bluuebunny/crossref_metadata_2025 huggingface dataset:
Quetiapine, QTc interval prolongation, and torsade de pointes: a review of case reports
Authors: Hasnain Mehrul , Vieweg W. Victor R. , Howland Robert H. , Kogut Christopher , Breden Crouse Ericka L. , Koneru Jayanthi N. , Hancox Jules C. , Digby Geneviève C. , Baranchuk Adrian , Deshmukh Anand , Pandurangi Ananda K.
Published: November 2013

Recently, both the manufacturer of quetiapine and the US Food and Drug Administration warned healthcare providers and patients about quetiapine-induced QTc interval prolongation and torsade de pointes ( TdP) when using this drug within the approved labeling.

 We reviewed the case-report literature and found 12 case reports of QTc interval prolongation in the setting of quetiapine administration. There were no cases of quetiapine-induced TdP or sudden cardiac death (SCD) among patients using quetiapine appropriately and free of additional risk factors for QTc interval prolongation and TdP. Among the 12 case reports risk factors included female sex (nine cases), coadministration of a drug associated with QTc interval prolongation (eight cases), hypokalemia or hypomagnesemia (six cases) quetiapine overdose (five cases), cardiac problems (four cases), and coadministration of cytochrome P450 3A4 inhibitors (two cases). There were four cases of TdP. As drug-induced TdP is a rare event, prospective studies to evaluate the risk factors associated with QTc prolongation and TdP are difficult to design, would be very costly, and would require very large samples to capture TdP rather than its surrogate markers. Furthermore, conventional statistical methods may not apply to studies of TdP, which is rare and an ‘outlier’ manifestation of QTc prolongation. We urge drug manufacturers and regulatory agencies to periodically publish full case reports of psychotropic drug-induced QTc interval prolongation, TdP, and SCD so that clinicians and investigators may better understand the clinical implications of prescribing such drugs as quetiapine.
An animal model of adult T-cell leukemia: humanized mice with HTLV-1–specific immunity
Authors: Tezuka Kenta , Xun Runze , Tei Mami , Ueno Takaharu , Tanaka Masakazu , Takenouchi Norihiro , Fujisawa Jun-ichi
Published: November 2013

Key Points

Humanized mice, IBMI-huNOG, were generated by intra–bone marrow injection of human CD133+ hematopoietic stem cells. HTLV-1–infected IBMI-huNOG mice recapitulated distinct ATL-like symptoms as well as HTLV-1–specific adaptive immune responses.
Comparative transcriptome analysis of geographically distinct virulent and attenuated Babesia bovis strains reveals similar gene expression changes through attenuation
Authors: Pedroni Monica J , Sondgeroth Kerry S , Gallego-Lopez Gina M , Echaide Ignacio , Lau Audrey OT
Published: November 2013

Background

Loss of virulence is a phenotypic adaptation commonly seen in prokaryotic and eukaryotic pathogens. This mechanism is not well studied, especially in organisms with multiple host and life cycle stages such as Babesia, a tick-transmitted hemoparasite of humans and animals. B. bovis, which infects cattle, has naturally occurring virulent strains that can be reliably attenuated in vivo. Previous studies suggest the virulence loss mechanism may involve post-genomic modification. We investigated the transcriptome profiles of two geographically distinct B. bovis virulent and attenuated strain pairs to better understand virulence loss and to gain insight into pathogen adaptation strategies.

Results

Expression microarray and RNA-sequencing approaches were employed to compare transcriptome profiles of two B. bovis strain pairs, with each pair consisting of a virulent parental and its attenuated derivative strain. Differentially regulated transcripts were identified within each strain pair. These included genes encoding for VESA1, SmORFs, undefined membrane and hypothetical proteins. The majority of individual specific gene transcripts differentially regulated within a strain were not shared between the two strains. There was a disproportionately greater number of ves genes upregulated in the virulent parental strains. When compared with their attenuated derivatives, divergently oriented ves genes were included among the upregulated ves genes in the virulent strains, while none of the upregulated ves genes in the attenuated derivatives were oriented head to head. One gene family whose specific members were consistently and significantly upregulated in expression in both attenuated strains was spherical body protein (SBP) 2 encoding gene where SBP2 truncated copies 7, 9 and 11 transcripts were all upregulated.

Conclusions

We conclude that ves heterodimer pair upregulation and overall higher frequency of ves gene expressions in the virulent strains is consistent with the involvement of this gene family in virulence. This is logical given the role of VESA1 proteins in cytoadherence of infected cells to endothelial cells. However, upregulation of some ves genes in the attenuated derivatives suggests that the consequence of upregulation is gene-specific. Furthermore, upregulation of the spherical body protein 2 gene family may play a role in the attenuated phenotype. Exactly how these two gene families may contribute to the loss or gain of virulence is discussed.
Visual pursuit response in the severe disorder of consciousness: modulation by the central autonomic system and a predictive model
Authors: Riganello Francesco , Cortese Maria D , Dolce Giuliano , Sannita Walter G
Published: November 2013

Background

A visual pursuit response is reportedly observed in ~20-30% of subjects in vegetative state (VS/UWS) and predicts better outcome; it is a key marker of evolution into the minimally conscious state (MCS). The probability of observing a positive response, however, has proven variable during the day, with comparable timing of the minima and maxima in VS/UWS and MCS. We verified if measures of sympathetic/parasympathetic balance are possible independent variables on which the occurrence of a pursuit response could depend and be predicted.

