bluuebunny/crossref_metadata_2025 huggingface dataset:
Combinatorial Therapy Using Dovitinib and ICI182.780 (Fulvestrant) Blocks Tumoral Activity of Endometrial Cancer Cells
Authors: Eritja Nuria , Domingo Mónica , Dosil Maria Alba , Mirantes Cristina , Santacana Maria , Valls Joan , Llombart-Cussac Antonio , Matias-Guiu Xavier , Dolcet Xavier
Published: January 2014

Mutations in fibroblast growth factor receptor 2 (FGFR2) have been recently described as a molecular-specific feature in endometrial carcinomas and the presence of activated FGFR2 mutations is associated with poor prognosis. For that reason, inhibition of FGFR2 could be a therapeutic target in the treatment of endometriod carcinomas. In this work, we investigated the antitumoral activity of dovitinib (a multiple kinase inhibitor) in human endometrial cancer cell (ECC) lines. We found that dovitinib caused cell growth arrest, loss of clonogenic growth, and cell-cycle arrest in FGFR2-mutated ECCs in in vitro and in vivo experiments. Next, we investigated the mechanistic basis of dovitinib effects. We could determine that dovitinib modified expression levels of well-known key cell-cycle regulatory proteins that induce cellular senescence. To further investigate the role of dovitinib, we analyzed its effect on estrogen receptor α (ER-α) expression. Surprisingly, we discovered that dovitinib enhances ER-α expression in FGFR2-mutant ECCs. Because blocking one signaling pathway is often not sufficient to cause total tumor regression and the effectiveness of individual inhibitors is often short-lived, we examined the impact of targeting FGFR2 with dovitinib in combination with a selective ER antagonist, fulvestrant (ICI182.780). Combination of dovitinib plus ICI182.780 resulted in a significantly higher inhibition of cell growth than dovitinib treatment alone. These findings suggest that combinatory therapies using dovitinib plus ICI182.780 treatment can be truly effective in patients with endometrial carcinomas carrying FGFR2 mutations. Mol Cancer Ther; 13(4); 776–87. ©2014 AACR.
Benign Breast and Gynecologic Conditions, Reproductive and Hormonal Factors, and Risk of Thyroid Cancer
Authors: Braganza Melissa Z. , Berrington de González Amy , Schonfeld Sara J. , Wentzensen Nicolas , Brenner Alina V. , Kitahara Cari M.
Published: January 2014

The higher incidence of thyroid cancer in women compared with men suggests an influence of sex steroid hormones in the etiology of this malignancy. We investigated a comprehensive set of potential indicators of lifetime sex steroid hormone exposure in relation to thyroid cancer risk. Using data from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which enrolled 70,047 women, 50 to 78 years old, we prospectively examined associations of self-reported history of benign breast and gynecologic conditions, reproductive factors, and exogenous sex hormone use with thyroid cancer risk. Multivariable-adjusted HRs and 95% confidence intervals (CI) were calculated in models using age as the time metric. During follow-up (median, 11 years), 127 women were diagnosed with first primary thyroid cancer. Older age at natural menopause (≥55 vs. <50 years; HR, 2.24; 95% CI, 1.20–4.18), greater estimated lifetime number of ovulatory cycles (≥490 vs. <415 cycles; HR, 2.40; 95% CI, 1.33–4.30), greater number of live births (≥5 vs. 1–2; HR, 1.72; 95% CI, 1.05–2.82), and history of uterine fibroids (HR, 1.72; 95% CI, 1.18–2.50) were associated with an increased risk of thyroid cancer. Earlier age at menarche, greater number of reproductive years, history of a tubal ligation, and history of ovarian cysts were nonsignificantly associated with increased thyroid cancer risk. No associations were observed for oral contraceptive use, menopausal hormone therapy, or history of benign breast disease or endometriosis. In general, we found that factors reflecting a greater length of exposure to endogenous hormones, particularly during the reproductive years, were associated with risk of postmenopausal thyroid cancer. Cancer Prev Res; 7(4); 418–25. ©2014 AACR.
Thyroidectomy for Graves' Disease: A Feasibility Study of the Robotic Transaxillary Approach
Authors: Noureldine Salem I. , Yao Lu , Wavekar Rohan R. , Mohamed Salah , Kandil Emad
Published: January 2014

Introduction: Graves' disease (GD) is considered a relative contraindication for endoscopic approaches to the thyroid gland, due to a larger gland size and increased vascularity. Methods: A retrospective analysis of a single surgeon's experience was performed. We included all patients who underwent thyroidectomy for the treatment of GD over a 3-year period. Results: Twenty-five patients with GD were identified. Twelve of them underwent robotic thyroidectomy and 13 patients underwent conventional thyroidectomy. Age, gender, and BMI were similar in both groups (p > 0.05). The conventional approach allowed for resection of larger thyroid volumes (147.3 ± 153.6 ml), as compared to the robotic approach (62.3 ± 47.8 ml, p = 0.08). The average total operative times were similar in both groups (p = 0.98). There was no difference with respect to intraoperative blood loss (p = 0.49), duration of hospital stay (p = 0.38), and complication rates (p = 0.99). Conclusion: Robotic thyroidectomy is feasible and can be safely performed in appropriately selected patients with GD.
Associations between Severity of Motor Function and Nonmotor Symptoms in Parkinson's Disease: A Post Hoc Analysis of the RECOVER Study
Authors: Swick Todd J. , Friedman Joseph H. , Chaudhuri K. Ray , Surmann Erwin , Boroojerdi Babak , Moran Kimberly , Ghys Liesbet , Trenkwalder Claudia
Published: January 2014

