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Πέμπτη 20 Ιουλίου 2017

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Publication date: August 2017
Source:Trends in Cell Biology, Volume 27, Issue 8





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Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review

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Publication date: Available online 21 July 2017
Source:Cancer Treatment Reviews
Author(s): Abrahim Al-Mamgani, Erik van Werkhoven, Arash Navran, Baris Karakullukcu, Olga Hamming-Vrieze, Melanie Machiels, Lilly-Ann van der Velden, Wouter V. Vogel, W. Martin Klop
Background: The head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted.Methods: PubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated.Results: Eleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0-5.9%, 95% CI 1.6-3.5%). The incidence of cRF correlated only with T-stage (p=0.008), and involvement of midline (p=0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p=0.344).Conclusion: The incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups.



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Structural characterisation of galacto-oligosaccharides (VITAGOS™) sythesized by transgalactosylation of lactose

Publication date: Available online 21 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): Qingbin Guo, H. Douglas Goff, Steve W. Cui
A galacto-oligosaccharide product (VITAGOS™) was prepared by glycoside hydrolases (β-galactosidase from Aspergillus oryzae and Kluyveromyces lactis) using lactose as substrate. Monosaccharide composition analysis indicated that VITAGOS™ contained 40.3% (w/w, dry basis) glucose and 51.1% (w/w, dry basis) galactose. According to high performance size exclusion chromatography (HPSEC) analysis, VITAGOS™ was a sugar mixture with degree of polymerisation (DP) ranging from 1 to 7, with DP2 and DP3 as the dominant fractions (32% and 33%, w/w). In addition, more than three fractions were observed for each DP pool indicated by the oligosaccharides profiles obtained from high performance anion exchange chromatography (HPAEC) analysis. Six sub-fractions (F1-F6, corresponding to DP1 to DP6 rich fraction, respectively) were then collected using biogel P-2 column, followed by structural characterisation through methylation analysis combined with 1D & 2D NMR spectroscopy. The detailed molecular structures of VITAGOS™ with DP up to 4 are provided.

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Occurrence and distribution of six selected endocrine disrupting compounds in surface- and groundwaters of the Romagna area (North Italy)

Abstract

Endocrine disrupting compounds (EDCs) are a wide group of contaminants of emerging concern known to be harmful for organisms. The aim of the study was to assess the occurrence and distribution of six EDCs (estrone—E1, ß-estradiol—E2, 17α-ethinylestradiol—EE2, bisphenol A—BPA, perfluooctanoic acid—PFOA, perfluorooctane sulfonate—PFOS) in the Apenninic rivers and groundwaters of the Romagna area (North of Italy). Groundwaters were unaffected by EDC contamination, while all classes of compounds were detected at concentrations above the method quantification limit (MQL) in the majority of the river bodies. In detail, PFOA and PFOS concentrations varied between <MQL and 17.7 ng/l (PFOA) and between <MQL and 5.5 ng/l (PFOS), and their occurrence in the aquatic compartment was related to the discharge of wastewater treatment plant effluents. Concerning estrogens, EE2 was below the MQL in all samples, whereas E1 and E2 reached concentrations up to 39.7 ng/l (E2) and 28 ng/l (E1) in surface waters. The highest estrogen values were registered in those areas where livestock and farming are the main activities, indicating a close relation between these activities and estrogen release into the aquatic compartment. BPA (<MQL–171.3 ng/l) distribution in river waters did not show any correlation with a specific anthropic activity; a mixture of sources of contamination (e.g., industries of food packaging and plastic production) is rather responsible for its detection in river bodies. Overall, the northern part of the Romagna area showed a higher contamination by EDCs, in contrast with the southern part, which was almost unaffected by this kind of microcontamination.



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Clinically proven bone regeneration solutions



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Interactive group therapy for the management of myofascial temporomandibular pain



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Hygienist appointments: Pain vs non pain



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Superior soft tissue management



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Dental education: All of the picture



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Public health: Extraordinary heroism



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Revolutionary self-clearing dental mirror



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Pharmacology: Common side effects



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A topical solution?



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NHS dental service utilisation and social deprivation in older adults in North West England



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Innovative dentists wanted



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Smarter endodontic after care



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New cover series celebrates teeth in literature



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Who's chilling in your chair?



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Ultimate versatility in one dental unit



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Glasgow creates 'world's biggest smile'



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Introducing a new online community



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The buried dermal pennant stitch for the correction of symmastia following breast reduction

Abstract

Symmastia is a difficult surgical problem to correct. Symmastia has various etiologies and can occur following reduction mammoplasty. Techniques previously described have been criticized for their limited success due to temporary results, inadequate correction, or creation of secondary deformities. In this study, we present a novel approach to correct symmastia in a patient who developed the deformity following reduction mammoplasty. The technique described uses a buried dermal pennant suture, local advancement flaps, and liposuction to correct the symmastia and improve medial breast contour. We believe this technique provides adequate and long-term correction of symmastia in the breast reduction patient and avoids the shortcomings of previously described approaches.

Level of Evidence: Level V, therapeutic study



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Research progress on osteoarthritis treatment mechanisms

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Yun-Yao Gu, Jian Chen, Zhu-Long Meng, Wan-Yu Ge, Yang-Yang Bian, Shao-Wen Cheng, Chen-Kun Xing, Jiang-Ling Yao, Jian Fu, Lei Peng
Osteoarthritis is a common disease and is frequently encountered in the older population; the incidence rises sharply with age. It is estimated that more than 360 million people suffer from OA. However, the pathogenesis of osteoarthritis remains unclear, and we cannot effectively prevent the progression of OA. The aim of this review was to explore the molecular markers and signaling pathways that induce chondrocyte apoptosis in OA. We searched, using the key words osteoarthritis, chondrocyte apoptosis, autophagy, endoplasmic reticulum stress, molecular targets, and biomarkers, in PubMed, Web of Science, and Google Scholar from 1994 to 2017. We also reviewed the signaling pathways and molecular markers associated with chondrocyte apoptosis and approaches aimed at inhibiting the apoptosis-inducing mechanism to at least delay the progression of cartilage degeneration in OA. This article provides an overview of targeted therapies and the related signaling pathways in OA.



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Magnetic iron oxide nanoparticles as novel and efficient tools for atherosclerosis diagnosis

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): María Gabriela Montiel Schneider, Verónica Leticia Lassalle
Cardiovascular complications derivate from atherosclerosis are the main cause of death in western world. An early detection of vulnerable atherosclerotic plaques is primordial for a better care of patients suffering the pathology. In this context nanotechnology has emerged as a promising tool to achieve this goal. Nanoparticles based on magnetic iron oxide (MNPs) have been extensively studied in cardiovascular diseases diagnosis, as well as in the treatment and diagnostic of other pathologies. The present review aims to describe and analyze the most current literature regarding to this topic, offering the level of detail required to reproduce the experimental tasks providing a critical input of the latest available reports. The current diagnostic features are presented and compared, highlighting their advantages and disadvantages. Information on novel technology intended to this purpose is also recompiled and in deep analyzed. Special emphasis is placed in magnetic nanotechnology, remarking the possibility to assess selective and multifunctional systems to the early detection of artherosclerotic pathologies.Finally, in view of the state of the art, the future perspectives about the trends on MNPs in artherosclerorsis diagnostic and treatment have also been addressed.

