Modelling anaerobic, aerobic and partial nitritation-anammox granular sludge reactors - A review

https://ift.tt/2rwBWJ9

Two challenges for a boolean approach to constitutive inference

Abstract

This paper discusses two challenges for a Boolean method for establishing constitutive regularity statements which, according to the regularity theory of mechanistic constitution, form the core of any mechanistic explanation in neuroscience. After presenting the regularity definition for the constitution relation and a methodology for constitutive inference, the paper discusses the problem of full variation of tested mechanistic factors and the problem of informational redundancy. A solution is offered for each problem. The first requires some adjustments to the original theory by introducing the technical notion of a set of types satisfying independent instantiability. The second one is resolved by demonstrating that the problem of informational redundancy is based on a confusion that fails to challenge the theory. It is concluded that the methodology of constitutive inference is consistent and plausible with respect to actual practice in neuroscience.

https://ift.tt/2LfBEzK

Multiple Realizability as a design heuristic in biological engineering

Abstract

Recently, several critics of the multiple realizability thesis (MRT) have argued that philosophers have tended to accept the thesis on too weak grounds. On the one hand, the analytic challenge has problematized how philosophers have treated the multiple realization relation itself, claiming that assessment of the sameness of function and the relevant difference of realizers has been uncritical. On the other hand, it is argued that the purported evidence of the thesis is often left empirically unverified. This paper provides a novel strategy to answer these worries by introducing a role for multiple realizability in the context of biological engineering. In the field of synthetic biology, bioengineers redesign the evolutionary realizations of biological functions, even constructing artificial chemical surrogates in the laboratory. I show how in the rational design approach to biological engineering, multiple realizability can function as a design heuristic in which the sameness of function and difference of realizers can be controlled. Although practically motivated, this engineering approach has also a theoretical, exploratory component that can be used to study the empirical limitations of multiple realizability. Successful realization of the engineering designs would amount to a concrete demonstration of multiple realizability, taking evidence for MRT beyond what is readily found in nature.

https://ift.tt/2C7khhp

Epistemology for interdisciplinary research – shifting philosophical paradigms of science

Abstract

In science policy, it is generally acknowledged that science-based problem-solving requires interdisciplinary research. For example, policy makers invest in funding programs such as Horizon 2020 that aim to stimulate interdisciplinary research. Yet the epistemological processes that lead to effective interdisciplinary research are poorly understood. This article aims at an epistemology for interdisciplinary research (IDR), in particular, IDR for solving 'real-world' problems. Focus is on the question why researchers experience cognitive and epistemic difficulties in conducting IDR. Based on a study of educational literature it is concluded that higher-education is missing clear ideas on the epistemology of IDR, and as a consequence, on how to teach it. It is conjectured that the lack of philosophical interest in the epistemology of IDR is due to a philosophical paradigm of science (called a physics paradigm of science), which prevents recognizing severe epistemological challenges of IDR, both in the philosophy of science as well as in science education and research. The proposed alternative philosophical paradigm (called an engineering paradigm of science) entails alternative philosophical presuppositions regarding aspects such as the aim of science, the character of knowledge, the epistemic and pragmatic criteria for accepting knowledge, and the role of technological instruments. This alternative philosophical paradigm assume the production of knowledge for epistemic functions as the aim of science, and interprets 'knowledge' (such as theories, models, laws, and concepts) as epistemic tools that must allow for conducting epistemic tasks by epistemic agents, rather than interpreting knowledge as representations that objectively represent aspects of the world independent of the way in which it was constructed. The engineering paradigm of science involves that knowledge is indelibly shaped by how it is constructed. Additionally, the way in which scientific disciplines (or fields) construct knowledge is guided by the specificities of the discipline, which can be analyzed in terms of disciplinary perspectives. This implies that knowledge and the epistemic uses of knowledge cannot be understood without at least some understanding of how the knowledge is constructed. Accordingly, scientific researchers need so-called metacognitive scaffolds to assist in analyzing and reconstructing how 'knowledge' is constructed and how different disciplines do this differently. In an engineering paradigm of science, these metacognitive scaffolds can also be interpreted as epistemic tools, but in this case as tools that guide, enable and constrain analyzing and articulating how knowledge is produced (i.e., explaining epistemological aspects of doing research). In interdisciplinary research, metacognitive scaffolds assist interdisciplinary communication aiming to analyze and articulate how the discipline constructs knowledge.