Background: RECOVER (NCT00474058), a double-blind, placebo-controlled trial in patients with Parkinson's disease (PD) and unsatisfactory early-morning motor symptom control, demonstrated significant improvements with rotigotine in early-morning motor function (Unified Parkinson's Disease Rating Scale [UPDRS] III), and nocturnal sleep disturbances (modified Parkinson's Disease Sleep Scale [PDSS-2]), and improvements in nonmotor symptoms (NMS; Non-Motor Symptom Scale [NMSS]). Methods: Post hoc analyses investigated the correlation between motor symptom and NMS severity in PD by evaluating associations between UPDRS III and both NMSS and PDSS-2 scores. Categories were defined for UPDRS III, NMSS, and PDSS-2 total scores; analyses were conducted for the full analysis set (n = 267). Results: There was a trend toward increasing PDSS-2 and NMSS total and domain scores with increasing UPDRS III category at baseline and end of maintenance (EoM). Pearson correlation coefficients between UPDRS III and both NMSS and PDSS-2 total and domain scores were r = 0.12-0.44 (r2 = 0.01-0.19) at baseline, r = 0.05-0.38 (r2 = 0.00-0.14) at EoM, and r = -0.02-0.36 (r2 = 0.00-0.13) for change from baseline to EoM. Conclusion: There was only a small correlation between severity of early-morning motor symptoms and overall burden of NMS and nocturnal sleep disturbances in RECOVER, suggesting that motor symptoms and NMS originate, at least partly, from distinct pathophysiological pathways.
Dysphagia following Acute Thalamic Haemorrhage: Clinical Correlates and Outcomes
Authors: Maeshima Shinichiro , Osawa Aiko , Yamane Fumitaka , Ishihara Shoichiro , Tanahashi Norio
Published: January 2014

Objective: A high incidence of dysphagia is seen during the acute phase of cerebral haemorrhage; however, there have been only rare reports of dysphagia caused by thalamic haemorrhage. We studied cases of thalamic haemorrhage during the acute period after hospitalization and examined the relationships between the frequency of dysphagia, stroke focus and haematoma volume. Methods: There were 113 subjects in this study, selected from 247 patients with thalamic haemorrhage who visited our rehabilitation centre. Patients were excluded if they had a history of dementia, stroke, confusion, epileptic seizure, surgical treatment or tracheotomy. We conducted a bedside swallowing assessment (BSA) by using the repetitive saliva swallowing test and modified water swallowing test. The relationships between oral intake condition at the time of hospital discharge, discharge destination (e.g. home), type of haematoma and haematoma volume were examined. Results: Abnormal BSA was found in 55% of the subjects (n = 62) with thalamic haemorrhage. Existence of a swallowing disorder was related to haematoma type and haematoma volume. A regular diet was possible in 41% of the subjects (n = 46). Age, haematoma volume, initial BSA evaluation and cognitive function had the greatest influence on a subject's ability to eat a general diet at the time of hospital discharge. Of those subjects in whom the initial BSA evaluation was normal, 70% were able to eat a regular diet at discharge. However, of those in whom the BSA evaluation was abnormal, >70% were discharged with enteral feeding. Furthermore, the rates of discharge to home were 95% in patients who could eat a regular diet and 30% in patients who needed enteral feeding. Conclusions: In the acute phase of thalamic haemorrhage, dysphagia was found in a high percentage of subjects. Dysphagia is associated with a poor prognosis for early hospital discharge.
Effects of Inhibitors of the Renin-Angiotensin System on the Efficacy of Interferon beta-1b: A post hoc Analysis of the BEYOND Study
Authors: Doerner M. , Beckmann K. , Knappertz V. , Kappos L. , Hartung H.P. , Filippi M. , O'Connor P.W. , Arnason B. , Cook S. , Jeffery D. , Comi G. , Limmroth V.
Published: January 2014

Background: In experimental autoimmune encephalomyelitis, inhibition of the renin-angiotensin system with angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors resulted in a significantly ameliorated disease course. We evaluated the effects of ARBs and ACE inhibitors on the efficacy of interferon beta-1b in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: In this post hoc analysis of the BEYOND (Betaferon Efficacy Yielding Outcomes of a New Dose) study, clinical and MRI end points were compared between patients treated with interferon beta-1b 250 or 500 µg and concomitant ARBs or ACE inhibitors and patients treated with interferon beta-1b 250 or 500 µg only (reference group). Results: Patients in the ARB group (n = 22) tended to have a higher relapse rate (0.48 vs. 0.23, p = 0.051) and a higher number of new gadolinium-enhancing lesions (0.6 vs. 0.3, p = 0.057) than patients in the reference group. Patients in the ACE inhibitor group (n = 49) also tended to have a higher relapse rate (0.29 vs. 0.22, p = 0.357). No differences were observed for the other end points. Conclusion: In the BEYOND study cohort, a concomitant medication with ARBs or ACE inhibitors did not have a beneficial effect in patients with RRMS treated with interferon beta-1b. As patients appeared to have a higher relapse rate, our results warrant further investigation.
High Prevalence of Severe Circulatory Complications with Diazoxide in Premature Infants
Authors: Yoshida Kayo , Kawai Masahiko , Marumo Chieko , Kanazawa Hoshinori , Matsukura Takashi , Kusuda Satoshi , Yorifuji Tohru , Heike Toshio
Published: January 2014