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Dissolving microneedles for transdermal drug delivery: Advances and challenges

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Kevin Ita
Over the last number of years, a significant body of evidence has shown the benefit of using dissolving microneedles (DMNs) for transdermal drug delivery. These devices are prepared from a wide range of materials such as sugars and polymers. DMNs are mainly fabricated by micromolding, photopolymerization, drawing lithography and droplet-airborne blowing. In this review, we have focused on the advances made in the field in recent years using a representative set of studies. Although the list of studies is not exhaustive, they highlight the challenges encountered such as the need to increase mechanical strength as well as medication dose while ensuring fast release of the active ingredient. DMNs can be used to delivery low molecular drugs as well as peptides, proteins and other high molecular weight compounds.

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Regulatory players of DNA damage repair mechanisms: Role in Cancer Chemoresistance

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Kunnathur Murugesan Sakthivel, Sreedharan Hariharan
DNA damaging agents are most common in chemotherapeutic molecules that act against cancer. However, cancer cells possess inherent biological features to overcome DNA damages by activating various distinct repair mechanisms and pathways. Importantly, various oncogenes, cancer stem cells (CSCs), hypoxic environment, transcription factors and bystander signaling that are activated in the cancer cells influence DNA repair, thereby effectively repairing the DNA damage. Repaired cancer cells often become more resistance to further therapy and results in disease recurrence. In this review, we summarize how the various signaling pathways in cancer cells regulates DNA repair and induce chemoresistance.

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Dermoscopy of a pigmented apocrine porocarcinoma arising from a pigmented hidroacanthoma simplex



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Herbal multicomponent extracts enhance wound healing after incision of perianal abscess and in a rat model of infected wounds



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Primary Cutaneous Small/Medium CD4+ T-CELL Lymphoproliferative Disorder Occurring in a Patient With Metastatic Melanoma.

Therapeutic agents designed to stimulate the immune system are now cornerstones in the treatment of metastatic melanoma. These drugs promote lymphocyte growth and survival, which could plausibly result in clinical lymphoproliferative disorders. We report the case of a 62-year-old female with metastatic melanoma who developed primary cutaneous small/medium CD4+ T-cell lymphoproliferative disorder (PC-SMTCL) after treatment with vemurafenib and recombinant high-dose interleukin-2 (IL-2). The patient developed a painless red papule behind the ear. A biopsy showed a dense population of CD4+ lymphocytes with a T-follicular helper cell phenotype. Molecular studies confirmed the presence of a clonal population of T cells, and the process was classified as PC-SMTCL. The patient was diagnosed with metastatic melanoma approximately 3 years before the development of the cutaneous lymphoma and had been treated with vemurafenib followed by 2 courses of IL-2. The patient's last course of IL-2 was completed in April of 2013. She developed the cutaneous lymphoma behind her ear in December of 2015. An association between PC-SMTCL and vemurafenib treatment for advanced melanoma has been reported previously in one patient; however, an association between PC-SMTCL and IL-2 treatment has not been documented. The immunostimulatory properties of IL-2 or vemurafenib may be responsible for the development of PC-SMTCL in our patient. Additionally, antigenic stimulation of the immune system by melanoma itself could contribute to clonal selection of lymphocytes. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Leukocytoclastic Vasculitis and Dermal Perivascular Hemophagocytosis Associated With Adalimumab Therapy for Rheumatoid Arthritis.

Tumor necrosis factor (TNF)-[alpha] inhibitors target TNF-[alpha] to effectively treat autoimmune inflammatory conditions, such as rheumatoid arthritis. However, many cases of cutaneous and systemic vasculitis related to TNF-[alpha] inhibitors have been reported in the literature. Here, the authors report the first case of a 61-year-old Japanese woman who developed leukocytoclastic vasculitis with cutaneous perivascular hemophagocytosis, which was related to elevated cytokines and immune complexes after initiating adalimumab for rheumatoid arthritis without evidence of hemophagocytic syndrome and rarely encountered in the skin. The patient was successfully treated by discontinuing adalimumab and initiating corticosteroid therapy, which should be considered as the treatment of choice. We believe that our case confirms and adds to the evidence pertaining to the involvement of TNF-[alpha] in dermal perivascular hemophagocytosis, a histologic finding rarely observed in the skin. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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A 12-Day-Old Male With a "Skin Tag" on the Chin.

No abstract available

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Comparative Analysis of Chilblain Lupus Erythematosus and Idiopathic Perniosis: Histopathologic Features and Immunohistochemistry for CD123 and CD30.

Distinction of chilblain lupus erythematosus (CLE) from idiopathic perniosis (IP) could predict an underlying connective tissue disease; however, histopathologic discrimination of the two is difficult. Increased CD123+ plasmacytoid dendritic cells and CD30+ lymphocytes have been demonstrated in various forms of cutaneous lupus erythematosus and IP, respectively. To our knowledge, CD123 and CD30 have not been examined in CLE. Our objective was to identify helpful histopathologic and immunohistochemical features in distinguishing CLE and IP. Skin biopsies classified as CLE (n = 20) and IP (n = 39) based on clinicopathologic correlation were collected from 2000 to 2015. Various histopathologic features were examined on hematoxylin and eosin and alcian blue stains. CD123 and CD30 immunostains were performed and characterized. We identified dermal interstitial fibrin exudate (P = 0.0352) and increased dermal mucin (P = 0.0002) as features significantly associated with CLE. Other histopathologic features and CD123 failed to distinguish between groups. CD30+ lymphocytes were sparse in all cases. Despite being the largest series of CLE and IP to date, the number of CLE cases in this study remained relatively limited, and some patients in the IP group may have yet to develop diagnostic features of systemic lupus erythematosus. In conclusion, histopathologic distinction between CLE and IP remains challenging. Interstitial fibrin and abundant dermal mucin help favor CLE. The number and distribution of CD123+ plasmacytoid dendritic cells and CD30+ lymphocytes have no discriminatory role. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Papulonodular Eruption on the Hands in a Patient With Arthritis.

No abstract available

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Onychomatricoma in a Patient With Extensive Vitiligo.

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Cutaneous Atypical Neurofibroma: A Case Report and Review of Literature.

No abstract available

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Atopy as a risk factor for subclinical hypothyroidism development in children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


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Prevalence of chromosomal aberrations in Argentinean agricultural workers

Abstract

Little is known about biosecurity measures and toxic effects during pesticide application in the province of Jujuy, Argentina, particularly concerning the protective measures and mixture of pesticides used by rural workers. We carried out an observational study of agricultural workers from Jujuy (76 exposed subjects and 53 controls) to investigate the prevalence of chromosomal aberrations (CAs) in human lymphocytes as well as the activity level of acetylcholinesterase (AChE) in red blood cell erythrocytes. Whole blood samples (5 mL) were collected in heparinized Vacutainer tubes for cytogenetic analysis and erythrocyte cholinesterase activity determination according to Ellman's method. Cytogenetic results showed a significant CA increase in pesticide-exposed individuals as compared with controls (4.20 ± 0.15 vs. 1.00 ± 0.05, respectively; p < 0.001), suggesting that pesticides are clastogenic agents causing DNA damage. Erythrocyte cholinesterase activity was significantly lower in exposed individuals, evidencing the possible occurrence of perturbations in blood as well as neurotoxicity in pesticide sprayers. These results suggest the need for periodic biomonitoring of these biomarkers together with education and training of occupational workers for the safe application of potentially harmful pesticides.



