bluuebunny/crossref_metadata_2025 huggingface dataset:
Tackling the Diversity of Triple-Negative Breast Cancer
Authors: Turner Nicholas C. , Reis-Filho Jorge S.
Published: December 2013

Triple-negative breast cancer (TNBC) comprises a highly diverse collection of cancers. Here, we review this diversity both in terms of gene expression subtypes and the repertoire of genetic events. Transcriptomic analyses of TNBC have revealed at least six subtypes, with the luminal androgen receptor (luminal AR) or molecular apocrine cancers forming a distinct group within triple-negative disease. Distinct from the gene expression subtypes, a diverse set of genetic events have been described in TNBC, with a number of potentially targetable genetic events found although all at relatively low frequency. Clinical trials to define the clinical utility of therapies targeting these low-frequency events will require substantial screening efforts to identify sufficient patients. Set against the diversity of TNBC, clinical studies of patients with triple-negative disease will need to be either focused on molecularly defined subsets with upfront molecular stratification, or powered for a secondary endpoint analysis of a molecularly defined subset. Such approaches will be crucial to realize the potential of precision medicine for patients with TNBCs. Clin Cancer Res; 19(23); 6380–8. ©2013 AACR.
External Quality Control of Cervical Cytopathology: Interlaboratory Variability
Authors: Ázara Cinara Zago Silveira , Manrique Edna Joana Cláudio , Alves de Souza Nádja Lindany , Rodrigues Andryne Rego , Tavares Suelene Brito do Nascimento , Amaral Rita Goreti
Published: December 2013

Objective: To compare the variability of screening tests held at laboratories with the Unit for External Quality Control (UEQC), checking the frequency of cases that were discordant, false-positive, false-negative, unsatisfactory or that had a delay in clinical management and diagnostic agreement. Materials and Methods: The study analyzed 10,053 screening tests from January 2007 to December 2008, including all positive cases, all those that fall under unsatisfactory and at least 10% of negative screening tests. The magnitude of the agreement was analyzed using the kappa coefficient. Results: Out of the 10,053 cases analyzed, 7.59% were considered disagreeing, and it was estimated that 1.1% were false-negative. There was a delay in the clinical procedure regarding 2.44% cases. There were 2.82% of cases identified as false-positive and 1.24% as unsatisfactory. The diagnostic agreement was excellent (kappa = 0.81). The agreement of most laboratories concerning screening tests was classified as very good. The agreement of the sample adequacy was reasonable (kappa = 0.30) and the agreement regarding the representation of epithelia was considered excellent. Conclusion: Most laboratories showed very good agreement; however, it is worthy of note that to establish the standardization of diagnostic criteria, and enhance the accuracy of screening and improve the quality of cytopathology test results, it is necessary to perform external quality control.
Problems and Perspectives of Ophthalmic Research in Germany: Results from a National Survey
Authors: Wolfram Christian , Pfeiffer Norbert
Published: December 2013

Purpose: To identify and describe the most relevant obstacles to carrying out ophthalmic research in Germany. Methods: Two research methods were used to assess current problems in ophthalmic research. First, 55 expert interviews were conducted with major stakeholders in ophthalmic research, and key problems were identified. An online questionnaire was then sent to 3,080 German ophthalmologists, of whom 927 responded by evaluating the current research situation within ophthalmology in Germany. We devised a score to rank areas of concern by multiplying the responders' rate, ranging between -3 (‘I disagree completely') and +3 (‘I fully agree'), with the percentage of response frequencies. The maximum possible score was 300. Results: The lack of opportunities to combine clinical work and research (score: 231.8) as well as unattractive career perspectives (175.7) were identified as the most relevant problems. Further barriers were difficulties in acquiring research funds (155.7), organizational problems at the local level (143.7) and a lack of support for women (24.1; among women: 122.3). Potential improvement was expected in particular from exemption from clinical work for scientific purposes; this was found to be more appealing than more prestigious awards for research achievements. A widely held position was that research projects should focus more closely on common eye diseases, and that vision research needs a more prominent profile among politicians and in the public arena. Conclusion: Our findings may help to initiate improvements in both research performance and outcomes.
Castrate-Resistant Prostate Cancer with Peritoneal Metastases Treated with Docetaxel-Based Chemotherapy
Authors: Rizk Rita , Danse Etienne , Aydin Selda , Tombal Bertrand , Machiels Jean-Pascal
Published: December 2013

Introduction: To identify the risk factors, characteristics and prognosis of patients treated with docetaxel-based chemotherapy for peritoneal carcinomatosis due to metastatic castrate-resistant prostate cancer (mCRPC). Methods: We retrospectively reviewed our series of mCRPC patients with peritoneal metastases treated with docetaxel-based chemotherapy between 2004 and 2010. Results: Six patients were identified from our institutions' internal cancer registry. Three out of these patients had been treated with laparoscopic radical prostatectomy (LRP). In addition to peritoneal metastases, other metastatic sites were mainly visceral. Only 1 patient developed bone metastases. Peritoneal carcinomatosis occurred mainly in patients with a high Gleason (= or >6) score since 5 out of our 6 patients had a Gleason score ≥7. All 6 patients were treated with docetaxel-based chemotherapy when they developed castration resistance. Five patients benefitted from chemotherapy according to their PSA or RECIST responses. Median survival from the start of docetaxel was 24.5 months. Conclusions: Our retrospective analysis suggests that peritoneal carcinomatosis occurs mainly in patients with a high Gleason score. It is also possible that tumor seeding occurs during LRP. Patients with peritoneal carcinomatosis resistant to castration seem to benefit from docetaxel-based chemotherapy.
Oral Administration of Lactobacillus reuteri during the First Year of Life Reduces Caries Prevalence in the Primary Dentition at 9 Years of Age
Authors: Stensson M. , Koch G. , Coric S. , Abrahamsson T.R. , Jenmalm M.C. , Birkhed D. , Wendt L.-K.
Published: December 2013

