Retroperitoneal follicular dendritic cell sarcoma in a young woman: Diagnosis and treatment challenges

Publication date: Available online 6 January 2018
Source:Current Problems in Cancer
Author(s): Rym Bouriga, Nihed Abdessaied, Makram Hochlef, Najoua Mallat, Mohamed Mahjoub, Badereddine Sriha, Slim Ben Ahmed
IntroductionFollicular dendritic cell sarcoma (FDCS) is an uncommon tumor that usually arises in lymph nodes, especially in the cervical, mediastinal, or axillary areas, but rarely in extranodal sites. Few cases have been reported in English literature so far. The scarcity may be partially due to under-recognition of this entity. Through this case report we analyzed the difficulties of clinical and pathological diagnosis of this rare tumor with its unusual location mistaken it with gynecological cancer′s iliac lymph nodes metastases. We also discussed its systemic treatment options.Case reportA 48-year-old female presented with a loss of weight and epigastralgia. Computed tomography (CT) showed a mass of 5cm of diameter, located close to iliac vessels. Investigation for gynecologic cancers was negative and a partial tumor resection was performed. Pathological examination readdressed the diagnosis of (FDCS). Microscopically, the tumor was composed of a proliferation of spindle to ovoid cells arranged in fascicles, whorls and storiform pattern, accompanied by sprinkling of small lymphocytes. The nuclei of the tumor cells were elongated spindled or ovoid shape with vesicular chromatin and distinct small nuclei. Immunohistochemically, the tumor cells were positive for CD21, CD23 but negative for any type of cytokeratin. Even pathological diagnosis was misleading, therapeutic management was more challenging with this unusual locationparticularlyassociated with anaggressive clinical course. Two lines of chemotherapy gave different responses.ConclusionClinical and pathological diagnosis of retroperitoneal FDCS needs vigilance. Both lymphoma and sarcoma chemotherapy regimens are effective. Due to this pathology′s rareness we highlighted a lack of treatment consensus and proposed options.



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Immunotherapy for cervical cancer - can it do another lung cancer?

Publication date: Available online 6 January 2018
Source:Current Problems in Cancer
Author(s): Ramanathan Priya, Dhandapani Hemavathi, Jayakumar Hascitha, Seetharaman Abirami, Thangarajan Rajkumar
Cervical cancer, although preventable, is still the second most common cancer among women worldwide. In developing countries like India, where screening for cervical cancer is virtually absent, most women seek treatment only at advanced stages of the disease. Although standard treatment is curative in more than 90% of women during the early stages, for Stage IIIb and above this rate drops to 50% or less. Hence, novel therapeutic adjuvants are required to improve survival at advanced stages. Lung cancer has shown the way forward with the use of Immunotherapeutic interventions as standard line of treatment in advanced stages. In this review, we provide an overview of mechanisms of immune evasion, strategies that can be employed to boost the immune system in order to improve the overall survival of the patients and summarize briefly the clinical trials that have been completed or that are underway to bring therapeutic vaccines for cervical cancer to the clinics.



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Liver PD-1 Immunobiology

Publication date: Available online 6 January 2018
Source:Seminars in Oncology
Author(s): Colleen S. Curran, Elad Sharon
Disruption of liver immune tolerance allows for the development autoimmune hepatitis (AIH) and hepatocellular carcinoma (HCC). AIH rarely progresses to HCC but the diseases similarly induce the production of IL-18 and matrix metalloproteinases. These molecules have distinct effects on the immune response, including the Programmed cell-death 1 (PD-1) axis. In this review, differences in PD-1 function and possible cell signals in AIH and HCC are highlighted.



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Microwaves promote transesterification in the rapid synthesis of methoxy-poly(ethylene glycol)-block-poly(l-lactide-random-glycolide)

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Yihan Jing, Mingliang Yang, Shulin Dai, Changyun Quan, Jie Liu, Qing Jiang, Chao Zhang, Bo Liu
Methoxy-poly(ethylene glycol)-block-poly(l-lactide-random-glycolide) (mPEG-PLGA) with relatively high monomer conversion, fixed LA/GA ratio, controlled molar mass, and random PLGA sequences was synthesized under microwave irradiation at 120 °C. The microstructure, i.e., the sequence of lactyl and glycolyl units, of the PLGA block was analyzed using proton and carbon-13 nuclear magnetic resonance spectroscopy. It was found that the second mode transesterification of glycoldyl units (-GG-) happened shortly after the reaction started and lasted during the reaction, and that of lactidyl units (-LL-) happened gradually from 1 to 30 min under microwave. Compared with traditional oil-bath heating copolymerization, microwave irradiation not only greatly increases polymerization rate but also induces rapid transesterification and achieves high randomness of the PLGA block at low reaction temperature. Nanoparticles with diameter ranging from 60 to 100 nm were also prepared from these mPEG-PLGA copolymers with varied molar mass of PEG (2k and 5k g/mol) and PLGA blocks (20k-160k g/mol), showing such block copolymer can be harnessed as drug delivery matrix in nanomedicine.

Graphical abstract

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Adhesion control of human umbilical vein endothelial cells using clickable poly(2-oxazoline)-grafted biosynthesized extracellular matrix protein

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Saki Morita, Akinori Takasu
A bacterial expression host was used for in vivo incorporation of p-azidophenylalanine (p-N3Phe), a phenylalanine (Phe) analog, into an artificial extracellular matrix protein (aECM-CS5-ELF). The host harbors the mutant phenylalanyl-tRNA synthetase (PheRS) which has an enlarged binding pocket, where the Ala294Gly/Thr251Gly mutant PheRS (PheRS**) was expressed under the control of T7 promoters. Biosynthesized aECM-CS5-ELF containing p-N3Phe (aECM-CS5-ELF-N3) was coupled with alkyne-containing poly(2-oxazoline) prepared via ring-opening polymerization of 2-oxazolines (2-methyl-2-oxazoline, 2-ethyl-2-oxazoline, and 2-iso-propyl-2-oxazoline) using methyl triflate (TfOMe) and propiolic acid as the initiator and terminator, respectively. A copper-catalyzed alkyne-azide click reaction was used to graft the poly(2-oxazoline)s onto the aECM. Examination of the solubility in organic and aqueous media, and the lower critical transition temperature (LCST), revealed a dependence on the incorporation ratio of p-N3Phe and graft chain species; the LCST behavior was markedly altered when poly(2-oxazoline) moieties were present as side chains. Circular dichroism measurements indicate that grafting was not responsible for conformational changes, because the conformation was retained both at below and above the LCST. Specific adhesion and subsequent temperature-sensitive detachment of human umbilical vein endothelial cells (HUVECs) onto the cross-linked aECM-CS5-ELF-N3-graft-poly(2-oxazoline) surfaces was also demonstrated.

Graphical abstract

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High Tg, melt processable copolyimides based on isomeric 3,3′ and 4,4′-hydroquinone diphthalic anhydride (HQDPA)

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Lala Rukh Sidra, Guofei Chen, Nafeesa Mushtaq, Lubo Xu, Xiaoqi Chen, Yantao Li, Xingzhong Fang
To extend the upper operating temperature range of melt processable PIs, two series of end-capped copolyimides based on hydroquinone diphthalic anhydride (HQDPA) isomers were designed by varying the contents of appropriate diamines. Thus, copolyimides PI-(0a∼20a) based on 3,3′-HQDPA were prepared by varying the ratio of rigid 2-(4-aminophenyl)-5-aminobenzimidazole (BIA) and flexible 4,4′-oxydianiline (ODA). The resulting copolyimides demonstrated good properties, such as excellent solubility, high Tg ranging from 328 to 354 °C as determined by dynamic mechanical analyzer (DMA), besides, exhibited good thermal stability based on 5% weight loss temperature (T5%) of 502–514 °C and low melt viscosity in the range of 291–935 Pa·s. Most importantly, PI-20a showed a good combination of low melt viscosity simultaneously with significantly high Tg (328 °C). Furthermore, this system was modified by copolymerization with different feed ratio of 4,4′-HQDPA isomer and produced another series PI-(20a∼20e), that exhibited high Tg in the range of 315–330 °C with T5% of 502–543 °C and minimum complex viscosity in the range of 291–479 Pa·s. All PIs form tough and flexible films that have remarkable tensile strength and moduli in the range of 93–116 MPa and 3.7–4.7 GPa, respectively.

Graphical abstract

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Presynaptic endocytic factors in autophagy and neurodegeneration

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Domenico Azarnia Tehran, Marijn Kuijpers, Volker Haucke
Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration. These findings reveal unanticipated connections between the machineries for synaptic neurotransmission and neuronal proteostasis and identify presynaptic endocytic proteins as potential targets to treat neurodegenerative diseases.



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Expansion microscopy: development and neuroscience applications

Publication date: June 2018
Source:Current Opinion in Neurobiology, Volume 50
Author(s): Emmanouil D Karagiannis, Edward S Boyden
Many neuroscience questions center around understanding how the molecules and wiring in neural circuits mechanistically yield behavioral functions, or go awry in disease states. However, mapping the molecules and wiring of neurons across the large scales of neural circuits has posed a great challenge. We recently developed expansion microscopy (ExM), a process in which we physically magnify biological specimens such as brain circuits. We synthesize throughout preserved brain specimens a dense, even mesh of a swellable polymer such as sodium polyacrylate, anchoring key biomolecules such as proteins and nucleic acids to the polymer. After mechanical homogenization of the specimen-polymer composite, we add water, and the polymer swells, pulling biomolecules apart. Due to the larger separation between molecules, ordinary microscopes can then perform nanoscale resolution imaging. We here review the ExM technology as well as applications to the mapping of synapses, cells, and circuits, including deployment in species such as Drosophila, mouse, non-human primate, and human.



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mGlu5-mediated signalling in developing astrocyte and the pathogenesis of autism spectrum disorders

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Francesco Petrelli, Paola Bezzi
Astrocytes, the largest glial population in human and murine brains, are crucial to the regulation of synaptic connectivity. During the first three weeks of postnatal development, immature astrocytes express mGlu5 and expands several fold while undergoing a transition towards their mature phase. Although mGlu5-mediated signalling in astrocyte functions has been extensively studied in the last decades, whether this signalling is implicated in the mechanisms governing their development, as well as the effects of dysregulated astrocytic development on neurodevelopmental disorders, are still unclear. The aim of this review is to examine what is known about the mGlu5-mediated signalling in the developing astrocytes and its possible contribution to the pathophysiology of autism spectrum disorders.