Methods

Fourteen subjects in VS/UWS and sixteen in MCS for more than one year were studied. A mirror was used to test the pursuit response for a total 231 useful trials. Non-invasive measures of the sympathetic/parasympathetic functional state (Heart rate variability descriptors nuLF and peakLF) used in the study of responsiveness in VS/UWS and MCS subjects were recorded and processed by descriptive statistics and advanced Support Vector Machine (SVM).

Results

A pursuit response was observed in 33% and 78.2% of subjects in VS or MCS, respectively. Incidence was higher at HRV nuLF values in the 20–60 range and peakLF values at 0.06-0.12 Hz (76.6%) and at nuLF values in the 10–60 range and peakLF values at 0.05-0.10 Hz (80.7%) in the VS and MCS, respectively. The SVM generated model confirmed the results in the training leave one out and 10 fold cross validation tests (81% and 81.4%).

Conclusion

The pursuit response incidence depends to a relevant extent on the sympathetic/parasympathetic balance and autonomic functional state. Extensive monitoring appears advisable.
Assessment of early changes in 3H-fluorothymidine uptake after treatment with gefitinib in human tumor xenograft in comparison with Ki-67 and phospho-EGFR expression
Authors: Zhao Songji , Kuge Yuji , Zhao Yan , Takeuchi Satoshi , Hirata Kenji , Takei Toshiki , Shiga Tohru , Dosaka-Akita Hirotoshi , Tamaki Nagara
Published: November 2013

Background

The purpose of this study was to evaluate whether early changes in 3′-deoxy-3′-3H-fluorothymidine (3H-FLT) uptake can reflect the antiproliferative effect of gefitinib in a human tumor xenograft, in comparison with the histopathological markers, Ki-67 and phosphorylated EGFR (phospho-EGFR).

Methods

An EGFR-dependent human tumor xenograft model (A431) was established in female BALB/c athymic mice, which were divided into three groups: one control group and two treatment groups. Mice in the treatment groups were orally administered a partial regression dose (100 mg/kg/day) or the maximum tolerated dose of gefitinib (200 mg/kg/day), once daily for 2 days. Mice in the control group were administered the vehicle (0.1% Tween 80). Tumor size was measured before and 3 days after the start of treatment. Biodistribution of 3H-FLT and 18F-FDG (%ID/g/kg) was examined 3 days after the start of the treatment. Tumor cell proliferative activity with Ki-67 was determined. Immunohistochemical staining of EGFR and measurement of phospho-EGFR were also performed.

Results

High expression levels of EGFR and Ki-67 were observed in the A431 tumor. After the treatment with 100 and 200 mg/kg gefitinib, the uptake levels of 3H-FLT in the tumor were significantly reduced to 67% and 61% of the control value, respectively (0.39 ± 0.09, 0.36 ± 0.06, 0.59 ± 0.11%ID/g/kg for 100 mg/kg, 200 mg/kg, and control groups, respectively; p < 0.01 vs. control), but those of 18F-FDG were not. After the treatment with 100 and 200 mg/kg gefitinib, the expression levels of Ki-67 in the tumor were markedly decreased (4.6 ± 2.4%, 6.2 ± 1.8%, and 10.4 ± 5.7% for 100 mg/kg, 200 mg/kg, and control groups, respectively, p < 0.01 vs. control). The expression levels of the phospho-EGFR protein also significantly decreased (29% and 21% of the control value for 100, and 200 mg/kg, respectively p < 0.01 vs. control). There was no statistically significant difference in tumor size between pre- and post-treatments in each group.

Conclusion

In our animal model, 3H-FLT uptake levels significantly decreased after the treatment with two different doses of gefitinib before a significant change in tumor size was observed. These results were confirmed by the immunohistochemical staining of Ki-67 and phospho-EGFR protein immunoassay. Thus, it was indicated that early changes in 3H-FLT uptake may reflect the antiproliferative effect of gefitinib in a mouse model of a human epidermoid cancer.
Relationships between self-rated oral health, subjective symptoms, oral health behavior and clinical conditions in Japanese university students: a cross-sectional survey at Okayama University
Authors: Kojima Azusa , Ekuni Daisuke , Mizutani Shinsuke , Furuta Michiko , Irie Koichiro , Azuma Tetsuji , Tomofuji Takaaki , Iwasaki Yoshiaki , Morita Manabu
Published: November 2013

Background

Self-rated oral health is a valid and useful summary indicator of overall oral health status and quality of life. However, few studies on perception of oral health have been conducted among Japanese young adults. This study investigated whether oral health behavior, subjective oral symptoms, or clinical oral status were associated with self-rated oral health in Japanese young adults.

Methods

This cross-sectional survey included 2,087 students (1,183 males, 904 females), aged 18 and 19 years, at Okayama University, Japan. A self-administered questionnaire was distributed and an oral examination was performed.

Results

In a structural equation modeling analysis, the score of decayed, missing and filled teeth (DMFT) significantly affected self-rated oral health (p <0.05) and the effect size was highest. Malocclusion, subjective symptoms of temporomandibular disorders (TMD) and stomatitis, and poor oral health behavior significantly induced self-rated poor oral health with small effect sizes (p <0.05). Clinical periodontal conditions and Oral Hygiene Index-simplified were not related to self-rated oral health.