The aim of this study was to evaluate the effect on oral health, at age 9 years, of daily oral supplementation with the probiotic Lactobacillus reuteri, strain ATCC 55730, to mothers during the last month of gestation and to children through the first year of life. The study was a single-blind, placebo-controlled, multicenter trial involving 113 children: 60 in the probiotic and 53 in the placebo group. The subjects underwent clinical and radiographic examination of the primary dentition and carious lesions, plaque and gingivitis were recorded. Saliva and plaque were sampled for determination of mutans streptococci (MS) and lactobacilli (LB) in saliva and plaque as well as salivary secretory IgA (SIgA). Forty-nine (82%) children in the probiotic group and 31 (58%) in the placebo group were caries-free (p < 0.01). The prevalence of approximal caries lesions was lower in the probiotic group (0.67 ± 1.61 vs. 1.53 ± 2.64; p < 0.05) and there were fewer sites with gingivitis compared to the placebo group (p < 0.05). There were no significant differences between the groups with respect to frequency of toothbrushing, plaque and dietary habits, but to intake of fluoride supplements (p < 0.05). There were no intergroup differences with respect to L. reuteri, MS, LB or SIgA in saliva. Within the limitation of this study it seems that daily supplementation with L. reuteri from birth and during the first year of life is associated with reduced caries prevalence and gingivitis score in the primary dentition at 9 years of age.
Effect of Continuous Positive Airway Pressure Treatment for Obstructive Sleep Apnoea on Visual Processing of Degraded Words
Authors: Proudlove Katie , Manuel Ari , Hall Rachel , Rieu Romelie , Villarroel Mauricio , Stradling John
Published: December 2013

Background: In a previous uncontrolled study, continuous positive airway pressure (CPAP) therapy for obstructive sleep apnoea (OSA) improved vision in patients with diabetic macular oedema. Objectives: We investigated whether the above improvement in vision (or visual processing) might have been due to reduced sleepiness, rather than a true improvement in retinal function. Methods: Twelve normal control subjects and 20 patients with OSA were tested for their ability to recognise degraded words, by means of a computer programme displaying 5-letter words every 4 s for 10 min, with variable amounts of the bottom half of the word missing; the percentage of the word necessary to achieve correct identification on average half the time was ‘hunted' (the test score). All subjects were tested twice, 2-3 weeks apart; the OSA group after the commencement of CPAP. The Epworth Sleepiness Score (ESS) in patients was measured at the same visit. Results: The test score at visit 1 was 26.7% for normal subjects and 31.6% for patients with OSA. At visit 2, the test score was 25.0% for normal subjects and 29.9% for patients with OSA. The groups showed a small and identical improvement over the trial period in the test score, of 1.7% (p = 0.01 and p = 0.03 for the normal and OSA groups, respectively). The group with OSA experienced a drop in ESS of 7.5 (SD 5.5) points following treatment. Conclusion: The small and identical improvement in both groups suggests only a similar learning effect rather than any improvement due to reduced sleepiness.
Corneal Involvement in Uneventful Cataract Surgery: An in vivo Confocal Microscopy Study
Authors: De Cillà Stefano , Fogagnolo Paolo , Sacchi Matteo , Orzalesi Nicola , Carini Elisa , Ceresara Gaia , Rossetti Luca
Published: December 2013

Purpose: To evaluate corneal subbasal layer changes after uneventful cataract surgery by means of in vivo confocal microscopy. Methods: This prospective study included 30 patients. Before surgery, and 1, 3, 6, 8 and 10 months after cataract surgery, all patients underwent a complete ophthalmological and confocal microscopy examination in the central and temporal corneal areas. Number of fibers, beading, tortuosity and reflectivity were analyzed. Results: Important changes were shown in the central cornea up to 3 months after surgery: a reduction in nerve fiber number (baseline: 4.4 ± 1.7; month 1: 1.2 ± 0.5, p < 0.0001; month 3: 2.5 ± 1.2, p < 0.005) and reflectivity (baseline: 3.6 ± 0.5; month 1: 1.4 ± 0.6, p < 0.0001; month 3: 1.9 ± 0.9, p < 0. 0001), and an increase in beading (baseline: 0.3 ± 0.5 beads/100 µm2; month 1: 2.7 ± 0.6 beads/100 µm2, p < 0.0001; month 3: 2.6 ± 0.5 beads/100 µm2, p < 0. 0001). The confocal parameters completely progressively recovered thereafter (60% at 6 months, 87% at 8 and 10 months). The temporal plexus was absent at 1 month and fully recovered in all patients at month 8. Conclusion: Uneventful cataract surgery induces relevant corneal modifications when inspected by means of confocal microscopy.
Acoustic-Perceptual Relationships in Variants of Clear Speech
Authors: Lam Jennifer , Tjaden Kris
Published: December 2013