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The criterion validity and intra-rater reliability of the Japanese version of the Functional Mobility Scale in children with cerebral palsy

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Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Nobuaki Himuro, Hisato Nishibu, Hirokazu Abe, Mitsuru Mori
ObjectiveThe purpose of this study was to develop a Japanese version of the Functional Mobility Scale (FMS), and examine the criterion validity and intra-rater reliability of the FMS in Japan.MethodsThe translation of the FMS was performed according to international standards for the translation of measurements. For criterion validity, 111 children with cerebral palsy (mean age; 12year 1mo±3year 7mo; range 5–18) were rated the Japanese version of the FMS and Gross Motor Function Classification System (GMFCS). For intra-rater reliability, the Japanese version of the FMS was rated twice by 24 parents of children with cerebral palsy by interview and/or telephone with a one- to two-week interval between assessments.ResultsThe criterion validity was confirmed with a strong correlation between GMFCS level and FMS scores (r2=−0.71 to −0.75). For intra-rater reliability, there was a substantial to excellent level of agreement (kappa=0.72–0.87).ConclusionThe study provides evidence of the criterion validity and intra-rater reliability of the Japanese version of the FMS as a measurement of mobility in children with cerebral palsy.



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Gender comparisons in children with ASD entering early intervention

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Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Alexandra M. Fulton, Jessica M. Paynter, David Trembath
BackgroundMales are diagnosed with Autism Spectrum Disorder (ASD) approximately four times as often as females. This has led to interest in recent years of potential under-diagnosis of females, as well as negative consequences for females with ASD due to under-identification. A number of potential explanations for gender bias in diagnosis are discussed including that females and males may present differently despite showing the same core symptoms. Previous research has shown inconsistent findings in comparisons between genders in young children with ASD for whom early intervention is vital. Thus, the aim of the present study was to investigate the social, communication, and cognitive functioning, as well as level of ASD symptoms, in a cohort of children who presented for early intervention to inform understanding of gender differences in this population, as well as to inform understanding of the mechanisms by which gender bias may occur.MethodParticipants included 254 children (42 females) aged 29–74 months who completed measures of cognition, communication skills, adaptive behaviour, and ASD symptoms on entry to early intervention.ResultsConsistent with hypotheses, no significant gender differences were found both overall, and when split by functioning level. However, a similar ratio of males and females was found in both high- and low-functioning groups contrary to predictions.ConclusionsThese results are consistent with some of the previous research that suggests gender differences may not be apparent in clinical samples at this young age. We highlight a need for further research that may use universal screening or longitudinal methods to understand the trajectory of development for females with ASD specifically. Such research could better inform timely and tailored intervention from the preschool years onwards.



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Longitudinal assessment of gait quality in children with bilateral cerebral palsy following repeated lower limb intramuscular Botulinum toxin-A injections

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Publication date: September 2017
Source:Research in Developmental Disabilities, Volume 68
Author(s): Felicity A. Read, Roslyn N. Boyd, Lee A. Barber
BackgroundSerial lower limb intramuscular Botulinum toxin-A (BoNT-A) injections are administered to children with bilateral spastic cerebral palsy (BCP) to reduce spasticity, improve walking and functional mobility, and delay the need for orthopaedic surgery. Gait quality is clinically assessed following BoNT-A with 2D video gait assessments (2DVGA) using the Edinburgh Visual Gait Score (EVGS).AimTo determine the effect of three consecutive treatment cycles of lower limb intramuscular BoNT-A injections on gait quality using the EVGS in children with BCP by retrospectively reviewing repeated 2DVGA measures.Methods and proceduresSeventeen children with BCP and dynamic equinus (8 females and 9 males, age mean (SD), 4.0 (2.2) years, GMFCS I=2 and II=15) were included in the study after a retrospective audit of the records of the Queensland Children's Gait Laboratory (QCGL), Children's Health Queensland, Brisbane. The medical records of children who attended the QCGL between January 2001 and January 2016 were searched for eligibility. Children who had undertaken pre- and post-treatment 2DVGA for the first three lower limb BoNT-A treatment cycles (6 assessments) were reviewed using the EVGS. BoNT-A treatments were administered 7.7 (2.3) months apart and post-BoNT-A reviews occurred 12.6 (6.7) weeks after injection. Mixed-effects linear regression assessed the change from baseline to each subsequent assessment (p<0.05).Outcomes and resultsEVGS reduced significantly by a mean of 2.4 points from pre- to post-BoNT-A in the first treatment cycle (p=0.001). Compared to baseline, mean total EVGS reduced significantly during the second (pre-BoNT-A −1.7 (p=0.020), post BoNT-A −2.8 (p<0.001)) and third (pre-BoNT-A −2.6 (p=0.001), post BoNT-A −2.4 (p=0.002)) treatment cycles. There was no difference in EVGS between post-BoNT-A in the first treatment cycle and scores for the second and third treatment cycles.Conclusions and implicationsImprovements in gait quality were statistically significant, but did not reach the EVGS smallest real difference value of 4 points. Repeated lower limb intramuscular BoNT-A injections to improve gait quality in children with BCP should be reconsidered.



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Fast carotid artery MR angiography with compressed sensing based three-dimensional time-of-fight sequence

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Publication date: Available online 20 July 2017
Source:Magnetic Resonance Imaging
Author(s): Bo Li, Hao Li, Li Dong, Guofu Huang
ObjectiveIn this study, we sought to investigate the feasibility of fast carotid artery MR angiography (MRA) by combining three-dimensional time-of-flight (3D TOF) with compressed sensing method (CS-3D TOF).Materials and methodsA pseudo-sequential phase encoding order was developed for CS-3D TOF to generate hyper-intense vessel and suppress background tissues in under-sampled 3D k-space. Seven healthy volunteers and one patient with carotid artery stenosis were recruited for this study. Five sequential CS-3D TOF scans were implemented at 1, 2, 3, 4 and 5-fold acceleration factors for carotid artery MRA. Blood signal-to-tissue ratio (BTR) values for fully-sampled and under-sampled acquisitions were calculated and compared in seven subjects. Blood area (BA) was measured and compared between fully sampled acquisition and each under-sampled one.ResultsThere were no significant differences between the fully-sampled dataset and each under-sampled in BTR comparisons (P>0.05 for all comparisons). The carotid vessel BA measured from the images of CS-3D TOF sequences with 2, 3, 4 and 5-fold acceleration scans were all highly correlated with that of the fully-sampled acquisition. The contrast between blood vessels and background tissues of the images of 2 to 5-fold acceleration is comparable to that of fully sampled images. The images at 2× to 5× exhibit the comparable lumen definition to the corresponding images at 1×.ConclusionBy combining pseudo-sequential phase encoding order, CS reconstruction, and 3D TOF sequence, this technique provides excellent visualizations for carotid vessel and calcifications in a short scan time. It has the potential to be integrated into current multiple blood contrast imaging protocol.



