bluuebunny/crossref_metadata_2025 huggingface dataset:
Kisspeptin cell-specific PI3K signaling regulates hypothalamic kisspeptin expression and participates in the regulation of female fertility
Authors: Beymer Matthew , Negrón Ariel L. , Yu Guiqin , Wu Samuel , Mayer Christian , Lin Richard Z. , Boehm Ulrich , Acosta-Martínez Maricedes
Published: October 2014

Hypothalamic kisspeptin neurons integrate and translate cues from the internal and external environments that regulate gonadotropin-releasing hormone (GnRH) secretion and maintain fertility in mammals. However, the intracellular signaling pathways utilized to translate such information into changes in kisspeptin expression, release, and ultimately activation of the kisspeptin-receptive GnRH network have not yet been identified. PI3K is an important signaling node common to many peripheral factors known to regulate kisspeptin expression and GnRH release. We investigated whether PI3K signaling regulates hypothalamic kisspeptin expression, pubertal development, and adult fertility in mice. We generated mice with a kisspeptin cell-specific deletion of the PI3K catalytic subunits p110α and p110β (kiss-p110α/β-KO). Using in situ hybridization, we examined Kiss1 mRNA expression in gonad-intact, gonadectomized (Gdx), and Gdx + steroid-replaced mice. Kiss1 cell number in the anteroventral periventricular hypothalamus (AVPV) was significantly reduced in intact females but not in males. In contrast, compared with WT and regardless of steroid hormone status, Kiss1 cell number was lower in the arcuate (ARC) of kiss-p110α/β-KO males, but it was unaffected in females. Both intact Kiss-p110α/β-KO males and females had reduced ARC kisspeptin-immunoreactive (IR) fibers compared with WT animals. Adult kiss-p110α/β-KO males had significantly lower circulating luteinizing hormone (LH) levels, whereas pubertal development and fertility were unaffected in males. Kiss-p110α/β-KO females exhibited a reduction in fertility despite normal pubertal development, LH levels, and estrous cyclicity. Our data show that PI3K signaling is important for the regulation of hypothalamic kisspeptin expression and contributes to normal fertility in females.
Dynamic Shaping of Cellular Membranes by Phospholipids and Membrane-Deforming Proteins
Authors: Suetsugu Shiro , Kurisu Shusaku , Takenawa Tadaomi
Published: October 2014

All cellular compartments are separated from the external environment by a membrane, which consists of a lipid bilayer. Subcellular structures, including clathrin-coated pits, caveolae, filopodia, lamellipodia, podosomes, and other intracellular membrane systems, are molded into their specific submicron-scale shapes through various mechanisms. Cells construct their micro-structures on plasma membrane and execute vital functions for life, such as cell migration, cell division, endocytosis, exocytosis, and cytoskeletal regulation. The plasma membrane, rich in anionic phospholipids, utilizes the electrostatic nature of the lipids, specifically the phosphoinositides, to form interactions with cytosolic proteins. These cytosolic proteins have three modes of interaction: 1) electrostatic interaction through unstructured polycationic regions, 2) through structured phosphoinositide-specific binding domains, and 3) through structured domains that bind the membrane without specificity for particular phospholipid. Among the structured domains, there are several that have membrane-deforming activity, which is essential for the formation of concave or convex membrane curvature. These domains include the amphipathic helix, which deforms the membrane by hemi-insertion of the helix with both hydrophobic and electrostatic interactions, and/or the BAR domain superfamily, known to use their positively charged, curved structural surface to deform membranes. Below the membrane, actin filaments support the micro-structures through interactions with several BAR proteins as well as other scaffold proteins, resulting in outward and inward membrane micro-structure formation. Here, we describe the characteristics of phospholipids, and the mechanisms utilized by phosphoinositides to regulate cellular events. We then summarize the precise mechanisms underlying the construction of membrane micro-structures and their involvements in physiological and pathological processes.
Astrocyte Reactivity and Reactive Astrogliosis: Costs and Benefits
Authors: Pekny Milos , Pekna Marcela
Published: October 2014

Astrocytes are the most abundant cells in the central nervous system (CNS) that provide nutrients, recycle neurotransmitters, as well as fulfill a wide range of other homeostasis maintaining functions. During the past two decades, astrocytes emerged also as increasingly important regulators of neuronal functions including the generation of new nerve cells and structural as well as functional synapse remodeling. Reactive gliosis or reactive astrogliosis is a term coined for the morphological and functional changes seen in astroglial cells/astrocytes responding to CNS injury and other neurological diseases. Whereas this defensive reaction of astrocytes is conceivably aimed at handling the acute stress, limiting tissue damage, and restoring homeostasis, it may also inhibit adaptive neural plasticity mechanisms underlying recovery of function. Understanding the multifaceted roles of astrocytes in the healthy and diseased CNS will undoubtedly contribute to the development of treatment strategies that will, in a context-dependent manner and at appropriate time points, modulate reactive astrogliosis to promote brain repair and reduce the neurological impairment.
Hip Resurfacing Arthroplasty and Perioperative Blood Testing
Authors: Cook Andrew , Cook Steven , Smith Ian , Weinrauch Patrick
Published: October 2014

