, due to its confined nuclear localization. Therefore, promoting the nuclear export of ATF2, which sensitizes melanoma cells to apoptosis, represents a novel therapeutic modality.

Experimental Design: We conducted a pilot high-throughput screen of 3,800 compounds to identify small molecules that promote melanoma cell death by inducing the cytoplasmic localization of ATF2. The imaging-based ATF2 translocation assay was conducted using UACC903 melanoma cells that stably express doxycycline-inducible GFP-ATF2.

Results: We identified two compounds (SBI-0089410 and SBI-0087702) that promoted the cytoplasmic localization of ATF2, reduced cell viability, inhibited colony formation, cell motility, and anchorage-free growth, and increased mitochondrial membrane permeability. SBI-0089410 inhibited the 12-O-tetradecanoylphorbol-l3-acetate (TPA)–induced membrane translocation of protein kinase C (PKC) isoforms, whereas both compounds decreased ATF2 phosphorylation by PKCϵ and ATF2 transcriptional activity. Overexpression of either constitutively active PKCϵ or phosphomimic mutant ATF2T52E attenuated the cellular effects of the compounds.

Conclusion: The imaging-based high-throughput screen provides a proof-of-concept for the identification of small molecules that block the oncogenic addiction to PKCϵ signaling by promoting ATF2 nuclear export, resulting in mitochondrial membrane leakage and melanoma cell death. Clin Cancer Res; 19(10); 2710–22. ©2013 AACR.
Electrocardiographic Studies of Romidepsin Demonstrate Its Safety and Identify a Potential Role for KATP Channel
Authors: Noonan Anne M. , Eisch Robin A. , Liewehr David J. , Sissung Tristan M. , Venzon David J. , Flagg Thomas P. , Haigney Mark C. , Steinberg Seth M. , Figg William D. , Piekarz Richard L. , Bates Susan E.
Published: April 2013

Purpose: Romidepsin is a histone deacetylase inhibitor (HDI) approved for the treatment of both cutaneous and peripheral T-cell lymphoma (CTCL and PTCL). During development, a thorough assessment of cardiac toxicity was conducted.

Experimental Design: A phase II single-agent nonrandomized study of romidepsin was conducted in patients with CTCL or PTCL who had progressed after at least 1 prior systemic therapy.

Results: Results for the first 42 patients enrolled on the NCI 1312 phase II study of romidepsin in CTCL or PTCL showed no cardiac toxicity based on serial electrocardiograms (ECG), troponins, and MUGA scans/echocardiograms. The cardiac assessments reported herein confirm the safety of romidepsin among 131 enrolled patients, while supporting a role for electrolyte replacement. Heart rate increased an average 11 bpm following romidepsin infusion; there was no evidence of increased arrhythmia. Criteria for potassium/magnesium replacement were met before 55% of 1365 romidepsin doses; an association with hypoalbuminemia was confirmed. We propose a mechanism for ST segment flattening and depression, the most common ECG abnormalities observed: HDI-induced alteration of the activity or expression of KATP channels. In addition, examination of the variants of the active transporter of romidepsin, ABCB1, showed a trend toward smaller heart rate changes in the peri-infusion period among wild-type than variant diplotypes.

Conclusions: We conclude that in the context of appropriate attention to electrolyte levels, the data support the cardiac safety of romidepsin. Clin Cancer Res; 19(11); 3095–104. ©2013 AACR.
Development of Virus-Like Particle Technology from Small Highly Symmetric to Large Complex Virus-Like Particle Structures
Authors: Pushko Peter , Pumpens Paul , Grens Elmars
Published: April 2013

Virus-like particle (VLP) technology is a promising approach for the construction of novel vaccines, diagnostic tools, and gene therapy vectors. Initially, VLPs were primarily derived from non-enveloped icosahedral or helical viruses and proved to be viable vaccine candidates due to their effective presentation of epitopes in a native conformation. VLP technology has also been used to prepare chimeric VLPs decorated with genetically fused or chemically coupled epitope stretches selected from immunologically defined target proteins. However, structural constraints associated with the rigid geometrical architecture of icosahedral or helical VLPs pose challenges for the expression and presentation of large epitopes. Complex VLPs derived from non-symmetric enveloped viruses are increasingly being used to incorporate large epitopes and even full-length foreign proteins. Pleomorphic VLPs derived from influenza or other enveloped viruses can accommodate multiple full-length and/or chimeric proteins that can be rationally designed for multifunctional purposes, including multivalent vaccines. Therefore, a second generation of VLP carriers is represented by complex particles reconstructed from natural or chimeric structural proteins derived from complex enveloped viruses. Further development of safe and efficient VLP nanotechnology may require a rational combination of both approaches.
B-Lymphoblastic Leukemia/Lymphoma Associated with t(8;13)(p11;q12)/ZMYM2 (ZNF198)-FGFR1: Rare Case and Review of the Literature
Authors: Trimaldi Janese , Carballido Estrella M. , Bowers Jeremy W. , Anguiano Arturo L. , Zhang Zhong J. , Shah Bijal D. , Bruno Salvador , List Alan F. , Moscinski Lynn C. , Grady Terrence , Agosti Steven J. , Kang Loveleen , Zhang Ling
Published: April 2013