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Assessment of MRI issues for a new cerebral spinal fluid shunt, gravitational valve (GV)

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Publication date: Available online 20 July 2017
Source:Magnetic Resonance Imaging
Author(s): Daniel Moghtader, Hans-Joachim Crawack, Christoph Miethke, Zinah Dörlemann, Frank G. Shellock
PurposeA gravitational valve (GV) may be used to treat hydrocephalus, offering possible advantages that include avoidance of over drainage and long-term complications. Because a GV is made from metal, there are potential safety and other problems related to the use of MRI. The objective of this investigation was to evaluate MRI-related issues (i.e., magnetic field interactions, heating, and artifacts) for a newly developed, metallic GV.MethodsTests were performed on the GV (GAV 2.0) using well-accepted techniques to assess magnetic field interactions (translational attraction and torque, 3-Tesla), MRI-related heating (1.5-T/64-MH and 3-T/128-MHz, whole body averaged SAR, 2.7-W/kg and 2.9-W/kg, respectively), artifacts (3-Tesla; gradient echo and T1-weighted, spin echo sequences), and possible functional changes related to exposures to different MRI conditions (exposing six samples each to eight different pulse sequences at 1.5-T/64-MHz and 3-T/128-MHz).ResultsMagnetic field interactions were not substantial (deflection angle 2°, no torque) and heating was minor (highest temperature rise, ≥1.9°C, highest background temperature rise, ≥1.7°C). Artifacts on the gradient echo pulse sequence extended approximately 10mm from the size and shape of the GV. The different exposures to 1.5-T/64-MHz and 3-T/128-MHz conditions did not alter or damage the operational aspects of the GV samples.ConclusionsThe findings demonstrated that MRI can be safely used in patients with this GV and, thus, this metallic implant is deemed acceptable or "MR Conditional" (i.e., using current labeling terminology), according to the conditions used in this study.



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Predicting the nodal status in gastric cancers: The role of apparent diffusion coefficient histogram characteristic analysis

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Publication date: Available online 20 July 2017
Source:Magnetic Resonance Imaging
Author(s): Song Liu, Yujuan Zhang, Jie Xia, Ling Chen, Wenxian Guan, Yue Guan, Yun Ge, Jian He, Zhengyang Zhou
PurposeTo explore the application of histogram analysis in preoperative T and N staging of gastric cancers, with a focus on characteristic parameters of apparent diffusion coefficient (ADC) maps.Materials and methodsEighty-seven patients with gastric cancers underwent diffusion weighted magnetic resonance imaging (b=0, 1000s/mm2), which generated ADC maps. Whole-volume histogram analysis was performed on ADC maps and 7 characteristic parameters were obtained. All those patients underwent surgery and postoperative pathologic T and N stages were determined.ResultsFour parameters, including skew, kurtosis, s-sDav and sample number, showed significant differences among gastric cancers at different T and N stages. Most parameters correlated with T and N stages significantly and worked in differentiating gastric cancers at different T or N stages. Especially skew yielded a sensitivity of 0.758, a specificity of 0.810, and an area under the curve (AUC) of 0.802 for differentiating gastric cancers with and without lymph node metastasis (P<0.001). All the parameters, except AUClow, showed good or excellent inter-observer agreement with intra-class correlation coefficients ranging from 0.710 to 0.991.ConclusionCharacteristic parameters derived from whole-volume ADC histogram analysis could help assessing preoperative T and N stages of gastric cancers.



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Monitoring of Free Flaps with Combined Tissue Spectrophotometry and Laser Doppler Flowmetry in an Animal Experimental Model

J reconstr Microsurg
DOI: 10.1055/s-0037-1603735

Background When mobilizing free flaps, postoperative monitoring of perfusion is crucial to detect ischemia. Continuous monitoring may be feasible by applying a combination of tissue spectrophotometry and laser Doppler flowmetry (oxygen-2-see [O2C]). Material and Methods On 10 pigs, two symmetrical myocutaneous flaps were mobilized on each side of the abdomen based on the deep inferior epigastric vessels. Flaps were randomized to clamp either the artery or the vein and measurements using O2C were performed before, during, and after the intervention yielding information on blood flow, saturation (sat), and relative tissue hemoglobin (rHgb) concentration. Results Baseline values were similar in all groups. Introduction of ischemia caused a rapid decline in arterial ischemic flaps which all reached threshold levels in 3 minutes, whereas that was only the case for three of six venous ischemic flaps. Venous clamping resulted in a decline in sat, while the response to arterial clamping was an initial decline followed by an increase in sat. In all arterial ischemic flaps, rHgb concentration either decreased or remained at baseline levels but increased in all venous ischemic flaps. The median time to a 30% rise was 1 minute at an 8-mm depth. The rate of decreasing flow along with the rHgb measurements made it possible to distinguish the arterial ischemia (AI) from the venous ischemia (VI) within the first few minutes. Conclusion In this animal experimental model, O2C measurements of blood flow reliably detected ischemia. By adding information about rHgb, it was possible to distinguish between AI and VI.
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To coil or not to coil: application practices, perception and efficacy of mosquito coils in a malaria-endemic community in Ghana

Abstract

Although evidence of mosquito coils' impact on disease epidemiology is limited, they are popularized as mosquito-borne disease prevention devices. Their usage affects the environment, human and mosquito health. This study investigated the perception, usage pattern and efficacy of coils in a predominantly poor malaria-endemic Ghanaian peri-urban area. Information on protection methods, perception and usage pattern was garnered using questionnaires. The efficacy of commonly used coils in the area was then assessed on the malaria vector, Anopheles gambiae, in a glass chamber. Sole or co-application of mosquito control methods and risky usage practices were reported. Coils were deemed harmful to humans and mosquitoes, and their perceived effectiveness varied, with several factors influencing their purchase. High d-allethrin concentration coils induced quicker mosquito knockdown; however, mortality was less than 85%. The coil usage pattern compromises users' health and can enhance mosquito tolerance to d-allethrin. The coils were ineffective against the vector, outlining a dichotomy between the users' perception of efficacy and the observed efficacy. Hence, the usage of other safer and more effective vector control methods should be encouraged to protect households.



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Outcomes of radioembolization for unresectable hepatocellular carcinoma in patients with marginal functional hepatic reserve

Publication date: Available online 20 July 2017
Source:Clinical Imaging
Author(s): Derek M. Biederman, Raghuram Posham, Raisa J. Durrani, Joseph J. Titano, Rahul S. Patel, Nora E. Tabori, Francis S. Nowakowski, Aaron M. Fischman, Robert A. Lookstein, Edward Kim
PurposeTo evaluate the outcomes of radioembolization (RE) as a therapy for unresectable hepatocellular carcinoma (HCC) in patients with marginal functional hepatic reserve.MethodsA retrospective review of 471 patients (1/2010–7/2015) treated with RE (Therasphere, BTG, UK) was performed. A total of 36 patients (mean age: 66.1±9.3, male: 86.1%) underwent therapy for HCC with a MELD≥15 (median: 16, range: 15–22). Baseline demographics of the study cohort were as follows: etiology (HCV: 26, 72.2%), cirrhosis (n=32, 88.9%), ECOG 0 (n=16, 44.4%), Child-Pugh class (A=15, B=19, C=2), unilobar distribution (n=27, 75%), AFP>200 (n=11, 30.6%), portal vein thrombosis (PVT, n=7, 19.4%), metastasis (n=3, 8.3%). Outcomes analyzed included CTCAEv4.03 laboratory toxicities (120-day), imaging response (mRECIST), progression-free survival (PFS), and overall survival (OS).ResultsA total of 42 treatments were performed with mean dose of 2.02±1.23GBq. The cumulative grade 3/4 toxicity was 28% overall and 21% for bilirubin at 120-days. The objective response and disease control rates were 48.3% (14/29) and 69% (20/29) respectively. The median (95% CI) PFS was 5.9 (4.4–7.7) months. Ten (27.8%) patients received additional locoregional therapy at a median (IQR) of 138 (102–243) days post RE. The mean (95% CI) OS was 21.9 (14.8–29.0) months. The absence of PVT was associated with improved OS (p=0.005) Disease control at 90-days was also associated with an OS benefit (p=0.037).ConclusionsPatients with unresectable HCC and marginal functional hepatic reserve treated with RE had favorable objective response and disease control rates, both predictive of overall survival.