It is standard practice in many institutions to routinely perform preoperative and postoperative haemoglobin level testing in association with hip joint arthroplasty procedures. It is our observation, however, that blood transfusion after uncomplicated primary hip arthroplasty in healthy patients is uncommon and that the decision to proceed with blood transfusion is typically made on clinical grounds. We therefore question the necessity and clinical value of routine perioperative blood testing about the time of hip resurfacing arthroplasty. We present analysis of perioperative blood tests and transfusion rates in 107 patients undertaking unilateral hybrid hip resurfacing arthroplasty by the senior author at a single institution over a three-year period. We conclude that routine perioperative testing of haemoglobin levels for hip resurfacing arthroplasty procedures does not assist in clinical management. We recommend that postoperative blood testing only be considered should the patient demonstrate clinical signs of symptomatic anaemia or if particular clinical circumstances necessitate.
Are Attributes of Pregnancy and the Delivery Room Experience Related to Development of Autism? A Review of the Perinatal and Labor Risk Factors and Autism
Authors: Dhawan Naveen , Emerson Blaze , Popara Romana , Lin Catherine , Rawji Adam , Zeiden Rita , Rashid Leeda , Phyu Pwint , Bahl Jaya , Gupta Vineet
Published: October 2014

Autism is a neurodevelopmental disorder marked by severe deficits in social communication and interactions. It is a complex condition that lacks an established preventive method, warranting a need for research to identify possible environmental triggers. The identification of external factors particularly perinatal risk factors forms the initial critical step in preventing and alleviating risks. We conducted a literature review to assess evidence suggested in the worldwide literature. Perinatal risk factors that have a suggested association include β2 adrenergic receptor agonists, labor induction and augmentation, maternal infection and disease (i.e., antiphospholipid syndrome), antiepileptic drugs, cocaine use, and oral supplements. Smoking has not been found to have a direct association. Pollutants, selective serotonin reuptake inhibitors, artificial insemination, and fertility medications may have a link, but results are often conflicted. Factors related to the delivery room experience may be associated with meconium aspiration syndrome, birth weight, and labor time. Several risk factors during the pregnancy and labor periods have been associated with autism; yet further studies with large populations are needed to establish definitive associations. The fact that several risk factors during the prenatal and labor periods are implicated in autism should prompt the medical community to focus on the pregnancy and labor periods as preventive measures to curb the incidence of autism.
Immediate Free Jejunum Transfer for Salvage Surgery of Gastric Tube Necrosis
Authors: Umezawa Hiroki , Matsutani Takeshi , Ogawa Rei , Hyakusoku Hiko
Published: October 2014

Gastric tube necrosis after esophagus cancer surgery is a rare but critical situation. Salvage reconstruction of the esophagus remains a challenging procedure for head and neck surgeons. Historically, surgeons have employed a two-stage salvage surgery consisting of debridement followed by reconstruction. While this procedure generates good results, the time to restart oral alimentation is long. The present report describes the case of a 62-year-old male who developed gastric tube necrosis 3 days after undergoing surgery for thoracic-cervical esophageal cancer and immediate reconstruction with the retrosternal gastric pullup technique. He was treated with debridement and simultaneous free jejunum transfer 4 days after the primary surgery. He was able to restart oral alimentation 10 days after the salvage surgery. This rapid return to oral alimentation is a major advantage of the one-stage immediate esophagus salvage reconstruction. Another advantage is the ease of the reconstructive procedure: the absence of scarring and prolonged inflammation, which are disadvantages of the two-stage procedure, meant that recipient vessel selection and anastomosis were uncomplicated. The one-step procedure may be particularly useful in cases where the inflammation is discovered early.
Vision‐Based Bicycle Detection Using Multiscale Block Local Binary Pattern
Authors: Hu Hongyu , Tao Pengfei , Gao Zhenhai , Wang Qingnian , Li Zhihui , Qu Zhaowei
Published: October 2014

Bicycle traffic has heavy proportion among all travel modes in some developing countries, which is crucial for urban traffic control and management as well as facility design. This paper proposes a real‐time multiple bicycle detection algorithm based on video. At first, an effective feature called multiscale block local binary pattern
(MBLBP) is extracted for representing the moving object, which is a well‐classified feature to distinguish between bicycles and nonbicycles; then, a cascaded bicycle classifier trained by AdaBoost algorithm is proposed, which has a good computation efficiency. Finally, the method is tested with video sequence captured from the real‐world traffic scenario. The bicycles in the test scenario are successfully detected.
Pregnancy following Radical Resection of Solid Pseudopapillary Tumor of the Pancreas
Authors: O’Brien James M. , Gussman Debra , Hagopian Ellen , Matulewicz Theodore
Published: October 2014

Solid pseudopapillary tumor of the pancreas is a rare tumor seen in predominately young women and carries a low malignant potential. We discuss a patient, who presented to our high risk clinic, with a clinical history of solid pseudopapillary tumor of the pancreas, predating her pregnancy. The patient had undergone previous surgery and imaging which had excluded recurrence of disease; however, increased attention was paid to the patient during her pregnancy secondary to elevated hormonal levels of progesterone, which any residual disease would have a heightened sensitivity to. In cases of pregnant patients with a history of pancreatic tumors, a multidisciplinary approach with maternal fetal medicine, medicine, and general surgery is appropriate and can result in a healthy mother and healthy term infant.
Comparative Analysis ofSorghum bicolorProteome in Response to Drought Stress and following Recovery
Authors: Jedmowski Christoph , Ashoub Ahmed , Beckhaus Tobias , Berberich Thomas , Karas Michael , Brüggemann Wolfgang
Published: October 2014

The adaptive response ofSorghum bicolorlandraces from Egypt to drought stress and following recovery was analyzed using two-dimensional difference gel electrophoresis, 2D-DIGE. Physiological measurements and proteome alterations of accession number 11434, drought tolerant, and accession number 11431, drought sensitive, were compared to their relative control values after drought stress and following recovery. Differentially expressed proteins were analysed by Matrix assisted laser desorption ionisation time-of-flight mass spectrometry, MALDI-TOF-MS. Alterations in protein contents related to the energy balance, metabolism (sensuMewes et al. 1997), and chaperons were the most apparent features to elucidate the differences between the drought tolerant and sensitive accessions. Further alterations in the levels of proteins related to transcription and protein synthesis are discussed.
A Clinical Prediction Formula for Apnea-Hypopnea Index
Authors: Sahin Mustafa , Bilgen Cem , Tasbakan M. Sezai , Midilli Rasit , Basoglu Ozen K.
Published: October 2014