Myeloid and lymphoid neoplasms with fibroblastic growth factor receptor-1 (FGFR1) abnormalities originate from mutated pluripotent stem cells and have a heterogeneous clinical presentation. There are 12 identified partner genes commonly involved in FGFR1 translocation at an 8p11 breakpoint. In FGFR1-related neoplasms, T-lymphoblastic lymphoma with eosinophilia is the most common clinical scenario, whereas acute B-lymphoblastic leukemia/lymphoma (B-ALL/LBL) is rare. To date, only 7 cases of B-ALL/LBL with FGFR1 abnormalities have been reported. Here, we report an additional case of a 64-year-old gentleman with leukocytosis, eosinophilia and diffuse mediastinal and general lymphadenopathy. Bone marrow examination showed patchy infiltrates of immature precursors/blasts, along with myeloid/eosinophilic hyperplasia. Immunophenotyping confirmed increased B lymphoblasts (30-40%). Karyotyping revealed cytogenetic abnormalities, including t(8;13)(p11;q12)/ZMYM2 (ZNF198)-FGFR1 and trisomy 21. The patient did not respond to hyper-CVAD chemotherapy and within 4 months developed acute myelomonocytic leukemia and expired 11 months after the initial diagnosis. Similar cases from the literature are reviewed.
Two-Center Observational Study of the Accuracy of a Bayes Network for Short-Term Outcome Prediction in Cholecystectomy Patients
Authors: Udelnow Andrej , Schmidt Agnes , Muche Rainer , Henne-Bruns Doris , Würl Peter , Lippert Hans
Published: April 2013

Background: A Bayes Network was developed for individual risk prediction after cholecystectomy. Validity and robustness were compared with logistic regression analysis (LR). Methods: Clinical databases were created at the Ulm University and St. Franziskus Flensburg hospitals between 2001 and 2010 were comprised of hospitalized cholecystolithiasis patients serving as model and test cohorts, respectively. The probabilities of in-hospital death, prolonged hospitalization (>7 days), relaparotomy and erythrocyte transfusions were predicted based solely on admission data by BN and LR. ROC curves were calculated. Results: The Ulm and Flensburg cohorts consisted of 1,029 and 1,842 patients, respectively. The areas under the ROC curves for predicting death were 94% (p = 0.8) for both BN and LR, 70 vs. 76% (p < 0.001) for prolonged hospitalization, 69 vs. 68% (p = 0.8) for relaparotomy, and 84 vs. 78% (p = 0.1) for ET. Predictability declined for both methods when explanatory values were changed randomly. In contrast to LR, the BN revealed a good robustness to missing values. Conclusion: Both BN and MR predicted the death risk quite accurately. The advantage of BN consists of its robustness to missing values. Moreover, its graphical representation may be helpful for clinical decision making.
Influence of Osmotic Shock on Escherichia coli Insoluble Protein Fraction in the Presence of Exogenous Osmolytes
Authors: Labeikyte Danute , Sereikaite Jolanta
Published: April 2013

The influence of osmotic shock in the presence of exogenous osmolytes on the formation and composition of insoluble protein fraction in Escherichia coli was investigated. Interferon-α5 (IFN-α5) expressed in E. coli BL21(DE3) was used as a model protein. Cells were cultivated at three different temperatures of 25, 30, and 37°C. Two different osmolytes were used. Glycine as an amino acid metabolized by E. coli, or betaine which is not metabolized by cells, was added to the growth medium in the presence of salt. In both cases (i.e. when metabolized or non-metabolized amino acid was used), IFN-α5 formed the aggregates, except at 25°C of cultivation. Moreover, the differences in the quantitative composition of insoluble protein fraction were revealed by the proteomic analysis. The amount of some identified proteins increased, decreased, or did not change in the samples cultivated under osmotic shock in the presence of betaine as compared with the sample cultivated without salt and betaine in growth medium.
Primary Prevention of Sudden Cardiac Death in a Nonischemic Dilated Cardiomyopathy Population
Authors: Gatzoulis Konstantinos A. , Vouliotis Apostolos-Ilias , Tsiachris Dimitris , Salourou Maria , Archontakis Stefanos , Dilaveris Polychronis , Gialernios Theodoros , Arsenos Petros , Karystinos Georgios , Sideris Skevos , Kallikazaros Ioannis , Stefanadis Christodoulos
Published: April 2013

Background—

We considered the role of programmed ventricular stimulation in primary prevention of sudden cardiac death in an idiopathic dilated cardiomyopathy population.

