bluuebunny/crossref_metadata_2025 huggingface dataset:
Using tumor phenotype, histological tumor distribution, and mammographic appearance to explain the survival differences between screen‐detected and clinically detected breast cancers
Authors: Chuang Shu‐Lin , Chen Sam Li‐Sheng , Yu Cheng‐Ping , Chang King‐Jen , Yen Amy Ming‐Fang , Chiu Sherry Yueh‐Hsia , Fann Jean Ching‐Yuan , Tabár László , Stephen Duffy W. , Smith Robert A. , Chen Hsiu‐Hsi
Published: July 2014

In the era of mass screening for breast cancer with mammography, it has been noted that conventional tumor attributes and mammographic appearance are insufficient to account for the better prognosis of screen‐detected tumors. Such prognostication may require additional updated pathological information regarding tumor phenotype (e.g., basal status) and histological tumor distribution (focality). We investigated this hypothesis using a Bayesian approach to analyze breast cancer data from Dalarna County, Sweden. We used data for tumors diagnosed in the Swedish Two‐County Trial and early service screening period, 1977–1995, and from the mature service screening period, 1996–1998. In the early period of mammographic screening (1977–1995), the crude hazard ratio (HR) of breast cancer death for screen‐detected cases compared with symptomatic ones was 0.22 (95% CI: 0.17–0.29) compared with 0.53 (95% CI: 0.34–0.76) when adjusted for conventional tumor attributes only. Using the data from the mature service screening period, 1996–1998, the HR was 0.23 (95% CI: 0.08–0.44) unadjusted and 0.71 (95% CI: 0.26–1.47) after adjustment for tumor phenotype, mammographic appearance, histological tumor distribution, and conventional tumor attributes. The area under the ROC curve (AUC) for the prediction of breast cancer deaths using these variables without the detection mode was 0.82, only slightly less than that observed when additionally including the detection mode (AUC = 0.83). Using Freedman statistics, conventional tumor attributes and mammographic appearances explained 58% (95% CI: 57.5–58.6%) of the difference of breast cancer survival between the screen‐detected and the clinically detected breast cancers, whereas the corresponding figure was increased to 77% (95% CI: 75.6–77.6%) when adding the two information on tumor phenotype and histological tumor distribution. The results indicated that conventional tumor attributes and mammographic appearance are not sufficient to be interim markers for explaining the survival difference between screen‐detected and clinically detected cancers in the era marked by the widespread use of mammography. Additional information on tumor phenotype and histological distribution may be added as effective interim markers for explaining the benefit of the early detection of breast cancer with mammography.
A common hypofunctional genetic variant of GPER is associated with increased blood pressure in women
Authors: Feldman Ross D. , Gros Robert , Ding Qingming , Hussain Yasin , Ban Matthew R. , McIntyre Adam D. , Hegele Robert A.
Published: July 2014

Aims

Activation of vascular GPER has been linked to vasodepressor effects in animals. However, the significance of GPER regulation on chronic blood pressure control in humans is unknown.

Methods

To examine this question we determined the functional significance of expression of a common missense single nucleotide variant of GPER, P16L in vascular smooth muscle cells, and its association with blood pressure in humans. Further, to validate the importance of carrying GPER P16L in the development of hypertension we assessed allele frequency in a cohort of hard‐to‐treat hypertensive patients referred to a tertiary care clinic.

Results

Expression of the GPER P16L variant (V) vs. wild type (WT) in rat aortic vascular smooth muscle cells, was associated with a significant decrease in G1 (1 μm, a GPER agonist)‐mediated ERK phosphorylation (slope of the function of G1‐stimulated ERK phosphorylation: GPER content WT: 16.2, 95% CI 9.9, 22.6; V: 5.0, 95% CI 1.0, 9.0; P < 0.005) and apoptosis (slope of the function of G1‐stimulated apoptosis: GPER content: WT: 4.4, 95% CI: 3.4, 5.4; V: 2.5, 95% CI 1.6, 2.3 P < 0.005). Normotensive female subjects, but not male subjects, carrying this hypofunctional variant (allele frequency 22%) have increased blood pressure [mean arterial pressure: P16/P16: 80 ± 1 mmHg (n = 204) vs. P16L carriers: 82 ± 1 mmHg (n = 127), 95% CI for difference: 0.6, 4.0 mmHg, P < 0.05], [systolic blood pressure: P16/P16: 105 ± 1 mmHg vs. P16L carriers: 108 ± 1 mmHg, 95% CI for difference:1.0, 5.1 mmHg, P < 0.05], [diastolic blood pressure: P16/P16: 66 ± 0.5 mmHg vs. P16L carriers 68 ± 0.7, 95% CI for difference: 0.2, 3.6 mmHg, P < 0.05]. Further, the P16L allele frequency was almost two‐fold higher in female vs. male hypertensive patients (31% vs. 16%, allele ratio 0.5, 95% CI 0.32, 0.76, P < 0.05).

