Dehydroepiandrosterone: molecular mechanisms and therapeutic implications in osteoarthritis

Publication date: Available online 19 May 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Kai Huang, Li-dong Wu
Dehydroepiandrosterone (DHEA), a 19-carbon steroid hormone primarily synthesized in the adrenal gland, exerts a chondroprotective effect against osteoarthritis (OA) and has been considered an effective candidate of disease-modifying OA drugs (DMOADs) that slow disease progression. We and others previously demonstrated that DHEA exerted a beneficial effect on osteoarthritic cartilage by positively modulating the balance between anabolic and catabolic factors (e.g., MMPs/TIMP-1, ADAMTS/TIMP-3 and cysteine proteinases/cystatin C), inhibiting catabolic signaling pathways (e.g., Wnt/β-catenin), and suppressing proinflammatory cytokines-mediated low-grade synovial inflammation (e.g., IL-1β). However, the full picture of the pharmacological molecular mechanism(s) underlying the activity of DHEA against OA is still incomplete, and a comprehensive and up-to-date review article in this field is unavailable. In this review, recent findings (apart from the well documented pathogenesis of OA) regarding disease-related mechanisms involving low grade synovial inflammation, cartilage matrix stiffness, chondrocyte autophagy and the roles of a variety of catabolic cellular signaling pathways are discussed. Moreover, the possible relationship between these disease-related mechanisms and DHEA action is discussed. Emerging evidence from in vivo and in vitro studies were scrutinized and are concisely presented to demonstrate the investigational and putative mechanisms underlying the anti-OA potential of DHEA.

Graphical abstract

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Water decontamination containing nitrate using biosorption with Moringa oleifera in dynamic mode

Abstract

This study was conducted to assess the feasibility of using Moringa oleifera Lam. (MO) seeds in the biosorption of nitrate present in aqueous solutions by means of batch and fixed-bed column biosorption processes. The batch assays showed that nitrate biosorption is enhanced under experimental conditions of pH 3 and a biosorbent mass of 0.05 g. For the experiments in dynamic mode, the results obtained from the statistical parameters showed that lesser pH, lesser feed flow rate, and higher initial concentration will result in an increase of the maximum capacity of the bed. These conditions were confirmed by experimental analysis. The best experimental conditions, according to the values for percentage removal (91.09%) and maximum capacity (7.69 mg g⁻¹) of the bed, were those used in assay 1, which utilized pH 3, feed flow rate of 1 mL min⁻¹, and initial nitrate concentration of 100 mg L⁻¹.

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Effects of physical and chemical aspects on membrane fouling and cleaning using interfacial free energy analysis in forward osmosis

Abstract

Natural organic matter (NOM) in micro-polluted water purification using membranes is a critical issue to handle. Understanding the fouling mechanism in the forward osmosis (FO) process, particularly identifying the predominant factor that controls membrane fouling, could have significant effects on exerting the advantages of FO technique. Cellulose triacetate no-woven (CTA-NW) membrane is applied to experiments with a high removal efficiency (> 99%) for the model foulant. Tannic acid (TA) is used as a surrogate foulant for NOM in the membrane fouling process, thus enabling the analysis of the effects of physical and chemical aspects of water flux, retention, and adsorption. The membrane fouling behavior is affected mainly by the combined effects of the osmotic dragging force and the interaction of the pH in the working solution, foulants, and calcium ions, as demonstrated by the water flux loss and the changes of membrane retention and adsorption. The fouled CTA-NW membrane (in PRO mode) could be flux-recovered by > 85% through physical cleaning methods. The interfacial free energy analysis theory was used to analyze the membrane fouling behavior with calculating the interfacial cohesion and adhesion free energies. The cohesion free energy refers to the deposition of foulants (TA or TA combined with calcium ions) on a fouled membrane. In addition, the adhesion free energy could be used to evaluate the interaction between foulants and a clean membrane.

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Tumor necrosis and clinical outcomes following neoadjuvant therapy in soft tissue sarcoma: A systematic review and meta-analysis

Publication date: Available online 19 May 2018
Source:Cancer Treatment Reviews
Author(s): Samer Salah, Jeremy Lewin, Eitan Amir, Albiruni Abdul Razak
BackgroundThe prognostic role of tumor necrosis following neoadjuvant therapy is established in bone sarcomas but remains unclear in soft tissue sarcomas (STS).MethodsWe searched MEDLINE, MEDLINE in progress, EMBASE and Cochrane to identify studies that investigated neoadjuvant therapy in STS. Studies were required to report survival data based on extent of necrosis, or provided individual patient data allowing estimation thereof. Hazard ratios (HR) for relapse-free (RFS) and overall survival (OS) and odds ratios (OR) for recurrence at 3 years and for death at 5 years were pooled in a random effect meta-analysis. Associations between patient characteristics and attainment of ≥90% necrosis were explored.Results21 studies comprising 1663 patients were included. Extremity tumors were most common (n=1554; 93%). Induction regimens included chemotherapy with radiotherapy (n=924; 56%), chemotherapy alone (n=412; 25%), radiotherapy alone (n=78; 5%), isolated limb perfusion (ILP) (n=231; 14%), and targeted therapy/radiotherapy (n=18; 1%). Patients with < 90% necrosis had higher hazard of recurrence (hazard ratio [HR] 1.47; 95% CI: 1.06-2.04; p = 0.02) and death (HR 1.86; 95% CI: 1.41-2.46; p < 0.001). Risk of recurrence at 3 years (OR=3.35; 95% CI: 2.27-4.92; p < 0.001) and of death at 5 years (OR 2.60; 95% CI: 1.59-4.26; p < 0.001) were similarly increased. Compared to other modalities, ILP was associated with higher odds of achieving ≥90% necrosis (OR 12.1; 95% CI: 3.69-39.88; p < 0.001).ConclusionTumour necrosis < 90% following neoadjuvant therapy is associated with increased recurrence risk and inferior OS in patients with STS.



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Self-Stabilized Silk Sericin-Based Nanoparticles: In Vivo Biocompatibility and Reduced Doxorubicin-Induced Toxicity

Publication date: Available online 19 May 2018
Source:Acta Biomaterialia
Author(s): Doudou Hu, Ting Li, Zongpu Xu, Di Liu, Mingying Yang, Liangjun Zhu
A variety of colloid stabilizers and cryoprotectants confer improved nanoparticle (NP) colloidal stability and redisperability. However, the discounted tumor targetability, delivery efficacy and possible side effects limit the application in the vascular delivery of NPs. Here we present the water-soluble silk sericin (SS) not only as a material for the preparation of NPs, but also both a dispersion stabilizer and a cryoprotectant. In the absence of any stabilizers, SS-based NPs (SSC@NPs) could resist to the serum protein adsorption, preventing the formation of particle agglomerates. Following freeze-drying without addition of cryoprotectants, the SSC@NPs powder could be easily resuspended into NP dispersion with a nearly monodispersed distribution. Additionally, SSC@NPs do not result in acute toxicity in mice at a dose of 400 mg/kg with a slow injection. Moreover, doxorubicin (DOX)-loaded SSC@NPs (DOX-SSC@NPs) diminish the biodistribution of DOX in the heart, mitigating the DOX-induced cardiotoxicity of mice without compromising therapeutic efficacy. Our results suggest that the self-stabilized SSC@NPs could be a secure and effective drug carrier for intravenous administration when deprived of protective agents.Statement of SignificanceIn this work, we have demonstrated that water-soluble silk sericin (SS)-based NPs (SSC@NPs) could keep stable in biological media in the absence of dispersion stabilizers and that SSC@NPs powder after freeze-drying lacking any cryoprotectants can be easily redispersed to NP suspension. This study represents the first work showing water-soluble SS could both act as a dispersion stabilizer and a cryoprotectant due to its hydrophilicity. Meanwhile, these merits stemmed from SS also give self-stability to another type of NPs containing SS. Therefore, it may be promising that SS can be generally used as a surface-modified material or bulk material for other NPs to maintain colloidal stability in biological media.

Graphical abstract

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Evaluation of Genotoxicity and Mutagenic Effects of Vector/DNA Nanocomplexes in Transfected Mesenchymal Stem Cells by Flow Cytometry

Publication date: Available online 19 May 2018
Source:Acta Biomaterialia
Author(s): Alireza Nomani, Xuguang Chen, Arash Hatefi
In recent years, there has been a great deal of interest in ex-vivo genetic modification of mesenchymal stem cells (MSCs) to meet various biomedical needs. Considering the self-renewal potential of MSCs, it is critically important to ensure that transfection vectors (gene carriers) do not induce genotoxicity because they could theoretically turn a single stem cell into a cancer-initiating cell. Unfortunately, there is currently no reliable, unbiased, and quantitative method to measure genotoxicity (micronuclei formation) of gene carriers directly in transfected MSCs. Consequently, it has not been possible to study the correlation of vectors' physicochemical characteristics with their impact on stem cell genome stability. To address this deficiency, a flow cytometry-based method with a specialized gating protocol was developed that not only measures micronuclei formation, but also determines the mechanism of mutagenesis (i.e., clastogenic vs. aneugenic) of each vector in transfected MSCs. This gating protocol effectively eliminates all interfering signals associated with aggregated nanoparticles (viral and non-viral), exogenous DNA, and apoptotic/necrotic bodies from the micronuclei measurement process. The presented gating protocol for flow cytometry, which is provided as a template, enables investigators in academia, industry and regulatory bodies to rapidly and reliably evaluate the genosafety profiles of gene carriers. The findings of this study also indicate that highly positively charged lipid- and polymeric-based vectors can induce genotoxicity even without manifesting substantial somatic toxicity. Thus, extreme care must be taken before implanting ex-vivo-modified MSCs back into a patient's body.Statement of SignificanceThere is a great interest in genetic modification of stem cells (SCs) by using vectors for various biomedical needs. Considering the self-renewal potential of SCs, it is essential to ensure that such vectors do not induce genetic aberrations (genotoxicity) because they could theoretically turn a single stem cell into a cancer-initiating cell. Unfortunately, there is currently no reliable method to measure genotoxicity of vectors directly in transfected SCs. To address this deficiency, a specialized flow cytometry-based method was developed that quantitatively analyzed genotoxicity and determined the mechanism of mutagenesis that occurred in transfected SCs during the transfection process. The developed technique will enable scientists to design safer vectors for genetic modification of stem cells.

