bluuebunny/crossref_metadata_2025 huggingface dataset:
Adverse Influence of Cigarette Smoking on the Endothelium
Authors: Blann Andrew D , McCollum Charles N
Published: July 2018

The effect of smoking on the blood vessel intima was examined by comparing indices of endothelial activity in serum from smokers with that from non-smokers. Serum from smokers contained higher levels of von Willebrand factor (p <0.01), the smoking markers cotinine (p <0.02) and thiocyanate (p <0.01), and was more cytotoxic to endothelial cells in vitro (p <0.02) than serum from non-smokers. The acute effects of smoking two unfiltered medium tar cigarettes was to briefly increase von Willebrand factor (p <0.001) and cytotoxicity of serum to endothelial cells in vitro (p <0.005), but lipid peroxides or thiocyanate were not increased by this short exposure to tobacco smoke. Although there were correlations between von Willebrand factor and smokers consumption of cigarettes (r = 0.28, p <0.02), number of years smoking (r = 0.41, p <0.001) and cotinine (r = 0.45, p <0.01), the tissue culture of endothelial cells with physiological levels of thiocyanate or nicotine suggested that these two smoking markers were not cytotoxic. They are therefore unlikely to be directly responsible for increased von Willebrand factor in the serum of smokers. We suggest that smoking exerts a deleterious influence on the endothelium and that the mechanism is complex.
A Prospective, Randomized Trial of Prednisone and Cyclophosphamide in the Treatment of Patients with Factor VIII Autoantibodies
Authors: Green David , Rademaker Alfred W , Briët Ernest
Published: July 2018

Thirty-one non-hemophilic patients with acquired antibodies to factor VIII were entered into a prospective, randomized, multi- institutional trial to determine the safety and efficacy of prednisone (P), cyclophosphamide ©, or the combination in the treatment of this disorder. Patients were eligible if they had antibody demonstrated by the Bethesda assay, had not received these agents previously, and gave informed consent. All patients were treated initially with P, 1 mg/kg, for 3 weeks. If the antibody persisted and there was no rise in factor VIII activity, patients were randomized to either continue P for an additional 6 weeks; taper P and begin C, 2 mg per kg; or continue P and add C. Antibody disappeared in 10 during the initial P therapy, and in three of four others randomized to continue on P; one patient was discontinued because of an herpetic infection. Antibody disappeared in three of six patients treated with C alone, and five of ten given C and P. The titer of antibody was significantly lower in responders than in non-responders (p = 0.003), but seven patients with titers of more than five Bethesda units had complete remissions. There was no difference in antibody titers between those responding to P and those responding to C. We conclude that all patients with acquired antibodies to factor VIII should receive initial management with P, and that C is effective as second-line therapy for many of those who are steroid-resistant.
Female Twins with Severe Christmas Disease (Hemophilia B)
Authors: Wollina Karin , Bowen D J , Syrbe G , Zintl F
Published: July 2018

Hemophilia B is an X-linked bleeding disorder. We report on female twins, who were conspicious in prolonged bleeding after venipuncture as well as hematomas after intramuscular injections even in the first months of their life. Their father suffering from a severe hemophilia B deceased in 1992. Their mother, half-brother and grandmother from their father’s side had no signs of bleeding disorders. Clotting analysis performed in both twins revealed a markedly prolonged partial thromboplastin time (>100 s). The factor IX levels were below 2%. In order to detect mutations, a general screen using the polymerase chain reaction (PCR) followed by single strand conformation polymorphism (SSCP) analysis of the PCR products have been performed. PCR products have been cut into smaller fragments using restriction endonucleases (RE) for an in-depth SSCP screen. A general screen for gross abnormalities in the factor IX gene including deletions, insertions and rearrangements was performed by Southern blot analysis of RE-digests of genomic DNA using the factor IX cDNA as a hybridization probe. Furthermore, we screened for mutations in the CG dinucleotides comprising part of RE-recognition sequences (exon 1, 2, 3, 4, 5, and 8). By all methods applied herein, no mutations have been detected in these twins. On the basis of our results the hemophilia B of these twins might be explained by extreme non-random lyonization.
Synergistic Antiplatelet Effect of Ridogrel, a Combined Thromboxane Receptor Antagonist and Thromboxane Synthase Inhibitor, and UDCG-212, a cAMP-Phosphodiesterase Inhibitor
Authors: Hoet B , Arnout J , Deckmyn H , Vermylen J
Published: July 2018

Ridogrel, a combined thromboxane receptor antagonist and thromboxane synthase inhibitor (1), inhibits platelet aggregation. Following stimulation with arachidonic acid, cAMP-levels are increased in human platelets preincubated with ridogrel, this is due to the known reorientation of the metabolism of the formed endoperoxides towards adenylate cyclase stimulating prostaglandins.

Pretreatment of resting platelets with UDCG-212, a cAMP-phosphodiesterase inhibitor (2), also inhibits platelet aggregation induced by arachidonic acid, concomitant with an increase in cAMP levels, due to an inhibition of its breakdown. Under basal conditions, cAMP also is increased.