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Cd, Pb, and Zn mobility and (bio)availability in contaminated soils from a former smelting site amended with biochar

Abstract

Biochar is a potential candidate for the remediation of metal(loid)-contaminated soils. However, the mechanisms of contaminant-biochar retention and release depend on the amount of soil contaminants and physicochemical characteristics, as well as the durability of the biochar contaminant complex, which may be related to the pyrolysis process parameters. The objective of the present study was to evaluate, in a former contaminated smelting site, the impact of two doses of wood biochar (2 and 5% w/w) on metal immobilization and/or phytoavailability and their effectiveness in promoting plant growth in mesocosm experiments. Different soil mixtures were investigated. The main physicochemical parameters and the Cd, Pb, and Zn contents were determined in soil and in soil pore water. Additionally, the growth, dry weight, and metal concentrations were analyzed in the different dwarf bean plant (Phaseolus vulgaris L.) organs tested. Results showed that the addition of biochar at two doses (2 and 5%) improved soil conditions by increasing soil pH, electrical conductivity, and water holding capacity. Furthermore, the application of biochar (5%) to metal-contaminated soil reduced Cd, Pb, and Zn mobility and availability, and hence their accumulation in the different P. vulgaris L. organs. In conclusion, the data clearly demonstrated that biochar application can be effectively used for Cd, Pb, and Zn immobilization, thereby reducing their bioavailability and phytotoxicity.



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Central line–associated bloodstream infection rate elevation: Attributable to National Healthcare Safety Network surveillance definition changes, ongoing opportunities for infection prevention, or both?

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Publication date: Available online 20 July 2017
Source:American Journal of Infection Control
Author(s): Andrew Corley, Maggie Cantara, Julia Gardner, Polly Trexler, Clare Rock, Lisa L. Maragakis
Calendar year 2015 intensive care unit (ICU) central line–associated bloodstream infections (CLABSIs) from 1 hospital were reviewed using 2014 CLABSI surveillance definitions to assess the relative impact of definition changes and infection control practices on CLABSI rates. Increased ICU primary CLABSI rates were found to be a result of both surveillance definition changes and infection control practices.



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Additive effects of sensory-enhanced satiety and memory for recent eating on appetite

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Martin R. Yeomans, Millie Ruder Milton, Lucy Chambers
The sensory characteristics of a product have been shown to interact with actual nutrient content to generate satiety. Separately, cued recall of recent eating has also been shown to reduce food intake. Here we explore for the first time how these two effects interact, with the hypothesis that sensory enhancement of satiety might be mediated by more vivid memory of the earlier consumed item. On each of two test sessions, 119 women volunteers consumed a control drink (lemonade) on one morning and then one of two test drinks on the next day 30 min before an ad libitum lunch. The test drinks were equicaloric but one was noticeably thicker and creamier, and expected to generate stronger satiety. Just prior to the test lunch, participants were asked to recall either the test drink (test recall) or the drink from the previous day (control recall). Overall, lunch intake was significantly lower after the thicker and creamier (enhanced sensory ES) than thinner (low sensory: LS) test drink (p < 0.001, η2 = 0.11) regardless of recall condition (p = 0.65, η2 < 0.01), but was significantly lower after the test than control recall condition (p < 0.001, η2 = 0.14). Rated hunger was lower after consuming the ES than LS drink both immediately after consumption (p < 0.001, η2 = 0.11) and prior to the test lunch (p = 0.007, η2 = 0.06), while rated hunger just before lunch tended to be lower after recalling the test than control drink (p = 0.052, η2 = 0.03) regardless of the sensory characteristics (p = 0.27, η2 = 0.01). Overall these data further demonstrate the power of 'sensory-enhanced satiety' and cued recall of earlier eating as methods to reduce acute food intake, but suggest these effects operate independently.



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FTO genotype and weight status among preadolescents: Assessing the mediating effects of obesogenic appetitive traits

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Jennifer A. Emond, Alison Tovar, Zhigang Li, Reina K. Lansigan, Diane Gilbert-Diamond
Polymorphisms in the Fat Mass and Obesity Associated (FTO) gene are robustly associated with overweight and obesity among children, although the underlying mechanisms are poorly understood. We tested if appetitive traits partially mediated the association between FTO genotype and increased BMI among a sample of US preadolescents. Data were from 178 unrelated 9–10 year olds who participated in an experimental study between 2013 and 2015. Children's DNA was isolated from buccal swabs, and the rs9939609 SNP in the FTO gene was genotyped. Children's age- and sex-adjusted BMI z-scores were computed using height and weight measured at the laboratory. Parents completed the Child Eating Behavior Questionnaire that includes three validated scales of habitual appetitive traits related to drive and regulation: satiety responsiveness, enjoyment of food and food responsiveness. Structural equation modeling was used to assess if those traits mediated the relationship between FTO and BMI z-score. The sample of children was 48.9% male and 91.0% non-Hispanic white. FTO distribution was in Hardy Weinberg equilibrium, and 16.3% of participants were homozygous for the high-risk allele. Mean BMI z-score was greatest among those with the high-risk genotype (ANOVA P < 0.01). In separate structural equation models adjusted for the child's sex and maternal education, decreased satiety responsiveness and increased food responsiveness each partially mediated the positive association between the high-risk genotype and increased BMI z-score (P-value for each indirect effect <0.05). Continued research is needed to better understand how other known genetic obesity risk factors may impact appetitive traits among children.



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Repetitive eating questionnaire [Rep(eat)-Q]: Enlightening the concept of grazing and psychometric properties in a Portuguese sample.

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Eva M. Conceição, James E. Mitchell, Paulo P.P. Machado, Ana R. Vaz, Ana Pinto-Bastos, Sofia Ramalho, Isabel Brandão, Joana Botelho Simões, Marta de Lourdes, Ana Catarina Freitas
Background/objectiveGrazing has been associated with poor weight loss or weight regain in obese patients undergoing bariatric surgery, but research remains scarce and complicated by the use of different non-validated measures. The aim of this paper is to describe the validation of the Rep(eat)-Q, a self-report measure developed to assess grazing, and investigates its relationship with BMI and psychopathology.Subjects/Methods1223 university students and community participants (non-clinical; Study A) and 154 pre-bariatric and 84 post-bariatric patients (Study B) completed a set of self-report measures, including the Rep(eat)-Q (worded in Portuguese), to assess disordered eating, depression, anxiety, stress and impulsivity. Exploratory and confirmatory factor analyses tested the factor structure; internal consistency construct, convergent and divergent validity were also tested.ResultsThe Rep(eat)-Q scales showed good internal consistency (α ≥ 0.849) and temporal stability (rsp = 0.824, p < 0.000). Factor analyses generated two subscales: compulsive grazing and repetitive eating. Significant correlations (p < 0.05) were found between the Rep(eat)-Q and BMI in the non-clinical population and weight loss and weight regain in the bariatric sample. Generally, the correlations with psychological distress were weak (rsp < 0.4). Strong and significant (rsp≥0.4; p's < 0.05) correlations were found between compulsive grazing and eating disorder psychopathology. Repetitive eating subscale was inversely correlated with cognitive restraint (rsp −0.321, p < 0.05) and directly correlated with uncontrolled eating and emotional eating (rsp = 0.754; rsp = 0.691; p < 0.05).Discussion/conclusionThe Rep(eat)-Q is a valid measure to assess grazing in non-clinical and in bariatric surgery populations. Grazing can be conceptualized on the spectrum of disordered eating behavior, and appears associated with loss of control over eating. Considering the link between grazing and weight outcomes, the Rep(eat)-Q represents a necessary strategy for the systematic screening of grazing.