Objectives. There are many studies regarding unnecessary polysomnography (PSG) when obstructive sleep apnea syndrome (OSAS) is suspected. In order to reduce unnecessary PSG, this study aims to predict the apnea-hypopnea index (AHI) via simple clinical data for patients who complain of OSAS symptoms.Method. Demographic, anthropometric, physical examination and laboratory data of a total of 390 patients (290 men, average age 50 ± 11) who were subject to diagnostic PSG were obtained and evaluated retrospectively. The relationship between these data and the PSG results was analyzed. A multivariate linear regression analysis was performed step by step to identify independent AHI predictors.Results. Useful parameters were found in this analysis in terms of body mass index (BMI), waist circumference (WC), neck circumference (NC), oxygen saturation measured by pulse oximetry (SpO2), and tonsil size (TS) to predict the AHI. The formula derived from these parameters was the predicted AHI = (0.797 × BMI) + (2.286 × NC) − (1.272 × SpO2) + (5.114 × TS) + (0.314 × WC).Conclusion. This study showed a strong correlation between AHI score and indicators of obesity. This formula, in terms of predicting the AHI for patients who complain about snoring, witnessed apneas, and excessive daytime sleepiness, may be used to predict OSAS prior to PSG and prevent unnecessary PSG.
Lifetime Autism Spectrum Features in a Patient with a Psychotic Mixed Episode Who Attempted Suicide
Authors: Simoncini Marly , Miniati Mario , Vanelli Federica , Callari Antonio , Vannucchi Giulia , Mauri Mauro , Dell’Osso Liliana
Published: October 2014

We present a case report of a young man who attempted suicide during a mixed episode with psychotic symptoms. The patient’s history revealed the lifetime presence of signs and features belonging to the autism spectrum realm that had been completely overlooked. We believe that this case is representative of an important and barely researched topic: what happens to children with nondiagnosed and nontreated subthreshold forms of autism when they grow old. The issue of early recognition of autism spectrum signs and symptoms is discussed, raising questions on the diagnostic boundaries between autism and childhood onset psychotic spectrums among patients who subsequently develop a full-blown psychotic disorder.
Malaria, Typhoid Fever, and Their Coinfection among Febrile Patients at a Rural Health Center in Northwest Ethiopia: A Cross-Sectional Study
Authors: Birhanie Meseret , Tessema Belay , Ferede Getachew , Endris Mengistu , Enawgaw Bamlaku
Published: October 2014

Background.Malaria and typhoid fever are major public health problems in tropical and subtropical countries. People in endemic areas are at risk of contracting both infections concurrently.Objectives.The study was aimed at determining the prevalence and associated risk factors of malaria, typhoid, and their coinfection among febrile patients.Methods.A cross-sectional study was conducted on 200 febrile patients suspected for malaria and/or typhoid fever from April to May, 2013, at Ayinba Health Center, Northwest Ethiopia. Blood samples were collected for blood culture, Widal test, and blood film preparation. Data were analyzed using SPSS version 20 statistical software.Results.The prevalence of malaria was 36.5% (n=73). Among these 32 (43.8%), 30 (41.1%) and 11 (15.1%) were positive forP. falciparum, P. vivax,and mixed infections, respectively. The seroprevalence of typhoid fever was 38 (19%), but 1 (0.5%) with blood culture. Malaria typhoid fever coinfection was 13 (6.5%). 2–5-year-old children and poor hand washing habit were significantly associated with malaria and typhoid infection, respectively (P<0.05).Conclusions.The prevalence of malaria and typhoid fever was found high. Further studies should be done on the other determinants of malaria and typhoid fever coinfection in different seasons and different study areas.
Portraying Persons Who Inject Drugs Recently Infected with Hepatitis C Accessing Antiviral Treatment: A Cluster Analysis
Authors: Bamvita Jean-Marie , Roy Elise , Zang Geng , Jutras-Aswad Didier , Artenie Andreea Adelina , Levesque Annie , Bruneau Julie
Published: October 2014

Objectives. To empirically determine a categorization of people who inject drug (PWIDs) recently infected with hepatitis C virus (HCV), in order to identify profiles most likely associated with early HCV treatment uptake. Methods. The study population was composed of HIV-negative PWIDs with a documented recent HCV infection. Eligibility criteria included being 18 years old or over, and having injected drugs in the previous 6 months preceding the estimated date of HCV exposure. Participant classification was carried out using a TwoStep cluster analysis. Results. From September 2007 to December 2011, 76 participants were included in the study. 60 participants were eligible for HCV treatment. Twenty-one participants initiated HCV treatment. The cluster analysis yielded 4 classes: class 1: Lukewarm health seekers dismissing HCV treatment offer; class 2: multisubstance users willing to shake off the hell; class 3: PWIDs unlinked to health service use; class 4: health seeker PWIDs willing to reverse the fate. Conclusion. Profiles generated by our analysis suggest that prior health care utilization, a key element for treatment uptake, differs between older and younger PWIDs. Such profiles could inform the development of targeted strategies to improve health outcomes and reduce HCV infection among PWIDs.
Nitro Derivatives of Naturally Occurring β-Asarone and Their Anticancer Activity
Authors: Shenvi Suvarna , Diwakar Latha , Reddy G. Chandrasekara
Published: October 2014