Objective: The acoustic basis of intelligibility associated with varied clear speech instructions was studied. Methods: Twelve healthy speakers read 18 sentences in ‘habitual', ‘clear', ‘hearing impaired' and ‘overenunciate' conditions. The latter 3 conditions are varieties of clear speech. Acoustic measures included tense and lax vowel space area, a measure of vowel spectral change, articulation rate and sentence-level vocal intensity. Sentences were mixed with multitalker babble to prevent ceiling effects and were orthographically transcribed by 40 listeners. Percent-correct scores were obtained for each speaker and condition. Regression analyses were used to quantify relationships between acoustic measures and intelligibility. Results: Univariate regressions indicated that greater magnitudes of acoustic change in nonhabitual conditions were associated with greater increases in intelligibility. Multivariate regression analysis further indicated that lax vowel space, articulation rate and vocal intensity were significant predictors of intelligibility. Conclusions: Acoustic variables associated with intelligibility differed depending on whether relationships were examined using univariate or multivariate statistics. Multivariate statistics indicated that articulation rate was the strongest predictor of improvements in intelligibility above and beyond all other variables studied. The findings have implications for optimizing therapeutic use of clear speech for clinical populations.
Effect of Bosentan on Pulmonary Hypertension Secondary to Systolic Heart Failure
Authors: Padeletti Margherita , Caputo Maria , Zacà Valerio , Tsioulpas Charilos , Bernazzali Sonia , Mondillo Sergio , Maccherini Massimo , Jelic Sanja
Published: December 2013

Objectives: The dual endothelin receptor antagonist bosentan improves pulmonary vascular resistance (PVR) in patients with primary pulmonary hypertension (PH). The effects of bosentan on secondary PH due to systolic heart failure (HF) are not well defined. This study evaluates the effect and tolerability of bosentan in patients with PH secondary to HF. Methods: Seventeen adult HF patients with PH and New York Heart Association class III-IV symptoms were treated with bosentan, 62.5 mg twice daily, for 1 month, which was gradually increased to 125 mg twice daily thereafter. Right heart catheterization (RHC), a clinical evaluation and echocardiographic measurements were performed at baseline and at 4 ± 3 (mean ± SD) months of follow-up. Response to bosentan was defined as an improvement in clinical, echocardiographic and RHC parameters. Results: Six patients did not complete the study (therapy was discontinued due to hypotension, elevated liver enzymes or acute decompensation of HF), 11 patients completed the follow-up; 9 patients responded to therapy. Systemic arterial pressures, pulmonary pressures, PVR and the transpulmonary gradient significantly decreased compared with baseline levels in 9 responders (p = 0.05, 0.05, 0.01 and 0.004, respectively), and 4 became eligible for heart transplantation and 3 for left ventricular assist device implantation. Conclusions: Bosentan decreased pulmonary pressures and PVR in the majority of patients with PH secondary to systolic HF, thereby allowing them to be considered candidates for heart transplantation.
The Human IgE Repertoire
Authors: Gadermaier Elisabeth , Levin Mattias , Flicker Sabine , Ohlin Mats
Published: December 2013

IgE is a key mediator in allergic diseases. However, in strong contrast to other antibody isotypes, many details of the composition of the human IgE repertoire are poorly defined. The low levels of human IgE in the circulation and the rarity of IgE-producing B cells are important reasons for this lack of knowledge. In this review, we summarize the current knowledge on these repertoires both in terms of their complexity and activity, i.e. knowledge which despite the difficulties encountered when studying the molecular details of human IgE has been acquired in recent years. We also take a look at likely future developments, for instance through improvements in sequencing technology and methodology that allow the isolation of additional allergen-specific human antibodies mimicking IgE, as this certainly will support our understanding of human IgE in the context of human disease in the years to come.
Dissemination and Implementation of the ARIA Guidelines for Allergic Rhinitis in General Practice
Authors: Van Hoecke Helen , Vandeplas Griet , Acke Frederic , Thas Olivier , De Sutter An , Gevaert Philippe , Van Cauwenberge Paul , Dhooge Ingeborg
Published: December 2013

Background: Allergic rhinitis (AR) is a prevalent problem in general practice. The first evidence-based guidelines for AR, the ARIA guidelines, were published and have been updated repeatedly since 2001 in order to improve the care of AR patients. Very limited information, however, is available on the impact of these guidelines on everyday clinical practice. The aim of this study was to evaluate the dissemination and implementation of the ARIA guidelines in general practice. Methods: Three hundred and fifty Flemish general practitioners (GPs) were recruited to complete a questionnaire covering their demographic and professional characteristics, awareness, perception and implementation of the ARIA guidelines. To assess compliance with the ARIA treatment recommendations, 4 fictitious case scenarios of AR were presented, in which the respondents were asked to select the treatment of choice. Results: Of the 350 GPs included, only 31% were aware of the ARIA guidelines and 10% stated that they implement them. For the diagnosis of AR, 71% of the GPs ask specific IgE tests or perform skin prick tests, whereas only 29% perform an anterior rhinoscopy. ARIA users are more likely to screen for concomitant asthma. In the clinical-case section, there was a large variability in proposed therapeutic strategies. Adherence to the evidence-based ARIA treatment guidelines was low, but recent graduation was a significant predictor of compliance with these recommendations. Conclusions: The ARIA guidelines remain relatively unknown among Flemish GPs and even those who are aware of them still tend to treat AR independently of the guideline recommendations.
The Role of Squash Cytology in Rapid On-Site Adequacy Checking and Rapid Diagnosis in Image-Guided Gun Biopsy at a Tertiary Cancer Center
Authors: Kane Shubhada V. , Prabhudesai Neelam M. , Ojha Sandeep S. , Shetty Nitin S. , Kulkarni Aniruddha V. , Kulkarni Suyash S.
Published: December 2013