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Night eating among veterans with obesity

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Lindsey M. Dorflinger, Christopher B. Ruser, Robin M. Masheb
The obesity rate is higher among veterans than the general population, yet few studies have examined their eating behaviors, and none have examined the presence of night eating and related comorbidities. This study examines night eating syndrome (NES) among veterans seeking weight management treatment, and relationships between NES and weight, insomnia, disordered eating, and psychological variables. The sample consisted of 110 veterans referred to a weight management program at VA Connecticut Healthcare System. More than one out of ten veterans screened positive for NES, and one-third screened positive for insomnia. Most individuals screening positive for NES also screened positive for insomnia. Night eating was associated with higher BMI, and with higher scores on measures of binge eating, emotional overeating, and eating disorder symptomatology. Veterans screening positive for NES were also significantly more likely to screen positive for depression and PTSD. When controlling for insomnia, only the relationships between night eating and binge and emotional eating remained significant. Those screening positive for PTSD were more likely to endorse needing to eat to return to sleep. Findings suggest that both NES and insomnia are common among veterans seeking weight management services, and that NES is a marker for additional disordered eating behavior, specifically binge eating and overeating in response to emotions. Additional studies are needed to further delineate the relationships among NES, insomnia, and psychological variables, as well as to examine whether specifically addressing NES within behavioral weight management interventions can improve weight outcomes and problematic eating behaviors.



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Food marketing with movie character toys: Effects on young children's preferences for unhealthy and healthier fast food meals

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Publication date: 1 October 2017
Source:Appetite, Volume 117
Author(s): Helen Dixon, Philippa Niven, Maree Scully, Melanie Wakefield
This study aimed to test whether movie tie-in premiums (MTIPs) accompanying unhealthy and healthier fast food meals influenced children's meal preferences and their perceptions of these meals. Nine hundred and four Grade 1 and 2 students (aged 5–9 years) from Melbourne, Australia participated in a between-subjects online experiment comprising the following conditions: (A) unhealthy and healthier meals with no MTIP (control); (B) unhealthy and healthier meals with MTIP (current situation in Australia); (C) unhealthy meals with MTIP and healthier meals without MTIP; (D) unhealthy meals without MTIP and healthier meals with MTIP. The latter condition tested a potential regulatory model restricting premiums to healthier meals. Participants were shown a trailer for a current children's movie followed by an advertisement for an associated McDonald's Happy Meal® (conditions B-D) or an advertisement for a children's leisure activity (condition A). They were then shown four McDonald's Happy Meal® options on screen and asked to select their preferred meal before completing detailed meal ratings. Overall, children showed a preference for unhealthy meals over healthier ones. Children were significantly more likely to select a healthier meal over an unhealthy meal when only the healthier meals were accompanied by a MTIP (condition D) compared to the other three conditions. When healthier meals were accompanied by a MTIP, children reported the meal looked better, would taste better, they would be more likely to ask their parents for this meal, and they would feel happier if their parents bought them this meal, compared to when the healthier meal was not accompanied by a MTIP. Results suggest that modifying the food marketing environment to restrict MTIPs to healthier meals should encourage healthier fast food meal choices by children.



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Clinical predictors of survival in patients with castration-resistant prostate cancer receiving sipuleucel-T cellular immunotherapy

Abstract

Background

We evaluated the patterns of progression and determined clinical predictors of survival in patients with castration-resistant prostate cancer (CRPCa) who received sipuleucel-T.

Methods

We retrospectively analyzed 56 consecutive patients with asymptomatic or minimally symptomatic CRPCa treated with sipuleucel-T. Age, number of bone metastases, history of prior systemic treatment, and alkaline phosphatase level (ALP) were tested as predictors of survival in a multivariate Cox proportional hazards regression model. The Kaplan–Meier method was used to estimate event-free probabilities.

Results

The 56 patients were a median age of 67 years (range 51–84 years). After sipuleucel-T treatment, 25 patients developed bone progression after a median of 22 months of follow-up (54% of patients were event free at 2 years) and 10% (6/56 patients) developed rapid progression. Eleven deaths were observed after a median of 28 months of follow-up. Forty-eight patients were included in the multivariate analysis for overall survival. The analysis showed that age >70 years (p = 0.012), number of bone metastases >20 (p = 0.018), prior systemic treatment (p = 0.018), and ALP level >90 IU/L (p = 0.010) significantly predicted worse overall survival. Two-year overall survival was 36% among the 16 patients with two or more of these factors and was 93% among the 32 patients with one or none of these factors (p = 0.0004).

Conclusions

CRPCa patients with age (>70 years), increased tumor burden in bone (>20 metastases and/or elevated ALP level), and/or prior systemic treatment are more likely to experience rapid deterioration after sipuleucel-T. These results need to be prospectively validated.



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Unusual Eruption on the Arm

imageNo abstract available

http://ift.tt/2vGbzAy

“Joining the Spots in Adults and Young Tots”: A Clinicopathological Study of Henoch–Schönlein Purpura (IgA Vasculitis)

imageIntroduction: Henoch–Schönlein Purpura (HSP; IgA vasculitis), the most common vasculitis of childhood, has a wide spectrum of clinical manifestations ranging from palpable purpura with abdominal pain and arthritis to the more morbid renal involvement. Aims and Objectives: To study and correlate the clinical presentation, laboratory values, skin and renal histopathology and immunofluoroscence findings in HSP. Material and Methods: A total of 44 cases of HSP from March 2011 to February 2014 were studied for the above features along with their clinical outcomes. Results: The mean age of the patients at presentation was 28.4 years (range 4.5–69 years) with 26.2% being children younger than 15 years. Purpura at presentation was seen in all with 77.1% cases exhibiting extracutaneous involvement. Skin biopsy revealed leukocytoclastic vasculitis in all cases, dominant IgA deposition in the papillary dermal vessels in 43 cases (97.7%), associated C3 in 10 cases (23.3%), and full-house positivity in 1 case. One case without skin immunofluorescence had renal mesangial IgA deposits. Nine cases (20.9%) with an average age of 39 years had renal symptoms and displayed varied histology from focal mesangioproliferative glomerulonephritis to crescentic. All of them had dominant mesangial IgA deposits, majority falling into International Study of Kidney Disease in Children (ISKDC) class IIIb. Peritubular capillaritis was noted in 3 cases. Two patients (4.5%) progressed to end stage renal disease, one of whom had cellular crescents at presentation. Conclusions: HSP was seen both in children and adults. Renal involvement was seen in 20.9% cases, all older than 14 years, and 66.7% with extracutaneous manifestations. The outcome in this series was favorable in 96% cases.

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Collagen Anomalies as Clues for Diagnosis: Part 1

imageBackground: Collagen is the most abundant protein in the body and the main structural component of the skin. Objective: To provide a review of the histopathology of collagen alterations and to propose a classification with the most important types of collagen anomalies in dermatopathology. The authors describe some of the main morphological clues of collagen anomalies for specific diagnosis of some cutaneous inflammatory and neoplastic conditions. Methods: The authors review histopathologic collagen anomalies, concerning both morphology and disposition in some inflammatory and neoplastic cutaneous conditions, and they review previous terminology and proposed a classification of the most important types of collagen anomalies that can be seen in dermatopathological practice. Results: Collagen anomalies in skin can be classified into lamellar fibrosis, sclerosis, and "balls" and "rings" of collagen. Lamellar fibrosis presents as long and thin collagen bundles forming a delicate network, which can be disposed in a parallel pattern, onion-bulb-like pattern, and storiform pattern. Sclerosis is characterized by large, thick, and eosinophilic bundles of collagen, which may present as a homogenous-diffuse pattern or as individual thick bundles of collagen with few or abundant number of fibroblasts between them. Finally, the authors propose the terms "balls" and "rings" of collagen. The term "balls" of collagen stands for thick, homogenous, eosinophilic, globular collagen bundles, with no distinguishable individual composing fibers, which include the floating sign and the free-floating sign. The term "rings" of collagen is characterized by sclerotic collagen arranged in a homogenous rimming pattern around vessels without independent fibers in its composition. Conclusions: Collagen anomalies may be important clues to establish specific clues for specific diagnoses in dermatopathology.