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Local and long-range circuit elements for cerebellar function

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Le Xiao, Peter Scheiffele
The view of cerebellar functions has been extended from controlling sensorimotor processes to processing 'contextual' information and generating predictions for a diverse range of behaviors. These functions rely on the computation of the local cerebellar microcircuits and long-range connectivity that relays cerebellar output to various brain areas. In this review, we discuss recent work on two of the circuit elements, which are thought to be fundamental for a wide range of non-sensorimotor behaviors: The role for cerebellar granule cells in multimodal integration in the cerebellar cortex and the long-range connectivity between the deep cerebellar nuclei and the basal ganglia. Lastly, we discuss how studies on synapses and circuits of the cerebellum in rodent models of autism-spectrum disorders might contribute to our understanding of the pathophysiology of this class of neurodevelopmental disorders.



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Synapse-to-nucleus communication: from developmental disorders to Alzheimer's disease

Publication date: February 2018
Source:Current Opinion in Neurobiology, Volume 48
Author(s): Elena Marcello, Monica Di Luca, Fabrizio Gardoni
In the last decade several synaptonuclear protein messengers including Jacob, CRTC1, AIDA-1, ProSaP2/Shank3 and RNF10 have been identified and characterized as key players for modulation of synaptic transmission and synaptic plasticity. Activation of excitatory glutamatergic synapses leads to their shuttling from the synapse to the nucleus, mostly importin-mediated, and subsequent regulation of gene transcription needed for long lasting modifications of synaptic function. Accordingly, increasing evidences show that alterations of the activity of synaptonuclear messengers are correlated to synaptic failure as observed in different synaptopathies. Specifically, recent studies demonstrate that the modulation of the activity of synaptonuclear messengers could represent a novel molecular target in the pathogenesis of both neurodevelopmental disorders and neurodegenerative diseases such as Alzheimer's disease.



http://ift.tt/2F76g2X

Thalamic Directional Deep Brain Stimulation for tremor: Spend less, get more

Publication date: Available online 6 January 2018
Source:Brain Stimulation
Author(s): P. Rebelo, A.L. Green, T.Z. Aziz, A. Kent, D. Schafer, L. Venkatesan, B. Cheeran
BackgroundDirectional Deep Brain Stimulation (D-DBS) allows axially asymmetric electrical field shaping, away from structures causing side-effects. However, concerns regarding the impact on device lifespan and complexity of the monopolar survey have contributed to sparing use of these features.ObjectiveTo investigate whether chronically implanted D-DBS systems can improve the therapeutic window, without a negative impact on device lifespan, in thalamic deep brain stimulation (DBS).MethodsWe evaluated stable outcomes of initial programming sessions (4–6 weeks post-implantation) retrospectively in 8 patients with drug-resistant disabling tremor syndromes. We assessed the impact of directional stimulation on the Therapeutic Window (TW), Therapeutic Current Strength (TCS), tremor scores, disability scores and total electrical energy delivered. Finally, we performed Volume of Tissue Activation (VTA) modelling, based on a range of parameters.ResultsWe report significant gains in TW (91%) and reductions in TCS (31%) with stimulation in the best direction compared to best omnidirectional stimulation alternative. Tremor and ADL scores improvements remained unchanged at six months. There was no increase in averaged IPG power consumption (there is a 6% reduction over the omnidirectional-only alternative). Illustrative VTA modelling shows that D-DBS achieves 85% of the total activation volume at just 69% of the stimulation amplitude of non-directional configuration.Conclusions: D-DBS can improve the therapeutic window over non-directional DBS, leading to significant reduction in disability that may be sustained without additional reprogramming visits. Device lifespan was not negatively impacted by the use of directional stimulation this study due to the programming approach.



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Altered structural network organization in cognitively normal individuals with amyloid pathology

Publication date: April 2018
Source:Neurobiology of Aging, Volume 64
Author(s): Olga Voevodskaya, Joana B. Pereira, Giovanni Volpe, Olof Lindberg, Erik Stomrud, Danielle van Westen, Eric Westman, Oskar Hansson
Recent findings show that structural network topology is disrupted in Alzheimer's disease (AD), with changes occurring already at the prodromal disease stages. Amyloid accumulation, a hallmark of AD, begins several decades before symptom onset, and its effects on brain connectivity at the earliest disease stages are not fully known. We studied global and local network changes in a large cohort of cognitively healthy individuals (N = 299, Swedish BioFINDER study) with and without amyloid-β (Aβ) pathology (based on cerebrospinal fluid Aβ42/Aβ40 levels). Structural correlation matrices were constructed based on magnetic resonance imaging cortical thickness data. Despite the fact that no significant regional cortical atrophy was found in the Aβ-positive group, this group exhibited an altered global network organization, including decreased global efficiency and modularity. At the local level, Aβ-positive individuals displayed fewer and more disorganized modules as well as a loss of hubs. Our findings suggest that changes in network topology occur already at the presymptomatic (preclinical) stage of AD and may precede detectable cortical thinning.



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Contrasting effects of individual versus combined estrogen and progestogen regimens as working memory load increases in middle-aged ovariectomized rats: one plus one does not equal two

Publication date: April 2018
Source:Neurobiology of Aging, Volume 64
Author(s): Alesia V. Prakapenka, Ryoko Hiroi, Alicia M. Quihuis, Catie Carson, Shruti Patel, Claire Berns-Leone, Carly Fox, Rachael W. Sirianni, Heather A. Bimonte-Nelson
Most estrogen-based hormone therapies are administered in combination with a progestogen, such as Levonorgestrel (Levo). Individually, the estrogen 17β-estradiol (E2) and Levo can improve cognition in preclinical models. However, although these hormones are often given together clinically, the impact of the E2 + Levo combination on cognitive function has yet to be methodically examined. Thus, we investigated E2 + Levo treatment on a cognitive battery in middle-aged, ovariectomized rats. When administered alone, E2 and Levo treatments each enhanced spatial working memory relative to vehicle treatment, whereas the E2 + Levo combination impaired high working memory load performance relative to E2 only and Levo only treatments. There were no effects on spatial reference memory. Mitogen-activated protein kinases/extracellular signal-regulated kinases pathway activation, which is involved in memory formation and estrogen-induced memory effects, was evaluated in 5 brain regions implicated in learning and memory. A distinct relationship was seen in the E2-only treatment group between mitogen-activated protein kinases/extracellular signal-regulated kinases pathway activation in the frontal cortex and working memory performance. Collectively, the results indicate that the differential neurocognitive effects of combination versus sole treatments are vital considerations as we move forward as a field to develop novel, and to understand currently used, exogenous hormone regimens across the lifespan.



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Association study of Essential Tremor genetic loci in Parkinson’s disease

Publication date: Available online 6 January 2018
Source:Neurobiology of Aging
Author(s): Jay P. Ross, Sadaf Mohtashami, Etienne Leveille, Amelie M. Johnson, Lan Xiong, Patrick A. Dion, Edward Fon, Yves Dauvilliers, Nicolas Dupre, Guy A. Rouleau, Ziv Gan-Or
A recent Genome-Wide Association Study (GWAS) identified variants associated with Essential Tremor (ET). The current study aimed to examine potential genetic overlap between ET and Parkinson's disease (PD). The top 22 variants identified by the ET GWAS, and four additional variants from previous studies were genotyped in a cohort of French and French-Canadian PD patients (n=717) and controls (n=595). Logistic regression analysis, adjusted for age and sex, was used to test for association between genotype and PD. None of the variants tested in the current study was significantly associated with PD. Our results do not support a role of ET-associated genetic variants in PD.



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A novel BODIPY-based fluorescent probe for selective detection of hydrogen sulfide in living cells and tissues

Publication date: 1 May 2018
Source:Talanta, Volume 181
Author(s): Yan Ji, Li-Jun Xia, Liu Chen, Xiao-Feng Guo, Hong Wang, Hui-Juan Zhang
Hydrogen sulfide (H2S) is a critical biological messenger in numerous physiological and pathophysiological processes. Small-molecule fluorescent probes combined with fluorescent microscopy have been developed for the sensitive detection of H2S. Here, we designed and synthesized a long-wavelength BODIPY-based probe (TMSDNPOB) based on the thiolysis of dinitrophenyl ether according to photo-induced electron transfer theory and the results of computational calculation. 4,4-Difluoro-8-phenyl-1,5,7-trimethyl-3-(4-(2,4-dinitrophenoxy)styryl- 4-bora-3a,4a-diaza-s-indacene (TMSDNPOB) is nearly non-fluorescent, but the reaction product (TMSHOB) emits strong red fluorescence at 592nm when excited at 574nm. The long wavelengths of the designed probe indicate low background interference from biological matrix and little photo damage on fluorescence imaging of H2S. With the advantages of the turn-on probe for H2S including high sensitivity, high selectivity, good biocompatibility and low toxicity, the probe has been used for imaging H2S in living cells and liver tissues.

Graphical abstract

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Dr. Martin Citardi Recognized with AAO-HNS Distinguished Service Award

Martin J. Citardi, MD, professor and chair of the Department of Otorhinolaryngology-Head and Neck Surgery at UTHealth's McGovern Medical School,... Read the full article...

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Evaluating Resident On-Call Performance: Does Volume Affect Discrepancy Rate?

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Benjamin Wildman-Tobriner, Brendan Cline, Christopher Swenson, Brian C. Allen, Charles M. Maxfield




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Bronchiectasis Revisited: Imaging Based Pattern Approach to Diagnosis

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Anuradha Singh, Ashu Seith Bhalla, Manisha Jana
Bronchiectasis is one of the causes of non-resolving, persistent or recurrent pulmonary infection which, if uncorrected may have deleterious consequences on the lung parenchyma and pulmonary circulation. Chest radiograph is done at the initial suspicion which is supplemented by HRCT to confirm the diagnosis. Imaging diagnosis supplemented by the recognition of the pattern of involvement is essential to outline the differential diagnosis, map the complications and, hence, guiding the further management. Identification of the causative aetiology may not only prevent its further progression but obviate recurrent insults to the lung parenchyma as well. This article focuses on an algorithmic approach to bronchiectasis based on the distribution on imaging.



