bluuebunny/crossref_metadata_2025 huggingface dataset:
Guide Catheter-Induced Aortic Dissection Complicated by Pericardial Effusion with Pulsus Paradoxus: A Case Report of Successful Medical Management
Authors: Fiddler Magdalene , Avadhani Sriya A. , Marmur Jonathan D.
Published: January 2015

Aortic dissection is a rare but potentially fatal complication of percutaneous coronary intervention (PCI). Management strategies of PCI induced dissection are not clearly identified in literature; such occurrences often mandate surgical repair of the aortic root with reimplantation of the coronary arteries. Another trend seen in case reports is the use of coronary-aortic stenting if such lesions permit. Several factors impact the management decision including the hemodynamic stability of the patient; mechanism of aortic injury; size, severity, and direction of propagation of the dissection; presence of an intimal flap; and preexisting atherosclerotic disease. We describe a case of a 65-year-old woman who underwent PCI for a chronic right coronary artery (RCA) occlusion, which was complicated by aortic dissection and pericardial effusion. Our case report suggests that nonsurgical management may also be appropriate for PCI induced dissections, and potentially even those associated with new pericardial effusion.
Computational Study of Correlated Domain Motions in the AcrB Efflux Transporter
Authors: Schulz Robert , Vargiu Attilio V. , Ruggerone Paolo , Kleinekathöfer Ulrich
Published: January 2015

As active part of the major efflux system inE. colibacteria, AcrB is responsible for the uptake and pumping of toxic substrates from the periplasm toward the extracellular space. In combination with the channel protein TolC and membrane fusion protein AcrA, this efflux pump is able to help the bacterium to survive different kinds of noxious compounds. With the present study we intend to enhance the understanding of the interactions between the domains and monomers, for example, the transduction of mechanical energy from the transmembrane domain into the porter domain, correlated motions of different subdomains within monomers, and cooperative effects between monomers. To this end, targeted molecular dynamics simulations have been employed either steering the whole protein complex or specific parts thereof. By forcing only parts of the complex towards specific conformational states, the risk for transient artificial conformations during the simulations is reduced. Distinct cooperative effects between the monomers in AcrB have been observed. Possible allosteric couplings have been identified providing microscopic insights that might be exploited to design more efficient inhibitors of efflux systems.
Analysis of the Seismic Performance of Isolated Buildings according to Life-Cycle Cost
Authors: Dang Yu , Han Jian-ping , Li Yong-tao
Published: January 2015

This paper proposes an indicator of seismic performance based on life-cycle cost of a building. It is expressed as a ratio of lifetime damage loss to life-cycle cost and determines the seismic performance of isolated buildings. Major factors are considered, including uncertainty in hazard demand and structural capacity, initial costs, and expected loss during earthquakes. Thus, a high indicator value indicates poor building seismic performance. Moreover, random vibration analysis is conducted to measure structural reliability and evaluate the expected loss and life-cycle cost of isolated buildings. The expected loss of an actual, seven-story isolated hospital building is only 37% of that of a fixed-base building. Furthermore, the indicator of the structural seismic performance of the isolated building is much lower in value than that of the structural seismic performance of the fixed-base building. Therefore, isolated buildings are safer and less risky than fixed-base buildings. The indicator based on life-cycle cost assists owners and engineers in making investment decisions in consideration of structural design, construction, and expected loss. It also helps optimize the balance between building reliability and building investment.
Hair Barrette Induced Cochlear Implant Receiver Stimulator Site Infection with Extrusion
Authors: Le Trung N. , Hochman Jordan , Leitao Darren
Published: January 2015

Background. Cochlear implant infections and extrusion are uncommon but potentially devastating complications. Recent literature suggests conservative management can be employed. Local measures inclusive of aggressive surgical debridement with vascularized flaps and parenteral antibiotics represent a viable option and often permit device salvage. However, explantation should be considered if there is evidence of systemic, intracranial, or intractable infection.Method. A Case report and literature review.Case Report. This case illustrates a complicated local wound infection associated with cochlear implantation due to transcutaneous adherence of a ferrous hair barrette to a cochlear implant magnet. Reconstruction of computed tomography (CT) data with 3D volume rendering significantly improved the value of the images and facilitated patient counseling as well as operative planning.Conclusion. Cochlear implant infections can be associated with foreign bodies. CT images are beneficial in the evaluation of cochlear implant complications. 3D CT images provide a comprehensive view of the site of interest, displaying the relationship of the hardware to the skull and soft tissues, while minimizing associated artifacts. Cochlear implant patients should consider use of nonmetallic hair devices.
On Transitive Points in a Generalized Shift Dynamical System
Authors: Taherkhani Bahman , Ayatollah Zadeh Shirazi Fatemah
Published: January 2015

Considering point transitive generalized shift dynamical system (XΓ, σφ) for discrete X with at least two elements and infinite Γ, we prove that X is countable and Γ has at most elements. Then, we find a transitive point of the dynamical system for with τ(n, m) = (n, m + 1) and show that point transitive (XΓ, σφ), for infinite countable Γ, is a factor of .
Immobilization of Papain on Chitin and Chitosan and Recycling of Soluble Enzyme for Deflocculation of Saccharomyces cerevisiae from Bioethanol Distilleries
Authors: Silva Douglas Fernandes , Rosa Henrique , Carvalho Ana Flavia Azevedo , Oliva-Neto Pedro
Published: January 2015

