Τρίτη 27 Φεβρουαρίου 2018
HLA-DRB1*04:05 in two cases of Vogt–Koyanagi–Harada disease-like uveitis developing from an advanced melanoma patient treated by sequential administration of nivolumab and dabrafenib/trametinib therapy
Abstract
Although uveitis is reported as a rare adverse event (AE) associated with dabrafenib/trametinib therapy or nivolumab, the occurrence of severe uveitis is extremely rare. We describe two cases of Vogt–Koyanagi–Harada (VKH)-like uveitis developing after the sequential administration of nivolumab and dabrafenib/trametinib therapy. Interestingly, both cases had HLA-DRB1*04:05, which is strongly associated with VKH disease, and achieved biologically complete remission after the treatment for uveitis. Our cases suggest a possible correlation between VKH-like uveitis as an AE and the clinical outcomes of sequential administration of nivolumab and dabrafenib/trametinib therapy for the treatment of advanced melanoma.
Mechanisms of copper stress alleviation in Citrus trees after metal uptake by leaves or roots
Abstract
Nutritional disorders caused by copper (Cu) have affected citrus orchards. Since Cu is foliar sprayed as a pesticide to control citrus diseases, this metal accumulates in the soil. Thereby, we evaluated the effects of Cu leaf absorption after spray of different metal sources, as well as roots absorption on growth, nutritional status, and oxidative stress of young sweet orange trees. Two experiments were carried out under greenhouse conditions. The first experiment was set up with varying Cu levels to the soil (nil Cu, 0.5, 2.0, 4.0 and 8.0 g of Cu per plant as CuSO4.5H2O), whereas the second experiment with Cu application via foliar sprays (0.5 and 2.0 g of Cu per plant) and comparing two metal sources (CuSO4.5H2O or Cu(OH)2). Copper was mainly accumulated in roots with soil supply, but an increase of oxidative stress levels was observed in leaves. On the other hand, Cu concentrations were higher in leaves that received foliar sprays, mainly as Cu(OH)2. However, when sulfate was foliar sprayed, plants exhibited more symptoms of injuries in the canopy with decreased chlorophyll contents and increased hydrogen peroxide and lipid peroxidation levels. Copper toxicity was characterized by sap leakage from the trunk and twigs, which is the first report of this specific Cu excess symptom in woody trees. Despite plants with 8.0 g of Cu soil-applied exhibiting the sap leakage, growth of new plant parts was more vigorous with lower oxidative stress levels and injuries compared to those with 4.0 g of Cu soil-applied (without sap leakage). With the highest level of Cu applied via foliar as sulfate, Cu was eliminated by plant roots, increasing the rhizospheric soil metal levels. Despite citrus likely exhibiting different mechanisms to reduce the damages caused by metal toxicity, such as responsive enzymatic antioxidant system, metal accumulation in the roots, and metal exclusion by roots, excess Cu resulted in damages on plant growth and metabolism when the metal was taken up either by roots or leaves.
Melanoma risk prediction using a multi-locus genetic risk score in the Women’s Health Initiative cohort
Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies (GWASs). However, the combined impact of these SNPs on melanoma development remains unclear, particularly in post-menopausal women who carry lower melanoma risk.
The Risk of Cardiovascular Events in Psoriasis Patients Treated with Tumor Necrosis Factor-alpha Inhibitors versus Phototherapy: An Observational Cohort Study
Psoriasis is a risk factor for cardiovascular events.
Title: Opioid, Alcohol, and Cannabis Misuse Among Patients with Hidradenitis Suppurativa: a population-based analysis in the United States
Patients with hidradenitis suppurativa (HS) experience chronic pain and have significant physical, emotional and psychological disease impact. These patients may be at risk for substance abuse.
Similar survival of patients with multiple vs. single primary melanomas based on Utah SEER data (1973-2011)
Survival data are mixed comparing patients with multiple primary melanomas (MPM) to those with single primary melanomas (SPM).
Routine Pathologic Evaluation of Plastic Surgery Specimens: Are We Wasting Time and Money?