Objective: To evaluate the role of squash cytology in rapid on-site adequacy checking (ROSAC) of image-guided gun biopsy and to determine its diagnostic accuracy at a tertiary cancer center. Study Design: This was a prospective study on 183 patients undergoing image-guided biopsy. Squash smears were prepared from biopsy cores and checked for adequacy by cytotechnologists. When adequate, more cores were sampled from the same area for histopathology. If inadequate, the procedure was repeated at the same sitting on a different area. The squash smears were reported by cytopathologists within 4 h after staining with conventional Papanicoloau stain. The results were compared with the final histopathology report. Results: The sampling was representative in 95.6% cases with concordance for adequacy in 97.3% cases. The sensitivity, specificity, positive predictive value and negative predictive value of squash cytology for diagnosis of the lesion were 99.4, 92.7, 97.7 and 97.4%, respectively. Conclusions: Squash cytology is an ideal and cost-effective technique for ROSAC of image-guided biopsies, which ensures adequacy, avoids repeat procedures and prevents delay in diagnosis. It can be effectively performed by trained cytotechnologists in radiology clinics. Squash cytology is also a cost-effective tool offering rapid diagnosis which expedites planning of treatment.
A Classic Clinical Case: Neutrophilic Eccrine Hidradenitis
Authors: Copaescu Ana-Maria , Castilloux Jean-François , Chababi-Atallah Myrna , Sinave Christian , Bertrand Janie
Published: December 2013

Background: Neutrophilic eccrine hidradenitis (NEH) is a rare condition described mostly in adult patients receiving chemotherapy for acute myelogenous leukemia. When it affects the facial region, it can mimic cellulitis and delay the diagnostic, thus proper recognition is essential. Objective: This article describes a classic case of NEH. We will review the diagnostic, the differential diagnostic (mostly cellulitis) and the management of this condition. Methods: After a literature review, the patient's file was properly studied in order to portray a clear picture of this condition. Medical photographs and appropriate physical examination upon presentation are also included. Results: The diagnostic for NEH was suggested by the clinical presentation and confirmed histopathologically (skin biopsy). Conclusion: The diagnostic of NEH is essential in order to prevent multiple unnecessary antibiotics.
Rapid Detection for Rabbit-Derived Dermatophytes Using Microsatellite-Primed Polymerase Chain Reaction
Authors: Miao Zengmin , Li Song , Li Daijun , Cai Chunmei , Cai Yumei
Published: December 2013

A method exhibiting high sensitivity, specificity and rapidity to detect pathogenic dermatophytes was developed using microsatellite-primed polymerase chain reaction (PCR) in combination with a clustering method. The DNA fragments of Trichophyton mentagrophyton, Microsporum gypseum and Microsporum canis were amplified by using the primer (GACA)4 to detect the DNA polymorphism fingerprints. Twenty-one clinical strains identified as T. mentagrophyton, M. gypseum or M. canis by morphological methods were distinguished according to the differences of standard stains' bands combined with NTSYS-pc2.10 software. The results showed that there were obvious and direct differences in the bands of the three pathogenic dermatophytes, and the similarity of isolated strains and standard strains were above 90%, in line with the results of morphological identification. The method is more accurate, rapid and simple, which is meaningful for the clinical diagnosis and epidemic research of the dermatophytes.
Protective Effects of Cariporide on Endothelial Dysfunction Induced by Homocysteine
Authors: Wu Shujin , Gao Xiang , Yang Shehua , Liu Liying , Ge Bin , Yang Qingshan
Published: December 2013

Aims: Recent studies have reported that intracellular calcium (Ca2+) mobilization is involved in homocysteine (Hcy)-induced endothelial dysfunction and the Na+/H+ exchanger (NHE) is responsible for an increase in the intracellular Ca2+ concentration in cardiovascular disease. We hypothesized that inhibition of the NHE had protective effects on Hcy-induced endothelial dysfunction. Methods: Acetylcholine-induced endothelium-dependent relaxation (EDR) and biochemical parameters were measured in the rat isolated aorta. The level of reactive oxygen species (ROS) was designed by a specific fluorescent probe. The phosphorylation of the nuclear factor-κB (NF-κB) system was studied by Western blot. Results: Cariporide significantly prevented Hcy-impaired EDR and increased nitric oxide (NO) release; endothelial NO synthase activity simultaneously decreased ROS production. We also found that cariporide blocked Hcy-induced NF-κB activation and inhibitor-κB degradation, thus inhibiting the production of tumor necrosis factor-a and intercellular adhesion molecule-1. Conclusions: The mechanisms of protective effects of cariporide may be related to the inhibition of NHE and the decrease in oxidative stress and inflammatory injury.
Innate Type 2 Response to Alternaria Extract Enhances Ryegrass-Induced Lung Inflammation
Authors: Kim Hee-Kyoo , Lund Sean , Baum Rachel , Rosenthal Peter , Khorram Naseem , Doherty Taylor A.
Published: December 2013