https://ift.tt/2Le9ogw

Stellenwert der Sialendoskopie an deutschen HNO-Kliniken im Jahr 2016

Laryngo-Rhino-Otol
DOI: 10.1055/a-0805-5846

Hintergrund Eine Umfrage aus dem Jahr 2009 zeigte, dass lediglich etwa 24 % aller deutschen HNO-Kliniken die Sialendoskopie anboten. Durch die Wiederholung der Untersuchung im Jahr 2016 sollte die Entwicklung der Sialendoskopie an deutschen HNO-Kliniken reevaluiert werden. Material und Methoden Erneut wurde ein selbstentwickelter Fragebogen mit elf Fragen an alle deutschen HNO-Kliniken verschickt. Der gleiche Fragebogen wurde bereits im Jahr 2009 verwendet. Die aktuellen Umfrageergebnisse wurden mit den Ergebnissen von damals verglichen und ausgewertet. Ergebnisse Die Zahl der sialendoskopierenden HNO-Kliniken konnte sich mehr als verdoppeln. Die Anzahl der Interventionen verdreifachte sich. Die Gründe dafür, dass eine Klinik keine Sialendoskopien durchführte, waren verschieden. Ein Hauptargument war ein Mangel an Patienten. Kaum Veränderungen ergaben sich bei ambulanten und stationären Therapien und der Eingriffsdauer. Die Sonographie wird unverändert von allen Kliniken präoperativ durchgeführt. Schlussfolgerung Auffallend ist, dass bei zunehmender Anzahl an Kliniken, die die Sialendoskopie anbieten und steigenden Fallzahlen, ein Teil der Kliniken einen Patientenmangel angibt. Dies könnte für die Etablierung von spezialisierten Zentren sprechen. Inzwischen werden neben der obstruktiven Sialadenitis weitere Krankheitsbilder durch die Sialendoskopie therapiert. Die Sonographie bleibt die präoperative Diagnostik der Wahl. Die Auswertung zeigt, dass die Sialendoskopie in den vergangenen sieben Jahren eine steigende Akzeptanz an deutschen HNO-Kliniken erfahren hat.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Donor-derived hepatocytes in human hematopoietic cell transplant recipients: evidence of fusion

Abstract

Reconstitution of hepatocytes by hematopoietic stem cells—a phenomenon which occurs in rodents under highly selective conditions—results from infrequent fusion between incoming myelomonocytes and host hepatocytes, with subsequent proliferation. Human hematopoietic stem cell transplant recipients have been little studied, with some support for transdifferentiation (direct differentiation). We studied routinely obtained autopsy liver tissue of four female hematopoietic cell transplant recipients with male donors, using a highly specific conjoint immunohistochemistry in situ hybridization light microscopic technique. Hepatocyte nuclei were identified by cytokeratin (Cam5.2) staining and evaluated for X and Y chromosome content. Over 1.6 million hepatocytes were assessed for rare instances of donor origin, revealing a Y chromosome in 67. Mixed tetraploids (XXXY) and their nuclear truncation products (XXY, XY, Y) were directly demonstrated, with no detection of the male tetraploids (XXYY) that may result from transdifferentiation with subsequent tetraploidization, nor their unique truncation products (XYY, YY), implicating fusion as the mechanism. To determine whether it is the sole mechanism, we modeled the chromosome distribution based on the same probability of detection of each X chromosome, deriving parameters of sensitivity and female tetraploidy by best fit. We then hypothesized that the distribution of Y chromosome–containing cells could be predicted by a similar model. After modification to account for "clumpy" Y chromosomes, the observed results were in accord with the predicted results (p = 0.6). These results suggest that all the Y-containing cells, including apparent XY cells, derive from mixed tetraploids, consistent with fusion as the sole mechanism.

https://ift.tt/2RTkA4M

Perioperative Intravenous Fluid in Children Undergoing Brain Tumor Resection: Balancing the Threats to Homeostasis

No abstract available

https://ift.tt/2B9Ie6b

Epidemiology and Resource Utilization of Simple Febrile Seizure-associated Hospitalizations in the United States, 2003-2012