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Customized Residency Leadership Tracks: A Review of What Works, What We’re Doing and Ideas for the Future

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): S.A. Matalon, S.A. Howard, G. Gaviola, O. Johnson, C.H. Phillips, S.E. Smith, W.W. Mayo-Smith




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Why is this Auntminnie a Diagnostic Conundrum? - A Knowledge-Based Approach to Balo’s Concentric Sclerosis from Reports of Three Cases and Pooled Data from Sixty-Eight other Patients in The Literature

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Mohit Agarwal, John L. Ulmer, Andrew P. Klein, Leighton P. Mark
We came across three cases of Balo′s concentric sclerosis (BCS). The first of these patients presented to an outside hospital and was transferred to our institution due to complications resulting from a biopsy. The other two patients, despite having a characteristic imaging appearance and despite insistence on our part on the diagnosis of BCS, underwent a surgical procedure, which could have been prevented. This led us to review the available literature on BCS. 68 patients diagnosed with BCS between 1995 and 2015 were studied and the data collected for the clinical presentation and course, imaging, spinal fluid analysis, treatment, and clinical and imaging outcome. A 25% surgery rate (biopsy or resection) was found in the study. We concluded that this relatively high surgery rate in this auntminnie non-surgical disease is multifactorial; and includes factors like non-familiarity with the disease, anxiety on the part of patients and physicians, due to a sometimes rapidly deteriorating clinical picture; and resemblance of the disease with other entities such as tumor and infection. However, characteristic imaging appearance combined with acute/subacute presentation and dramatic improvement in clinical status after high dose steroid chemotherapy; are highly suggestive of the disease, and can prevent unnecessary surgery.



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Thyroid Fine Needle Aspiration: Successful Prospective Implementation of Strategies to Eliminate Unnecessary Biopsy in the Veteran Population

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Sean D. Raj, Rohit Ram, David J. Sabbag, Mark A. Sultenfuss, Rebecca Matejowsky
ObjectiveThyroid nodules are prevalent in over half the general population. Several multi-disciplinary societies have management recommendations. However, the majority of data to support these guidelines are derived from studies of predominantly younger and female populations. This study′s aim was to evaluate characteristics of thyroid nodules in a largely older and male Veteran population and apply these findings prospectively to reduce unnecessary thyroid fine needle aspiration (FNA).Materials and MethodsOver a 4-year period, all ultrasound-guided FNA of thyroid nodules performed in our department were reviewed. Sonographic features, patterns, and histopathology were evaluated. A prospective strategy of avoiding FNA in all lesions matching imaging patterns of benignity was implemented and positive predictive value of malignancy was calculated and compared to the retrospective data.ResultsRetrospectively, FNA was performed on 351 successive thyroid nodules, 9 of which were malignant. Statistically significant malignant features include presence of microcalcifications, irregular/amorphous morphology, taller-than-wide shape, spiculated margins, vascularity, and lymphadenopathy. Positive predictive value (PPV) of thyroid FNA was 2.6% in this period. Four sonographic patterns were 100% specific for benignity, including: "spongiform", "cyst with a colloid clot", "giraffe", and "white knight" patterns. Over 23 months, prospective avoidance of FNA of lesions characterized as a benign pattern (159 nodules) was implemented and PPV was calculated as 7.2% resulting in a cost savings of $477,000.ConclusionFour sonographic patterns were 100% specific for benignity in the older and predominantly male Veteran population. Strict prospective application of avoiding biopsy in these benign patterns resulted in a decrease of unnecessary biopsies, decrease in patient morbidity and improved allocation of healthcare resources.



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Patient Knowledge Regarding Colorectal Cancer Risk, Opinion of Screening, and Preferences for a Screening Test

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Courtney C. Moreno, Thomas Jarrett, Brianna L. Vey, Pardeep K. Mittal, Elizabeth A. Krupinski, David L. Roberts
A survey assessing knowledge about colorectal cancer incidence and prognosis as well as willingness to undergo screening with various tests (e.g., optical colonoscopy, stool-based tests, CT colonography) was administered to consecutive patients of a general academic-based internal medicine clinic. Survey response rate was 86.3%. A majority of respondents (55%) reported being aware of general information about colorectal cancer, and 99% indicated a belief that colorectal cancer screening was a good idea. A majority of respondents (73%) were willing to undergo optical colonoscopy, and some were willing to undergo stool-based tests (48%) or CT colonography (40%). A majority reported being more willing to undergo a colorectal cancer screening test if the test did not involve radiation (86%), did not involve insertion of a tube or device into the rectum (78%), did not involve a pre-procedural bowel cleansing regimen (73%), or did not involve sedation (60%). In conclusion, improved patient education about the negligible radiation risk associated with CT colonography and/or development of a non-invasive imaging test that did not involve a pre-procedural bowel cleansing regimen may increase rates of colorectal cancer screening.



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Common resident errors when interpreting CT of the abdomen and pelvis: A review of types, pitfalls, and strategies for improvement

Publication date: Available online 6 January 2018
Source:Current Problems in Diagnostic Radiology
Author(s): Benjamin Wildman-Tobriner, Brian C. Allen, Charles M. Maxfield
ObjectiveThe purpose of this study was to identify common errors that radiology residents make when interpreting abdominopelvic (AP) CT while on call, to review the typical imaging findings of these cases, and to discuss strategies for improvement.Materials and MethodsAP (or chest, abdomen, pelvis) CTs from 518 weekend senior call shifts (R3 or R4) were retrospectively reviewed. Discrepancies between preliminary and final reports were identified and then rated by whether the miss could impact short-term management. The imaging findings from the cases were reviewed.Results4695 CTs were reviewed, revealing a total of 145 discrepancies that could affect short-term clinical management (miss rate 3.1%). The most common misses were related to blood clots (13.8%), colitis (8.3%), misplaced lines/tubes (6.9%), or pyelonephritis (5.5%). Common pitfalls and strategies from improved detection are discussed using image examples.ConclusionsThrough increased attention to the vasculature, colon, devices, and kidneys, trainees may improve their discrepancy rates and improve on-call reporting.



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Evolutionary design of nonuniform cellular structures with optimized Poisson's ratio distribution

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Yafeng Han, Wenfeng Lu
For negative Poisson's ratio (NPR) cellular structures, most previous research focus on the design of unit cells, and then repeat the unit cell to construct uniform cellular structures. However, there is a disadvantage that these structures do not have much design freedom to achieve high-level functions, such as performing a desired deformation. As a solution, an evolutionary design method is proposed to develop nonuniform cellular structures. To conduct this method, the design domain is divided into finite unit cells with tunable Poisson's ratio (PR). With a given objective deformation, the value of each unit cell's PR is optimized using evolutionary algorithm (EA). In order to reduce the computational cost of the algorithm, discrete cosine transform (DCT) is applied to encode the structure for evolving. Considering the geometrical complexity of the optimized nonuniform cellular structures, additive manufacturing (AM) is chosen to build them physically. Both two-dimensional (2D) and three-dimensional (3D) design cases were developed and analyzed to validate the proposed method. The computational and experimental results showed good conformation with each other. Most importantly, this novel design method brings huge potential to NPR cellular structures with high-level functions and much wider applications.

Graphical abstract

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Bistable metallic materials produced by nanocrystallization process

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Shenghui Yi, Xiaoqiao He, Jian Lu
Through a localized nanocrystallization process using surface mechanical attrition treatment (SMAT), a new method is proposed to build bistable and multistable metallic shells. The impacts from randomly fast-moving balls during the nanocrystallization process accumulate plastic deformations, which induce nanotwins and mesh grains into nanoscales significantly increasing elastic behavior range of the treated shells. The in-plane self-equilibrium residual stress field, which is induced from the stretching plastic deformations in the treated region under the constraint of the untreated region, renders nanostructured shells bistable characteristics. An effective numerical modelling is carried out to analyze the bistable behavior and predict their stable configurations. A flat plate with multiple nanostructured regions is manufactured and numerically studied, which is capable of holding multiple stable configurations. In addition, the developed bistable and multistable shells can be further mechanically processed to modify their stable configurations.

Graphical abstract

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Editorial: Correspondence from Chirumbolo and Bjorklund

Publication date: Available online 6 January 2018
Source:International Immunopharmacology
Author(s): François Marceau




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Soluble Tim-3 and Gal-9 are associated with renal allograft dysfunction in kidney transplant recipients: A cross-sectional study

Publication date: February 2018
Source:International Immunopharmacology, Volume 55
Author(s): Ya Mei Li, Yun Ying Shi, Yi Li, Lin Yan, Jiang Tao Tang, Yang Juan Bai, Xiao Juan Wu, Bo Dai, Yuan Gao Zou, Lan Lan Wang
BackgroundT cell immunoglobulin mucin-3 (Tim-3) has been reported to participate in the regulation of immune response and the induction of allograft tolerance. However, the association between Tim-3 and renal allograft dysfunction is unclear. We studied the expression of cellular and soluble Tim-3 (sTim-3), soluble galectin-9 (sGal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (sCEACAM-1) in kidney transplantation recipients (KTRs) to explore their roles in allograft dysfunction.Methods96 KTRs (53 with stable graft and 43 with graft dysfunction) and 30 healthy controls (HC) were enrolled. Among the KTRs, 55 used Tacrolimus (TAC) and 41 used Sirolimus (SRL). In the dysfunction group, 29 recipients have undergone graft biopsy and 14 were classified as biopsy-proven rejection (BPR). Cellular Tim-3 was determined by flow cytometry. sTim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex® suspension array system.ResultsKTRs with renal dysfunction showed significantly higher levels of sTim-3 and sGal-9 but similar levels of cellular Tim-3 and sCEACAM-1 compared with stable recipients. Correlation analysis revealed that estimated glomerular filtration rate (eGFR) was negatively associated with sTim-3 and sGal-9. Both BPR and non-BPR groups showed comparable levels of Tim-3, Gal-9 and CEACAM-1. Moreover, SRL group showed significantly higher levels of sCEACAM-1 than TAC and HC groups.ConclusionssTim-3 and sGal-9 were promising biomarkers for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in KTRs. Moreover, long-term administration of sirolimus would up-regulate sCEACAM-1 level, while exert similar regulatory effects on Tim-3 and Gal-9 compared to tacrolimus.



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Effect of transcranial direct current stimulation on short-term and long-term treatment of chronic tinnitus

This study was conducted to investigate the effectiveness of anodal and cathodal methods in reducing the intensity of tinnitus and to compare them with the control.

http://ift.tt/2Cye3VA

An assessment of the use of antihistamines in the management of atopic dermatitis

Antihistamines are often used to treat pruritus associated with atopic dermatitis (AD) despite lack of evidence for their efficacy. The American Academy of Dermatology does not recommend the general use of antihistamines in the management of AD, although the value of short-term sedating antihistamine use for insomnia secondary to itch is recognized.

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Just A Quick Pic: Ethics of Medical Photography

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In vitro assessment of the broad-spectrum ultraviolet protection of clothing

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Post-diagnosis aspirin use and overall survival in patients with melanoma

Mouse studies show that tumor-derived prostaglandins and platelets promote melanoma progression and immune-evasion.