Conclusions

The common genetic variant, GPER P16L, is hypofunctional and female carriers of this allele have increased blood pressure. There was an increased prevalence in a population of hard‐to‐treat hypertensive female patients. Cumulatively, these data suggest that in females, impaired GPER function might be associated with increased blood pressure and risk of hypertension.
Combined treatment: impact of optimal psychotherapy and medication in bipolar disorder
Authors: Parikh Sagar V , Hawke Lisa D , Velyvis Vytas , Zaretsky Ari , Beaulieu Serge , Patelis‐Siotis Irene , MacQueen Glenda , Young L Trevor , Yatham Lakshmi N , Cervantes Pablo
Published: July 2014

Objectives

The current study investigated the longitudinal course of symptoms in bipolar disorder among individuals receiving optimal treatment combining pharmacotherapy and psychotherapy, as well as predictors of the course of illness.

Methods

A total of 160 participants with bipolar disorder (bipolar I disorder: n = 115; bipolar II disorder: n = 45) received regular pharmacological treatment, complemented by a manualized, evidence‐based psychosocial treatment – that is, cognitive behavioral therapy or psychoeducation. Participants were assessed at baseline and prospectively for 72 weeks using the Longitudinal Interval Follow‐up Evaluation (LIFE) scale scores for mania/hypomania and depression, as well as comparison measures (clinicaltrials.gov identifier: NCT00188838).

Results

Over a 72‐week period, patients spent a clear majority (about 65%) of time euthymic. Symptoms were experienced more than 50% of the time by only a quarter of the sample. Depressive symptoms strongly dominated over (hypo)manic symptoms, while subsyndromal symptoms were more common than full diagnosable episodes for both polarities. Mixed symptoms were rare, but present for a minority of participants. Individuals experienced approximately six significant mood changes per year, with a full relapse on average every 7.5 months. Participants who had fewer depressive symptoms at intake, a later age at onset, and no history of psychotic symptoms spent more weeks well over the course of the study.

Conclusions

Combined pharmacological and adjunctive psychosocial treatments appeared to provide an improved course of illness compared to the results of previous studies. Efforts to further improve the course of illness beyond that provided by current optimal treatment regimens will require a substantial focus on both subsyndromal and syndromal depressive symptoms.
A new hope: novel therapeutic approaches to treatment of chronic lymphocytic leukaemia with defects inTP53
Authors: Shindiapina Polina , Brown Jennifer R. , Danilov Alexey V.
Published: July 2014

Chronic lymphocytic leukaemia (CLL) is an indolent B‐cell malignancy with heterogeneous outcomes. Chromosomal abnormalities inCLLare predictive of the natural disease course; del(11q) and del(17p) are recognized as high risk genetic lesions. Del(17p) is associated with an impaired function ofTP53, a key tumour suppressor, and is particularly problematic. Such patients respond poorly to chemo‐immunotherapy and have significantly shorter survival compared to patients with standard and low‐risk cytogenetics. WhileTP53 pathway defects are rare at initial diagnosis, their frequency increases in relapsedCLL. Until very recently, this group of patients represented an unmet clinical need with few therapeutic options. However, the advent of targeted therapies has expanded the drug armamentarium and introduced new hope for these highly refractory patients. Agents that target B‐cell receptor signalling,BH3‐mimetics and others induce apoptosis of the neoplastic B‐cells in aTP53‐independent manner. Their use in the clinic is associated with remarkable activity in patients with del(17p). In this review we discuss the frequency and clinical significance of del(17p) and genetic mutations leading to disruptedTP53, the putative role of otherTP53 homologues, and the results of key clinical trials involving both conventional chemotherapy and novel agents.
Cytotoxic chemotherapy in the contemporary management of metastatic castration‐resistant prostate cancer (mCRPC)
Authors: Sonpavde Guru , Wang Christopher G. , Galsky Matthew D. , Oh William K. , Armstrong Andrew J.
Published: July 2014

For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration‐resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long‐term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration‐sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies.
Comparison of magnetic resonance imaging and ultrasound (MRI‐US) fusion‐guided prostate biopsies obtained from axial and sagittal approaches
Authors: Hong Cheng W. , Rais‐Bahrami Soroush , Walton‐Diaz Annerleim , Shakir Nabeel , Su Daniel , George Arvin K. , Merino Maria J. , Turkbey Baris , Choyke Peter L. , Wood Bradford J. , Pinto Peter A.
Published: July 2014

Objective

To compare cancer detection rates and concordance between magnetic resonance imaging and ultrasound (MRI‐US) fusion‐guided prostate biopsy cores obtained from axial and sagittal approaches.

Patients and Methods

Institutional records of MRI‐US fusion‐guided biopsy were reviewed. Detection rates for all cancers, Gleason ≥3 + 4 cancers, and Gleason ≥4 + 3 cancers were computed. Agreement between axial and sagittal cores for cancer detection, and frequency where one was upgraded the other was computed on a per‐target and per‐patient basis.

Results

In all, 893 encounters from 791 patients that underwent MRI‐US fusion‐guided biopsy in 2007–2013 were reviewed, yielding 4688 biopsy cores from 2344 targets for analysis. The mean age and PSA level at each encounter was 61.8 years and 9.7 ng/mL (median 6.45 ng/mL). Detection rates for all cancers, ≥3 + 4 cancers, and ≥4 + 3 cancers were 25.9%, 17.2%, and 8.1% for axial cores, and 26.1%, 17.6%, and 8.6% for sagittal cores. Per‐target agreement was 88.6%, 93.0%, and 96.5%, respectively. On a per‐target basis, the rates at which one core upgraded or detected a cancer missed on the other were 8.3% and 8.6% for axial and sagittal cores, respectively. Even with the inclusion of systematic biopsies, omission of axial or sagittal cores would have resulted in missed detection or under‐characterisation of cancer in 4.7% or 5.2% of patients, respectively.