Background: Simple febrile seizure (SFS) affects 2% to 4% of children under 6 years of age. The purpose of this study is to examine the epidemiologic patterns and resource utilization of SFS-associated hospitalizations in children aged younger than 6 years of age in the United States. Materials and Methods: This study is a serial, retrospective analysis of the Healthcare Cost and Utilization Project Kids' Inpatient Databases for the years 2003, 2006, 2009, and 2012. SFS-associated hospitalizations were identified based on International Classification of Diseases, Ninth Revision, Clinical Modification, diagnosis code 780.31. We calculated the proportion of hospitalizations in pediatric patients under 6 years of age due to SFS and all other nonbirth causes, the rate of SFS-associated hospitalizations per 100,000 population, the mean length of stay and inflation-adjusted hospital costs of SFS-associated hospitalizations, as well as patient demographics and hospital characteristics. Results: From 2003 to 2012, the weighted proportion of hospitalizations due to SFS declined from 0.83% to 0.41% (P

https://ift.tt/2C4ItAW

Developmental Neurotoxicity: An Update

In the section of "Developmental Neurotoxicity: An Update" of the Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) symposium 2018 the speakers presented the current literature in translational and clinical research. Dr. Brambrink spoke about translational research in anesthetic neurotoxicity, beginning with discovery in the rodent model, then focusing on evidence from nonhuman primates. Dr. Waspe applied the methodology of Adverse Outcome Pathways from the field of toxicology to developmental neurotoxicity of anesthetics. Dr. O'Leary presented relevant clinical studies that were published in 2017 divided by a focus on academic performance, clinical outcomes or diagnoses, or neuropsychological testing.

https://ift.tt/2UB5bbh

Engaging Stakeholders to Promote Safe Anesthesia and Sedation Care in Young Children

An important aspect of any research endeavor is engaging various stakeholders to work toward the common goal of pushing knowledge forward about the question at hand. Research into pediatric anesthetic neurotoxicity could benefit greatly from interventions designed to improve the efforts and dedication of government agencies, pharmaceutical companies, research communities, and most importantly, patients. The Pediatric Anesthesia Neurodevelopment Assessment (PANDA) symposium is a biennial meeting where updates in research in the field are presented, and issues relevant to the community are discussed in round table discussions. Here, we summarize a discussion that took place at the 2018 meeting regarding new methods of engaging various stakeholders, as well as perspectives from other stakeholders. Topics discussed included an online portal to better reach patients, experiences with a public-private partnership, steps by the National Institutes of Health to improve engagement with research and improve the dissemination of results, and the experiences of the United States Food and Drug Administration attempting to improve stakeholder engagement following the passage of a new law to promote drug development. The round table discussion provided interesting insights into a critical research topic, and shared first-hand experience of attempts to improve engagement with a variety of stakeholders.

https://ift.tt/2Uvl7M2

Using Neuroimaging to Study the Effects of Pain, Analgesia, and Anesthesia on Brain Development

Neuroimaging has been increasingly used as a modality to study the impact of pain, analgesia, and anesthetics on pediatric neurodevelopment. The sixth biennial Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium addressed the 2016 US Food and Drug Administration drug safety warning regarding the potential neurotoxic effects of commonly used anesthetic and sedative medications in children, and included a session discussing the use of various neuroimaging techniques, to detect structural, metabolic, and functional brain changes that can occur with exposure to pain and to anesthetic medications. The presenters concluded that advanced multimodal magnetic resonance imaging techniques are useful in detecting the aforementioned changes, which were found to be pain-specific and anesthetic agent-specific.

https://ift.tt/2UCDMpb

Anesthesia and Neurodevelopment in Children: Many Important Questions Remain Unanswered

No abstract available

https://ift.tt/2B9I7HN

Introduction to “Anesthesia and Neurodevelopment in Children”: A Supplement from the Sixth Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) Symposium

No abstract available

https://ift.tt/2UAvoXn

Phenytoin-induced Excessive Sedation During Awake Craniotomy: An Unusual Observation

No abstract available

https://ift.tt/2UCbDyP

Cognitive Aids for the Diagnosis and Treatment of Neuroanesthetic Emergencies: Consensus Guidelines on Behalf of the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Education Committee