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Defining the Key Competencies in Radiation Protection for Endovascular Procedures: A Multispecialty Delphi Consensus Study

Publication date: Available online 5 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Bart Doyen, Blandine Maurel, Jonathan Cole, Heidi Maertens, Tara Mastracci, Isabelle Van Herzeele
ObjectivesRadiation protection training courses currently focus on broad knowledge topics which may not always be relevant in daily practice. The goal of this study was to determine the key competencies in radiation protection that every endovascular team member should possess and apply routinely, through multispecialty clinical content expert consensus.MethodsConsensus was obtained through a two round modified Delphi methodology. The expert panel consisted of European vascular surgeons, interventional radiologists, and interventional cardiologists/angiologists experienced in endovascular procedures. An initial list of statements, covering knowledge skills, technical skills and attitudes was created, based on a literature search. Additional statements could be suggested by the experts in the first Delphi round. Each of the statements had to be rated on a 5- point Likert scale. A statement was considered to be a key competency when the internal consistency was greater than alpha = 0.80 and at least 80% of the experts agreed (rating 4/5) or strongly agreed (rating 5/5) with the statement. Questionnaires were emailed to panel members using the Surveymonkey service.ResultsForty-one of 65 (63.1%) invited experts agreed to participate in the study. The response rates were 36 out of 41 (87.8%): overall 38 out of 41(92.6%) in the first round and 36 out of 38 (94.7%) in the second round. The 71 primary statements were supplemented with nine items suggested by the panel. The results showed excellent consensus among responders (Cronbach's alpha = 0.937 first round; 0.958 s round). Experts achieved a consensus that 30 of 33 knowledge skills (90.9%), 23 of 27 technical skills (82.1%), and 15 of 20 attitudes (75.0%) should be considered as key competencies.ConclusionsA multispecialty European endovascular expert panel reached consensus about the key competencies in radiation protection. These results may serve to create practical and relevant radiation protection training courses in the future, enhancing radiation safety for both patients and the entire endovascular team.



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Commentary on “Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial Cells in vitro”

Publication date: Available online 6 January 2018
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Sandro Lepidi




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In vivo response of the human epigenome to vitamin D: A proof-of-principle study

Publication date: Available online 6 January 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Carsten Carlberg, Sabine Seuter, Tarja Nurmi, Tomi-Pekka Tuomainen, Jyrki K. Virtanen, Antonio Neme
In vitro cell culture studies showed that the hormonal form of vitamin D3, 1α,25-dihydroxyvitamin D3, significantly (p < 0.05) affects the human epigenome at thousands of genomic loci. Phase II of the VitDbol vitamin D intervention trial (NCT02063334) involved a proof-of-principle study of one individual, who was exposed three times every 28 days to an oral bolus (2,000 µg) of vitamin D3. Blood samples were taken directly before each supplementation as well as one and two days after, chromatin was isolated from peripheral blood mononuclear cells without any further in vitro culture and at all nine time points epigenome-wide chromatin accessibility was assessed by applying FAIRE-seq (formaldehyde-assisted isolation of regulatory elements sequencing). The vitamin D3 bolus resulted in an average raise in 25-hydroxyvitamin D3 (25(OH)D3) serum concentration of 11.9 and 19.4 nM within one and two days, respectively. Consistently accessible chromatin was detected at 5,205 genomic loci, the 853 most prominent of which a self-organizing map algorithm classified into early, delayed and non-responding genomic regions: 70 loci showed already after one day and 361 sites after two days significant (p < 0.0001) chromatin opening or closing. Interestingly, more than half of these genomic regions overlap with transcription start sites, but the change of chromatin accessibility at these sites has no direct effect on the transcriptome. Some of the vitamin D responsive chromatin sites cluster at specific loci within the human genome, the most prominent of which is the human leukocyte antigen region in chromosome 6. In conclusion, this study demonstrates that under in vivo conditions a rather minor rise in 25(OH)D3 serum levels is sufficient to result in significant changes at hundreds of sites within the epigenome of human leukocytes.



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Association of serotonergic pathway genes with smoking cessation in a Chinese rural male population

Publication date: May 2018
Source:Addictive Behaviors, Volume 80
Author(s): Qiang Wang, Suyun Li, Huijie Li, Chongqi Jia
IntroductionPrevious studies have found serotonergic pathway genes have inhibitory effects on dopamine system which may influence smoking addiction. This study examined the associations of serotonergic pathway genes (serotonergic receptor genes, solute carrier family 6 member4 and tryptophan hydroxylase gene) with smoking cessation.Materials and methodsMale current and former smokers (n=819) were recruited from 17 villages of three counties in Shandong province, China. DNA was extracted from the blood samples. Eleven single nucleotide polymorphisms (SNPs) in serotonergic pathway genes were genotyped. Multiple logistic regression was used to assess associations between SNPs and smoking cessation. Pearson's χ² test was performed to explore associations of haplotypes with smoking cessation. Multiple logistic regression was used to detect the interaction between SNPs on smoking cessation.ResultsIn multiple logistic regression, rs1042173 of Solute carrier family 6 member 4 was significantly related to smoking cessation in additive and dominant model (p=0.03 and 0.02, respectively). Rs4570625 of tryptophan hydroxylase 2 was significantly associated with smoking cessation in dominant model (p=0.03). Nine significant interactions were detected between SNPs in serotonergic pathway genes.ConclusionsThe present study reveals that serotonergic pathway genes were significantly related to smoking cessation. Future research should expand upon these findings to confirm them.



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Editorial Board

Publication date: January 2018
Source:Medical Hypotheses, Volume 110





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Patterns of Involved-Field Radiation Therapy (IFRT) Protocol Deviations in Pediatric versus Adolescent and Young Adults with Hodgkin Lymphoma: A Report from the Children’s Oncology Group (COG) AHOD0031

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): A. Parzuchowski, Rizvan Bush, Qinglin Pei, D.L. Friedman, T.J. FitzGerald, S.L. Wolden, K.V. Dharmarajan, L.S. Constine, F. Laurie, S.K. Kessel, B. Appel, K. Fernandez, A. Punnett, C.L. Schwartz, J. Cox, S.A. Terezakis
BackgroundThis protocol for pediatric intermediate-risk Hodgkin Lymphoma (IRHL) evaluated the use of a dose-intensive chemotherapy regimen (ABVE-PC) with response-based therapy augmentation (addition of DECA) or therapy reduction (elimination of radiation). Central review of radiotherapy data for quality assurance (QA) was performed, and the association between radiation protocol deviation (RPD) and relapse was assessed in pediatric (<15) and AYA (≥15-21) groups.ProcedureIFRT treatment planning was reviewed prior to the start of treatment and at the completion of treatment. Records were reviewed through the Quality Assurance Review Center's (QARC) central review to identify RPD, classified according to dose (DD), volume (VD), under-treatment (UT), and over-treatment (OT). DD and VD were further classified as major or minor.ResultsOf the 1,712 patients enrolled, 1,155 received IFRT and 216 (18.7%) had RPD. DD and VD patterns were similar between pediatric and AYA groups. Minor VD was most common. UT RPD accounted for 69% in the pediatric group and 75% in the AYA group. Of 35 relapses and RPD, 29 had an under-treatment RPD. Among the patients who received IFRT, there was a significant difference in the cumulative incidence rates of relapse between pediatric and AYA groups (p=0.03) but no significant difference between patients with and without RPD (p=0.2).ConclusionsThe majority of RPD were minor and under-treatments in both the AYA and pediatrics population. There was no observed difference in RPD between the pediatric and AYA patients. Thus, in a well-defined and standardized protocol, RPD distributions for AYA patients are similar to the pediatrics population. However, the increased cumulative incidence of relapse in the AYA population who received IFRT compared to the pediatrics population needs to be further explored given the potential differences in clinical outcomes in the AYA population.

Teaser

As ******** is the largest phase III study to date on intermediate-risk Hodgkin Lymphoma in pediatric patients, we investigated the patterns of radiation protocol deviation and relapse between the pediatric and adolescent and young adult patient cohorts. We demonstrate that there were no statistically significant differences in deviation patterns between the two cohorts, though of those that received IFRT, there was a significant difference in cumulative incidence rates of relapse between the two groups.


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Phase II Study of Bortezomib in Combination with Temozolomide and Regional Radiation Therapy for Upfront Treatment of Patients with Newly-Diagnosed Glioblastoma Multiforme: Safety and Efficacy Assessment

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Xiao-Tang Kong, Nhung T. Nguyen, Yoon J. Choi, Guicheng Zhang, HuyTram N. Nguyen, Emese Filka, Stacey Green, William H. Yong, Linda M. Liau, Richard M. Green, Tania Kaprealian, Whitney B. Pope, P. Leia Nghiemphu, Tim Cloughesy, Andrew Lassman, Albert Lai
Purpose/ObjectiveTo assess the safety and efficacy of upfront treatment using bortezomib in combination with standard radiation therapy (RT) and temozolomide, followed by adjuvant bortezomib and temozolomide for up to 24 cycles in patients with newly-diagnosed glioblastoma multiforme (GBM).Patients and MethodsTwenty-four newly-diagnosed GBM patients were enrolled. Patients received standard external beam regional RT with concurrent temozolomide commencing 3-6 weeks after surgery, followed by adjuvant temozolomide and bortezomib for up to 24 cycles or until tumor progression. During RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, 11, 29, 32, 36, and 39. Post RT, bortezomib was given at 1.3 mg/m² on days 1, 4, 8, and 11 every 4 weeks.ResultsNo unexpected adverse events occurred from the addition of bortezomib. Efficacy analysis showed median progression free survival (PFS) of 6.2 months (95% CI, 3.7-8.8) with promising PFS rates at 18 months and beyond compared to historical norms (25.0% at 18 and 24 months, 16.7% at 30 months). In terms of overall survival (OS), the median OS was 19.1 months (95% CI, 6.7-31.4) with improved OS rates at 12 months and beyond (87.5% at 12, 50.0% at 24, 34.1% at 36 throughout 60 months) compared to historical norms. Median PFS was 24.7 months (95% CI 8.5-41.0) in 10 MGMT methylated and 5.1 months (95% CI 3.9-6.2) in 13 unmethylated patients. The estimated median OS was 61 months in the methylated (the upper bound of 95% CI could not be reached) and 16.4 months (95% CI 11.8-21.0) in the unmethylated patients.ConclusionAddition of bortezomib to current standard radio-chemotherapy in newly-diagnosed GBM patients was tolerable. The PFS and OS rates appeared promising with more benefit to MGMT methylated patients. Further clinical investigation is warranted in a larger cohort of patients.

Teaser

We conducted a phase II study of bortezomib in combination with temozolomide and regional radiotherapy (RT) in 24 newly-diagnosed GBM patients. Addition of bortezomib to current standard care was well-tolerated, and observed toxicities were acceptable. Overall survival rates were improved compared to historical norms, especially in MGMT methylated patients. Further clinical investigation is warranted in larger cohort of patients.