Background: Recent health care changes have encouraged efforts to decrease costs. In plastic surgery, an area of potential cost savings includes appropriate use of pathologic examination. Specimens are frequently sent because of hospital policy, insurance request, or habit, even when clinically unnecessary. This is an area where evidence-based guidelines are lacking and significant cost-savings can be achieved. Methods: All specimen submitted for pathologic examination at two hospitals between January and December of 2015 were queried for tissue expanders, breast implants, fat, skin, abdominal pannus, implant capsule, hardware, rib, bone, cartilage, scar, and keloid. Specimens not related to plastic surgery procedures were excluded. Pathologic diagnosis and cost data were obtained. Results: A total of 759 specimens were identified. Of these, 161 were sent with a specific request for gross examination only. There were no clinically significant findings in any of the specimens. There was one incidental finding of a seborrheic keratosis on breast skin. The total amount billed in 2015 was $430,095. Conclusions: The infrequency of clinically significant pathologic examination results does not support routine pathologic examination of all plastic surgery specimens. Instead, the authors justify select submission only when there is clinical suspicion or medical history that warrants evaluation. By eliminating unnecessary histologic or macroscopic examination, significant cost savings may be achieved.Sifting through the Evidence: A Comprehensive Review and Analysis of Neurotization in Breast Reconstruction
Background: An untoward outcome following breast reconstruction is diminished or complete loss of sensation. As the reconstructive paradigm continues to evolve, sensory restoration following reconstruction remains a research focus. Despite the multitude of published outcomes, there is marked heterogeneity across studies, thus confounding published outcomes. This study critically appraises the literature to summarize outcomes and establish a framework to guide clinical practice and future research. Methods: A literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines in an effort to perform a meta-analysis. The Ovid MEDLINE, PubMed, Embase, Scopus, Cochrane, and ClinicalTrials.gov online databases were queried to capture all publications between 1990 and 2017 that investigated postreconstruction breast sensation. The primary outcome of interest was breast sensation following both implant-based and autologous reconstruction with or without neurotization. Secondary outcomes of interest included time to sensory testing and patient-reported outcomes. Results: Overall, 503 titles were screened, from which 37 articles were ultimately included for analysis, accounting for 1299 patients. There was major methodologic variability and inconsistent measurable outcomes across studies. It can be deduced that postoperative sensation returns spontaneously and unpredictably, neurotization enhances the magnitude and rapidity of sensory restoration when compared to nonneurotized reconstruction, and a sensate reconstruction improves patient-reported outcomes. Conclusions: Significant study design discrepancies exist, making it difficult to combine data and assess results. To effectively study breast sensation and the impact of neurotization, future investigation will depend on standardizing the way in which breast sensation is measured.Is the Right Research Being Conducted to Advance Knowledge about Breast Reconstruction? An Analysis of the Research Pipeline
Background: It has been estimated that up to 85 percent of research is of limited value or wasted, in part because of the wrong research questions being addressed. In this study, the authors identified research gaps for breast reconstruction using guideline recommendations based on low-quality or no evidence. The authors then evaluated whether research was currently being conducted to fill these gaps. Methods: The authors extracted grade C and D options, which are based on limited evidence, from the American Society of Plastic Surgeon's clinical practice guideline for breast reconstruction. For each option, the authors created Participants, Intervention, Comparator, Outcome questions and search strings using a systematic process. Searches were conducted of ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform to locate new and ongoing studies. The authors also catalogued studies on breast reconstruction funded by the Plastic Surgery Foundation. Results: Of the 10 research gaps, only six were being addressed by new and ongoing research. Timing of reconstruction (immediate or delayed) and use of acellular dermal matrix were most frequently studied. Preoperative referral of a plastic surgeon before mastectomy, complications associated with preoperative breast size, effects of hormone therapy on postoperative outcomes, and methods for detecting local recurrence after mastectomy were not being addressed by new research. Studies funded by the Plastic Surgery Foundation showed a similar pattern. Conclusions: Of the areas identified, some have received more attention than others. Gaps remain. The authors' results should spark interest in conducting research on these topics and, by so doing, strengthen the clinical practice guideline recommendations.Where Do We Look? Assessing Gaze Patterns in Breast Reconstructive Surgery with Eye-Tracking Technology
Background: Aesthetics plays a large role in determining a successful outcome in plastic and reconstructive surgery. As such, understanding perceptions of favorable aesthetics is crucial for optimizing patient satisfaction. Eye-tracking technology offers an unbiased way of measuring how viewers evaluate breast reconstructions. Methods: Twenty-nine raters with varied plastic surgery experience were shown 20 images of breast reconstruction at various stages. Breasts were divided into those with nipples and no reconstruction scars, those with nipples and reconstruction scars, and those with reconstruction scars and no nipples. Raters viewed each image for 8 seconds to evaluate aesthetic outcomes. Eye-tracking equipment and software were used to track raters' gaze and analyze the distribution of attention. Results: In breasts with reconstruction scars and no nipples, viewers spent 53.9 percent of the view time examining scars, whereas viewers' attention was divided evenly in breasts with both reconstruction scars and nipples, spending 27.5 percent and 27.7 percent of view time examining the nipples and reconstruction scars, respectively. When examining complete reconstructions, viewers spent more time scanning the entire image before fixating on scars and spent less time on single-site fixation. Conclusions: Complete reconstructions, which notably include the final nipple-areola complex, appear to play an important role in restoring normal viewing parameters. In essence, completed breast reconstructions with nipple-areola complexes divert attention from extraneous surgical scars and lead viewers to assess the breasts more holistically. Eye-tracking technology provides a powerful link between objective gaze and viewer attention that may potentially be used to predict subjective aesthetic preferences.