Background: Exposure to the fungal allergen Alternaria alternata as well as ryegrass pollen has been implicated in severe asthma symptoms during thunderstorms. We have previously shown that Alternaria extract induces innate type 2 lung inflammation in mice. We hypothesized that the innate eosinophilic response to Alternaria extract may enhance lung inflammation induced by ryegrass. Methods: Mice were sensitized to ryegrass allergen and administered a single challenge with A. alternata extract before or after final ryegrass challenges. Levels of eosinophils, neutrophils, Th2 cells, innate lymphoid cells (ILC2), interleukin (IL)-5 and IL-13 in bronchoalveolar lavage (BAL) as well as inflammation and mucus were assessed. Results: Mice receiving ryegrass sensitization and challenge developed an eosinophilic lung response. A single challenge with Alternaria extract given 3 days before or 3 days after ryegrass challenges resulted in increased eosinophils, peribronchial inflammation and mucus production in the airways compared with ryegrass-only challenges. Type 2 ILC2 and Th2 cell recruitment to the airways was increased after Alternaria extract exposure in ryegrass-challenged mice. Innate immune challenges with Alternaria extract induced BAL eosinophilia, Th2 cell recruitment as well as ILC2 expansion and proliferation. Conclusions: A single exposure to Alternaria extract in ryegrass-sensitized and -challenged mice enhances the type 2 lung inflammatory response, including airway eosinophilia, peribronchial infiltrate, and mucus production, possibly through Th2 cell recruitment and ILC2 expansion. If translated to humans, exposure to both grass pollen and Alternaria may be a potential cause of thunderstorm-related asthma.
Retroperitoneal, Paraspinal Migration of Distal Ventriculoperitoneal Shunt Catheter: A Peculiar Complication of Cerebrospinal Fluid Shunt
Authors: Greene Jr. Clarence , Valerie Evans
Published: December 2013

We describe a case of a ventriculoperitoneal shunt malfunction in which the tip of the peritoneal catheter found its way to the paraspinal subcutaneous tissues. The specific findings on physical examination and the results of the imaging made to make the diagnosis are presented. No prior report of migrating shunt tubing into this anatomic area was found in the literature. This curiosity is added to the list of organs or spaces shunts are capable of wandering into.
Significance of Foamy Histiocytes in Cervical Smears from Postmenopausal Women
Authors: Kir Gozde , Yilmaz Muberra Segmen , Çetiner Handan , Gocmen Ahmet , Alptekin Filiz
Published: December 2013

Objective: To determine the significance of the presence of foamy histiocytes (FH) in postmenopausal cervicovaginal smears for the detection of endometrial carcinomas (EC). Study Design: Endometrial sampling was performed over 6 months in 53 of 102 cases that presented with postmenopausal FH, benign endometrial cells (BEC), FH with BEC (FH + BEC), and atypical endometrial cells (AEC), resulting in a total of 41,150 cervicovaginal smears. The control group consisted of 58 cases with a cytologic diagnosis of a normal smear (NS). Results: There were 0 (0%), 1 (4.54%), 2 (13.33%), 2 (33.33%), and 5 (50.00%) cases of EC diagnosed on histopathologic evaluation in patients with NS (n = 58), BEC (n = 22), FH (n = 15), FH + BEC (n = 6), and AEC (n = 10), respectively. The sensitivities and specificities of the cytologic diagnoses of FH, FH + BEC, and AEC for the detection of EC were 81.7 and 100%, 93.6 and 100%, and 92.1 and 100%, respectively. Conclusion: The cytologic diagnoses of FH and FH + BEC had reasonably high sensitivities and specificities for the diagnosis of EC by cervicovaginal smear. Additional studies are needed.
Novel Use of Rituximab for Steroid-Dependent Nephrotic Syndrome in Children
Authors: Kimata Takahisa , Hasui Masafumi , Kino Jiro , Kitao Tetsuya , Yamanouchi Sohsaku , Tsuji Shoji , Kaneko Kazunari
Published: December 2013

Background: Though rituximab (RTX) is effective for childhood steroid-dependent nephrotic syndrome (SDNS), an established regimen does not exist. The relapses tend to occur when the peripheral blood B-cell count re-arises at 3 months upon single RTX infusion. This study was conducted to clarify whether the long-term remission of SDNS can be obtained by repeated RTX administrations. Methods: RTX was administered 4 times at 3-month intervals at 375 mg/m2/time to 5 children with SDNS. The changes in the clinical indicators were analyzed. Results: The median (range) observation period was 6.3 (0.9-8.4) years before RTX and 3.2 (1.9-3.8) years following the commencement of RTX. The changes in the clinical indicators were as follows (median and range): (1) annual number of relapses: before administration 1.4 (1.1-3.5) times/year, after administration 0.0 (0.0-0.0) times/year, and (2) median steroid dosage: before administration 0.80 (0.23-0.96) mg/kg/day, after administration 0.00 (0.00-0.00) mg/kg/day. All changes were significant at p < 0.05. Relapse occurred 3 times following the start of RTX (the period to relapse was 2.2, 1.9, and 2.3 years, respectively). No serious side effects were seen. Conclusions: Repeated RTX against SDNS in children may be a useful therapeutic option.
Microbiome Composition by Pyrosequencing in Mesenteric Lymph Nodes of Rats with CCl4-Induced Cirrhosis
Authors: Cuenca Silvia , Sanchez Elisabet , Santiago Alba , El Khader Ismail , Panda Suchita , Vidal Silvia , Camilo Nieto Juan , Juárez Cándido , Sancho Francesc , Guarner Francisco , Soriano German , Guarner Carlos , Manichanh Chaysavanh
Published: December 2013