Conclusion

Cancer detection rates, Gleason scores, and core involvement from axial and sagittal cores are similar, but significant cancer may be missed if only one core is obtained for each target. Discordance between axial and sagittal cores is greatest in intermediate‐risk scenarios, where obtaining multiple cores may improve tissue characterisation.
Transrectal ultrasonography (TRUS)‐guided pelvic plexus block to reduce pain during prostate biopsy: a randomised controlled trial
Authors: Jindal Tarun , Mukherjee Subhabrata , Sinha Rajan K. , Kamal Mir R. , Ghosh Nabankur , Saha Barun , Mitra Nilanjan , Sharma Pramod K. , Mandal Soumendra N. , Karmakar Dilip
Published: July 2014

Objective

To assess the role of pelvic plexus block (PPB) in reducing pain during transrectal ultrasonography(TRUS)‐guided prostate biopsy, compared with the conventional periprostatic nerve block (PNB).

Patients and Methods

A prospective, double‐blind observational study was conducted with patients being randomised into three groups. Group‐1 (47 patients) received intrarectal local anaesthesia (IRLA) with 10 mL 2% lignocaine jelly along with pelvic plexus block (PPB) with 2.5 mL 2% lignocaine injection bilaterally. Group‐2 (46 patients) received IRLA with periprostatic nerve block (PNB). Group‐3 (46 patients) received only IRLA without any type of nerve block. The patients were requested to rate the level of pain from 0 to 10 on a visual analogue scale (VAS) at two time points: VAS‐1: during biopsy procedure and VAS‐2: 30 min after the procedure.

Results

The mean age of the patients, mean volume of the prostates and mean serum PSA values were comparable among the three groups. The mean pain score during biopsy was significantly less in the PPB group [mean (range) sore of 2.91 (2–4)] compared with the PNB group [mean (range) score of 4 (3–5)], and both these groups were superior to the no nerve block group [mean score of 5.4 (3–7)]. There was no significant difference between the mean pain scores, 30 min after the procedure among the three groups with the mean (range) scores being 2.75 (2–4), 2.83 (2–4) and 2.85 (2–4), respectively.

Conclusion

PPB is superior to conventional periprostatic nerve block (PNB) for pain control during TRUS‐guided biopsy and both are in turn superior to no nerve block.
Design, Synthesis, Antibacterial Evaluation and Docking Study of Novel 2‐Hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived Quinolone
Authors: Li Qing , Xing Junhao , Cheng Haibo , Wang Hui , Wang Jing , Wang Shuai , Zhou Jinpei , Zhang Huibin
Published: July 2014

A novel series of 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl‐derived quinolones 6a–o were synthesized and evaluated for their in vitro antibacterial activity. Most of the target compounds exhibited potent activity against Gram‐positive strains. Among them, moxifloxacin analog 6n displayed the most potent activity against Gram‐positive strains including S. epidermidis (MIC = 0.06 μg/mL), MSSE (MIC = 0.125 μg/mL), MRSE (MIC = 0.03 μg/mL), S. aureus (MIC = 0.125 μg/mL), MSSA (MIC = 0.125 μg/mL), (MIC = 2 μg/mL). Its activity against MRSA was eightfold more potent than reference drug gatifloxacin. Finally, docking study of the target compound 6n revealed that the binding model of quinolone nucleus was similar to that of gatifloxacin and the 2‐hydroxy‐3‐(nitroimidazolyl)‐propyl group formed two additional hydrogen bonds.
The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases
Authors: Inoue N , Watanabe M , Ishido N , Katsumata Y , Kagawa T , Hidaka Y , Iwatani Y
Published: July 2014

Vitamin D is a multi-functional immune regulator, and a low serum concentration of vitamin D promotes autoimmune inflammation. In this study, we evaluate the association between the prognosis of autoimmune thyroid disease (AITD) and the functional polymorphisms of genes that regulate vitamin D metabolism. For 139 Graves’ disease (GD) patients, 116 Hashimoto's disease (HD) patients and 76 control subjects, we genotyped the following polymorphisms using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP): vitamin D receptor (VDR): rs731236, rs7975232, rs2228570 and rs1544410; group-specific component (GC): rs7041 and rs4588; and CYP2R1: rs10741657. The frequency of the TT genotype for the rs731236 polymorphism was higher in GD patients than in HD patients (P = 0·0147). The frequency of the C allele for the rs7975232 polymorphism was higher in GD patients than in control subjects (P = 0·0349). The proportion of GD patients whose anti-thyrotrophin receptor antibody (TRAb) level was >51% was higher in those with the CC genotype than in those with the CA+AA genotypes (P = 0·0065). The frequency of the CC genotype for the rs2228570 polymorphism was higher in HD patients than in control subjects (P = 0·0174) and GD patients (P = 0·0149). The frequency of the Gc1Gc1 genotype for the GC polymorphism and the AG genotype for the CYP2R1 polymorphism were lower in intractable GD than in GD in remission (P = 0·0093 and 0·0268, respectively). In conclusion, genetic differences in the VDR gene may be involved in the development of AITD and the activity of GD, whereas the genetic differences in the GC and CYP2R1 genes may be involved with the intractability of GD.
Detection rate of FNA cytology in medullary thyroid carcinoma: a meta‐analysis
Authors: Trimboli Pierpaolo , Treglia Giorgio , Guidobaldi Leo , Romanelli Francesco , Nigri Giuseppe , Valabrega Stefano , Sadeghi Ramin , Crescenzi Anna , Faquin William C. , Bongiovanni Massimo , Giovanella Luca
Published: July 2014