Graphical abstract

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Environmental Signals Influencing Myeloid Cell Metabolism and Function in Diabetes

Publication date: Available online 19 May 2018
Source:Trends in Endocrinology & Metabolism
Author(s): Jacqueline M. Ratter, Cees J. Tack, Mihai G. Netea, Rinke Stienstra
The environment induces metabolic reprogramming of immune cells via specific signaling pathways. Recent studies have revealed that changes in cell metabolism affect key immune cell functions including cytokine production and migration. In diabetes, these functions are either insufficiently or excessively activated, translating into diabetes-associated complications, including increased susceptibility to infection and accelerated cardiovascular disease. Diabetes alters the abundance of environmental signals, including glucose, insulin, and lipids. Subsequently, changes in environmental signals drive metabolic reprogramming, impair immune cell function, and ultimately contribute to diabetes-associated complications. We review here recent studies on changes in innate immune cell metabolism, especially in myeloid cells, that are driven by environmental signals relevant to diabetes, and discuss therapeutic perspectives of targeting metabolism of immune cells in diabetes.



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Emerging biomarkers for immune checkpoint inhibition in lung cancer

Publication date: Available online 19 May 2018
Source:Seminars in Cancer Biology
Author(s): George Cyriac, Leena Gandhi
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker. However, both are hampered by being imperfect predictors of response and both can be dynamic during the course of illness. In this review, we will discuss the development of PD-L1 expression as a biomarker as well as the ongoing emergence of other genomic and proteomic markers that can help refine our use of immunotherapies to maximize benefit in the most patients.



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Understanding and Manipulating Viral Immunity: Antibody Immunodominance Enters Center Stage

Publication date: Available online 19 May 2018
Source:Trends in Immunology
Author(s): Davide Angeletti, Jonathan W. Yewdell
Adaptive immune responses against antigenically variable viruses and cellular pathogens are efficient in many cases, but largely limited to the infecting or immunizing strain. A major factor that limits immunity is immunodominance (ID), the hierarchical focusing of adaptive immune responses on a subset of antigenic determinants. While CD8⁺ T cell ID has been extensively studied, studies of basic mechanisms of B cell ID are limited, despite the importance of antibodies (Abs) for durable protection against pathogens. Here, we review recent progress in understanding the basic rules and mechanisms of B cell ID, compare B and CD8⁺ T cell ID, and outline challenges to overcoming ID to develop Ab-based 'universal' vaccines for influenza A and other highly variable viruses.



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Heart rate variability response to affective pictures processed in and outside of conscious awareness: Three consecutive studies on emotional regulation

Publication date: Available online 19 May 2018
Source:International Journal of Psychophysiology
Author(s): Necati Serkut Bulut, Axel Würz, Neşe Yorguner Küpeli, Gresa Çarkaxhıu Bulut, Mehmet Zihni Sungur
Previous research has increased understanding of the neurobiological basis of emotional regulation. However, less is known concerning the unconscious processing of affective information. Three experiments were performed to investigate the extent to which complex affective stimuli can be processed outside of consciousness and demonstrate possible mechanisms for regulation of resulting emotional responses. In Experiment 1, participants were either instructed to passively observe blocked-picture cues (neutral and negative) or to downregulate their emotions by distancing. Resulting emotional regulation activity was assessed with 0.1-Hz heart rate variability (HRV) indices. In Experiment 2, participants were presented with affective pictures that were rendered consciously invisible by means of continuous flash suppression (CFS). In Experiment 3, two equivalent sets of negative affective pictures were covertly presented and the effect of a cognitive task on emotional regulation was evaluated. Our findings revealed that 0.1-Hz HRV indices exhibited greater change over baseline in response to negative compared to neutral stimuli for both presentation conditions (consciously perceived or not). The implementation of distancing and the cognitive task were both associated with higher 0.1-Hz HRV change scores. These results indicate that even complex affective stimuli can be processed without awareness, resulting in a congruent emotional response that is physiologically detectable. Cognitive strategies can help more effectively regulate this response, implying that conscious perception of a triggering stimulus may not be essential for cognitive regulation.



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The cognitive up- and down-regulation of positive emotion: Evidence from behavior, electrophysiology, and neuroimaging

Publication date: Available online 19 May 2018
Source:Biological Psychology
Author(s): Fenghua Li, Shouhang Yin, Pan Feng, Na Hu, Cody Ding, Antao Chen
Although numerous studies have investigated emotion regulation, the physiological responses and neural substrates of positive emotion regulation remain unclear. To address this question, we explored the effect of reappraisal on subjective experience, zygomatic electromyography (zEMG) response, and blood oxygen level response, using the same materials across three independent experiments. Behaviorally, up-regulating positive emotion increased the valence, arousal, and zEMG response, whereas down-regulating positive emotion decreased the valence, but not arousal or the zEMG response. The neuroimaging results indicate that reappraisal-related prefrontal and cingulate regions were recruited in both the up- and down-regulation conditions, while the bilateral occipital lobe was more active in the up-regulation than in the down-regulation. The psychophysiological interaction analysis revealed that the prefrontal-subcortical (amygdala and ventral striatal) connections were primarily recruited during up-regulation. This study expands the research on emotion regulation and enhances the understanding of the mechanisms underlying the cognitive regulation of positive emotion.



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Genetics and management of congenital hypothyroidism

Publication date: Available online 19 May 2018
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): Luca Persani, Giuditta Rurale, Tiziana de Filippis, Elena Galazzi, Marina Muzza, Laura Fugazzola
Several evidences support a relevant genetic origin for Congenital Hypothyroidism (CH), however familial forms are uncommon. CH can be due to morphogenetic or functional defects and several genes have been originally associated either with thyroid dysgenesis or dyshormonogenesis, with a highly variable expressivity and a frequently incomplete penetrance of the genetic defects. The phenotype-driven genetic analyses rarely yielded positive results in more than 10% of cases, thus raising doubts on the genetic origin of CH. However, more recent unsupervised approaches with systematic Next Generation Sequencing (NGS) analysis revealed the existence of hypomorphic alleles of these candidate genes whose combination can explain a significant portion of CH cases. The co-segregation studies of the hypothyroid phenotype with multiple gene variants in pedigrees confirmed the potential oligogenic origin of CH, which finally represents a suitable explanation for the frequent sporadic occurrence of this disease.



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Standing up to bullying: A social ecological review of peer defending in offline and online contexts

Publication date: Available online 19 May 2018
Source:Aggression and Violent Behavior
Author(s): Laura J. Lambe, Victoria Della Cioppa, Irene K. Hong, Wendy M. Craig
Bullying is a relationship problem that most often occurs in the presence of peers. Peers who witness bullying play a critical role in intervening. Peer intervention, or defending, is a complex behavior. Defending a victimized peer can occur offline and online, with many similarities between the two contexts. This paper guided by the Social Ecological Model systematically reviewed the correlates associated with defending at different levels including: individual, peer, family, and school. Inclusion criteria retrieved a final sample of 130 original, peer-reviewed research articles on offline defending, and 25 articles for online defending.Consistent results across both contexts reveal that individuals who defend tend to be girls, have high empathy and low moral disengagement, are popular and well-liked by their peers, and perceive supportive relationships with their parents, teachers, and schools. More research is needed to understand interactions that may occur between levels of the model, as defending is a complex behavior that cannot be characterized by isolated correlates.



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Advancing statistical analysis of ambulatory assessment data in the study of addictive behavior: A primer on three person-oriented techniques

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Katherine T. Foster, Adriene M. Beltz
Ambulatory assessment (AA) methodologies have the potential to increase understanding and treatment of addictive behavior in seemingly unprecedented ways, due in part, to their emphasis on intensive repeated assessments of an individual's addictive behavior in context. But, many analytic techniques traditionally applied to AA data - techniques that average across people and time - do not fully leverage this potential. In an effort to take advantage of the individualized, temporal nature of AA data on addictive behavior, the current paper considers three underutilized person-oriented analytic techniques: multilevel modeling, p-technique, and group iterative multiple model estimation. After reviewing prevailing analytic techniques, each person-oriented technique is presented, AA data specifications are mentioned, an example analysis using generated data is provided, and advantages and limitations are discussed; the paper closes with a brief comparison across techniques. Increasing use of person-oriented techniques will substantially enhance inferences that can be drawn from AA data on addictive behavior and has implications for the development of individualized interventions.



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Editorial Board

Publication date: August 2018
Source:Addictive Behaviors, Volume 83





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The association between perceived distress tolerance and cannabis use problems, cannabis withdrawal symptoms, and self-efficacy for quitting cannabis: The explanatory role of pain-related affective distress

Publication date: October 2018
Source:Addictive Behaviors, Volume 85
Author(s): Kara Manning, Andrew H. Rogers, Jafar Bakhshaie, Julianna B.D. Hogan, Julia D. Buckner, Joseph W. Ditre, Michael J. Zvolensky
Rates of cannabis use and related problems continue to rise, ranking as the third most common substance use disorder in the United States, behind tobacco and alcohol use. Past work suggests that perceived distress tolerance is related to several clinically significant features of cannabis use (e.g., coping-oriented use). However, there has been little exploration of the mechanisms that may underlie relations between perceived distress tolerance and cannabis use problems, withdrawal severity, and self-efficacy for quitting. The current study sought to examine the experience of pain, which frequently co-occurs with cannabis use (Ashrafioun, Bohnert, Jannausch, & Ilgen, 2015), as an underlying factor in the relation between perceived distress tolerance and cannabis related problems among 203 current cannabis-using adults (29.2% female, M = 37.7 years, SD = 10.2, 63% African American). Results indicated that perceived distress tolerance via pain related affective distress significantly predicted the severity of cannabis use problems (Pm = 0.60), degree of cannabis withdrawal (Pm = 0.39), and lower self-efficacy for quitting cannabis (Pm = 0.36). Future work may usefully explore the role of pain-related affective distress as a mechanistic factor in the context of perceived distress tolerance-cannabis relations.



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Combining ecological momentary assessment with objective, ambulatory measures of behavior and physiology in substance-use research

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Jeremiah W. Bertz, David H. Epstein, Kenzie L. Preston
Whereas substance-use researchers have long combined self-report with objective measures of behavior and physiology inside the laboratory, developments in mobile/wearable electronic technology are increasingly allowing for the collection of both subjective and objective information in participants' daily lives. For self-report, ecological momentary assessment (EMA), as implemented on contemporary smartphones or personal digital assistants, can provide researchers with near-real-time information on participants' behavior and mood in their natural environments. Data from portable/wearable electronic sensors measuring participants' internal and external environments can be combined with EMA (e.g., by timestamps recorded on questionnaires) to provide objective information useful in determining the momentary context of behavior and mood and/or validating participants' self-reports. Here, we review three objective ambulatory monitoring techniques that have been combined with EMA, with a focus on detecting drug use and/or measuring the behavioral or physiological correlates of mental events (i.e., emotions, cognitions): (1) collection and processing of biological samples in the field to measure drug use or participants' physiological activity (e.g., hypothalamic-pituitary-adrenal axis activity); (2) global positioning system (GPS) location information to link environmental characteristics (disorder/disadvantage, retail drug outlets) to drug use and affect; (3) ambulatory electronic physiological monitoring (e.g., electrocardiography) to detect drug use and mental events, as advances in machine learning algorithms make it possible to distinguish target changes from confounds (e.g., physical activity). Finally, we consider several other mobile/wearable technologies that hold promise to be combined with EMA, as well as potential challenges faced by researchers working with multiple mobile/wearable technologies simultaneously in the field.



