bluuebunny/crossref_metadata_2025 huggingface dataset:
Linear Immunoglobulin A Bullous Dermatosis: Need for an Agreement on Diagnostic Criteria
Authors: Antiga Emiliano , Caproni Marzia , Fabbri Paolo
Published: September 2013

Linear immunoglobulin A bullous dermatosis (LABD) is a rare, heterogeneous, autoimmune blistering disorder. Although the main characteristics of the disease seem to be well identified, international accepted diagnostic criteria are lacking. Several authors suggested their own criteria, but they are often not complete or even in contrast with clinical and immunopathological findings from the literature, while others are too selective. In this review, the current views and the problems with the definition of reliable diagnostic criteria for LABD will be discussed.
Systematic Review of Metformin Use in Obese Nondiabetic Children and Adolescents
Authors: Brufani Claudia , Crinò Antonino , Fintini Danilo , Patera Patrizia Ippolita , Cappa Marco , Manco Melania
Published: September 2013

Objective: Childhood obesity has become epidemic and has been accompanied by an increase in prevalence of type 2 diabetes (T2DM) in youth. Addressing obesity and insulin resistance by drug treatment represents a rational strategy for the prevention of T2DM. A systematic review was performed to evaluate the effectiveness of metformin in reducing weight and ameliorating insulin resistance in obese nondiabetic children. Methods: A PubMed database search was conducted, using ‘metformin', ‘obesity', ‘insulin resistance', ‘children', ‘adolescents' as search terms. Results: Eleven trials were included in the present review. Metformin was administered for 6-12 months at a dosage of 1,000-2,000 mg/daily, decreasing BMI by 1.1-2.7 compared with placebo or lifestyle intervention alone. Concomitantly, fasting insulin resistance improved after metformin therapy. Posttreatment follow-up was performed in one study, showing that after 1 year of discontinuation of therapy the decrease in BMI disappears. Conclusions: Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents, with a concomitant improvement in fasting insulin sensitivity. Further studies with longer treatment period are needed to establish how much metformin can reduce weight and its real utility in preventing T2DM development in pediatric patients.
Material Properties of the Internal Limiting Membrane and Their Significance in Chromovitrectomy
Authors: Henrich Paul B. , Monnier Christophe A. , Loparic Marko , Cattin Philippe C. ,   International Chromovitrectomy Collaboration
Published: September 2013

Intraoperative visualization of the internal limiting membrane (ILM), the choice of a point of vantage for lifting an initial flap, the precision with which the ILM is grasped, adhesion between the forceps and the ILM, thickness, stiffness and elasticity of the ILM as well as monitoring of the completeness of ILM removal are all important factors for safety and efficacy of a chromovitrectomy intervention. The understanding of the underlying physical features of the ILM, such as contrast behavior and bioanatomical and biomechanical properties represent, thus, useful prerequisites for successful macular surgery. New analytical tools, such as atomic force microscopy and chromaticity analysis, allow new insights into ILM material characteristics, permitting a systematic approach to refinement of surgical technique.
The Retinal Biocompatibility of Dyes in the ex vivo Model of the Isolated Superfused Vertebrate Retina
Authors: Lüke Matthias , Grisanti Salvatore , Lüke Julia ,   International Chromovitrectomy Collaboration
Published: September 2013

Background: Peeling of the internal limiting membrane or epiretinal membranes is a successful principle in macular surgery to achieve a functional benefit. Different dyes are used to facilitate the identification of intraocular tissues. The aim of our work was to investigate the retinal tolerance to the different dyes and their solvent carriers to provide valuable data for surgeons in handling for an optimal intraoperative use. Methods: Using the ex vivo model of the isolated superfused vertebrate retina technique, the effects of the dyes were tested on human and bovine retinal function. The retinas were perfused with an oxygen preequilibrated standard solution. The electroretinogram (ERG) was recorded using Ag/AgCl electrodes. After recording stable ERG amplitudes, the dyes brilliant blue G, indocyanine green, trypan blue, patent blue, triamcinolone and their solvent carriers were investigated. Results: Reductions of the ERG amplitudes were found for each tested dye. The effects after application of the dyes were dependent on time and concentration of the applied dyes, which were different for each dye. Conclusion: In part, the ERG has shown strong effects already after a short period of dye application. Surgeons who rely on the intraocular use of the dyes should keep in mind our findings, and the use of some dyes should be limited to selected cases. The well-considered use of the dyes by the surgeons could lead to a better functional outcome and avoid a possible harmful outcome of the surgery after mishandling.
Improved Brilliant Blue G Staining of the Internal Limiting Membrane with Sharp Cut Filters of a Novel Viewing Filter System
Authors: Enaida Hiroshi , Yoshida Shigeo , Nakao Shintaro , Ikeda Yasuhiro , Hachisuka Yoshiyuki , Oshima Yusuke , Kadonosono Kazuaki , Ueno Akifumi , Ishibashi Tatsuro ,   International Chromovitrectomy Collaboration
Published: September 2013