Background: Since diazoxide was approved for clinical use in Japan in 2008, its prescription for the treatment of infants with hyperinsulinemic hypoglycemia (HIH) has rapidly expanded. Concomitantly, reports of complications associated with diazoxide are increasing. Objectives: To clarify the trends and problems associated with the treatment of infants with HIH, we planned a nationwide surveillance in Japan. Methods: Questionnaires were sent to 255 institutions belonging to the Japanese Neonatologist Association inquiring about neonatal cases of HIH from 2009 to 2011. Results: One hundred nineteen cases of neonates with transient HIH (THIH) related to perinatal problems and 15 cases with permanent HIH (PHIH; hypoglycemia persisting beyond a year) or genetic HIH were reported. Sixty-four infants (53.8%) with THIH were administered diazoxide, and the administration was completed within 3 months in 46 infants (71.9%). Fourteen of the PHIH or genetic cases were treated with diazoxide and 7 of them (50%) had hypoglycemia persisting beyond a year. Circulatory complications were reported in 15 infants, i.e. 10 with THIH and 5 with PHIH. Multiple regression analysis revealed that a younger gestational age at birth and higher maximum doses of diazoxide were significant risk factors for circulatory complications. Conclusions: Diazoxide is widely prescribed for infants with HIH as a first-line medicine in Japan, but prophylactic diuretics are uncommon. Under these circumstances, a high prevalence of severe circulatory complications in very-low-birth-weight infants was reported.
Short-Term Changes in Ambient Temperature and Risk of Ischemic Stroke
Authors: Mostofsky Elizabeth , Wilker Elissa H. , Schwartz Joel , Zanobetti Antonella , Gold Diane R. , Wellenius Gregory A. , Mittleman Murray A.
Published: January 2014

Background: Despite consistent evidence of a higher short-term risk of cardiovascular mortality associated with ambient temperature, there have been discrepant findings on the association between temperature and ischemic stroke. Moreover, few studies have considered potential confounding by ambient fine particulate matter air pollution <2.5 μm in diameter (PM2.5) and none have examined the impact of temperature changes on stroke in the subsequent hours rather than days. The aim of this study was to evaluate whether changes in temperature trigger an ischemic stroke in the following hours and days and whether humid days are particularly harmful. Methods: We reviewed the medical records of 1,705 patients residing in the metropolitan region of Boston, Mass., USA, who were hospitalized with neurologist-confirmed ischemic stroke, and we abstracted data on the time of symptom onset and clinical characteristics. We obtained hourly meteorological data from the National Weather Service station and hourly PM2.5 data from the Harvard ambient monitoring station. We used the time-stratified case-crossover design to assess the association between ischemic stroke and apparent temperature averaged over 1-7 days prior to stroke onset adjusting for PM2.5. We assessed whether differences in apparent temperature trigger a stroke within shorter time periods by examining the association between stroke onset and apparent temperature levels averaged in 2-hour increments prior to stroke onset (0-2 h through 36-38 h). We tested whether the association varied by health characteristics or by PM2.5, ozone or relative humidity. Results: The incidence rate ratio of ischemic stroke was 1.09 (95% confidence interval 1.01-1.18) following a 5°C decrement in average apparent temperature over the 2 days preceding symptom onset. The higher risk associated with cooler temperatures peaked in the first 14-34 h. There was no statistically significant difference in the association between temperature and ischemic stroke across seasons. The risk of ischemic stroke was not meaningfully different across subgroups of patients defined by health characteristics. The association between ischemic stroke and ambient temperature was stronger on days with higher levels of relative humidity. Conclusions: Lower temperatures are associated with a higher risk of ischemic stroke onset in both warm and cool seasons, and the risk is higher on days with higher levels of relative humidity. Based on this study and the body of literature on ambient temperature and cardiovascular events, identifying methods for mitigating cardiovascular risk may be warranted.
Validation of the Thai Five-Minute Hearing Test to Screen Hearing Loss in the Community
Authors: Yimtae Kwanchanok , Kasemsiri Pornthep , Thanawirattananit Panida , Siripaopradith Pipop
Published: January 2014

Background: Hearing impairment affects communication, social interactions, and quality of life. Audiometry is the gold standard method for hearing assessment. However, it is impractical in a country with limited resources. This study aimed to validate the Thai version of the Five-Minute Hearing Test (Thai-FMHT) to screen hearing loss in the community. Methods: This prospective cohort study was conducted in Phu Wieng district, Khon Kaen Province, Thailand during July to September 2011. Subjects who were older than 18 years, could read or understand the Thai language, and wanted to participate were enrolled. Those who had aphasia, severe mental disability, or other conditions that precluded audiometry were excluded. The Thai-FMHT was first administered, followed by standard audiometry performed by audiologists who were blinded to the result of Thai-FMHT, and finally an ear examination was performed. This trial was registered with ClinicalTrial.gov as No. NCT01408992. Results: The 558 subjects, including 176 males (32%) and 382 females (68%), completed all of the procedures. The optimal cutoff point for hearing loss in this screen was 8. The sensitivity, specificity, and positive likelihood ratio of the Thai-FMHT to screen mild hearing loss (PTA0.5-2 kHz >25 dB) were 64.7% (95% CI, 56.1-72.7%), 60.0% (95% CI, 55.1-64.7%), and 1.62 (95% CI, 1.36-1.92), respectively. Regarding screening moderate hearing loss (PTA0.5-2 kHz >40 dB), the sensitivity, specificity, and positive likelihood ratio of the Thai-FMHT were 93.1% (95% CI, 77.2-99.2%), 56.5% (95% CI, 55.1-64.7%), and 2.1 (95% CI, 1.9-2.5), respectively. Conclusion: The Thai-FMHT has a lower cutoff point than does the original one. This test is suitable for use as a screening tool for hearing loss in the community.
Tripartite Conflicts of Interest and High Stakes Patent Extensions in the DSM-5
Authors: Cosgrove Lisa , Krimsky Sheldon , Wheeler Emily E. , Kaitz Jenesse , Greenspan Scott B. , DiPentima Nicole L.
Published: January 2014