β-Asarone (2, 4, 5-trimethoxy-(Z)-1-propenylbenzene) was obtained from Acorus calamus. Nitration of β-asarone with AgNO2/I2 in ether yielded 1-(2, 4, 5-trimethoxy phenyl)-2-nitropropene (1) but with NaNO2/I2 in ethylene glycol obtained 1-(2, 4, 5-trimethoxy phenyl)-1-nitropropene (2). Compound 2 was prepared for the first time and characterized using IR, 1H-NMR, 13C-NMR, and GC-MS spectra and it was converted into 1-(2, 4, 5-trimethoxy) phenyl-1-propanone (3) using modified Nef reaction. Based on 1D NOESY experiments, compounds 1 and 2 have been assigned E configuration. Compounds 1 and 2 were subjected to cytotoxic activity using five human cancer cell lines, namely, MCF-7, SW-982, HeLa, PC-3, and IMR-32 by MTT assay. Except in breast cancer line (MCF-7) compound 2 exhibited five- to tenfold increase in activity compared to β-asarone and twofold increase over compound 1.
Acquired Resistance to Fractionated Radiotherapy Can Be Overcome by Concurrent PD-L1 Blockade
Authors: Dovedi Simon J. , Adlard Amy L. , Lipowska-Bhalla Grazyna , McKenna Conor , Jones Sherrie , Cheadle Eleanor J. , Stratford Ian J. , Poon Edmund , Morrow Michelle , Stewart Ross , Jones Hazel , Wilkinson Robert W. , Honeychurch Jamie , Illidge Tim M.
Published: October 2014

Radiotherapy is a major part in the treatment of most common cancers, but many patients experience local recurrence with metastatic disease. In evaluating response biomarkers, we found that low doses of fractionated radiotherapy led to PD-L1 upregulation on tumor cells in a variety of syngeneic mouse models of cancer. Notably, fractionated radiotherapy delivered in combination with αPD-1 or αPD-L1 mAbs generated efficacious CD8+ T-cell responses that improved local tumor control, long-term survival, and protection against tumor rechallenge. These favorable outcomes were associated with induction of a tumor antigen–specific memory immune response. Mechanistic investigations showed that IFNγ produced by CD8+ T cells was responsible for mediating PD-L1 upregulation on tumor cells after delivery of fractionated radiotherapy. Scheduling of anti–PD-L1 mAb was important for therapeutic outcome, with concomitant but not sequential administration with fractionated radiotherapy required to improve survival. Taken together, our results reveal the mechanistic basis for an adaptive response by tumor cells that mediates resistance to fractionated radiotherapy and its treatment failure. With attention to scheduling, combination immunoradiotherapy with radiotherapy and PD-1/PD-L1 signaling blockade may offer an immediate strategy for clinical evaluation to improve treatment outcomes. Cancer Res; 74(19); 5458–68. ©2014 AACR.
Host Deficiency in Caveolin-2 Inhibits Lung Carcinoma Tumor Growth by Impairing Tumor Angiogenesis
Authors: Liu Yajun , Jang Sungchan , Xie Leike , Sowa Grzegorz
Published: October 2014

Caveolin-2 (Cav-2), a member of caveolin protein family, is largely different from better known caveolin-1 (Cav-1) and thus might play distinct functions. Here, we provide the first genetic evidence suggesting that host-expressed Cav-2 promotes subcutaneous tumor growth and tumor-induced neovascularization using two independent syngeneic mouse models. Host deficiency in Cav-2 resulted in defective and reduced growth of subcutaneously implanted Lewis lung carcinoma (LLC) and B16-F10 melanoma tumors, respectively. Consistent with the defective growth, LLC and B16-F10 melanoma tumors implanted into Cav-2 KO mice displayed reduced microvascular density (MVD) determined by IHC with anti-CD31 antibodies, suggesting impaired pathologic angiogenesis. Additional studies involving LLC tumors extracted from Cav-2 KO mice just 10 days after implantation determined reduced cell proliferation, massive necrotic cell death, and fibrosis. In contrast with day 10, only MVD but not cell proliferation and survival was reduced in the earliest palpable LLC tumors extracted 6 days after implantation into Cav-2 KO mice, suggesting that impaired angiogenesis is the causative factor. Mechanistically, impaired LLC tumor growth and angiogenesis in Cav-2 KO mice was associated with increased expression levels of antiangiogenic thrombospondin-1 and inhibited S1177 phosphorylation of endothelial nitric oxide synthase. Taken together, our data suggest that host deficiency in Cav-2 impairs tumor-induced angiogenesis, leading to compromised tumor cell survival/proliferation manifested by the defective tumor growth. In conclusion, host-expressed Cav-2 may promote tumor growth via supporting tumor-induced angiogenesis. Thus, Cav-2 expressed in tumor microenvironment may potentially become a novel target for cancer therapy. Cancer Res; 74(22); 6452–62. ©2014 AACR.
A CREB1–TGFβ2 Self-Sustaining Loop in Glioblastoma
Authors: Wotton David
Published: October 2014

Summary: A subset of glioblastomas (GBM) has high levels of TGFβ signaling, and anti-TGFβ therapies are being pursued as treatments for GBM. The work presented here identifies CREB1 as a potential biomarker for TGFβ-dependent GBM. CREB1 integrates signaling from TGFβ and the PI3K pathway and nucleates a self-sustaining signaling loop that maintains TGFβ2 expression in GBM with high CREB1 levels. Cancer Discov; 4(10); 1123–5. ©2014 AACR.

See related article by Rodón et al., p. 1230
Understanding and Targeting Alkylator Resistance in Glioblastoma
Authors: Wick Wolfgang , Platten Michael
Published: October 2014

Summary: Alkylating chemotherapy is the mainstay in the treatment of pediatric and adult glioblastoma despite primary and acquired resistance and scientific efforts to precisely define therapies for individual patients. A focus on non–MGMT-mediated temozolomide resistance for pediatric glioblastoma suggests options for new drug combinations. Cancer Discov; 4(10); 1120–2. ©2014 AACR.