Background: The cross talk between the gut microbiota and the immune system, which is essential to maintain homeostasis, takes place at the intestinal lymphoid tissue such as the mesenteric lymph nodes (MLNs). Here, we investigated the presence of bacterial DNA in MLNs of control and cirrhotic rats and its relationship with inflammatory responses. Methods: The MLN microbiome of cirrhotic rats with ascites, which was induced by carbon tetrachloride (CCl4), was compared to that of control rats using quantitative real-time PCR and pyrosequencing of the 16S rRNA gene. Cytokines in blood samples were assessed by ELISA. Results: Unexpectedly, sequence analysis revealed a high microbial diversity in the MLNs of both control and cirrhotic rats with Proteobacteria as one of the most dominant phylum. CCl4-induced liver injury was not associated with a change in bacterial load, but it was linked to a decrease in microbial diversity (p < 0.05) and alterations in the microbial community in MLNs. A high proportion of Bifidobacterium animalis was also positively correlated with elevated interleukin-10 expression (p = 0.002, false discovery rate = 0.03, r = 0.94). Conclusions: For the first time, the high microbial diversity observed in MLNs of both controls and CCl4-induced cirrhotic rats provides evidence that bacterial translocation is more than a mere dichotomic phenomenon.
Molecular Characterization of Repetitive DNA Sequences from B Chromosome in Plantago lagopus L.
Authors: Kour G. , Kaul S. , Dhar M.K.
Published: December 2013

In Plantagolagopus the B chromosome has been reported by our laboratory to be the result of massive amplification of ribosomal DNA sequences. However, the presence of transposable elements and other repetitive DNA sequences together with rDNA could not be ruled out. The present study clearly demonstrated the presence of transposable elements in the B chromosomes. These transposable elements were characterized and their nature assessed. Physical mapping using double fluorescent in situ hybridization was performed using DNA probes for 5S and copia elements. The results clearly proved that the B chromosome is a mix of 5S, 45S rDNA and transposable elements. Based on the FISH and Fiber-FISH patterns, it can be concluded that while 45S rDNA sequences are restricted to the subtelomeric regions, the 5S rDNA sequences are interspersed with transposons in the body of the B chromosome. These results have further enhanced our understanding of the organization and evolution of B chromosomes.
Maternal Hypomethylation of KvDMR in a Monozygotic Male Twin Pair Discordant for Beckwith-Wiedemann Syndrome
Authors: Elalaoui S.C. , Garin I. , Sefiani A. , Perez de Nanclares G.
Published: December 2013

Beckwith-Wiedemann syndrome (BWS; OMIM 130650) is a heterogeneous overgrowth syndrome characterized by visceromegaly, macroglossia, tumor predisposition, and other congenital abnormalities. BWS is usually associated with abnormalities of chromosome 11p15, including (epi)genetic changes, paternal disomy and point mutations. A number of identical twin pairs, mostly female, have been reported to be clinically discordant for BWS. Studies of monozygotic twins discordant for BWS provide more information about failure in the DNA methylation maintenance machinery during very early embryonic development. Here, we report a case of monozygotic male twins discordant for BWS phenotype. Methylation analysis of the 2 imprinted domains at 11p15.5 (H19DMR and KvDMR) was performed by methylation-specific MLPA and pyrosequencing of DNA extracted from peripheral blood and buccal swabs of both twins. Hypomethylation at KvDMR was identified in both cell types of the affected twin, whereas his healthy brother presented hypomethylation only in blood cells and a normal methylation profile in buccal swab. For diagnostic purposes, it is important to remember that twins can share fetal circulation and possibly share hematopoietic stem cells early in development; therefore, the affected and unaffected twins can share an epigenotype that will resemble partial hypomethylation. If a patient is a twin, it is valuable to obtain a sample from a tissue other than blood.
Cardiorenal Metabolic Syndrome and Diabetic Cognopathy
Authors: Hayden M.R. , Banks W.A. , Shah G.N. , Gu Z. , Sowers J.R.
Published: December 2013

The prevalence of the cardiorenal metabolic syndrome (CRS) is increasing in parallel with obesity, type 2 diabetes mellitus, Alzheimer's disease, and other forms of dementia. Along with metabolic, inflammatory, and immunological abnormalities, there is maladaptive structural remodeling of the heart, kidney, and brain. The term ‘diabetic cognopathy' (DC) may be used when discussing functional and structural changes in the brain of the diabetic patient. DC likely represents an advanced form of these changes in the brain that evolve with increasing duration of the CRS and subsequent clinical diabetes. We posit that DC develops due to a convergence of aging, genetic and lifestyle abnormalities (overnutrition and lack of exercise), which result in multiple injurious metabolic and immunologic toxicities such as dysfunctional immune responses, oxidative stress, inflammation, insulin resistance, and dysglycemia (systemically and in the brain). These converging abnormalities may lead to endothelial blood-brain barrier tight junction/adherens junction (TJ/AJ) complex remodeling and microglia activation, which may result in neurodegeneration, impaired cognition, and dementia. Herein, we describe the brain ultrastructural changes evolving from a normal state to maladaptive remodeling in rodent models of CRS including microglia activation/polarization and attenuation and/or loss of the TJ/AJ complexes, pericytes and astrocytes of the neurovascular unit. Further, we discuss the potential relationship between these structural changes and the development of DC, potential therapeutic strategies, and future directions.
Coincidence of Varicella-Zoster Virus Anterior Uveitis in a Patient with Chandler's Syndrome
Authors: Joko Takeshi , Suzuki Takashi , Inoue Tomoyuki , Kikuchi Masaaki , Hara Yuko , Shiraishi Atsushi , Ohashi Yuichi
Published: December 2013