Cognitive aids and evidence-based checklists are frequently utilized in complex situations across many disciplines and sectors. The purpose of such aids is not simply to provide instruction so as to fulfill a task, but rather to ensure that all contingencies related to the emergency are considered and accounted for and that the task at hand is completed fully, despite possible distractions. Furthermore, utilization of a checklist enhances communication to all team members by allowing all stakeholders to know and understand exactly what is occurring, what has been accomplished, and what remains to be done. Here we present a set of evidence-based critical event cognitive aids for neuroanesthesia emergencies developed by the Society for Neuroscience in Anesthesiology and Critical Care (SNACC) Education Committee.

https://ift.tt/2BeABvk

Protecting the Brain With Xenon Anesthesia for Neurosurgical Procedures

Xenon possesses some, but not all, of the clinical features of an ideal anesthetic agent. Besides well-known advantages of rapid awakening, stable hemodynamics and lack of biotransformation, preclinical data lead to the expectation of xenon's advantageous use for settings of acute ongoing brain injury; a single randomized clinical trial using an imaging biomarker for assessing brain injury corroborated xenon's preclinical efficacy in protecting the brain from further injury. In this review, we discuss the mechanisms and hence the putative applications of xenon for brain protection in neurosurgery. Although the expense of this rare monoatomic gas will likely prevent its widespread penetration into routine clinical neurosurgical practice, we draw attention to the theoretical benefits of xenon anesthesia over other anesthetic regimens for awake craniotomy and for neurosurgery in older, high-risk, and sicker patients.

https://ift.tt/2B9HZrN

The Best of the Old With Promise of the New: The Format of the Annual Meeting of the Society for Neuroscience in Anesthesiology and Critical Care is Changing

No abstract available

https://ift.tt/2UDTY9J

Balanced Crystalloids Versus Saline for Perioperative Intravenous Fluid Administration in Children Undergoing Neurosurgery: A Randomized Clinical Trial

Background: Balanced crystalloid solutions induce less hyperchloremia than normal saline, but their role as primary fluid replacement for children undergoing surgery is unestablished. We hypothesized that balanced crystalloids induce less chloride and metabolic derangements than 0.9% saline solutions in children undergoing brain tumor resection. Methods: In total, 53 patients (age range, 6 mo to 12 y) were randomized to receive balanced crystalloid (balanced group) or 0.9% saline solution (saline group) during and after (for 24 h) brain tumor resection. Serum electrolyte and arterial blood gas analyses were performed at the beginning of surgery (baseline), after surgery, and at postoperative day 1. The primary trial outcome was the absolute difference in serum chloride concentrations (post-preopΔCl−) measured after surgery and at baseline. Secondary outcomes included the post-preopΔ of other electrolytes and base excess (BE); hyperchloremic acidosis incidence; and the brain relaxation score, a 4-point scale evaluated by the surgeon for assessing brain edema. Results: Saline infusion increased post-preopΔCl (6 [3.5; 8.5] mmol/L) compared with balanced crystalloid (0 [−1.0; 3.0] mmol/L; P

https://ift.tt/2B9HWfB

The Effects of Leukocyte Filtration on Cell Salvaged Autologous Blood Transfusion on Lung Function and Lung Inflammatory and Oxidative Stress Reactions in Elderly Patients Undergoing Lumbar Spinal Surgery

Background: This study was designed to investigate the effects of leukocyte filtration of autologous salvaged blood on lung function, lung inflammatory reaction, and oxidative stress reaction in elderly patients undergoing lumbar spinal surgery. Materials and Methods: Sixty elderly patients undergoing lumbar spinal surgery were randomly divided into 2 groups: Leukocyte Filter group and Control group. Serum levels of inflammatory markers including white blood cell and polymorphonuclear count, neutrophil elastase, serum surfactant protein A, methane dicarboxylic aldehyde, superoxide dismutase, interleukin (IL)-6, IL-8, tumor necrosis factor-α, and respiratory function markers including dynamic respiratory system compliance, oxygenation index, and respiratory index were measured immediately before induction of anesthesia (T0), immediately before blood transfusion (T1), and 1 (T2), 6 (T3), and 12 hours (T4) after end of blood transfusion. Results: The Leukocyte Filter group had higher dynamic respiratory system compliance at T2, oxygenation index at T2 and T3, respiratory index and superoxide dismutase at T2, T3, and T4 than those in the Control group (P

https://ift.tt/2B9HTjV

Outcomes of Anesthesia Selection in Endovascular Treatment of Acute Ischemic Stroke