Background: The revision process for and recent publication of the DSM-5 initiated debates about the widening of diagnostic boundaries. The pharmaceutical industry had a major financial stake in the outcome of these debates. This study examines the three-part relationship among DSM panel members, principal investigators (PIs) of clinical trials for new DSM-5 diagnoses, and drug companies. Methods: Financial conflicts of interest (FCOI) of DSM panel members responsible for some new diagnoses in the DSM-5 and PIs of clinical trials for related drug treatments were identified. Trials were found by searching ClinicalTrials.gov. Patent and revenue information about these drugs was found using the US Food and Drug Administration's Orange Book and manufacturer Annual Reports. Results: Thirteen trials met inclusion criteria (testing drugs for some new DSM disorders). Sixty-one percent of the DSM Task Force members and 27% of Work Group members reported FCOI to the trial drug manufacturers. In 5 of the 13 trials (38%), PIs reported ties other than research funding to the drug manufacturer. In 3 of the trials (23%), a PI had financial ties to the drug manufacturer and was also a DSM panel member who had decision-making authority over the revision process. Conclusions: These findings suggest that increased transparency (e.g., registration on ClinicalTrials.gov) and mandatory disclosure policies (e.g., the American Psychiatric Association's disclosure policy for DSM-5 panel members) alone may not be robust enough strategies to prevent the appearance of bias in both the DSM revision process as well as clinical decisions about appropriate interventions for DSM disorders.
Amino Acid Change in the Carbohydrate Response Element Binding Protein Is Associated With Lower Triglycerides and Myocardial Infarction Incidence Depending on Level of Adherence to the Mediterranean Diet in the PREDIMED Trial
Authors: Ortega-Azorín Carolina , Sorlí Jose V. , Estruch Ramón , Asensio Eva M. , Coltell Oscar , González José I. , Martínez-González Miguel Ángel , Ros Emilio , Salas-Salvadó Jordi , Fitó Montserrat , Arós Fernando , Lapetra José , Serra-Majem Lluís , Ruiz-Gutiérrez Valentina , Gómez-Gracia Enrique , Fiol Miquel , Flores Gemma , Pintó Xavier , Saiz Carmen , Ordovás José M. , Corella Dolores
Published: January 2014

Background—

A variant (rs3812316, C771G, and Gln241His) in the
MLXIPL
(Max-like protein X interacting protein-like) gene encoding the carbohydrate response element binding protein has been associated with lower triglycerides. However, its association with cardiovascular diseases and gene–diet interactions modulating these traits are unknown.

Methods and Results—

We studied 7166 participants in the PREvención with DIeta MEDiterránea trial testing a Mediterranean diet (MedDiet) intervention versus a control diet for cardiovascular prevention, with a median follow-up of 4.8 years. Diet, lipids,
MLXIPL
polymorphisms, and cardiovascular events were assessed. Data were analyzed at baseline and longitudinally. We used multivariable-adjusted Cox regression to estimate hazard ratios for cardiovascular outcomes. The
MLXIPL
-rs3812316 was associated with lower baseline triglycerides (
P
=5.5×10
−5
) and lower hypertriglyceridemia (odds ratio, 0.73; 95% confidence interval [CI], 0.63–0.85;
P
=1.4×10
−6
in G-carriers versus CC). This association was modulated by baseline adherence to MedDiet. When adherence to MedDiet was high, the protection was stronger (odds ratio, 0.63; 95% CI, 0.51–0.77;
P
=8.6×10
−6
) than when adherence to MedDiet was low (odds ratio, 0.88; 95% CI, 0.70–1.09;
P
=0.219). Throughout the follow-up, both the
MLXIPL
-rs3812316 (
P
=3.8×10
−6
) and the MedDiet intervention (
P
=0.030) were significantly associated with decreased triglycerides. Likewise in G-carriers MedDiet intervention was associated with greater total cardiovascular risk reduction and specifically for myocardial infarction. In the MedDiet, but not in the control group, we observed lower myocardial infarction incidence in G-carriers versus CC (hazard ratios, 0.34; 95% CI, 0.12–0.93;
P
=0.036 and 0.90; 95% CI, 0.35–2.33;
P
=0.830, respectively).

Conclusions—

Our novel results suggest that MedDiet enhances the triglyceride-lowering effect of the
MLXIPL
-rs3812316 variant and strengthens its protective effect on myocardial infarction incidence.

Clinical Trial Registration—

URL:
www.controlled-trials.com
. Unique Identifier: ISRCTN35739639.
Hyperactive Adverse Mechanical Stress Responses in Dystrophic Heart Are Coupled to Transient Receptor Potential Canonical 6 and Blocked by cGMP–Protein Kinase G Modulation
Authors: Seo Kinya , Rainer Peter P. , Lee Dong-ik , Hao Scarlett , Bedja Djahida , Birnbaumer Lutz , Cingolani Oscar H. , Kass David A.
Published: January 2014

Rationale:

The heart is exquisitely sensitive to mechanical stimuli to adapt rapidly to physiological demands. In muscle lacking dystrophin, such as Duchenne muscular dystrophy, increased load during contraction triggers pathological responses thought to worsen the disease. The relevant mechanotransducers and therapies to target them remain unclear.

Objectives:

We tested the role of transient receptor potential canonical (TRPC) channels TRPC3 and TRPC6 and their modulation by protein kinase G (PKG) in controlling cardiac systolic mechanosensing and determined their pathophysiological relevance in an experimental model of Duchenne muscular dystrophy.