Purpose: We developed a new artificial image enhancement system aimed at intraoperative visibility improvement as a clinical prototype. We examined each optical characteristic and change in intraoperative visibility using brilliant blue G (BBG) staining with various sharp cut filters (SCFs). Method: This was a retrospective and observational study. The system was composed of several filters attached to the operating microscope. Six eyes from 6 patients who presented with macular hole and underwent surgery using this system were studied. As a clinical examination, the intraoperative visibility of BBG staining intensities was compared for 4 kinds of SCFs during vitrectomy. Quantitative evaluation was calculated using the International Commission on Illumination 1976 (L*, a*, b*) color space (CIELAB) method. Furthermore, we evaluated each optical characteristic of 4 types of SCFs using extracted porcine eyes and a spectroradiometer as a clinical simulation. Results: Suitable filter selection was possible for this system. The observed color tone and spectral irradiance changes with SCF insertion changed dynamically. In macular hole cases, the color intensities between BBG-stained and nonstained areas were improved using SCF-455 and SCF-520, which was statistically significant (p < 0.05) by CIELAB. Conclusion: The system improved BBG staining intensity with the use of selective SCFs.
Effect of Novel Vital Dyes on Outer Blood-Retina Barrier Function in Cultured Human Retinal Pigment Epithelium
Authors: Liu Zengping , Meyer Carsten H. , Stanzel Boris V. ,   International Chromovitrectomy Collaboration
Published: September 2013

Purpose: To assess tight junction (TJ) integrity in cultured human fetal retinal pigment epithelium (HFRPE) after exposure to clinically relevant novel vital dyes. Methods: HFRPE floater cells were harvested from RPE primary cultures of 4 donor eyes and seeded on polyester Transwell® for 4-6 weeks. The apical compartments of well-differentiated cultures were exposed to 0.005 mg/ml Coomassie violet R200 (CVR), methyl 2B (M2B) or Orange II. Periods of 30-300 s were chosen to mimic surgical exposure times, while 3 h was used for toxicity assays, with subsequent washout. Cell-cell junctions were studied by immunofluorescence (zonula occludens-1, ZO-1). Transepithelial electrical resistance (TER) was measured regarding blood-retina barrier (BRB) function. Results: At 4-6 weeks after confluence, HFRPE had grown into pigmented hexagonal monolayers with stable TER values (451-1,520 Ω·cm2). After 300-second dye treatments, a continuous ZO-1 signal was detected in all vital dye-treated groups 1.5 h after exposure, whereas trypsin controls showed patchy loss of the TJ stain. TER of CVR-, M2B- and Orange-II-treated groups had dropped 1.5 h after exposure to 148 ± 58.4, 162 ± 23.7 and 164 ± 18.5 Ω·cm2, respectively, compared to 73 ± 44.9 Ω·cm2 in positive controls. After 3 h of exposure to 0.005 mg/ml vital dyes in thick drops, TER maintained similar levels to those prior to exposure (90.8 ± 4.7% of the original values, 93.8 ± 6.5 and 91.9 ± 3.6%, respectively), together with no difference from the vehicle controls (94.8 ± 6.6%). TER values recovered in all groups to prior levels within 3 days. Conclusion: Novel vital dyes (CVR, M2B and Orange II) caused no outer BRB function alteration.
Biochemical Analysis and Decomposition Products of Indocyanine Green in Relation to Solvents, Dye Concentrations and Laser Exposure
Authors: Penha Fernando M. , Rodrigues Eduardo B. , Maia Mauricio , Meyer Carsten H. , de Paula Fiod Costa Elaine , Dib Eduardo , Bechara Etelvino , Lourenço Andréia , Lima Filho Acácio A.S. , Freymüller Edna H. , Farah Michel Eid ,   International Chromovitrectomy Collaboration
Published: September 2013

Purpose: To investigate pH, ions, osmolarity and precipitation of indocyanine green (ICG), as well as the profile of ICG decomposition products (DPs) after laser exposure and the interaction with quenchers. Methods: ICG was diluted in water, 5% glucose (GL) or balanced salt solution (BSS) to achieve concentrations of 2.5, 1, 0.25 and 0.1 mg/ml. Osmolarity, pH and precipitation were analyzed immediately and after 24 h. Precipitation analyses were done with a scanning electron microscope. Anion and iodate analyses of ICG and infracyanine green (IfCG) were performed by capillary zone electrophoresis. With regard to DPs, 0.5 mg/ml of ICG was assessed with high-performance liquid chromatography (HPLC) after 810-nm laser irradiation. DP profiles were evaluated with ICG dilution in quenchers (Trolox, histidine and DABCO) in 3 concentrations (0.1, 1 and 10 M). Results: BSS promoted iso-osmotic ICG solutions of 208 mOsm (147-266) compared to GL with 177 mOsm. BSS solutions had a higher physiological pH of 7.2 compared with the GL one of 6.55. ICG precipitated more when diluted with BSS (5.95 mg); in contrast, GL showed less precipitate (3.6 mg). IfCG has no iodine derivates and other ICGs have an average 4.6% of iodate derivates. From HPLC analysis, 5 DPs were observed. The rate of DPs was higher when BSS was used (p < 0.05). Five DPs have been generated with ICG, and they may be altered with the quenchers DABCO, histidine and Trolox. Conclusions: BSS dilution induces more precipitation and DPs. ICG dilution in any solvent induces DPs. Quencher use reduces the amount of toxic DPs.
Internetbasierte psychologische Behandlung bei Depressionen
Authors: Klein Jan Philipp , Berger Thomas
Published: September 2013