Background

The early detection of medullary thyroid carcinoma (MTC) can improve patient prognosis, because histological stage and patient age at diagnosis are highly relevant prognostic factors. As a consequence, delay in the diagnosis and/or incomplete surgical treatment should correlate with a poorer prognosis for patients. Few papers have evaluated the specific capability of fine‐needle aspiration cytology (FNAC) to detect MTC, and small series have been reported. This study conducts a meta‐analysis of published data on the diagnostic performance of FNAC in MTC to provide more robust estimates.

Research Design and Methods

A comprehensive computer literature search of the PubMed/MEDLINE, Embase and Scopus databases was conducted by searching for the terms ‘medullary thyroid’ AND ‘cytology’, ‘FNA’, ‘FNAB’, ‘FNAC’, ‘fine needle’ or ‘fine‐needle’. The search was updated until 21 March 2014, and no language restrictions were used.

Results

Fifteen relevant studies and 641 MTC lesions that had undergone FNAC were included. The detection rate (DR) of FNAC in patients with MTC (diagnosed as ‘MTC’ or ‘suspicious for MTC’) on a per lesion‐based analysis ranged from 12·5% to 88·2%, with a pooled estimate of 56·4% (95% CI: 52·6–60·1%). The included studies were statistically heterogeneous in their estimates of DR (I‐square >50%). Egger's regression intercept for DR pooling was 0·03 (95% CI: −3·1 to 3·2, P = 0·9). The study that reported the largest MTC series had a DR of 45%. Data on immunohistochemistry for calcitonin in diagnosing MTC were inconsistent for the meta‐analysis.

Conclusions

The presented meta‐analysis demonstrates that FNAC is able to detect approximately one‐half of MTC lesions. These findings suggest that other techniques may be needed in combination with FNAC to diagnose MTC and avoid false negative results.
Combined immunomodulatory therapies resulted in stepwise recovery in autoimmune autonomic ganglionopathy
Authors: Nishihara Hideaki , Koga Michiaki , Higuchi Osamu , Tasaki Ayako , Ogasawara Jun‐ichi , Kawai Motoharu , Nakane Shunya , Kanda Takashi
Published: July 2014

Some intractable cases of autoimmune autonomic ganglionopathy are treated with diverse combinations of immunomodulatory therapies. However, it is unclear which of the immunotherapies directly contributed to the relief of dysautonomia when several immunotherapies have been utilized. To evaluate which of the immunomodulatory therapies are effective, we describe a 60‐year‐old man with autoimmune autonomic ganglionopathy who was successfully treated by combined immunomodulatory therapies. The patient showed subacute pure autonomic failure without antecedent infectious symptoms, and was admitted to Yamaguchi University Hospital, Yamaguchi, Japan. He demonstrated involvement of cardiovascular, pupillary, sudomotor, gastrointestinal and bladder functions. Serum ganglionic acetylcholine receptor autoantibody titer was highly elevated. The diagnosis of autoimmune autonomic ganglionopathy was made. Plasma exchange was repeated nine times, resulting in minimal improvement. Subsequently, intravenous immunoglobulin therapy followed by steroid administration was initiated, after which his symptoms gradually improved. Plasma noradrenaline levels showed a stepwise elevation after each treatment, including plasma exchange. Our case adds to the evidence that combining several immunomodulatory therapies is beneficial for some intractable cases of autoimmune autonomic ganglionopathy that do not adequately respond to a single immunomodulatory therapy. Each immunomodulatory therapy should be effective even though they are not enough to show clinical improvement.
Predictive genetic testing for adult‐onset disorders in minors: a critical analysis of the arguments for and against the 2013 ACMG guidelines
Authors: Anderson J.A. , Hayeems R.Z. , Shuman C. , Szego M.J. , Monfared N. , Bowdin S. , Zlotnik Shaul R. , Meyn M.S.
Published: July 2014

The publication of the ACMG recommendations has reignited the debate over predictive testing for adult‐onset disorders in minors. Response has been polarized. With this in mind, we review and critically analyze this debate. First, we identify long‐standing inconsistencies between consensus guidelines and clinical practice regarding risk assessment for adult‐onset genetic disorders in children using family history and molecular analysis. Second, we discuss the disparate assumptions regarding the nature of whole genome and exome sequencing underlying arguments of both supporters and critics, and the role these assumptions play in the arguments for and against reporting. Third, we suggest that implicit differences regarding the definition of best interests of the child underlie disparate conclusions as to the best interests of children in this context. We conclude by calling for clarity and consensus concerning the central foci of this debate.
Living laboratory: whole‐genome sequencing as a learning healthcare enterprise
Authors: Angrist M. , Jamal L.
Published: July 2014