Conclusion

Self-rated oral health was influenced by subjective symptoms of TMD and stomatitis, oral health behavior, the score of DMFT, and malocclusion. The evaluation of these parameters may be a useful approach in routine dental examination to improve self-rated oral health in university students.
Effects of coenzyme Q10 supplementation (300 mg/day) on antioxidation and anti-inflammation in coronary artery disease patients during statins therapy: a randomized, placebo-controlled trial
Authors: Lee Bor-Jen , Tseng Yu-Fen , Yen Chi-Hua , Lin Ping-Ting
Published: November 2013

Background

High oxidative stress and chronic inflammation can contribute to the pathogenesis of coronary artery disease (CAD). Coenzyme Q10 is an endogenous lipid-soluble antioxidant. Statins therapy can reduce the biosynthesis of coenzyme Q10. The purpose of this study was to investigate the effects of a coenzyme Q10 supplement (300 mg/d; 150 mg/b.i.d) on antioxidation and anti-inflammation in patients who have CAD during statins therapy.

Methods

Patients who were identified by cardiac catheterization as having at least 50% stenosis of one major coronary artery and who were treated with statins for at least one month were enrolled in this study. The subjects (n = 51) were randomly assigned to the placebo (n = 24) and coenzyme Q10 groups (Q10-300 group, n = 27). The intervention was administered for 12 weeks. The concentrations of coenzyme Q10, vitamin E, antioxidant enzymes activities (superoxide dismutase, catalase, and glutathione peroxidase), and inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6)] were measured in the 42 subjects (placebo, n = 19; Q10-300, n = 23) who completed the study.

Results

The levels of the plasma coenzyme Q10 (P < 0.001) and antioxidant enzymes activities (P < 0.05) were significantly higher after coenzyme Q10 supplementation. The levels of inflammatory markers (TNF-α, P = 0.039) were significantly lower after coenzyme Q10 supplementation. The subjects in the Q10-300 group had significantly higher vitamin E (P = 0.043) and the antioxidant enzymes activities (P < 0.05) than the placebo group at week 12. The level of plasma coenzyme Q10 was significantly positively correlated with vitamin E (P = 0.008) and antioxidant enzymes activities (P < 0.05) and was negatively correlated with TNF-α (P = 0.034) and IL-6 (P = 0.027) after coenzyme Q10 supplementation.

Conclusion

Coenzyme Q10 supplementation at 300 mg/d significantly enhances antioxidant enzymes activities and lowers inflammation in patients who have CAD during statins therapy.

Trial registration

Clinical Trials.gov Identifier: NCT01424761.
Quantitative assessment of carotid plaque surface irregularities and correlation to cerebrovascular symptoms
Authors: Kanber Baris , Hartshorne Timothy C , Horsfield Mark A , Naylor A Ross , Robinson Thompson G , Ramnarine Kumar V
Published: November 2013

Background

The purpose of this study was to determine whether surface irregularities measured from ultrasound images of carotid artery plaques and quantified using a novel method, correlate with the presence of ipsilateral hemispheric cerebrovascular symptoms.

Methods

A plaque surface irregularity index (SII) was measured in 47 carotid artery plaques (32 subjects, stenosis range 10% -95%, 49% symptomatic) using ultrasound image sequences spanning several cardiac cycles. The differences in the distribution of SII in plaques with ipsilateral hemispheric symptoms versus those without symptoms and the correlation between the SII of plaques and the degrees of stenosis of the corresponding arteries were assessed. Diagnostic performance of plaque SII was evaluated on its own and in combination with the degree of stenosis.

Results

The mean SII was significantly greater for plaques with ipsilateral hemispheric symptoms (1.89 radians/mm) than for asymptomatic plaques (1.67 radians/mm, p = 0.03). There was no statistically significant association between the SII and the degree of stenosis (p = 0.30). SII predicted the presence of cerebrovascular symptoms with an accuracy of 66% (sensitivity 65%, specificity 67%) on its own and with an accuracy of 83% (sensitivity 96%, specificity 71%) in combination with the degree of stenosis.

Conclusions

Quantitative assessment of carotid plaque surface irregularities using a novel SII parameter correlates with the presence ipsilateral hemispheric cerebrovascular symptoms and may increase diagnostic performance beyond that provided by the degree of stenosis.
Cytogenetic analysis of quinoa chromosomes using nanoscale imaging and spectroscopy techniques
Authors: Yangquanwei Zhong , Neethirajan Suresh , Karunakaran Chithra
Published: November 2013

Here we present a high-resolution chromosomal spectral map derived from synchrotron-based soft X-ray spectromicroscopy applied to quinoa species. The label-free characterization of quinoa metaphase chromosomes shows that it consists of organized substructures of DNA-protein complex. The analysis of spectra of chromosomes using the scanning transmission X-ray microscope (STXM) and its superposition of the pattern with the atomic force microscopy (AFM) and scanning electron microscopy (SEM) images proves that it is possible to precisely locate the gene loci and the DNA packaging inside the chromosomes. STXM has been successfully used to distinguish and quantify the DNA and protein components inside the quinoa chromosomes by visualizing the interphase at up to 30-nm spatial resolution. Our study represents the successful attempt of non-intrusive interrogation and integrating imaging techniques of chromosomes using synchrotron STXM and AFM techniques. The methodology developed for 3-D imaging of chromosomes with chemical specificity and temporal resolution will allow the nanoscale imaging tools to emerge from scientific research and development into broad practical applications such as gene loci tools and biomarker libraries.
Integrating multiple ‘omics’ analyses identifies serological protein biomarkers for preeclampsia
Authors: Liu Linda Y , Yang Ting , Ji Jun , Wen Qiaojun , Morgan Alexander A , Jin Bo , Chen Gongxing , Lyell Deirdre J , Stevenson David K , Ling Xuefeng B , Butte Atul J
Published: November 2013

Background

Preeclampsia (PE) is a pregnancy-related vascular disorder which is the leading cause of maternal morbidity and mortality. We sought to identify novel serological protein markers to diagnose PE with a multi-’omics’ based discovery approach.