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Living on the Edge: Diagnosing Sarcomatoid Melanoma Using Histopathologic Cues at the Edge of a Dedifferentiated Tumor: A Report of 2 Cases and Review of the Literature

imageAbstract: Sarcomatoid melanoma is a rare type of melanoma lacking typical histologic features of melanoma and often lacks expression of S100 protein and melanocyte-specific markers. Given the rarity of this entity, its clinicopathologic findings are not well defined. We report 2 cases of sarcomatoid melanoma received in consultation: a 65-year-old woman with a right breast mass and a 62-year-old man with a left plantar heel mass. Both lesions were ulcerated, pedunculated, highly cellular proliferations of atypical spindle cells arranged as fascicles and/or sheets. The tumor cells of the breast mass expressed CD10 and vimentin diffusely but S100 protein only focally. The tumor cells of the heel mass lacked expression of melanocytic markers altogether, except for weak, very focal S100 protein expression. At the junctional edge of the breast mass and in the ulcer base of the heel mass, focal precursor melanoma was present and exhibited melanocytic differentiation. We report these cases to emphasize the importance of meticulous histologic inspection at the lesion's edge and/or ulcer base to correctly identify the conventional precursor melanoma in these rare lesions to ensure appropriate diagnosis and subsequent clinical management as treatment options may be significantly different from those offered for sarcomas.

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Histological Features of Methylene Blue–Induced Phototoxicity Administered in the Context of Parathyroid Surgery

imageAbstract: Methylene blue is a chromophore dye known for its photosensitizing properties. It is also administered intravenously as a tracer in parathyroid surgery to identify abnormal glands. We describe 2 cases of acute methylene blue–induced phototoxicity in patients who underwent parathyroidectomy. Both patients developed an acute vesiculopustular inflammatory rash on the anterior neck corresponding to the site exposed intraoperatively to overhanging surgical lights. One of the patients also developed a bulla on her finger at the site of attachment of the oxygen probe. Biopsies were taken from both patients at different time points. The histological findings included destruction of sebaceous glands and deposition of diastase-periodic acid-Schiff–positive hyaline material around dermal blood vessels. These features are similar to those seen in skin treated with photodynamic therapy and systemic photosensitivity disorders such as the porphyrias. The wavelengths of light emitted by the surgical lights and oxygen probe overlap with the absorption spectrum of methylene blue. This resulted in excitation of the systemically administered methylene blue at exposed sites, with resultant local tissue damage and a phototoxic reaction.

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An Immunohistochemical Study of Anogenital Mammary-Like Glands

imageAbstract: Although the normal histology of anogenital mammary-like glands (AGMLG) has been studied, no systemic investigation has been performed on the immunoprofile of these structures. We studied intact AGMLG with a broad panel of antibodies. The immunoprofile of AGMLG is similar to that of a normal breast tissue, and there are similarities to eccrine glands and coils about cytokeratin expression. Our immunohistochemical data may contribute to understanding of the pathogenesis of lesions arising from AGMLG.

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Erythema Multiforme Following lines of Blaschko

imageNo abstract available

http://ift.tt/2vFXSl5

High-Velocity Paint Gun Injuries

imageAbstract: Cutaneous injuries due to industrial high-pressure paint guns are well-documented in the literature; however, the histologic characteristics are uncommonly described, and facial involvement has not been previously reported. Histopathologic features of paint gun injuries vary depending on the time since injection and type of material. Early lesions display an acute neutrophilic infiltrate, edema, and thrombosis, with varying degrees of skin, fat, and muscle necrosis. More developed lesions (120–192 hours after injury) have prominent histiocytes and fibrosis around necrotic foci, possibly with the pitfall of muscle regenerative giant cells that could be mistaken for sarcoma. Continuing inflammation, swelling, and resultant vascular compression could explain ongoing necrosis months after the accident. The histopathologic differential diagnosis in the absence of clinical history includes paint in an abrasion, foreign body reaction to tattoo, giant cell tumor of tendon sheath, and various neoplasms. If available, radiologic studies can substitute for clinical photographs to indicate the extent of injury. The radiologic differential, uninformed by history, may include calcific periarthritis, gouty tophus, and tumoral calcinosis. Seven cases of injury due to high-velocity paint guns are presented with 4 additional cases mimicking paint gun injury and with review of the literature.

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Nodular Lesion in Cheek With a Hair Tuft

Abstract: Trichostasis spinulosa is a rarely diagnosed disorder of the pilosebaceous unit, characterized by retention of telogen hairs within the dilated follicles. A hair tuft can be seen protruding from the follicles. We present a case of trichostasis spinulosa associated with intradermal melanocytic nevi, where dermoscopy helps to identify this entity.

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Lichenoid Granulomatous Mycosis Fungoides

imageAbstract: The presence of a granulomatous reaction in cutaneous lymphomas has been described in the past, especially in mycosis fungoides (MF), where a "granulomatous" variant of the disease is well known. We describe a patient with granulomatous MF (GMF) who has been followed for 13 years presenting with erythematosquamous plaques on his fingers and toes, ankles, heels, and abdomen, which on microscopic examination showed a lichenoid granulomatous reaction admixed with a neoplastic proliferation of small-sized, atypical CD4+ lymphocytes. GMF is characterized by a granulomatous reaction intermingled with the dermal infiltrate of MF which may even reach the subcutaneous tissue. Only 7 cases of GMF in which the granulomas were located within the papillary or superficial dermis have been described to date. We report for the first time a unique case of lichenoid GMF where the granulomatous reaction obscures the interface between the epidermis and dermis. Sequential biopsies and complete phenotypic studies were necessary to get an accurate diagnosis.

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Abstracts Presented at the 20th Joint Meeting of the International Society of Dermatopathology, March 1–2, 2017, Hilton Orlando Lake Buena Vista in the Walt Disney World Resort, Lake Buena Vista, Florida, USA

No abstract available

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Metastatic Cellular Blue Nevus: A Rare Case With Metastasis Beyond Regional Nodes

imageAbstract: In this study, we present a rare case of a 35-year-old man with a long-standing blue-black lesion on his left hand with subsequent infraclavicular and axillary lymph node tumor deposits. The hand lesion and lymph nodes were excised revealing histological, immunohistochemical, and molecular findings consistent with cellular blue nevus. Despite nonregional lymph node involvement, there has been no progression at 12-months follow-up. This is an index case of a cellular blue nevus with metastasis to both regional and nonregional lymph nodes. The lack of atypical/malignant features in this lesion makes the metastatic behavior extraordinary, and hence the prognosis of lesions of this type is indeterminate.