With the proliferation of affordable large‐scale human genomic data come profound and vexing questions about management of such data and their clinical uncertainty. These issues challenge the view that genomic research on human beings can (or should) be fully segregated from clinical genomics, either conceptually or practically. Here, we argue that the sharp distinction between clinical care and research is especially problematic in the context of large‐scale genomic sequencing of people with suspected genetic conditions. Core goals of both enterprises (e.g. understanding genotype–phenotype relationships; generating an evidence base for genomic medicine) are more likely to be realized at a population scale if both those ordering and those undergoing sequencing for diagnostic reasons are routinely and longitudinally studied. Rather than relying on expensive and lengthy randomized clinical trials and meta‐analyses, we propose leveraging nascent clinical‐research hybrid frameworks into a broader, more permanent instantiation of exploratory medical sequencing. Such an investment could enlighten stakeholders about the real‐life challenges posed by whole‐genome sequencing, such as establishing the clinical actionability of genetic variants, returning ‘off‐target’ results to families, developing effective service delivery models and monitoring long‐term outcomes.
Use of genetic technologies to compare medicines
Authors: Kolitz S.E. , Towfic F. , Grossman I. , Hayden M.R. , Zeskind B.
Published: July 2014

In order to ensure that patients receive the safest and most effective medicines possible, it is often necessary to compare medicines and assess the extent to which they are similar in their clinical impact. Full clinical trials with appropriate endpoints remain the only method to compare the clinical impact of two medicines with absolute certainty. Other available methods (including physicochemical analysis, genomics, and transcriptomics) can provide partial information about certain aspects of a medicine's biological impact, with possible clinical implications. Especially for biologics and non‐biological complex drugs, which are more difficult to characterize by physicochemical means than small molecules, genomics and transciptomic studies can yield valuable insights for physicians, regulators, and drug developers. In this review, we cite and summarize a variety of studies that exemplify the emerging science of applying genomics and transcriptomics technologies to compare medicines. We discuss key aspects of experimental design, conduct of genetic assays, and advanced data analysis, all of which are critical for the successful execution of such studies. Finally, we propose new areas for which such studies can be applied to maximize patient benefit and reduce safety issues.
CHIPS for genetic testing to improve a regional clinical genetic service
Authors: Niida Y. , Ozaki M. , Inoue M. , Takase E. , Kuroda M. , Mitani Y. , Okumura A. , Yokoi A. , Fujita S. , Yamada K.
Published: July 2014

In current practice of clinical genetics, molecular diagnosis has become more widely used than ever before. DNA diagnosis is important for appropriate medical care of the patient, and proper genetic counseling to the family. However, genetic testing of orphan disease cannot always be performed easily. In multiple congenital anomalies (MCA) syndromes by monogenic cause, the broad mutational spectrum and large size of responsible genes often make molecular diagnosis expensive and cumbersome. We solve this problem with on‐demand genetic testing by CHIPS (CEL nuclease mediated heteroduplex incision with polyacrylamide gel electrophoresis and silver staining) technology, which is the ultimately conventional and economical mutation screening system. In this article, we show eight patients with MCA syndromes who were recently treated at our hospital, and demonstrate that CHIPS successfully offers efficient and inexpensive genetic testing and facilitates clinical genetic service in our local region.
Available web‐based dental implants information for patients. How good is it?
Authors: Leira‐Feijoo Yago , Ledesma‐Ludi Yanina , Seoane‐Romero Juan M. , Blanco‐Carrión Juan , Seoane Juan , Varela‐Centelles Pablo
Published: July 2014

Background

Massive use of the Internet for health issues has raised concerns about the quality of the information available and about consumers' ability to tell “good” from “bad” information.

Purpose

To assess the quality of patient‐addressed, dental implants‐related websites in terms of reliability, accessibility, usability and readability.

Materials and Methods

Two search engines (Google and Yahoo) were used in this study. The first 100 sites, as listed by each engine, were considered for the study. Each site was categorised and analysed for quality using the DISCERN and the LIDA instruments. The Flesch‐Kinkaid Reading Grade Level (FKRGL) and the Flesh Reading Ease Score (FRES) were used to assess legibility.

Results

After applying the inclusion and exclusion criteria, 32 single websites entered the study. The median score for the DISCERN instrument (3 [2–3]) indicated serious or potentially important shortcoming in the quality of the information obtained. LIDA scores showed modest percentages for accessibility (79.36 [74.60–85.31]) and intermediate for usability (59.20 (50.46‐68.51)) and reliability (55.55 [45.37–66.66]). Legibility indices reached scores within the range of difficult to read (FRES = 51.72 [38.70–55.27]); FKRGL = 12.76 [10.07–14.87]).

Conclusions

Available e‐health information on dental implants in English language is difficult to read for the average patient and poor in terms of quality.
Cost estimation of single‐implant treatment in the periodontally healthy patient after 16–22 years of follow‐up
Authors: Dierens M. , Vandeweghe S. , Kisch J. , Nilner K. , Cosyn J. , De Bruyn H.
Published: July 2014

Background

Costs for single‐implant treatment are mostly described for the initial treatment. Information on the additional cost related to aftercare is scarce.

Objective

To make an estimation of complication costs of single implants in periodontally healthy patients after 16–22 years and to compare costs for various prosthetic designs.