Methods and Results:

Contracting isolated papillary muscles and cardiomyocytes from controls and mice genetically lacking either TRPC3 or TRPC6 were subjected to auxotonic load to induce stress-stimulated contractility (SSC, gradual rise in force and intracellular Ca
2+
). Incubation with cGMP (PKG activator) markedly blunted SSC in controls and
Trpc3
−/−
; whereas in
Trpc6
−/−
, the resting SSC response was diminished and cGMP had no effect. In Duchenne muscular dystrophy myocytes (
mdx
/utrophin deficient), the SSC was excessive and arrhythmogenic. Gene deletion or selective drug blockade of TRPC6 or cGMP/PKG activation reversed this phenotype. Chronic phosphodiesterase 5A inhibition also normalized abnormal mechanosensing while blunting progressive chamber hypertrophy in Duchenne muscular dystrophy mice.

Conclusions:

PKG is a potent negative modulator of cardiac systolic mechanosignaling that requires TRPC6 as the target effector. In dystrophic hearts, excess SSC and arrhythmia are coupled to TRPC6 and are ameliorated by its targeted suppression or PKG activation. These results highlight novel therapeutic targets for this disease.
Does Transendocardial Injection of Mesenchymal Stem Cells Improve Myocardial Function Locally or Globally?
Authors: Suncion Viky Y. , Ghersin Eduard , Fishman Joel E. , Zambrano Juan Pablo , Karantalis Vasileios , Mandel Nicole , Nelson Katarina H. , Gerstenblith Gary , DiFede Velazquez Darcy L. , Breton Elayne , Sitammagari Kranthi , Schulman Ivonne H. , Taldone Sabrina N. , Williams Adam R. , Sanina Cristina , Johnston Peter V. , Brinker Jeffrey , Altman Peter , Mushtaq Muzammil , Trachtenberg Barry , Mendizabal Adam M. , Tracy Melissa , Da Silva Jose , McNiece Ian K. , Lardo Alberto C. , George Richard T. , Hare Joshua M. , Heldman Alan W.
Published: January 2014

Rationale:

Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown.

Objective:

To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments.

Methods and Results:

Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (−43.7±4.4%; n=95;
P
<0.01) and noninjected segments (−25.1±7.8%; n=148;
P
<0.001; between-group comparison
P
<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9±3.3–26.3±3.5%;
P
=0.003) but not in noninjected scar segments (21.3±2.6–23.5±3.2%;
P
=0.20; between-group comparison
P
<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20% (12.1±1.2–19.9±2.7%; n=18;
P
=0.003), versus <20% (31.7±3.4–35.5±3.3%; n=12;
P
=0.33, between-group comparison
P
<0.0001).

Conclusions:

These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.
Plasmin Cleavage of von Willebrand Factor as an Emergency Bypass for ADAMTS13 Deficiency in Thrombotic Microangiopathy
Authors: Tersteeg Claudia , de Maat Steven , De Meyer Simon F. , Smeets Michel W.J. , Barendrecht Arjan D. , Roest Mark , Pasterkamp Gerard , Fijnheer Rob , Vanhoorelbeke Karen , de Groot Philip. G. , Maas Coen
Published: January 2014

Background—

Von Willebrand factor (VWF) multimer size is controlled through continuous proteolysis by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type I motif, member 13). This prevents spontaneous platelet agglutination and microvascular obstructions. ADAMTS13 deficiency is associated with thrombotic thrombocytopenic purpura, in which life-threatening episodes of microangiopathy damage kidneys, heart, and brain. Enigmatically, a complete ADAMTS13 deficiency does not lead to continuous microangiopathy. We hypothesized that plasmin, the key enzyme of the fibrinolytic system, serves as a physiological backup enzyme for ADAMTS13 in the degradation of pathological platelet–VWF complexes.

Methods and Results—

Using real-time microscopy, we determined that plasmin rapidly degrades platelet–VWF complexes on endothelial cells in absence of ADAMTS13, after activation by urokinase-type plasminogen activator or the thrombolytic agent streptokinase. Similarly, plasmin degrades platelet–VWF complexes in platelet agglutination studies. Plasminogen directly binds to VWF and its A1 domain in a lysine-dependent manner, as determined by enzyme-linked immunosorbent assay. Plasma levels of plasmin–α
2
-antiplasmin complexes increase with the extent of thrombocytopenia in patients with acute episodes of thrombotic thrombocytopenic purpura, independent of ADAMTS13 activity. This indicates that plasminogen activation takes place during microangiopathy. Finally, we show that the thrombolytic agent streptokinase has therapeutic value for
Adamts13
−/−
mice in a model of thrombotic thrombocytopenic purpura.

Conclusions—

We propose that plasminogen activation on endothelial cells acts as a natural backup for ADAMTS13 to degrade obstructive platelet–VWF complexes. Our findings indicate that thrombolytic agents may have therapeutic value in the treatment of microangiopathies and may be useful to bypass inhibitory antibodies against ADAMTS13 that cause thrombotic thrombocytopenic purpura.
IL‐6 Regulates Extracellular Matrix Remodeling Associated With Aortic Dilation in a Fibrillin‐1 Hypomorphic mgR/mgR Mouse Model of Severe Marfan Syndrome
Authors: Ju Xiaoxi , Ijaz Talha , Sun Hong , LeJeune Wanda , Vargas Gracie , Shilagard Tuya , Recinos Adrian , Milewicz Dianna M. , Brasier Allan R. , Tilton Ronald G.
Published: January 2014

Background

Development of thoracic aortic aneurysms is the most significant clinical phenotype in patients with Marfan syndrome. An inflammatory response has been described in advanced stages of the disease. Because the hallmark of vascular inflammation is local interleukin‐6 (IL‐6) secretion, we explored the role of this proinflammatory cytokine in the formation of aortic aneurysms and rupture in hypomorphic fibrillin‐deficient mice (mgR/mgR).