Background: The association between anesthesia type and outcomes in patients with acute ischemic stroke undergoing endovascular treatment (EVT) remains a subject of ongoing debate. Methods: This prospective nonrandomized controlled trial included 149 consecutive patients with acute anterior circulation stroke who underwent EVT. The primary outcome was functional independence assessed by the modified Rankin Scale (mRS) after 3 months. Results: A total of 105 (70.5%) and 44 (29.5%) patients undergoing EVT who received conscious sedation (CS) and general anesthesia (GA), respectively. The patients who received GA had similar demographics and basic National Institute of Health Stroke Scale scores (17 vs. 16, P>0.05) as the patients who received CS. The recanalization time (304 vs. 311 min, P=0.940) and the recanalization rate (86.4% vs. 84.1%, P=0.170) did not differ between the patients receiving the different types of anesthesia. The National Institute of Health Stroke Scale at 24 hours was lower in the patients who received CS than in those who received GA (β=−2.26, 95% confidence interval, −5.30 to 0.79). The independence (modified Rankin Scale score 0 to 2) at 3 months was equal between patients who received GA and those who received CS (odds ratio=0.73, 95% confidence interval, 0.32-1.68). The mortality and the morbidity rates did not differ. Conclusions: The data indicated that the selection of GA or CS during EVT had no impact on the independent outcomes of patients with anterior circulation occlusion.

https://ift.tt/2B9lwuW

Prolonged Anesthetic Exposure in Children and Factors Associated With Exposure Duration

Introduction: Anesthetic exposure duration has come under scrutiny because of a Food and Drug Administration warning against prolonged use of anesthesia in children, defined as exposures longer than 3 hours. Methods: Data for 2,613,344 pediatric anesthetic records from the American Society of Anesthesiologist's National Anesthesia Clinical Outcomes Registry from 2010 to 2015 were analyzed to describe anesthetic duration and the prevalence of prolonged exposures in children. Common pediatric inpatient procedures were independently assessed to determine factors associated with exposure duration. Results: The overall mean pediatric anesthetic duration was 83.3±107.4 minutes (median, 57 min). Prolonged exposures comprised 7% of pediatric anesthetic records, and 15% of anesthetic records in infants. After restricting to common pediatric inpatient procedures (n=96,603) and adjusting for procedure type using a Poisson model, compared with children 10 years or older, exposures in infants were 20.5% longer (anesthetic duration ratio [ADR], 1.205; 95% confidence interval [CI], 1.202–1.208). Longer exposures were also seen with a variety of other patient and hospital factors including ASA 4 patients versus ASA 1 patients, (ADR, 1.381; 95% CI, 1.376-1.386), and university hospitals versus surgery centers (ADR, 1.241; 95% CI, 1.236-1.246). Conclusions: Most pediatric anesthetic exposures last

https://ift.tt/2UAPIYD

Radiographic Predictors of Difficult Laryngoscopy in Acromegaly Patients

Background: Patients with acromegaly have a high risk of difficult laryngoscopy. However, clinical predictors, such as upper lip bite test or modified Mallampati class, show limited predictive performance for difficult laryngoscopy in such patients. In this retrospective study, we evaluated radiographic indices obtained from skull lateral x-ray and ostiomeatal unit computed tomography images to predict difficult laryngoscopy in acromegaly patients. Materials and Methods: Data on demographics, preoperative serum levels of pituitary hormones, and radiographic indices were collected from 90 acromegaly patients that underwent transsphenoidal removal for pituitary tumor from January 2010 to December 2016. Difficult laryngoscopy was defined as Cormack-Lehane grade ≥III. Results: Difficult laryngoscopy occurred in 21 (23%) patients. In univariate analysis, age and radiographic indices indicating tongue size, such as tongue area (TA) on ostiomeatal unit computed tomography, linear distance from the alveolar line of the mandible to the hyoid bone, and linear distance from the interior border of the mandible to the hyoid bone on skull lateral x-ray, were associated with difficult laryngoscopy. In multivariate analysis, age (odds ratio [95% confidence interval], 1.084 [1.037-1.190]; P=0.002) and TA (1.002 [1.000-1.003], P=0.014) were independent risk factors for difficult laryngoscopy. The area under the curve of the combined model of age and TA was 0.80. Conclusions: Old age and radiographic predictors indicating large tongue size (large TA, long alveolar line of the mandible to the hyoid bone and mandible to the hyoid bone) were associated with an increased rate of difficult laryngoscopy in acromegaly patients. Preoperative radiographic measurements of tongue size can be helpful for safe airway management in such patients.