Materials and methods

Patients with a single implant were recalled for a clinical examination and file investigation. Prosthetic designs included single‐tooth (ST) and CeraOne (CO) abutments supporting a porcelain‐fused‐to‐metal (PFM), all‐ceramic (CER), or gold‐acrylic (ACR) crown. Costs related to failures or technical, biologic, and aesthetic complications were retrieved from patient's records. Total and yearly additional complication costs were calculated as a percentage relative to the initial cost. Chair time needed to solve the complication was recorded and prosthetic designs were compared by Kruskal–Wallis tests.

Results

Fifty patients with 59 surviving implants were clinically investigated. Additional complication costs after a mean follow‐up of 18.5 years amounted to 23% (range 0–110%) of the initial treatment cost. In total, 39% of implants presented with no costs, whereas 22% and 8% encountered additional costs over 50% and 75%, respectively. In 2%, the complication costs exceeded the initial cost. The mean yearly additional cost was 1.2% (range 0–6%) and mean complication time per implant was 67 min (range 0–345 min). Differences between prosthetic designs (CO, ST‐PFM, ST‐ACR) were statistically significant for total cost (P = 0.011), yearly cost (P = 0.023), and time (P = 0.023). Pairwise comparison revealed significant lower costs for CO compared with ST‐ACR reconstructions.

Conclusion

Patients should be informed about additional costs related to complications with single implants. The mean additional cost spent on complications was almost one‐quarter of the initial treatment price. A majority of implants presented with lower additional costs, whereas the highest complication costs were related to a smaller group with 22% of the implants needing more than half of the initial cost for complication management. Expenses were significantly different for various prosthetic designs.
The potential for biodiversity offsetting to fund effective invasive species control
Authors: Norton David A. , Warburton Bruce
Published: July 2014

Compensating for biodiversity losses in 1 location by conserving or restoring biodiversity elsewhere (i.e., biodiversity offsetting) is being used increasingly to compensate for biodiversity losses resulting from development. We considered whether a form of biodiversity offsetting, enhancement offsetting (i.e., enhancing the quality of degraded natural habitats through intensive ecological management), can realistically secure additional funding to control biological invaders at a scale and duration that results in enhanced biodiversity outcomes. We suggest that biodiversity offsetting has the potential to enhance biodiversity values through funding of invasive species control, but it needs to meet 7 key conditions: be technically possible to reduce invasive species to levels that enhance native biodiversity; be affordable; be sufficiently large to compensate for the impact; be adaptable to accommodate new strategic and tactical developments while not compromising biodiversity outcomes; acknowledge uncertainties associated with managing pests; be based on an explicit risk assessment that identifies the cost of not achieving target outcomes; and include financial mechanisms to provide for in‐perpetuity funding. The challenge then for conservation practitioners, advocates, and policy makers is to develop frameworks that allow for durable and effective partnerships with developers to realize the full potential of enhancement offsets, which will require a shift away from traditional preservation‐focused approaches to biodiversity management.

El Potencial de la Compensación de la Biodiversidad para Financiar Controles Efectivos de Especies Invasoras
Xyleborus glabratus attacks and systemic colonization by Raffaelea lauricola associated with dieback of Cinnamomum camphora in the southeastern United States
Authors: Fraedrich S. W. , Harrington T. C. , Best G. S.
Published: July 2014

Laurel wilt, caused by Raffaelea lauricola, is responsible for extensive mortality of redbay and other American members of the Lauraceae in the southeastern United States. Raffaelea lauricola is a mycangial symbiont of the redbay ambrosia beetle (Xyleborus glabratus), and the beetle and fungus were accidentally introduced from Asia. Branch dieback of camphortree (Cinnamomum camphora), an Asian member of the Lauraceae, has been occasionally observed in areas where laurel wilt has decimated redbay populations, and R. lauricola was isolated from such camphortrees. However, the role of X. glabratus and R. lauricola in this branch dieback remains unclear. Examination of camphortrees on Jekyll Island, Georgia showed that healthy‐appearing trees and those with branch dieback had been attacked by X. glabratus, but the trees with branch dieback had four times as many beetle attacks. Raffaelea lauricola was routinely isolated from discoloured xylem near beetle tunnels in healthy trees and those with dieback. Single‐point inoculations with R. lauricola on stems of mature, healthy camphortree trees failed to induce wilt‐like symptoms or branch dieback, although areas of discoloration were scattered throughout the xylem, and R. lauricola was reisolated irregularly at various heights in some inoculated trees. In growth chamber experiments, single‐point inoculations with R. lauricola resulted in systemic colonization but no wilt symptoms or branch dieback in camphortree saplings. In contrast, inoculations at multiple points along the stem (simulating multiple attacks by the vector) caused branch dieback and wilt‐like symptoms, including a brownish, diffuse discoloration of the xylem. Camphortree appears to be more resistant than American species of Lauraceae to the vascular wilt caused by R. lauricola. The fungus does colonize camphortrees systemically, however, and can apparently cause branch dieback. This suggests that the fungus may provide brood material for X. glabratus in Asia as it does in the southeastern United States.
Testing the role of preBötzinger Complex somatostatin neurons in respiratory and vocal behaviors
Authors: Tupal Srinivasan , Rieger Michael A. , Ling Guang‐Yi , Park Thomas J. , Dougherty Joseph D. , Goodchild Ann K. , Gray Paul A.
Published: July 2014