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Mobile phone sensors and supervised machine learning to identify alcohol use events in young adults: Implications for just-in-time adaptive interventions

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Sangwon Bae, Tammy Chung, Denzil Ferreira, Anind K. Dey, Brian Suffoletto
BackgroundReal-time detection of drinking could improve timely delivery of interventions aimed at reducing alcohol consumption and alcohol-related injury, but existing detection methods are burdensome or impractical.ObjectiveTo evaluate whether phone sensor data and machine learning models are useful to detect alcohol use events, and to discuss implications of these results for just-in-time mobile interventions.Methods38 non-treatment seeking young adult heavy drinkers downloaded AWARE app (which continuously collected mobile phone sensor data), and reported alcohol consumption (number of drinks, start/end time of prior day's drinking) for 28days. We tested various machine learning models using the 20 most informative sensor features to classify time periods as non-drinking, low-risk (1 to 3/4 drinks per occasion for women/men), and high-risk drinking (>4/5 drinks per occasion for women/men).ResultsAmong 30 participants in the analyses, 207 non-drinking, 41 low-risk, and 45 high-risk drinking episodes were reported. A Random Forest model using 30-min windows with 1day of historical data performed best for detecting high-risk drinking, correctly classifying high-risk drinking windows 90.9% of the time. The most informative sensor features were related to time (i.e., day of week, time of day), movement (e.g., change in activities), device usage (e.g., screen duration), and communication (e.g., call duration, typing speed).ConclusionsPreliminary evidence suggests that sensor data captured from mobile phones of young adults is useful in building accurate models to detect periods of high-risk drinking. Interventions using mobile phone sensor features could trigger delivery of a range of interventions to potentially improve effectiveness.



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Introduction to the special issue: Utilizing ambulatory assessment to better understand the etiology, maintenance, treatment, and remission of addictive disorders

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Rachel L. Tomko, Erin A. McClure




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The use of ambulatory assessment in smoking cessation

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Christine Vinci, Aaron Haslam, Cho Y. Lam, Santosh Kumar, David W. Wetter
Ambulatory assessment of smoking behavior has greatly advanced our knowledge of the smoking cessation process. The current article first provides a brief overview of ecological momentary assessment for smoking cessation and highlights some of the primary advantages and scientific advancements made from this data collection method. Next, a discussion of how certain data collection tools (i.e., smoking topography and carbon monoxide detection) that have been traditionally used in lab-based settings are now being used to collect data in the real world. The second half of the paper focuses on the use of wearable wireless sensors to collect data during the smoking cessation process. Details regarding how these sensor-based technologies work, their application to newer tobacco products, and their potential to be used as intervention tools are discussed. Specific focus is placed on the opportunity to utilize novel intervention approaches, such as Just-In-Time Adaptive Interventions, to intervene upon smoking behavior. Finally, a discussion of some of the current challenges and limitations related to using sensor-based tools for smoking cessation are presented, along with suggestions for future research in this area.



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Assessment of alcohol intake: Retrospective measures versus a smartphone application

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Antoinette Poulton, Jason Pan, Loren Richard Bruns, Richard O. Sinnott, Robert Hester
IntroductionResearch investigating problem drinking often relies on retrospective measures to assess alcohol consumption behaviour. Limitations associated with such instruments can, however, distort actual consumption levels and patterns. We developed the smartphone application (app), CNLab-A, to assess alcohol intake behaviour in real-time.MethodsHealthy individuals (N=671, M age 23.12) completed demographic questions plus the Alcohol Use Questionnaire and a 21-day Timeline Followback before using CNLab-A for 21days. The app asked participants to record alcohol consumption details in real time. We compared data reported via retrospective measures with that captured using CNLab-A.ResultsOn average, participants submitted data on 20.27days using CNLab-A. Compared to Timeline Followback, a significantly greater percentage of drinking days (24.79% vs. 26.44%) and significantly higher total intake (20.30 vs. 24.26 standard drinks) was recorded via the app. CNLab-A captured a substantially greater number of high intake occasions at all levels from 8 or more drinks than Timeline Followback. Additionally, relative to the Alcohol Use Questionnaire, a significantly faster rate of consumption was recorded via the app.ConclusionsCNLab-A provided more nuanced information regarding quantity and pattern of alcohol intake than the retrospective measures. In particular, it revealed higher levels of drinking than retrospective reporting. This will have implications for how particular at-risk alcohol consumption patterns are identified in future and might enable a more sophisticated exploration of the causes and consequences of drinking behaviour.



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Obtaining continuous BrAC/BAC estimates in the field: A hybrid system integrating transdermal alcohol biosensor, Intellidrink smartphone app, and BrAC Estimator software tools

Publication date: August 2018
Source:Addictive Behaviors, Volume 83
Author(s): Susan E. Luczak, Ashley L. Hawkins, Zheng Dai, Raphael Wichmann, Chunming Wang, I.Gary Rosen
Biosensors have been developed to measure transdermal alcohol concentration (TAC), but converting TAC into interpretable indices of blood/breath alcohol concentration (BAC/BrAC) is difficult because of variations that occur in TAC across individuals, drinking episodes, and devices. We have developed mathematical models and the BrAC Estimator software for calibrating and inverting TAC into quantifiable BrAC estimates (eBrAC). The calibration protocol to determine the individualized parameters for a specific individual wearing a specific device requires a drinking session in which BrAC and TAC measurements are obtained simultaneously. This calibration protocol was originally conducted in the laboratory with breath analyzers used to produce the BrAC data. Here we develop and test an alternative calibration protocol using drinking diary data collected in the field with the smartphone app Intellidrink to produce the BrAC calibration data. We compared BrAC Estimator software results for 11 drinking episodes collected by an expert user when using Intellidrink versus breath analyzer measurements as BrAC calibration data. Inversion phase results indicated the Intellidrink calibration protocol produced similar eBrAC curves and captured peak eBrAC to within 0.0003%, time of peak eBrAC to within 18min, and area under the eBrAC curve to within 0.025% alcohol–hours as the breath analyzer calibration protocol. This study provides evidence that drinking diary data can be used in place of breath analyzer data in the BrAC Estimator software calibration procedure, which can reduce participant and researcher burden and expand the potential software user pool beyond researchers studying participants who can drink in the laboratory.

Graphical abstract

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Development of postural control in infancy in cerebral palsy and cystic periventricular leukomalacia

Publication date: July 2018
Source:Research in Developmental Disabilities, Volume 78
Author(s): Anke G. Boxum, Linze-Jaap Dijkstra, Sacha la Bastide-van Gemert, Elisa G. Hamer, Tjitske Hielkema, Heleen A. Reinders-Messelink, Mijna Hadders-Algra
BackgroundDevelopment of postural problems in Cerebral Palsy (CP) is largely unknown. Postural muscle activity is organized into two levels: 1) direction-specificity; 2) fine-tuning of direction-specific activity.AimTo study development of postural control until 21 months corrected age in subgroups of infants at very high-risk (VHR) of CP: a) with and without CP at 21 months; b) with and without cystic periventricular leukomalacia (cPVL), the brain lesion with highest risk of CP.Methods and proceduresLongitudinal electromyography recordings of postural muscles during reaching were made in 38 VHR-infants (severe brain lesion or clear neurological signs) between 4.7 and 22.6 months (18 CP, of which 8 with cPVL). Developmental trajectories were calculated using linear mixed effect models.Outcomes and resultsVHR-infants with and without CP showed virtually similar postural development throughout infancy. The subgroup of VHR-infants with cPVL improved performance in direction-specificity with increasing age, while they performed throughout infancy worse in fine-tuning of postural adjustments than infants without cPVL.Conclusions and implicationsVHR-infants with and without CP have a similar postural development that differs from published trajectories of typically developing infants. Infants with cPVL present from early age onwards dysfunctions in fine-tuning of postural adjustments; they focus on direction-specificity.



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Cutaneous Features and Diagnosis of Primary Sjogren’s Syndrome: An Update and Review

SS is diagnostically challenging due to clinical and immunologic features which overlap with other connective tissue diseases, SS patients with cutaneous vasculitis, especially cryoglobulinemic vasculitis, have worse prognosis with increased risk of systemic vasculitis and lymphoma. SS patients with photosensitive annular erythema tend to have milder systemic and glandular involvement, Characteristic cutaneous features of SS are early diagnostic signs correlating with prognosis.

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Increased Severity and Epidermal Alterations in Persistent versus Evanescent Skin lesions in Adult Onset Still’s disease

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Mesotherapy with Botulinum toxin for the treatment of refractory vascular and papulopustular rosacea

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Adalimumab Alleviates Skin Pain in Patients with Moderate to Severe Hidradenitis Suppurativa: Secondary Efficacy Results from the PIONEER I and PIONEER II Randomized Controlled Trials

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Teaching pediatric dermoscopy in a resource limited setting

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In response to Stiegel et al, “Prognostic value of sentinel lymph node biopsy according to Breslow thickness for cutaneous melanoma”

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Reply to MS#JAAD-D-18-00555

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Optimal Surgical Modality for Early Merkel Cell Carcinoma—Results from the National Cancer Data Base

https://ift.tt/2kbdjOI

Relative survival analysis in patients with stage I-II Merkel cell carcinoma treated with Mohs micrographic surgery or wide local excision

https://ift.tt/2rYfkBn

Undifferentiated Pleomorphic Sarcoma: Factors Predictive of Adverse Outcomes

Undifferentiated pleomorphic sarcoma (UPS) embodies various spindle cell tumors; we sought to identify those with aggressive behavior, Invasion beyond subcutaneous fat and tumor size >2 cm predicted more aggressive behavior, We propose subcategorization to superficial and deep UPS

https://ift.tt/2kbOHp9

In vivo imaging of neuronal calcium during electrode implantation: Spatial and temporal mapping of damage and recovery

Publication date: August 2018
Source:Biomaterials, Volume 174
Author(s): James R. Eles, Alberto L. Vazquez, Takashi D.Y. Kozai, X. Tracy Cui
Implantable electrode devices enable long-term electrophysiological recordings for brain-machine interfaces and basic neuroscience research. Implantation of these devices, however, leads to neuronal damage and progressive neural degeneration that can lead to device failure. The present study uses in vivo two-photon microscopy to study the calcium activity and morphology of neurons before, during, and one month after electrode implantation to determine how implantation trauma injures neurons. We show that implantation leads to prolonged, elevated calcium levels in neurons within 150 μm of the electrode interface. These neurons show signs of mechanical distortion and mechanoporation after implantation, suggesting that calcium influx is related to mechanical trauma. Further, calcium-laden neurites develop signs of axonal injury at 1–3 h post-insert. Over the first month after implantation, physiological neuronal calcium activity increases, suggesting that neurons may be recovering. By defining the mechanisms of neuron damage after electrode implantation, our results suggest new directions for therapies to improve electrode longevity.



