bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety of treatment with biologics for psoriasis in daily practice: 5‐year data
Authors: van Lümig P.P.M. , Driessen R.J.B. , Berends M.A.M. , Boezeman J.B.M. , van de Kerkhof P.C.M. , de Jong E.M.G.J.
Published: March 2011

Background  The cumulative exposition to biologics is increasing with prolonged treatment with a certain biologic or consecutive biological treatment. However, long‐term safety data are limited available.

Objectives  The aim of this study was to prospectively evaluate the 5‐year safety of biological treatment for psoriasis in daily practice.

Methods  A cohort of 173 psoriasis patients on biologics was prospectively followed for 5 years. All adverse events reported were documented and analysed. Primary endpoint was the percentage of patients reporting at least one serious adverse event. The rate of malignancies, serious infections and serious cardiovascular events was compared with the general population incidence rate. The nature and rate of dermatological adverse events was compared with a group of prospectively followed rheumatoid arthritis patients on TNF‐α blocking therapy.

Results  Between February 2005 and April 2010, 173 patients were enrolled in the registry and went through a total number of 263 treatment episodes. The total number of patient‐years of follow‐up in the registry was 409. The number of patient‐years was the highest for etanercept. Forty‐nine patients (28%) reported 88 serious adverse events. Only one serious adverse event was certainly causally related to the biologic and 21 events (24% of SAEs) were considered possibly related. The incidence of malignancies, serious infections and serious cardiovascular events was comparable with the population incidence rate, except for skin malignancies. The incidence of skin malignancies was significantly higher than the general population incidence rate. The nature and rate of dermatological adverse events differed from the rheumatoid arthritis cohort.

Conclusions  In this cohort, the safety of biological therapies for psoriasis was favourable with a low incidence of therapy‐related serious adverse events.
ASSESSING THE ROBUSTNESS OF COMPOSITE INDICES RANKINGS
Authors: PERMANYER IÑAKI
Published: March 2011

Ranking objects in terms of different attributes is a crucial practice that is typically sensitive to the choice of attributes' weights. In this paper we present rigorous methods to assess the extent to which the weight‐based rankings are robust to the choice of alternative weights. Empirical illustrations are provided, showing the robustness of country rankings arising from the values of the UNDP Human Development Index, the Gender‐related Development Index, or the Human Poverty Index among others. The ideas and techniques presented in this paper can be used to assess the reliability of multiattribute rankings.
MONITORING ABSOLUTE AND RELATIVE POVERTY: “NOT ENOUGH” IS NOT THE SAME AS “MUCH LESS”
Authors: NOTTEN GERANDA , DE NEUBOURG CHRIS
Published: March 2011

Financial poverty indicators assess which people have few financial resources and are thereby at risk of having an unacceptably low living standard. Most countries use one or several “official” poverty indicators, but they typically use either an absolute or a relative benchmark to determine what is unacceptable; absolute benchmarks are based on basic needs or rights while relative benchmarks depend on what is considered to be a “normal” living standard. Applying the absolute U.S. and the relative EU poverty indicators on the U.S. and 15 EU member states, this research shows that it makes sense to use both benchmarks.
Is Langerhan Cell Histiocytosis Complicated with Hydrops Fetalis Exclusively Lethal in Premature Neonates?
Authors: CHENG I , CHEN YI‐LIN , TSAI YU‐LUAN , CHOU YUH‐YU , SUNG TSENG‐CHEN , MU SHU‐CHI
Published: March 2011

Abstract:  Langerhans cell histiocytosis is a rare disease and is lethal in premature neonates. A male premature neonate born at gestational 33 weeks presented with generalized vesicles, hydrops fetalis with pleural effusion, bilateral cataracts, and severe respiratory distress syndrome complicated with persistent pulmonary hypertension. Skin biopsy confirmed the diagnosis of Langerhans cell histiocytosis.
Caregiver and Noncaregiver Attitudes Toward Dementia Screening
Authors: Boustani Malaz A. , Justiss Michael D. , Frame Amie , Austrom Mary G. , Perkins Anthony J. , Cai Xueya , Sachs Greg A. , Torke Alexia M. , Monahan Patrick , Hendrie Hugh C.
Published: March 2011

OBJECTIVES: To compare attitudes toward dementia screening of older adults with and without an experience of dementia caregiving.

DESIGN: A cross‐sectional study.

SETTING: Primary care clinics in Indianapolis, Indiana.

PARTICIPANTS: Eighty‐one participants with dementia caregiving experience (CG) and a random sample of 125 participants without dementia caregiving experience (NCG).

MEASUREMENTS: Attitudes of dementia screening, including acceptance of dementia screening and its perceived harms and benefits, as determined according to the Perceptions Regarding Investigational Screening for Memory in Primary Care questionnaire.

RESULTS: After adjusting for age, race, sex, and education, CGs had a lower dementia screening acceptance mean score (53.9 vs 60.6; P=.03) and a higher perceived suffering score (61.6 vs 55.9, P=.04) than NCGs, but there were no differences in perceived benefits of dementia screening (72.8 vs 69.0; P=.50), perceived stigma (32.9 vs 37.5; P=.12), and perceived negative effect on independence (47.6 vs 54.0; P=.20). The top three barriers to screening identified by both groups were emotional suffering by the family (86% of CGs and 75% of NCGs), loss of driving privileges (75% of CGs and 78% of NCGs), and becoming depressed (64% of CGs and 43% of NCGs).