Methods and Results—

One hundred fifty-eight patients with idiopathic dilated cardiomyopathy underwent programmed ventricular stimulation. Ventricular tachycardia/ventricular fibrillation was triggered in 44 patients (group I, 27.8%) versus 114 patients (group II), where ventricular tachycardia/ventricular fibrillation was not induced. Sixty-nine patients with idiopathic dilated cardiomyopathy underwent implantable cardioverter-defibrillator (ICD) implantation: 41/44 in group I and 28/114 in group II. The major end points of the study were overall mortality and appropriate ICD activation. Overall mortality during the 46.9 months of mean follow-up was not significantly different between the 2 groups. Patients with left ventricular ejection fraction ≤35% (n=119) demonstrated a higher overall mortality rate compared with the patients with left ventricular ejection fraction >35% (n=39; 16.8% versus 10.3%, log-rank
P
=0.025). Advanced New York Heart Association class (III and IV versus I and II) was the single independent and strongest prognostic factor of overall mortality (hazard ratio, 11.909;
P
<0.001; confidence interval, 3.106–45.65), as well as of cardiac mortality (hazard ratio, 14.787;
P
=0.001; confidence interval, 2.958–73.922). Among ICD recipients, ICD activation rate was significantly higher in group I compared with group II (30 of 41 patients–73.2% versus 5 of 28 patients–17.9%; log-rank
P
=0.001), either in the form of antitachycardia pacing (68.3% versus 17.9%; log-rank
P
=0.001) or in the shock delivery form (51.2% versus 17.9%; log-rank
P
=0.05). Induction of ventricular tachycardia/ventricular fibrillation during programmed ventricular stimulation in contrast to left ventricular ejection fraction was the single independent prognostic factor for future ICD activation (hazard ratio, 4.195;
P
=0.007; confidence interval, 1.467–11.994).

Conclusions—

Inducibility of ventricular tachycardia/ventricular fibrillation was associated with an increased likelihood of subsequent ICD activation and sudden cardiac death surrogate.
Radulphus Brito’s Commentary on Aristotle’s De anima
Authors: de Boer Sander W.
Published: April 2013

Abstract

In 1974, Winfried Fauser published his edition of Radulphus Brito’s commentary on the third book of Aristotle’s De anima. This contribution continues his project by providing an edition of Brito’s commentary on the first book and the first third of the second book. An analysis of this part of the commentary shows that Brito developed some original views that had an impact on the fourteenth-century commentary tradition.
Review of the fish-parasitic genus Cymothoa Fabricius, 1793 (Isopoda, Cymothoidae, Crustacea) from the southwestern Indian Ocean, including a new species from South Africa
Authors: HADFIELD KERRY A. , BRUCE NIEL L. , SMIT NICO J.
Published: April 2013

The genus Cymothoa Fabricius, 1793 is revised for southwestern Indian Ocean waters. Cymothoa borbonica Schioedte & Meinert, 1884 and C. eremita Brünnich, 1783 are redescribed. Cymothoa rotundifrons Haller, 1880, from Mauritius lacks type material and the host is unknown, therefore it is here relegated to nomen dubium. Cymothoa sodwana sp. nov., from Trachinotus botla (Carangidae), collected from the Kwazulu-Natal coast of South Africa, is described and is distinguished by the large, ovoid, hunched body with rugose dorsal surfaces; the anterolateral angles of pereonite 1 are narrow and rounded reaching half the length of the cephalon; the ischium of pereopod 7 has a large protrusion and pereonite 7 which laterally overlaps the pleon margins, extending posteriorly to the pleotelson.
Calibration and Stability of Oxygen Sensors on Autonomous Floats
Authors: D'Asaro Eric A. , McNeil Craig
Published: April 2013

The calibration accuracy and stability of three Aanderaa 3835 optodes and three Sea-Bird Electronics SBE-43 oxygen sensors were evaluated over four years using in situ and laboratory calibrations. The sensors were mostly in storage, being in the ocean for typically only a few weeks per year and operated for only a few days per year. Both sensors measure partial pressure of oxygen, or equivalently saturation at standard pressure; results are expressed in this variable. It is assumed that sensor drift occurs in the oxygen sensitivity of the sensors, not the temperature compensation; this is well justified for the SBE-43 based on multiple calibrations. Neither sensor had significant long-term drift in output when sampling anoxic water. Sensor output at 100% saturation differed from the factory calibrations by up to ±6% (averaging −2.3% ± 3%) for the SBE-43 and up to −12.6% for the optodes. The optode output at 100% saturation is well described by a single decaying exponential with a decay constant of approximately 2 yr and an amplitude of 28%. The mechanism of this drift is unknown but is not primarily due to sensor operation. It may be different from that experienced by sensors continuously deployed in the ocean. Thus, although the optodes in this study did not have a stable calibration, their drift was stable and, once calibrated, allowed optode and SBE-43 pairs mounted on the same autonomous floats to be calibrated to an accuracy of ±0.4% over a 4-yr period.
Three Hundred Years of Glory and Gloom
Authors: Givental Elena
Published: April 2013

The Ural Mountains in Russia are recognized for their picturesque scenery, exceptional mineral wealth, and geopolitical significance in Russian history. The Urals are also notoriously known as a site of the Soviet military industrial complex, the birthplace of the Soviet nuclear program, and the most polluted region in Russia. The evolving Urals’ imagery as Russia’s “treasure box” and “Russia’s defender” has been a continual theme through the region’s identity and economic progression over the period of 300 years. At different times and by different powers, the Urals was glorified or ostracized, however, preserving its iconic image. The article explores the origins of the Ural’s identity and the evolution of the Urals’ diverse meanings using the evidence from published scholarly sources and works of art.
Weighted kernel operators in variable exponent amalgam spaces
Authors: Kokilashvili Vakhtang , Meskhi Alexander , Zaighum Muhammad Asad
Published: April 2013

The paper is devoted to weighted inequalities for positive kernel operators in variable exponent amalgam spaces. In particular, a characterization of a weight v governing the boundedness/compactness of the weighted kernel operators

K
v

and

K
v

, defined on

R
+

and ℝ, respectively, under the log-Hölder continuity condition on exponents of spaces is established. These operators involve, for example, weighted variable parameter fractional integrals. The results are new even for constant exponent amalgam spaces.