Yeast flocculation (Saccharomyces cerevisiae) is one of the most important problems in fuel ethanol production. Yeast flocculation causes operational difficulties and increase in the ethanol cost. Proteolytic enzymes can solve this problem since it does not depend on these changes. The recycling of soluble papain and the immobilization of this enzyme on chitin or chitosan were studied. Some cross-linking agents were evaluated in the action of proteolytic activity of papain. The glutaraldehyde (0.1–10% w·v−1), polyethyleneimine (0.5% v·v−1), and tripolyphosphate (1–10% w·v−1) inactivated the enzyme in this range, respectively. Glutaraldehyde inhibited all treatments of papain immobilization. The chitosan cross-linked with TPP in 5 h of reaction showed the yield of active immobilized enzyme of 15.7% and 6.07% in chitosan treated with 0.1% PEI. Although these immobilizations have been possible, these levels have not been enough to cause deflocculation of yeast cells. Free enzyme was efficient for yeast deflocculation in dosages of 3 to 4 g·L−1. Recycling of soluble papain by centrifugation was effective for 14 cycles with yeast suspension in time perfectly compatible to industrial conditions. The reuse of proteases applied after yeast suspension by additional yeast centrifugation could be an alternative to cost reduction of these enzymes.
Articular Cartilage Repair Using Marrow Stimulation Augmented with a Viable Chondral Allograft: 9-Month Postoperative Histological Evaluation
Authors: Hoffman James K. , Geraghty Sandra , Protzman Nicole M.
Published: January 2015

Marrow stimulation is frequently employed to treat focal chondral defects of the knee. However, marrow stimulation typically results in fibrocartilage repair tissue rather than healthy hyaline cartilage, which, over time, predisposes the repair to failure. Recently, a cryopreserved viable chondral allograft was developed to augment marrow stimulation. The chondral allograft is comprised of native viable chondrocytes, chondrogenic growth factors, and extracellular matrix proteins within the superficial, transitional, and radial zones of hyaline cartilage. Therefore, host mesenchymal stem cells that infiltrate the graft from the underlying bone marrow following marrow stimulation are provided with the optimal microenvironment to undergo chondrogenesis. The present report describes treatment of a trochlear defect with marrow stimulation augmented with this novel chondral allograft, along with nine month postoperative histological results. At nine months, the patient demonstrated complete resolution of pain and improvement in function, and the repair tissue consisted of 85% hyaline cartilage. For comparison, a biopsy obtained from a patient 8.2 months after treatment with marrow stimulation alone contained only 5% hyaline cartilage. These outcomes suggest that augmenting marrow stimulation with the viable chondral allograft can eliminate pain and improve outcomes, compared with marrow stimulation alone.
Feasibility Study of Automated Framework for Estimating Lung Tumor Locations for Target-Based Patient Positioning in Stereotactic Body Radiotherapy
Authors: Yoshidome Satoshi , Arimura Hidetaka , Nakamura Katsumasa , Shioyama Yoshiyuki , Atsumi Kazushige , Nakamura Yasuhiko , Yoshikawa Hideki , Nishikawa Kei , Hirata Hideki
Published: January 2015

Objective.To investigate the feasibility of an automated framework for estimating the lung tumor locations for tumor-based patient positioning with megavolt-cone-beam computed tomography (MV-CBCT) during stereotactic body radiotherapy (SBRT).Methods.A lung screening phantom and ten lung cancer cases with solid lung tumors, who were treated with SBRT, were employed to this study. The locations of tumors in MV-CBCT images were estimated using a tumor-template matching technique between a tumor template and the MV-CBCT. Tumor templates were produced by cropping the gross tumor volume (GTV) regions, which were enhanced by a Sobel filter or a blob structure enhancement (BSE) filter. Reference tumor locations (grand truth) were determined based on a consensus between a radiation oncologist and a medical physicist.Results.According to the results of the phantom study, the average Euclidean distances of the location errors in the original, Sobel-filtered, and BSE-filtered images were 2.0 ± 4.1 mm, 12.8 ± 9.4 mm, and 0.4 ± 0.5 mm, respectively. For clinical cases, these were 3.4 ± 7.1 mm, 7.2 ± 11.6 mm, and 1.6 ± 1.2 mm, respectively.Conclusion.The feasibility study suggests that our proposed framework based on the BSE filter may be a useful tool for tumor-based patient positioning in SBRT.
The Associations of Novel Vitamin D3Metabolic GeneCYP27A1Polymorphism, Adiponectin/Leptin Ratio, and Metabolic Syndrome in Middle-Aged Taiwanese Males
Authors: Cheng Kai-Hung , Hsi Edward , Liu Chia-Chu , Huang Chun-Nung , Lee Yung-Chin , Chu Chih-Sheng , Bao Bo-Ying , Chang Chu-Fen , Huang Shu-Pin , Kuo Po-Lin , Lai Wen-Ter
Published: January 2015

Metabolic syndrome (MetS) confers increased risks of cardiovascular disease (CVD). Both vitamin D3and adipocytokines (especially adiponectin and leptin) have a great impact on CVD and MetS. In vitamin D3metabolism, the vitamin D325-hydroxylase (CYP27A1) and 25-hydroxyvitamin D31-alpha-hydroxylase (CYP27B1) are two key enzymes. This study aimed to examine the influence of vitamin D3CYP27 single nucleotide polymorphisms (SNPs) on adipocytokines and MetS. Cross-sectional data and DNA samples were collected from male volunteers (n=649, age: 55.7 ± 4.7 years). Two tagging SNPs,CYP27A1 rs4674344andCYP27B1 rs10877012, were selected from the HapMap project. MetS was significantly associated with theCYP27A1 rs4674344SNP(P=0.04)and the ratio of adiponectin/leptin (A/L ratio) was most correlated to theCYP27A1 rs4674344SNP, appearing to be significantly lower in T-carriers than in AA subjects (3.7 ± 4.0 versus 5.1 ± 6.0,P=0.001) and significantly negatively associated after adjustment. For each MetS component associated with theCYP27A1 rs4674344SNP, the A/L ratios were significantly negative in preclinical stage (condition not meeting the individual criteria), except the blood pressure. In conclusion,CYP27A1 rs4674344SNP, A/L ratio, and MetS are significantly associated and T-carriers might have a higher risk of developing MetS due to low A/L ratios in the preclinical stage.
Fibroblast Growth Factors Stimulate Hair Growth throughβ-Catenin and Shh Expression in C57BL/6 Mice
Authors: Lin Wei-hong , Xiang Li-Jun , Shi Hong-Xue , Zhang Jian , Jiang Li-ping , Cai Ping-tao , Lin Zhen-Lang , Lin Bei-Bei , Huang Yan , Zhang Hai-Lin , Fu Xiao-Bing , Guo Ding-Jiong , Li Xiao-Kun , Wang Xiao-Jie , Xiao Jian
Published: January 2015