See related article by Agnihotri et al., p. 1198
Hearing Preservation Outcomes with Different Cochlear Implant Electrodes: Nucleus® Hybrid™-L24 and Nucleus Freedom™ CI422
Authors: Jurawitz Marie-Charlot , Büchner Andreas , Harpel Theo , Schüssler Mark , Majdani Omid , Lesinski-Schiedat Anke , Lenarz Thomas
Published: October 2014

Objectives: In recent years, it has been possible to preserve hearing after cochlear implantation in patients with significant amounts of low-frequency residual hearing. Due to the dimensions and characteristics of the cochlear implants (CIs) Nucleus® Hybrid™-L24 and Nucleus Freedom™ CI422, both can be used to preserve residual hearing. The aim was to investigate the degree and progression of hearing preservation over a longitudinal postoperative period in a large consecutive cohort of implanted patients with preoperative residual hearing who received either the Nucleus Hybrid-L24 or the Nucleus Freedom CI422 implant. The intention was to examine potential characteristics and triggers of resulting postoperative hearing loss which may support a differentiation of CI candidacy criteria for a certain implant type. Methods: A retrospective data analysis of patient files on consecutively implanted subjects presenting with a severe-to-profound sensorineural hearing loss at frequencies >1,500 Hz and substantial residual hearing at frequencies ≤1,500 Hz, implanted with a Nucleus Hybrid-L24 (n = 97) or a CI422 implant (n = 100), was undertaken. A single-subject repeated-measure design comparing the mean threshold shift for pure-tone thresholds under headphones up to 24 months after implantation was used. Results: Hearing preservation is observed in the majority of subjects with either implant (250-1,500 Hz frequency range). Hybrid-L24 patients exhibited a median hearing loss of 10 dB at initial fitting (n = 97) and of 15 dB after 24 months (n = 51). A 14.4-dB decrease in median hearing loss at initial fitting (n = 100) and a 30-dB decrease after 24 months (n = 28) was observed with the CI422 electrode. At initial fitting, 54.6% of the Hybrid-L24 (n = 97) and 49.0% of the CI422 (n = 100) subjects showed a mean threshold shift <15 dB. After 24 months, 58.8% (Hybrid-L24, n = 51) and 28.6% (CI422, n = 28) of the patients showed a mean threshold shift <15 dB. Conclusions: The results indicate that residual hearing was preserved for the majority of implanted patients with the Hybrid-L24 and the CI422 implant. Patients implanted with the Hybrid-L24 implant demonstrate greater stability and less median hearing loss over time than those with the CI422 implant. Assessments of onset and stability of hearing loss prior to implantation are important factors to consider during candidacy evaluation for electrode selection to potentially maximize the performance outcome for each patient.
Erfolge und Grenzen zielgerichteter Therapien beim Nierenzellkarzinom
Authors: Pracht Marc , Berthold Dominik
Published: October 2014

Bis vor Kurzem war die Standardtherapie beim metastasierenden Nierenzellkarzinom (RCC) eine unspezifische Immuntherapie mit Interleukin-2 oder Interferon-α. Hiermit assoziiert waren ein bescheidener lebensverlängernder Effekt und eine erhebliche klinische Toxizität. Die Erforschung zahlreicher molekularer Signalwege beim RCC, darunter HIF, VEGF und mTOR, und die sequenzielle Anwendung mehrerer zielgerichteter Therapieansätze seit Anfang 2005 haben die Behandlungserfolge bei Patienten mit metastasierendem RCC signifikant verbessert und das Gesamtüberleben auf mehr als 2 Jahre verlängert. Derzeit sind mindestens 7 zielgerichtete Wirkstoffe für die Erst- und Zweitlinientherapie des klarzelligen metastasierenden RCC zugelassen. Ein langfristiger Nutzen und ein längeres Überleben lassen sich möglicherweise durch die optimale Anwendung zielgerichteter Therapien erzielen, das heißt, durch optimale Dosierung, Beherrschung unerwünschter Ereignisse, Behandlungsdauer und Compliance. Fortschritte bei der Identifizierung prognostischer Faktoren unterstreichen das Potenzial einer personalisierten Therapie für Patienten mit metastasierendem RCC. Daten zur besten Abfolge von zielgerichteten Therapien, zu prädiktiven Biomarkern, zum optimalen Zeitpunkt für einen chirurgischen Eingriff, zu Patienten-Risikoprofilen, zu den Hintergründen der Resistenzentwicklung und zur Sicherheit von zielgerichteten Therapien liegen in zunehmendem Umfang vor und werden weitere Fortschritte im Management des fortgeschrittenen RCC ermöglichen. Parallel dazu ist eine neue Klasse von Therapeutika zur Behandlung des RCC im Kommen: Immuntherapien, insbesondere Antikörper zur Checkpoint-Inhibition, zeigen äußerst vielversprechende Ergebnisse.
Nutzen einer Zweitmeinung bei Bronchialkarzinom: Keine Nierenmetastase, sondern eine synchrone renale Primärneoplasie
Authors: ter Avest Marleen J. , Schook Romane M. , Koudstaal Lyan G. , Grünberg Katrien , Paul Marinus A. , Smit Egbert F. , Postmus Pieter E.
Published: October 2014