By combining the two drugs, a more than additive action was observed on platelet aggregation and on both resting and stimulated platelet cAMP content. The appropriate combination may result in a more effective antiplatelet strategy.
Two Independent Binding Sites on Monolayers of Human Endothelial Cells Are Responsible for Interaction with Coagulation Factor VII and Factor VIIa
Authors: Reuning Ute , Preissner Klaus T , Müller-Berghaus Gert
Published: July 2018

The interaction of radiolabeled factor VII (FVII) and factor VIIa (FVIIa) with endotoxin-stimulated endothelial cells (EC), known to express tissue factor (TF), and unstimulated EC was studied. FVII/FVIIa binding to EC-monolayers was saturable within 4.5-6 h, reversible, temperature and calcium dependent on both, endotoxin-stimulated and on unstimulated EC. Upon 2 h of incubation on EC, FVII was partially converted to FVIIa in the absence of protease inhibitors. The affinity of this binding was K
d = 45.4 ± 18.7 nM with a calculated number of binding sites B
max = 3.75 ± 0.31 × 106 molecules/cell. In addition to unlabeled FVII and FVIIa, other vitamin K-dependent proteins reduced binding of [125I]-FVII/FVIIa to about 60-70%, and this type of common binding site for vitamin K-dependent proteins revealed a K
d = 32.2 ± 5.6 nM and a B
max = 3.03 ± 0.14 × 106 molecules/cell. Moreover, in the presence of 1 μM prothrombin to suppress common binding sites, only on endotoxin-stimulated EC additional inhibition of FVII/FVIIa binding was achieved by anti-TF antibodies. The characteristics of the FVII/FVIIa-TF interaction with a K
d = 17.2 ± 5.2 nM and a B
max = 342,000 ± 1,100 binding sites/cell revealed a similar saturation kinetics in radioligand binding and in functional factor X activation within 90-120 min. These data indicate the presence of at least two independent binding sites for FVII/FVIIa on stimulated EC of which about 10% are TF specific. The existence of binding sites common for vitamin K-dependent proteins on both types of EC may improve the availability of FVII/FVIIa once EC become stimulated and express TF on their surface.
Influence of Long Term Oral Anticoagulants upon Prothrombin Fragment 1 + 2, Thrombin-Antithrombin III Complex and D-Dimer Levels in Patients Affected by Proximal Deep Vein Thrombosis
Authors: Elias A , Bonfils S , Daoud-Elias M , Gauthier B , Sié P , Boccalon H , Boneu B
Published: July 2018

We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 ± 17 years, mean ± SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 ± 10 years) and to an age-matched healthy population (63 ± 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 ± 0.7, 2.9 ± 0.9 and 2.8 ± 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process.

This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis. Whether or not it is possible to reduce the intensity of the anticoagulant treatment 1 month after its initiation on the basis of very low levels of F1 + 2 can only be determined by prospective clinical trials.
Thrombotic and Hemorrhagic Complications in Patients with Mechanical Heart Valve Prosthesis Attending an Anticoagulation Clinic
Authors: Cortelazzo S , Finazzi G , Viero P , Galli M , Remuzzi A , Parenzan L , Barbui T
Published: July 2018

This study evaluated the advantage of an anticoagulation clinic in terms of the improvement of the clinical quality of oral anticoagulation (i.e. prevention of thromboembolism and low rate of hemorrhagic complications). The incidence of thromboembolic events and major hemorrhagic complications was assessed in a series of 271 patients on oral anticoagulation for mechanical heart valve prosthesis before and after their enrollment in our anticoagulation clinic from January 1987 to December 1990. Risk factors for hemostatic events were also analyzed. The incidence of major hemostatic complications was significantly lower when patients attended the clinic: 1.0 vs 4.9%/pt-yr for hemorrhage and 0.6 vs 6.6%/pt-yr for thrombosis. This depended on three main factors: better dose regulation of warfarin, continuous patient education and early identification of clinical conditions potentially at risk for thrombosis and hemorrhage. Only previous hemorrhagic or thromboembolic events were recognized as major risk factors for hemostatic complications.

In conclusion, our study shows that an anticoagulation clinic offers a real advantage to patients with mechanical heart valve prosthesis in terms of prevention of thromboembolic events and hemorrhagic complications.
Distribution of Tissue Factor Pathway Inhibitor in Normal and Malignant Human Tissues
Authors: Werling Robert W , Zacharski Leo R , Kisiel Walter , Bajaj S Paul , Memoli Vincent A , Rousseau Sandra M
Published: July 2018

Specific antibodies to tissue factor pathway inhibitor (TFPI) were used in immunohistochemical procedures to determine the distribution of TFPI in normal and neoplastic human tissues. TFPI was restricted to megakaryocytes and the endothelium of the microvasculature in normal and abnormal tissues, but was not found in the endothelium of larger vessels or in hepatocytes. TFPI was also detected in macrophages in the villi of term placenta. Tumor-associated macrophages in several types of malignancy that we have shown previously to express a complete tissue factor-initiated pathway of coagulation and thrombin generation also manifested TFPI. By contrast, malignant cells in small cell carcinoma of the lung, renal cell carcinoma, and malignant melanoma that we have shown previously to express coagulation factors together with tumor cell-associated fibrin formation failed to stain for TFPI. We postulate that TFPI may be lacking from the latter malignancies because of the absence of the appropriately configured tissue factor – factor VII a – factor Xa complex required for TFPI binding.
Role of Urokinase Type Plasminogen Activator (u-PA) in Corneal Epithelial Migration
Authors: Morimoto Keisuke , Mishima Hiroshi , Nishida Teruo , Otori Toshifumi
Published: July 2018