The Effect of Radiation on Quality of Life throughout the Breast Reconstruction Process: A Prospective, Longitudinal Pilot Study of 200 Patients with Long-Term Follow-Up
Background: Despite well-established correlation of postmastectomy radiotherapy and surgical complications in breast reconstruction, its impact on patient reported outcomes is less clear. We sought to determine the effect of postmastectomy radiotherapy on patient reported outcomes throughout the breast reconstruction process. Methods: Patients undergoing prosthetic and autologous breast reconstruction from November 2010 to June 2013 were prospectively followed with BREAST-Q surveys (preoperatively, after expander placement, and 6 and 12 months after final reconstruction). Paired t test, Wilcoxon rank sum test, and multiple linear regression were used to determine the effect of radiation on patient reported outcomes. Results: Two hundred patients were included in the study, of which 51 (25.5 percent) received postmastectomy radiotherapy. Prosthetic reconstruction was performed in 75 patients (37.5 percent), autologous reconstruction was performed in 118 (59 percent), and pure fat grafting was performed in seven (3.5 percent). At one-year follow-up, the nonirradiated group reported higher BREAST-Q scores when compared with the irradiated group, in Satisfaction with Breasts (p = 0.003), Psychosocial Well-being (p = 0.003), Sexual Well-being (pIntraoperative Nerve Blocks Fail to Improve Quality of Recovery after Tissue Expander Breast Reconstruction: A Prospective, Double-Blinded, Randomized, Placebo-Controlled Clinical Trial
Background: The authors' study represents the first level I evidence to assess whether intraoperative nerve blocks improve the quality of recovery from immediate tissue expander/implant breast reconstruction. Methods: A prospective, randomized, double-blinded, placebo-controlled clinical trial was conducted in which patients undergoing immediate tissue expander/implant breast reconstruction were randomized to either (1) intraoperative intercostal and pectoral nerve blocks with 0.25% bupivacaine with 1:200,000 epinephrine and 4 mg of dexamethasone or (2) sham nerve blocks with normal saline. The 40-item Quality of Recovery score, pain score, and opioid use in the postoperative period were compared statistically between groups. Power analysis ensured 80 percent power to detect a 10-point (clinically significant) difference in the 40-item Quality of Recovery score. Results: Forty-seven patients were enrolled. Age, body mass index, laterality, mastectomy type, and lymph node dissection were similar between groups. There were no statistical differences in quality of recovery, pain burden as measured by visual analogue scale, opioid consumption, antiemetic use, or length of hospital stay between groups at 24 hours after surgery. Mean global 40-item Quality of Recovery scores were 169 (range, 155 to 182) for the treatment arm and 165 (range, 143 to 179) for the placebo arm (p = 0.36), indicating a high quality of recovery in both groups. Conclusion: Although intraoperative nerve blocks can be a safe adjunct to a comprehensive postsurgical recovery regimen, the authors' results indicate no effect on overall quality of recovery from tissue expander/implant breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.Vertical Skin Paddle Orientation for the Latissimus Dorsi Flap in Breast Reconstruction: A Modification to Simultaneously Correct Inferior Pole Constriction and Improve Projection
Summary: The latissimus dorsi myocutaneous flap is a reliable and frequently used option to bring vascularized skin and soft tissue to improve the stability and aesthetic result in breast reconstruction. Standard techniques with skin paddle inset in a horizontal or oblique fashion preferentially improve anterior projection (when inset at the mastectomy scar) or lower pole and inframammary fold constriction (when inset into the inframammary fold). Here, the authors describe a modification for inset of the latissimus dorsi myocutaneous flap that improves both anterior projection and lower pole/inframammary fold constriction, and also allows the latissimus muscle to fan out and provide complete implant coverage. The vertical inset modification brings new skin and soft tissue into both the inferior pole and the central mastectomy scar, allowing simultaneous improvement in both areas and full use of the latissimus muscle to cover the implant or expander. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.
Evaluation of Preoperative and Postoperative Patient Satisfaction and Quality of Life in Patients Undergoing Rhinoplasty: A Systematic Review and Meta-Analysis
Background: Improvement of nasal aesthetics by means of rhinoplasty is a highly sought-after procedure and leads to increased patient confidence. The aim of the study was to provide a quantitative synthesis of existing data regarding the ability of cosmetofunctional rhinoplasty to improve patient satisfaction and quality of life measured by the Rhinoplasty Outcomes Evaluation scale. Methods: Electronic databases were searched for studies evaluating quality of life following aesthetic rhinoplasty. Study results were pooled and analyzed using a random effects model. Effect size was estimated using standardized mean difference at a 95 percent confidence interval. Heterogeneity and benefit were assessed and reported using the I2 and standard mean difference. Subgroup analyses were performed based on follow-up period and age group segregation. Results: A total of 377 articles were retrieved, of which eight studies were included in the final analysis. Overall, patient satisfaction analyzed by pooling eight observational studies improved following cosmetofunctional rhinoplasty (standard mean difference, 5.87; 95 percent CI, 3.55 to 8.19; I2 = 100 percent). In addition, further subgroup analyses revealed that maximum benefit was derived by younger patients (standard mean difference, 6.69; 95 percent CI, 3.65 to 9.74; I2 = 99 percent) compared with older patients (standard mean difference, 3.48; 95 percent CI, 3.01 to 3.96; I2 = 0 percent). Postoperative patient satisfaction levels showed maximum improvement during a follow-up period of 6 to 12 months (standard mean difference, 11.07; 95 percent CI, −8.79 to 32.12; I2 = 100 percent). Conclusion: Cosmetofunctional rhinoplasty improves patients' quality of life as evidenced by an improvement in Rhinoplasty Outcomes Evaluation scores. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.Thread-Lift Sutures: Still in the Lift? A Systematic Review of the Literature