Depression ist die häufigste psychische Erkrankung, aber nur ein geringer Anteil der Betroffenen erhält eine angemessene Behandlung. Internetbasierte Interventionen stellen eine vielversprechende Ergänzung zu traditionellen Behandlungsformen dar, denn über das Internet können breite Bevölkerungsschichten mit wenig Aufwand erreicht werden. Die vorliegende Übersicht stellt den aktuellen Forschungsstand zu internetbasierten Interventionen bei Depressionen dar. Mehrere randomisierte kontrollierte Studien, Metaanalysen und Reviews legen nahe, dass mit strukturierten internetbasierten Interventionen, die regelmäßige Kontakte mit Therapeuten beinhalten (z.B. geleitete Selbsthilfeansätze, E-Mail- oder Chat-Therapien), Effekte erzielt werden können, die mit den Effekten von traditionellen Psychotherapien vergleichbar sind. Ungeleitete Selbsthilfeprogramme sind typischerweise mit hohen Abbrecherquoten und geringeren Effekten verbunden. Die zukünftige Forschung sollte sich vermehrt mit der Frage beschäftigen, wie internetbasierte Interventionen bei Depressionen optimal in die psychosoziale Versorgung integriert werden können. Mögliche Einsatzbereiche und die Einbettung internetbasierter Interventionen in das Versorgungssystem werden dargestellt und diskutiert.
Outcome of Early Breast Cancer Treated in an Urban and a Rural Breast Cancer Unit in Germany
Authors: Heitz Florian , Bender Alexandra , Barinoff Jana , Lorenz-Salehi Fatemeh , Fisseler-Eckhoff Annette , Traut Alexander , Hils Rita , Harter Philipp , Kullmer Uwe , du Bois Andreas
Published: September 2013

Background: Conflicting evidence has been published concerning survival disadvantages in the outcome of breast cancer patients in relationship to their residency in urban or rural communities. Methods: The primary aim of this study was to evaluate differences in patients and treatment characteristics between an urban and a rural breast cancer unit. Therefore, all early breast cancer patients treated consecutively between 1999 and 2007 in a rural and an urban breast cancer unit were included. Patient and tumor characteristics, treatment strategies, and guideline adherence were included to evaluate the prognoses of both populations. Results: Overall, data from 2,566 patients were included in this analysis. The 610 patients treated in the rural unit showed significantly more negative prognostic criteria than the 1,956 patients treated in the urban center. No differences were observed with respect to surgical and systemic treatment after adjustment for prognostic parameters. Adherence to national guidelines did not differ significantly between both settings and ranged between 78.0 and 95.6%. Furthermore, no differences regarding recurrence-free and overall survival were observed. Conclusions: The stage-adjusted pattern of care was similar in 2 German breast care units in a rural region and an urban area. Nevertheless, an earlier diagnosis of breast cancer should be enforced in rural areas to avoid extended treatment burden.
SMS-Nachsorge: Sektorenübergreifende Versorgung für Patientinnen mit Bulimia nervosa
Authors: Bauer Stephanie , Okon Eberhard , Meermann Rolf , Kordy Hans
Published: September 2013

Hintergrund: Über den Zusammenhang zwischen der Teilnahme an E-Mental-Health-Interventionen und der Inanspruchnahme regulärer Psychotherapie ist bisher wenig bekannt. In der vorliegenden Studie wurde untersucht, inwiefern ein SMS-basiertes Nachsorgeprogramm mit einem veränderten Inanspruchnahmeverhalten ambulanter Therapie im Anschluss an eine stationäre Behandlung für Essstörungen assoziiert ist. Methode: 165 Patientinnen, die aufgrund einer vollausgeprägten oder subsyndromalen Bulimia nervosa stationär behandelt wurden, wurden randomisiert jeweils einer Kontrollgruppe (KG: treatment as ususal (TAU)) oder Interventionsgruppe (IG: 16-wöchige Nachsorge über SMS zusätzlich zu TAU) zugewiesen. Erfasst wurden die Rückfallrate und die Inanspruchnahme ambulanter Therapie innerhalb des 8-monatigen Follow-up-Zeitraums. Ergebnisse: In der KG wurden signifikant mehr Rückfälle beobachtet als in der IG (KG: 42,0%; IG: 26,8%). Vergleichbar viele Teilnehmerinnen nahmen ambulante Therapie in Anspruch (KG: 52,2%; IG: 53,5%). Innerhalb der Teilnehmerinnen, die eine ambulante Therapie aufnahmen, unterschieden sich die Rückfallraten von KG und IG nicht signifikant (KG: 38,9%; IG: 28,9%). Ein bedeutsamer Unterschied wurde hingegen in der Untergruppe festgestellt, die keine ambulante Therapie nutzte (KG: 45,5%; IG: 24,2%). Schlussfolgerung: Die Studie unterstreicht den Bedarf an sektorenübergreifenden Versorgungsangeboten (stationär-ambulant). Die Studie liefert erste Hinweise, dass das SMS-Programm das Inanspruchnahmeverhalten bezüglich ambulanter Therapie positiv beeinflussen könnte. Weitere Studien sind notwendig, um diesen möglichen kausalen Effekt zu untersuchen.
Internet-Based Interventions for Social Anxiety Disorder - an Overview
Authors: Boettcher Johanna , Carlbring Per , Renneberg Babette , Berger Thomas
Published: September 2013