The role of plasminogen activator (PA) in the migration of comeal reepithelialization was studied. Rabbit corneal blocks were cultured, and both the extent of epithelial migration over the exposed corneal stroma and the activity of PA released into the culture media were measured. A significant, direct correlation between epithelial migration and PA activity in the medium was observed, even when the migration was stimulated by fibronectin or EGF, or was inhibited by cytochalasin B or cycloheximide. Zymography confirmed that the PA released into the culture medium was of the urokinase type (u-PA). Immunohistochemical studies showed that u-PA and plasmin(ogen) were present at the leading edge of the migrating epithelium. Studies of corneal cell cultures indicated that epithelial cells rather than endothelial cells or fibroblasts were the source of the u-PA. The addition of anti-human u-PA IgG or protease inhibitors retarded the migration of the comeal epithelium in a dose-dependent manner, indicating that u-PA activity is essential for the migration of the corneal epithelium. These findings suggest that the migration of corneal epithelial cells requires not only cell attachment to the extracellular matrix through the fibronectin but also degradation of the fibronectin by the release of cellular u-PA.
Characterization of a Form of Bovine Factor VIII Which Does Not Aggregate Human Platelets
Authors: Kirby Edward P
Published: July 2018

Fractionation of partially purified bovine factor VIII on tricalcium citrate columns produces a material which contains high levels of factor VIII procoagulant activity and factor VIII- related antigen, but does not aggregate human platelets. The procoagulant activity can be blocked by human inhibitors of factor VIII: C and by rabbit antibody to bovine factor VIII. Its activity can be increased by thrombin modification. The apparent molecular weight of this form of factor VIII is significantly lower than that of the forms of factor VIII which contain platelet aggregating activity, and it exhibits a higher mobility on agarose electrophoresis.
Quantitation of Human Platelet Transformation on Siliconized Glass: Comparison of “Normal” and “Abnormal” Platelets
Authors: Rosenstein R , Zacharski L R , Allen R D
Published: July 2018

A series of typical morphological stages, representing progression of transformation, may be defined following adhesion of platelets to a siliconized glass surface. Platelets are visualized by new light microscopic techniques that allow quantitative categorization of transformation of large platelet populations by morphological stage, and thus the detection and elucidation of platelet defects which influence transformation. Living platelets from each of five subjects with bleeding disorders, due to platelet defects, exhibited a pattern of morphologic transformation which differed from normal. In addition, the pattern observed with the platelets from a subject with Glanzmann’s thrombasthenia was sufficiently different from that observed with the platelets from four subjects with thrombopathy, so as to point to a qualitative difference in the activity of the platelets in the two disorders. These findings indicate that the analysis of platelet transformation in vitro through the use of light microscopy may allow for detection and further classification of platelet abnormalities.
Testosterone Potentiation of Ionophore and ADP Induced Platelet Aggregation : Relationship to Arachidonic Acid Metabolism
Authors: Pilo R , Aharony D , Raz A
Published: July 2018

The role of arachidonic acid oxygenated products in human platelet aggregation induced by the ionophore A23187 was investigated. The ionophore produced an increased release of both saturated and unsaturated fatty acids and a concomitant increased formation of TxA2 and other arachidonate products. TxA2 (and possibly other cyclo oxygenase products) appears to have a significant role in ionophore-induced aggregation only when low concentrations (<1 μM) of the ionophore are employed.

Testosterone added to rat or human platelet-rich plasma (PRP) was shown previously to potentiate platelet aggregation induced by ADP, adrenaline, collagen and arachidonic acid (1, 2). We show that testosterone also potentiates ionophore induced aggregation in washed platelets and in PRP. This potentiation was dose and time dependent and resulted from increased lipolysis and concomitant generation of TxA2 and other prostaglandin products. The testosterone potentiating effect was abolished by preincubation of the platelets with indomethacin.
The In Vitro Inhibitory Effect on Thrombin by 2,3-Diphosphoglycerate
Authors: Principe D Del , Strappini P M , Vecchio S Del , Menichelli A , Biancini G , Cosmi E V , Bastianon V , D’Arcangelo C
Published: July 2018

Thrombin, incubated with 2,3-diphosphoglycerate (150 nmol 2,3-DPG/1 NIH thrombin unit) lost up to 70% of its clotting activity, whereas the esterase activity remained unchanged. No fibrinopeptide release by thrombin was observed in the presence of 2,3-DPG. The fibrin polymerization was normal. By chromatography on Amberlite IRC-50, α-thrombin was eluted at pH 8.0. In presence of 2,3-DPG, α-thrombin was not eluted. Likely, 2,3-DPG can interfere with thrombin.
Thermography in the Diagnosis of DVT
Authors: Lockner Dieter , Paul Christer , Hedlund Birger , Schulman Sam , Nyman Dag
Published: July 2018

161 consecutively admitted medical patients with the clinical suspicion of acute deep venous thrombosis (DVT) were thermographed and phlebographed in order to study the congruence of these methods. The sensitivity of thermography in the detection of DVT was found to be 99%, whereas the specificity was only 49%.

The low specificity is explained by the fact that all thermographs suggestive of DVT were classified as pathologic to keep the sensitivity of the method as high as possible. Patients with dilated veins which may closely resemble DVT on thermography may in these cases give false positive results.