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Local Control following Stereotactic Body Radiation Therapy for Liver Tumors

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Nitin Ohri, Wolfgang A. Tomé, Alejandra Méndez Romero, Moyed Mifften, Randall K. Ten Haken, Laura A. Dawson, Jimm Grimm, Ellen Yorke, Andrew Jackson
PurposeNumerous dosing and fractionation schedules have been used to treat hepatic tumors with stereotactic body radiation therapy (SBRT). In this report, we have quantitatively evaluated published experiences with hepatic SBRT to determine local control rates following treatment of primary and metastatic liver tumors and to examine if outcomes are affected by SBRT dosing regimen.MethodsWe identified published articles that reported local control rates following SBRT for primary or metastatic liver tumors. Biologically effective doses (BEDs) were calculated for each dosing regimen using the Linear Quadratic Equation. We excluded series in which a wide range of BEDs was used. Individual lesion data for local control were extracted from actuarial survival curves, and data were aggregated to form a single dataset. Actuarial local control curves were generated using the Kaplan-Meier method after grouping lesions by disease type and BED (<100 Gy10 v. >100 Gy10). Comparisons were made using logrank testing.ResultsThirteen papers met all inclusion criteria and formed the dataset for this analysis. One, two, and three-year actuarial local control rates following SBRT for primary liver tumors (n=431) were 93%, 89%, and 86%, respectively. Lower one (90%), two (79%), and three-year (76%) actuarial local control rates were observed for liver metastases (n=290, logrank p=0.011). Among patients treated with SBRT for primary liver tumors, there was no evidence that local control is influenced by BED within the range of schedules used. For liver metastases, on the other hand, outcomes were significantly better for lesions treated with BEDs exceeding 100 Gy10 (3-year local control 93%) than for those treated with BEDs less than or equal to 100 Gy10 (3-year local control 65%, p<0.001).ConclusionSBRT for primary liver tumors provides high rates of durable local control, with no clear evidence for a dose-response relationship among commonly-utilized schedules. Excellent local control rates are also seen following SBRT for liver metastases when biologically effective doses above 100 Gy10 are utilized.

Teaser

We have quantitatively evaluated published experiences with hepatic SBRT to determine local control rates for primary and metastatic liver tumors and have examined if outcomes are affected by SBRT dosing regimen. We found that for primary liver tumors SBRT provides high rates of durable local control, with no clear evidence of a dose-response relationship for commonly-utilized schedules. While for liver metastases following SBRT excellent local control rates are seen when utilizing biologically effective doses above 100 Gy10.


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Radiation Dose-Volume Effects for Liver SBRT

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Moyed Miften, Yevgeniy Vinogradskiy, Vitali Moiseenko, Jimm Grimm, Ellen Yorke, Andrew Jackson, Wolfgang A. Tomé, Randall Ten Haken, Nitin Ohri, Alejandra Méndez Romero, Karyn A. Goodman, Lawrence B. Marks, Brian Kavanagh, Laura A. Dawson
Stereotactic Body Radiation Therapy (SBRT) has emerged as an effective, non-invasive treatment option for primary liver cancer and metastatic disease occurring in the liver. While SBRT can be highly effective for establishing local control in hepatic malignancies, there is a tradeoff between tumor control and normal tissue complications. The objective of this work was to review the normal tissue dose-volume effects for SBRT-induced liver and gastrointestinal (GI) toxicities, and derive normal tissue complication probability models.



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Radiation as an Effective Salvage Therapy for Secondary CNS Lymphoma

Publication date: Available online 6 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Sarah A. Milgrom, Chelsea C. Pinnix, T Linda Chi, Thinh H. Vu, Jillian R. Gunther, Tommy Sheu, Nathan Fowler, Jason R. Westin, Loretta J. Nastoupil, Yasuhiro Oki, Luis E. Fayad, Sattva Neelapu, Maria Alma Rodriguez, Frederick B. Hagemeister, Michelle A. Fanale, Hun J. Lee, Chitra Hosing, Sairah Ahmed, Yago Nieto, Elizabeth J. Shpall, Bouthaina S. Dabaja
We assessed the efficacy of radiation therapy (RT) in the management of secondary central nervous system (CNS) lymphoma. The cohort comprised 44 patients with systemic diffuse large-B cell lymphoma (DLBCL) secondarily involving the brain and/or leptomeninges at initial diagnosis or relapse, who received RT. Twenty-nine patients (66%) were in systemic remission when diagnosed with CNS disease. The overall response rate to RT by magnetic resonance imaging was 88% (42% complete, 46% partial). The median overall survival (OS) after RT initiation was 7 months (95% CI: 4-10 months). The OS curve plateaued at 31% from 2 to 8 years. OS was superior in patients who achieved a complete or partial response to RT, underwent stem cell transplantation (SCT) after RT, and had brain parenchymal (vs. leptomeningeal) disease. Eight cases of CNS disease progression occurred after RT: one involved the brain parenchyma and 7 involved the spine and/or CSF/meninges. We conclude that RT is associated with high response rates and may contribute to long-term OS. Additionally, RT may provide CNS disease control that facilitates successful salvage with SCT in patients with chemorefractory disease.

Teaser

We reviewed the outcomes of patients with secondary central nervous system involvement by diffuse large-B cell lymphoma, who were treated with radiation therapy (RT) at a single institution. RT was associated with high rates of radiographic disease response and local control. Overall survival was superior in patients who achieved a complete or partial response to RT, who underwent autologous stem cell transplantation after RT, and who had brain parenchymal (vs. leptomeningeal) disease.


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Effects of different peracetic acid formulations on post space radicular dentin

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Lauriê Garcia Belizário, Milton Carlos Kuga, Gabriela Mariana Castro-Núñez, Wilfredo Gustavo Escalante-Otárola, Marcus Vinicius Reis Só, Jefferson Ricardo Pereira
Statement of problemThe optimal irrigating solution with antimicrobial and dentin cleansing properties for post space preparation for fiber posts is unclear. Peracetic acid is one option but is available in various chemical formulations that require evaluation.PurposeThe purpose of this in vitro study was to evaluate dentin surface cleanliness based on the presence of a smear layer and the number of open dentin tubules. It also investigates the chemical composition of residues after canal irrigation with a 1% peracetic acid solution (PA) at low or high concentration of hydrogen peroxide during the preparation of intracanal fiber posts.Material and methodsAfter filling the root canals of 40 mandibular incisors, a rotary instrument was used for intracanal preparation to place fiber posts. The teeth were divided into 4 groups (n=10) according to the post space irrigation protocol as follows: CG (control): distilled water; NA (NaOCl): 2.5% sodium hypochlorite; LH: PA with low concentration of hydrogen peroxide; and HH: PA with high concentrations of hydrogen peroxide. After irrigation, the teeth were sectioned, and the intracanal dentin surface was subjected to analysis using energy dispersive spectroscopy to evaluate chemical composition and to scanning electron microscopy (×500) to evaluate the presence of the smear layer. The number of open dentin tubules was measured by scanning electron microscopy analysis (×2000) using photo-editing software. ANOVA and the Tukey test (α=.05) were used to evaluate the data, except for the presence of a smear layer, for which the Kruskal-Wallis and Dunn tests were used (α=.05).ResultsThe highest concentrations of oxygen in the dentin residues were detected in LH and HH (P<.05); CG and NA showed similar oxygen concentrations (P>.05). NA had a higher concentration of chlorine (P<.05), whereas LH had a lower amount of smear layer and a larger number of open dentin tubules than the other groups (P<.05). These were equivalent to each other (P>.05), except for HH, which also had a larger number of open dentin tubules than CG and NA (P<.05).ConclusionsPA 1% with a low concentration of hydrogen peroxide yielded a lower amount of smear layer and a larger number of open dentin tubules in the dentin of the post space when compared with PA 1% with a high concentration of hydrogen peroxide, despite maintaining a similar oxygen concentration in these dentin residues.



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Comparison of the mechanical properties of translucent zirconia and lithium disilicate

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Sung Joon Kwon, Nathaniel C. Lawson, Edward E. McLaren, Amir H. Nejat, John O. Burgess
Statement of problemThree mol% yttria-stabilized tetragonal zirconia polycrystal (3Y-TZP) possesses excellent mechanical properties but is relatively opaque. Five mol% yttria-stabilized zirconia polycrystal (5Y-ZP) offers improved translucency, but many of its clinical properties have not been compared with those of 3Y-TZP and lithium disilicate.PurposeThe purpose of this in vitro study was to compare the flexural strength, translucency parameter, bond strength, and enamel and material wear of 5Y-ZP (Katana UTML) with 3Y-TZP (Katana HT) and lithium disilicate (e.max CAD).Material and methodsFlexural strength bars were sectioned (n=10, 25×4×2 mm), sintered or crystallized, polished, and fractured at 1 mm/min. Translucency specimens (1 mm thick) were fabricated (n=10). Their L*a*b* values were measured against a black-and-white background with a spectrophotometer, and ΔE00 was calculated. Zirconia bond strength specimens were airborne-particle abraded with 50 μm alumina followed by the application of a 10-methacryloxydecyl dihydrogen phosphate–containing primer (Clearfil Ceramic Primer). Lithium disilicate bond strength specimens were etched with 5% hydrofluoric acid followed by application of a silane-containing primer (Clearfil Ceramic Primer). A Tygon tube filled with resin cement (Panavia SA) was fixed to the surface of the ceramics and light-polymerized. After 1 day or 150 days of water storage, the resin cement was debonded in a macroshear test (n=10). The cusps of extracted human molars were isolated and mounted into the University of Alabama at Birmingham wear-testing device. Wear testing was performed with a 20-N load for 300000 cycles in 33% glycerin. The volumetric wear of polished zirconia, lithium disilicate, and enamel were measured along with the wear of the opposing enamel cusps using a noncontact profilometer (n=8). The data were compared by ANOVA and Tukey-Kramer analysis (α=.05).ResultsNo statistical difference was seen between the bond strengths (P=.155) or the opposing enamel wear (P=.533) of different ceramics. A statistically significant difference was seen between the flexural strength (P<.001), translucency parameter (P<.001), and wear (P<0.01) of the materials. The flexural strength values (MPa) were 1194 ±111 (Katana HT), 688 ±159 (Katana UTML), and 450 ±53 (e.max LT). The translucency parameter values were 6.96 ±0.53 (Katana HT), 8.30 ±0.24 (Katana UTML), 9.28 ±0.36 (e.max LT), and 12.64 ±0.48 (e.max HT). Bond strength values (MPa) at 1 and 150 days were 34.22 ±5.14 and 28.37 ±6.03 (Katana HT), 35.04 ±5.69 and 25.03 ±6.44 (Katana UTML), and 35.50 ±3.45 and 22.32 ±3.45 (e.max LT). Material and enamel wear (mm³) were 0 and 0.24 ±0.19 (Katana HT), 0 and 0.23 ±0.09 (Katana UTML), 0.28 ±0.13 and 0.31 ±0.10 (e.max CAD), and 0.09 ±0.03 and 0.31 ±0.14 (enamel).Conclusions5Y-TZP has a flexural strength and translucency parameter between those of 3Y-TZP and lithium disilicate. Both the short-term and long-term bond strength of 5Y-ZP and 3Y-TZP was shown to be similar to lithium disilicate. 5Y-ZP demonstrated no measurable material wear and opposing enamel wear similar to that of all the other materials tested.