MSC:46E30, 47B34.
Sufficient conditions for starlike functions associated with the lemniscate of Bernoulli
Authors: Kumar S Sivaprasad , Kumar Virendra , Ravichandran V , Cho Nak Eun
Published: April 2013

Let

−
1
≤
B
<
A
≤
1

. The condition on β is determined so that

1
+
β
z

p
′

(
z
)
/

p
k

(
z
)
≺
(
1
+
A
z
)
/
(
1
+
B
z
)

(

−
1
<
k
≤
3

) implies

p
(
z
)
≺

1
+
z

. Similarly, the condition on β is determined so that

1
+
β
z

p
′

(
z
)
/

p
n

(
z
)

or

p
(
z
)
+
β
z

p
′

(
z
)
/

p
n

(
z
)
≺

1
+
z

(

n
=
0
,
1
,
2

) implies

p
(
z
)
≺
(
1
+
A
z
)
/
(
1
+
B
z
)

or

1
+
z

. In addition to that, the condition on β is derived so that

p
(
z
)
≺
(
1
+
A
z
)
/
(
1
+
B
z
)

when

p
(
z
)
+
β
z

p
′

(
z
)
/
p
(
z
)
≺

1
+
z

. A few more problems of the similar flavor are also considered.

MSC:30C80, 30C45.
New bounds for Randic and GA indices
Authors: Lokesha V , Shetty B Shwetha , Ranjini PS , Cangul Ismail Naci , Cevik Ahmet Sinan
Published: April 2013

The main goal of this paper is to present some new lower and upper bounds for the Randic and GA indices in terms of Zagreb and modified Zagreb indices.

MSC: 05C05, 05C20, 05C90.
Cytological maps of lampbrush chromosomes of European water frogs (Pelophylax esculentuscomplex) from the Eastern Ukraine
Authors: Dedukh Dmitry , Mazepa Glib , Shabanov Dmitry , Rosanov Juriy , Litvinchuk Spartak , Borkin Leo , Saifitdinova Alsu , Krasikova Alla
Published: April 2013

Background

Hybridogenesis (hemiclonal inheritance) is a kind of clonal reproduction in which hybrids between parental species are reproduced by crossing with one of the parental species. European water frogs (Pelophylax esculentuscomplex) represent an appropriate model for studying interspecies hybridization, processes of hemiclonal inheritance and polyploidization.P. esculentuscomplex consists of two parental species,P. ridibundus(the lake frog) andP. lessonae(the pool frog), and their hybridogenetic hybrid –P. esculentus(the edible frog).Parental and hybrid frogs can reproduce syntopically and form hemiclonal population systems. For studying mechanisms underlying the maintenance of water frog population systems it is required to characterize the karyotypes transmitted in gametes of parental and different hybrid animals of both sexes.

Results

In order to obtain an instrument for characterization of oocyte karyotypes in hybrid female frogs, we constructed cytological maps of lampbrush chromosomes from oocytes of both parental species originating in Eastern Ukraine. We further identified certain molecular components of chromosomal marker structures and mapped coilin-rich spheres and granules, chromosome associated nucleoli and special loops accumulating splicing factors. We recorded the dissimilarities betweenP. ridibundusandP. lessonaelampbrush chromosomes in the length of orthologous chromosomes, number and location of marker structures and interstitial (TTAGGG)n-repeat sites as well as activity of nucleolus organizer.Satellite repeat RrS1 was mapped in centromere regions of lampbrush chromosomes of the both species. Additionally, we discovered transcripts of RrS1 repeat in oocytes ofP. ridibundusandP. lessonae. Moreover, G-rich transcripts of telomere repeat were revealed in association with terminal regions ofP. ridibundusandP. lessonaelampbrush chromosomes.

Conclusions

The constructed cytological maps of lampbrush chromosomes ofP. ridibundusandP. lessonaeprovide basis to define the type of genome transmitted within individual oocytes ofP. esculentusfemales with different ploidy and from various population systems.
Long-range transcriptional regulation by the p110 CUX1 homeodomain protein on theENCODE array
Authors: Vadnais Charles , Awan Arif A , Harada Ryoko , Clermont Pier-Luc , Leduy Lam , Bérubé Ginette , Nepveu Alain
Published: April 2013

Background

Overexpression of the Cut homeobox 1 gene, CUX1, inverselycorrelates with patient survival in breast cancers. Cell-based assays andmolecular studies have revealed that transcriptional regulation byCUX1 involves mostly the proteolytically processed p110isoform. As there is no antibody specific to p110 CUX1 only, an alternatestrategy must be employed to identify its targets.