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Medical and Preoperative Evaluation of the Older Adult

Because of age, increased rates of multimorbidity, polypharmacy, functional changes, and cognitive impairment, older adults are at higher risk for perioperative complications. Identifying modifiable risk factors and educating patients and families about what to expect can improve surgical outcomes and satisfaction. Comprehensive preoperative evaluation assesses these potential factors and should include recommendations for risk reduction. The optimal preoperative evaluation for older adults should address medical conditions and other areas pertinent to the care of older adults including assessments of cognition, capacity, delirium risk, function, frailty, nutrition, medications, and treatment preferences.

https://ift.tt/2LeneiL

Bizarre multilobated myeloma cells mimicking megakaryocytes

Publication date: Available online 19 May 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Sunil Pasricha, Neha Singh, Ajit Panaych, Anurag Mehta




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Current Frontline Endocrine Treatment Options for Women with Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Advanced-Stage Breast Cancer

Publication date: Available online 19 May 2018
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Hikmat N. Abdel-Razeq
Despite the recent advances in breast cancer early detection and awareness, a significant portion of patients present with an advanced-stage disease and more patients will progress to stage IV despite adequate treatment of their initial early-stage disease. Hormone receptor (HR)-positive, Human Epidermal Growth Factor Receptor-2 (HER2)-negative subtype is the commonest among all breast cancer subtypes. The management of the advanced-stage disease of this subtype has evolved significantly over the past few years. The emergence of estrogen receptor down regulators (fulvestrant), mTOR-inhibitors and the recent introduction of CDK4/6 inhibitors, like palbociclib, abemaciclib and ribociclib, has resulted in a significant and a historical improvement in treatment outcomes.In this paper, we review many of the recently reported clinical trials that led to the approval of these new drugs in the first-line settings, along with the current international guidelines.



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A simple, inexpensive method for subcortical stereotactic targeting in nonhuman primates

Publication date: Available online 18 May 2018
Source:Journal of Neuroscience Methods
Author(s): J. Nicole Bentley, Siri S.S. Khalsa, Michael Kobylarek, Karen E. Schroeder, Kevin Chen, Ingrid L. Bergin, Derek M. Tat, Cynthia A. Chestek, Parag G. Patil
BackgroundMany current neuroscience studies in large animal models have focused on recordings from cortical structures. While sufficient for analyzing sensorimotor systems, many processes are modulated by subcortical nuclei. Large animal models, such as nonhuman primates (NHP), provide an optimal model for studying these circuits, but the ability to target subcortical structures has been hampered by lack of a straightforward approach to targeting.New MethodHere we present a method of subcortical targeting in NHP that uses MRI-compatible titanium screws as fiducials. The in vivo study used a cellular marker for histologic confirmation of accuracy.ResultsHistologic results are presented showing a cellular stem cell marker within targeted structures, with mean errors ± standard deviations (SD) of 1.40 ± 1.19 mm in the X-axis and 0.9 ± 0.97 mm in the Z-axis. The Y-axis errors ± SD ranged from 1.5 ± 0.43 to 4.2 ± 1.72 mm.Comparison with existing methodsThis method is easy and inexpensive, and requires no fabrication of equipment, keeping in mind the goal of optimizing a technique for implantation or injection into multiple interconnected areas.ConclusionThis procedure will enable primate researchers to target deep, subcortical structures more precisely in animals of varying ages and weights.



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Intraepidermal nerve fibres are not the exclusive tranducers of nociception

Publication date: Available online 19 May 2018
Source:Journal of Neuroscience Methods
Author(s): Matthieu Talagas, Nicolas Lebonvallet, Laurent Misery
This article is a commentary on a article entitled Micropatterned surface electrode for massive selective stimulation of intraepidermal nociceptive fibres and published last January in your journal (Leandri et al., 2018 Jan 1; 293; 17–26). The goal of this article is to provide an insight of the most recent datas on cutaneous nociception. Indeed recent studies have demonstrated that keratinocytes closely participate in sensory transduction, and therefore, intraepidermal free nerve endings are not exclusive transducers of pain. Therefore, the results presented by Leandri et al., should be interpreted in the light of this information.



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Fas/FasL interaction mediates imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Rui Dou, Zhenya Hong, Xiaosheng Tan, Fenfen Hu, Yajie Ding, Wei Wang, Zhihui Liang, Rongrong Zhong, Xiongwen Wu, Xiufang Weng
The rapid antitumor cytokine production and direct cytotoxicity confer invariant NKT (iNKT) cells ideal candidates for cancer therapy. However, the therapeutic potential of iNKT cells in T-cell malignant diseases remains elusive, as antigen presentation by T cells (T-T presentation) has been suggested to induce hyporesponsiveness of iNKT cells. In this study, we found discrepancies in iNKT cell responses against two T cell-origin cell lines (Jurkat and Molt-4). Human iNKT cells exhibited more intensive cytotoxicity and less efficient cytokine production in response to Fas-bearing Jurkat cells than those to the Fas-negative tumor cells (Molt-4 and myeloid-derived K562). The imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells were CD1d-dependent and relied mostly on Fas/FasL interaction. The impairment in cytokine production could be overcome by Fas/FasL blocking antibodies and exogenous IL-2. Elevated CD1d levels as well as CD1d and Fas co-localization were found in T-cell lymphomas. However, defects in frequency and function of circulating iNKT cells were observed in the patients, which could be partly rescued by exogenous IL-2. Collectively, the Fas/FasL-dependent aberrant iNKT cell responses and the reversibility of the defects suggest the distinct iNKT cell manipulation in CD1d- and Fas-bearing T cell malignancies.



https://ift.tt/2wVuIUV

Genome-wide analysis reveals TNFAIP8L2 as an immune checkpoint regulator of inflammation and metabolism

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Ting Li, Wei Wang, Shunyou Gong, Honghong Sun, Huqin Zhang, An-Gang Yang, Youhai H. Chen, Xinyuan Li
The interplay between inflammation and metabolism is widely recognized, yet the underlying molecular mechanisms remain poorly characterized. Using experimental database mining and genome-wide gene expression profiling methods, we found that in contrast to other TNFAIP8 family members, TNFAIP8L2 (TIPE2) was preferentially expressed in human myeloid cell types. In addition, Tnfaip8l2 expression drastically decreased in lipopolysaccharide (LPS)-stimulated macrophages. Consequently, Tnfaip8l2 deficiency led to heightened expression of genes that were enriched for leukocyte activation and lipid biosynthesis pathways. Furthermore, mitochondrial respiration rate was increased in Tnfaip8l2-deficient macrophages, as measured by Seahorse metabolic analyzer. Taken together, these results indicate that Tnfaip8l2 serves as a "brake" for immunometabolism, which needs to be released for optimized metabolic reprogramming as well as mounting effective inflammatory responses. The unique anti-inflammatory and metabolic-modulatory function of TNFAIP8L2 renders it a novel therapeutic target for cardiovascular diseases and cancer.



https://ift.tt/2IxG5Ys

Operative technique for benign submandibular gland mass without identifying the mandibular branch of the facial nerve

The marginal mandibular branch of the facial nerve must be protected during surgery for benign diseases of submandibular gland. Methods for protecting the marginal mandibular branch include the nerve identification method and the non-identification method.

https://ift.tt/2Iw7S7v

Steroid pulse therapy transiently destroys the discriminative histological structure of tonsils in IgA nephropathy: Tonsillectomy should be performed before or just after steroid pulse therapy

Tonsillectomy combined with steroid-pulse therapy is a widely accepted method for the treatment of IgA nephropathy (IgAN) in Japan. However, the indication of tonsillectomy for IgAN is still controversial, and the timing of tonsillectomy is not clearly defined for the protocol of this therapy. Based on the results of a randomized control trial in Japan, the Evidence-Based Clinical Practice Guidelines for IgA nephropathy 2014 (edited in Japan) recommended tonsillectomy combined with steroid-pulse therapy for Grade C1.

https://ift.tt/2LeX7s7

Concurrence of symmetrical peripheral gangrene and venous limb gangrene following polytrauma: a case report

Symmetrical peripheral gangrene is characterized as acral (distal extremity) ischemic limb injury affecting two or more extremities, without large vessel obstruction, typically in a symmetrical fashion. Risk f...

https://ift.tt/2Iw6uBW

Fas/FasL interaction mediates imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Rui Dou, Zhenya Hong, Xiaosheng Tan, Fenfen Hu, Yajie Ding, Wei Wang, Zhihui Liang, Rongrong Zhong, Xiongwen Wu, Xiufang Weng
The rapid antitumor cytokine production and direct cytotoxicity confer invariant NKT (iNKT) cells ideal candidates for cancer therapy. However, the therapeutic potential of iNKT cells in T-cell malignant diseases remains elusive, as antigen presentation by T cells (T-T presentation) has been suggested to induce hyporesponsiveness of iNKT cells. In this study, we found discrepancies in iNKT cell responses against two T cell-origin cell lines (Jurkat and Molt-4). Human iNKT cells exhibited more intensive cytotoxicity and less efficient cytokine production in response to Fas-bearing Jurkat cells than those to the Fas-negative tumor cells (Molt-4 and myeloid-derived K562). The imbalanced cytokine/cytotoxicity responses of iNKT cells against Jurkat cells were CD1d-dependent and relied mostly on Fas/FasL interaction. The impairment in cytokine production could be overcome by Fas/FasL blocking antibodies and exogenous IL-2. Elevated CD1d levels as well as CD1d and Fas co-localization were found in T-cell lymphomas. However, defects in frequency and function of circulating iNKT cells were observed in the patients, which could be partly rescued by exogenous IL-2. Collectively, the Fas/FasL-dependent aberrant iNKT cell responses and the reversibility of the defects suggest the distinct iNKT cell manipulation in CD1d- and Fas-bearing T cell malignancies.



https://ift.tt/2wVuIUV

Genome-wide analysis reveals TNFAIP8L2 as an immune checkpoint regulator of inflammation and metabolism