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Comparison between masticatory index and mixing index among complete denture wearers and associated factors: A multivariate analysis

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Hala A. Elmoula, Nadia Khalifa, Mohammed Nasser Alhajj
Statement of problemMasticatory performance is an important and complex multifactorial process in clinical practice. An exploration of the relationships and effects of the associated factors is lacking.PurposeThis clinical survey compared masticatory efficiency (mixing index) with perceived masticatory ability (masticatory index) among complete denture wearers and sought to clarify the relationship between these indices and other factors.Materials and methodsThe study consisted of 58 complete denture wearers (37 men, 21 women) ranging between 37 and 80 years of age. Participants were interviewed and examined clinically. The perceived masticatory ability of participants regarding 15 types of Sudanese food was evaluated. The degree of mixing of a 2-colored chewing gum was used to measure masticatory efficiency. Multiple regression and structural equation modeling analyses were used to assess the association between both indices and other related factors.ResultsMost of the complete denture wearers could eat soft foods easily but found it difficult to eat hard foods and avoided them. No significant differences in masticatory efficiency could be observed regarding sex or age. Values of the mixing index ranged from 13 (well-mixed colors) to 34 (poorly mixed). Perceived masticatory ability was significantly associated with previous denture experience and the duration of denture wearing (P=.01). Masticatory efficiency was significantly associated with denture quality (P=.001) and with perceived masticatory ability (P=.004).ConclusionsA significant association was noted between denture quality and masticatory performance. A significant association was also observed between perceived masticatory ability and masticatory efficiency, and both can be used to evaluate masticatory performance among complete denture wearers.



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Disinfection of polyvinyl siloxane impression material by gaseous ozone

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Hakki Celebi, Emine Begüm Büyükerkmen, Emrah Torlak
Statement of problemImpression materials must be disinfected to avoid cross-contamination before they are sent to the dental laboratory. However, whether aqueous state disinfectants affect material wettability is unclear.PurposeThe purpose of this in vitro study was to compare the efficacy of gaseous ozone and sodium hypochlorite (NaOCl) in disinfecting light-body consistency hydrophilized polyvinyl siloxane (PVS) impression specimens inoculated with a cocktail of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis. The effect of both disinfectants on the wettability of the material was also evaluated on uninoculated specimens.Material and methodsDisk-shaped specimens (N=140) were subjected to the either gaseous ozone or NaOCl for up to 30 minutes at room temperature. In the ozone group, the specimens were ozonated under a continuous stream of gaseous ozone at a concentration of 12.8 mg/L, while the specimens in the NaOCl group were immersed into 0.5% NaOCl solution. Reductions in the size of the bacterial population at the end of the exposure times were determined by the plate count technique. The contact angle measurements on the impression surface were used to determine the wettability of the specimens. Results were analyzed with 1-way ANOVA followed by the Tukey post hoc test (α=.05).ResultsThe material exposed to both disinfectants for 30 minutes demonstrated a reduction in the number of bacteria of up to more than 3 log. The contact angle of water on the material increased significantly (P<.001) after only 5 minutes of contact with the NaOCl solution. However, the treatment with gaseous ozone for 30 minutes resulted in a reduced contact angle (P<.001).ConclusionsGaseous ozone treatment was identified as a promising method of disinfecting polymerized PVS impression materials because of its positive effect on the wettability of the material.



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Fracture analysis of CAD-CAM high-density polymers used for interim implant-supported fixed, cantilevered prostheses

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Burak Yilmaz, Gülce Alp, Jeremy Seidt, William M. Johnston, Roger Vitter, Edwin A. McGlumphy
Statement of problemThe load-to-fracture performance of computer-assisted design and computer-assisted manufacturing (CAD-CAM) high-density polymer (HDP) materials in cantilevers is unknown.PurposeThe purposes of this in vitro study were to evaluate the load-to-fracture performance of CAD-CAM–fabricated HDPs and to compare that with performance of autopolymerized and injection-molded acrylic resins.Material and methodsSpecimens from 8 different brands of CAD-CAM HDPs, including Brylic Solid (BS); Brylic Gradient (BG); AnaxCAD Temp EZ (AE); AnaxCAD Temp Plus (AP); Zirkonzahn Temp Basic (Z); GDS Tempo-CAD (GD); Polident (Po); Merz M-PM-Disc (MAT); an autopolymerized acrylic resin, Imident (Conv) and an injection-molded acrylic resin, SR-IvoBase High Impact (Inj) were evaluated for load-to-fracture analysis (n=5). CAD-CAM specimens were milled from poly(methyl methacrylate) (PMMA) blocks measuring 7 mm in buccolingual width, 8 mm in occlusocervical thickness, and 30 mm in length. A wax pattern was prepared in the same dimensions used for CAD-CAM specimens, flasked, and boiled out. Autopolymerizing acrylic resin was packed and polymerized in a pressure container for 30 minutes. An identical wax pattern was flasked and boiled out, and premeasured capsules were injected (SR-IvoBase) and polymerized under hydraulic pressure for 35 minutes for the injection-molded PMMA. Specimens were thermocycled 5000 times (5°C to 55°C) and fixed to a universal testing machine to receive static loads on the 10-mm cantilever, vertically at a 1 mm/min crosshead speed until fracture occurred. Maximum load-to-fracture values were recorded. ANOVA was used to analyze the maximum force values. Significant differences among materials were analyzed by using the Ryan-Einot-Gabriel-Welsch multiple range test (α=.05).ResultsStatistically significant differences were found among load-to-fracture values of different HDPs (P<.001). GD and Po materials had significantly higher load-to-fracture values than other materials (P<.001), and no statistically significant differences were found between GD and Po. The lowest load-to-fracture values were observed for autopolymerized and BG materials, which were significantly lower than those of GD, Po, AE, AP, Z, MAT, Inj, and BS. The load-to-fracture value of autopolymerized acrylic resin was not significantly different from that of BG CAD-CAM polymer.ConclusionsGD and Po CAD-CAM materials had the highest load-to-fracture values. AE, AP, Z, MAT, and BS CAD-CAM polymers and injection-molded acrylic resin had similar load-to-fracture values, which were higher than those of BG and autopolymerized acrylic resin. Autopolymerized acrylic resin load-to-fracture value was similar to that of BG CAD-CAM polymer, which is colored in a gradient pattern.



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Optical behaviors of esthetic CAD-CAM restorations after different surface finishing and polishing procedures and UV aging: An in vitro study

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Hamiyet Kilinc, Sedanur Turgut
Statement of problemEsthetic computer-aided design and computer-aided manufacturing (CAD-CAM) materials have various chemical compositions and can be prepared by using different finishing and polishing procedures. Their optical properties may change over time, depending on these factors. However, information about their stain resistance is still scarce.PurposeThe purpose of this in vitro study was to evaluate the optical properties of esthetic CAD-CAM materials after different finishing and polishing procedures and ultraviolet (UV) aging.Material and methodsLava Ultimate, Cerasmart, Vita Enamic, Vita Suprinity, and Vita Mark II materials were used. A total of 150 specimens (14×12×1 mm) were prepared (n=10). A spectrophotometer was used to measure color parameters after different finishing and polishing procedures (control, manual polishing, glazing) and ultraviolet (UV) aging. Lightness (L*), green-red (a*), blue-yellow (b*), chroma (Ch), and hue (h) parameters were recorded, and change in lightness (ΔE*) values were calculated. Statistical analyses were performed with 2-way ANOVA, the Fisher least significant difference test, and the paired samples t test (α=.05).ResultsSignificant interactions were noted between the aging conditions, material type, and finishing and polishing procedures for all evaluated parameters (P<.001). Vita Suprinity and Vita Mark II glazing groups resulted in significantly higher L1* values (P<.05) after the first color measurements. The b1* and C1 values of Vita Suprinity were higher than for other materials (P<.05). The highest ΔE* value was observed in the Lava Ultimate-glazing group (ΔE*=22.7) and the lowest in the Vita Mark II-control group (ΔE*=0.86).ConclusionsThe optical properties of CAD-CAM materials can be affected by the material type and the applied surface finishing and polishing procedure. Manual polishing seems to be a better choice for Lava Ultimate and Cerasmart and glazing for Vita Enamic. For ceramic materials, manual polishing or glazing can be recommended in terms of color stability.



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Effect of ceramic material and resin cement systems on the color stability of laminate veneers after accelerated aging

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Seong-Min Lee, Yu-Sung Choi
Statement of problemLaminate veneers are susceptible to color change during clinical service. Studies that compare the effects of different ceramic and resin cement systems on color stability are lacking.PurposeThe purpose of this in vitro study was to evaluate the color stability of laminate veneers after accelerated aging using different ceramic and resin cement systems.Material and methodsCeramic specimens (N=168; shade A1; thickness, 0.50 ±0.05 mm; diameter, 10.00 ±0.10 mm) were prepared using nanofluorapatite and lithium disilicate (high translucency [HT] to low translucency [LT]) ceramics. Light-polymerizing (LP) cements were classified by brightness (high or low). Dual-polymerizing cements were classified by composition (base-only [DB] or base-catalyst [DC]) for comparison of color stability on the basis of polymerization type. DB cement was light-polymerizing, whereas DC cement was dual-polymerizing. They were further classified by shade (transparent, white, or yellow [n=7, each]). Color difference (ΔE) values were obtained by spectrophotometric quantification of L* (lightness), a* (green-red), and b* (blue-yellow) values before and after aging. The Kruskal-Wallis, Mann-Whitney U, Wilcoxon signed rank, and Bonferroni post hoc tests were used for statistical analysis.ResultsAfter specimens were subjected to accelerated aging, HT ceramic specimens luted with yellow-shade DC cement exhibited the greatest color change (ΔE=2.11), whereas HT and LT ceramic specimens luted with low-brightness LP cement exhibited the least color change (ΔE=1.37). In HT ceramic specimens, which exhibited the greatest color change of the 3 ceramic types, transparent shade cement exhibited significantly lower ΔE values than the other shades with DB (P<.001) and DC cements (P=.010). High-brightness cement exhibited significantly higher ΔE values than low-brightness cement when used with NF (P=.017), HT (P<.001), and LT (P<.001) ceramics. The ΔE values of DB cement were not always lower than those of DC cement. For all specimens, the aging of laminate veneers decreased the L* values and increased the a* and b* values.ConclusionsCeramic and resin-cement systems affected the color stability of laminate veneers. Relative to other ceramics, HT lithium disilicate ceramics exhibited greater color changes upon aging. For HT ceramics, the use of transparent shade resin cement is recommended. The lower the brightness of resin cement, the higher the color stability of veneers. For luting of 0.5-mm-thick laminate veneers with dual-polymerizing cement, light polymerization did not yield better color stability than dual polymerization over time.