Results

We expressed physiological levels of a tagged-p110 CUX1 protein and performedchromatin affinity purification followed by hybridization on ENCODE andpromoter arrays. Targets were validated by chromatin immunoprecipitation andtranscriptional regulation by CUX1 was analyzed in expression profiling andRT-qPCR assays following CUX1 knockdown or p110 CUX1 overexpression.Approximately 47% and 14% of CUX1 binding sites were respectively mappedless than 4 Kbp, or more than 40 Kbp, away from a transcription start site.More genes exhibited changes in expression following CUX1 knockdown thanp110 CUX1 overexpression. CUX1 directly activated or repressed 7.4% and 8.4%of putative targets identified on the ENCODE and promoter arraysrespectively. This proportion increased to 11.2% for targets with 2 bindingsites or more. Transcriptional repression was observed in a slightly higherproportion of target genes. The CUX1 consensus binding motif, ATCRAT, wasfound at 47.2% of the CUX1 binding sites, yet only 8.3% of the CUX1consensus motifs present on the array were bound in vivo. Thepresence of a consensus binding motif did not have an impact on whether atarget gene was repressed or activated. Interestingly, the distance betweena binding site and a transcription start site did not significantly reducedthe ability of CUX1 to regulate a target gene. Moreover, CUX1 not only wasable to regulate the next adjacent gene, but also regulated the gene locatedbeyond this one as well as the gene located further away in the oppositedirection.

Conclusion

Our results demonstrate that p110 CUX1 can activate or repress transcriptionwhen bound at a distance and can regulate more than one gene on certaingenomic loci.
Cardiovascular fitness associated with cognitive performance in heart failure patients enrolled in cardiac rehabilitation
Authors: Garcia Sarah , Alosco Michael L , Spitznagel Mary Beth , Cohen Ronald , Raz Naftali , Sweet Lawrence , Josephson Richard , Hughes Joel , Rosneck Jim , Oberle Morgan L , Gunstad John
Published: April 2013

Background

Reduced cognitive function is common in persons with heart failure (HF). Cardiovascular fitness is a known contributor to cognitive function in many patient populations, but has only been linked to cognition based on estimates of fitness in HF. The current study examined the relationship between fitness as measured by metabolic equivalents (METs) from a standardized stress test and cognition in persons with HF, as well as the validity of office-based predictors of fitness in this population.

Methods

Forty-one HF patients enrolled in cardiac rehabilitation completed a standardized exercise stress test protocol, a brief neuropsychological battery, the 2-minute step test (2MST), and a series of medical history and self-report questionnaires.

Results

Maximum METs from stress testing demonstrated incremental predictive validity for attention (β = .41,p = .03), executive function (β = .37,p = .04), and memory domains (β = .46,p = .04). Partial correlations accounting for key medical and demographic characteristics revealed greater METs was associated with the 2MST (r(32) = .41,p = .02) but not with the Duke Activity Status Index (DASI) (r(32) = .24,p = .17).

Conclusion

The current findings indicate that better fitness levels measured by METs is independently associated with better cognitive function in older adults with HF. Results also showed that METs was closely associated with one office-based measure of fitness (2MST), but not another (DASI). Prospective studies are needed to clarify the mechanisms linking fitness and cognitive function in HF.
Physical activity and its correlates in children: a cross-sectional study (the GINIplus & LISAplus studies)
Authors: Ortlieb Sandra , Schneider Gabriel , Koletzko Sibylle , Berdel Dietrich , von Berg Andrea , Bauer Carl-Peter , Schaaf Beate , Herbarth Olf , Lehmann Irina , Hoffmann Barbara , Heinrich Joachim , Schulz Holger ,   GINIplus and LISAplus Study Groups
Published: April 2013

Background

Physical inactivity among children is an increasing problem that adversely affects children’s health. A better understanding of factors which affect physical activity (PA) will help create effective interventions aimed at raising the activity levels of children. This cross-sectional study examined the associations of PA with individual (biological, social, behavioral, psychological) and environmental (East vs. West Germany, rural vs. urban regions) characteristics in children.

Methods

Information on PA and potential correlates was collected from 1843 girls and 1997 boys using questionnaires during the 10-year follow-up of two prospective birth cohort studies (GINIplus and LISAplus). Study regions represent urban and rural sites as well as East and West of Germany. Logistic regression modeling was applied to examine cross-sectional associations between individual as well as environmental factors and PA levels.

Results

Five of fourteen variables were significantly associated with PA. Among children aged 10, girls tended to be less active than boys, especially with respect to vigorous PA (OR = 0.72 for summer). Children who were not a member of a sports club showed a substantially reduced amount of PA in winter (OR = 0.15). Rural environments promote moderate PA, particularly in winter (OR = 1.88), whereas an increased time outdoors primarily promotes moderate PA in summer (OR = 12.41). Children with abnormal emotional symptoms exhibited reduced physical activity, particularly in winter (OR = 0.60). BMI, puberty, parental BMI, parental education, household income, siblings, TV/PC consumption, and method of arriving school, were not associated with PA.