Hintergrund: Wenn bei vorliegendem Lungentumor mittels Bildgebung eine Raumforderung in der Niere entdeckt wird, lässt das ein metastasiertes nichtkleinzelliges Bronchialkarzinom vermuten, kann aber auch eine andere Ursache haben.Vorstellung des Falls: Wir beschreiben den Fall einer Patientin, bei der eine Nierenmetastase und, darauf basierend, ein Stadium-IV-Bronchialkarzinom diagnostiziert worden waren. Um zu einer Zweitmeinung zu gelangen, wurden die histopathologischen Daten überprüft und zusätzliche bildgebende Untersuchungen durchgeführt, gefolgt von einer Lungenoperation und einer Kryoablation der Nierenläsion. Hierbei stellte sich heraus, dass die beiden Tumoren unterschiedlichen Ursprungs waren; einerseits handelte es sich um ein nichtkleinzelliges Bronchialkarzinom, andererseits um ein Nierenzellkarzinom.Diskussion: Wenn im CT-Scan eines Patienten mit Bronchialkarzinom eine Raumforderung in der Niere zu sehen ist, bedeutet das nicht zwingend eine Metastasierung. Die Diagnose muss unbedingt durch eine Gewebeprobe gesichert werden, insbesondere wenn ein synchroner Primärtumor möglich ist.
Virtual Bronchoscopic Navigation for Peripheral Pulmonary Lesions
Authors: Asano Fumihiro , Eberhardt Ralf , Herth Felix J.F.
Published: October 2014

Virtual bronchoscopic navigation (VBN) is a method in which the bronchoscope is guided on the bronchial route to a peripheral lesion using virtual bronchoscopic images. In reports on VBN for peripheral pulmonary lesions searched in PubMed as of November 2013, the diagnostic yield by ultrathin bronchoscopy in combination with computed tomography and VBN was within the range of 65.4-81.6%. Using endobronchial ultrasonography with a guide sheath (EBUS-GS) and VBN, it was between 63.3 and 84.4%, and using X-ray fluoroscopy and VBN, it was between 62.5 and 78.7%. The overall diagnostic yield was 73.8% [95% confidence interval (CI) 70.9-76.8%] and that for lesions ≤2 cm was 67.4% (95% CI 63.3-71.5%). These values indicate high diagnostic rates. In randomized comparative trials, the combination of VBN with EBUS-GS improved the diagnostic yield and shortened the examination time. The diagnostic yields for lesions in the right upper lobe, those invisible on posterior-anterior radiographs and those located in the peripheral third of the lung field were improved by VBN on ultrathin bronchoscopy in combination with X-ray fluoroscopy. The usefulness of VBN was also found on meta-analysis. Taken together, VBN is a promising navigational bronchoscopy method as it requires no specific training, has a low overall complication rate of 1.0% (95% CI 0.2-1.8%) and does not directly induce or cause severe complications. To maximize the full potential of VBN and promote its use, investigation of cases in which it is useful, determination of the optimum combination of procedures, a cost/benefit analysis and advancement of the VBN system are warranted.
Intravitreal Injection of Bevacizumab for Retinopathy of Prematurity in an Infant with Peters Anomaly
Authors: Minami Tsuyoshi , Kuniyoshi Kazuki , Kusaka Shunji , Sugioka Koji , Sakuramoto Hiroyuki , Sakamoto Masuo , Izu Akane , Wada Norihisa , Shimomura Yoshikazu
Published: October 2014

Purpose: To report our findings in an infant with Peters anomaly type II whose retinopathy of prematurity (ROP) was treated with an anti-VEGF agent and surgeries. Case Report: A male infant weighing 548 g was born prematurely at 23 weeks and 1 day with corneal opacity and shallow anterior chambers in both eyes. At the postmenstrual age of 35 weeks and 3 days, the infant was tentatively diagnosed with stage 3 ROP because of a dilated tunica vasculosa lentis and ultrasonographic findings. The boy was treated with bilateral intravitreal injections of bevacizumab (IVB) because laser photocoagulation of the retina could not be performed due to the corneal opacity. The retina in the right eye detached 3 times, namely 5 days, 16 days, and 7 months after the IVB; encircling the scleral buckle and a vitrectomy with endolaser photocoagulation were therefore required. In his left eye, the retina was reattached after the initial IVB, and no additional treatment was required. ROP was not reactivated in both eyes until the last examination at the age of 2 years and 6 months. Conclusions: Our results showed that IVB is a useful treatment for ROP in patients with Peters anomaly. However, a retinal detachment can be a complication after IVB. The optimal timing of IVB for ROP in infants with hazy media needs to be determined.
Breastfeeding Shows a Protective Trend toward Adolescents with Higher Abdominal Adiposity
Authors: Rousseaux Julien , Duhamel Alain , Turck Dominique , Molnar Denes , Salleron Julia , Artero Enrique Garcia , De Henauw Stefaan , Dietrich Sabine , Manios Yannis , Piccinelli Raffaela , Sjöström Michael , Moreno Luis Aznar , Gottrand Frédéric
Published: October 2014

Objective: The question of whether breastfeeding has a protective effect against the development of overweight or obesity later in life remains controversial, especially during adolescence. The objective was to assess the relationship between breastfeeding and adolescents' body composition. Methods: The HELENA study is a cross-sectional study involving 3,528 adolescents from 10 European cities. The outcome measures were body weight and height, subscapular skinfolds as well as waist circumferences. Breastfeeding, smoking status, and parental socioeconomic status were assessed by self-administered questionnaires. Dietary intake was recorded using two 24-hour recall surveys. Two adjustment approaches were used: i) covariance analysis adjusted for confounding factors (propensity score adjustment) and ii) multivariate quantile regression. Results: After adjustment, no significant associations were observed between breastfeeding and body composition parameters (BMI Z-score; sum of skinfolds; waist-to-height ratio). An adjusted quantile regression analysis showed a non-significant trend for a protective effect of breastfeeding toward the highest percentiles of adiposity in boys but not in girls. This is of particular interest with respect to the superiority of the waist-to-height ratio over waist circumference and BMI for detecting cardiometabolic risk factors. Conclusion: This first European study, including a large set of factors influencing adolescents' body composition, showed a non-significant trend toward a protective effect of breastfeeding on highest percentiles of adolescent's abdominal adiposity.
Impact of Aortic Annulus Size on Valve Hemodynamics and Clinical Outcomes After Transcatheter and Surgical Aortic Valve Replacement
Authors: Rodés-Cabau Josep , Pibarot Philippe , Suri Rakesh M. , Kodali Susheel , Thourani Vinod H. , Szeto Wilson Y. , Svensson Lars G. , Dumont Eric , Xu Ke , Hahn Rebecca T. , Leon Martin B.
Published: October 2014