Background: In 2006, Villa et al. published a review article concerning the use of thread-lift sutures and concluded that the technique was still in its infancy but had great potential to become a useful and effective procedure for nonsurgical lifting of sagged facial tissues. As 11 years have passed, the authors now performed again a systematic review to determine the real scientific current state of the art on the use of thread-lift sutures. Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using the PubMed database and using the Medical Subject Headings search term "Rhytidoplasty." "Rhytidoplasty" and the following entry terms were included by this Medical Subject Headings term: "facelift," "facelifts," "face Lift," "Face Lifts," "Lift," "Face," "Lifts," "Platysmotomy," "Platysmotomies," "Rhytidectomy," "Rhytidectomies," "Platysmaplasty," "and "Platysmaplasties." The Medical Subject Headings term "Rhytidoplasty" was combined with the following search terms: "Barbed suture," "Thread lift," "APTOS," "Suture suspension," "Percutaneous," and "Silhouette suture." RefWorks was used to filter duplicates. Three of the authors (H.A.G., B.C., and B.L.) performed the search independently. Results: The initial search with all search terms resulted in 188 articles. After filtering the duplicates and the articles about open procedures, a total of 41 articles remained. Of these, the review articles, case reports, and letters to the editor were subsequently excluded, as were reports dealing with nonbarbed sutures, such as Vicryl and Prolene with Gore-Tex. This resulted in a total of 12 articles, seven additional articles since the five articles reviewed by Villa et al. Conclusions: The authors' review demonstrated that, within the past decade, little or no substantial evidence has been added to the peer-reviewed literature to support or sustain the promising statement about thread-lift sutures as made by Villa et al. in 2006 in terms of efficacy or safety. All included literature in the authors' review, except two studies, demonstrated at best a very limited durability of the lifting effect. The two positive studies were sponsored by the companies that manufacture the thread-lift sutures.Comparing Efficacy and Costs of Four Facial Fillers in Human Immunodeficiency Virus–Associated Lipodystrophy: A Clinical Trial
Background: The objective of this study was to evaluate and compare the safety and effectiveness of four different dermal fillers in the treatment of facial lipoatrophy secondary to human immunodeficiency virus. Methods: The authors conducted a clinical trial including 147 patients suffering from human immunodeficiency virus–induced lipoatrophy treated with Sculptra (poly-L-lactic acid), Radiesse (calcium hydroxylapatite), Aquamid (polyacrylamide), or autologous fat. Objective and subjective changes were evaluated during a 24-month follow-up. Number of sessions, total volume injected, and overall costs of treatment were also analyzed. A comparative cost-effectiveness analysis of the treatment options was performed. Results: Objective improvement in facial lipoatrophy, assessed by the surgeon in terms of changes from baseline using the published classification of Fontdevila, was reported in 53 percent of the cases. Patient self-evaluation showed a general improvement after the use of facial fillers. Patients reported being satisfied with the treatment and with the reduced impact of lipodystrophy on their quality of life. Despite the nonsignificant differences observed in the number of sessions and volume, autologous fat showed significantly lower costs than all synthetic fillers (pCombined toxicities of copper nanoparticles with carbon nanotubes on marine microalgae Skeletonema costatum
Abstract
To investigate the combined toxicities of copper nanoparticles (nano-Cu) with carbon nanotubes (CNTs) on marine microalgae Skeletonema costatum, algal growth inhibition tests were carried out. Toxicities of nano-Cu with CNTs and without CNTs on microalgae were determined, respectively. Chlorophyll content and photosynthetic efficiency (ΦPSII) were determined to compare negative effects of nano-Cu with CNTs and without CNTs on photosynthesis. The concentration of Cu2+ released by nano-Cu into the medium was determined, and interactions between nano-Cu and CNTs were analyzed to study toxic mechanisms of combined toxicities of nano-Cu with CNTs. It was found that both nano-Cu and CNTs could inhibit the growth of the microalgae; however, the toxicity of CNTs on the microalgae was far lower than that of nano-Cu. The maximum growth inhibition ratio (IR) of nano-Cu on the microalgae was 86% appearing at 96 h under 1.0 mg/L nano-Cu treatment, while the maximum IR of CNTs on the microalgae was 58% at 96 h under 200 mg/L CNT treatment. CNTs could reduce the toxicity of nano-Cu on the microalgae in processes of growth and photosynthesis. Adsorption of Cu2+ on CNTs and aggregate between Cu and CNTs in the medium were main reasons for attenuation of toxicity of nano-Cu with adding CNTs.
Books Received
ALEXANDER, ZEYNEP ÇELIK. Kineasthetic Knowing: Aesthetics, Epistemology, and Modern Design. (Chicago: University of Chicago Press). 2017. pp. 311. £40.54 (hbk).
Notes on Contributors
CHRISTOPHER BARTEL is an Associate Professor in Philosophy at Appalachian State University. His research interests primarily lie within aesthetics with a special focus on philosophy of music and philosophy of video games. He has published essays on the ontology of musical works, the ethics of video games, and historical inaccuracies in works of fiction. His essays have appeared in the British Journal of Aesthetics, Ethics and Information Technology, the European Journal of Philosophy, and the Journal of Aesthetics and Art Criticism.
Nahlowsky’s Psychological Aesthetics
Abstract
My article aims to revisit the aesthetic thought of the Austrian psychologist and philosopher Joseph Wilhelm Nahlowsky (1812–1885), as expounded in his formerly famous monograph Das Gefühlsleben. I show that although Nahlowsky was a direct heir of Herbart, his ideas were in keeping with both the contemporary debate about form and content and the then-emerging paradigm of psychological aesthetics. I describe his developments on aesthetic feelings and his remarkable attempt to elaborate a general psycho-affective theory on the experience of the aesthetic object. I also discuss the importance of the notion of form, inherited from Herbart, in his psychological aesthetics. Finally, I demonstrate that, in addition to having marked an 'affective' turn in Herbartianism, Nahlowsky was a key actor in the evolution of ideas in psychological aesthetics in the second half of the nineteenth century.The Value of Fidelity in Adaptation
The adaptation of literary works into films has been almost completely neglected as a philosophical topic. I discuss two questions about this phenomenon:
- What do we mean when we say that a film is faithful to its source?
- Is being faithful to its source a merit in a film adaptation?