Methods and Results

MgR/mgR mice developed ascending aortic aneurysms with significant dilation of the ascending aorta by 12 weeks (2.7±0.1 and 1.3±0.1 for mgR/mgR versus wild‐type mice, respectively;
P
<0.001). IL‐6 signaling was increased in mgR/mgR aortas measured by increases in IL‐6 and SOCS3 mRNA transcripts (
P
<0.05) and in cytokine secretion of IL‐6, MCP‐1, and GM‐CSF (
P
<0.05). To investigate the role of IL‐6 signaling, we generated mgR homozygous mice with IL‐6 deficiency (DKO). The extracellular matrix of mgR/mgR mice showed significant disruption of elastin and the presence of dysregulated collagen deposition in the medial‐adventitial border by second harmonic generation multiphoton autofluorescence microscopy. DKO mice exhibited less elastin and collagen degeneration than mgR/mgR mice, which was associated with decreased activity of matrix metalloproteinase‐9 and had significantly reduced aortic dilation (1.0±0.1 versus 1.6±0.2 mm change from baseline, DKO versus mgR/mgR,
P
<0.05) that did not affect rupture and survival.

Conclusion

Activation of IL‐6‐STAT3 signaling contributes to aneurysmal dilation in mgR/mgR mice through increased MMP‐9 activity, aggravating extracellular matrix degradation.
Prevention Opportunities for Oral Contraceptive–Associated Ischemic Stroke
Authors: Ryan Kathleen A. , Cole John W. , Saslow Keely , Mitchell Braxton D. , McArdle Patrick F. , Sparks Mary J. , Cheng Yu-Ching , Kittner Steven J.
Published: January 2014

Background and Purpose—

Literature suggests a small increased risk of ischemic stroke with oral contraception (OC) use. We evaluated the association of stroke and OC use in women on the basis of whether they recalled being advised by a physician not to use OC or to discontinue OC use because of the presence of stroke risk modifiers, and whether such advice resulted in behavioral change.

Methods—

A total of 572 women (224 strokes and 348 controls) aged 15 to 49 years were interviewed about OC use and risk modifiers, including cigarette smoking and headaches, among others.

Results—

The adjusted odds ratio for OC use and stroke was 2.00 (95% confidence interval, 1.29–3.09). The association of OC use with stroke was stronger in women that reported receiving doctor’s advice against OC use because of the presence of other stroke risk modifiers (odds ratio, 3.12; 95% confidence interval, 1.62–6.00) than in women who did not recall receiving such advice (odds ratio, 1.31; 95%confidence interval, 0.71–2.43). Of 256 women who recalled being advised by their doctor not to start OC or to discontinue OC use because of the presence of other stroke risk modifiers, 24% were still on OC at the time of stroke or interview.

Conclusions—

We confirm that certain medical conditions increase the risk of stroke during OC use and demonstrate the importance of physician counseling in those using OC in the setting of concurrent high-risk conditions and the need for improved patient compliance with such counseling.
Homocysteine as a Predictor of Early Neurological Deterioration in Acute Ischemic Stroke
Authors: Kwon Hyung-Min , Lee Yong-Seok , Bae Hee-Joon , Kang Dong-Wha
Published: January 2014

Background and Purpose—

Hyperhomocysteinemia is a well-known risk factor for vascular disease. However, its action, mechanism, and role in the acute phase of stroke have not been determined. We tried to determine whether an association existed between elevated serum homocysteine levels and early neurological deterioration (END) in patients with acute ischemic stroke.

Methods—

We performed a secondary analysis from the Cilostazol in Acute Ischemic Stroke Treatment (CAIST) trial, which was a double-blinded, randomized, multicenter trial, assessing the noninferiority of cilostazol over aspirin within 48 hours of an acute ischemic stroke. END was defined as an increase of ≥1 point in motor power or an increase of ≥2 points in the total National Institute of Health Stroke Scale score within 7 days.

Results—

The mean (±SD) serum homocysteine level was 11.4±4.7 μmol/L. Of the 396 patients studied, 57 (14.4%) patients worsened during the 7 days after inclusion. Most (68%) of the END cases occurred within the first 24 hours after treatment. High levels (>10.3 μmol/L) of serum homocysteine were independent predictors for END (third quartile odds ratio, 3.45; 95% confidence intervals, 1.25–9.50;
P
=0.016; fourth quartile odds ratio, 3.36; 95% confidence intervals 1.18–9.52;
P
=0.023) in multivariate analysis.

Conclusions—

Patients with acute stroke with elevated serum homocysteine levels are at an increased risk for END.
Tangible User Interface Design for Climate Change Education in Interactive Installation Art
Authors: de Bérigny Caitilin , Gough Phillip , Faleh Majdi , Woolsey Erika
Published: January 2014

The authors discuss how tangible user interface objects can be important educational and entertainment tools in environmental education. The authors describe their interactive installation artwork Reefs on the Edge, which incorporates tangible user interface objects and combines environmental science and multiple art forms to explore coral reef ecosystems that are threatened by the effects of climate change. The authors/artists argue that the use of tangible user interface in an installation-art setting can help engage and inform the public about crucial environmental issues.
Artist as Scientist in a Reflective Universe: A Process of Discovery
Authors: Hirsch Gilah Yelin
Published: January 2014

Combining years as an artist in solitary wilderness sojourns with biomedical and neuroscientific investigation concerning mind/body patterning, the author has blended art and science to reveal existing relationships between form in nature, form in human physiology and behavior, and the forms that are universally present in all alphabets. Her understanding that the artist brings abstraction into form, while the scientist brings form into abstraction, coupled with her experience in diverse world cultures, has prompted her to contemplate the hardwired wisdom of the body as the repository of intrinsic knowledge leading toward health and behavior benefiting the greater good.
Art as a Stimulus for Structural DNA Nanotechnology
Authors: Seeman Nadrian C.
Published: January 2014