CONCLUSION: The experience of being a dementia caregiver may influence one's own attitude about accepting dementia screening for oneself.
Prosthodontic Treatment of a Class IV ACP PDI Patient, with Langerhans Cell Histiocytosis (LCH)
Authors: Papavasiliou George , Kamposiora Phophi , Sklavounou Alexandra , Christopoulos Panos
Published: March 2011

Langerhans cell histiocytosis (LCH) is a disease of unknown etiology with a frustrating and unpredictable course. Surviving adult patients suffering from the multisystem type of the disease present with problems in most organs. This article presents the oral rehabilitation of a 28‐year‐old patient, with multisystem sequelae that included the oral cavity, classifying him as a Class IV American College of Prosthodontists Prosthodontic Diagnostic Index patient. A 5‐year course of treatment is analyzed, starting from merely replacing missing teeth with a removable partial denture. The second stage of prosthetic rehabilitation included replacement of the removable prosthesis with fixed partial dentures. The final and most important aspect of treatment was the 2‐year follow‐up, when the patient presented with no problems or adverse effects. The purpose of this presentation is to offer an insight to prosthodontic treatment possibilities for patients suffering from multisystem LCH and to show the value of a “team approach” to achieving a positive outcome.
Multidisciplinary Management of Limited Interocclusal Space: A Clinical Report
Authors: Geckili Onur , Sakar Olcay , Yurdakuloglu Tugce , Firatli Sonmez , Bilhan Hakan , Katiboglu Bulent
Published: March 2011

Prosthetic management of partial edentulism can be challenging with the presence of limited interocclusal space. The extrusion of opposing teeth combined with the alveolar extrusion of the edentulous areas reduces the space needed for fabricating a removable or fixed prosthesis when edentulous areas are present in the maxilla. This clinical report describes the treatment provided to a patient who presented with a limited interocclusal space on the posterior right quadrant. Before prosthetic rehabilitation, mandibular right posterior teeth were intruded, and the maxillary right posterior alveolar crest was reduced by alveoloplasty. After gaining adequate space, prosthetic rehabilitation was completed with a maxillary removable partial denture. During the 2‐year follow‐up period, the patient's chewing functions and physical appearance improved, and no complications occurred.
Pulmonary Cement Embolism after Kyphoplasty
Authors: Chong Timothy , Lieu John , Alamin Todd , Mitra Raj
Published: March 2011

Abstract:  An 80‐year‐old female with a history of osteoporosis was evaluated for sudden onset axial low back pain with bilateral lower extremity weakness, hyperreflexia, pain, urinary retention, and decreased rectal tone. Computed tomography of the lumbar spine revealed L1 compression fracture, retropulsion of bone causing spinal canal compromise with associated severe central canal stenosis. Following cement kyphoplasty of L1 with polymethyl methacrylate, the patient developed tachycardia and dyspnea. Chest radiograph and computed tomographic pulmonary angiogram revealed a large collection of hyperdense material within the right lower lobe pulmonary artery, consistent with pulmonary cement emboli. Management and imaging are discussed.
Recruitment of platelets, white blood cells, and hematopoietic progenitor cells during high‐yield plateletpheresis
Authors: Fontana Stefano , Rados Lenka , Schmid Pirmin , Leibundgut Elisabeth Oppliger , Taleghani Behrouz Mansouri
Published: March 2011

BACKGROUND: Previous observations suggested recruitment of platelets (PLTs) and white blood cells (WBCs) during plateletpheresis and recruitment of hematopoietic progenitor cells (HPCs) by HPC apheresis. Quantification of recruitment helps to optimize yields and safety of these procedures; detection of WBC or HPC recruitment during plateletpheresis may further elucidate the mechanisms.

STUDY DESIGN AND METHODS: This study was a prospective cohort study with 68 single‐needle plateletpheresis donations (23 double, PLT yield ≥4.8 × 1011; 23 triple, ≥7.2 × 1011; 22 quadruple, ≥9.6 × 1011). We measured PLTs, WBCs, WBC subpopulations, and circulating HPCs (CD34 mRNA) before, during, and after apheresis; calculated PLT recruitment and ratio of recruited to yielded PLT; and propose a novel concept to optimize the prediction of the PLT counts after apheresis (PLTpost).

RESULTS: PLT recruitment (mean ± SD, 1.56 ± 0.31) caused a higher PLTpost than predicted by the instrument (164 × 109 ± 23 × 109 vs. 111 × 109 ± 31 × 109/L; p < 0.0001) in all three groups. The ratio of recruited to yielded PLT was 0.36 ± 0.15. The WBC count decreased by 9% to the time before rinse‐back and returned to the baseline thereafter. No changes in circulating HPCs occurred.

CONCLUSIONS: PLT recruitment during high‐yield plateletpheresis facilitates the harvest of multiple PLT units in a single donation. The use of the ratio of recruited to yielded PLT may optimize the algorithm to predict PLTpost. There was no recruitment of WBCs and HPCs during plateletpheresis. Therefore, the previously observed recruitment of HPCs during HPC apheresis seems to be related to other factors than the apheresis procedure itself.
Reduction of Right Ventricular Pacing with Advanced Atrioventricular Search Hysteresis: Results of the PREVENT Study
Authors: KOLB CHRISTOF , SCHMIDT ROLAND , DIETL JOSEF U. , WEYERBROCK SONJA , MORGENSTERN MARTIN , FLECKENSTEIN MARTIN , BEIER THOMAS , VON BARY CHRISTIAN , MACKES KARL G. , WIDMAIER JOCHEN , KREUZER JÖRG , SEMMLER VERENA , ZRENNER BERNHARD ,   on behalf of the PREVENT study group
Published: March 2011

Background: Right ventricular pacing predisposes to the development of heart failure and atrial fibrillation. Automatic atrioventricular search hysteresis (AVSH) is a commonly used strategy to decrease the percentage of right ventricular pacing (%VP) in patients without permanent AV block, but the results have not been optimal.