Of 76 patients with phlebographically verified DVT, 22% became thermographically normal within 22 days, whereas 78% did not normalize within the mean observation time of 31 days.

In another part of the study all medical patients (101) who were residing in our wards during a period of a week were screened by means of thermography. From this unselected group 17 patients were found to have thermographs suggestive of DVT. In 5 of these patients no reason for pathological thermography could be found.

Thermography is a cheap and highly sensitive screening method for DVT, but findings of false positives caused by older thromboses and dilated veins are not unusual. The frequency of such false positives may be minimized by performing thermography after exercise.
Autopsy Findings in an Elderly Man Suffering from Severe von Willebrand’s Disease
Authors: Kernoff Leslie M , Rose Alan G , Hughes Jane , Jacobs Peter
Published: July 2018

A platelet derived growth factor released following platelet adhesion to the subendothelium of damaged arteries may promote the development of atherosclerotic lesions. Consequently patients with von Willebrand’s disease in whom platelet adhesion is abnormal may be protected from atherosclerosis. This possibility was investigated by performing an autopsy study on an elderly patient who had suffered from severe von Willebrand’s disease. Extensive atherosclerotic lesions were found at post mortem suggesting that platelets may not play a clinically significant role in the causation of atherosclerosis
The Lupus Inhibitor: A Study of Its Heterogeneity
Authors: Coots M C , Miller M A , Glueck H I
Published: July 2018

The plasmas of six patients with prolonged activated partial thromboplastin times were studied in detail. In five of the six, the Russell’s viper venom and prothrombin times were likewise prolonged. Five of the patients had documented systemic lupus erythematosus; one lacked the necessary criteria for this diagnosis. On quantitation, factor XI was decreased in all six; factors X and XII were diminished in five of the six. When tested for inhibitory activity, plasma from each of the patients prolonged the celite eluate inhibition test for factor XII and/or XI inhibition. In the formation of the Xa-V-phospholipid-Ca2+ complex (prothrombinase), factors X and Xa were inhibited to a greater degree than factor V or the phospholipid. Finally, each plasma was isofocused, the inhibitory fractions were identified and the clotting factor specificity of each inhibitory peak was determined.Fractions inhibitory against factors XI and XII isofocused with the IgG in each patient’s plasma. Based on the data presented from these six patients, the “lupus inhibitor” is in fact a heterogeneous collection of inhibitors directed against factors XII, XI and X rather than a homogeneous entity.
Prostanoide in der Behandlung der chronisch arteriellen Verschlußkrankheit
Authors: Gruß J. D.
Published: July 2018

Vasodilatation, Hemmung der Thrombozytenaktivierung und Verbesserung der Fließeigenschaften des Blutes machten die intraarterielle Applikation von Prostanoiden bei der inoperablen peripheren AVK im Stadium III und IV zum interessanten Therapiekonzept. Günstige Erfahrungen mit der intravenösen Applikation blieben zunächst ohne rationale pharmakologische Erklärung, da 70-80% der Substanz PGE1 bei einer einzigen Lungenpassage metabolisiert werden. Erst die Entdeckung des stabilen Metaboliten 13,14-Dihydro-PGE-1 lieferte eine Erklärung für eine Vielzahl günstiger Therapiestudien. In der Gefäßchirurgie wird die intraarterielle PGE1 Therapie adjuvant bei femorodistalen Venenbypasses mit eingeschränkter Ausstrombahn eingesetzt. Die intravenöse adjuvante Therapie erwies sich als günstig beim Drei-Etagen- Verschluß im Stadium III und IV bei dem lediglich noch eine Profundaplastik möglich war. Weitere Einsatzbereiche sind das Trash-Syndrom, die Phlegmasia coerulea dolens, wenn es trotz erfolgreicher Thrombektomie zur fortschreitenden Nekrose kommt, der Ergotismus, das Ulcus cruris unterschiedlicher Genese, die arterielle Verschlußkrankheit vom digitalen Typ sowie die in Mitteleuropa relativ seltene Endangiitis obliterans.
Prävention intrakardialer Thromben und systemischer Embolien nach Herzklappenersatz
Authors: Horstkotte D.
Published: July 2018

Obwohl bislang keine prospektiven Dosisfindungsstudien durchgeführt wurden, wird für Patienten mit mechanischen Herzklappenprothesen eine orale Dauerantikoagulation mit einer Intensität von INR 3,0-4,5 empfohlen. Jüngste Untersuchungen zum optimalen Management einer oralen Antikoagulation bei Kunstklappenträgern belegen (a) die Unzulänglichkeit der Therapiesteuerung mittels des Quick-Wertes, (b) Unterschiede in der Thrombogenität älterer wie auch der heute verfügbaren Prothesen, (c) die Notwendigkeit einer individuellen Antikoagulation aufgrund der patientenseitigen Koagulabilität, (d) die Berücksichtigung der unabhängig von der implantierten Prothese zu intrakardialen Thrombosen und konsekutiven Embolien prädisponierenden kardialen Morphologie und Physiologie.
An introduction to achieving policy impact for early career researchers
Authors: Evans Megan C , Cvitanovic Christopher
Published: July 2018