The linear, double-helical structure of DNA was initially recognized as beautiful, as well as being informative about the mechanism of heredity. Recently, branched DNA molecules have been used to produce nanoscale objects, crystals and machines, all the products of a new field: structural DNA nanotechnology. The inspiration for much of this work has been art, starting from the notion that Escher's woodcut Depth was analogous to a molecular crystal of branched DNA. The article describes how connecting branched molecules together with the “sticky ends” used by genetic engineers has led to 3D crystals, and how Dalí's Butterfly Landscape illuminates the relationship between wrappings of DNA and the crossings in knots or links. Disparate aesthetic patterns are related to branched DNA motifs and constructions.
Information-Based Development Trend of Building Skin Design
Authors: Feng Liang , Yuhong Liang , Jian Li
Published: January 2014

From the perspective of Information design science, this thesis discusses the fact that in the transition of the entire society toward informatization, building skins have unprecedentedly picked up more complex functions and borne more social responsibilities, as shown in the following aspects: As the interaction between outdoor advertising media and humans and environment, as the media that link up indoor and outdoor information and as the media for indoor householders to express their needs, the infiltration of being digital into the architectural field has made building skins the interface for human-computer interaction in a broad sense. Accordingly, in addition to professional skills, architectural designers must keep on learning the knowledge and methods of digital interactive design and develop the awareness of studying inhabitants' behaviors. Architectural design has become an integration process of massive information in a way that is different from traditional design ideas. Therefore, designers need to look for more appropriate building skin design methods in this new period of architectural design.
Fusion of Art and Technology in Professional Cycling Sportswear Design
Authors: Luo Jie , Mao Aihua , Au Joe S. , Li Yi , Zhang Xing
Published: January 2014

Cycling sportswear that meets the multiple functional requirements of thermal comfort, biomechanical protection and aesthetics is highly demanded by cyclists. These multiple functional requirements lead to innovations in cycling sportswear design based on multi-disciplinary knowledge integration and fusion of art and technology. A theoretical model for cycling sportswear design is developed in this paper to model the design process by systematically integrating different knowledge and identifying the relationships between them. This model demonstrates that the design innovation of cycling sportswear is the fusion of aesthetic design with thermal and biomechanical functional design, which meets cyclists' demand for wearing comfort, relief of muscle fatigue and beautiful appearance.
Ancient Chinese Thought of Character Formation & Modern Logo Design
Authors: Wusan Dai
Published: January 2014

The pictograph is the core of ancient Chinese characters. In recent years, Chinese characters, especially the ancient oracle-bone inscriptions and seal characters, are often adopted in logo design in China. This article analyzes the concise thought adopted in ancient character-creating, such as “highlighting characteristics”, “simplifying”, and “less for more”, and probes into the application of such ancient thought with modern design cases, in an attempt to establish evaluation standards for the integration of culture and art.
Review of the grassland leafhopper genus Nephotettix Matsumura (Hemiptera: Cicadellidae: Deltocephalinae: Chiasmini) from the Chinese mainland
Authors: DUAN YANI , ZHANG YALIN
Published: January 2014

The Chinese mainland species of the leafhopper genus Nephotettix Matsumura (Hemiptera: Cicadellidae: Deltocephalinae: Chiasmini) (Nephotettix cincticeps (Uhler), Nephotettix malayanus Ishihara & Kawase, Nephotettix nigropictus (Stål), Nephotettix parvus Ishihara & Kawase rec. n., and Nephotettix virescens (Distant)) are reviewed. This genus is redescribed. Variation is described and illustrated. Keys for their separation are provided together with a worldwide checklist.
Spazigasteroides a new genus from China with a black face and scutellum in the Syrphini (Diptera: Syrphidae)
Authors: HUO KE-KE
Published: January 2014

In the present paper, the genus Spazigasteroides gen. nov. (Diptera, Syrphidae), with Spazigasteroides caeruleus sp. nov. as type species, is described from China. The new genus bears the following characters: Head strongly concave posteriorly and closely appressed to thorax so that the bare postpronota are entirely hidden. Face black in ground colour. Antennae short, with basoflagellomeres slightly longer than wide. Scutellum black. Postmetacoxal bridge incomplete. Legs simple, slender. Wing vein R4+5 straight, vein r-m at basal third of cell dm. Abdomen petiolate, longer than head and thorax together. Male aedeagus two segmented. Based on the subdivision of Syrphinae by Vockeroth (1992), the new genus belongs to the tribe Syrphini, it is separated from the genera of the tribe Syrphini by both the face and scutellum black. In appearance the new genus is also similar to the genus Spazigaster Rondani, the tribe Bacchini, but it is differentiated from the genera of the tribe Bacchini by the two segmented aedeagus.
Cottus schitsuumsh, a new species of sculpin (Scorpaeniformes: Cottidae) in the Columbia River basin, Idaho-Montana, USA
Authors: LEMOINE MICHAEL , YOUNG MICHAEL K. , MCKELVEY KEVIN S. , EBY LISA , PILGRIM KRISTINE L. , SCHWARTZ MICHAEL K.
Published: January 2014