Identifying neurons essential for the generation of breathing and related behaviors such as vocalisation is an important question for human health. The targeted loss of preBötzinger Complex (preBötC) glutamatergic neurons, including those that express high levels of somatostatin protein (SST neurons), eliminates normal breathing in adult rats. Whether preBötC SST neurons represent a functionally specialised population is unknown. We tested the effects on respiratory and vocal behaviors of eliminating SST neuron glutamate release by Cre‐Lox‐mediated genetic ablation of the vesicular glutamate transporter 2 (VGlut2). We found the targeted loss of VGlut2 in SST neurons had no effect on viability in vivo, or on respiratory period or responses to neurokinin 1 or μ‐opioid receptor agonists in vitro. We then compared medullary SST peptide expression in mice with that of two species that share extreme respiratory environments but produce either high or low frequency vocalisations. In the Mexican free‐tailed bat, SST peptide‐expressing neurons extended beyond the preBötC to the caudal pole of the VII motor nucleus. In the naked mole‐rat, however, SST‐positive neurons were absent from the ventrolateral medulla. We then analysed isolation vocalisations from SST‐Cre;VGlut2F/F mice and found a significant prolongation of the pauses between syllables during vocalisation but no change in vocalisation number. These data suggest that glutamate release from preBötC SST neurons is not essential for breathing but play a species‐ and behavior‐dependent role in modulating respiratory networks. They further suggest that the neural network generating respiration is capable of extensive plasticity given sufficient time.
The vegetative state/unresponsive wakefulness syndrome: a systematic review of prevalence studies
Authors: van Erp W. S. , Lavrijsen J. C. M. , van de Laar F. A. , Vos P. E. , Laureys S. , Koopmans R. T. C. M.
Published: July 2014

One of the worst outcomes of acquired brain injury is the vegetative state, recently renamed ‘unresponsive wakefulness syndrome’ (VS/UWS). A patient in VS/UWS shows reflexive behaviour such as spontaneous eye opening and breathing, but no signs of awareness of the self or the environment. We performed a systematic review of VS/UWS prevalence studies and assessed their reliability. Medline, Embase, the Cochrane Library, CINAHL and PsycINFO were searched in April 2013 for cross‐sectional point or period prevalence studies explicitly stating the prevalence of VS/UWS due to acute causes within the general population. We additionally checked bibliographies and consulted experts in the field to obtain ‘grey data’ like government reports. Relevant publications underwent quality assessment and data‐extraction. We retrieved 1032 papers out of which 14 met the inclusion criteria. Prevalence figures varied from 0.2 to 6.1 VS/UWS patients per 100 000 members of the population. However, the publications’ methodological quality differed substantially, in particular with regards to inclusion criteria and diagnosis verification. The reliability of VS/UWS prevalence figures is poor. Methodological flaws in available prevalence studies, the fact that 5/14 of the studies predate the identification of the minimally conscious state (MCS) as a distinct entity in 2002, and insufficient verification of included cases may lead to both overestimation and underestimation of the actual number of patients in VS/UWS.
Effect of thrombus size on recanalization by bridging intravenous thrombolysis
Authors: Behrens L. , Möhlenbruch M. , Stampfl S. , Ringleb P. A. , Hametner C. , Kellert L. , Pham M. , Herweh C. , Bendszus M. , Rohde S.
Published: July 2014

Background and purpose

Thrombus length has been reported as an important predictor of successful recanalization by intravenous thrombolysis but its influence on bridging thrombolysis has not been investigated yet. The effect of thrombus length on recanalization rates evaluated by catheter angiography early after intravenous bridging thrombolysis was analyzed.

Methods

Ninety‐six consecutive patients with acute cerebral artery occlusion were included. Occlusion site and thrombus length on initial computed tomography angiography or magnetic resonance angiography were related to recanalization after intravenous bridging thrombolysis on the initial series of catheter angiography.

Results

Eleven of 96 patients (11.5%) showed successful recanalization (TICI 2a, 2b or 3) after intravenous bridging thrombolysis. Mean thrombus length in these patients was 10.8 mm as opposed to 15.6 mm in patients without successful recanalization. No thrombus longer than 16 mm showed complete recanalization. Binary logistic regression demonstrated a significant influence of thrombus length on probability of recanalization (odds ratio 0.78, 95% confidence interval 0.65–0.95; P = 0.014).

Conclusions

Thrombus length is a significant predictor of recanalization rates after bridging thrombolysis. Overall recanalization rate within the time frame until interventional treatment is started was 11.5% after bridging thrombolysis.
Shyness–Boldness, but not Exploration, Predicts Glucocorticoid Stress Response in Richardson's Ground Squirrels (Urocitellus richardsonii)
Authors: Clary Dawson , Skyner Lindsay J. , Ryan Calen P. , Gardiner Laura E. , Anderson W. Gary , Hare James F.
Published: July 2014

The relationship between stress and personality has often been studied using captive animals in a laboratory context, yet less often in wild populations. Wild populations, however, may reveal aspects of the personality–stress relationship that laboratory‐based studies cannot. Here, we assessed the personality and stress hormone response of adult females within a free‐living population of Richardson's ground squirrels (Urocitellus richardsonii). Personality was assessed by quantifying individual responses to a novel object, and physiological stress was measured from faecal glucocorticoid metabolites. Principal component and principal component regression analyses were performed to determine whether the behavioural and endocrine measures were related. Based on these analyses, shyness–boldness was found to best predict glucocorticoid levels, in that individuals expressing the greatest vigilance in response to the novel object also had the highest measured concentrations of faecal glucocorticoids. Exploration, however, was independent of measured glucocorticoid levels, consistent with a multidimensional interpretation of non‐human animal personality.
When EU Citizens become Foreigners
Authors: Kostakopoulou Dora
Published: July 2014