Appearance and History: the Autographic/Allographic Distinction Revisited
Abstract
Nelson Goodman notoriously distinguished between autographic works, whose instances should be identified by taking history of production into account, and allographic works, whose instances can be identified independently of history of production. Scholars such as Jerrold Levinson, Flint Schier, and Gregory Currie have criticized Goodman's autographic/allographic distinction arguing that all works are such that their instances should be identified by taking history of production into account. I will address this objection by exploiting David Davies' distinction between e-instances and p-instances of a work, thereby restating the autographic/allographic distinction. Then, I will show that this way of restating this distinction leads us to effective accounts of relevant related phenomena such as forgery, plagiarism, and digital technologies. Finally, I will show the theoretical advantages of my account of the autographic/allographic distinction in comparison with an alternative account recently proposed by Jason D'Cruz and P.D. Magnus.‘Nothing but Nonsense’: A Kantian Account of Ugliness1
Abstract
What does it mean for something to be judged ugly? On Kant's account of aesthetic judgment, an object judged beautiful brings about a 'free play of the imagination and the understanding', and is thus given as though 'purposive without purpose'; but ugliness, Kant claims, is the 'contrary to beauty'. Assuming Kant is correct on all counts, we would have to conclude that the object judged ugly would bring about a dynamic that is contrary to this ' free play', but that is nevertheless not its mere absence—since its absence is what is exhibited in usual cognitive, non-aesthetic judgment. Likewise, an ugly object is one that would have to be given as though contrapurposive, yet without running counter to any specific end of ours. In this essay, I try to clear up what this can mean, in order to clarify the judgment of ugliness.‘It’s Just a Story’: Pornography, Desire, and the Ethics of Fictive Imagining
Abstract
Is it ever morally wrong for a consumer to imagine something immoral? Brandon Cooke has recently argued that it cannot be. On Cooke's account, fictive imagining is immune to moral criticism because such cases of imagining do not amount to the consumer's endorsement of the immoral content, nor do they imply that the authors of such fictions necessarily endorse their contents. We argue against Cooke that in fact fictively imagining something immoral can be morally blameworthy for the consumer, specifically in cases where fictive imagining is engaged in the service of immoral desires. Taking one potent case—namely, rape-fantasy pornography—we argue that the proper engagement with pornography requires the engagement of the consumer's desires, and that consumers often engage with works of pornography as a way of 'trying on' desires. Insofar as it is morally wrong to desire something immoral, then it is also morally wrong to cultivate an immoral desire; and for some consumers, fictive imagining is a means of cultivating immoral desires. In this restricted sense, we argue that it can be morally wrong for a consumer to engage in fictively imagining immoral things.Eat this Book: A Carnivore’s ManifestoTaste as Experience. The Philosophy and Aesthetics of Food
Eat This Book: A Carnivore's ManifestoLestelDominique, Trans. Gary Steiner.Columbia University Press. 2016. pp. 160. £14.95 (pbk).
Strange Tools: Art and Human Nature
Strange Tools: Art and Human NatureNoëAlvaHill and Wang. 2015. pp. 304. £;21.81 (hbk).
Excellent Beauty: The Naturalness of Religion and the Unnaturalness of the World
Excellent Beauty: The Naturalness of Religion and the Unnaturalness of the WorldDietrichEricColumbia University Press. 2015. pp. xvi + 191xvi + 191. £25.00 (hbk).
Emotional Intimacy in Literature BSA Prize Essay, 2016
Abstract
When reading literature, we might have an emotional connection with the author, or at least what appears to be such, even when that literature is a work of fiction. But it is unclear how a work of fictional literature could supply the resources for such an experience. It is, after all, a work of fiction, not a report of the author's experience, as with memoir or autobiography. The task of this paper is twofold: first, to explain the nature and value of this emotional experience; second, to argue that a fictional literary work can supply the resources for such an experience.Cerebrospinal fluid γδ T cell frequency is age-related: a case control study of 435 children with inflammatory and non-inflammatory neurologic disorders
Summary
Studies of cerebrospinal fluid (CSF) γδ T cells in children are limited, especially due to the lack of control data. In adults, gamma/delta T cells (TCR-γδ) residing in the intrathecal space are sometimes involved in neuroinflammation. To evaluate the possible role of γδ T cells in pediatric neuroinflammation, we immunophenotyped CSF and blood lymphocytes using flow cytometry in a case-control study of 100 children with non-inflammatory neurologic disorders (NIND), 312 with opsoclonus-myoclonus (OMS), and 23 with other inflammatory neurologic disorders (OIND). In NIND, the negative correlation between CSF γδ T cell frequency and patient age was striking: median frequency 27% in infants, 3.3% in teens. Inter-individual variations were largest in the youngest. There was no gender effect. In all OMS, after correcting for age, only a small effect of OMS severity remained. Measurement of markers for γδ T cell activation (HLA-DR), maturation (CD45RA, CD45RO), or intracellular cytokine staining (IL-4, IFN-γ) failed to discriminate OMS and NIND groups. Of 7 OMS immunotherapies/combinations, none significantly altered the frequency of total CSF γδ T cells or subsets. In OIND, the CSF γδ T cell frequency was <10% for single samples of other paraneoplastic disorders (ANNA-1, ANNA-2, teratoma-associated syndrome), cerebellar ataxia (post-infectious, ataxia-telangiectasia), acute disseminated encephalomyelitis, neuroborreliosis, and encephalitis. This study provides new insights into CSF γδ T cells in the pediatric population. Though their role in CSF remains elusive, the negative age correlation, resistance to immunotherapy, and our age cut-off references for NIND are important findings for the design of future pediatric studies. This article is protected by copyright. All rights reserved.
Use of oral immunosuppressive drugs in the treatment of atopic dermatitis in the Netherlands
Abstract
Background
Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult to treat AD are scarce. From socio-economic perspective it is important to have more insight in these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult to treat AD. Estimating the number of AD patients using oral immunosuppressive drugs can give an impression of the percentage of difficult to treat patients in the total AD population.
Objective
To give an overview of the use of oral immunosuppressive drugs in patients with AD in the Netherlands.
Methods
Prescription data of oral immunosuppressive drugs in the Netherlands were extracted from a pharmaceutical database (NControl) containing data of 557 million prescriptions and 7.2 million patients. An algorithm, based on the WHO Anatomical Therapeutic Chemical (ATC) codes, was used to identify patients with AD. The prescription of oral immunosuppressive drugs in patients with AD between January 1st 2012 and January 1st 2017 was evaluated.