Methods: The randomized, crossover PREVENT study evaluated whether an enhanced AVSH with two new features can reduce %VP compared with standard AVSH. The new features are the repetitive hysteresis [switch from extended to basic AV delay after a consistent loss of intrinsic AV conduction (IAVC) lasting for six consecutive atrial cycles] and the scan hysteresis (periodic IAVC search extension over six consecutive atrial cycles). Both standard AVSH and enhanced AVSH performed a periodic IAVC search every 180 cardiac cycles and operated with a basic AV‐delay of 225 ms and a rate‐independent maximum AV‐delay of 300 ms for paced and sensed atrial events.

Results: Among 178 patients, 53.4% had no evidence of AV block at enrollment and 46.6% had history of intermittent AV block. The median %VP was decreased by enhanced AVSH compared to standard AVSH (4.0% vs 5.5%, P < 0.001), particularly in patients with a history of AV block (21.4% vs 25.5%, P < 0.001). The primary study hypothesis that 25% of all patients would experience > 20% relative %VP reduction was not met as 46 (25.8%) patients (95% confidence interval, 20.5–31.8%) presented such relative reduction.

Conclusion: The enhanced AVSH algorithm reduces %VP compared with standard AVSH in patients with intermittent AV block. (PACE 2011; 34:975–983)
Effect of Depression on Mortality in Implantable Cardioverter Defibrillator Recipients—Findings from the Prospective LICAD Study
Authors: TZEIS STYLIANOS , KOLB CHRISTOF , BAUMERT JENS , REENTS TILKO , ZRENNER BERNHARD , DEISENHOFER ISABEL , RONEL JORAM , ANDRIKOPOULOS GEORGE , LADWIG KARL‐HEINZ
Published: March 2011

Introduction: Depression predicts mortality in patients with coronary artery disease and heart failure. However, its effect on patient outcome in the presence of an implantable cardioverter defibrillator (ICD) has not been investigated.

Methods: A total of 236 ICD patients (76 females, 58.6 ± 14.0 years) were screened for depressive symptoms using the Hospital Anxiety and Depression Scale (HADS). The outcome measure was all‐cause mortality and the prognostic effect of depression was evaluated with Cox proportional hazards regression analysis.

Results: Fifty (21%) patients reported depressive symptoms (HADS score ≥ 8). Renal failure (odds ratio [OR]= 4.0, 95% confidence intervals [CI]= 1.47–10.87, P = 0.007), prior angina (OR = 2.1, 95% CI = 1.07–4.12, P = 0.03), but not the experience of ICD shocks were associated with baseline depressive symptoms. In a mean follow‐up period of 6.1 ± 2.5 years, 74 patients (31%) died. Mortality significantly increased from 45.1 deaths per 1,000 person‐years among patients without depression to 80.3 deaths per 1,000 person‐years in patients with depressive symptoms (P = 0.039). In the univariate model, depression (HADS score ≥8) was a significant predictor of mortality (OR = 1.81, 95% CI = 1.1–3.0, P = 0.02). However, in the multivariate model, depression lost its prognostic significance.

Conclusions: In our prospective patient cohort, one‐fifth of ICD recipients reported depressive symptoms. Depression increased the absolute mortality risk but was not an independent predictor of mortality. (PACE 2011; 34:991–997)
Safety and Effectiveness of Primary Prevention Cardioverter defibrillators in Octogenarians
Authors: STRIMEL WILLIAM , KOPLIK SHERI , CHEN H. ROBERT , SONG JUHEE , HUANG SHOEI K. STEPHEN
Published: March 2011

Background: Implantable cardioverter‐defibrillators (ICDs) reduce the rate of sudden cardiac death (SCD) in patients with cardiomyopathy and reduced left ventricular systolic function. It is unclear if this benefit extends to the very elderly patient population.

Methods: Patients who underwent initial ICD implantation at age 80 or older between January 1995 and April 2010 for primary SCD prevention were identified. Clinical data were collected from the medical record, including periprocedural complications, device type, and therapies delivered.

Results: Three‐hundred eighty patients were identified; 84 patients met eligibility criteria. The mean age was 82.68 years; mean follow‐up was 34 months. Mean left ventricular ejection fraction was 28.1%. Mortality during follow‐up was 17.9%. One‐ and 5‐year survival estimates were 100% and 60%, respectively. Periprocedural complications occurred in 9.4% of patients; serious complications occurred in 4.8% with no periprocedural deaths. Device therapies occurred in 11.9% (n = 10) of patients (9.5% appropriate, n = 8; 2.4% inappropriate, n = 2). Cardiac resynchronization therapy‐defibrillator (CRT‐D) implantation was associated with prolonged median survival and decreased risk of death (hazard ratio 0.212; 95% confidence interval 0.048−.942, P = 0.042) compared to ICD alone.