Growth factors are involved in the regulation of hair morphogenesis and cycle hair growth. The present study sought to investigate the hair growth promoting activities of three approved growth factor drugs, fibroblast growth factor 10 (FGF-10), acidic fibroblast growth factor (FGF-1), and basic fibroblast growth factor (FGF-2), and the mechanism of action. We observed that FGFs promoted hair growth by inducing the anagen phase in telogenic C57BL/6 mice. Specifically, the histomorphometric analysis data indicates that topical application of FGFs induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to the control group. Moreover, the immunohistochemical analysis reveals earlier induction ofβ-catenin and Sonic hedgehog (Shh) in hair follicles of the FGFs-treated group. These results suggest that FGFs promote hair growth by inducing the anagen phase in resting hair follicles and might be a potential hair growth-promoting agent.
A Rare Case of Unrecognized and Uncommon Bladder Perforation after Transobturator Tape Procedure
Authors: Kılınç Ercüment , Akpak Yaşam Kemal
Published: January 2015

The transobturator tape (TOT) procedure has become practically widespread worldwide. Complications seem to be rare, but recognizing them intraoperatively is the most significant step because some of the complications which may appear in postoperative period can be challenging for both physicians and patients. The purpose of this case, with this patient who was operated on with open surgery, is to evaluate this rarely seen unrecognized and uncommon bladder perforation after TOT procedure and thus make some contribution to the literature. Here, we present a case report about the treatment of a 48-year-old woman patient with unrecognized and uncommon bladder perforation after TOT procedure, 5 months postoperatively. Cystoscopic evaluation is not recommended routinely, but it must be performed if the patient is complicated enough to create doubt and also the surgeon's skill and ability are not sufficient enough to operate decently.
Feasibility Analysis and Simulation of Integrated Renewable Energy System for Power Generation: A Hypothetical Study of Rural Health Clinic
Authors: Ani Vincent Anayochukwu , Abubakar Bahijjahtu
Published: January 2015

This paper presents the feasibility analysis and study of integrated renewable energy (IRE) using solar photovoltaic (PV) and wind turbine (WT) system in a hypothetical study of rural health clinic in Borno State, Nigeria. Electrical power consumption and metrology data (such as solar radiation and wind speed) were used for designing and analyzing the integrated renewable energy system. The health clinic facility energy consumption is 19 kWh/day with a 3.4 kW peak demand load. The metrological data was collected from National Aeronautics and Space Administration (NASA) website and used to analyze the performance of electrical generation system using HOMER program. The simulation and optimization results show that the optimal integrated renewable energy system configuration consists of 5 kW PV array, BWC Excel-R 7.5 kW DC wind turbine, 24 unit Surrette 6CS25P battery cycle charging, and a 19 kW AC/DC converter and that the PV power can generate electricity at 9,138 kWh/year while the wind turbine system can generate electricity at 7,490 kWh/year, giving the total electrical generation of the system as 16,628 kWh/year. This would be suitable for deployment of 100% clean energy for uninterruptable power performance in the health clinic. The economics analysis result found that the integrated renewable system has total NPC of 137,139 US Dollar. The results of this research show that, with a low energy health facility, it is possible to meet the entire annual energy demand of a health clinic solely through a stand-alone integrated renewable PV/wind energy supply.
Deep Venous Thrombosis of the Leg, Associated with Agenesis of the Infrarenal Inferior Vena Cava and Hypoplastic Left Kidney (KILT Syndrome) in a 14-Year-Old Child
Authors: Bami Sakshi , Vazquez Yarelis , Chorny Valeriy , Goldfisher Rachelle , Amodio John
Published: January 2015

Agenesis of the inferior vena cava (IVC) is a rare anomaly which can be identified as incidental finding or can be associated with iliofemoral vein thrombosis. IVC agenesis has a known association with renal anomalies which are mainly confined to the right kidney. We describe a case of a 14-year-old male who presented with left leg swelling and pain. Ultrasonography confirmed the presence of left leg deep vein thrombosis (DVT). No underlying hematologic risk factors were identified. A CT scan was obtained which demonstrated absent infrarenal IVC and extensive thrombosis in the left deep venous system and development of collateral venous flow into the azygous/hemiazygous system, with extension of thrombus into paraspinal collaterals. An additional finding in the patient was an atrophic left kidney and stenosis of an accessory left renal artery. Agenesis of the IVC should be considered in a young patient presenting with lower extremity DVT, especially in patients with no risk factors for thrombosis. As agenesis of the IVC cannot be corrected, one should be aware that there is a lifelong risk of lower extremity DVT.
D-Aspartate Modulates Nociceptive-Specific Neuron Activity and Pain Threshold in Inflammatory and Neuropathic Pain Condition in Mice
Authors: Boccella Serena , Vacca Valentina , Errico Francesco , Marinelli Sara , Squillace Marta , Guida Francesca , Di Maio Anna , Vitucci Daniela , Palazzo Enza , De Novellis Vito , Maione Sabatino , Pavone Flaminia , Usiello Alessandro
Published: January 2015