Internet-based interventions hold specific advantages and disadvantages in the treatment of social anxiety disorder (SAD). The present review examines different approaches in the internet-based treatment of SAD and reviews their efficacy and effectiveness. 21 studies investigated the potential of guided and unguided internet-based cognitive-behavioral treatments (ICBT) for SAD, comprising a total of N = 1,801 socially anxious individuals. The large majority of these trials reported substantial reductions of social anxiety symptoms through ICBT programs. Within effect sizes were mostly large and comparisons to waitlist and more active control groups were positive. Treatment gains were stable from 3 months to 5 years after treatment termination. In conclusion, ICBT is effective in the reduction of social anxiety symptoms. At the same time, not all participants benefit from these treatments to a sufficient degree. Future research should focus on what makes these interventions work in which patient populations, and at the same time, examine ways to implement internet-based treatment in the routine care for socially anxious patients.
Effectiveness of Guided Internet-Based Cognitive Behavior Therapy in Regular Clinical Settings
Authors: Andersson Gerhard , Hedman Erik
Published: September 2013

Therapist-guided internet-based cognitive behavior therapy (ICBT) has been tested in numerous controlled trials conducted in research settings. It is now established that this novel treatment format works for a range of clinical conditions. It is less well known if the promising results from efficacy studies can be transferred to routine clinical practice. In this paper we review the evidence from effectiveness studies and highlight challenges when implementing ICBT. Following literature searches we identified 4 controlled trials and 8 open studies, involving a total of 3,888 patients. There is now an increasing number of effectiveness studies on ICBT with studies on panic disorder, social anxiety disorder, generalized anxiety disorder, post-traumatic stress disorder, depression, tinnitus, and irritable bowel syndrome. All indicate that it is possible to transfer ICBT to clinical practice with sustained effects and moderate to large effect sizes. However, it is not clear which model to use for service delivery, and more work remains to be done on dissemination of ICBT. Moreover, the knowledge about outcome predictors from controlled efficacy trials is probably less relevant, and studies with large clinically representative samples are needed to investigate for which patients ICBT is suitable. In this work existing data could be combined and reanalyzed to study predictors of outcome.
CBASP@home: Ein internetbasiertes Situationsanalysen-Training zur Stabilisierung des Therapieerfolgs nach stationärer Therapie für chronisch depressive Patienten
Authors: Brakemeier Eva-Lotta , Marchner Janina , Gutgsell Simone , Engel Vera , Radtke Martina , Tuschen-Caffier Brunna , Normann Claus , Berking Matthias
Published: September 2013

Hintergrund: Aufbauend auf einer ambulanten CBASP-Behandlung wurde ein stationäres multidisziplinäres Konzept zur Behandlung chronischer Depression entwickelt. Eine Pilotstudie zeigte positive Ergebnisse hinsichtlich der Wirkung dieses Konzepts, jedoch berichteten einige Patienten, dass die 12-wöchige Therapie zu kurz und die Zeit unmittelbar nach Entlassung schwierig sei. Daher wurde CBASP@home als ein internetbasiertes Situationsanalysen (SA)-Training zur Stabilisierung des erzielten Behandlungserfolgs konzipiert. CBASP@home ist eine 3-monatige Step-down-Onlineintervention. Die Patienten werden dabei unterstützt, die erlernten SA zu Hause fortzuführen und in den Alltag zu transferieren. An insgesamt 9 Terminen füllten die Patienten das SA-Formular über einen Sicherheitsserver aus und erhielten von ihrem stationären Psychotherapeuten zeitnah Rückmeldung. Fallbericht: In der vorliegenden Phase-I-Studie wurde die Akzeptanz und Durchführbarkeit von CBASP@home an 2 Einzelfällen untersucht. CBASP@home wurde von beiden Patienten sehr gut angenommen und als sinnvolle Unterstützung bewertet. Zudem konnte bei beiden Patienten eine zunehmende Leistungssteigerung in der SA-Durchführung bei gleichzeitig rückläufiger depressiver Symptomatik bis zur Remission beobachtet werden. Schlussfolgerungen: Die beiden Einzelfallauswertungen liefern Hinweise, dass CBASP@home Transferprozesse vom stationären Setting in den Alltag erleichtern, Behandlungserfolge beibehalten bzw. Rückfällen vorbeugen kann. Wenn sich diese positiven Erfahrungen in zukünftigen Studien bestätigen sollten, kann CBASP@home wesentlich zur Verbesserung der langfristigen Versorgung chronisch depressiver Patienten beitragen.
Symmetrical Dimethylarginine Predicts Mortality in the General Population
Authors: Gore M. Odette , Lüneburg Nicole , Schwedhelm Edzard , Ayers Colby R. , Anderssohn Maike , Khera Amit , Atzler Dorothee , de Lemos James A. , Grant Peter J. , McGuire Darren K. , Böger Rainer H.
Published: September 2013

Objective—

Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years.

Approach and Results—

SDMA and ADMA were measured by liquid chromatography-tandem mass-spectrometry (n=3523), coronary artery calcium by electron-beam computed tomography, and abdominal aortic wall thickness by MRI. In unadjusted analyses, categories of increasing SDMA and ADMA were associated with higher prevalence of cardiovascular risk factors, increased risk markers, and all-cause and cardiovascular mortality (median follow-up, 7.4 years). After adjustment for age, sex, and race, traditional cardiovascular risk factors, and renal function, SDMA and ADMA analyzed as continuous variables were associated with coronary artery calcium >10, but only SDMA was associated with abdominal aortic wall thickness. SDMA, but not ADMA, was associated with cardiovascular mortality (hazard ratio per log unit change, 3.36 [95% confidence interval, 1.49–7.59];
P
=0.004). SDMA and ADMA were both associated with all-cause mortality, but after further adjustment for N-terminal pro–brain-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin T, only SDMA was associated with all-cause mortality (hazard ratio per log unit change, 1.86 [95% confidence interval, 1.04–3.30];
P
=0.01).