Results
Based on the algorithm, 65 943 patients with AD were selected. 943 AD patients (1.4%) used cyclosporine A, methotrexate, azathioprine or mycophenolic acid. Methotrexate was most commonly used, followed by azathioprine and cyclosporine A. A switch in medication was rarely seen. In the evaluation period a decrease in the prescription of cyclosporine A was seen, together with an increase of the prescription of methotrexate. In 31% of the patients who stopped treatment, the discontinuation took place within the first months of treatment.
Conclusion
In this study population, 1.4% of the AD patients used oral immunosuppressive drugs for their eczema in a five year period. Methotrexate was the most commonly used systemic drug in the Netherlands for the treatment of AD.
This article is protected by copyright. All rights reserved.
Surgical treatment of hidradenitis suppurativa: an analysis of postoperative outcome, cosmetic results and quality of life in 255 patients
Abstract
Background
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with increasing incidence. Severe disease stages are seen as a therapeutic challenge and pose the threat of significant restrictions in patients' life quality.
Objectives
We evaluated postoperative outcome after wide local excision for HS as well as postoperative course, cosmetic results, disease recurrence and quality of life.
Methods
All patients receiving radical surgical treatment for HS (Hurley III) between 2006-2015 were identified and received a letter-based survey. They were asked about postoperative course, cosmetic results, recurrence and life quality.
Results
255 patients (103 men, 152 women) answered the questionnaire. 95% of patients reported disease-specific restrictions in everyday life. 72% of patients did not experience any postoperative adverse events, however, postoperative pain with need for analgesics was reported in 38%. The majority of patients (80%) were very satisfied or satisfied after surgery, 85% of patients would recommend surgery to other affected persons.
Limitations
The retrospective design of the study was a limitation.
Conclusions
The well-known negative psychological and social effects are a relevant part of HS and emphasize the importance of immediate therapy. Since long-lasting local disease-control can be achieved, surgery should be considered as first-line therapy.
This article is protected by copyright. All rights reserved.
Thumb necrotic ulcers caused by weeverfish. Case report and review of the literature
Abstract
a 59-year-old Caucasian man presented to our department with a three weeks history of erythema and edema of the left hand, and a necrotic ulcer of the left thumb, after a holiday in Greece, associated with extreme pain. No other skin or mucosal lesions were present. Systemic symptoms such as nausea, vomiting, hypotension, seizures, cardiac arrhythmias, or paralysis were denied. The local erythematous reaction started after fishing, during which the patient was attacked by a weeverfish (Fig. 1A); the wound was treated with topical antiseptics and antibioticum ointments, and seemed to granulate, but in the following week massive edema of the left hand developed (Fig. 1B), together with a rapidly progressive necrotic ulceration of the left thumb (Fig. 1C).
This article is protected by copyright. All rights reserved.
Imiquimod anal tampons treatment of anal intraepithelial neoplasia
Abstract
The prevalence of Human Papillomavirus (HPV) in men who have sex with men (MSM) is high, reaching 85-93% prevalence in HIV-positive men. High-risk HPV are strongly associated with development of high degrees of anal intraepithelial neoplasia (AIN) which, later on, can develop in anal squamous carcinoma. The growing incidence of anal cancer during last years is particularly important in MSM and HIV-positive patients, in which the coexistence of multiple serotypes of HPV reduces the probability of eliminating the AIN. The treatments for anal dysplasia have shown limited effectiveness. Imiquimod (1-[2-methylpropyl]-1H-imidazo-[4,5-c]-quinolin-4-amine) has been successfully used for different neoplasia.
This article is protected by copyright. All rights reserved.
Insulin resistance in hidradenitis suppurativa: a case-control study
Abstract
Background
The association between chronic inflammatory diseases, such as rheumatoid arthritis and psoriasis, and insulin resistance (IR) has been well established. Hidradenitis suppurativa (HS) is a chronic inflammatory cutaneous disease that affects the apocrine gland-bearing areas of the body.
Objective
We aimed to determine the prevalence of IR in patients with HS.
Methods
This cross-sectional, case-control study enrolled 137 subjects, 76 patients with HS and 61 age- and gender-matched controls. Demographic data, clinical examination of HS patients, anthropometric measures, cardiovascular risk factors and laboratory studies were recorded. The homeostasis model assessment of IR (HOMA-IR) was calculated in all participants by measuring fasting plasma glucose and insulin levels.
Results
The median (IQR) HOMA-IR value in HS patients was significantly higher [2.0 (1.0-3.6)] than in controls [1.5(0.9-2.3)] (p=0.01). The prevalence of IR was significantly higher in cases (43.4%) compared with controls (16.4%) (p=0.001). In the linear regression multivariable analysis after adjusting for age, sex and body mass index (BMI), HS remained as a significant factor for a higher HOMA-IR [2.51(0.18) vs 1.92(0.21); p=0.04]. The HOMA-IR value and the prevalence of IR did not differ significantly among HS patients grouped by severity of the disease.
Conclusion
Our results show an increased frequency of IR in HS. Thus, we suggest HS patients to be evaluated for IR and managed accordingly.
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Commentary on the paper: “efficacy of a novel strategy for poststernotomy deep sternal infection after thoracic aorta replacement using a prosthetic graft”
Publication date: Available online 26 February 2018
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Raymund E. Horch
Effect of atopic skin stressors on natural moisturizing factors and cytokines in healthy adult epidermis
Abstract
Background
Epidermal deficiency of filaggrin, and the derived natural moisturizing factors (NMF), is associated with increased risk of atopic dermatitis (AD). While filaggrin gene mutations cause filaggrin deficiency, there is limited insight in causative environmental factors.
Objective
To explore the effect of selected exogenous skin stressors on NMF and skin cytokines levels in healthy adult epidermis.