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The hemi-engaging fixed dental implant prosthesis: A technique for improved stability and handling

Publication date: Available online 6 January 2018
Source:The Journal of Prosthetic Dentistry
Author(s): Todd R. Schoenbaum, Richard G. Stevenson, Eric Balinghasay
Clinicians commonly contend that the screw-retained, implant-supported fixed dental prosthesis (FDP) should be fabricated with all nonengaging abutments to allow for the inherent nonparallelism of the implants and the inability of the abutment connections to draw together during insertion and removal. The problem with a fully nonengaging FDP is difficulty in handling and more strain on the abutment screws, ultimately leading to increased rates of breakage and loosening. The hemi-engaging FDP design regains much of the advantage afforded by the internal connection and improves prosthetic handing both clinically and in the laboratory. The benefits of this technique are best seen for short-span (fewer than 5 units), screw-retained, implant-supported FDPs.



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C-Cbl and Cbl-b expression in skull base chordomas is associated with tumor progression and poor prognosis

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): Peng Luo, Xin Wang, Jinpeng Zhou, Long Li, Zhitao Jing
Chordomas are rare, locally aggressive malignancies that are often difficult to eradicate. Surgery and radiotherapy are the first-line treatments, but the probability of local recurrence is high. According to our previous research, c-Cbl and Cbl-b have been linked to tumor progression and poor prognosis of glioma. However, their role in skull base chordomas is unclear. To clarify this issue, in the present study we analyzed the expression of c-Cbl and Cbl-b in relation to the clinicopathological features and clinical outcome of skull base chordomas patients (n=70). C-Cbl and Cbl-b expression was evaluated by immunohistochemistry and a survival analysis was performed based on clinical data. We found that c-Cbl and Cbl-b were upregulated in 30/70 (42.9%) and 32/70 (45.7%) patient with skull base chordomas, respectively. A Kaplan-Meier analysis and log-rank test indicated that high c-Cbl and Cbl-b levels were significantly associated with overall survival (P=0.003 and P=0.008, respectively) and progression-free survival (P<0.001 and P=0.022, respectively). These data indicated that c-Cbl and Cbl-b expression in skull base chordomas can predict tumor invasion and poor prognosis and are therefore potential therapeutic targets for chordomas treatment.



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Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with the diagnosis of spindle cell/pleomorphic lipoma

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): David Creytens, Thomas Mentzel, Liesbeth Ferdinande, Joost van Gorp, Jo Van Dorpe, Uta Flucke




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Differentiating Breast Carcinoma with Signet-Ring Features from Gastrointestinal Signet-Ring Carcinoma: Assessment of Immunohistochemical Markers

Publication date: Available online 6 January 2018
Source:Human Pathology
Author(s): Yiang Hui, Yihong Wang, Gahie Nam, Jacqueline Fanion, Ashlee Sturtevant, Kara A. Lombardo, Murray B. Resnick
Signet-ring morphology is recognized throughout the gastrointestinal tract. However, this pattern may be observed in other primary sites giving rise to diagnostic challenges in the work-up of metastases. Relatively newer immunohistochemical markers have not been evaluated in this context. We assessed expression patterns of several common immunohistochemical markers in tumors with signet-ring morphology to delineate a pragmatic approach to this differential diagnosis. Primary breast and gastrointestinal carcinomas showing signet-ring features were reviewed. Non-mammary and non-gastrointestinal tumors with this morphology were included for comparison. Estrogen receptor (ER), progesterone receptor (PR), e-cadherin, CK7, CK20, GCDFP-15, mammaglobin, CDX2, GATA-3, and HepPar-1 immunohistochemistry was performed. Expression patterns were compared between breast and gastrointestinal tumors as well as lobular breast and gastric tumors. Ninety-three cases were identified: 33 breast carcinomas including 13 lobular, 50 gastrointestinal tumors including 23 gastric, and 10 from other sites. ER (Sensitivity=81.8%, Specificity=100%, Positive predictive value (PPV)=100%, Negative predictive value (NPV)=89.3%) and GATA-3 (Sensitivity=100%, Specificity=98%, PPV=96.8%, NPV=100%) expression were associated with breast origin. CK20 (Sensitivity=66.7%, Specificity=93.3%, PPV=94.1%, NPV=63.6%) and CDX2 (Sensitivity=72%, Specificity=100%, PPV=100%, NPV=68.9%) demonstrated the strongest discriminatory value for gastrointestinal origin. These markers exhibited similar discriminatory characteristics when comparing lobular and gastric signet ring carcinomas. In a limited trial on metastatic breast and gastric cases, these markers successfully discriminated between breast and gastric primary sites in 15 of 16 cases. ER and GATA-3 are most supportive of mammary origin and constitute an effective panel for distinguishing primary breast from primary gastrointestinal signet-ring tumors when combined with CK20 and CDX2 immunohistochemistry.



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Ex-vivo generation of drug-eluting islets improves transplant outcomes by inhibiting TLR4-Mediated NFkB upregulation

Publication date: March 2018
Source:Biomaterials, Volume 159
Author(s): Charles A. Chang, Babatope Akinbobuyi, Jeremy M. Quintana, Gumpei Yoshimatsu, Bashoo Naziruddin, Robert R. Kane
The systemic administration of immunosuppressive and anti-inflammatory drugs is routinely employed in organ transplantation to minimize graft rejection and improve graft survival. Localized drug delivery has the potential to improve transplant outcomes by providing sustained exposure to efficacious drug concentrations while avoiding systemic immunosuppression and off-target effects. Here, we describe the synthesis of a novel prodrug and its direct covalent conjugation to pancreatic islets via a cleavable linker. Post-transplant, linker hydrolysis results in the release of a potent anti-inflammatory antagonist of TLR4, localized to the site of implantation. This covalent islet modification significantly reduces the time and the minimal effective dose of islets necessary to achieve normoglycemia in a murine transplantation model. In streptozotocin-induced diabetic C57BL/6 mice a syngeneic transplant of ∼100 modified islets achieved a 100% cure rate by the end of a 4-week monitoring period, compared to a 0% cure rate for untreated control islets. Overall, this direct prodrug conjugation to islets is well tolerated and preserves their functionality while affording significantly superior transplant outcomes. The development of drug-eluting tissues that deliver sustained and localized doses of small-molecule therapeutics represents a novel pathway for enhancing success in transplantation.



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Safety and immunogenicity of single-dose live oral cholera vaccine strain CVD 103-HgR in healthy adults age 18–45

Publication date: Available online 6 January 2018
Source:Vaccine
Author(s): James M. McCarty, Michael D. Lock, Kristin M. Hunt, Jakub K. Simon, Marc Gurwith
The attenuated recombinant Vibrio cholerae O1 vaccine strain CVD 103-HgR, re-developed as PXVX0200, elicits a rapid serum vibriocidal antibody (SVA) response and protects against cholera diarrhea in volunteer challenge studies. We performed a phase 3, placebo controlled, double blind, multi-center study to further assess the safety, immunogenicity, and lot-to-lot consistency of PXVX0200. Adult volunteers 18–45 years of age were randomized 8:1 to receive a single dose of 1 × 10⁹ CFU of PXVX0200 from three production lots or saline placebo. Immunogenicity endpoints included SVA and anti-cholera toxin (CT) antibody levels on days 1, 11, 29, 91 and 181. Safety was assessed by comparing solicited signs and symptoms on days 1–8, unsolicited adverse events through day 29 and serious adverse events through day 181. A total of 3146 participants were enrolled, including 2795 vaccine and 351 placebo recipients. The SVA seroconversion rates at day 11 were 94% and 4% in the PXVX0200 and placebo recipients, respectively (P < .0001). Cumulative SVA seroconversion occurred among 96% of vaccine recipients. PXVX0200 SVA GMTs peaked on day 11 and remained significantly higher than placebo through day 181 while the fold-rise over baseline in PXVX0200 anti-CT antibody was significantly greater than placebo at every post-vaccination time point. Most reactogenicity was mild and resolved within 1–3 days with headache and diarrhea more frequently reported in PXVX0200 recipients. There were no differences in unsolicited adverse events and no study-related serious adverse events. Immunogenicity and safety endpoints were equivalent between the three production lots. PXVX0200 is immunogenic and well tolerated across multiple production lots.Clinical Trials Registration: Clinicaltrials.gov NCT02094586.



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Measles, mumps, and rubella antibody patterns of persistence and rate of decline following the second dose of the MMR vaccine

Publication date: Available online 6 January 2018
Source:Vaccine
Author(s): Emma E. Seagle, Robert A. Bednarczyk, Tenisha Hill, Amy Parker Fiebelkorn, Carole J. Hickman, Joseph P. Icenogle, Edward A. Belongia, Huong Q. McLean
BackgroundAntibodies to measles, mumps, and rubella decline 3% per year on average, and have a high degree of individual variation. Yet, individual variations and differences across antigens are not well understood. To better understand potential implications on individual and population susceptibility, we reanalyzed longitudinal data to identify patterns of seropositivity and persistence.MethodsChildren vaccinated with the second dose of measles, mumps, rubella vaccine (MMR2) at 4–6 years of age were followed up to 12 years post-vaccination. The rates of antibody decline were assessed using regression models, accounting for differences between and within subjects.ResultsMost of the 302 participants were seropositive throughout follow-up (96% measles, 88% mumps, 79% rubella). The rate of antibody decline was associated with MMR2 response and baseline titer for measles and age at first dose of MMR (MMR1) for rubella. No demographic or clinical factors were associated with mumps rate of decline. One month post-MMR2, geometric mean titer (GMT) to measles was high (3892 mIU/mL), but declined on average 9.7% per year among those with the same baseline titer and <2-fold increase post-MMR2. Subjects with ≥2-fold experienced a slower decline (≤7.4%). GMT to rubella was 149 one month post-MMR2, declining 2.6% and 5.9% per year among those who received MMR1 at 12–15 months and >15 months, respectively. GMT to mumps one month post-MMR2 was 151, declining 9.2% per year. Only 14% of subjects had the same persistence trends for all antigens.ConclusionsThe rate of antibody decay varied substantially among individuals and the 3 antigen groups. A fast rate of decline coupled with high variation was observed for mumps, yet no predictors were identified. Future research should focus on better understanding waning titers to mumps and its impacts on community protection and individual susceptibility, in light of recent outbreaks in vaccinated populations.