Methods

Seven previous placental expression studies were combined for a multiplex analysis, and in parallel, two-dimensional gel electrophoresis was performed to compare serum proteomes in PE and control subjects. The combined biomarker candidates were validated with available ELISA assays using gestational age-matched PE (n=32) and control (n=32) samples. With the validated biomarkers, a genetic algorithm was then used to construct and optimize biomarker panels in PE assessment.

Results

In addition to the previously identified biomarkers, the angiogenic and antiangiogenic factors (soluble fms-like tyrosine kinase (sFlt-1) and placental growth factor (PIGF)), we found 3 up-regulated and 6 down-regulated biomakers in PE sera. Two optimal biomarker panels were developed for early and late onset PE assessment, respectively.

Conclusions

Both early and late onset PE diagnostic panels, constructed with our PE biomarkers, were superior over sFlt-1/PIGF ratio in PE discrimination. The functional significance of these PE biomarkers and their associated pathways were analyzed which may provide new insights into the pathogenesis of PE.
Construction of a full-length infectious bacterial artificial chromosome clone of duck enteritis virus vaccine strain
Authors: Chen Liu , Yu Bin , Hua Jionggang , Ye Weicheng , Ni Zheng , Yun Tao , Deng Xiaohui , Zhang Cun
Published: November 2013

Background

Duck enteritis virus(DEV) is the causative agent of duck viral enteritis, which causes an acute, contagious and lethal disease of many species of waterfowl within the orderAnseriformes. In recent years, two laboratories have reported on the successful construction of DEV infectious clones in viral vectors to express exogenous genes. The clones obtained were either created with deletion of viral genes and based on highly virulent strains or were constructed using a traditional overlapping fosmid DNA system. Here, we report the construction of a full-length infectious clone of DEV vaccine strain that was cloned into a bacterial artificial chromosome (BAC).

Methods

A mini-F vector as a BAC that allows the maintenance of large circular DNA inE. coliwas introduced into the intergenic region between UL15B and UL18 of a DEV vaccine strain by homologous recombination in chicken embryoblasts (CEFs). Then, the full-length DEV clone pDEV-vac was obtained by electroporating circular viral replication intermediates containing the mini-F sequence intoE. coliDH10B and identified by enzyme digestion and sequencing. The infectivity of the pDEV-vac was validated by DEV reconstitution from CEFs transfected with pDEV-vac. The reconstructed virus without mini-F vector sequence was also rescued by co-transfecting the Cre recombinase expression plasmid pCAGGS-NLS/Cre and pDEV-vac into CEF cultures. Finally, thein vitrogrowth properties and immunoprotection capacity in ducks of the reconstructed viruses were also determined and compared with the parental virus.

Results

The full genome of the DEV vaccine strain was successfully cloned into the BAC, and this BAC clone was infectious. Thein vitrogrowth properties of these reconstructions were very similar to parental DEV, and ducks immunized with these viruses acquired protection against virulent DEV challenge.

Conclusions

DEV vaccine virus was cloned as an infectious bacterial artificial chromosome maintaining full-length genome without any deletions or destruction of the viral coding sequence, and the viruses rescued from the DEV-BAC clone exhibited wild-type phenotypes bothin vitroandin vivo. The generated infectious clone will greatly facilitate studies on the individual genes of DEV and applications in gene deletion or live vector vaccines.
Lack of P2Y13 in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport
Authors: Lichtenstein Laeticia , Serhan Nizar , Annema Wijtske , Combes Guillaume , Robaye Bernard , Boeynaems Jean-Marie , Perret Bertrand , Tietge Uwe J F , Laffargue Muriel , Martinez Laurent O
Published: November 2013

Background

The protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and biliary secretion. Mechanistically, the purinergic P2Y13 ADP-receptor is involved in hepatic HDL endocytosis (i.e., uptake of both HDL protein + lipid moieties), which is considered an important step of RCT. Accordingly, chow-fed P2Y13 knockout (P2Y13
-/-) mice exhibit lower hepatic HDL uptake, which translates into a decrease of hepatic free cholesterol content and biliary cholesterol and phospholipid secretion.

Findings

The aim of this study was to determine the effect of high cholesterol diet (HCD) in P2Y13
-/- mice, in order to mimic high dietary cholesterol intake, which is a major cause of dyslipidemia in humans. As previously reported with chow-diet, HCD did not affect plasma lipid levels in P2Y13
-/- compared with control mice but decreased hepatic free and esterified cholesterol content (p < 0.05, P2Y13
-/- versus control). Interestingly, biliary lipid secretion and macrophages-to-feces RCT were more dramatically impaired in P2Y13
-/- mice fed a HCD than chow-diet. HCD did not enhance atherosclerosis in P2Y13
-/- compared with control mice.