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Epidermotropic Bullous and Erosive Metastatic Melanoma

imageNo abstract available

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Factitious Dermatitis Due to Thermal Burn With Histologic Features Simulating Fixed Drug Eruption

imageAbstract: Factitious dermatitis (FD) (dermatitis artefacta) is rare and often difficult to diagnose because of conflicting history and nonspecific clinical and histologic findings. It can present with varied clinical features including geometric ulcers, erosions, and less commonly bullae secondary to external trauma from chemicals, electric burns, heat, and suction. Herein, we describe a case of bullous FD due to thermal burn with histologic features demonstrating overlap with fixed drug eruption. Histopathology demonstrated a subepidermal blister with epidermal necrosis along with pigment incontinence and dermal eosinophils and neutrophils. Although these features, and the clinician's impression, were suggestive of fixed drug eruption, several morphologic findings allowed accurate diagnosis of FD: sharp demarcation of necrotic keratinocytes from adjacent uninvolved epidermis, elongated keratinocytes reminiscent of thermal or electrical artifact, and multinucleated keratinocytes. Although FD is often considered a diagnosis of exclusion, these clues may help dermatopathologists distinguish this entity from inflammatory dermatoses.

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In Response

No abstract available

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Actinic Granuloma Annulare With Scarring and Open Comedones

imageAbstract: Actinic granuloma and annular elastolytic giant cell granuloma are variants of granuloma annulare affecting, respectively, sun-exposed and sun-covered skin sites on where, besides classical findings, abundant elastophagocytosis is observed. Here, we report a case of exuberant actinic granuloma annulare that, in addition to extensive scarring, showed multiple overlying open comedones. Markedly dilated follicular infundibula filled with compact masses of laminated keratinous material were observed in proximity to dermal inflammation composed of many histiocytes and multinucleated giant cells in close association with degenerated elastic fibers and abundant elastophagocytosis.

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Refractory Intertrigo in the Right Inguinal Crease: Answer

imageNo abstract available

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Unusual Eruption on the Arm: Challenge

imageNo abstract available

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Follicular Porokeratosis, a Porokeratosis Variant

imageAbstract: Porokeratosis derives from a process of abnormal keratinization, resulting in clinical and histologic variants. Follicular involvement is infrequently described, with previous suggestions that it may represent a distinct condition. We describe a case of typical disseminated superficial actinic porokeratosis with additional clinically prominent folliculocentric keratosis. Histologically, this represented follicular cornoid lamellae. These findings support follicular porokeratosis as an anatomic site variant of porokeratosis, as opposed to a distinct condition. We also want to raise awareness of this variant which clinically should be considered when presented with a discrete papular keratotic eruption.

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Refractory Intertrigo in the Right Inguinal Crease: Challenge

imageNo abstract available

http://ift.tt/2vGiyd0

Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia

Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Martha S. Windrem, Mikhail Osipovitch, Zhengshan Liu, Janna Bates, Devin Chandler-Militello, Lisa Zou, Jared Munir, Steven Schanz, Katherine McCoy, Robert H. Miller, Su Wang, Maiken Nedergaard, Robert L. Findling, Paul J. Tesar, Steven A. Goldman
In this study, we investigated whether intrinsic glial dysfunction contributes to the pathogenesis of schizophrenia (SCZ). Our approach was to establish humanized glial chimeric mice using glial progenitor cells (GPCs) produced from induced pluripotent stem cells derived from patients with childhood-onset SCZ. After neonatal implantation into myelin-deficient shiverer mice, SCZ GPCs showed premature migration into the cortex, leading to reduced white matter expansion and hypomyelination relative to controls. The SCZ glial chimeras also showed delayed astrocytic differentiation and abnormal astrocytic morphologies. When established in myelin wild-type hosts, SCZ glial mice showed reduced prepulse inhibition and abnormal behavior, including excessive anxiety, antisocial traits, and disturbed sleep. RNA-seq of cultured SCZ human glial progenitor cells (hGPCs) revealed disrupted glial differentiation-associated and synaptic gene expression, indicating that glial pathology was cell autonomous. Our data therefore suggest a causal role for impaired glial maturation in the development of schizophrenia and provide a humanized model for its in vivo assessment.

Graphical abstract

image

Teaser

Goldman and colleagues use mice chimerized with human patient-derived glial progenitor cells to find out whether glia contribute to childhood-onset schizophrenia. The defects in cell differentiation, myelination, and behavior they see strongly suggest that glial cells do, in fact, have a previously unappreciated role in the pathogenesis of this disease.


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Pathogen-Induced TLR4-TRIF Innate Immune Signaling in Hematopoietic Stem Cells Promotes Proliferation but Reduces Competitive Fitness

Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Hitoshi Takizawa, Kristin Fritsch, Larisa V. Kovtonyuk, Yasuyuki Saito, Chakradhar Yakkala, Kurt Jacobs, Akshay K. Ahuja, Massimo Lopes, Annika Hausmann, Wolf-Dietrich Hardt, Álvaro Gomariz, César Nombela-Arrieta, Markus G. Manz
Bacterial infection leads to consumption of short-lived innate immune effector cells, which then need to be replenished from hematopoietic stem and progenitor cells (HSPCs). HSPCs express pattern recognition receptors, such as Toll-like receptors (TLRs), and ligation of these receptors induces HSPC mobilization, cytokine production, and myeloid differentiation. The underlying mechanisms involved in pathogen signal transduction in HSCs and the resulting biological consequences remain poorly defined. Here, we show that in vivo lipopolysaccharide (LPS) application induces proliferation of dormant HSCs directly via TLR4 and that sustained LPS exposure impairs HSC self-renewal and competitive repopulation activity. This process is mediated via TLR4-TRIF-ROS-p38, but not MyD88 signaling, and can be inhibited pharmacologically without preventing emergency granulopoiesis. Live Salmonella Typhimurium infection similarly induces proliferative stress in HSCs, in part via TLR4-TRIF signals. Thus, while direct TLR4 activation in HSCs might be beneficial for controlling systemic infection, prolonged TLR4 signaling has detrimental effects and may contribute to inflammation-associated HSPC dysfunction.

Graphical abstract

image

Teaser

Takizawa et al. show that self-renewing hematopoietic cells directly sense gram-negative bacterial infection through Toll-like receptor 4 (TLR4) activation, which leads to impaired function via proliferative stress. Genetic and pharmacological blockage of the TLR4-TRIF-ROS-p38 axis can maintain HSC function without disrupting emergency granulopoietic responses to infection.


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High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain

Publication date: Available online 20 July 2017
Source:Cell Stem Cell
Author(s): Ting Zhou, Lei Tan, Gustav Y. Cederquist, Yujie Fan, Brigham J. Hartley, Suranjit Mukherjee, Mark Tomishima, Kristen J. Brennand, Qisheng Zhang, Robert E. Schwartz, Todd Evans, Lorenz Studer, Shuibing Chen
Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients.

Graphical abstract

image

Teaser

Chen, Studer, and colleagues utilize human pluripotent stem cell-derived neural progenitors to perform a high-content screen for anti-ZIKV drug discovery. Hippeastrine hydrobromide was identified and shown to eliminate ZIKV in infected human neural progenitors, rescue a ZIKV-induced microcephaly phenotype in human forebrain organoids, and suppress virus propagation in adult mice with active ZIKV infection.


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Efficacy and safety of taxane monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: a multicenter retrospective study

Abstract

Purpose

Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS.

Methods

We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0–2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function.

Results

A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27–75/42–75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death.

Conclusions

Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients.



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Ειδοποίηση Μελετητή:[ ΛΟΓΟΣ ]

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MN Albert, JP Perouma - Humanistic Management Journal, 2017
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