Material and methods
40 healthy volunteers (18-49 years) were exposed to hard, soft, and chlorinated water, 0.5% SLS, house dust mite, cat allergen, staphylococcal enterotoxin B (SEB), cooling and histamine. Participants were tape-stripped and biophysiological measurements were performed. NMF was determined after 24 and 48 hours, while skin cytokines were measured after 24 hours for selected exposures.
Results
At 24 hours, a significant decrease in NMF was observed for soft (0.51±0.19) and hard water (0.61±0.32) compared to occlusion alone (0.71±0.18). Hard water led to increased levels of IL-4, IFN-ɣ and IL-10. Exposure to house dust mite and SEB led to a significant decrease in NMF after 24 hours (0.77 ±0.28 and 0.80±0.28, respectively) compared to occlusion alone (1.00±0.42). House dust mite led to an increase in IFN-ɣ, IL-2 and IL-4, as compared to the non-occluded control site.
Conclusion
Based on experimental exposure to selected atopic skin stressors such as different water types, allergens and SEB, we conclude that NMF levels are decreased along with increased secretion of various skin cytokines in healthy individuals. Our data highlight environmental factors that might play a role in AD pathophysiology, but needs confirmation in AD patients.
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Globular adiponectin acts as a melanogenic signal in human epidermal melanocytes
Summary
Background
Adiponectin is an adipocyte-derived cytokine which circulates as a full-length protein and a fragment containing the globular domain of adiponectin (gAd). A recent study has reported the anti-melanogenic effects of full-length adiponectin.
Objectives
To examine the involvement of gAd in melanogenesis and its action mechanisms.
Methods
The effects of gAd on melanogenesis and its mechanism of action were investigated in human epidermal melanocytes and reconstructed epidermis, and they included the levels of melanin content, cellular tyrosinase activity, cAMP production and protein kinase A (PKA) activity, expression and phosphorylation of signaling molecules.
Results
Exogenous gAd increased the melanin content, and the mRNA levels of microphthalmia-associated transcription factor (MITF) and its downstream genes tyrosinase and tyrosinase-related protein (TRP)-1, but not TRP-2, were increased by gAd. However, cAMP production and PKA activity were not affected by gAd. Moreover, attempts to elucidate the underlying mechanism behind the gAd-mediated effect revealed that gAd could regulate melanogenesis by upregulating MITF through phosphorylation of the cAMP response element-binding protein (CREB). In addition, upregulation of MITF was mediated through activation of adenosine monophosphate-activated protein kinase (AMPK)-p38MAPK signaling. Taken together, these findings indicate that promotion of melanogenesis by gAd occurs through increased expression of the MITF gene, which is mediated by activation of the AMPK-p38MAPK-CREB pathway.
Conclusions
These findings suggest that gAd contributes to epidermal homeostasis via its effect on melanocyte biology, and products of adipose tissue could affect epidermal biology.
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Nonlinear Optical Microscopy for Melanoma: Challenges, Tools, and Opportunities
Abstract
The natural pigments known as melanins are thought to play a role in the etiology and progression of melanoma, but many of their roles are currently not well understood. While quantification of melanins have, up until now, have been performed in bulk, new imaging technologies have unlocked the means to visualize and quantify melanins. The nonlinear imaging methods known as Pump-Probe, Coherent Raman, and Sum Frequency Absorption microscopies, provide subcellular resolution imaging of melanins, enabling label-free, longitudinal quantification of both eumelanin and pheomelanin in situ and in vivo. These nonlinear imaging toolkits have been well proven in both animal models and human samples, moving them tantalizingly close to clinical application. Future efforts integrating these tools into practical, mobile imaging systems will provide immense benefit both to clinical research and practice.
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Annual Ambient UVB at Wavelengths that Induce Vitamin D Synthesis is Associated with Reduced Oesophageal and Gastric Cancer Risk: a Nested Case-Control Study
Abstract
Vitamin D has been shown to be beneficial at reducing the risk of cancer, however studies examining oesophageal and gastric cancer have been scarce and findings inconsistent. The UK Biobank cohort was used for this nested case-control study (N=3,732). Primary, incident oesophageal and gastric cancer cases diagnosed after recruitment were identified via linkage to National Cancer Registries. Tropospheric emissions monitoring internet service database was used to calculate ambient annual UVB dose (D-UVB). Conditional logistic regression was used to investigate the relationship between annual ambient D-UVB and risk of oesophageal and gastric cancer and odds ratios (OR) are reported. In total, 373 oesophageal and 249 gastric cancer cases and 3,110 age- and gender-matched controls were included in the study. We found a strong inverse association between annual ambient UVB and odds of developing oesophageal or gastric cancer: compared to the lowest tertile, OR for the highest tertile was 0.64 (95%CI:0.51-0.79) in adjusted analysis. The association was strengthened when restricted to oesophageal cancer (OR=0.60;95%CI:0.45-0.80), and oesophageal adenocarcinoma cases (OR=0.48;95%CI:0.34-0.68). Similar results were found in unadjusted and stratified analysis. In conclusion, ambient UVB radiation is inversely associated with the development of oesophageal and gastric cancer, even in a high latitude country.
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UV-irradiated 2-methyl-4′-(methylthio)-2-morpholinopropiophenone-containing injection solution produced frameshift mutations in the Ames mutagenicity assay
Abstract
In previous studies, we detected the photoinitiators 1-hydroxycyclohexyl phenyl ketone (1-HCHPK), methyl 2-benzoylbenzoate (MBB), and 2-methyl-4′-(methylthio)-2-morpholinopropiophenone (MTMP) in intravenous injection solutions. In addition, we reported that 1-HCHPK, MBB, and MTMP exhibited cytotoxicity towards normal human peripheral blood mononuclear cells. A previous in vitro study reported that a free-radical photoinitiator introduced covalently bound purine residues into DNA. However, little is known about the in vitro mutagenicity of 1-HCHPK, MBB, and MTMP. In the present in vitro study, we evaluated the mutagenicity of 1-HCHPK, MBB, and MTMP using the Ames test. We found that untreated 1-HCHPK, MBB, and MTMP were not mutagenic in S. typhimurium strain TA97, TA98, TA100, TA102, or TA1535, regardless of the presence/absence of S9 activation. However, ultraviolet (UV) light-irradiated MTMP exhibited mutagenicity in S. typhimurium strain TA97 in the absence of S9 activation. In conclusion, we suggest that exposure to UV-irradiated MTMP, including in intravenous injection solutions, can result in frameshift mutations.