Conclusions—

SDMA, but not ADMA, was an independent predictor of all-cause and cardiovascular mortality in a large multiethnic population-based cohort.
Mechanistic Target of Rapamycin Complex 2 Protects the Heart From Ischemic Damage
Authors: Völkers Mirko , Konstandin Mathias H. , Doroudgar Shirin , Toko Haruhiro , Quijada Pearl , Din Shabana , Joyo Anya , Ornelas Luis , Samse Kaitleen , Thuerauf Donna J. , Gude Natalie , Glembotski Christopher C. , Sussman Mark A.
Published: September 2013

Background—

The mechanistic target of rapamycin (mTOR) comprises 2 structurally distinct multiprotein complexes, mTOR complexes 1 and 2 (mTORC1 and mTORC2). Deregulation of mTOR signaling occurs during and contributes to the severity of myocardial damage from ischemic heart disease. However, the relative roles of mTORC1 versus mTORC2 in the pathogenesis of ischemic damage are unknown.

Methods and Results—

Combined pharmacological and molecular approaches were used to alter the balance of mTORC1 and mTORC2 signaling in cultured cardiac myocytes and in mouse hearts subjected to conditions that mimic ischemic heart disease. The importance of mTOR signaling in cardiac protection was demonstrated by pharmacological inhibition of both mTORC1 and mTORC2 with Torin1, which led to increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. Predominant mTORC1 signaling mediated by suppression of mTORC2 with Rictor similarly increased cardiomyocyte apoptosis and tissue damage after myocardial infarction. In comparison, preferentially shifting toward mTORC2 signaling by inhibition of mTORC1 with PRAS40 led to decreased cardiomyocyte apoptosis and tissue damage after myocardial infarction.

Conclusions—

These results suggest that selectively increasing mTORC2 while concurrently inhibiting mTORC1 signaling is a novel therapeutic approach for the treatment of ischemic heart disease.
PERK‐eIF2α‐ATF4‐CHOP Signaling Contributes to TNFα‐Induced Vascular Calcification
Authors: Masuda Masashi , Miyazaki‐Anzai Shinobu , Levi Moshe , Ting Tabitha C. , Miyazaki Makoto
Published: September 2013

Background

Vascular calcification is a common feature in patients with chronic kidney disease (
CKD
).
CKD
increases serum levels of tumor necrosis factor‐α (TNFα), a critical mediator of vascular calcification. However, the molecular mechanism by which
TNF
α promotes
CKD
‐dependent vascular calcification remains obscure. The purpose of the present study was to investigate whether
TNF
α‐induced vascular calcification in
CKD
is caused by the endoplasmic reticulum response involving protein kinase
RNA
‐like endoplasmic reticulum kinase (
PERK
), eukaryotic initiation factor 2α (eIF2α), activating transcription factor 4 (
ATF
4), and C/
EBP
homologous protein (
CHOP
).

Methods and Results

We examined the effects of
TNF
α on the endoplasmic reticulum (
ER
) stress response of vascular smooth muscle cells (
VSMC
s).
TNF
α treatment drastically induced the
PERK
‐eIF2α‐
ATF
4‐
CHOP
axis of the
ER
stress response in
VSMC
s.
PERK
,
ATF
4, and
CHOP
sh
RNA
‐mediated knockdowns drastically inhibited mineralization and osteogenesis of
VSMC
s induced by
TNF
α.
CKD
induced by 5/6 nephrectomies activated the
PERK
‐eIF2α‐
ATF
4‐
CHOP
axis of the
ER
stress response in the aortas of ApoE
−/−
mice with increased aortic
TNF
α expression and vascular calcification. Treatment of 5/6 nephrectomized ApoE
−/−
mice with the
TNF
α neutralizing antibody or chemical Chaperones reduced aortic
PERK
‐eIF2α‐
ATF
4‐
CHOP
signaling of the
ER
stress increased by
CKD
. This resulted in the inhibition of
CKD
‐dependent vascular calcification.

Conclusions

These results suggest that
TNF
α induces the
PERK
‐eIF2α‐
ATF
4‐
CHOP
axis of the
ER
stress response, leading to
CKD
‐dependent vascular calcification.
Nasal Administration of Recombinant Osteopontin Attenuates Early Brain Injury After Subarachnoid Hemorrhage
Authors: Topkoru Basak Caner , Altay Orhan , Duris Kamil , Krafft Paul R. , Yan Junhao , Zhang John H.
Published: September 2013

Background and Purpose—

Neuronal apoptosis is a key pathological process in subarachnoid hemorrhage (SAH)–induced early brain injury. Given that recombinant osteopontin (rOPN), a promising neuroprotectant, cannot pass through the blood–brain barrier, we aimed to examine whether nasal administration of rOPN prevents neuronal apoptosis after experimental SAH.

Methods—

Male Sprague–Dawley rats (n=144) were subjected to the endovascular perforation SAH model. rOPN was administered via the nasal route and neurological scores as well as brain water content were evaluated at 24 and 72 hours after SAH induction. The expressions of cleaved caspase-3, phosphorylated focal adhesion kinase (FAK), and phosphorylated Akt were examined using Western blot analysis. Neuronal cell death was demonstrated with terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling. We also administered FAK inhibitor 14 and phosphatidylinositol 3-kinase inhibitor, Wortmannin, prior to rOPN to establish its neuroprotective mechanism. ELISA was used to measure rOPN delivery into the cerebrospinal fluid.