Background—

The objective was to evaluate the effects of aortic annulus size on valve hemodynamics and clinical outcomes in those patients included in the Placement of Aortic Transcatheter Valves (PARTNER) randomized controlled trial cohort A and the nonrandomized continued access cohort.

Methods and Results—

Patients included the randomized controlled trial (n=574) and nonrandomized continued access (n=1358) cohorts were divided in tertiles according to aortic annulus diameter (small aortic annulus tertile, medium aortic annulus tertile, and large aortic annulus tertile [LAA], respectively) as measured by transthoracic echocardiography. Severe prosthesis–patient mismatch was defined as an effective aortic orifice area of <0.65 cm
2
/m
2
. In the randomized controlled trial cohort, patients in the small aortic annulus tertile who underwent transcatheter aortic valve replacement had a lower incidence of severe prosthesis–patient mismatch (19.7% versus 37.5%;
P
=0.03) and only a trend toward a higher incidence of moderate-to-severe paravalvular leaks compared with surgical aortic valve replacement (5.7% versus 0%;
P
=0.06). In the LAA tertile, there were no differences in the rate of prosthesis–patient mismatch between groups, and a significant increase in moderate-to-severe paravalvular leaks was associated with transcatheter aortic valve replacement (9% versus 0%;
P
=0.01). There were no differences in mortality between transcatheter aortic valve replacement and surgical aortic valve replacement. In the nonrandomized continued access cohort, there were no differences in prosthesis–patient mismatch between the small aortic annulus and LAA tertiles, but a higher rate of moderate-to-severe paravalvular leaks was observed in the LAA tertile (5.9% versus 11.5%;
P
=0.009). Patients in the LAA tertile had a higher mortality rate at 1-year follow-up (
P
=0.02), and differences persisted in multivariable analysis (
P
=0.048 for LAA versus medium aortic annulus tertile,
P
=0.035 for LAA versus small aortic annulus tertile).

Conclusions—

Aortic annulus size had a major impact on valve hemodynamics and clinical outcomes after transcatheter aortic valve replacement and surgical aortic valve replacement. This study highlights the importance of considering aortic annulus size in the evaluation of high-risk patients who are candidates for aortic valve replacement.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00530894.
β-Blockers and Cardiovascular Events in Patients With and Without Myocardial Infarction
Authors: Bangalore Sripal , Bhatt Deepak L. , Steg Ph. Gabriel , Weber Michael A. , Boden William E. , Hamm Christian W. , Montalescot Gilles , Hsu Amy , Fox Keith A.A. , Lincoff A. Michael
Published: October 2014

Background—

The long-term efficacy of β-blockers in patients with and without myocardial infarction (MI) is controversial.

Methods and Results—

This is post hoc analysis from the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial of 4772 patients with prior MI, 7804 patients with known atherothrombosis, and 2101 patients with risk factors alone but without heart failure. Primary outcome was a composite of nonfatal MI, stroke, or cardiovascular mortality. The cohorts were divided into 2 groups based on baseline β-blocker use. In the propensity score–matched prior MI cohort, after 28 months of follow-up, β-blocker use was associated with a 31% lower risk of the primary outcome (70 [7.1%] versus 100 [10.2%]; hazards ratio, 0.69; 95% confidence interval, 0.50–0.94;
P
=0.021), driven by a lower risk of recurrent MI (33 [3.4%] versus 48 [4.9%]; hazards ratio, 0.62; 95% confidence interval, 0.39–1.00;
P
=0.049) with no difference in mortality (52 [5.3%] versus 66 [6.7%];
P
=0.20). In the known atherothrombotic disease and the risk factors alone cohorts, β-blocker use was not associated with lower ischemic outcomes, whereas a trend toward a higher risk of stroke (3.5% versus 1.5%; hazards ratio, 2.13; 95% confidence interval, 0.92–4.92;
P
=0.079) was observed in the risk factors alone cohort. This higher stroke risk was significant in the regression model adjusted to the propensity score (hazards ratio, 2.69; 95% confidence interval, 1.33–5.44;
P
=0.006) and in the multivariable models.

Conclusions—

β-blocker use in patients with prior MI but no heart failure was associated with a lower composite cardiovascular outcome driven by lower risk of recurrent MI with no difference in mortality. However, β-blocker use was not associated with lower cardiovascular events in those without MI, with a suggestion of inferior outcome with regard to stroke risk.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00050817.
Book review: Utilitarianism and the Art School in Nineteenth-Century Britain, written by Malcolm Quinn
Authors: Beech Dave
Published: October 2014

Malcolm Quinn’s book,Utilitarianism and the Art School in Nineteenth-Century Britain, is an historical study of the birth pangs of the state-funded art school that interrogates the politics of art’s reproduction within the context of Victorian reformism in which the art school was proposed as a mechanism to improve the standards of taste of manufacturers and factory workers, as well as of artists, designers, art teachers and others. The review locates the political and cultural transition from the academy to the art school as the construction of a specifically bourgeois institution of art.
Morphometric and karyological study of Genista sericea (Cytiseae-Fabaceae)
Authors: Conti Fabio , Bernardo Liliana , Velari Tiziana Cusma , Kosovel Vera , Chiapella Laura Feoli
Published: October 2014