Conclusions

When considering correlates of PA from several domains simultaneously, only few factors (sex, sports club membership, physical environment, time outdoors, and emotional symptoms) appear to be relevant. Although the causality needs to be ascertained in longitudinal studies, variables which cannot be modified should be used to identify risk groups while modifiable variables, such as sports club activities, may be addressed in intervention programs.
Chronic kidney disease in Nicaragua: a qualitative analysis of semi-structured interviews with physicians and pharmacists
Authors: Ramirez-Rubio Oriana , Brooks Daniel R , Amador Juan Jose , Kaufman James S , Weiner Daniel E , Scammell Madeleine Kangsen
Published: April 2013

Background

Northwestern Nicaragua has a high prevalence of chronic kidney disease (CKD) of unknown cause among young adult men. In addition, frequent occurrence of urinary tract infections (UTI) among men and a dysuria syndrome described by sugarcane workers as “chistata” are both reported. This study examines health professionals´ perceptions regarding etiology of these conditions and their treatment approaches, including use of potentially nephrotoxic medications.

Methods

Nineteen in-person semi-structured interviews were conducted in November 2010 among ten physicians and nine pharmacists practicing in the region.

Results

Health professionals perceived CKD as a serious and increasing problem in the region, primarily affecting young men working as manual laborers. All interviewees regarded occupational and environmental exposure to sun and heat, and dehydration as critical factors associated with the occurrence of CKD. These factors were also considered to play a role in the occurrence of chistata in the region. Health professionals indicated that reluctance among workers to hydrate might be influenced by perceptions of water contamination. Symptoms often were treated with non-steroidal anti-inflammatory drugs (NSAIDs), diuretics and antibiotics. Physicians acknowledged that the diagnosis of UTI usually was not based on microbial culture and opined that the use of potentially nephrotoxic medications may be contributing to CKD.

Conclusions

Interviews provided evidence suggesting that medications such as diuretics, antibiotics and NSAIDs are widely used and sold over the counter for symptoms that may be related to dehydration and volume depletion. These factors, alone or in combination, may be possible contributors to kidney damage. Acute kidney damage coupled with volume depletion and exposures including medications and infectious agents should be further evaluated as causal factors for CKD in this region.
Influence of untranslated regions on retroviral mRNA transfer and expression
Authors: Prel Anne , Sensébé Luc , Pagès Jean-Christophe
Published: April 2013

Background

Deliberate cellular reprogramming is becoming a realistic objective in the clinic. While the origin of the target cells is critical, delivery of bioactive molecules to trigger a shift in cell-fate remains the major hurdle. To date, several strategies based either on non-integrative vectors, protein transfer or mRNA delivery have been investigated. In a recent study, a unique modification in the retroviral genome was shown to enable RNA transfer and its expression.

Results

Here, we used the retroviral mRNA delivery approach to study the impact of modifying gene-flanking sequences on RNA transfer. We designed modified mRNAs for retroviral packaging and used the quantitative luciferase assay to compare mRNA expression following viral transduction of cells. Cloning the untranslated regions of the vimentin or non-muscular myosin heavy chain within transcripts improved expression and stability of the reporter gene while slightly modifying reporter-RNA retroviral delivery. We also observed that while the modified retroviral platform was the most effective for retroviral mRNA packaging, the highest expression in target cells was achieved by the addition of a non-viral UTR to mRNAs containing the packaging signal.

Conclusions

Through molecular engineering we have assayed a series of constructs to improve retroviral mRNA transfer. We showed that an authentic RNA retroviral genomic platform was most efficiently transferred but that adding UTR sequences from highly expressed genes could improve expression upon transfection while having only a slight effect on expression from transferred RNA. Together, these data should contribute to the optimisation of retroviral mRNA-delivery systems that test combinations of UTRs and packaging platforms.
Motor recovery monitoring using acceleration measurements in post acute stroke patients
Authors: Gubbi Jayavardhana , Rao Aravinda S , Fang Kun , Yan Bernard , Palaniswami Marimuthu
Published: April 2013

Background

Stroke is one of the major causes of morbidity and mortality. Its recovery and treatment depends on close clinical monitoring by a clinician especially during the first few hours after the onset of stroke. Patients who do not exhibit early motor recovery post thrombolysis may benefit from more aggressive treatment.

Method

A novel approach for monitoring stroke during the first few hours after the onset of stroke using a wireless accelerometer based motor activity monitoring system is developed. It monitors the motor activity by measuring the acceleration of the arms in three axes. In the presented proof of concept study, the measured acceleration data is transferred wirelessly using iMote2 platform to the base station that is equipped with an online algorithm capable of calculating an index equivalent to the National Institute of Health Stroke Score (NIHSS) motor index. The system is developed by collecting data from 15 patients.

Results

We have successfully demonstrated an end-to-end stroke monitoring system reporting an accuracy of calculating stroke index of more than 80%, highest Cohen’s overall agreement of 0.91 (with excellentκcoefficient of 0.76).

Conclusion

A wireless accelerometer based ‘hot stroke’ monitoring system is developed to monitor the motor recovery in acute-stroke patients. It has been shown to monitor stroke patients continuously, which has not been possible so far with high reliability.
Bisphenol A-associated epigenomic changes in prepubescent girls: a cross-sectional study in Gharbiah, Egypt
Authors: Kim Jung H , Rozek Laura S , Soliman Amr S , Sartor Maureen A , Hablas Ahmed , Seifeldin Ibrahim A , Colacino Justin A , Weinhouse Caren , Nahar Muna S , Dolinoy Dana C
Published: April 2013

Background

There is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends.

Methods

Urinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N = 46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing.

Results

CpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change.