Conclusions: Implantation of primary prevention ICDs in patients 80 years of age or older was associated with a low risk of serious complications and a 5‐year survival estimate of 60%. Inappropriate therapies after implantation were uncommon. CRT‐D implantation was associated with a decreased risk of death compared to ICD alone. These data suggest that, in selected patients in this age group, ICD implantation is safe and effective. (PACE 2011; 34:900–906)
Gender Disparities in Psychological Distress and Quality of Life among Patients with an Implantable Cardioverter Defibrillator
Authors: BROUWERS CORLINE , VAN DEN BROEK KRISTA C. , DENOLLET JOHAN , PEDERSEN SUSANNE S.
Published: March 2011

A subset of patients with an implantable cardioverter defibrillator (ICD) reports psychological distress and poor quality of life (QoL). Gender is one of the factors that has been proposed to explain individual differences in these outcomes. In this viewpoint, we (1) review the evidence for gender disparities in psychological distress and QoL in ICD patients by means of a systematic review, and (2) provide recommendations for future research and clinical implications. A systematic search of the literature identified 18 studies with a sample size ≥ 100 that examined gender disparities in anxiety/depression and QoL in ICD patients (mean prevalence of women = 21%; mean age = 62 years). Our review shows that there is insufficient evidence to conclude that gender per se is a major autonomous predictor for disparities in psychological distress and QoL in ICD patients. Women had a higher prevalence of anxiety and poorer QoL in some studies, but there was no statistically significant gender effect in relation to 80% (26/32) of the outcomes reported in the 18 studies. Studies are warranted that are designed a priori and sufficiently powered to examine gender disparities in distress and QoL outcomes in order to establish the exact gender‐specific effect. Due to a need to explore the complexity of this issue further, at this time, caution is warranted with respect to the clinical implications. (PACE 2011; 34:798–803)
Dimensional profile of oral mucosa around combined tooth‐implant‐supported bridgework in macaque mandible
Authors: Siar Chong Huat , Toh Chooi Gait , Ali Tara Bai Taiyeb , Seiz Doris , Ong Siew Tin
Published: March 2011

Purpose: A stable oral mucosa is crucial for long‐term survival and biofunctionality of implants. Most of this evidence is derived from clinical and animal studies based solely on implant‐supported prosthesis. Much less is known about the dimensions and relationships of this soft tissue complex investing tooth‐implant‐supported bridgework (TISB). The aim here was to obtain experimental evidence on the dimensional characteristics of oral mucosa around TISB with two different abutment designs.

Methods: Sixteen 3‐unit TISB were constructed bilaterally in the mandible of eight adult Macaca fascicularis. An implant system with a standard progressive thread design was the bone‐anchoring implant in the second mandibular molar region while the second mandibular premolar served as the natural tooth abutment. Eight implants were connected with the tapered abutment, the remaining with butt‐joint abutment, in a split‐mouth design. These were allowed to functional load for 6 months before sacrification for histomorphometry. Six soft tissue indices were scored: coronal gingival mucosa‐to‐implant top distance (DIM); sulcus depth (SD); junctional epithelium (JE); connective tissue contact (CTC); implant top to first bone‐to‐implant contact distance (DIB); and biologic width (BW=SD+JE+CTC); corresponding parameters in the natural tooth abutment were also measured.

Results: Mucosal dimensions in tapered implants (*BW=3.33±0.43; SD=1.03±0.24; JE=1.08±0.13; CTC=1.22±0.23 mm) were comparable with those of natural tooth abutments (BW=3.04±0.18; SD=0.93±0.1; JE=0.78±0.1; Attachment=1.33±0.09 mm), but differed from butt‐joint implants (*BW=4.88±1.24; SD=1.47±0.38; JE=1.49±0.4; CTC=1.92±0.93 mm) (*P<0.05).

Conclusions: Results suggested that soft tissue dimensions around TISB are influenced by the implant–abutment interface and abutment material used. Mucosa investing tapered abutment tends to recapitulate soft tissue physiologic dimensions of natural tooth.

To cite this article: Siar CH, Toh CG, Ali TBT, Seiz D, Ong ST. Dimensional profile of oral mucosa around combined tooth‐implant‐supported bridgework in macaque mandible. Clin. Oral Impl. Res. 23, 2012 438–446. doi: 10.1111/j.1600‐0501.2010.02145.x
Biomechanical and histologic evaluation of non‐washed resorbable blasting media and alumina‐blasted/acid‐etched surfaces
Authors: Coelho Paulo G. , Marin Charles , Granato Rodrigo , Giro Gabriela , Suzuki Marcelo , Bonfante Estevam A.
Published: March 2011

Objectives: To compare the biomechanical fixation and histomorphometric parameters between two implant surfaces: non‐washed resorbable blasting media (NWRBM) and alumina‐blasted/acid‐etched (AB/AE), in a dog model.

Material and methods: The surface topography was assessed by scanning electron microscopy, optical interferometry and chemistry by X‐ray photoelectron spectroscopy (XPS). Six beagle dogs of ∼1.5 years of age were utilized and each animal received one implant of each surface per limb (distal radii sites). After a healing period of 3 weeks, the animals were euthanized and half of the implants were biomechanically tested (removal torque) and the other half was referred to nondecalcified histology processing. Histomorphometric analysis considered bone‐to‐implant contact (BIC) and bone area fraction occupancy (BAFO). Following data normality check with the Kolmogorov–Smirnov test, statistical analysis was performed by paired t‐tests at 95% level of significance.