Publication date: July 2018
Source:Molecular Immunology, Volume 99
Author(s): Ting Li, Wei Wang, Shunyou Gong, Honghong Sun, Huqin Zhang, An-Gang Yang, Youhai H. Chen, Xinyuan Li
The interplay between inflammation and metabolism is widely recognized, yet the underlying molecular mechanisms remain poorly characterized. Using experimental database mining and genome-wide gene expression profiling methods, we found that in contrast to other TNFAIP8 family members, TNFAIP8L2 (TIPE2) was preferentially expressed in human myeloid cell types. In addition, Tnfaip8l2 expression drastically decreased in lipopolysaccharide (LPS)-stimulated macrophages. Consequently, Tnfaip8l2 deficiency led to heightened expression of genes that were enriched for leukocyte activation and lipid biosynthesis pathways. Furthermore, mitochondrial respiration rate was increased in Tnfaip8l2-deficient macrophages, as measured by Seahorse metabolic analyzer. Taken together, these results indicate that Tnfaip8l2 serves as a "brake" for immunometabolism, which needs to be released for optimized metabolic reprogramming as well as mounting effective inflammatory responses. The unique anti-inflammatory and metabolic-modulatory function of TNFAIP8L2 renders it a novel therapeutic target for cardiovascular diseases and cancer.



https://ift.tt/2IxG5Ys

LotS/LotR/Clp, a novel signal pathway responding to temperature, modulating protease expression via c-di-GMP mediated manner in Stenotrophomonas maltophilia FF11

Publication date: Available online 19 May 2018
Source:Microbiological Research
Author(s): Qingling Wang, Fangling Ji, Jianli Guo, Yuepeng Wang, Yanyan Li, Jingyun Wang, Lijia An, Yongming Bao
Stenotrophomonas maltophilia as one of increasing food spoilage bacteria and fish pathogens has become a threat to aquiculture industry. A major factor contributing to the success of bacterium is its outstanding ability to secrete protease at low temperatures. Here, a cAMP receptor like protein (Clp) shows a positive regulation on this protease, named S. maltophilia temperature-response protease (SmtP). Interestingly, a two-component system, comprising of LotS sensor and LotR regulator, for low-temperature response is also confirmed to modulate SmtP expression with similar effect to Clp. Evidence is presented that LotS/LotR modulates smtP (coding SmtP) expression via Clp: clp promoter activity was reduced significantly at low temperatures and protease activity was partially restored by Clp overexpressed in lotS or lotR deletion strain. Furthermore, as a Clp negative effector, the binding ability of c-di-GMP with Clp is not impacted by temperature. c-di-GMP level was increased in S. maltophilia growing at high temperature, but not exhibited significantly in lotR deleted strain, these indicate that LotR is required for temperature modulating c-di-GMP level, although the synthesis or degradation activity of c-di-GMP by LotR was not detected. These findings suggest that LotS/LotR/Clp play an important role in responding to temperature stimuli via c-di-GMP mediated manner.

Graphical abstract

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Complexity of systems and actions underlying neurogenic inflammation

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Sirolimus Gel vs Placebo for Facial Angiofibromas in Patients With Tuberous Sclerosis Complex

This randomized clinical trial assesses the efficacy and safety of sirolimus gel, 0.2% vs placebo for treatment of angiofibromas and skin lesions in adult and pediatric patients with tuberous sclerosis complex.

https://ift.tt/2k8001l

A comprehensive review on green nanomaterials using biological systems: Recent perception and their future applications

Publication date: Available online 19 May 2018
Source:Colloids and Surfaces B: Biointerfaces
Author(s): Rijuta Ganesh Saratale, Indira Karuppusamy, Ganesh Dattatraya Saratale, Arivalagan Pugazhendhi, Gopalakrishanan Kumar, Yooheon Park, Gajanan S. Ghodake, Ram Naresh Bhargava, J. Rajesh Banu, Han Seung Shin
Over the last few years, nanotechnology is increasingly developing in scientific sector, which has attracted a great deal of interest because of its abundant applications in almost all the areas. In recent times, green nanotechnology is a relative and multidisciplinary field that has emerged as a rapidly developing research area. This is serving as an important technique that spotlight on making the procedure which are clean, safe and in particular environtmentally friendly, in a gap with the currently employed methods such as chemical and physical methods for nanosynthesis. The present review recaps the existing knowledge on various biogenic synthesis methods relying on bacteria, fungi, yeast, algae, viruses and on using biomolecules. The green nanosynthesis refers to the employment of reducing and stabilizing agents from plants and other natural resources, to fabricate nanomaterials. The green synthesis method does not engage the use of exceedingly venomous chemicals or elevated energy inputs during the synthesis. Nanoparticles (NPs) with distinct shapes, sizes and bioactivity can be produced from the variations in the bio-reducing agents employed for nanosynthesis. Hence, this review article summarizes the present information regarding the biological methods which are employed to fabricate greener, safer, and environmentally sustainable nanosynthesis routes. This review mainly highlights the wide-scale fabrication of NPs via green synthesis for biomedical and agricultural applications.

Graphical abstract

https://ift.tt/2rYnV6O

A comprehensive review on green nanomaterials using biological systems: Recent perception and their future applications

Publication date: Available online 19 May 2018
Source:Colloids and Surfaces B: Biointerfaces
Author(s): Rijuta Ganesh Saratale, Indira Karuppusamy, Ganesh Dattatraya Saratale, Arivalagan Pugazhendhi, Gopalakrishanan Kumar, Yooheon Park, Gajanan S. Ghodake, Ram Naresh Bhargava, J. Rajesh Banu, Han Seung Shin
Over the last few years, nanotechnology is increasingly developing in scientific sector, which has attracted a great deal of interest because of its abundant applications in almost all the areas. In recent times, green nanotechnology is a relative and multidisciplinary field that has emerged as a rapidly developing research area. This is serving as an important technique that spotlight on making the procedure which are clean, safe and in particular environtmentally friendly, in a gap with the currently employed methods such as chemical and physical methods for nanosynthesis. The present review recaps the existing knowledge on various biogenic synthesis methods relying on bacteria, fungi, yeast, algae, viruses and on using biomolecules. The green nanosynthesis refers to the employment of reducing and stabilizing agents from plants and other natural resources, to fabricate nanomaterials. The green synthesis method does not engage the use of exceedingly venomous chemicals or elevated energy inputs during the synthesis. Nanoparticles (NPs) with distinct shapes, sizes and bioactivity can be produced from the variations in the bio-reducing agents employed for nanosynthesis. Hence, this review article summarizes the present information regarding the biological methods which are employed to fabricate greener, safer, and environmentally sustainable nanosynthesis routes. This review mainly highlights the wide-scale fabrication of NPs via green synthesis for biomedical and agricultural applications.

Graphical abstract

https://ift.tt/2rYnV6O

Randomized phase II trial of cixutumumab alone or with cetuximab for refractory recurrent/metastatic head and neck squamous cell carcinoma

Publication date: July 2018
Source:Oral Oncology, Volume 82
Author(s): Renata Ferrarotto, William N. William, Jennifer E. Tseng, Shanthi Marur, Dong M. Shin, Barbara Murphy, Ezra E.W. Cohen, Christopher Y. Thomas, Richard Willey, Jan Cosaert, Nusrat Harun, J. Jack Lee, Ignacio W. Wistuba, Robert I. Haddad, Bonnie S. Glisson
ObjectivesCixutumumab (CIX) and cetuximab (CET) monoclonal antibodies block ligand-binding to insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) respectively. The objective of this study was to assess the efficacy of CIX alone or combined with CET in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients.MethodsIn this open-label phase II trial, 91 R/M HNSCC patients who progressed within 90 days of platinum-based chemotherapy, were randomized to CIX 10 mg/kg alone or with CET 500 mg/m² every 2 weeks. Patients were stratified by prior CET use. The primary endpoint was median progression-free survival (PFS). Exploratory biomarker assessments included relevant markers on archival tumor and serial cytokine/angiogenic-factor profiles in blood.ResultsForty-seven patients were treated with CIX monotherapy and 44 with combination. The median PFS was 1.9 and 2.0 months and clinical benefit rate (complete or partial responses and stable disease) was 5.9% and 15.3%, respectively. There was no exacerbation of CET toxicity by concurrent CIX exposure. Higher tumor expression of IGF-1 was associated with improved PFS in the CIX + CET arm while increased p-EGFR expression correlated with shorter PFS in patients receiving single agent CIX. Higher serum baseline levels of IGF-1 and IGFBP-3 correlated with improved PFS and overall survival (OS) in the CIX arm. Neither regimen resulted in improved PFS or OS compared to historical data with CET alone.ConclusionThe results of this study do not support the use of cixutumumab alone or with cetuximab in unselected patients with R/M HNSCC.



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Clinical Thyroidology®for the Public – Highlighted Article

From Clinical Thyroidology^® for the Public: Radioactive iodine therapy is an important part of the treatment of advanced thyroid cancer. Read More…

We welcome your feedback and suggestions. Let us know what you want to see in this publication.

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Clinical Thyroidology®for the Public – Highlighted Article

From Clinical Thyroidology^® for the Public: Radioactive iodine therapy is an important part of the treatment of advanced thyroid cancer. Read More…

We welcome your feedback and suggestions. Let us know what you want to see in this publication.

Feedback & Suggestions

The post Clinical Thyroidology^®for the Public – Highlighted Article appeared first on American Thyroid Association.

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The Role of Anastomotic Vessels in Controlling Tissue Viability and Defining Tissue Necrosis with Special Reference to Complications Following Injection of Hyaluronic Acid Fillers

BACKGROUND: Most target areas for facial volumization procedures relate to the anatomical location of the facial or ophthalmic artery. Occasionally, inadvertent injection of hyaluronic acid (HA) filler into the arterial circulation occurs, and unrecognised, is irreparably associated with disastrous vascular complications. Of note, the site of complications, irrespective of the injection site, is similar, and falls into only 5 areas of the face, all within the functional angiosome of the facial or ophthalmic artery. MATERIAL AND METHODS: Retrospective and prospective studies were made to assess the site and behaviour of anastomotic vessels connecting the angiosomes of the face and their possible involvement in the pathogenesis of tissue necrosis. In-vivo studies of pig and rabbit, and archival human total body and prospective selective lead oxide injections of the head and neck were analysed. Results were compared with documented patterns of necrosis following inadvertent HA intra-arterial injection. RESULTS: Studies showed the location of TRUE and CHOKE anastomoses connecting the facial artery with neighbouring angiosomes predicted the tissue at risk of necrosis following inadvertent intra-arterial HA injection. CONCLUSION: Complications related to HA injections are intimately associated with: (i) the anatomical distribution of TRUE and CHOKE anastomoses connecting the facial artery to neighbouring ophthalmic and maxillary angiosomes where CHOKE vessels define the boundary of necrosis of an involved artery but TRUE anastomoses allow free passage to a remote site; or possibly (ii) retrograde perfusion of HA into avalvular facial veins, especially in the periorbital region, and thereby the ophthalmic vein, cavernous sinus and brain. ** Joint first authors * Presented at 50 Years of Aesthetics, American Society of Aesthetic Plastic Surgeons (ASAPS ), San Diego California Meeting, 27 April – 2 May 2017. Financial Disclosure: The authors have no financial interest to declare in relation to the content of this article. Acknowledgments: We would like to thank Mrs Prue Dodwell for her help with preparing the manuscript and images. Thanks also to Dr Adam Gascoigne for assistance with the dissections and Dr Louie Ye for his time with the Literature Review. The work would not have been possible without support from Mr Jim Carroll and The Donald Ratcliffe and Phyllis Macleod Trust. Corresponding Author: Professor Ian Taylor, Taylor-Lab, Department of Anatomy and Neurosciences, University of Melbourne, Parkville, Victoria 3052, Email: g.taylor@unimelb.edu.au ©2018American Society of Plastic Surgeons