Purpose: We report a patient who, based on the clinical manifestations, was originally diagnosed as having Chandler's syndrome and later developed varicella-zoster virus (VZV) DNA-positive anterior uveitis. Methods: The patient with Chandler's syndrome who manifested anterior uveitis underwent a complete ophthalmologic examination. Polymerase chain reaction (PCR) was used to amplify the viral DNA in the aqueous humor to determine the cause of the intraocular inflammation. Results: Slit-lamp biomicroscopy showed focal iris atrophy and peripheral anterior synechiae (PAS); specular microscopy of the corneal endothelium disclosed the hammered-silver appearance. Based on these clinical findings, we diagnosed this patient as having Chandler's syndrome. During the follow-up period, however, the inflammatory cells suddenly appeared in the anterior chamber with formation of keratic precipitates and an increased intraocular pressure (IOP). VZV DNA was displayed in the aqueous humor by PCR. Based upon the diagnosis of VZV anterior uveitis, corticosteroids and acyclovir were given topically and systemically. The inflammation subsided with these medications; however, trabeculectomy was finally needed to control the IOP due to PAS progression. Conclusion: The coincidence of VZV anterior uveitis with Chandler's syndrome may constitute an implication for the possible viral etiology of iridocorneal endothelial syndrome.
A new species of Campomanesia (Myrtaceae) from Bahia, Brazil, and its relationships with the C. xanthocarpa complex
Authors: Oliveira Marla Ibrahim Uehbe , Landrum Leslie Roger , Oliveira Reyjane Patrícia , Funch Ligia Silveira
Published: December 2013

Results of studies with multiple approaches involving a species complex which includes Campomanesia xanthocarpa (Myrtaceae) indicate that specimens collected in Morro do Chapéu, the northern region of the Chapada Diamantina, Bahia, are distinct from those distributed farther south in Brazil. A description, comments, distribution map and an illustration of the new species, C. costata, are provided herein.
A contribution to Centaurea sect. Acrocentron (Asteraceae) from Iran
Authors: RANJBAR MASSOUD , NEGARESH KAZEM
Published: December 2013

Centaurea sanandajensis is described and illustrated as a new species from Kurdestan Province, W Iran. The characters that distinguish the new species from its nearest relative C. longipedunculata are given. In addition, C. elegantissima is reported as new to Iran, and its chromosome number (2n = 2x = 22) is counted for the first time. The description of C. elegantissima is completed with the characters of mature achenes, and its differences from the nearest relative C. kandavanensis are summarized. The geographical distribution of discussed species is presented.
Leprose and leproid lichens of the Galapagos, with a particular focus on Lepraria (Stereocaulaceae) and Septotrapelia (Pilocarpaceae)
Authors: Bungartz Frank , Hillmann Georg , Kalb Klaus , Elix John A.
Published: December 2013

As part of an ongoing species inventory for the Galapagos Archipelago, sterile leprose and leproid lichens have been revised. Differences between leprose vs. leproid growth forms are discussed in the light of significant recent advances in the taxonomy of Lepraria. Five species have a strictly leprose morphology: Lepraria achariana, L. aff. incana, L. finkii, and L. vouauxii (all new to Galapagos), and L. lendemeri sp. nov. A sixth species, L. tenella, forms minutely fruticose thalli, but its recent transfer from Leprocaulon into Lepraria confirms its close affinity to species with similar chemistry such as L. vouauxii. Even though L. vouauxii does not develop pseudopodetia, it forms thalli that closely resemble immature specimens of L. tenella. Fertile material of a seventh species, “Lepraria” usnica, also new to Galapagos, confirms that this species does indeed belong in the Pilocarpaceae as molecular studies previously indicated. Its apothecia are identical to those of a Septotrapelia. Consequently, the recently described genus Nelsenium is reduced to synonymy and the new combination Septotrapelia usnica proposed. Many other sterile lichens occur in Galapagos and several have a very similar, leproid or even leprose morphology. A key for all those taxa is presented, emphasizing their inconspicuous, though distinct morphological differences.
Correlating Storm Surge Heights with Tropical Cyclone Winds at and before Landfall
Authors: Needham Hal F. , Keim Barry D.
Published: December 2013

This paper investigates relationships between storm surge heights and tropical cyclone wind speeds at 3-h increments preceding landfall. A unique dataset containing hourly tropical cyclone position and wind speed is used in conjunction with a comprehensive storm surge dataset that provides maximum water levels for 189 surge events along the U.S. Gulf Coast from 1880 to 2011. A landfall/surge classification was developed for analyzing the relationship between surge magnitudes and prelandfall winds. Ten of the landfall/surge event types provided useable data, producing 117 wind–surge events that were incorporated into this study. Statistical analysis indicates that storm surge heights correlate better with prelandfall tropical cyclone winds than with wind speeds at landfall. Wind speeds 18 h before landfall correlated best with surge heights. Raising wind speeds to exponential powers produced the best wind–surge fit. Higher wind–surge correlations were found when testing a more recent sample of data that contained 63 wind–surge events since 1960. The highest correlation for these data was found when wind speeds 18 h before landfall were raised to a power of 2.2, which provided R2 values that approached 0.70. The R2 values at landfall for these same data were only 0.44. Such results will be useful to storm surge modelers, coastal scientists, and emergency management personnel, especially when tropical cyclones rapidly strengthen or weaken while approaching the coast.
An Empirical Analysis on the Relationship between Tropical Cyclone Size and Storm Surge Heights along the U.S. Gulf Coast
Authors: Needham Hal F. , Keim Barry D.
Published: December 2013