Results: Surface roughness parameters Sa (average surface roughness) and Sq (mean root square of the surface) were significantly lower for the NWRBM compared with AB/AE. The XPS spectra revealed the presence of Ca and P in the NWRBM. While no significant differences were observed for both BIC and BAFO parameters (P>0.35 and P>0.11, respectively), a significantly higher level of torque was observed for the NWRBM group (P=0.01). Bone morphology was similar between groups, which presented newly formed woven bone in proximity with the implant surfaces.

Conclusion: A significant increase in early biomechanical fixation was observed for implants presenting the NWRBM surface.

To cite this article: Coelho PG, Marin C, Granato R, Giro G, Suzuki M, Bonfante EA. Biomechanical and histologic evaluation of non‐washed resorbable blasting media and alumina‐blasted/acid‐etched surfaces. Clin. Oral Impl. Res. 23, 2012; 132–135. doi: 10.1111/j.1600‐0501.2010.02147.x
Retracted: Peri‐implant bone reactions to immediate implants placed at different levels in relation to crestal bone. Part I: a pilot study in dogs
Authors: Negri Bruno , Calvo‐Guirado Jose Luis , Pardo‐Zamora Guillermo , Ramírez‐Fernández Ma Piedad , Delgado‐Ruíz Rafael Arcesio , Muñoz‐Guzón Fernando
Published: March 2011

Purpose: The aim of the present study was to evaluate bone remodeling and bone‐to‐implant contact (BIC) after immediate placement at different levels in relation to the crestal bone of Beagle dogs.

Materials and methods: The mandibular bilateral second, third and fourth premolars of six Beagle dogs were extracted and six implants were immediately placed in the hemi‐arches of each dog. Randomly, three cylindrical and three tapered implants were inserted crestally (control group) and 2 mm subcrestally (experimental group). Both groups were treated with a minimal mucoperiosteal flap elevation approach. A gap from the buccal cortical wall to the implant was always left. Three dogs were allowed a 4‐week submerged healing period and the other three an 8‐week submerged healing period. The animals were sacrificed and biopsies were obtained. Biopsies were processed for ground sectioning. Histomorphometric analysis was carried out in order to compare buccal and lingual bone height loss, and BIC between the two groups.

Results: All implants osseointegrated clinically and histologically. Healing patterns examined microscopically at 4 and 8 weeks for both groups (crestal and subcrestal) yielded similar qualitative bone findings. The distance from the top of the implant collar to the first BIC in the lingual crest (A–Lc) showed a significant difference (P=0.0313): 1.91 ± 0.2 mm in the control group and 1.08 ± 0.2 mm in the experimental group. There was less bone resorption in subcrestal implants than crestal implants. The mean percentage of newly formed BIC was greater with the cylindrical implant design (46.06 ± 4.09%) than with the tapered design (32.64 ± 3.72%).

Conclusion: These findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri‐implant tissue remodeling. However, less resorption of the Lc may be expected when implants are placed 2 mm subcrestally.

To cite this article: Negri B, Calvo‐Guirado JL, Pardo‐Zamora G, Ramírez‐Fernández MP, Delgado‐Ruíz RA, Muñoz‐Guzón F. Peri‐implant bone reactions to immediate implants placed at different levels in relation to crestal bone. Part I: a pilot study in dogs. Clin. Oral Impl. Res. 23, 2012; 228–235.  doi: 10.1111/j.1600‐0501.2011.02158.x
Neuroimaging study in subjects at high risk of psychosis revealed by the Rorschach test and first-episode schizophrenia
Authors: Ota Miho , Obu Satoko , Sato Noriko , Asada Takashi
Published: March 2011

Objective: There is increasing evidence of neuroanatomical pathology in schizophrenia, but it is unclear whether changes exist prior to disease onset. This study aimed to examine whether changes exist prior to disease onset, especially in the temporal lobes.

Methods: T1-weighted and diffusion tensor magnetic resonance imaging were performed on 9 first-episode schizophrenia patients, 10 patients who were at high risk of schizophrenia and 10 healthy controls. Voxel-based analysis using the normalised images of cortical volume data was examined, and the fractional anisotropy value at three component fibres of the temporal lobes, inferior longitudinal fasciculus, superior longitudinal fasciculus (SLF) and cingulum hippocampal part was compared among the three groups.

Results: There were statistically significant volume differences at the bilateral temporal lobe between the healthy subjects and high-risk group. Between the schizophrenic group and healthy subjects, statistically significant volume differences were detected at the bilateral temporal lobes and anterior cingulate cortex. The fractional anisotropy values of the SLF in the schizophrenic and high-risk groups were significantly lower than in the healthy subjects.

Conclusion: Our findings indicate that some brain alterations may progress in patients at psychosis pre-onset, possibly because of disrupted developmental mechanisms, and these pathological changes may be predictive of functional outcome.
Disclosure of potential conflicts of interest in dermatological guidelines in Germany – an analysis – status quo and quo vadis
Authors: Rosumeck Stefanie , Sporbeck Birte , Rzany Berthold , Nast Alexander
Published: March 2011

Background: In order to ensure the reliability of clinical practice guidelines it is essential to consider potential conflicts of interest with regard to its development.

Methods: All valid dermatological practice guidelines, which were developed by the German Dermatologic Society (DDG) or the Professional Association of German Dermatologists (BVDD), were recorded. Details about financing and conflicts of interest were systematically evaluated by two independent appraisers according to Domain 6 of the guidelines evaluation instruments AGREE and AGREE II.

Results: 38 practice guidelines of the DDG/BVDD were identified. Data about financing of the guidelines are included in 12 of 38 guidelines (32 %) only. Conflicts of interest are stated in no more than 7 of the 38 guidelines (18 %). Wherever a connection with the pharmaceutical industry was stated, no further information on how possible conflicts of interests were dealt with was found.