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Intralesional laser treatment for dermal fillers complications

Background: For complications due to filler treatments, in general two treatment regimens are advised: systemic drugs or surgical removal of the material. Another possible treatment option would be removal of the material by intralesional laser treatment (ILT) Methods: 242 patients with complications due to fillers were treated with intralesional laser treatment. Results: In the majority of patients an improvement was achieved (92%), in 9% the complication was resolved and in 3% it was not improved (rest unknown). Conclusion: Considering the large number of patients treated up to date, the efficacy and good safety profile of this treatment, we plead that ILT may be considered as a treatment option before surgery. Financial Disclosure Statement: Dr. Velthuis is trainer for Allergan (hyaluronic acid and botulin toxin), the other authors have nothing to disclose. No funding was received for this article. Corresponding author: L.W. Schelke, MD, Department of Dermatology, Erasmus MC, Postbus 2040, 3000 CA ROTTERDAM, The Netherlands. Lschelke@outlook.com ©2018American Society of Plastic Surgeons

https://ift.tt/2rPhyUn

Quality of Surgical Outcomes Reporting in Plastic Surgery: A 15 Year Analysis of Complication Data

Background: Postoperative complication data are integral to assessing patient outcomes and identifying areas to improve quality in surgical care. Accurate appraisal of surgical techniques requires consistency and reliability in complication data reporting. The purpose of this study was to analyze the quality of complication reporting in plastic surgery. Methods: The authors critically reviewed the literature from January 1st, 2000 to December 31st, 2014 to identify articles reporting surgical outcomes after 3 index procedures (autologous breast reconstruction, prosthetic breast reconstruction and reduction mammaplasty). Studies were extracted from the journals Plastic and Reconstructive Surgery and Annals of Plastic Surgery. Two authors independently analyzed data using a modification of established criteria for complication reporting that incorporates 10 critical elements. Results: 296 articles reporting outcomes for 299,819 procedures in 249,942 patients were analyzed. Of the 10 reporting criteria, no articles met all criteria,

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Immediate two-stage prosthetic breast reconstruction failure: radiation is not the only culprit

Background: Immediate prosthetic breast reconstruction produces a satisfactory aesthetic result with high levels of patient satisfaction. However, with the broader indication for post-mastectomy adjuvant radiation, many patients are advised against immediate breast reconstruction because of concerns of implant loss and infection particularly as most patients also require chemotherapy. This retrospective cohort study examines outcomes for patients who underwent immediate two-stage prosthetic breast reconstruction after mastectomy with or without adjuvant chemotherapy or radiotherapy (RT). Methods: Between 1998 and 2010, 452 patients undergoing two-stage prosthetic immediate breast reconstruction involving a total of 562 breasts were included in this study. Stage one was defined as insertion of the temporary expander and stage two insertion of the final silicone implant. Post-operative adjuvant radiotherapy was recommended with tissue expander in-situ for 114 patients. Complications, including loss of prosthesis, seroma and infection were recorded and analysed. Cosmetic result was assessed using a 4-point scale. Results: Post-operative prosthesis loss was 2.7%, 5.3% for patients undergoing adjuvant chemotherapy increasing to 11.3% for patients receiving chemotherapy+RT. Chemotherapy and radiotherapy independently were the main, statistically significant, risk factors for expander or implant loss; IRR: 13.85 (p=0.012) and 2.23 (p=0.027), respectively. Prosthesis loss for patients undergoing combination chemotherapy+RT was also significant; IRR: 4.791 (p

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Prospective, Randomized, Controlled Comparison of Local Anesthetic Infusion Pump versus DepoFoam Bupivacaine For Pain Management After Unilateral Delayed Deep Inferior Epigastric Perforator Free Flap Reconstruction.

Background: Effective postsurgical analgesia is a critical aspect of patient recovery. The goal of this prospective, randomized, controlled, blinded study was to examine the effect that liposomal bupivacaine delivered via a transversus abdominis plane (TAP) block has on pain control in women undergoing unilateral deep inferior epigastic perforator reconstruction. Methods: IRB approval was granted for this prospective study. Patients were eligible if they were undergoing unilateral, delayed DIEP reconstruction. Patients were randomized to one of three groups; liposomal bupivacaine or bupivacaine TAP block or bupivacaine pain pump. Charts were reviewed for demographics, length of stay, and post-operative narcotic utilization. Results: There were eight patients in the liposomal bupivacaine and bupivacaine groups and 5 patients in the pain pump group. A retrospective cohort of six patients who did not receive any intervention was included. Patients who received a liposomal bupivacaine TAP block used statistically significantly less intravenous and total post-operative narcotics in mg and mg/kg/day compared to all other cohorts. They were able to get out of bed earlier time point. Overall hospital costs were similar amongst the groups. Conclusion: This is the first study to investigate liposomal bupivacaine delivered as a TAP block in a prospective, randomized, blinded study in women undergoing unilateral, delayed abdominally-based autologous breast reconstruction. We were able to demonstrate a significant reduction in intravenous and total narcotic utilization when a liposomal bupivacaine TAP block was utilized. Future studies are needed to prospectively investigate the effect that liposomal bupivacaine would have on immediate and bilateral reconstructions. There are no financial disclosures Corresponding Author: Risal Djohan, MD, Crile Building, Mail Code A60, 2049 East 100th Street, Cleveland, OH 44195, Email: Djohanr@ccf.org, Phone: 216-445-2433 ©2018American Society of Plastic Surgeons

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“Toradol® following breast surgery: Is there an increased risk of hematoma?”

Background: Ketorolac tromethamine (Toradol®), a nonsteroidal antiinflammatory drug, is used with increased frequency given its success in postoperative pain control and the subsequent decreased need for narcotics. Its use has been limited in plastic surgery for fear of postoperative bleeding and hematoma formation. In this study of breast surgery patients, we investigated whether ketorolac increased the risk of postoperative hematoma formation. Methods: After obtaining institutional review board approval, we retrospectively reviewed the records of patients undergoing breast surgery (breast reduction and autologous or implant based reconstruction) from January 2012 through December 2014. Excluded were patients who underwent the first stage of breast reconstruction before January 2012. We compared the incidence of postoperative hematomas in patients who did, versus those who did not, receive ketorolac postoperatively. In addition, we documented other risk factors, such as chronic anticoagulation, aspirin use, or coagulopathies. Results: For our entire cohort, the overall hematoma rate was 2.8%. Of the patients who received ketorolac, the rate was 3.5% of those who did not, 2.5%. Of the breast reduction patients, the rate was 4% in those who received ketorolac vs. 3.2% in those who did not. Of the breast reconstruction patients, the rate was 4% in those who received ketorolac vs. 3.2% in those who did not. Conclusion: In recent years, the high rates of prescribing postoperative narcotics have received increased attention. Aside from the risk of increased availability of narcotics in the community, the side effects of nausea, pruritus, and constipation can delay patient recovery. Ketorolac is controversial for postoperative pain control because of the potential risk of bleeding, but in our 3-year retrospective study, it was not associated with an increased risk of hematoma formation. Financial Disclosure Statement: The authors have nothing to disclose. Presented at: Aesthetica Super Symposium 2017 in New Orleans, LA, Minnesota Surgical Society 2017 in Minneapolis, MN Corresponding Author: Brittany Nguyen, BS, 420 Delaware ST SE, Minneapolis, MN 55455 nguy446@umn.edu, 651-492-3098 ©2018American Society of Plastic Surgeons

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The Functional Anatomy of the Superficial Fat Compartments of the Face – A Detailed Imaging Study

Background: The superficial (subcutaneous) facial fat compartments contribute to the signs of facial aging, but a comprehensive anatomic description of their location and their functional behavior during the application of soft tissue fillers still remains elusive. Methods: We investigated 30 fresh frozen cephalic specimens from 13 male and 17 female Caucasian body donors (age: 78.3 ± 14.2 years, body mass index: 23.1 ± 5.3 kg/m2). Upright positioned contrast enhanced CT scans and additional MR imaging was performed. 3D reconstruction based measures were conducted to evaluate the position of the applied contrast agent in each compartment separately. Successive anatomical dissections were performed to confirm the imaging findings. Results: Positive correlations were detected between the amounts of injected material and the inferior displacement for the superficial nasolabial (rp = 0.92, p = 0.003), middle cheek (rp = 0.70, p = 0.05) and jowl (rp = 0.92, p = 0.03) compartments but not for the medial cheek (rp = 0.20, p = 0.75), lateral cheek (rp = 0.15, p = 0.75), the superior superficial temporal compartments superior: rp = -0.32, p = 0.41; or the inferior superficial temporal compartment: rp = -0.52, p = 0.29. Conclusion: This study confirms the presence of distinct subcutaneous fat compartments and provides evidence for an individual behavior when soft tissue fillers are applied: inferior displacement of the superficial nasolabial, middle cheek and jowl compartments, in contrast to an increase in volume without displacement, i.e. an increase in projection of the medial cheek, lateral cheek and both superficial temporal compartments. Author disclosure: None of the other authors listed have commercial associations or financial disclosures that might pose or create a conflict of interest with the methods applied or the results presented in this article. Funding: The imaging part of this study received funding from Q-Med AB, Sweden (Grant Nr: 15092016). Acknowledgements: We would like to thank Markus Schlager for his support in the imaging parts of this study and Robert H. Gotkin, MD for his guidance during the writing process. Corresponding author: Sebastian Cotofana, MD, PhD, Associate Professor, Albany Medical College, 47 New Scotland Avenue MC-135, Albany, NY 12208, Phone: 518-262-5667, Email: ©2018American Society of Plastic Surgeons

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“Relationship Between Tamoxifen And The Absorption Of Subfascial Autologous Fat Grafts”