Results—

Cerebrospinal fluid level of rOPN increased after its nasal administration. This was associated with improved neurological scores and reduced brain edema at 24 hours after SAH. rOPN increased phosphorylated FAK and phosphorylated Akt expressions and decreased caspase-3 cleavage, resulting in attenuation of neuronal cell death within the cerebral cortex. These effects were abolished by FAK inhibitor 14 and Wortmannin.

Conclusions—

Nasal administration of rOPN decreased neuronal cell death and brain edema and improved the neurological status in SAH rats, possibly through FAK–phosphatidylinositol 3-kinase–Akt–induced inhibition of capase-3 cleavage.
Ischemic Stroke Brain Sends Indirect Cell Death Signals to the Heart
Authors: Ishikawa Hiroto , Tajiri Naoki , Vasconcellos Julie , Kaneko Yuji , Mimura Osamu , Dezawa Mari , Borlongan Cesar V.
Published: September 2013

Background and Purpose—

Ischemic stroke is a leading cause of mortality and morbidity in the world and may be associated with cardiac myocyte vulnerability. However, it remains uncertain how an ischemic brain contributes to cardiac alternations. Here, we used experimental stroke models to reveal the pathological effects of the ischemic brain on the heart.

Methods—

For the in vitro study, primary rat neuronal cells were subjected to 90-minute oxygen–glucose deprivation (OGD). Two hours after OGD, the supernatant was collected and cryopreserved until further biological assays. Primary rat cardiac myocytes were exposed to ischemic–reperfusion injury and subsequently to the supernatant derived from either the OGD or non–OGD-exposed primary rat neuronal cells for 2, 6, 24, or 48 hours. Thereafter, we measured cell viability and mitochondrial activity in rat cardiac myocytes. For the in vivo study, we subjected adult rats to transient middle cerebral artery occlusion, and their brains and hearts were harvested for immunohistochemical analyses at 3 months later.

Results—

The supernatant from the OGD, but not the non–OGD-exposed primary rat neuronal cells, caused significant reduction in cell viability and mitochondrial activity in rat cardiac myocytes. Ischemic stroke animals displayed phenotypic expression of necrosis, apoptosis, and autophagy in their hearts, which paralleled the detection of these same cell death markers in their brains.

Conclusions—

Ischemic stroke was accompanied by cardiac myocyte death, indicating a close pathological link between brain and heart. These results suggest a vigilant assessment of the heart condition in stroke patients, likely requiring the need to treat systemic cardiac symptoms after an ischemic brain episode.
Variation in Risk Factors for Recent Small Subcortical Infarcts With Infarct Size, Shape, and Location
Authors: Del Bene Alessandra , Makin Stephen D.J. , Doubal Fergus N. , Inzitari Domenico , Wardlaw Joanna M.
Published: September 2013

Background and Purpose—

Lacunar infarction is attributable to a perforating arteriolar abnormality. Possible causes include embolism, atheromatosis, or intrinsic disease. We examined whether the size, shape, or location of the lacunar infarct varied with embolic sources, systemic atheroma, or vascular risk factors.

Methods—

We examined data from 3 prospective studies of patients with clinical and diffusion-weighted imaging–positive symptomatic lacunar infarction who underwent full clinical assessment and investigation for stroke risk factors. Lacunar infarct sizes (maximum diameter; shape, oval/tubular; location, basal ganglia/centrum semiovale/brain stem) were coded blind to clinical details.

Results—

Among 195 patients, 48 infarcts were tubular, 50 were 15 to 20 mm in diameter, and 97 and 74 were located in the basal ganglia and the centrum semiovale, respectively. There was no association between infarct size or shape and any of the risk factors. Centrum semiovale infarcts were less likely to have a potential relevant embolic source (4% versus 11%; odds ratio, 0.16; 95% confidence interval, 0.03–0.83) and caused a lower National Institute of Health Stroke Scale score (2 versus 3; odds ratio, 0.78; 95% confidence interval, 0.62–0.98) than basal ganglia infarcts. There were no other differences by infarct location.

Conclusions—

Lacunar infarcts in the basal ganglia caused marginally severer strokes and were 3 times more likely to have a potential embolic source than those in the centrum semiovale, but the overall rate of carotid or known cardiac embolic sources (11%) was low. We found no evidence that other risk factors differed with location, size, or shape, suggesting that most lacunar infarcts share a common intrinsic arteriolar pathology.
Reconciling Ground-Based and Space-Based Estimates of the Frequency of Occurrence and Radiative Effect of Clouds around Darwin, Australia
Authors: Protat A. , Young S. A. , McFarlane S. A. , L’Ecuyer T. , Mace G. G. , Comstock J. M. , Long C. N. , Berry E. , Delanoë J.
Published: September 2013