Conclusions

These data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.
Alveolar ridge keratosis - a retrospective clinicopathological study
Authors: Bellato Lorenzo , Martinelli-Kläy Carla P , Martinelli Celso R , Lombardi Tommaso
Published: April 2013

Background

Alveolar ridge keratosis (ARK) is a distinct, benign clinicopathological entity, characterized by a hyperkeratotic plaque or patch that occurs on the alveolar edentulous ridge or on the retromolar trigone, considered to be caused by chronic frictional trauma. The aim of this retrospective study is to present the clinicopathological features of 23 consecutive cases of ARK.

Material and methods

The 23 biopsy samples of ARK were selected and pathological features were revised (keratosis, acanthosis, surface architecture, and inflammation). Factors such as the patient’s gender, age, anatomical location, tobacco and alcohol use were analyzed.

Results

Sixteen out of the 23 cases studied were men and 7 women with a mean age of 55.05 (age ranged from 17 to 88 years). Thirteen cases had a history of tobacco habit, amongst whom, 4 also presented alcohol consumption. All the cases presented only unilateral lesions. Nineteen cases involved the retromolar trigone while 4 cases involved edentulous alveolar ridges. When observed microscopically, the lesions were mainly characterized by moderate to important hyperorthokeratosis. Inflammation was scanty or absent. In four of the cases, the presence of melanin pigment in the superficial corium or in the cytoplasm of macrophages was detected. None of the cases showed any features of dysplasia.

Conclusion

Our results reveal that ARK is a benign lesion. However, the high prevalence of smokers amongst the patients might suggest that some potentially malignant disorders such as tobacco associated leukoplakia may clinically mimic ARK.
Gastroduodenal artery aneurysm, diagnosis, clinical presentation and management: a concise review
Authors: Habib Nicholas , Hassan Samer , Abdou Rafik , Torbey Estelle , Alkaied Homam , Maniatis Theodore , Azab Basem , Chalhoub Michel , Harris Kassem
Published: April 2013

Gastroduodenal artery (GDA) aneurysms are rare but a potentially fatal condition if rupture occurs. They represent about 1.5% of all visceral artery (VAA) aneurysms and are divided into true and pseudoaneurysms depending on the etiologic factors underlying their development. Atherosclerosis and pancreatitis are the two most common risk factors. Making the diagnosis can be complex and often requires the use of Computed Tomography and angiography. The later adds the advantage of being a therapeutic option to prevent or stop bleeding. If this fails, surgery is still regarded as the standard for accomplishing a definite treatment.
Novel 1H low field nuclear magnetic resonance applications for the field of biodiesel
Authors: Berman Paula , Leshem Adi , Etziony Oren , Levi Ofer , Parmet Yisrael , Saunders Michael , Wiesman Zeev
Published: April 2013

Background

Biodiesel production has increased dramatically over the last decade, raising the need for new rapid and non-destructive analytical tools and technologies. 1H Low Field Nuclear Magnetic Resonance (LF-NMR) applications, which offer great potential to the field of biodiesel, have been developed by the Phyto Lipid Biotechnology Lab research team in the last few years.

Results

Supervised and un-supervised chemometric tools are suggested for screening new alternative biodiesel feedstocks according to oil content and viscosity. The tools allowed assignment into viscosity groups of biodiesel-petrodiesel samples whose viscosity is unknown, and uncovered biodiesel samples that have residues of unreacted acylglycerol and/or methanol, and poorly separated and cleaned glycerol and water. In the case of composite materials, relaxation time distribution, and cross-correlation methods were successfully applied to differentiate components. Continuous distributed methods were also applied to calculate the yield of the transesterification reaction, and thus monitor the progress of the common and in-situ transesterification reactions, offering a tool for optimization of reaction parameters.

Conclusions

Comprehensive applied tools are detailed for the characterization of new alternative biodiesel resources in their whole conformation, monitoring of the biodiesel transesterification reaction, and quality evaluation of the final product, using a non-invasive and non-destructive technology that is new to the biodiesel research area. A new integrated computational-experimental approach for analysis of 1H LF-NMR relaxometry data is also presented, suggesting improved solution stability and peak resolution.
Transglutaminase-mediated restoration of historic silk and its ageing resistance
Authors: Zhu Zhanyun , Liu Liu , Gong Decai
Published: April 2013

Introduction

Transglutaminase-mediated polymerization, unlike the traditional restoration methods based on the application of synthetic polymers, has proved to be a potential strategy in the restoration of historic silk. In the present study, the treatment process has been adapted to satisfy the needs of consolidating historic silk fabrics in various cases. Artificially aged (dry thermal ageing) silk samples were restored using this method. The effects of the reaction on silk fibers were investigated by tensile tests, colour difference tests, scanning electron microscopy and FT-IR. The ageing resistance of the restored samples was evaluated.

Results

The results showed that tensile strength, elongation rate at breakage and micro morphology of the silk samples were remarkably improved without significant colour difference after restoration. FT-IR spectroscopy confirmed the existence of transglutaminase-induced biopolymers in the restored silk samples and demonstrated that the transglutaminase-mediated restoration did not change the basic structure of silk protein. The ageing resistance of the restored samples evaluated using standard methods ensured that the treatment would not introduce any long term problems. The method was then applied to genuine historic silk fabrics and achieved the desired results.