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Immunogenicity and protective efficacy of an inactivated cell culture-derived Seneca Valley virus vaccine in pigs

Publication date: Available online 5 January 2018
Source:Vaccine
Author(s): Fan Yang, Zixiang Zhu, Weijun Cao, Huanan Liu, Keshan Zhang, Hong Tian, Xiangtao Liu, Haixue Zheng
Seneca Valley virus (SVV) infection in pigs is associated with porcine idiopathic vesicular disease (PIVD). Outbreaks of SVV infection in pig herds have been reported in several Asia and Americas countries. Recently, a series of outbreaks of SVV infection occurred in China, Canada, Thailand and the United States. However, no available vaccines have been developed to limit the transmission of SVV. The SVV CH-FJ-2017 from Fujian province in China is a representative of the epidemic strains, and shows 98.5–99.9% capsid protein amino acid identity with the recent SVV strains. In the present study, we developed a SVV CH-FJ-2017 inactivated vaccine. The SVV was produced by cultivation of BHK-21 cells in roller bottles, inactivated with binary ethylenimine, and mixed with oil adjuvant (Montanide ISA). The immunogenicity of the inactivated vaccine in pigs was evaluated by neutralizing test, and the immunized pigs were challenged with SVV CH-FJ-2017. The results showed that animals receiving one dose of the inactivated vaccine (2 μg/dose) with oil adjuvant developed high neutralizing antibody titers and showed no clinical signs after virus challenge comparing with the non-vaccinated animals, indicating a good protective efficacy of the produced vaccine against SVV infection. This is the first reported SVV vaccine that can be used for control of SVV infection in pigs.



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Involvement of nucleoside transporters in the transcorneal permeation of topically instilled substrates in rabbits in-vivo

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Hanuman Prasad Sharma, Nabanita Halder, Sundararajan Baskar Singh, Thirumurthy Velpandian
The objective of the current study was to characterize and evaluate the functional importance of the Nucleoside Transporters (NTs) in the cornea of the rabbits. Reverse transcriptase polymerase chain reaction (RT-PCR) was used for the molecular characterization of the NTs. Their functionality was evaluated using two substrates, ribavirin and cytarabine. Dipyridamole was used as a blocker for the study. All the treatments were given topically. Molecular characterization of NTs revealed presence of ent1, ent2, ent3 and cnt3 in the cornea. The concentration vs time profile for cytarabine in Aqueous Humor (AH) exhibited a statistically significant (p<0.05) drop at 1h with blocker pretreatment. The mean AUC0–2 between the treatments was also differing in a significant (p<0.05) manner. The concentration vs time profile for ribavirin in AH also showed a significant (p<0.05) decrease in its concentration at 1h with blocker pretreatment. Dipyridamole was able to block ribavirin's entry with as low as 40nM concentration while complete blockade was achieved at 8mM and above. When cytarabine and ribavirin were co-administered, ribavirin at a concentration of 6.5mM significantly inhibited (p<0.05) the transcorneal permeation of cytarabine up to 80%. To conclude, this study showed the presence and functional importance of NTs in the transcorneal uptake of nucleoside substrates. This study further revealed the presence of concentration dependent competitive inhibition among substrates for their transcorneal permeation.

Graphical abstract

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Minimally invasive skin tape strip RNA-seq identifies novel characteristics of type 2-high atopic dermatitis disease endotype

Publication date: Available online 6 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Nathan Dyjack, Elena Goleva, Cydney Rios, Byung Eui Kim, Lianghua Bin, Patricia Taylor, Caroline Bronchick, Clifton F. Hall, Brittany N. Richers, Max A. Seibold, Donald Y. Leung
BackgroundExpression profiling of skin biopsies has established molecular features of the skin in atopic dermatitis (AD). Invasiveness of biopsies has prevented their use in defining individual level AD pathobiological mechanisms (endotypes) in large research studies.ObjectiveTo determine if minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes.MethodsWe sampled non-lesional and lesional skin tape strips and biopsies from adult Caucasian subjects AD patients (18 males, 12 females; age (Mean±SE) 36.3±2.2 yrs) and healthy controls (9 males, 16 females; age (Mean±SE) 34.8±2.2 yrs). Ampliseq whole transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsies, and clinical trait correlations were performed.ResultsSkin tape expression profiles were distinct from skin biopsy profiles and better sampled epidermal differentiation complex genes. Skin tape expression of 29 immune and epidermis-related genes (FDR<5%) separated AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of AD subjects exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes including overexpression of IL13, IL4R, CCL22, CCR4 (log2FC=5.5, 2.0, 4.0, and 4.1, respectively), and at a pathway level by T-helper 2/dendritic cell activation. Both expression and immunostaining of skin biopsies indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing the high affinity IgE receptor (FcεRI). The type 2-high endotype group exhibited more severe disease by both EASI score and body surface area covered by lesions.ConclusionMinimally invasive expression profiling of non-lesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.



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Do performance measures of strength, balance and mobility predict quality of life and community reintegration after stroke?

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Joshua W. Cohen, Tanya D. Ivanova, Brenda Brouwer, Kimberly J. Miller, Dianne Bryant, S. Jayne Garland
ObjectiveTo investigate the extent to which physical performance measures of strength, balance and mobility taken at discharge from inpatient stroke rehabilitation can predict health-related quality of life (HRQoL) and community reintegration after 6 months.DesignLongitudinal StudySettingUniversity LaboratoryParticipantsSeventy-five adults recruited within one month following discharge home from inpatient stroke rehabilitation. Inclusion criteria were: major unilateral hemispheric stroke, English speaking, able to communicate, discharged home. Serious comorbidities and a prior stroke affecting the opposite side were exclusion criteria.InterventionsNot applicable.Main Outcome Measure(s)Short Form 36-Item Health Survey (SF-36) for HRQoL and the Subjective Index of Physical and Social Outcome (SIPSO) for community reintegration. Physical performance measures were the 6-minute walk test (6MWT), Timed up and Go (TUG), Berg Balance Scale, Community Balance and Mobility scale, and isokinetic torque and power of hip, knee and ankle on the paretic and non-paretic sides. Other prognostic variables included age, sex, stroke type and location, comorbidities, and motor Functional Independence Measure.ResultsSeparate stepwise linear regressions were performed with the SF-36 and SIPSO as dependent variables. The total paretic lower limb torque and 6MWT predicted the SF-36 Physical Component Summary (Adjusted R²=0.30). Total paretic lower limb torque, and TUG predicted the SIPSO Physical component (Adjusted R²=0.47). Total paretic lower limb torque significantly predicted the SF-36 Mental Component Score, but the adjusted R² was very low (0.06). Similarly, the TUG significantly predicted the SIPSO social component, but again, the adjusted R² was low (0.09).ConclusionsMeasures of physical performance including muscle strength and mobility at discharge can partially predict HRQoL and community reintegration 6 months later. Further research is necessary for more accurate predictions.



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Changes in Energy Intake and Diet Quality during an 18-Month Weight-Management Randomized Controlled Trial in Adults with Intellectual and Developmental Disabilities

Publication date: Available online 6 January 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Lauren T. Ptomey, Felicia L. Steger, Jaehoon Lee, Debra K. Sullivan, Jeannine R. Goetz, Jeffery J. Honas, Richard A. Washburn, Cheryl A. Gibson, Joseph E. Donnelly
BackgroundPrevious research indicates that individuals with intellectual and developmental disabilities (IDDs) are at risk for poor diet quality.ObjectiveThe purpose of this secondary analysis was to determine whether two different weight-loss diets affect energy intake, macronutrient intake, and diet quality as measured by the Healthy Eating Index-2010 (HEI-2010) during a 6-month weight-loss period and 12-month weight-management period, and to examine differences in energy intake, macronutrient intake, and HEI-2010 between groups.DesignOverweight/obese adults with IDDs took part in an 18-month randomized controlled trial and were assigned to either an enhanced Stop Light Diet utilizing portion-controlled meals or a conventional diet consisting of reducing energy intake and following the 2010 Dietary Guidelines for Americans. Proxy-assisted 3-day food records were collected at baseline, 6 months, and 18 months, and were analyzed using Nutrition Data System for Research software. HEI-2010 was calculated using the data from Nutrition Data System for Research.Participants/settingThe study took place from June 2011 through May 2014 in the greater Kansas City metropolitan area.Main outcome measuresThis was a secondary analysis of a weight-management intervention for adults with IDDs randomized to an enhanced Stop Light Diet or conventional diet, to examine differences in energy intake, macronutrient intake, and HEI-2010 across time and between groups.Statistical analyses performedIndependent- and paired-samples t tests and general mixed modeling for repeated measures were performed to examine group differences and changes at baseline, 6 months, and 18 months between the enhanced Stop Light Diet and conventional diet groups.ResultsOne hundred and forty six participants (57% female, mean±standard deviation age=36.2±12.0 years) were randomized to either the enhanced Stop Light Diet or conventional diet group (77 enhanced Stop Light Diet, 69 conventional diet) and provided data for analysis at baseline, 124 completed the 6-month weight-loss period, and 101 completed the 18-month study. Participants on the enhanced Stop Light Diet diet significantly reduced energy intake at 6 and 18 months (both P<0.001), but those on the conventional diet did not (both P=0.13). However, when accounting for age, sex, race, education level, and support level (mild vs moderate IDD), there was a significant decrease during the 18-month intervention in energy intake for the enhanced Stop Light Diet and conventional diet groups combined (P<0.01 for time effect), but no significant group difference in this change (P=0.39 for group-by-time interaction). There was no significant change in total HEI-2010 score at 6 and 18 months (P=0.05 and P=0.38 for the enhanced Stop Light Diet group; P=0.22 and P=0.17 for the conventional diet group), and no significant group difference at 6 and 18 months (P=0.08 and P=0.42). However, when participants' age, sex, race, education level, and support level were accounted for, mixed modeling indicated a significant increase in total HEI-2010 scores for the enhanced Stop Light Diet and conventional diet groups combined during the 18-month intervention (P=0.01 for time effect).ConclusionsThe results of this study found that after controlling for demographic factors, individuals with IDDs can decrease their energy intake and increase their diet quality, with no significant differences between the enhanced Stop Light Diet and conventional diet groups.



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Equipping Future Generations of Registered Dietitian Nutritionists and Public Health Nutritionists: A Commentary on Education and Training Needs to Promote Sustainable Food Systems and Practices in the 21st Century

Publication date: Available online 6 January 2018
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Jessica Wegener




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