A morphometric and karyological study of several populations of Genista sericea, a northern Illyrian amphiadriatic species, with a disjunct distributional area centered on Pollino Massif (southern Italy), has been undertaken, based on herbarium specimens and field research. Morphometric analysis allowed to individuate three distinct groups of populations which are here attributed to three taxa at subspecific level. One of them is here newly described: G. sericea subsp. pollinensis, endemic to northern Calabria in Pollino and neighbouring areas of Basilicata. The taxonomic status of G. sericea var. rigida was re-evaluated and a name of a new rank is proposed: G. sericea subsp. rigida (occurring in southern Illyria), while subsp. sericea is a southeastern Alpine northern Illyrian taxon. The names G. sericea and G. sericea var. rigida are lectotypified. Karyologically, all the taxa are characterized by the same somatic number 2n = 48, sometimes with B chromosomes (up to four).
Discovery of substantial Oxalis (Oxalidaceae) diversity and endemism in an arid biodiversity hotspot
Authors: Oberlander Kenneth Carl , Roets Francois , Dreyer Leanne Laurette
Published: October 2014

Despite globally acknowledged diversity levels, the flora of the arid Richtersveld of South Africa remains poorly known for certain plant lineages, including the eudicot genus Oxalis. Cryptic habit, inaccessible and harsh terrain and the lack of focussed systematic attention has led to the assumption that the region is depauperate in this genus. However, recent exploration proved quite the opposite and revealed a wealth of Oxalis species, including at least ten undescribed species and many significant range extensions of known taxa. We are in the process of describing these new species, but an overarching work, placing the abundant new knowledge in the context of southern African Oxalis, is necessary. In this study we revise the state of knowledge regarding Richtersveld Oxalis and provide brief descriptions, diagnostic characters and a morphological identification key for the 20 species confirmed to occur in the region. Nine of the ten new species are currently only known from the Richtersveld, with seven having extremely limited known distributions. Surprisingly, levels of endemism in the Richtersveld are higher than the relatively well-explored central Namaqualand Oxalis flora, and suggest that, far from being depauperate in Oxalis, the Richtersveld region should be considered a centre of endemism for the genus in southern Africa.
Overview of Xanthoparmelia taxa from South Korea including the description of two new species (Parmeliaceae, Ascomycota)
Authors: Jayalal Udeni , Divakar Pradeep K , Joshi Santosh , Oh Soon Ok , Kim Jung A , Hur Jae-Seoun
Published: October 2014

In the genus Xanthoparmelia, species boundaries are based on morphological and chemical features such as the presence and/or absence of secondary metabolites, diagnostic reproductive structures, isidia morphology, and color of lower surface. Two new species of Xanthoparmelia are described from South Korea, X. kolriana with cylindrical isidia containing atranorin and salazinic acid as major components in the medulla together with cortical usnic acid, while X. volcanicola is characterised by a red coloured medulla, and subglobose isidia. The characteristics of Xanthoparmelia species and their distribution in South Korea are outlined and an identification key given. Additionally, we used ITS ribosomal DNA sequences to assess the monophyly of Xanthoparmelia species from South Korea. Our results reveal that traditionally circumscribed species were not recovered as monophyletic clades. Further, we here show that ITS is insufficient to estimate a well-supported phylogenetic hypothesis, but suggests that traditional taxonomy may not reflect natural groups. This communication provides an important framework for future studies assessing species boundaries in Xanthoparmelia species in South Korea.
Evolution of cyme architecture in Celastraceae
Authors: Li Jin-Yu , Li Yan-Nan , Tu Qiang , Zhang Zhi-Xiang
Published: October 2014

Celastraceae are characterized by a cymose pattern of inflorescence ramification. Under this basic pattern, many inflorescence forms have been described within the family, e.g., dichasium, monochasium, pleiochasium, botryoid, thyrsoid, fascicle. Thus, the question has arisen—how have these varieties evolved or transformed from one to another? Through morphogenetic observations using paraffin sections, scanning electron microscopy (SEM), and stereomicroscopy, we studied the architecture and developmental processes of the inflorescences of five species of Celastrus and Euonymus. We found in C. orbiculatus that the reduction of subtending leaves of the axillary dichasia on a developing flowering shoot made it become a terminal thyrsoid. A dichasium in the leaf axil as commonly seen in Euonymus is the most frequent type of inflorescence in Celastraceae. An analysis of character evolution suggested that a dichasium is the ancestral state for Celastraceae. Therefore, within Celeastaceae, an axillary dichasium may be the basic type or unit of inflorescences. Transitions from dichasium to thrysoid and other types of cymes, and even to solitary flowers might have occurred repeatedly in the family, probably a phenomenon of evolutionary convergence due to changing environmental conditions. The present study provided helpful information for understanding the evolution of the cymose type of inflorescence in flowering plants.
Review of amphipods of the Melita group (Amphipoda: Melitidae) from the coastal waters of Sakhalin Island (Far East of Russia). II. Genera Quasimelita Jarrett & Bousfield, 1996 and Melitoides Gurjanova, 1934
Authors: LABAY VJACHESLAV S.
Published: October 2014

Based on new material, three new species of the genus Quasimelita are described: Q. tolyza sp. nov., Q. jarettii sp. nov. and Q. serraticoxae sp. nov. from northern shelf of Sakhalin Island and contiguous area. The new species of the genus Melitoides, M. kawaii sp. nov. is described from north-east shelf of Sakhalin Island. Keys to the world species of genera Quasimelita and Melitoides are provided. Cladistic analysis of morphological relationships within genera Quasimelita and Melitoides are implemented.