Introduction: In the lipofilling procedures used in breast reconstruction, there is an unpredictability in the rate of reabsorption of the grafted fat. The objective of this study was to analyze the effect of Tamoxifen, a medication commonly prescribed for patients with breast cancer, as a possible alternative to reduce the rate of autologous fat graft resorption. Materials and methods: The fatty cushion of the inguinal region of 20 female adult Wistar rats was removed and then autografted, using a standard volume of 0.2 mL in the subfascial plane of the dorsal region. The subject animals were randomized into two groups, control and study. The study group animals were administed 20 mg/kg/day of Tamoxifen citrate over a period of 21 days, via gavage. At the end of the experiment, the animals were euthanized and the grafts underwent morphological and histopathological analysis, with emphasis on the predominant inflammatory response pattern and collagen maturation. Results: The rats undergoing treatment with Tamoxifen (study group) presented higher values in relation to the weight and the volume of fat grafts when compared to the initial values and to the control group. Histological analysis using Hematoxylin-Eosin staining showed that resolution of the inflammatory process was faster in the control group. Analysis using the Picrosirius method demonstrated higher percentages of immature collagen vs. mature collagen. Conclusion: The use of the drug Tamoxifen reduced the rates of resorption and fibrosis of the injected fat, resulting in a better integration of the autologous fat graft. Financial Disclosure Statement: Dr. Alfredo Silva, Mr. Felipe Haupenthal, Mr. André D. Morais, Dr. Adriana Sayuri, Dr. Ana Paula, Dr. Manoel Cavalcanti and Dr. Renato Freitas have nothing to disclose. No funding was received for this article. Ethical conduct of experimental studies with animals: All procedures performed involving animals were in accordance with the ethical standards of the institucional and national research committee or comparable ethical standards. Presented at: Congresso Paulista de Cirurgia 2016 in Sao Paulo, Brazil. Corresponding author: Adriana Sayuri Kurogi Ascenço, Plastic Surgeon, Rua Solimões, 1175, Curitiba, Paraná, Brazil. e-mail address: sayurikurogi@hotmail.com ©2018American Society of Plastic Surgeons

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Risk Factors for Delays in Adjuvant Chemotherapy Following Immediate Breast Reconstruction

Background: Concerns exist that immediate breast reconstruction may delay adjuvant chemotherapy initiation, impacting oncologic outcomes. Here, we determine how post-operative complications impact chemotherapy timing, and identify factors associated with greater risk for delays. Methods: Retrospective chart review identified patients undergoing immediate breast reconstruction and adjuvant chemotherapy at a single institution from 2010 to 2015. Patients were analyzed based on occurrence of post-operative complications and time to chemotherapy. Results: A total of 182 patients (244 breast reconstructions) were included in the study; 210 (86%) reconstructions did not experience post-operative complications, 34 (13.9%) did. Patients who experienced post-operative complications had a higher mean age (53.6 vs. 48.1 years, p=0.002), and higher rates of diabetes (23.5% vs. 3.8%, p48.5 days were of higher mean age (55.9 vs. 50.7 years, p=0.074), had increased rates of diabetes (36.8% vs. 6.7%, p=0.053), and immediate autologous reconstruction (31.6% vs. 0%, p=0.027). A predictive model based on these findings determined that patients with at least 1 of these 3 risk factors have a 74% chance of experiencing prolonged times to chemotherapy initiation vs. 18% without risk factors (p=0.003). Conclusions: Risk factors for delayed chemotherapy in the context of post-operative complications are age >51.7 years, diabetes, and autologous reconstruction. Reconstructive candidates who fit this profile are at highest risk and merit extra consideration and counseling. * Authors contributed equally to preparation of this manuscript FINANCIAL DISCLOSURES: None of the authors of this manuscript have commercial associations or financial disclosures to report that create a conflict of interest with information presented in this manuscript. Corresponding Author: Nolan Karp, M.D. 307 East 33rd Street, New York, NY 10016, (212) 263-5834, Nolan.Karp@nyumc.org ©2018American Society of Plastic Surgeons

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Tizanidine is not effective in treating EPMS

Publication date: Available online 19 May 2018
Source:Medical Hypotheses
Author(s): Helmut Niederhofer




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Transposable elements, placental development, and oocyte activation: Cellular stress and AMPK links jumping genes with the creation of human life

Publication date: Available online 19 May 2018
Source:Medical Hypotheses
Author(s): Jahahreeh Finley
Transposable elements (TEs), also known as "jumping genes", are DNA sequences first described by Nobel laureate Barbara McClintock that comprise nearly half of the human genome and are able to transpose or move from one genomic location to another. As McClintock also noted that a genome "shock" or stress may induce TE activation and transposition, accumulating evidence suggests that cellular stress (e.g. mediated by increases in intracellular reactive oxygen species [ROS] and calcium [Ca2+], etc.) induces TE mobilization in several model organisms and L1s (a member of the retrotransposon class of TEs) are active and capable of retrotransposition in human oocytes, human sperm, and in human neural progenitor cells. Cellular stress also plays a critical role in human placental development, with cytotrophoblast (CTB) differentiation leading to the formation of the syncytiotrophoblast (STB), a cellular layer that facilitates nutrient and gas exchange between the mother and the fetus. Syncytin-1, a protein that promotes fusion of CTB cells and is necessary for STB formation, and its receptor is found in human sperm and human oocytes, respectively, and increases in ROS and Ca2+ promote trophoblast differentiation and syncytin-1 expression. Cellular stress is also essential in promoting human oocyte maturation and activation which, similar to TE mobilization, can be induced by compounds that increase intracellular Ca2+ and ROS levels. AMPK is a master metabolic regulator activated by increases in ROS, Ca2+, and/or an AMP(ADP)/ATP ratio increase, etc. as well as compounds that induce L1 mobilization in human cells. AMPK knockdown inhibits trophoblast differentiation and AMPK-activating compounds that promote L1 mobility also enhance trophoblast differentiation. Cellular stressors that induce TE mobilization (e.g. heat shock) also promote oocyte maturation in an AMPK-dependent manner and the antibiotic ionomycin activates AMPK, promotes TE activation, and induces human oocyte activation, producing normal, healthy children. Metformin promotes AMPK-dependent telomerase activation (critical for telomere maintenance) and induces activation of the endonuclease RAG1 (promotes DNA cleavage and transposition) via AMPK. Both RAG1 and telomerase are derived from TEs. It is our hypothesis that cellular stress and AMPK links TE activation and transposition with placental development and oocyte activation, facilitating both human genome evolution and the creation of all human life. We also propose the novel observation that various cellular stress-inducing compounds (e.g. metformin, resveratrol, etc.) may facilitate beneficial TE activation and transposition and enhance fertilization and embryological development through a common mechanism of AMPK activation.



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Development of a Novel Self-administered Cognitive Assessment Tool and Normative Data for Older Adults

Background: Preexisting cognitive impairment in surgical patients is one of the leading risk factors for adverse cognitive outcomes such as postoperative delirium and postoperative cognitive dysfunction. We developed a self-administered tablet computer application intended to assess the individual risk for adverse postoperative cognitive outcomes. This cross-sectional study aimed to establish normative data for the tool. Materials and Methods: Healthy volunteers aged 65 years and above were administered the Mini-Mental State Examination, Geriatric Depression Scale, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery to assess cognitive health. All subjects completed the tablet computer application without assistance. Primary outcome measure was the test performance. Regression models were built for each cognitive domain score with the covariates age, sex, and education in cognitively healthy subjects. Demographically adjusted standard scores (z-scores) were computed for each subtest. Results: A total of 283 participants (155 women, 128 men) were included in the final analysis. Participants' age was 73.8±5.2 years (mean±SD) and their level of education was 13.6±2.9 years. Mini-Mental State Examination score was 29.2±0.9 points, Geriatric Depression Scale score was 0.4±0.7 points, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery total score was 98.7±5.7 points. Older age was associated with poorer performance in the visual recognition task and in Trail Making Test B (P

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Glasgow Coma Scale Score Fluctuations are Inversely Associated With a NIRS-based Index of Cerebral Autoregulation in Acutely Comatose Patients

Background: The Glasgow Coma Scale (GCS) is an essential coma scale in critical care for determining the neurological status of patients and for estimating their long-term prognosis. Similarly, cerebral autoregulation (CA) monitoring has shown to be an accurate technique for predicting clinical outcomes. However, little is known about the relationship between CA measurements and GCS scores among neurological critically ill patients. This study aimed to explore the association between noninvasive CA multimodal monitoring measurements and GCS scores. Methods: Acutely comatose patients with a variety of neurological injuries admitted to a neurocritical care unit were monitored using near-infrared spectroscopy–based multimodal monitoring for up to 72 hours. Regional cerebral oxygen saturation (rScO2), cerebral oximetry index (COx), GCS, and GCS motor data were measured hourly. COx was calculated as a Pearson correlation coefficient between low-frequency changes in rScO2 and mean arterial pressure. Mixed random effects models with random intercept was used to determine the relationship between hourly near-infrared spectroscopy–based measurements and GCS or GCS motor scores. Results: A total of 871 observations (h) were analyzed from 57 patients with a variety of neurological conditions. Mean age was 58.7±14.2 years and the male to female ratio was 1:1.3. After adjusting for hemoglobin and partial pressure of carbon dioxide in arterial blood, COx was inversely associated with GCS (β=−1.12, 95% confidence interval [CI], −1.94 to −0.31, P=0.007) and GCS motor score (β=−1.06, 95% CI, −2.10 to −0.04, P=0.04). In contrast rScO2 was not associated with GCS (β=−0.002, 95% CI, −0.01 to 0.01, P=0.76) or GCS motor score (β=−0.001, 95% CI, −0.01 to 0.01, P=0.84). Conclusions: This study showed that fluctuations in GCS scores are inversely associated with fluctuations in COx; as COx increases (impaired autoregulation), more severe neurological impairment is observed. However, the difference in COx between high and low GCS is small and warrants further studies investigating this association. CA multimodal monitoring with COx may have the potential to be used as a surrogate of neurological status when the neurological examination is not reliable (ie, sedation and paralytic drug administration). C.W.H. receives research funding from Medtronic/Covidien, Dublin, IR. C.W.H. is the PI on an NIH-sponsored clinical study (R01 HL 92259) and he serves as a consultant to Medtronic/Covidien and Ornim Medical Inc., Foxborough, MA. L.R.-L. is the PI on an American Academy of Neurology/American Brain Foundation, Covidien/Metronic, and Ornim grant. The remaining authors have no conflicts of interest to disclose. Address correspondence to: Ryan J. Healy, BSc, Departments of Neurology, Anesthesiology and Critical Care Medicine, The Johns Hopkins School of Medicine, 600 N Wolfe Street, Phipps 455, Baltimore, MD 21287 (e-mail: ryanhealy@comcast.net). Received November 21, 2017 Accepted April 19, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Rehabilitación del paciente laringectomizado. Recomendaciones de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello

Publication date: Available online 18 May 2018
Source:Acta Otorrinolaringológica Española
Author(s): Pedro Díaz de Cerio Canduela, Ismael Arán González, Rafael Barberá Durban, Alexander Sistiaga Suárez, Marc Tobed Secall, Pablo L. Parente Arias
La laringectomía total permanece como tratamiento fundamental para el carcinoma de laringe localmente avanzado asociándose a una mayor supervivencia. Sin embargo, supone para el paciente una serie de cambios, como la incapacidad de comunicarse verbalmente, la respiración o el cambio estético, que inciden en su calidad de vida y obligan a su rehabilitación integral.El presente documento ha sido elaborado por el grupo de trabajo de rehabilitación del paciente laringectomizado de la Comisión de Cabeza y Cuello y Base de Cráneo de la Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello con el objeto de unificar las recomendaciones sobre materiales, técnicas y medidas que aúnen la rehabilitación integral del paciente sometido a una laringectomía total para la mejora de su calidad de vida y está destinado a especialistas en otorrinolaringología, a profesionales relacionados con el cuidado del paciente laringectomizado total y también a los propios pacientes.Las recomendaciones del documento tienen como objetivo mejorar la atención del paciente al cual se le ha realizado una laringectomía total teniendo en cuenta las necesidades de personal y material, las consideraciones sobre los procedimientos necesarios antes de la cirugía, durante el propio acto quirúrgico y tras el alta hospitalaria del paciente. Se dan también recomendaciones específicas sobre los tipos de rehabilitación y seguimiento de la misma, así como la necesidad de llevar un registro de dichas actividades.Las recomendaciones expuestas pretenden ayudar a los profesionales sanitarios relacionados con el tratamiento de los pacientes laringectomizados totales a llevar a cabo la tarea de hacer que la vida de estos pacientes sea lo más parecida posible a la vida que llevaban antes de realizarse una laringectomía total.Total laryngectomy remains essential treatment for locally advanced laryngeal carcinoma, related to better survival rates. However, it involves changes for the patient, such as the inability to communicate verbally, breathing or aesthetic changes, which affect their quality of life and require comprehensive rehabilitation.This paper was written by the total laryngectomy rehabilitation workgroup of the National Head and Neck and Skull Base working committee of the Spanish Society of Otolaryngology and Head and Neck Surgery. The purpose of the article is to combine materials, surgical procedures and means towards the comprehensive rehabilitation of total laryngectomy patients, so that they can achieve a good quality of life. This paper is aimed at all health care professionals caring for total laryngectomy patients. It is also aimed at the patients themselves, as well as ENT surgeons.We have considered staffing and material needs, all procedures before, during and after surgery and after hospital discharge. There are also detailed recommendations about types of rehabilitation and follow-up, and the need for recording these events.The comprehensive rehabilitation total laryngectomy patients is very important if we want to improve their quality of life. The recommendations we mention aim to help the healthcare professionals involved in the treatment of total laryngectomy patients to help them achieve a good quality of life, as similar as possible to the life they led before surgery.



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Resultados auditivos del sistema activo de conducción ósea Bonebridge® en hipoacusias conductivas o mixtas

Publication date: Available online 18 May 2018
Source:Acta Otorrinolaringológica Española
Author(s): Claudio Carnevale, Guillermo Til-Pérez, Diego J. Arancibia-Tagle, Manuel D. Tomás-Barberán, Pedro L. Sarría-Echegaray
ObjetivoEl implante activo de conducción ósea transcutáneo Bonebridge^® está indicado en pacientes con hipoacusia conductiva/mixta bilateral o en casos de hipoacusia neurosensorial unilateral, mostrando resultados auditivos similares a otros dispositivos percutáneos de conducción ósea pero con menor tasa de complicaciones. El objetivo del siguiente trabajo ha sido analizar los resultados auditivos en una serie de 26 pacientes con hipoacusia conductiva/mixta tratados con Bonebridge^®.MétodosVeintiséis de un total de 30 pacientes implantados con Bonebridge^® entre octubre 2012 y mayo 2017 fueron incluidos en el estudio. Se compararon los umbrales de vía aérea a las frecuencias 500, 1.000, 2.000, 3.000 y 4.000Hz, umbral de reconocimiento verbal 50% y el porcentaje de aciertos a 50dB sin y con el implante.ResultadosEl umbral tonal medio en campo libre con el dispositivo en funcionamiento fue de 34,91dB, obteniendo unas ganancias medias de 33,46dB. La SRT 50% media con el implante fue de 34,33dB mientras que sin él nadie alcanzaba el 50% de aciertos a una intensidad de hasta 50dB. Con respecto al porcentaje de aciertos a 50dB, mejoró desde un 11% sin implante a un 85% con el mismo. Entre las complicaciones solo se observó un caso de extrusión del dispositivo en una paciente con antecedentes de 2 ritidoplastias previas.ConclusionesLos resultados audiológicos obtenidos en nuestro estudio son similares a los publicados en la literatura. Bonebridge^® representa una excelente alternativa en el tratamiento de la hipoacusia conductiva/mixta, pero con una tasa menor de complicaciones.ObjectiveThe active transcutaneous bone conduction implant Bonebridge^®, is indicated for patients affected by bilateral conductive/mixed hearing loss or unilateral sensorineural hearing loss, showing hearing outcomes similar to other percutaneous bone conduction implants, but with a lower rate of complications. The aim of this study was to analyze the hearing outcomes in a series of 26 patients affected by conductive or mixed hearing loss and treated with Bonebridge^®.Methods26 of 30 patients implanted with Bonebridge^® between October 2012 and May 2017, were included in the study. We compared the air conduction thresholds at the frequencies 500, 1000, 2000, 3000, 4000Hz, the SRT50% and the percentage of correct answers at an intensity of 50dB with and without the implant.Results"Pure tone average" with the implant was 34.91dB showing an average gain of 33.46dB. Average SRT 50% with the implant was 34.33dB, whereas before the surgery no patient achieved 50% of correct answers at a sound intensity of 50dB. The percentage of correct answers at 50dB changed from 11% without the implant to 85% with it. We only observed one complication consisting of an extrusion of the implant in a patient with a history of 2 previous rhytidectomies.ConclusionsThe hearing outcomes obtained in our study are similar to those published in the literature. Bonebridge^® represents an excellent alternative in the treatment of conductive or mixed hearing loss, and with a lower rate of complications.



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Manejo de las epistaxis graves y/o refractarias

Publication date: Available online 19 May 2018
Source:Acta Otorrinolaringológica Española
Author(s): Patricia García-Cabo, Laura Fernández-Vañes, Daniel Pedregal, Marta Menéndez del Castro, Eduardo Murias, Pedro Vega, José Luis Llorente, Juan Pablo Rodrigo, Fernando López
Introducción y objetivosEl objetivo fue determinar los resultados del tratamiento de las epistaxis graves y/o refractarias que requirieron ingreso hospitalario. Además se compararon los resultados del tratamiento mediante ligadura arterial o embolización.Material y métodoSe incluyeron de forma prospectiva 63 pacientes con epistaxis grave y/o refractaria que requirieron ingreso hospitalario entre agosto de 2014 y diciembre de 2016.ResultadosEn 11 pacientes (17%) se realizó embolización, 5 (8%) fueron intervenidos mediante endoscopia y en los 47 restantes (75%) se realizó tratamiento conservador. La edad media de los pacientes en los que las medidas conservadoras fueron suficientes fue de 72 años, mientras que la edad de aquellos tratados con embolización fue de 71 años y de los que fueron intervenidos quirúrgicamente fue de 53 años. En los pacientes sometidos a tratamiento conservador o a cirugía la estancia media fue de 6 días, frente a 9 días en aquellos en los que se realizó embolización. Un paciente sufrió un ictus hemisférico tras la embolización. No se observaron complicaciones posquirúrgicas.ConclusionesLa mayoría de los pacientes con epistaxis graves y/o refractarias se resuelven mediante taponamiento convencional. El tratamiento mediante ligadura arterial está asociado a una disminución de la estancia hospitalaria, sin observarse complicaciones graves. Es aconsejable disponer de todas las opciones terapéuticas posibles para lo cual la presencia de radiólogos intervencionistas y cirujanos experimentados es fundamental para evitar complicaciones y decidir el tratamiento a realizar de forma individual en cada paciente.ObjectiveThe objective was to determine the results of the treatment of severe and/or refractory epistaxis requiring hospital admission. In addition, the results of arterial ligation versus embolization were compared.Material and methodSixty-three patients with severe and/or refractory epistaxis requiring hospital admission between August 2014 and December 2016 were included prospectively.ResultsEleven patients (17%) underwent embolization, 5 (8%) endoscopy ligation and the remaining 47 (75%) underwent conservative treatment with tamponade. The mean age of the patients in which conservative measures were sufficient was 72 years, while the age of those treated with embolization was 71 years and of those who underwent surgery was 53 years. For the patients who underwent conservative treatment or surgery, the average stay was 6 days, compared to 9 days for those who underwent embolization. One patient suffered a hemispheric stroke after embolization. No post-surgical complications were observed.ConclusionsMost cases of severe and/or refractory epistaxis are resolved by conventional tamponade. Endoscopy ligation is associated with a decrease in hospital stay, without serious complications. It is advisable to have all the possible therapeutic options available, for which the presence of interventional radiologists and experienced surgeons is essential to avoid complications and decide the treatment to be performed individually for each patient.



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Frozen in Time: A History of the Synthesis of Nitrous Oxide and How the Process Remained Unchanged for Over 2 Centuries

Three major factors have contributed to the unrivaled popularity of nitrous oxide (N2O) among anesthetists in the 20th century and beyond: its impressive safety profile, its affordability, and its rapid induction and emergence times. These 3 characteristics of N2O have been discussed and written about extensively throughout the medical literature. Nonetheless, the characteristic that contributed most to N2O's initial discovery—the elegance and simplicity of its synthesis—has received substantially less attention. Although N2O was first used as an anesthetic in Hartford, CT, in 1844, it had been identified and synthesized as a distinct gas in the late 18th century. In this article, we track the developments in the recognition and early synthesis of N2O, highlight the major players credited with its discovery, and examine its evolution from the late 1700s to today. The discovery and assimilation of N2O into common medical practice, alongside ether and chloroform, heralded a new paradigm in surgical medicine—one that no longer viewed pain as a fundamental component of surgical medicine. Its continued usage in modern medicine speaks to the brilliance and skill of the chemists and scientists involved in its initial discovery. Accepted for publication March 30, 2018. Funding: Intramural. The authors declare no conflicts of interest. Reprints will not be available from the authors. Address correspondence to Manisha S. Desai, MD, University of Massachusetts Medical School, 55 Lake Ave North, Worcester, MA 01655. Address e-mail to manisha.desai@umassmemorial.org. © 2018 International Anesthesia Research Society

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In Response

No abstract available

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