Scientists are increasingly required to demonstrate the real world tangible impacts arising from their research. Despite significant advances in scholarship dedicated to understanding and improving the relationships between science, policy and practice, much of the existing literature remains high level, theoretical, and not immediately accessible to early career researchers (ECRs) who work outside of the policy sciences. In this paper, we draw on the literature and our own experiences working in the environmental sciences to provide an accessible resource for ECRs seeking to achieve policy impact in their chosen field. First, we describe key concepts in public policy to provide sufficient background for the non-expert. Next, we articulate a number of practical steps and tools that can help ECRs to identify and enhance the policy relevance of their research, better understand the policy world in practice and identify a range of pathways to achieving impact. Finally, we draw on our personal experiences to highlight some of the key individual characteristics and values that are needed to operate more effectively at the interface of science, policy and practice. Our hope is that the information and tools provided here can help to empower ECRs to create their own pathways to impact that best suit their individual goals, circumstances, interests and strengths.
Two-band ZnCdSe/ZnCdMgSe quantum well infrared photodetector
Authors: Kaya Yasin , Ravikumar Arvind , Chen Guopeng , Tamargo Maria C. , Shen Aidong , Gmachl Claire
Published: July 2018

An independently controllable, two-band quantum well infrared photo-detector (QWIP) based on the ZnCdSe/ZnCdMgSe material system is characterized. The two-band detector consists of two stacks of quantum wells absorbing in the mid- and long-wavelength infrared regime. Photocurrent and responsivity measurements resulted in 11 mA/W and 7 mA/W peak responsivities at 80 K with corresponding detectivities of 2 × 108 cm√Hz/W and 2 × 107 cm√Hz/W centered at 4.8 μm (258 meV) and 7.6 μm (163 meV). The two-band device can also perform as a broadband detector covering wavelengths from 4.4 μm (281 meV) to 8.2 μm (151 meV) at 80 K with a full width at half maximum of 130 meV. Two-band QWIP is tested for an absolute temperature detection application and good agreement is observed between theoretical calculation and experimental results.
Diode junction temperature in ultraviolet AlGaN quantum-disks-in-nanowires
Authors: Priante Davide , Elafandy Rami T. , Prabaswara Aditya , Janjua Bilal , Zhao Chao , Alias Mohd Sharizal , Tangi Malleswararao , Alaskar Yazeed , Albadri Abdulrahman M. , Alyamani Ahmed Y. , Ng Tien Khee , Ooi Boon S.
Published: July 2018

The diode junction temperature (Tj) of light emitting devices is a key parameter affecting the efficiency, output power, and reliability. Herein, we present experimental measurements of the Tj on ultraviolet (UV) AlGaN nanowire (NW) light emitting diodes (LEDs), grown on a thin metal-film and silicon substrate using the diode forward voltage and electroluminescence peak-shift methods. The forward-voltage vs temperature curves show temperature coefficient dVF/dT values of −6.3 mV/°C and −5.2 mV/°C, respectively. The significantly smaller Tj of ∼61 °C is measured for the sample on the metal substrate, as compared to that of the sample on silicon (∼105 °C), at 50 mA, which results from the better electrical-to-optical energy conversion and the absence of the thermally insulating SiNx at the NWs/silicon interface. In contrast to the reported higher Tj values for AlGaN planar LEDs exhibiting low lateral and vertical heat dissipation, we obtained a relatively lower Tj at similar values of injection current. Lower temperatures are also achieved using an Infrared camera, confirming that the Tj reaches higher values than the overall device temperature. Furthermore, the heat source density is simulated and compared to experimental data. This work provides insight into addressing the high junction temperature limitations in light-emitters, by using a highly conductive thin metal substrate, and it aims to realize UV AlGaN NWs for high power and reliable emitting devices.
α-Tocopherol modifies the expression of genes related to oxidative stress and apoptosis during in vitro maturation and enhances the developmental competence of rabbit oocytes
Authors: Arias-Álvarez M. , García-García R. M. , López-Tello J. , Rebollar P. G. , Gutiérrez-Adán A. , Lorenzo P. L.
Published: July 2018

The developmental competence of in vitro maturation (IVM) oocytes can be enhanced by antioxidant agents. The present study investigated, for the first time in the rabbit model, the effect of adding α-tocopherol (0, 100, 200 and 400 µM) during IVM on putative transcripts involved in antioxidant defence (superoxide dismutase 2, mitochondrial (SOD2), glutathione peroxidase 1 (GPX1), catalase (CAT)), cell cycle regulation and apoptosis cascade (apoptosis tumour protein 53 (TP53), caspase 3, apoptosis-related cysteine protease (CASP3)), cell cycle progression (cellular cycle V-Akt murine thymoma viral oncogene homologue 1 (AKT1)), cumulus expansion (gap junction protein, alpha 1, 43 kDa (GJA1) and prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclo-oxygenase) (PTGS2)) and metabolism (glucose-6-phosphate dehydrogenase (G6PD)). Meiotic progression, mitochondrial reallocation, cumulus cell apoptosis and the developmental competence of oocytes after IVF were also assessed. Expression of SOD2, CAT, TP53, CASP3 and GJA1 was downregulated in cumulus–oocyte complexes (COCs) after IVM with 100 μM α-tocopherol compared with the group without the antioxidant. The apoptotic rate and the percentage of a non-migrated mitochondrial pattern were lower in COCs cultured with 100 μM α-tocopherol, consistent with better-quality oocytes. In fact, early embryo development was improved when 100 μM α-tocopherol was included in the IVM medium, but remained low compared with in vivo-matured oocytes. In conclusion, the addition of 100 μM α-tocopherol to the maturation medium is a suitable approach to manage oxidative stress and apoptosis, as well as for increasing the in vitro developmental competence of rabbit oocytes.
Dramatherapy and Social Anxiety
Authors: Figge Peter A.W.
Published: July 2018

41 socially anxious students who sought psychotherapeutic help at the Counselling and Psychotherapy Center of Hamburg University were treated with dramatherapy In groups. Averaging a twelve-year problem duration of social anxiety, the dramatherapeutic subjects do not differ from the average non-therapy seeking student when compared in general social and family background or in intellectual capability. There are indications for a special helper-helpee relationship between parent and child as prerequisite for the development of social anxiety.