D-Aspartate (D-Asp) is a free D-amino acid found in the mammalian brain with a temporal-dependent concentration based on the postnatal expression of its metabolizing enzyme D-aspartate oxidase (DDO). D-Asp acts as an agonist on NMDA receptors (NMDARs). Accordingly, high levels of D-Asp in knockout mice forDdogene (Ddo−/−) or in mice treated with D-Asp increase NMDAR-dependent processes. We have here evaluated inDdo−/−mice the effect of high levels of free D-Asp on the long-term plastic changes along the nociceptive pathway occurring in chronic and acute pain condition. We found thatDdo−/−mice show an increased evoked activity of the nociceptive specific (NS) neurons of the dorsal horn of the spinal cord (L4–L6) and a significant decrease of mechanical and thermal thresholds, as compared to control mice. Moreover,Ddogene deletion exacerbated the nocifensive responses in the formalin test and slightly reduced pain thresholds in neuropathic mice up to 7 days after chronic constriction injury. These findings suggest that the NMDAR agonist, D-Asp, may play a role in the regulation of NS neuron electrophysiological activity and behavioral responses in physiological and pathological pain conditions.
Sonic Hedgehog and Gli1 Expression Predict Outcome in Resected Pancreatic Adenocarcinoma
Authors: Maréchal Raphaël , Bachet Jean-Baptiste , Calomme Annabelle , Demetter Pieter , Delpero Jean Robert , Svrcek Magali , Cros Jérôme , Bardier-Dupas Armelle , Puleo Francesco , Monges Geneviève , Hammel Pascal , Louvet Christophe , Paye François , Bachelier Philippe , Le Treut Yves Patrice , Vaillant Jean-Christophe , Sauvanet Alain , André Thierry , Salmon Isabelle , Devière Jacques , Emile Jean-François , Van Laethem Jean-Luc
Published: January 2015

Purpose: Aberrant activation of the hedgehog (Hh) pathway is implicated in pancreatic ductal adenocarcinoma (PDAC) tumorigenesis. We investigated the prognostic and predictive value of four Hh signaling proteins and of the tumor stromal density.

Experimental Design: Using tissue microarray and immunohistochemistry, the expression of Shh, Gli1, SMO, and PTCH1 was assessed in 567 patients from three independent cohorts who underwent surgical resection for PDAC. In 82 patients, the tumor stromal index (SI) was calculated, and its association with overall survival (OS) and disease-free survival (DFS) was investigated.

Results: Shh and Gli1 protein abundance were independent prognostic factors in resected PDACs; low expressors for those proteins experiencing a better OS and DFS. The combination of Shh and Gli1 levels was the most significant predictor for OS and defined 3 clinically relevant subgroups of patients with different prognosis (Gli1 and Shh low; HR set at 1 vs. 3.08 for Shh or Gli1 high vs. 5.69 for Shh and Gli1 high; P < 0.001). The two validating cohorts recapitulated the findings of the training cohort. After further stratification by lymph node status, the prognostic significance of combined Shh and Gli1 was maintained. The tumor SI was correlated with Shh levels and was significantly associated with OS (P = 0.023).

Conclusions: Shh and Gli1 are prognostic biomarkers for patients with resected PDAC. Clin Cancer Res; 21(5); 1215–24. ©2014 AACR.
Radiotherapy Combined with the Immunocytokine L19-IL2 Provides Long-lasting Antitumor Effects
Authors: Zegers Catharina M.L. , Rekers Nicolle H. , Quaden Dana H.F. , Lieuwes Natasja G. , Yaromina Ala , Germeraad Wilfred T.V. , Wieten Lotte , Biessen Erik A.L. , Boon Louis , Neri Dario , Troost Esther G.C. , Dubois Ludwig J. , Lambin Philippe
Published: January 2015

Purpose: Radiotherapy modifies the tumor microenvironment and causes the release of tumor antigens, which can enhance the effect of immunotherapy. L19 targets the extra domain B (ED-B) of fibronectin, a marker for tumor neoangiogenesis, and can be used as immunocytokine when coupled to IL2. We hypothesize that radiotherapy in combination with L19-IL2 provides an enhanced antitumor effect, which is dependent on ED-B expression.

Experimental Design: Mice were injected with syngeneic C51 colon carcinoma, Lewis lung carcinoma (LLC), or 4T1 mammary carcinoma cells. Tumor growth delay, underlying immunologic parameters, and treatment toxicity were evaluated after single-dose local tumor irradiation and systemic administration of L19-IL2 or equimolar controls.

Results: ED-B expression was high, intermediate, and low for C51, LLC, and 4T1, respectively. The combination therapy showed (i) a long-lasting synergistic effect for the C51 model with 75% of tumors being cured, (ii) an additive effect for the LLC model, and (iii) no effect for the 4T1 model. The combination treatment resulted in a significantly increased cytotoxic (CD8+) T-cell population for both C51 and LLC. Depletion of CD8+ T cells abolished the benefit of the combination therapy.