Conclusion

This study demonstrates that high dietary cholesterol intake accentuated the metabolic phenotype of P2Y13
-/- mice, with impaired hepatobiliary RCT. Although other animal models might be required to further evaluate the role of P2Y13 receptor in atherosclerosis, P2Y13 appears a promising target for therapeutic intervention aiming to stimulate RCT, particularly in individuals with lipid-rich diet.
Biochemical interaction of anti-HCV telaprevir with the ABC transporters P-glycoprotein and breast cancer resistance protein
Authors: Fujita Yuria , Noguchi Kohji , Suzuki Tomonori , Katayama Kazuhiro , Sugimoto Yoshikazu
Published: November 2013

Background

The ATP-binding cassette (ABC) transporters P-glycoprotein (P-gp)/ABCB1 and breast cancer resistance protein (BCRP)/ABCG2 are involved in the intestinal absorption and renal excretion of various substrate drugs. Their activities affect sub-therapeutic drug concentrations and excretion of natural transporter substrates. The new oral anti-HCV drug telaprevir has dramatically improved the efficacy of hepatitis-C virus (HCV) treatment, and recent studies have suggested a possible pharmacological interaction between telaprevir and P-gp. We studied the kinetics ofin vitrointeractions between telaprevir and P-gp and BCRP to understand the molecular basis of that interaction.

Findings

The effect of telaprevir on P-gp- and BCRP-mediated transport was evaluated by anin vitrovesicle transporter assay using different transport substrates, and the kinetics of transporter inhibition was determined. The results showed that telaprevir could inhibit P-gp- and BCRP-mediated transport in thein vitrovesicle transport assay, with each IC50values of ≈ 7 μmol/L and ≈ 30 μmol/L, respectively. Analyses of Lineweaver–Burk plots showed that telaprevir was likely to be a competitive inhibitor against P-gp and BCRP. Photoaffinity labeling experiments were employed to observe competitive inhibition by telaprevir using iodoarylazidoprazosin (IAAP) as a binding substrate for P-gp and BCRP. These experiments revealed that telaprevir inhibited [125I]-IAAP-binding with P-gp and BCRP.

Conclusion

Telaprevir competitively inhibited P-gp and BCRP, and P-gp-mediated transport was more sensitive to telaprevir compared with BCRP-mediated transport. These data suggest that telaprevir represses the transporter functions of P-gp and BCRPviadirect inhibition.
Metabolic syndrome and the early detection of impaired glucose tolerance among professionals living in Beijing, China: a cross sectional study
Authors: Zeng Ping , Zhu Xuefeng , Zhang Yi , Wu Sinan , Dong Jun , Zhang Tiemei , Wang Shu
Published: November 2013

Background

The purpose of this study is to investigate the association of metabolic syndrome (MS) and its components with the risk of impaired glucose tolerance (IGT) in high risk urban professionals. The goal is to improve the selection of candidates who would most benefit from an oral glucose tolerance test (OGTT).

Methods

This is a cross sectional study in which MS was identified by both the definitions proposed by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF).

Results

There were 928 eligible subjects in the study, and 23.9% of them failed in OGTT. The odds ratio of IGT was increased 3.16-fold for MS defined by the NCEP criteria and 2.79-fold for the hyperglycemia factor alone. Both MS and hyperglycemia were shown to be acceptable measures to discriminate subjects with IGT from those with normal glucose tolerance (NGT). The clustering of any 1, 2, or ≥3 metabolic components resulted in increased odds ratios for IGT: i.e., 1.71, 2.38 and 5.92, respectively. Even without hyperglycemia in the cluster, an increased odds ratio was still observed. The risk of IGT increased dramatically when the fasting plasma glucose and waist circumference were both at their highest defined level.

Conclusions

MS and its components are associated with the increased risk of IGT. People with MS, one of its components, especially hyperglycemia and central obesity, or a cluster of its components are strong candidates for an OGTT in order to achieve early cost-effective detection of IGT.
Shakespeare’s Hamlet and Familial Blessings: Historical Abruptions
Authors: Simmons J. L.
Published: November 2013

Epigraphs from William Roper’s “Life of Sir Thomas More” represent rituals of familial blessing in transition from the feudal to the early modern. They exemplify Shakespeare’s complex employment of the ritual in Hamlet and throughout his plays from the farcical to the serene. The “double blessing” that Polonius gives Laertes shows this ritual comically, as do those of earlier sons Launce and Launcelot in The Two Gentlemen of Verona and The Merchant of Venice; All’s Well That Ends Well renders it confusingly in feudal transition into a new age. King Lear offers it in the peaceful reconciliation of father and daughter, as, also tragically, does the final action between Gertrude and Hamlet when she wipes his forehead, fulfilling his promise that “when you are desirous to be blessed, / I’ll blessing beg of you.” The blessing of marriage between Hamlet and Ophelia exposes another abruption between the historical conception of political marriage argued by Polonius and Laertes and marriages of mutuality aborted by the adulterous and murderous one of Gertrude and Claudius. Hamlet is structured on the Danish history of Old Hamlet/Old Fortinbras abrupted by that of Young Hamlet/Young Fortinbras—with Hamlet blessed neither to leave home nor to marry.
Metaphysical Freedom
Authors: Kuzner James
Published: November 2013