Conclusions: In current guidelines details on the financing as well as the disclosures of potential conflicts of interest are stated insufficiently. Here an optimization is necessary. Furthermore strategies for handling conflicts of interest need to be developed. One possibility is a specific discussion on this issue at the beginning and during the process of the guidelines work. Furthermore in case of potential conflicts of interest a solution as e. g. abstention from voting on specific questions needs to be developed.
Inflammatory cytokines in gastric fluid at birth and the development of bronchopulmonary dysplasia
Authors: Stichel H , Bäckström E , Hafström O , Nilsson S , Lappalainen U , Bry K
Published: March 2011

Aim:  To assess whether the levels of inflammatory and anti‐inflammatory proteins in gastric fluid of premature infants shortly after birth are associated with the development of bronchopulmonary dysplasia (BPD).

Methods:  Gastric fluid retrieved within 1 h of birth of premature infants (gestational age <29 weeks) was analysed for interleukin (IL)‐8, growth‐related oncogene (Gro)‐α, epithelial cell–derived neutrophil‐activating peptide (ENA)‐78, IL‐1β and Clara cell secretory protein with ELISA.

Results:  Of 51 enrolled infants, 86% had BPD. Of these, 54% had mild BPD, 30% had moderate BPD and 16% had severe BPD. Clinical chorioamnionitis was associated with high levels of IL‐8, Gro‐α, Epithelial cell–derived neutrophil‐activating peptide‐78 (ENA‐78) and IL‐1β in gastric fluid. Gastric fluid levels of IL‐8, Gro‐α, ENA‐78 and IL‐1β were higher in infants with moderate or severe BPD than in those with no or mild BPD. Ligation of the patent ductus arteriosus was associated with the development of moderate or severe BPD. These associations were no longer significant after adjustment for gestational age.

Conclusion:  The levels of inflammatory mediators in gastric fluid samples retrieved soon after birth from intubated or nonintubated infants can be used to assess the infants’ perinatal exposure to inflammatory mediators and its association with neonatal outcome.
Binding of cGMP to the transducin‐activated cGMP phosphodiesterase, PDE6, initiates a large conformational change involved in its deactivation
Authors: Yamazaki Akio , Hayashi Fumio , Matsuura Isao , Bondarenko Vladimir A.
Published: March 2011

Retinal photoreceptor phosphodiesterase (PDE6), a key enzyme for phototransduction, consists of a catalytic subunit complex (Pαβ) and two inhibitory subunits (Pγs). Pαβ has two noncatalytic cGMP‐binding sites. Here, using bovine PDE preparations, we show the role of these cGMP‐binding sites in PDE regulation. Pαβγγ and its transducin‐activated form, Pαβγ, contain two and one cGMP, respectively. Only Pαβγ shows [3H]cGMP binding with a Kd∼ 50 nm and Pγ inhibits the [3H]cGMP binding. Binding of cGMP to Pαβγ is suppressed during its formation, implying that cGMP binding is not involved in Pαβγγ activation. Once bound to Pαβγ, [3H]cGMP is not dissociated even in the presence of a 1000‐fold excess of unlabeled cGMP, binding of cGMP changes the apparent Stokes’ radius of Pαβγ, and the amount of [3H]cGMP‐bound Pαβγ trapped by a filter is spontaneously increased during its incubation. These results suggest that Pαβγ slowly changes its conformation after cGMP binding, i.e. after formation of Pαβγ containing two cGMPs. Binding of Pγ greatly shortens the time to detect the increase in the filter‐trapped level of [3H]cGMP‐bound Pαβγ, but alters neither the level nor its Stokes’ radius. These results suggest that Pγ accelerates the conformational change, but does not add another change. These observations are consistent with the view that Pαβγ changes its conformation during its deactivation and that the binding of cGMP and Pγ is crucial for this change. These observations also imply that Pαβγγ changes its conformation during its activation and that release of Pγ and cGMP is essential for this change.

Structured digital abstract

PDE6 alpha
, PDE6 beta and PDE6 gamma physically interact by molecular sieving (View interaction)
Human kynurenine aminotransferase II – reactivity with substrates and inhibitors
Authors: Passera Elisabetta , Campanini Barbara , Rossi Franca , Casazza Valentina , Rizzi Menico , Pellicciari Roberto , Mozzarelli Andrea
Published: March 2011

Kynurenine aminotransferase (KAT) is a pyridoxal 5′‐phosphate‐dependent enzyme that catalyzes the conversion of kynurenine, an intermediate of the tryptophan degradation pathway, into kynurenic acid, an endogenous antagonist of ionotropic excitatory amino acid receptors in the central nervous system. KATII is the prevalent isoform in mammalian brain and a drug target for the treatment of schizophrenia. We have carried out a spectroscopic and functional characterization of both the human wild‐type KATII and a variant carrying the active site mutation Tyr142→Phe. The transamination and the β‐lytic activity of KATII towards the substrates kynurenine and α‐aminoadipate, the substrate analog β‐chloroalanine and the inhibitors (R)‐2‐amino‐4‐(4‐(ethylsulfonyl))‐4‐oxobutanoic acid and cysteine sulfinate were investigated with both conventional assays and a novel continuous spectrophotometric assay. Furthermore, for high‐throughput KATII inhibitor screenings, an endpoint assay suitable for 96‐well plates was also developed and tested. The availability of these assays and spectroscopic analyses demonstrated that (R)‐2‐amino‐4‐(4‐(ethylsulfonyl))‐4‐oxobutanoic acid and cysteine sulfinate, reported to be KATII inhibitors, are poor substrates that undergo slow transamination.
Fire and Host Abundance as Determinants of the Distribution of Three Congener and Sympatric Mistletoes in an Amazonian Savanna
Authors: Fadini Rodrigo F. , Lima Albertina P.
Published: March 2011