Conclusions

From the results of this study, the effectiveness of transglutaminase-mediated polymerisation to restore historic silk was demonstrated.
Mortality and quality of life in the five years after severe sepsis
Authors: Cuthbertson Brian H , Elders Andrew , Hall Sally , Taylor Jane , MacLennan Graeme , Mackirdy Fiona , Mackenzie Simon J ,   the Scottish Critical Care Trials Group and the Scottish Intensive Care Society Audit Group
Published: April 2013

Introduction

Severe sepsis is associated with high levels of morbidity and mortality, placing a high burden on healthcare resources. We aimed to study outcomes in the five years after severe sepsis.

Methods

This was a cohort study using data from a prospective audit in 26 adult ICUs in Scotland. Mortality was measured using clinical databases and quality of life using Short Form 36 (SF-36) at 3.5 and 5 years after severe sepsis.

Results

A total of 439 patients were recruited with a 58% mortality at 3.5 years and 61% mortality at 5 years. A total of 85 and 67 patients responded at 3.5 and 5 years follow-up, respectively. SF-36 physical component score (PCS) was low compared to population controls at 3.5 years (mean 41.8 (SD 11.8)) and at 5 years (mean 44.8 (SD 12.7)). SF-36 mental component score (MCS) was slightly lower than population controls at 3.5 years (mean 47.7 (SD 14.6)) and at 5 years after severe sepsis (mean 48.8 (SD 12.6)). The majority of patients were satisfied with their current quality of life (QOL) (80%) and all patients would be willing to be treated in an ICU again if they become critically ill despite many having unpleasant memories (19%) and recall (29%) of ICU events.

Conclusions

Patients with severe sepsis have a high ongoing mortality after severe sepsis. They also have a significantly lower physical QOL compared to population norms but mental QOL scores were only slightly below population norms up to five years after severe sepsis. All survivors would be willing to be treated in an ICU again if critically ill. Mortality and QOL outcomes were broadly similar to other critically ill cohorts throughout the five years of follow-up.
Genomic Medicine Frontier in Human Solid Tumors: Prospects and Challenges
Authors: Dienstmann Rodrigo , Rodon Jordi , Barretina Jordi , Tabernero Josep
Published: April 2013

Recent discoveries of genomic alterations that underlie and promote the malignant phenotype, together with an expanded repertoire of targeted agents, have provided many opportunities to conduct hypothesis-driven clinical trials. The ability to profile each unique cancer for actionable aberrations by using high-throughput technologies in a cost-effective way provides unprecedented opportunities for using matched therapies in a selected patient population. The major challenges are to integrate and make biologic sense of the substantial genomic data derived from multiple platforms. We define two different approaches for the analysis, interpretation, and clinical applicability of genomic data: (1) the genomically stratified model originates from the “one test-one drug” paradigm and is currently being expanded with an upfront multicategorical approach following recent advances in multiplexed genotyping platforms; and (2) the comprehensive assessment model is based on whole-genome, -exome, and -transcriptome data and allows identification of novel drivers and subsequent therapies in the experimental setting. Tumor heterogeneity and evolution of the diverse populations of cancer cells during cancer progression, influenced by the effects of systemic treatments, will need to be addressed in the new scenario of early drug development. Logistical issues related to prescreening strategies and trial allocation, in addition to concerns in the economic and ethical domains, must be taken into consideration. Here we present a historical view of how increased understanding of cancer genomics has been translated to the clinic and discuss the prospects and challenges for further implementation of a personalized treatment strategy for human solid tumors.
Ethical, Legal, and Counseling Challenges Surrounding the Return of Genetic Results in Oncology
Authors: Lolkema Martijn P. , Gadellaa-van Hooijdonk Christa G. , Bredenoord Annelien L. , Kapitein Peter , Roach Nancy , Cuppen Edwin , Knoers Nine V. , Voest Emile E.
Published: April 2013

In the last decade, an overwhelming number of genetic aberrations have been discovered and linked to the development of treatment for cancer. With the rapid advancement of next-generation sequencing (NGS) techniques, it is expected that large-scale DNA analyses will increasingly be used to select patients for treatment with specific anticancer agents. Personalizing cancer treatment has many advantages, but sequencing germline DNA as reference material for interpreting cancer genetics may have consequences that extend beyond providing cancer care for an individual patient. In sequencing germline DNA, mutations may be encountered that are associated with increased susceptibility not only to hereditary cancer syndromes but also to other diseases; in those cases, disclosing germline data could be clinically relevant and even lifesaving. In the context of personal autonomy, it is necessary to develop an ethical and legal framework for how to deal with identified hereditary disease susceptibilities and how to return the data to patients and their families. Because clear legislation is lacking, we need to establish guidelines on disclosure of genetic information and, in the process, we need to balance privacy issues with the potential advantages and drawbacks of sharing genetic data with patients and their relatives. Importantly, a strong partnership with patients is critical for understanding how to maximize the translation of genetic information for the benefit of patients with cancer. This review discusses the ethical, legal, and counseling issues surrounding disclosure of genetic information generated by NGS to patients with cancer and their relatives. We also provide a framework for returning these genetic results by proposing a design for a qualified disclosure policy.