Conclusions: These data provide the first evidence for an increased therapeutic potential by combining radiotherapy with L19-IL2 in ED-B–positive tumors. This new opportunity in cancer treatment will be investigated in a phase I clinical study for patients with an oligometastatic solid tumor (NCT02086721). An animation summarizing our results is available at https://www.youtube.com/watch?v=xHbwQuCTkRc. Clin Cancer Res; 21(5); 1151–60. ©2014 AACR.
A Meta-Analysis of the Efficacy of Acceptance and Commitment Therapy for Clinically Relevant Mental and Physical Health Problems
Authors: A-Tjak Jacqueline G.L. , Davis Michelle L. , Morina Nexhmedin , Powers Mark B. , Smits Jasper A.J. , Emmelkamp Paul M.G.
Published: January 2015

Background: The current study presents the results of a meta-analysis of 39 randomized controlled trials on the efficacy of acceptance and commitment therapy (ACT), including 1,821 patients with mental disorders or somatic health problems. Methods: We searched PsycINFO, MEDLINE and the Cochrane Central Register of Controlled Trials. Information provided by the ACBS (Association of Contextual Behavioral Science) community was also included. Statistical calculations were conducted using Comprehensive Meta-Analysis software. Study quality was rated using a methodology rating form. Results: ACT outperformed control conditions (Hedges' g = 0.57) at posttreatment and follow-up assessments in completer and intent-to-treat analyses for primary outcomes. ACT was superior to waitlist (Hedges' g = 0.82), to psychological placebo (Hedges' g = 0.51) and to treatment as usual (TAU) (we defined TAU as the standard treatment as usual; Hedges' g = 0.64). ACT was also superior on secondary outcomes (Hedges' g = 0.30), life satisfaction/quality measures (Hedges' g = 0.37) and process measures (Hedges' g = 0. 56) compared to control conditions. The comparison between ACT and established treatments (cognitive behavioral therapy) did not reveal any significant differences between these treatments (p = 0.140). Conclusions: Our findings indicate that ACT is more effective than treatment as usual or placebo and that ACT may be as effective in treating anxiety disorders, depression, addiction, and somatic health problems as established psychological interventions. More research that focuses on quality of life and processes of change is needed to understand the added value of ACT and its transdiagnostic nature.
The Effect of Isotretinoin on Retinol-Binding Protein 4, Leptin, Adiponectin and Insulin Resistance in Acne Vulgaris Patients
Authors: Karadag Ayse Serap , Ertugrul Derun Taner , Takci Zennure , Bilgili Serap Gunes , Namuslu Mehmet , Ata Naim , Sekeroglu Ramazan
Published: January 2015

Background: The effect of isotretinoin (ISO) on adipokines and insulin resistance has been investigated in a few studies, and the results are conflicting. Objective: The aim of this study was to investigate the effect of ISO treatment on insulin resistance and adipokines. Methods: Thirty-three patients with acne vulgaris and a control group of 30 healthy volunteers were included in our study. Screening for the biochemical parameters was performed just before the initiation and after 3 months of ISO treatment. Results: In the acne group, basal leptin levels were significantly lower (p = 0.003) and basal adiponectin levels significantly higher (p = 0.008) compared with the control group. After ISO treatment, leptin levels (p = 0.0005) decreased and adiponectin levels (p = 0.003) increased significantly. However, measurements of fasting blood glucose, insulin, C peptide, retinol-binding protein 4 (RBP4), homeostasis model assessment insulin resistance and BMI did not differ after ISO treatment. Conclusion: ISO may affect leptin and adiponectin levels. It does not, however, affect insulin resistance and RBP4 levels.
Successful Intermittent Intravenous Calcium Treatment via the Peripheral Route in a Patient with Hereditary Vitamin D-Resistant Rickets and Alopecia
Authors: Ersoy Betul , Kiremitci Seniha , Isojima Tsuyoshi , Kitanaka Sachiko
Published: January 2015

Background: Hereditary vitamin D-resistant rickets (HVDRR) is a rare genetic disorder caused by mutations in the vitamin D receptor (VDR) gene, which result in end-organ resistance to 1,25-(OH)2D3. Patients with HVDRR are mostly treated using i.v. calcium therapy with a central catheter. However, central catheter-related complications have been reported. Patient: The patient was a 3-year-old boy presenting with waddling gait and alopecia. He had hypocalcemia [8 mg/dl (2 mmol/l)], hyperparathyroidism (1,232 ng/l), and elevated 1,25-(OH)2D3 levels (>250 pmol/l). DNA sequence analyses of the VDR gene showed a homozygous C-T transition at codon 152, resulting in a non-sense mutation in exon 5. Interventions and Outcomes: The patient was initially treated with calcitriol (80 ng/kg/day) and high-dose oral calcium (150 mg/kg/day) for one year. At the end of the first year, intermittent (5 days per month) i.v. calcium therapy without a central catheter was initiated because of insufficient clinical and radiological improvement. After 2 years of intermittent i.v. calcium therapy, there was a clear improvement based on clinical progress and on X-ray and biochemical findings. No peripheral complications were reported either. Conclusion: HVDRR with a non-sense mutation in the ligand-binding domain and alopecia was successfully treated with intermittent i.v. calcium without a central catheter.
Montreal Cognitive Assessment for Screening Mild Cognitive Impairment: Variations in Test Performance and Scores by Education in Singapore
Authors: Ng Tze Pin , Feng Lei , Lim Wee Shiong , Chong Mei Sian , Lee Tih Shih , Yap Keng Bee , Tsoi Tung , Liew Tau Ming , Gao Qi , Collinson Simon , Kandiah Nagaendran , Yap Philip
Published: January 2015