In the past decade, several large tropical cyclones have generated catastrophic storm surges along the U.S. Gulf and Atlantic Coasts. These storms include Hurricanes Katrina, Ike, Isaac, and Sandy. This study uses empirical analysis of tropical cyclone data and maximum storm surge observations to investigate the role of tropical cyclone size in storm surge generation. Storm surge data are provided by the Storm Surge Database (SURGEDAT), a global storm surge database, while a unique tropical cyclone size dataset built from nine different data sources provides the size of the radius of maximum winds (Rmax) and the radii of 63 (34 kt), 93 (50 kt), and 119 km h−1 (64 kt) winds. Statistical analysis reveals an inverse correlation between storm surge magnitudes and Rmax sizes, while positive correlations exist between storm surge heights and the radius of 63 (34 kt), 93 (50 kt), and 119 km h−1 (64 kt) winds. Storm surge heights correlate best with the prelandfall radius of 93 km h−1 (50 kt) winds, with a Spearman correlation coefficient value of 0.82, significant at the 99.9% confidence level. Many historical examples support these statistical results. For example, the 1900 Galveston hurricane, the 1935 Labor Day hurricane, and Hurricane Camille all had small Rmax sizes but generated catastrophic surges. Hurricane Katrina provides an example of the importance of large wind fields, as hurricane-force winds extending 167 km [90 nautical miles (n mi)] from the center of circulation enabled this large storm to generate a higher storm surge level than Hurricane Camille along the same stretch of coast, even though Camille’s prelandfall winds were slightly stronger than Katrina’s. These results may be useful to the storm surge modeling community, as well as disaster science and emergency management professionals, who will benefit from better understanding the role of tropical cyclone size for storm surge generation.
The Atmospheric General Circulation in Thermodynamical Coordinates
Authors: Kjellsson Joakim , Döös Kristofer , Laliberté Frédéric B. , Zika Jan D.
Published: December 2013

The zonal and meridional components of the atmospheric general circulation are used to define a global thermodynamic streamfunction in dry static energy versus latent heat coordinates. Diabatic motions in the tropical circulations and fluxes driven by midlatitude eddies are found to form a single, global thermodynamic cycle. Calculations based on the Interim European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-Interim) dataset indicate that the cycle has a peak transport of 428 Sv (Sv ≡ 109 kg s−1). The thermodynamic cycle encapsulates a globally interconnected heat and water cycle comprising ascent of moist air where latent heat is converted into dry static energy, radiative cooling where dry air loses dry static energy, and a moistening branch where air is warmed and moistened. It approximately follows a tropical moist adiabat and is bounded by the Clausius–Clapeyron relationship for near-surface air. The variability of the atmospheric general circulation is related to ENSO events using reanalysis data from recent years (1979–2009) and historical simulations from the EC-Earth Consortium (EC-Earth) coupled climate model (1850–2005). The thermodynamic cycle in both EC-Earth and ERA-Interim widens and weakens with positive ENSO phases and narrows and strengthens during negative ENSO phases with a high correlation coefficient. Weakening in amplitude suggests a weakening of the large-scale circulation, while widening suggests an increase in mean tropical near-surface moist static energy.
The Impact of Observed Vegetation Changes on Land–Atmosphere Feedbacks During Drought
Authors: Meng X. H. , Evans J. P. , McCabe M. F.
Published: December 2013

Moderate Resolution Imaging Spectroradiometer (MODIS)-derived vegetation fraction data were used to update the boundary conditions of the advanced research Weather Research and Forecasting (WRF) Model to assess the influence of realistic vegetation cover on climate simulations in southeast Australia for the period 2000–08. Results show that modeled air temperature was improved when MODIS data were incorporated, while precipitation changes little with only a small decrease in the bias. Air temperature changes in different seasons reflect the variability of vegetation cover well, while precipitation changes have a more complicated relationship to changes in vegetation fraction. Both MODIS and climatology-based simulation experiments capture the overall precipitation changes, indicating that precipitation is dominated by the large-scale circulation, with local vegetation changes contributing variations around these.

Simulated feedbacks between vegetation fraction, soil moisture, and drought over southeast Australia were also investigated. Results indicate that vegetation fraction changes lag precipitation reductions by 6–8 months in nonarid regions. With the onset of the 2002 drought, a potential fast physical mechanism was found to play a positive role in the soil moisture–precipitation feedback, while a slow biological mechanism provides a negative feedback in the soil moisture–precipitation interaction on a longer time scale. That is, in the short term, a reduction in soil moisture leads to a reduction in the convective potential and, hence, precipitation, further reducing the soil moisture. If low levels of soil moisture persist long enough, reductions in vegetation cover and vigor occur, reducing the evapotranspiration and thus reducing the soil moisture decreases and dampening the fast physical feedback. Importantly, it was observed that these feedbacks are both space and time dependent.
The tragedy of justified war
Authors: Neu Michael
Published: December 2013

This article examines and critiques the binary structure of contemporary just war thinking. Theorists claim that the waging of war, and the committing of military acts within war, is either just or unjust. This binary distinction should be tempered by the awareness that justified wars are tragic: tragic in the broad sense of inescapably involving moral wronging, but not necessarily tragic in the narrow sense of not having been preventable by the tragic agent himself or herself. Justified war situations that fail to be tragic in the narrow sense are inauthentic. If contemporary just war theorists were to explicitly recognise the tragedy of justified war in the broad sense, as well as the dangers of lacking authenticity, their theory might become less susceptible to abuse by political moralists.