The objective of this paper is to investigate whether estimates of the cloud frequency of occurrence and associated cloud radiative forcing as derived from ground-based and satellite active remote sensing and radiative transfer calculations can be reconciled over a well-instrumented active remote sensing site located in Darwin, Australia, despite the very different viewing geometry and instrument characteristics. It is found that the ground-based radar–lidar combination at Darwin does not detect most of the cirrus clouds above 10 km (because of limited lidar detection capability and signal obscuration by low-level clouds) and that the CloudSat radar–Cloud–Aerosol Lidar with Orthogonal Polarization (CALIOP) combination underreports the hydrometeor frequency of occurrence below 2-km height because of instrument limitations at these heights. The radiative impact associated with these differences in cloud frequency of occurrence is large on the surface downwelling shortwave fluxes (ground and satellite) and the top-of-atmosphere upwelling shortwave and longwave fluxes (ground). Good agreement is found for other radiative fluxes. Large differences in radiative heating rate as derived from ground and satellite radar–lidar instruments and radiative transfer calculations are also found above 10 km (up to 0.35 K day−1 for the shortwave and 0.8 K day−1 for the longwave). Given that the ground-based and satellite estimates of cloud frequency of occurrence and radiative impact cannot be fully reconciled over Darwin, caution should be exercised when evaluating the representation of clouds and cloud–radiation interactions in large-scale models, and limitations of each set of instrumentation should be considered when interpreting model–observation differences.
Intrinsic Nonlinearity and Spectral Structure of Internal Tides at an Idealized Mid-Atlantic Bight Shelf Break
Authors: Zhang Weifeng G. , Duda Timothy F.
Published: September 2013

To quantify dynamical aspects of internal-tide generation at the Mid-Atlantic Bight shelf break, this study employs an idealized ocean model initialized by climatological summertime stratification and forced by monochromatic barotropic tidal currents at the offshore boundary. The Froude number of the scenario is subunity, and the bathymetric slope offshore of the shelf break is supercritical. A barotropic-to-baroclinic energy conversion rate of 335 W m−1 is found, with 14% of the energy locally dissipated through turbulence and bottom friction and 18% radiated onto the shelf. Consistent with prior studies, nonlinear effects result in additional super- and subharmonic internal waves at the shelf break. The subharmonic waves are subinertial, evanescent, and mostly trapped within a narrow beam of internal waves at the forcing frequency. They likely result from nonresonant triad interaction associated with strong nonlinearity. Strong vertical shear associated with the subharmonic waves tends to enhance local energy dissipation and turbulent momentum exchange (TME). A simulation with reduced tidal forcing shows an expected diminished level of harmonic energy. A quasi-linear simulation verifies the role of momentum advection in controlling the relative phases of internal tides and the efficiency of barotropic-to-baroclinic energy conversion. The local TME is tightly coupled with the internal-wave dynamics: for the chosen configuration, neglecting TME causes the internal-wave energy to be overestimated by 12%, and increasing it to high levels damps the waves on the continental shelf. This work implies a necessity to carefully consider nonlinearity and turbulent processes in the calculation of internal tidal waves generated at the shelf break.
Consumption and redistributive politics: The effect of credit and China
Authors: Kus Basak
Published: September 2013

This article attempts to bring consumption into the study of redistributive politics. Analyzing data from 20 OECD countries over the period 1995–2007, I investigate whether factors that allowed lower and middle-income households to sustain their consumption had any impact on governments’ redistributive efforts. The article focuses on two factors in particular: access to credit and access to cheap imports (notably, imports from China). I argue that by enhancing consumption these mechanisms moderated the effects of income inequality and suppressed public discontent with increasing income inequality, thereby lessening the political urgency of redistribution.
Public sector leadership: new perspectives for research and practice
Authors: Orazi Davide Christian , Turrini Alex , Valotti Giovanni
Published: September 2013

In this article, we aim to portray the state of the art in public sector leadership in order to recommend directions for research and training practice. To this end, we review the scattered strands of literature on public sector leadership (PSL) and classify them in a single framework. The results of the study suggest that public sector leadership is emerging as a distinctive and autonomous domain in public administration/public management studies, although the debate is still underdeveloped compared to business administration studies. Leadership skills truly do matter in improving the performance of public sector organizations, and it is highly likely that the optimum leadership style is an integrated one: Public sector leaders should behave mainly as transformational leaders, moderately leveraging transactional relationships with their followers and heavily leveraging the importance of preserving integrity and ethics in the fulfillment of tasks.

Points for practitioners

This study on public leadership suggests that administrative leaders in the public sector behave differently from their counterparts in the business world, and as a result there is a great need for leadership development programs which focus on these differences instead of merely mimicking programs designed for leaders in the private sector.
Personal perceptions and organizational factors influencing police discretion: evidence from the Turkish National Police
Authors: Tasdoven Hidayet , Kapucu Naim
Published: September 2013

Unsupervised police decisions taken under stress inherently involve the exercise of discretion and remain questionable when considering the legitimacy of police behavior. Law enforcement agencies seek ways to control discretion to avoid the undesirable consequences of police discretion and maintain organizational legitimacy. Drawing on expectancy and value-based approaches, this study examines the role of extrinsic motivation, intrinsic value orientation and selective enforcement attitudes on the responsiveness of Turkish patrol officers. The findings of the study suggest that reward expectancy which represents the extrinsic motivational perspective, did not have a statistically significant relationship to responsiveness. Public service motivation representing the intrinsic motives of respondents, on the other hand, indicated a strong, positive, and statistically significant relationship with responsiveness. Officer attitudes toward selective enforcement negatively influenced officer responsiveness.