Background: The Montreal Cognitive Assessment (MoCA) was developed as a screening instrument for mild cognitive impairment (MCI). We evaluated the MoCA's test performance by educational groups among older Singaporean Chinese adults. Method: The MoCA and Mini-Mental State Examination (MMSE) were evaluated in two independent studies (clinic-based sample and community-based sample) of MCI and normal cognition (NC) controls, using receiver operating characteristic curve analyses: area under the curve (AUC), sensitivity (Sn), and specificity (Sp). Results: The MoCA modestly discriminated MCI from NC in both study samples (AUC = 0.63 and 0.65): Sn = 0.64 and Sp = 0.36 at a cut-off of 28/29 in the clinic-based sample, and Sn = 0.65 and Sp = 0.55 at a cut-off of 22/23 in the community-based sample. The MoCA's test performance was least satisfactory in the highest (>6 years) education group: AUC = 0.50 (p = 0.98), Sn = 0.54, and Sp = 0.51 at a cut-off of 27/28. Overall, the MoCA's test performance was not better than that of the MMSE. In multivariate analyses controlling for age and gender, MCI diagnosis was associated with a <1-point decrement in MoCA score (η2 = 0.010), but lower (1-6 years) and no education was associated with a 3- to 5-point decrement (η2 = 0.115 and η2 = 0.162, respectively). Conclusion: The MoCA's ability to discriminate MCI from NC was modest in this Chinese population, because it was far more sensitive to the effect of education than MCI diagnosis.
Wearable Sensor-Based In-Home Assessment of Gait, Balance, and Physical Activity for Discrimination of Frailty Status: Baseline Results of the Arizona Frailty Cohort Study
Authors: Schwenk Michael , Mohler Jane , Wendel Christopher , D''Huyvetter Karen , Fain Mindy , Taylor-Piliae Ruth , Najafi Bijan
Published: January 2015

Background: Frailty is a geriatric syndrome resulting from age-related cumulative decline across multiple physiologic systems, impaired homeostatic reserve, and reduced capacity to resist stress. Based on recent estimates, 10% of community-dwelling older individuals are frail and another 41.6% are prefrail. Frail elders account for the highest health care costs in industrialized nations. Impaired physical function is a major indicator of frailty, and functional performance tests are useful for the identification of frailty. Objective instrumented assessments of physical functioning that are feasible for home frailty screening have not been adequately developed. Objective: To examine the ability of wearable sensor-based in-home assessment of gait, balance, and physical activity (PA) to discriminate between frailty levels (nonfrail, prefrail, and frail). Methods: In an observational cross-sectional study, in-home visits were completed in 125 older adults (nonfrail: n = 44, prefrail: n = 60, frail: n = 21) living in Tucson, Ariz., USA, between September 2012 and November 2013. Temporal-spatial gait parameters (speed, stride length, stride time, double support, and variability of stride velocity), postural balance (sway of hip, ankle, and center of mass), and PA (percentage of walking, standing, sitting, and lying; mean duration and variability of single walking, standing, sitting, and lying bouts) were measured in the participant's home using validated wearable sensor technology. Logistic regression was used to assess the most sensitive gait, balance, and PA variables for identifying prefrail participants (vs. nonfrail). Multinomial logistic regression was used to identify variables sensitive to discriminate between three frailty levels. Results: Gait speed (area under the curve, AUC = 0.802), hip sway (AUC = 0.734), and steps/day (AUC = 0.736) were the most sensitive parameters for the identification of prefrailty. Multinomial regression revealed that stride length (AUC = 0.857) and double support (AUC = 0.841) were the most sensitive gait parameters for discriminating between three frailty levels. Interestingly, walking bout duration variability was the most sensitive PA parameter for discriminating between three frailty levels (AUC = 0.818). No balance parameter discriminated between three frailty levels. Conclusion: Our results indicate that unique parameters derived from objective assessment of gait, balance, and PA are sensitive for the identification of prefrailty and the classification of a subject's frailty level. The present findings highlight the potential of wearable sensor technology for in-home assessment of frailty status.
Molecular Imaging of Carotid Plaque Vulnerability
Authors: Alonso Angelika , Artemis Dimitrios , Hennerici Michael G.
Published: January 2015

Background: Carotid endarterectomy (CEA) has been shown to be beneficial in patients with high-grade symptomatic carotid artery stenosis. Patients with high-grade asymptomatic stenosis may only exceptionally benefit from CEA during periods of increased plaque vulnerability. Imaging modalities to characterize unstable, vulnerable plaques are strongly needed for better risk stratification in these patients. Summary: Contrast-enhanced ultrasound (CEUS) is a novel and noninvasive technique capable to identify several surrogate markers of vulnerable carotid plaques. The use of specific ultrasound microbubbles allows a reliable detection of microulcerations due to an optimized visualization of the plaque-lumen border. As microbubbles are strictly intravascular tracers, the detection of individual microbubbles within the plaque corresponds to intraplaque neovessels. The accuracy of CEUS in the visualization of newly formed microvessels has been confirmed in histological studies on carotid endarterectomy specimens. Together with the formation of adventitial vasa vasorum, intraplaque neovascularization is a strong predictor for symptomatic disease. The phenomenon of late phase contrast enhancement is based on the adherence of microbubble-containing monocytes on inflamed endothelium. Recent studies suggest that late phase contrast enhancement may reflect endothelial inflammation or activation within carotid plaques. The development of conjugated microbubbles that bind to specific ligands such as thrombotic material or neovessels has led to the term ‘molecular imaging'. CEUS with microbubbles targeted to P-selectin and VCAM-1, key molecules in leukocyte trafficking, was used to detect an inflammatory plaque phenotype, whereas microbubbles coupled to the VEGF-receptor may allow for a detection of neovascularization. Even though imaging with targeted microbubbles is yet in an experimental stage, this technique can visualize active plaque reorganization with increased vulnerability leading to generation of arterio-arterial embolism. Key Messages: The use of contrast-enhanced ultrasound can be recommended to assess atherosclerotic carotid lesions at risk for rupture. Prospective clinical studies are needed to validate the use of CEUS in patients with high risks of recurrent large artery strokes. In particular, this applies to the detection of intraplaque neovascularization, a well-established marker in preclinical and observational studies, while the clinical significance of late phase contrast enhancement still needs to be determined.
Multiple Factors Influencing the Incidence of Congenital Hypothyroidism Detected by Neonatal Screening
Authors: Olivieri Antonella , Fazzini Cristina , Medda Emanuela ,   The Italian Study Group for Congenital Hypothyroidism
Published: January 2015