After four single therapy sessions, the treatment consisted of 16—three hour group sessions once a week, one of these being a three-day “intensive session” in the seclusion of a country meeting place. A therapy group consisted of eight clients (four female, four male) and one female, one male psychotherapist.

In comparing changes of an experimental group (n = 21) after dramatherapy with those of a control group (n = 20) who had been waiting for psychotherapy, drama games and exercises in combination with the work on a specially designed interaction hierarchy proved responsible for significant improvements of the experimental group on cognitive, emotional and behavioural levels. These effects having steadily developed during the process of the group therapy appear to be stable up to seven months after group therapy when follow up interviews were conducted. The therapy procedure Is illustrated, exemplary results are discussed.
Ultrafiltration and size exclusion chromatography combined with asymmetrical‐flow field‐flow fractionation for the isolation and characterisation of extracellular vesicles from urine
Authors: Oeyen Eline , Van Mol Kurt , Baggerman Geert , Willems Hanny , Boonen Kurt , Rolfo Christian , Pauwels Patrick , Jacobs An , Schildermans Karin , Cho William C , Mertens Inge
Published: July 2018

Extracellular vesicles (EVs) have a great potential in clinical applications. However, their isolation from different bodily fluids and their characterisation are currently not optimal or standardised. Here, we report the results of examining the performance of ultrafiltration combined with size exclusion chromatography (UF‐SEC) to isolate EVs from urine. The results reveal that UF‐SEC is an efficient method and provides high purity. Furthermore, we introduce asymmetrical‐flow field‐flow fractionation coupled with a UV detector and multi‐angle light‐scattering detector (AF4/UV‐MALS) as a characterisation method and compare it with current methods. We demonstrate that AF4/UV‐MALS is a straightforward and reproducible method for determining size, amount and purity of isolated urinary EVs.
Feeling European in a globalised world and the role of mobility, networks, and consumption: A comparative approach to British exceptionalism
Authors: Hanquinet Laurie , Savage Mike
Published: July 2018

This article rethinks European and global self-identification after the 2008 crash and the rise of populism and nationalism in Europe. Situating ourselves within the tradition of transactionalist theories, we run multinomial logistic regressions using data from the unusually comprehensive EUCROSS survey in Denmark, Germany, Italy, Romania, Spain, and the UK in 2012. We show that mobility, networks, and consumption practices are related to different kinds of national, European, and global identities among our respondents. Britain is distinctive in two ways. First, network and consumption practices induce a greater variation among British citizens in affecting their supranational feelings. Second, Britain sees a clearer differentiation between the forces of globalisation and Europeanisation. We conclude that the British are not, in any obvious ways, more nationalist than other nations, but that the strength of their ex-imperial networks means that their supranational identities can take a more anti-European form.
Development and Validation of an Electronic Medical Record–Based Algorithm to Identify Patient Milestones in the Hepatitis C Virus Care Cascade
Authors: Zucker Jason , Aaron Justin G , Feller Daniel J , Slowikowski Jacek , Evans Henry , Scherer Matthew L , Yin Michael T , Gordon Peter
Published: July 2018

Disease-specific care cascades are important public health and organizational tools to characterize gaps in care and target resources, but they are labor-intensive to maintain. Using data available from the electronic medical record, we developed an algorithm with high accuracy for correctly representing an individual’s status in the hepatitis C virus care cascade.
Recruitment and effectiveness by cohort in a case management intervention among American Indians and Alaska Natives with diabetes
Authors: Pratte Katherine A , Beals Janette , Johnson Ann , Bullock Ann , Manson Spero M , Jiang Luohua ,   Special Diabetes Program for Indians Healthy Heart Project Demonstration Project
Published: July 2018

In real-world settings, eligible populations and intervention effectiveness for a translational intervention likely vary across time. To determine the optimal strategies for effective large-scale implementation of evidence-based interventions, it is critical to investigate these potential variabilities. The purpose of this study is to evaluate whether patient characteristics and intervention effectiveness differed by year of enrollment in a multiyear evidence-based translational intervention. The Special Diabetes Program for Indians Healthy Heart (SDPI-HH) Demonstration Project is an intensive case management intervention designed to reduce cardiovascular disease risk among American Indians and Alaska Natives with diabetes. SDPI-HH participants recruited from 2006 through 2008 were included. Baseline characteristics were compared by year of enrollment. We also evaluated the differences in improvements in clinical and behavioral risk factors for cardiovascular disease among participants recruited in different years. The baseline characteristics of the three cohorts significantly differed in demographics, diabetes duration, health behaviors, level of motivation, and clinical measures. Improvements in 13 clinical and behavioral outcomes also differed by enrollment year with the 2006 cohort having the greatest number of significant improvements and the highest rates of participation and retention. Further investigation into the ways to modify the intensive case management model to address differences in levels of motivation and participation is warranted to improve the management of chronic disease in Indian health. Given the evolving nature of translational initiatives of this kind, our analysis results highlight the need to understand and adapt during the natural progression of health behavioral interventions.
PFLP-Intensified Disease Resistance Against Bacterial Soft Rot Through the MAPK Pathway in PAMP-Triggered Immunity
Authors: Hong Chuan-Yu , Zheng Jing-Lin , Chen Tzu-Yi , Chao How-Ran , Lin Yi-Hsien
Published: July 2018