Most mistletoe species that live in savanna patches are subjected to frequent fires. Although having similar habits, even congener species may parasitize very different host species and show different degrees of specialization that may differentially affect their resistance to fire. We studied three congener mistletoe species with a diverse degree of specificity to their hosts: Psittacanthus biternatus, Psittacanthus eucalyptifolius and Psittacanthus plagiophyllus, the first being the most generalist species, and the last the most specialist. We investigated their prevalence (proportion of hosts infected) in 35 plots of an Amazonian savanna, with different fire histories. Our aim was to understand if they respond similarly to fire frequency and the abundance of their hosts. Additionally, we experimentally applied fire to individuals of the three species using a portable propane flamethrower to test for the influence of mistletoe species, plant size and quantity of heat pulses (single or double burn) on mistletoe survivorship. Prevalence varied greatly among species: 1.5 percent for P. biternatus, 4.8 percent for P. eucalyptifolius and 20 percent for P. plagiophyllus. Prevalence of P. plagiophyllus was negatively related to fire frequency, while for the other two species it was not. Psittacanthus biternatus had a higher probability of survival compared with the other two species, and larger plants were more likely to survive under single burn treatment and to regenerate through sprouting. Our results suggest that, due to complex interactions between fire, hosts and mistletoes, even sympatric species may respond differently to fire frequency and host abundance.

Abstract in Portuguese is available in the online version of this article.
The Evolution of Group Stability and Roost Lifespan: Perspectives from Tent‐Roosting Bats
Authors: Sagot Maria , Stevens Richard D.
Published: March 2011

Although multiple hypotheses have been proposed to explain group formation, few fully explain the diversity of social interactions found in foliage‐roosting bats. Among these bats, tent‐roosting species are capable of constructing their own shelters. Although many bats utilize tents previously constructed by other species, it has been suggested that a particular subset of tent‐roosting bats specialize on making tents from particular plant species. Tents provide protection from weather and often a place to roost close to foraging sites. Moreover, tent lifespan is plant species specific and may last from a few weeks to more than a year. To better understand effects that roosts have on social bonds of tent‐roosting bats, we conducted a literature review to collect information on social systems and tent lifespan. We tested correlated evolution of group stability and group longevity with tent lifespan using Pagel's method for discrete characters. We found that group stability and group longevity are correlated with tent lifespan. That there is correlated evolution between these characters contributes to our understanding of how different mechanisms interact to produce a variety of social systems in mammals.
Optimizing Diversity Assessment Protocols for High Canopy Ants in Tropical Rain Forest
Authors: Yusah Kalsum M. , Fayle Tom M. , Harris Grant , Foster William A.
Published: March 2011

The canopies of tropical rain forests support highly diverse, yet poorly known, animal and plant communities. It is vital that researchers who invest the time needed to gain access to the high canopy are able efficiently to survey the animals and plants that they find there. Here, we develop diversity assessment protocols for one of the most ecologically important canopy animal groups, the ants, in lowland dipterocarp rain forest in Sabah, Malaysia. We design and test a novel trap (the purse‐string trap) that can be remotely collected, thus avoiding disturbance to ants. We compare this modified trap with two other methods for surveying canopy ants: precision insecticide fogging and baited pitfall trapping. In total, we collected 39,351 ants belonging to 173 species in 38 genera. Fogging collected the most individuals and species, followed by purse‐string trapping with baited pitfall trapping catching the fewest. Fogging also resulted in samples with a different species composition to purse‐string trapping and baited pitfall trapping, which were not different from one another. Using a ‘greedy algorithm’, which guides the selection of inventory methods in order to maximize new species discovered per researcher‐hour, we show that projects allocating fewer than 132 researcher‐hours to canopy ant collection and identification should sample exclusively using fogging. Those with more time should use a combination of methods. This prioritization technique could be used to accelerate species discovery in future rapid biodiversity assessments.

Abstract in Malay is available in the online version of this article.
Divergence-free interpolation of vector fields from point values — exact ∇ ⋅B = 0 in numerical simulations
Authors: McNally Colin P.
Published: March 2011

In astrophysical magnetohydrodynamics (MHD) and electrodynamics simulations, numerically enforcing the ∇·B= 0 constraint on the magnetic field has been difficult. We observe that for point-based discretization, as used in finite-difference type and pseudo-spectral methods, the ∇·B= 0 constraint can be satisfied entirely by a choice of interpolation used to define the derivatives of B. As an example we demonstrate a new class of finite-difference-type derivative operators on a regular grid which has the ∇·B= 0 property. This principle clarifies the nature of ∇·B≠ 0 errors. The principles and techniques demonstrated in this Letter are particularly useful for the magnetic field, but can be applied to any vector field. This Letter serves as a brief introduction to the method and demonstrates an implementation showing convergence.
Antiandrogenic activity of anthranilic acid ester derivatives as novel lead structures to inhibit prostate cancer cell proliferation
Authors: Roell Daniela , Rösler Thomas W. , Degen Stephanie , Matusch Rudolf , Baniahmad Aria
Published: March 2011