Points for practitioners

Unlike research that emphasizes the role of contingent incentives on controlling discretion, this study empirically reported that intrinsic rewards have an even stronger effect on officer behavior. The leader’s role is essential in making followers work towards the interests of the public and the well-being of society. Ill-designed extrinsic reward systems may crowd out intrinsic motives of employees and cause a decrease in work-related outcomes. This is especially true in hierarchical organizations where reward policies are more likely to be perceived as unfair.
Neptune or Poseidon: implementing EU and global maritime safety law in a national agency
Authors: Gulbrandsen Christer
Published: September 2013

Arguably, the EU represents a qualitatively different international order from traditional intergovernmental international organizations (IOs), as it has accumulated functions and capacities beyond these. This article compares how the EU and the International Maritime Organization impact three aspects of a national agency’s implementation of international rules: application, conflicts over policy agendas and how it deals with non-compliance. Interviews reveal the EU and the IMO as more similar than expected, but still different. Whereas application seems impacted by various supporting functions of both IOs, the EU’s heavy enforcement mechanisms may possibly hamper the detection of non-compliance and its independent agenda-setting powers may create animosity among national officials over the content of EU rules.

Points for practitioners

This article not only outlines similarities and differences between the EU and the IMO within the maritime safety sector, it also helps identify various channels whereby different types of IOs may impact national administrative processes. It should be of interest to those who work with construction and management of international regimes, as it explores practical effects they may have.
Demystifying the Hermit Kingdom: the constitution and public administration in North Korea
Authors: Jordan Sara R , Ip Eric CY
Published: September 2013

Background

Situations of extreme information deficit regarding administrative behavior are rare, but such conditions persist for the most enigmatic and troubling nations, such as North Korea. How might the behavior of public administrators be explained when systematic observation of individual administrators or institutions’ parties is not feasible?

Aim

Finding a way to estimate administrative behavior based upon the information available is an important task in understanding the complexities of closed states’ behavior in the international arena.

Method

We use constitutional analysis to explain public administration in North Korea, arguing that this is the best available method to explain administrative norms and behavior in this and other closed nations.

Results

We find that while administrative theorists predict that administrative norms can be predicted using constitutional analysis, administrative behavior in closed nations cannot be efficiently predicted using only a reconstructed set of norms as we do not have evidence to confirm that the suppositions of normative theorists hold in these conditions.

Conclusions

While we can better understand the values of administrators in North Korea through constitutional analysis, without harder evidence we can only speculate on the true values of administrators in North Korea. Points for practitioners Administrators working on cross-national issues with closed states like North Korea should familiarize themselves with the values of the states’ constitution, as this may be a stable source of preliminary norms for predicting administrators’ behavior.
Towards better results from the World Bank
Authors: Polidano Charles
Published: September 2013

This article briefly reviews the World Bank document The World Bank Approach to Public Sector Management 2011–2020: Better Results from Public Sector Institutions. The document proposes an eclectic, experimental, contingent approach to reform – ‘what works’ – as opposed to doctrinaire, ‘best practice’ orthodoxies. However, the document is frank in discussing the obstacles to realizing this vision, including among other things the incentives to which Bank staff themselves are subject. In overall terms, the document is noteworthy for its frank appraisal of the Bank’s efforts to support public sector reform in developing countries.

Points for practitioners

This article is of interest to practitioners involved in public sector reform in developing countries, particularly those who deal with the World Bank and other aid donors, because it reviews a document which represents an important statement of the World Bank’s thinking on the subject of public sector management and reform.
Public sector reform as problem-solving? Comment on the World Bank’s Public Sector Management Approach for 2011 to 2020
Authors: Grindle Merilee S
Published: September 2013

The World Bank has recently released its Public Sector Management (PSM) Approach for 2011–20. This commentary reviews the core messages of this document and then indicates how it embodies a convergence between academic research and practice in its approach and analytic framework. It then presents a ‘thought experiment’ about how practitioners might bring scholarship and practice together as suggested by the PSM approach. Nevertheless, effective implementation of the approach will depend on the convergence between the path it lays out for practice and the incentives that World Bank officials face in efforts to improve public sector management in real-world situations.
Performance-based public management reforms: experience and emerging lessons from service delivery improvement in Indonesia
Authors: Brinkerhoff Derick W , Wetterberg Anna
Published: September 2013

From both a practical and a theoretical perspective, improved public sector performance has preoccupied policymakers, managers, and analysts around the world. There is broad enthusiasm for performance-based initiatives to remedy service delivery failures, but conceptual boundaries are often vague, and empirical evidence for their effectiveness is mixed. This article reviews current thinking regarding service delivery improvement, and assesses several pathways to improved performance. We examine the pathways pursued in Indonesia’s rich experience with service delivery improvement, which shed particular light on the political economic factors shaping performance-based initiatives, and draw implications for reforms in other settings.

Points for practitioners

Our review of pathways for performance-enhancing reforms in Indonesia suggests that decentralization strongly influences the prospects of other pathways, but service improvements often depend on the center utilizing its leverage to monitor performance and strengthen incentives for implementing reforms. In the long term, unless accountabilities between districts and both providers and communities are strengthened, it is unlikely that existing performance incentives will operate as intended. Indonesia’s experience suggests that addressing political economic factors implies recognizing the multi-actor nature of governance and service delivery systems, and in pursuing both central and local levers for changed incentives.
The World Bank and public sector management: what next?
Authors: Pritchett Lant
Published: September 2013

The new World Bank strategy on Public Sector Management (PSM) has to be judged against the magnitude of the problems it faces. Two of these are what to do about failed and failing states and what to do about the stagnation of progress in ‘flailing’ states. On both of these fronts the gap between what the world of action wants – an implementable action plan to tackle tough problems like Afghanistan – and what the PSM strategy does (and quite probably can) deliver is wide. This article proposes ‘problem-driven iterative analysis’ as one way of bridging the gap.