Two cases of seborrheic keratosis of the external ear canal: involvement of PIK3CA and FGFR3 genes
Abstract
Background
Seborrheic keratosis (SK) of the outer ear canal is rarely described in literature. Etiological risk factors involved in SK such as exposure to human papillomavirus (HPV) and ultraviolet (UV) light are established but must still be confirmed. In recent years, new insights into the pathogenesis of SKs occurred in the area of molecular pathogenesis. Fibroblast growth factor receptor 3 (FGFR3) gene and p110α subunit of phosphoinositide 3-kinase (PIK3CA) oncogene mutations are known to be involved.
Methods
We describe two cases of SK of the outer ear canal. We conducted a review of literature and examined the role of etiological risk factors involved in our cases. The lesions were primarily treated with surgical resection. Postoperatively, in both patients, the lesions recurred after a considerably long disease-free interval. We tested both FGFR3 and PIK3CA genes for mutations, in the primary and recurrent lesions.
Results
We did not find any mutations in both genes in all samples.
Conclusion
Additional research is needed to further establish possible etiological risk factors and to clarify the involvement of PIK3CA and FGFR3 genes in the pathogenesis of seborrheic keratosis of the outer ear canal. These cases underscore the need for meticulous diagnosis, treatment, and sufficient long-term follow-up.
Review of Reconstructing ‘Education’ Through Mindful Attention: Positioning the Mind at the Center of Curriculum and Pedagogy , Oren Ergas
Abstract
This paper provides a review of Reconstructing 'Education' through Mindful Attention: Positioning the Mind at the Center of Curriculum and Pedagogy by Oren Ergas. The review examines the central argument of the book, namely that present educational theory and practice avoids substantial self-inquiry, paying lip service to reflective practice but stopping short of any real encounter with the complex dynamics of the self. In Ergas' bold inquiry, we are invited to attend and to see for ourselves by considering perspectives and practices rooted in contemplative traditions. The educational context becomes clear as attention to the self entails formation of the self. However, I argue that it is not clear why contemplative traditions (or mindful attention defined by the text) are best placed to engage in such formation. I suggest that a central problem with the book is the conflation here of education and socialisation, and that more systematic treatment of educational questions might obviate some of the troubling issues around the failures of what is called the inner curriculum.
Out-of-pocket expenditure on maternity care for hospital births in Uttar Pradesh, India
The studies measured Out-of-Pocket Expenditure (OOPE) for hospital births previously suffer from serious data limitations. To overcome such limitations, we designed a hospital-based study for measuring the lev...
In vivo characterization of pustules in Malassezia Folliculitis by reflectance confocal microscopy and optical coherence tomography. A case series study
Abstract
Background and objective
Malassezia Folliculitis (MaF) is an inflammatory condition of hair follicles caused by Malassezia yeast. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) are imaging technologies enabling in vivo visualization of superficial skin layers. This study explores morphology of pustules in MaF imaged by OCT and RCM.
Methods
Patients with microscopically verified MaF were included in this case series. Morphology was evaluated qualitatively with RCM and OCT, focusing on shape, border and content of selected pustules.
Results
Nine patients with MaF were included. Clinically, six patients presented monomorphic MaF with multiple superficial pustules, while three patients showed more polymorph MaF appearance. In total 13 pustules were investigated by RCM and OCT. In RCM images, pustules varied from having a well-defined border with homogenous content to ill-defined borders with heterogeneous content. A distinct black halo was occasionally observed around pustules as were dilated vessels. In OCT images, pustules appeared polymorphic, showing both well- and ill-defined structures with oval or irregular shape and more or less homogenous content. Malassezia fungi were not discernible by either RCM or OCT. Specific morphological image features in RCM and OCT did not reflect different clinical manifestations of MaF.
Conclusion
RCM and OCT images identify morphological aspects of MaF pustules, and confirm that MaF is a folliculitis with clinical as well as morphological variance.
Superficial Inferior Epigastric Artery Flap Salvage Technique Using Deep Inferior Epigastric Artery Graft
Summary: Superficial inferior epigastric artery (SIEA) flap salvage remains challenging, particularly in cases of arterial insufficiency due to vessel spasm, pedicle kinking, or thrombosis. The already small, short SIEA pedicle, in addition to its inherent tendency toward spasm, renders the SIEA flap more difficult to manage when anastomotic revision is required. Furthermore, arterial thrombosis will cause dilation of the internal mammary artery, exacerbating vessel mismatch. In our previously published experience with 145 SIEA flaps, no flap with postoperative arterial thrombosis was salvageable. Following this experience, a new salvage technique using deep inferior epigastric artery grafts has been utilized and is described here.
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Publication date: Available online 25 July 2018 Source: Journal of Photochemistry and Photobiology B: Biology Author(s): Marco Ballestr...
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Editorial AJR Reviewers: Heartfelt Thanks From the Editors and Staff Thomas H. Berquist 1 Share + Affiliation: Citation: American Journal...
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Publication date: Available online 28 September 2017 Source: Actas Dermo-Sifiliográficas Author(s): F.J. Navarro-Triviño