With emphasis on John Donne, George Herbert, and Henry Vaughan, this essay explores metaphysical poetry’s strange meditations on the theme of freedom. This poetry displays—vividly, idiosyncratically, and with important differences—what Alain Badiou suggests and what Hannah Arendt famously claims about freedom: that it is best understood not as sovereignty but as natality, being freed from life’s automatic routines and partaking, in a sense, of a second birth. Rather than conjure free movement—whether through self-control, capable pursuit of self-interest, or unimpeded intellectual inquiry—metaphysical freedom involves being drawn, overwhelmed, and transformed from without, all so as to enter a strange state of rest. While Arendt is ultimately humanistic in her understanding of freedom and natality, ascribing an important role to agency, freedom in metaphysical poetry plunges subjects into states to which they contribute virtually nothing, states of such intensity as to be hardly recognizable as human. Donne, Herbert, and Vaughan engage with concepts of liberty predictably, given their contexts and ours, but also in ways that are unpredictable and occasionally even startling.
The binomial edge ideal of a pair of graphs
Authors: Ene Viviana , Herzog Jürgen , Hibi Takayuki , Qureshi Ayesha Asloob
Published: November 2013

We introduce a class of ideals generated by a set of 2-minors of an (m×n)-matrix of indeterminates indexed by a pair of graphs. This class of ideals is a natural common generalization of binomial edge ideals and ideals generated by adjacent minors. We determine the minimal prime ideals of such ideals and give a lower bound for their degree of nilpotency. In some special cases we compute their Gröbner basis and characterize unmixedness and Cohen–Macaulayness.
Consumer Choice in Health Insurance Exchanges: Can We Make It Work?
Authors: Nadash Pamela , Day Rosemarie
Published: November 2013

Under the Patient Protection and Affordable Care Act (ACA), consumer choice plays a critical role: it drives the competitive market in health insurance plans that will operate through health insurance exchanges. As the 2014 deadline for establishing exchanges approaches, states face choices: they can either allow the federal government to manage an exchange on their behalf; take on a minimalist role by managing a state exchange or partnering with the federal exchange; or assume an activist role — by aiming to influence the price, design, and quality of the health insurance options available through exchanges and taking steps to support consumers' ability to choose among these options. This article discusses states' choices and the governance issues that they raise, first by describing the extent of discretion that states have in shaping the range of health plans on offer as well as the issues they will need to consider in choosing an exchange model. We then discuss the considerable body of evidence that addresses how people behave in individual insurance markets, concluding that it strongly supports the need for states to take an active role in shaping health insurance exchanges and ensuring that they support consumer choice.
Self-aggregation of Synthetic Zinc Hydroxylated Chlorophyll Derivatives inside Aqueous Micelles: Neighboring Effect of Additional O-Functional Groups
Authors: Machida Shinnosuke , Tamiaki Hitoshi
Published: November 2013

Zinc methyl bacteriopheophorbide-d possessing a 1-hydroxyethyl group at the 3-position self-aggregated in an aqueous Triton X-100 solution to afford a red-shifted Qy band, but the substitution of hydroxy and acetoxy groups at its 32-position completely disturbed their self-aggregation. Their neighboring groups intramolecularly interacted with the 31-hydroxy group to prevent them from producing chlorosomal J-aggregates.
Integrating small population effects on both detection and persistence probabilities in the design and interpretation of presence/absence surveys.
Authors: Hudgens Brian R. , Garcelon David K.
Published: November 2013

Determining whether or not a species has been extirpated from part of its range is one of the most important yet difficult challenges facing ecologists.  Presence/absence surveys are a primary method to determine local extinction, but negative results are difficult to interpret, particularly when informal sightings appear to support local persistence of elusive species.  Such conflicts are particularly likely for rare species, which are the most difficult to detect during a presence/absence survey due to small population size.  However, integrating small population effects on both detection and extinction probabilities resolves such conflicts by reframing occupancy questions from present to near future terms.  We developed methods for integrating the simultaneous effects of survey effort and population size on detection and extinction probabilities in the design and interpretation of presence/absence surveys.  We applied these methods to the design and interpretation of a wolverine survey in Sequoia-Kings Canyon National Parks, California, USA, to address questions about the appropriateness of translocations from other populations.  Ecological applications that can benefit from this type of analysis, simultaneously incorporating small population effects on both detection and population processes, include management of charismatic, yet elusive species, management of disease risk in translocations, and management of nonnative pests.
On Certain Notions of Municipal Law
Authors: Васильев Всеволод , Vasilev Vsevolod
Published: November 2013

The author analyzes some normative notions used in the Federal Law “On General Principles on Local Self-­Government in the Russian Federation” and suggests proposals for their adjusting.
Protection of Interests of Citizens in Case of Conflict of their Personal Nonproperty Rights
Authors: Богданова Елена , Bogdanova Elena
Published: November 2013

In presented article the author, applying the categories of good faith and reasonableness, investigates questions at issue of protection of interests of citizens in cases of the conflict of the personal non­-property rights, that is situations when the subjective civil rights belonging to different persons, can’t be performed by them in full. The possibility of application to such situations the compensation of non­pecuniary damage is analyzed.
Issues of Counteraction against Extremism in the Legislation of the CIS
Authors: Никитин Андрей , Nikitin Andrey
Published: November 2013

The conceptual and terminological analysis of the model and national legal system on counteraction of extremist activity of the states — participants of the CIS is given. The following problems of this sphere of the legislation are revealed: lack of a full­-fledged legal basis of counteraction to extremism; mismatch of a conceptual framework; existence of a large number of estimated concepts; pretentiousness of legal regulation.
Lynch Syndrome Presenting as Endometrial Cancer
Authors: Tafe Laura J , Riggs Eleanor R , Tsongalis Gregory J
Published: November 2013

BACKGROUND

Lynch syndrome (LS) is the most common form of the hereditary colon cancer syndromes. Because of its high prevalence, a nationwide campaign has begun to screen all colorectal cancers for the genetic abnormalities associated with LS.