A plant extract from the fruits of saw palmetto, which is currently used to treat the androgen‐dependent benign prostatic hyperplasia and PCa, served as source for new structure variants. We investigated the antiandrogenic potential of an ethanolic total extract and one of its main aromatic components anthranilic acid. An androgen receptor‐antagonistic (antiandrogenic) effect of the extract was evident, and although anthranilic acid itself revealed no remarkable effect, its methyl ester, methyl anthranilate, exhibited antiandrogenic potential. Based on this chemical structure, we synthesized and investigated the antiandrogenic activity of four AnA ester derivatives, which were either novel or only little described in literature. These AnA esters inhibit the androgen‐dependent transactivation of both the wild‐type (wt) androgen receptor and the androgen receptor point mutant T877A, which often occurs in refractory PCa. Moreover, they inhibit the androgen receptor‐induced expression of the endogenous prostate‐specific antigen. Importantly, AnA esters repress the growth of human PCa cells. Deletion analyses of androgen receptor propose that the antiandrogenic effect of anthranilic acid esters is mediated by the ligand‐binding domain, most likely through direct binding, without affecting androgen receptor protein levels. Taken together, the data suggest antiandrogenic potential of anthranilic acid ester derivatives, which can serve as lead structures for novel antiandrogens.
Dissecting the Wnt secretion pathway: key questions on the modification and intracellular trafficking of Wnt proteins
Authors: Harterink M. , Korswagen H. C.
Published: March 2011

The Wnt family of signalling proteins has essential functions in development and adult tissue homoeostasis throughout the animal kingdom. Although signalling cascades triggered by Wnt proteins have been extensively studied, much remains to be learned about how Wnts are produced and secreted. Over the past few years, it has become clear that the secretion of Wnt proteins requires a specialized trafficking pathway. As this pathway has been discussed in two recent reviews (Lorenowicz & Korswagen 2009, Port & Basler 2010), we will focus our discussion on the key questions that need to be addressed to gain a more complete understanding of the mechanism and regulation of this essential secretion pathway.
Lipogenic regulators are elevated with age and chronic overload in rat skeletal muscle
Authors: Rivas D. A. , Morris E. P. , Fielding R. A.
Published: March 2011

Aim:  Both muscle mass and strength decline with ageing, but the loss of strength far surpasses what is projected based on the decline in mass. Interestingly, the accumulation of fat mass has been shown to be a strong predictor of functional loss and disability. Furthermore, there is a known attenuated hypertrophic response to skeletal muscle overload with ageing. The purpose of this study was to determine the effect of 28 days of overload on the storage of intramuscular triglycerides (IMTG) and metabolic regulators of lipid synthesis in young and old skeletal muscle.

Methods:  The phosphorylation and expression of essential lipogenic regulators were determined in the plantaris of young (YNG; 6‐month‐old) and aged (OLD; 30‐month‐old) rats subjected to bilateral synergist ablation (SA) of two‐thirds of the gastrocnemius muscle or sham surgery.

Results:  We demonstrate that age‐induced increases in IMTG are associated with enhancements in the expression of lipogenic regulators in muscle. We also show that the phosphorylation and concentration of the 5′AMP‐activated protein kinase (AMPK) isoforms are altered in OLD. We observed increases in the expression of lipogenic regulators and AMPK signalling after SA in YNG, despite no increase in IMTG. Markers of oxidative capacity were increased in YNG after SA. These overload‐induced effects were blunted in OLD.

Conclusion:  These data suggest that lipid metabolism may be altered in ageing skeletal muscle and is unaffected by mechanical overload via SA. By determining the role of increased lipid storage on skeletal muscle mass during ageing, possible gene targets for the treatment of sarcopenia may be identified.
Taking enforcement on its own terms: EPA's heavy‐duty diesel engine litigation
Authors: Cannon Jonathan
Published: March 2011

The authors of Regulation by Litigation characterize the US Environmental Protection Agency (EPA)'s enforcement action against diesel engine manufacturers as an effort to achieve by litigation what the Agency was unable to achieve by regulation: immediate reductions in emissions of nitrogen oxides. By substituting litigation for rulemaking, the authors of the book argue, the Agency avoided political and judicial accountability and put itself on a suboptimal policy track. This comment argues that the diesel engine litigation may be better understood as what it purported to be, an enforcement action, not rulemaking in disguise. The authors' characterization of the litigation is questionable on at least two grounds. First, it fails to fully appreciate the distinct functions of enforcement and policymaking in a regulatory setting. The goal of enforcement is not primarily to make policy, but to enforce it – to punish violators, deter future violations, and mitigate harms caused by violations. That goal supplies the proper measure of the litigation's success. Second, in applying public choice analysis to create a story of agency circumvention of appropriate rulemaking procedures, the authors' account misses key features of how agency enforcement decisions are made – and were made in this litigation. This latter shortcoming raises broader questions about the difficulties of applying public choice analysis in complex institutional settings.
Regulation by litigation: Not so bad?
Authors: Funk William
Published: March 2011

This is a review essay concerning the book Regulation by Litigation. Utilizing public choice theory as the basis of its analysis, the book presents three case studies designed to demonstrate that regulation by litigation does not serve the public interest. This review essay attempts to show that public choice theory does not explain the decision to use litigation in these cases, that the alleged failure of litigation in these cases might not be failures at all, and that regulation by litigation is not the unmitigated evil the authors of the book suggest.