Although EU citizenship has matured as an institution, a combination of hope and caution ought to accompany the tale of its evolution. Contradictory processes of inclusion and greater equalisation coexist with exclusionary logics. These would have to be taken into account, and be addressed, by assessments of its present state and its future evolution. A focus on three key manifestations of state sovereignty, namely, the erasure of citizenship status, expulsion and the disappearance of individuals owing to extraordinary rendition, sheds light onto the edges of EU citizenship and the undesirable effects of untrammelled state power on the lives of individuals. Probing into the moments when EU citizens are treated as aliens or foreigners, and the troublesome ambiguities, tensions and limitations surrounding them, reveals the gaps in the protection of EU citizens and the constraints that stand in the way of change in the institutional scheme of things.
Characterisation of the faecal metabolome and microbiome of Thoroughbred racehorses
Authors: Proudman C. J. , Hunter J. O. , Darby A. C. , Escalona E. E. , Batty C. , Turner C.
Published: July 2014

Reasons for performing study

The intestinal bacterial community of the horse is a key determinant of intestinal and whole body health. Understanding the bacterial community structure and function is an important foundation for studies of intestinal health and disease.

Objectives

To describe the faecal bacterial community and volatile organic compounds (VOCs) of the faecal metabolome of healthy Thoroughbred racehorses and to characterise responses to dietary supplementation with amylase‐rich malt extract.

Study design

Intervention study.

Methods

Faecal samples were collected noninvasively before and 6 weeks after supplementation in 8 privately owned Thoroughbred racehorses in active race training. Faecal metabolome was characterised using thermal desorption‐gas chromatography‐mass spectrometry (TD‐GC‐MS), with spectral analysis performed using AMDIS and compared against the NIST database. Taxonomic description of the faecal microbiota was achieved using error‐corrected 454 pyrosequencing data from 16S rRNA gene amplicons.

Results

The faecal metabolome of our study population was dominated by organic acids, alcohols and ketones. We identified 81 different VOCs only 28 of which were present in >50% of samples indicating functional diversity. Faecal VOC profiles differed between first and second sampling point, some VOCs being significantly reduced post supplementation, consistent with a marked response to dietary amylase‐rich malt extract. Faecal microbiota was characterised as highly diverse; samples demonstrated verifiable diversity in the range 1200–3000 operational taxonomic units (OTUs) per individual. The methods used also describe high levels of infrequent, low abundance OTUs. Faecal microbial community structure was found to be different following dietary supplementation. Differences in several low abundance bacterial taxa were detected and also some evidence of interhorse variation in response.

Conclusions

The volatile faecal metabolome of Thoroughbred racehorses is dominated by organic acids, alcohols and ketones; this study demonstrates that dietary supplementation with amylase‐rich malt extract may significantly alter the profile of VOCs. The faecal microbiome is highly diverse, dominated by Firmicutes and Bacteroidetes. Small but significant changes in microbial community structure were detected following dietary supplementation. This study describes the faecal metabolome and microbiome of healthy Thoroughbred racehorses against which future studies of disease and dietary intervention can be benchmarked.
Role of endothelin‐1/endothelin receptor signaling in fibrosis and calcification in nephrogenic systemic fibrosis
Authors: Motegi Sei‐ichiro , Okada Etsuko , Uchiyama Akihiko , Yamada Kazuya , Ogino Sachiko , Yokoyama Yoko , Takeuchi Yuko , Monma Fumiko , Suzuki Tamio , Ishikawa Osamu
Published: July 2014

Nephrogenic systemic fibrosis (NSF) is characterized by systemic fibrosis and abnormal calcification in patients with severe renal dysfunction. It is considered that gadolinium (Gd)‐containing contrast agents used for magnetic resonance imaging trigger the development of NSF. However, the causative role of Gd and the mechanism of Gd‐induced fibrosis and calcification in NSF are unknown. Recently, it has been known that endothelin‐1 (ET‐1)/ET receptor (ETR) signalling regulates fibrosis and calcification. The objective was to elucidate the role of ET‐1/ETR signalling in Gd‐induced fibrosis and calcification in NSF. First, we demonstrated that Gd enhanced proliferation and calcification of human adipose tissue‐derived mesenchymal stem cells (hMSC) in vitro. Next, we examined the expression of ET‐1 and ETR‐A in hMSC using proliferation or calcification assay. ET‐1 and ETR‐A expression in hMSC treated with Gd were elevated. ET‐1/ETR signalling inhibitor, bosentan, inhibited Gd‐induced proliferation and calcification of hMSC. In addition, bosentan inhibited Gd‐induced phosphorylation of ERK and Akt in hMSC. Plasma ET‐1 levels of the patients were significantly higher than these of normal individuals and systemic sclerosis patients. In immunofluorescence staining, the expression of ETR‐A in fibroblasts in dermal fibrosis lesion of NSF was increased. We conclude that Gd induces proliferation and calcification of hMSC via enhancement of ET‐1/ETR signalling. Our results contribute to understand the pathogenesis of NSF.