Background/Aims: Over the years a rise in the incidence of congenital hypothyroidism (CH) has been described worldwide. The aim of our study was to investigate trends in the incidence of CH in Italy over the period 1987-2008, and to investigate which factors may have influenced the CH incidence in our country. Methods: Data were derived from the Italian National Registry of Infants with Congenital Hypothyroidism. Since 1998 the laboratory procedures related to neonatal screening for CH have changed drastically. Accordingly, we estimated the CH incidence during the period 1987-1998 (period 1) and the period 1999-2008 (period 2). Results: The incidence of CH confirmed at birth (including transient hypothyroidism) has increased from 1:3,000 liveborn infants in period 1 to 1:1,940 in period 2 (+54%), whereas the incidence of purely permanent CH increased from 1:3,200 to 1:2,320 (+38%). Lowering of the TSH cutoff was the most important factor contributing to the increase of CH incidence in Italy. Moreover, an increment of 58% of preterm babies with permanent CH was found in period 2 compared with period 1. Conclusion: Our results suggest that more than one cause is responsible for the rise in the increasing CH incidence, with lowering of the screening TSH cutoff and an increased survival rate of a growing number of preterm babies both playing an important role.
Overcoming Treatment Resistance in Chronic Depression: A Pilot Study on Outcome and Feasibility of the Cognitive Behavioral Analysis System of Psychotherapy as an Inpatient Treatment Program
Authors: Brakemeier Eva-Lotta , Radtke Martina , Engel Vera , Zimmermann Johannes , Tuschen-Caffier Brunna , Hautzinger Martin , Schramm Elisabeth , Berger Mathias , Normann Claus
Published: January 2015

Background: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP), initially developed as an outpatient treatment for chronic depression (CD), has been adapted as a multidisciplinary 12-week inpatient program for CD. Methods: Seventy inpatients with CD and treatment resistance were included in a noncontrolled trial. The Hamilton Depression Rating Scale served as the primary outcome measure. Prospective naturalistic follow-up assessments were conducted 6 and 12 months after discharge. Results: Dropout rate was 7.1%; 90.4% perceived the program as helpful. Pre-post comparisons yielded strong effect sizes; 75.7% of the intention-to-treat sample responded, and 40.0% remitted. Nonremission was associated with experiencing temporary deterioration of symptoms during treatment. After 6 months 75.0% and after 12 months 48.0% of patients sustained response. Conclusions: The CBASP program appears as a feasible acute treatment for treatment-resistant CD inpatients with promising outcome. However, the continuation of treatment after discharge should be optimized especially for patients with subjective deterioration during treatment.
SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression
Authors: Xie Ping , Duan Yingchun , Guo Xianzhi , Hu Lina , Yu Minghua
Published: January 2015

Background: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDLr expression, ER stress, and apoptosis under hypoxia condition. Methods: Human umbilical vein endothelial cells (HUVECs) pretreated with SalA were subjected to hypoxia stimulation. Endothelial ER stress and apoptosis were examined. The mRNA levels were tested by real-time RT-PCR, and the protein levels were determined by immunoblot analysis. Results: Pretreatment of HUVECs with SalA markedly attenuated hypoxia-induced endothelial ER stress and apoptosis. Hypoxia resulted in enhancement of VLDLr expression, which was effectively inhibited by SalA pretreatment. Furthermore, luciferase reporter gene assays indicated that SalA inhibited vldlr gene promoter activity, and ChIP assays showed that hypoxia increase the recruitment of HIF-1α to the vldlr gene promoter, and this process was hampered markedly by pretreatment of SalA. Finally, overexpression of VLDLr abolished SalA-mediated protection of endothelial cells from ER stress and apoptosis. Knockdown of VLDLr mimicked SalA protective effect. Conclusion: These results for the first time demonstrate that SalA protects against hypoxia-induced endothelial ER stress and apoptosis through inhibiting recruitment of HIF-1α to vldlr gene promoter and thus suppressing VLDLr expression.
MiR-146b-5p Promotes Metastasis and Induces Epithelial-Mesenchymal Transition in Thyroid Cancer by Targeting ZNRF3
Authors: Deng Xianzhao , Wu Bo , Xiao Ke , Kang Jie , Xie Jing , Zhang Xiaoping , Fan Youben
Published: January 2015

Background/Aims: Micro-RNA (miR)-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and associated with extrathyroidal invasion and advanced tumor stage. In the present study, we showed that miR-146b-5p is upregulated in PTC with lymph node metastasis. Methods: A computational search and luciferase assay identified zinc RING finger 3 (ZNRF3), a negative regulator of Wnt/β-catenin signaling, as a direct target of miR-146b-5p in PTC. Results: MiR-146b-5p promoted migration and invasiveness and induced epithelial-mesenchymal transition (EMT) of PTC cells, whereas ZNRF3 overexpression reversed this effect. MiR-146b-5p increased the cell surface levels of the Wnt receptors Frizzled-6 and LRP6 and enhanced Wnt/β-catenin signaling by downregulating ZNRF3, whereas an inhibitor of Wnt/β-catenin suppressed the effect of miR-146b-5p on migration, invasiveness and EMT of PTC cells. Conclusion: These results indicate that miR-146b-5p induces EMT and may promote PTC metastasis through the regulation of Wnt/β-catenin signaling, and suggest novel potential therapeutic targets for the treatment of PTC.
Ischaemic Strokes with Reversible Vasoconstriction and without Thunderclap Headache: A Variant of the Reversible Cerebral Vasoconstriction Syndrome?
Authors: Wolff Valérie , Armspach Jean-Paul , Lauer Valérie , Rouyer Olivier , Ducros Anne , Marescaux Christian , Gény Bernard
Published: January 2015