Fishes of the genus Cottus have long been taxonomically challenging because of morphological similarities among species and their tendency to hybridize, and a number of undescribed species may remain in this genus. We used a combination of genetic and morphological methods to delineate and describe Cottus schitsuumsh, Cedar Sculpin, a new species, from the upper Columbia River basin, Idaho-Montana, USA. Although historically confused with the Shorthead Sculpin (C. confusus), the genetic distance between C. schitsuumsh and C. confusus (4.84–6.29%) suggests these species are distant relatives. Moreover, the two species can be differentiated on the basis of lateral-line pores on the caudal peduncle, head width, and interpelvic width. Cottus schitsuumsh is also distinct from all other Cottus in this region in having a single small, skin-covered, preopercular spine. Haplotypes of mtDNA cytochrome oxidase c subunit 1 of C. schitsuumsh differed from all other members of the genus at three positions, had interspecific genetic distances typical for congeneric fishes (1.61–2.74% to nearest neighbors), and were monophyletic in maximum-likelihood trees. Microsatellite analyses confirmed these taxonomic groupings for species potentially sympatric with C. schitsuumsh and that fish used in morphological comparisons were unlikely to be introgressed. Its irregular distribution, in the Spokane River basin in Idaho and portions of the Clark Fork River basin in Montana, may have resulted from human-assisted translocation.
Eviota piperata, a new gobiid species from Palau (Teleostei: Gobiidae)
Authors: Greenfield David W. , WINTERBOTTOM RICHARD
Published: January 2014

A new species of dwarfgoby, Eviota piperata is described from Palau. It belongs to the cephalic sensory-pore system Group II (lacking only the IT pore); has a dorsal/anal-fin formula of 8/8; has some pectoral-fin rays branched; no dark spot over the ural centrum; the male genital papilla is not fimbriate; and the cheek and body are heavily peppered with chromatophores.
A revision of the subgenus Bessobates of the genus Netelia from Japan (Hymenoptera, Ichneumonidae, Tryphoninae)
Authors: KONISHI KAZUHIKO
Published: January 2014

Japanese species of the genus Netelia of the subgenus Bessobates are revised. Fourteen species are recognized. Four new species, N. (B.) longipad, N. (B.) nigridorsalis, N. (B.) nodai and N. (B.) yakushimensis, are described. Six species, N. (B.) comitor Tolkanitz, 1974, N. (B.) frenata Tolkanitz, 1981, N. (B.) gansuana (Kokujev, 1906), N. (B.) kiuhabona (Uchida, 1928), N. (B.) nanaki Kaur & Jonathan, 1979 and N. (B.) pallescens (Schmiedeknecht, 1910) are recorded from Japan for the first time and redescribed based on Japanese specimens. Male genitalia of N. (B.) yamatoensis (Uchida, 1934) are figured and described for the first time. Netelia (Bessobates) odaiensis (Uchida, 1934) is removed from synonym with virgata and treated as species incertae sedis. Three species, N. (B.) cristata (Thomson, 1888), N. (B.) latungula (Thomson, 1888) and N. (B.) virgata (Geoffroy, 1785) are redescribed based on Japanese specimens. A key to 14 Japanese species is given.
Checklist of the New Zealand Heteroptera (Insecta: Hemiptera): an update based on the 2004 to 2013 literature
Authors: Larivière Marie-Claude , Larochelle André
Published: January 2014

An updated checklist of the New Zealand Heteroptera (Insecta: Hemiptera) is provided as a supplement to the “Heteroptera (Insecta: Hemiptera): catalogue” of Larivière and Larochelle (2004: Fauna of New Zealand 50). A total of 142 genera and 319 species belonging to 28 families are recorded for New Zealand. Changes to the 2004 catalogue are documented. The synonymy and primary type information of taxa described between 2004 and July 2013 are also given. The presence of the anthocorid Macrotrachelia nigronitens in New Zealand is confirmed.
A new species of Palpomyia Meigen (Diptera: Ceratopogonidae) described in all life stages from Shillong plateau, India
Authors: PAUL NILOTPOL , MAZUMDAR ABHIJIT , MAZUMDAR ABHIJIT
Published: January 2014

Life stages of Palpomyia sohraensis sp. n. is described and illustrated with bio-ecological notes. Key to the adult of the all species from India of the genus Palpomyia Meigen is also provided. The complete life stages of any Palpomyia are described for the first time from the Oriental Region.
Cloud and Radiative Balance Changes in Response to ENSO in Observations and Models
Authors: Radley Claire , Fueglistaler Stephan , Donner Leo
Published: January 2014

The authors use observations and four GFDL AGCMs to analyze the relation between variations in spatial patterns and area-averaged quantities in the top-of-the-atmosphere radiative fluxes, cloud amount, and precipitation related to El Niño over the period 1979–2008. El Niño is associated with an increase in tropical average sea surface temperature of order +0.1 K (with a maxima of +0.5 K), large local anomalies of +2 K (maxima +6 K), and tropical tropospheric warming of +0.5 K (maxima +1 K). The authors find that model-to-observation biases in the base state translate into corresponding biases in anomalies in response to El Niño. The pattern and amplitude of model biases in reflected shortwave (SW) and outgoing longwave radiation (OLR) follows expectations based on their biases in cloud amount: models with a positive cloud amount bias, compared to observations, have too strong local responses to El Niño in cloud amount, SW, OLR, and precipitation.

Tropical average OLR increases in response to El Niño in observations and models [correlation coefficients (r) with Niño-3.4 index in the range 0.4–0.6]. Weaker correlations are found for SW (r: −0.6 to 0), cloud amount (r: −0.2 to +0.1), and precipitation (r: −0.2 to 0). Compositing El Niño events over the period 2001–07 yields similar results. These results are consistent with El Niño periods being warmer due to a heat pulse from the ocean, and a weak response in clouds and their radiative effect. These weak responses occur despite a large rearrangement in the spatial structure of the tropical circulation, and despite substantial differences in the mean state of observations and models.