CONTENT

Next to colorectal cancer, endometrial cancer is the most common form of malignancy found in women with LS. Identifying individuals who harbor the well-characterized mismatch-repair gene mutations via immunohistochemistry, microsatellite instability analysis, or direct gene sequencing is critical to managing the LS patient and to surveillance for the development of other associated tumor types.

Although many institutions have begun screening all colorectal tumors for LS, the evidence is sufficient to warrant the testing of all endometrial cancers for LS as well. Various testing algorithms, along with genetic-counseling efforts, can lead to a cost-efficient and beneficial screening program.
Vitamin D and Cardiovascular Disease: An Appraisal of the Evidence
Authors: Schnatz Peter F , Manson JoAnn E
Published: November 2013

BACKGROUND

Supplementation with vitamin D has received attention as a potential cardioprotective strategy. Biologically plausible mechanisms have been proposed to link vitamin D to coronary heart disease (CHD) prevention, and observational studies suggest an inverse association between serum 25-hydroxyvitamin D (25OHD) concentrations and CHD. Few randomized clinical trials of vitamin D supplementation and CHD have been conducted, however, and no trial with CHD as the primary prespecified outcome has been completed.

CONTENT

A search was conducted in PubMed to find prospective studies of the use of vitamin D supplementation and its relationship to cardiovascular risk factors (RFs) and/or cardiovascular disease (CVD). The exact search query was: ((vitamin D supplement*[Title/Abstract]) AND cardiovascular [Title/Abstract]) AND prospective [Title/Abstract]. This query yielded 42 results. “Randomized Controlled Trial” (article type) was used as a filter in a subsequent query with the same search terms. We review the evidence that vitamin D supplementation modifies coronary RFs, such as blood pressure, lipids, glucose tolerance, and/or affects the development of clinical CHD events. We address potential sources of confounding in observational epidemiologic studies of the relationship between serum 25OHD and CHD. We also address laboratory assay issues relevant to the reliable measurement of 25OHD.

Most vitamin D supplementation trials have not demonstrated improvement in CVD, but they have tested relatively low vitamin D doses. Thus, the evidence remains inconclusive, highlighting the need for rigorous randomized trials of higher vitamin D doses with cardiovascular events as prespecified outcomes. While we await the results of ongoing trials, the recommended dietary allowances from the Institute of Medicine remain the best guidepost for nutritional requirements.
Procesos actuales y perspectivas para el transporte ferroviario de viajeros en Andalucía
Authors: Gavira Narváez Antonio , Ventura Fernández Jesús
Published: November 2013

El papel que juega el ferrocarril en los sistemas urbanos e interurbanos de transporte, gracias al desarrollo técnico y organizativo, ha impulsado que tenga una participación cada vez más relevante en el tráfico especializado de viajeros en Andalucía. Además, su integración con otros medios de desplazamiento viabiliza su uso y competitividad. A pesar de la gran presencia que ha adquirido el medio, su estudio resulta novedoso y de gran actualidad, ya que ha sido bastante menos tratado, con respecto a otros sistemas de transporte, dentro de los trabajos científicos a nivel español y andaluz. La elección de la escala regional para analizar la red ferroviaria se fundamenta en tres factores, como son la extensión, la demografía y la localización de Andalucía. Éstos le confieren una identidad histórica y cultural propia, así como elementos suficientes para analizar la región de forma individualizada dentro del entramado ferroviario español. Además, la descentralización de algunas políticas de transporte le concede mayor consistencia al estudio realizado. La elección del ámbito andaluz pretende, por tanto, abordar este territorio como un espacio concreto de España y del conjunto de la Unión Europea.
Modelo territorial innovador y articulación urbana en el poniente almeriense
Authors: Sánchez Escolano Luis Miguel
Published: November 2013

El Poniente Almeriense es hoy un espacio altamente productivo que cuenta con una economía diversificada sostenida en la agricultura intensiva de alta tecnificación, la industria agroalimentaria, los servicios a empresas y el turismo de sol y playa. Así mismo, se ha consolidado como un territorio competitivo y con capacidad de adaptación a la realidad económica globalizada, propicio a la innovación empresarial y territorial. Pero el desarrollo y consagración de este modelo económico ha acarreado profundas transformaciones urbanas y territoriales que han reconfigurado por completo esta comarca, y todo ello en un marco de insostenibilidad ecológica marcado por la depredación de recursos muy escasos. El presente trabajo aborda, a partir del análisis de la dinámica territorial que configuró este espacio desde mediados del siglo XX, los principales efectos de estas transformaciones, focalizando nuestra atención en la dinámica urbana y los procesos de innovación territorial acaecidos en estos años.
El aprovechamiento de turbias en San Vicente del Raspeig (Alicante) como ejemplo de sistema de riego tradicional y sostenible
Authors: Morote Seguido Álvaro Francisco
Published: November 2013

En San Vicente del Raspeig, el sistema de riego tradicional, al igual que en otras partes del sureste peninsular, ha sido el aprovechamiento de turbias, también conocido como práctica de boqueras. Este sistema aprovechaba las escorrentías tras episodios de lluvias, para regar, abonar los campos, llenar cisternas y aljibes. Esta modalidad de aportación de aguas esporádicas fue abandonándose progresivamente durante la primera mitad del siglo XX con la implantación de nuevas técnicas agrícolas y la llegada de caudales de otras regiones que garantizaban un volumen de agua regular durante todo el año. Actualmente, el abandono de las antiguas áreas en las que se practicaba este aprovechamiento y la ocupación de éstas a favor de usos residenciales, ha favorecido la génesis de una serie de problemáticas ambientales y territoriales, que estas técnicas minimizaban.
El dengue en el nororiente de Venezuela y su incidencia en condiciones extremas de las lluvias durante los años 2009 y 2010
Authors: Sáez Sáez Vidal , Colmenares Suárez Luis A.
Published: November 2013