Background: Reversible vasoconstriction (RV) may cause ischaemic stroke (IS) in the absence of any other defined stroke aetiology. The three objectives of our study were to evaluate the frequency of RV in a prospective series of young IS patients, to describe the detailed clinical-radiological features in the patients with RV and IS, and to compare these characteristics with those of reversible cerebral vasoconstriction syndrome (RCVS). Methods: We identified between October 2005 and December 2010, 159 consecutive young patients (<45 years) hospitalized for an acute IS confirmed by cerebral magnetic resonance imaging. An extensive diagnostic work-up was performed including toxicological urinary screening for cannabis, cocaine and amphetamines, and the usual biological, cardiac and vascular investigations for an IS in the young. We specifically studied patients with IS and RV, which was defined as multifocal intracranial arterial stenoses confirmed by intracranial arterial imaging that resolved within 3-6 months. Results: Out of 159 patients with IS, 21 (13%, 12 males, 9 females; mean age 32 years) had multifocal cerebral arterial stenoses that were fully reversible at 3-6 months, and no other cause for stroke. IS were located on posterior territory in 71% of cases, and vasoconstriction predominated on posterior cerebral and superior cerebellar arteries. Precipitating factors of IS and RV were the use of cannabis resin (n = 14), nasal decongestants (n = 2) and triptan (n = 1). Most cases (74%) had unusual severe headache, but none had thunderclap headache. None of 21 cases had reversible posterior leukoencephalopathy, cortical subarachnoid or intracerebral haemorrhage. Conclusion: RV was the sole identified cause of IS in 13% of our cohort. These young patients with IS and RV may have a variant of RCVS, related to an increased susceptibility to vasoactive agents in some individuals. RV in our patients differs from the classical characteristics of RCVS by the absence of thunderclap headache, reversible brain oedema and subarachnoid or intracranial haemorrhage. Intracranial arteries should be looked for, by appropriate vascular imaging, in young patients with IS at the acute stage and during the follow-up period.
Effect of Prior Hemorrhage on Intracranial Arteriovenous Malformation Radiosurgery Outcomes
Authors: Ding Dale , Yen Chun-Po , Starke Robert M. , Xu Zhiyuan , Sheehan Jason P.
Published: January 2015

Background: Intracerebral hemorrhage is simultaneously the most frequent and most debilitating manifestation of intracranial arteriovenous malformations (AVM), but its impact on success and complications of radiosurgery has not been rigorously assessed. In this case-control study, we define the effect of prior hemorrhage on AVM radiosurgery outcomes. Methods: From a prospective, institutional database of 1,400 AVM patients treated with Gamma Knife radiosurgery, unruptured and ruptured AVMs were matched in a 1:1 fashion, blinded to outcome, based on patient demographics, prior embolization (26.6% of each cohort), AVM size (mean volume of unruptured AVMs 3.7 cm3 versus ruptured AVMs 3.5 cm3, p = 0.195), Spetzler-Martin grade (Grade I 17.0%, Grade II 37.8%, Grade III 34.8%, Grade IV 10.4% for each cohort), and radiosurgical treatment parameters (mean prescription dose for unruptured AVMs 20.9 Gy versus ruptured AVMs 21.0 Gy, p = 0.837). There were 270 patients in each cohort. Matched statistical analyses were used to compare the baseline characteristics, obliteration rates, post-radiosurgery latency period hemorrhage risks, and incidences of radiation-induced changes (RIC) between the two cohorts. Results: The actuarial obliteration rates of the two cohorts were similar (unruptured AVMs: 38, 58, and 76% at 3, 5, 10 years, respectively; ruptured AVMs: 40, 60, and 73% at 3, 5, 10 years, respectively; p = 0.592). However, for embolized AVMs, complete obliteration was more likely to be achieved in unruptured lesions (unruptured AVMs: 25, 32, and 54% at 3, 5, 10 years, respectively; ruptured AVMs: 18, 27, and 42% at 3, 5, 10 years, respectively; p = 0.038). Prior AVM rupture resulted in a higher annual risk of post-radiosurgery latency period hemorrhage (ruptured AVMs 2.3% versus unruptured AVMs 1.1%, p = 0.025) but a lower rate of cumulative and symptomatic RIC (cumulative RIC: ruptured AVMs 30.4% versus unruptured AVMs 48.9%, p < 0.0001; symptomatic RIC: ruptured AVMs 7.0% versus unruptured AVMs 12.2%, p = 0.041, respectively). The rates of permanent RIC were similar between the unruptured (2.2%) and ruptured (1.9%) AVM cohorts (p = 0.761). The mean time interval to onset of RIC (unruptured AVMs 13.3 months versus ruptured AVMs 12.1 months, p = 0.783), and the mean duration of RIC (unruptured AVMs 22.0 months versus ruptured AVMs 21.7 months, p = 0.599) were not significantly different between the two cohorts. Conclusions: Prior AVM rupture significantly alters the risk of latency period hemorrhage and RIC following radiosurgery. These effects should be taken into consideration with the multidisciplinary management of AVM patients. Radiosurgery does not significantly alter the natural history of the hemorrhage risks of unruptured and ruptured AVMs unless obliteration is achieved.