Bacterial soft rot is a devastating disease affecting a variety of vegetable crops worldwide. One strategy for controlling this disease could be the ectopic expression of the plant ferredoxin-like protein (pflp) gene. PFLP was previously shown to intensify pathogen-associated molecular pattern-triggered immunity (PTI), an immune response triggered, for example, by the flagellin epitope flg22. To gain further insight into how PFLP intensifies PTI, flg22 was used as an elicitor in Arabidopsis thaliana. First, PFLP was confirmed to intensify the rapid generation of H2O2, callose deposition, and the hypersensitive response when coinfiltrated with flg22. This response correlated with increased expression of the FLG22-induced receptor kinase 1 gene, which is part of the mitogen-activated protein kinase (MAPK) pathway. Although the increased response to flg22 alone did not depend on the MAPK pathway genes MEKK1, MKK5, and MPK6, the protective effect of PFLP decreased when plants mutated in these genes were inoculated with Pectobacterium carotovorum subsp. carotovorum. Furthermore, expression of PR1 and PDF1.2 also increased upon treatment with flg22 in the presence of PFLP. Taken together, these results suggest that activation of the MAPK pathway contributes to the increased resistance to bacterial soft rot observed in plants treated with PFLP.
A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats
Authors: Tarry-Adkins Jane L. , Aiken Catherine E. , Ashmore Thomas J. , Fernandez-Twinn Denise S. , Chen Jian-Hua , Ozanne Susan E.
Published: July 2018

Reduced fetal nutrition and rapid postnatal growth accelerates the aging phenotype in many organ systems; however, effects on the immune system are unclear. We addressed this by studying the thymus from a rat model of developmental programming. The recuperated group was generated by in utero protein restriction, followed by cross‐fostering to control‐fed mothers, and were then compared with controls. Fat infiltration and adipocyte size increased with age (P < 0.001) and in recuperated thymi (P < 0.05). Cortex/medulla ratio decreased with age (P < 0.001) and decreased (P < 0.05) in 12‐mo recuperated thymi. Age‐associated decreases in thymic‐epithelial cell (P < 0.01) and thymocyte markers (P < 0.01) were observed in both groups and was decreased (P < 0.05) in recuperated thymi. These data demonstrate effects of developmental programming upon thymic involution. The recuperated group had longer thymic telomeres than controls (P < 0.001) at 22 d and at 3 mo, which was associated with increased expression of telomere‐length maintenance molecules [telomerase RNA component (Terc; P < 0.01), P23 (P = 0.02), and Ku70 and Ku80 (P < 0.01)]. By 12 mo, recuperated offspring had shorter thymic telomeres than controls had (P < 0.001) and reduced DNA damage‐response markers [(DNA‐PKcs, Mre11 (P < 0.01), Xrcc4 (P = 0.02), and γ‐H2ax (P < 0.001], suggesting failure of earlier compensatory responses. Our results suggest that low birth weight with rapid postnatal growth results in premature thymic maturation, resulting in accelerated thymic aging. This could lead to increased age‐associated vulnerability to infection.—Tarry‐Adkins, J. L., Aiken, C. E., Ashmore, T. J., Fernandez‐Twinn, D. S., Chen, J.‐H., Ozanne, S. E. A suboptimal maternal diet combined with accelerated postnatal growth results in an altered aging profile in the thymus of male rats. FASEB J. 33, 239–253 (2019). www.fasebj.org
Perinatal short‐chain fructooligosaccharides program intestinal microbiota and improve enteroinsular axis function and inflammatory status in high‐fat diet‐fed adult pigs
Authors: Le Bourgot Cindy , Ferret‐Bernard Stéphanie , Apper Emmanuelle , Taminiau Bernard , Cahu Armelle , Le Normand Laurence , Respondek Frédérique , Le Huërou‐Luron Isabelle , Blat Sophie
Published: July 2018