El objetivo fue evaluar comparativamente la incidencia de dengue, la lluvia de los años 2009 y 2010 y el servicio de abastecimiento de agua potable a la población de la región nororiental del país. Considerando los registros de casos de dengue de los años 2009 y 2010, se llevaron a incidencia (casos/total de población*10.000 habitantes) y se compararon con registros históricos para la región y el país. Al contrastar las lluvias de los años 2009 y 2010 con los históricos de la región (en proporción) y el país determinamos las diferencias observadas. Por otra parte, y con el objeto de vincular el comportamiento de las lluvias de estos años con el índice de oscilación del sur (IOS; bloque del Pacifico 3,4) se identifican por analogía relaciones entre las variables. Examinamos el abastecimiento de los servicios de agua potable y frecuencia, en centros poblados rurales y urbanos, como un indicador que determina en la presencia del vector. Elaboramos una síntesis de las relaciones establecidas en una realidad geográfica oriental con el comportamiento de las lluvias de los dos años que permiten caracterizar la persistencia de la enfermedad. Conclusión: las reservas de agua manipuladas por el hombre, a causa de la irregularidad del servicio de suministro a la población, y la afectación por eventos externos han sido algunos de los factores determinantes en la incidencia del dengue y se debe ampliar la evaluación de un conjunto de variables vinculadas a este hecho geográfico.
Replacement of Fish Meal by Ribotricin in Diets of Carp (Cyprinus Carpio)
Authors: Pavlov Atanasoff Alexandar
Published: November 2013

Waste non-standard fish combined with wheat bran filler in ratio 60:40 were used for production of new non-traditional protein component called Ribotricin. The aim of this study was to elucidate the effects of the new protein component Ribotricin on growth performance, feed utilization and feed ingredients digestibility of carp (Cyprinus carpio L., 1758) fish. The experiment (90 days) involved 160 carp reared in eight concrete tanks with an initial average weight of 0.046 ± 8.04 g in (RT) tank, and fish with an initial average weight of 0.047 ± 6.52 g in (FM) tanks. The experimental carp were equally divided into two groups of 80 (four replicates of 20 carp each). The obtained results at the end of the experiment, showed no significant differences between the groups` Body Weight (BW), Feed Conversion Ratio (FCR), Specific Growth Rate (SGR), Protein Efficiency Ratio (PER) (p> 0.05). Based on the obtained data, we can conclude that Ribotricin (RT) can be used as fish meal substitution in the diets of carp fish without adverse effects on the measured parameters.
Role of oestrogens on oxidative stress and inflammation in ageing
Authors: Viña Jose , Gambini Juan , García-García Francisco José , Rodriguez-Mañas Leocadio , Borrás Consuelo
Published: November 2013

Females live longer than males. We have shown that this could be in part due to the higher levels of oestrogens in females, which protect them against ageing, by up-regulating the expression of antioxidant, longevity-related genes. However, the low concentration of oestrogens makes it unlikely that they exhibit significant antioxidant capacity in the organism. Our results show that physiological concentrations of oestrogens activate the expression of manganese superoxide dismutase and glutathione peroxidase by oestrogen receptors and the mitogen-activated protein kinase and nuclear factor kappa B pathway. Moreover, when considering oestrogen replacement therapy, it is of utmost importance to take into account when to start the therapy after menopause. We have shown that only early-onset administration of oestrogen replacement therapy is effective on oestrogen deprivation associated with oxidative and metabolic stress. This is due to a change in oestrogen receptor distribution after oestrogen deprivation. Oestrogens are also involved in inflammatory processes. Their role on inflammation is very complex, because their effects are different depending on the doses and also on the oestrogen receptor distribution.
Habitat selection by the viscacha rat (Octomys mimax, Rodentia: Octodontidae) in a spatially heterogeneous landscape
Authors: Campos Valeria E. , Giannoni Stella M.
Published: November 2013

The viscacha rat
Acoustic parameter investigation of polyvinyl acetate with acetic acid using ultrasonic technique
Authors: Kaur Baljinder , Juglan Kailash C.
Published: November 2013

Density, viscosity and ultrasonic velocity of polyvinyl acetate with acetic acid have been measured at a temperature of 299K for different concentrations. Density and viscosity have been measured for a binary liquid mixture with a specific gravity bottle and a viscometer. Ultrasonic velocity has been measured using a single crystal interferometer at a frequency of 2 MHz. Ultrasonic velocities for the binary mixture at 1 MHz and 2 MHz was compared by taking some values from the literature. The sound velocity (V), density (ρ) and viscosity (η) were used to calculate the parameters such as adiabatic compressibility (β), acoustic impedance (Z), intermolecular free length (Lf), ultrasonic attenuation (α/f2) and relaxation time (τ). The variations of experimentally obtained parameters indicate the presence of molecular interaction between the molecules of the mixture. The ultrasonic velocity increased with an increase in concentration. Solute-solvent interaction is further confirmed by viscosity values, which increased with increasing concentration suggesting more association between solute and solvent molecules. The linear variations in Rao’s constant and Wada’s constant suggest the absence of complex formation.