Perinatal nutrition programs physiologic and metabolic functions, with consequences on the susceptibility to develop metabolic diseases in adulthood. The microbiota represents a key factor of such programming. We investigated whether perinatal prebiotic [short‐chain fructooligosaccharides (scFOS)] supplementation improved adult metabolic health in association with microbiota changes in pigs used as human model. Sows were supplemented with scFOS or not during the end of gestation and the entire lactation, and offspring received scFOS accordingly during 1 mo after weaning. Pigs were then fed a standard diet for 5 mo, followed by a high‐fat diet for 3 mo once adults. Perinatal scFOS supplementation induced a persistent modulation of the composition of the fecal microbiota in adulthood, notably by increasing the Prevotella genus. Meanwhile, scFOS animals displayed improved capacity to secrete glucagon‐like peptide‐1 and improved pancreas sensitivity to glucose without any changes in peripheral insulin sensitivity. Perinatal scFOS supplementation also increased ileal secretory IgA secretion and alkaline phosphatase activity and decreased TNF‐α expression in adipose tissue. In conclusion, perinatal scFOS supplementation induced long‐lasting modulation of intestinal microbiota and had beneficial consequences on the host physiology in adulthood. Our results highlight the key role of perinatal nutrition on later microbiota and host metabolic adaptation to an unbalanced diet.—Le Bourgot, C., Ferret‐Bernard, S., Apper, E., Taminiau, B., Cahu, A., Le Normand, L., Respondek, F., Le Huerou‐Luron, I., Blat, S. Perinatal short‐chain fructooligosaccharides program intestinal microbiota and improve enteroinsular axis function and inflammatory status in high‐fat diet‐fed adult pigs. FASEB J. 33, 301–313 (2019). www.fasebj.org
Galectin‐1 is a new fibrosis protein in type 1 and type 2 diabetes
Authors: Al-Obaidi Noor , Mohan Sumathy , Liang Sitai , Zhao Zhenze , Nayak Bijaya K. , Li Boajie , Sriramarao P. , Habib Samy L.
Published: July 2018

Chronic exposure of tubular renal cells to high glucose contributes to tubulointerstitial changes in diabetic nephropathy. In the present study, we identified a new fibrosis gene called galectin‐1 (Gal‐1), which is highly expressed in tubular cells of kidneys of type 1 and type 2 diabetic mouse models. Gal‐1 protein and mRNA expression showed significant increase in kidney cortex of heterozygous Akita+/− and db/db mice compared with wild‐type mice. Mouse proximal tubular cells exposed to high glucose showed significant increase in phosphorylation of Akt and Gal‐1. We cloned Gal‐1 promoter and identified the transcription factor AP4 as binding to the Gal‐1 promoter to up‐regulate its function. Transfection of cells with plasmid carrying mutations in the binding sites of AP4 to Gal‐1 promoter resulted in decreased protein function of Gal‐1. In addition, inhibition of Gal‐1 by OTX‐008 showed significant decrease in p‐Akt/AP4 and protein‐promoter activity of Gal‐1 and fibronectin. Moreover, down‐regulation of AP4 by small interfering RNA resulted in a significant decrease in protein expression and promoter activity of Gal‐1. We found that kidney of Gal‐1−/− mice express very low levels of fibronectin protein. In summary, Gal‐1 is highly expressed in kidneys of type 1 and 2 diabetic mice, and AP4 is a major transcription factor that activates Gal‐1 under hyperglycemia. Inhibition of Gal‐1 by OTX‐008 blocks activation of Akt and prevents accumulation of Gal‐1, suggesting a novel role of Gal‐1 inhibitor as a possible therapeutic target to treat renal fibrosis in diabetes.—Al‐Obaidi, N., Mohan, S., Liang, S., Zhao, Z., Nayak, B. K., Li, B., Sriramarao, P., Habib, S. L. Galectin‐1 is a new fibrosis protein in type 1 and type 2 diabetes. FASEB J. 33, 373–387 (2019). www.fasebj.org
Creating a Culture of Mobility: Hospital-Based Pediatric Oncology Considerations
Authors: Spina Noel Marie , Augustine Leesha
Published: July 2018

Children with a diagnosis of cancer often have comprehensive treatment protocols spanning extensive periods of time. The disease and treatment process is frequently accompanied by multidimensional side effects, which impact physical performance and limit functional, independent mobility. With improving survival rates, physical activity limitations and mobility challenges have the potential to continue across the lifespan negatively impacting participation within designated life roles. Physical therapists can proactively address these concerns by creating a culture of mobility within the hospital setting that spans across service areas and health care disciplines, thereby engaging all members of the oncology team.
The International Classification of Functioning, Disability, and Health Model Guides Individualized Care for a Patient With Cancer: A Case Report
Authors: Baker Janine , Dominguez Jesus F. , Perdomo Marisa
Published: July 2018

Background and Purpose:

Individuals referred to physical therapy with a medical diagnosis of spinal accessory nerve palsy following medical intervention for head and neck cancer (HNC) are often managed by focusing on upper-quadrant impairments. Consequently, the presence of multisystem dysfunction may be overlooked. The International Classification of Functioning, Disability, and Health (ICF) model provides a useful framework to assess the patient with HNC and cues the physical therapist to formulate a comprehensive patient-centered treatment plan. This case study sought to assess the effectiveness of using the ICF model as a conceptual basis to develop a plan of care and assist a patient with HNC to realize his or her primary goal of returning to the workforce.

Case Summary:

The patient was seen as an outpatient in the University of Southern California faculty practice as part of a DPT student integrated project. His chief complaints included inability to work as a carpenter due to right shoulder pain, weakness, and generalized fatigue. During the initial examination, the physical therapist identified activity and participation restrictions and contextual barriers that limited the individual's ability to perform his work-related tasks. Guided by the ICF model theoretical construct, physical therapy interventions targeted the barriers that prevented him from fulfilling his role as a carpenter.

Conclusion:

Utilization of the ICF model for evaluation and treatment of an individual with HNC proved to be effective in guiding the physical therapy plan of care and in assisting the patient to achieve his primary goal of returning to work.