https://ift.tt/2B9HM7Z

A Summary of Preclinical Poster Presentations at the Sixth Biennial Pediatric Anesthesia Neurodevelopment Assessment (PANDA) Symposium

The potential for long-term neurotoxic effects of anesthetics on the developing human brain has led to intensified research in this area. To date, the human evidence has been inconclusive, but a large body of animal evidence continues to demonstrate cause for concern. On April 14 and 15, 2018 the sixth biennial Pediatric Anesthesia and Neurodevelopmental Assessment (PANDA) study symposium was held at Morgan Stanley Children's Hospital of New York. This symposium brought together clinicians and researchers and served as a platform to review preclinical and clinical data related to anesthesia and neurotoxicity in developing brains. The program participants included many active investigators in the field of anesthesia neurotoxicity as well as stakeholders from different backgrounds with the common interest of potential anesthetic neurotoxicity in children. The moderated poster session included presentations of preclinical animal research studies. These studies focused on defining the anesthetic-induced neurotoxicity phenotype, understanding the mechanism of injury and discovering potential inhibitors of neurotoxic effects.

https://ift.tt/2UyZcDK

Analgesia Nociception Index Monitoring During Supratentorial Craniotomy

Background: Objective monitoring of pain during and after surgery has been elusive. Recently, Analgesia Nociception Index (ANI) monitor based on the high frequency component of heart rate variability has been launched into clinical practice. We monitored analgesia during craniotomy using ANI monitor and compared it with cardiovascular parameters and response entropy (RE) of entropy monitor. Materials and Methods: In 21 patients undergoing a craniotomy for a supratentorial lesion, we monitored ANI, heart rate (HR), mean arterial pressure (MAP), state entropy, and RE throughout the surgery. Also, ANI, hemodynamic variables and spectral entropy values were noted at the times of maximal stimulation, such as induction, intubation, head pin fixation, skin incision, craniotomy, durotomy, and skin closure. We also compared ANI with RE during administration of bolus doses of fentanyl. Results: There was an inverse correlation between ANI values and the hemodynamic changes. When the HR and MAP increased, ANI decreased suggesting a good correlation between hemodynamics and ANI values during the times of maximal stimulation. State entropy and RE did not change significantly in response to bolus doses of fentanyl administered during the course of surgery, while ANI increased significantly. Conclusion: In neurosurgical patients undergoing elective supratentorial craniotomy, ANI measures response to noxious stimuli with at least as much reliability as hemodynamic variables and changes in ANI parallel the changes in HR and MAP. ANI is superior to RE for measurement of response to noxious stimuli.

https://ift.tt/2BaEWzn

Chemical Eye Injury in a Case of Cervical Spine Surgery

No abstract available

https://ift.tt/2UBYSnG

The Impact of Intraoperative Magnetic Resonance Imaging on Patient Safety Management During Awake Craniotomy

Background: Awake craniotomy paired with intraoperative magnetic resonance imaging (iMRI) is now the established technique for maximizing surgical resection, while preserving neurological function. However, leaving an unsecured airway patient in the iMRI gantry represents considerable risk. Our study aimed at identifying the incidence of critical adverse events in unsecured airway patients during iMRI as part of awake craniotomy. Materials and Methods: We conducted a clinical chart review of consecutive awake craniotomies performed between November 1999 and December 2015. Sequences of iMRI performed without invasive airway management were selected for assessment and the incidence of critical adverse events, including general convulsive seizure, respiratory arrest, nausea/vomiting and agitation, was identified. Results: Critical adverse events occurred in 21 of 356 unsecured airway patients within 24 of the 579 iMRI sequences. In cases using the low-field strength open MRI scanner, emergency termination of scans due to patient decline was recorded in only 4 cases: no cases of cardiac arrest, accidental death, or thermal injury were recorded. Compared with cardiovascular monitoring, patient respiratory status was poorly recorded. Conclusions: In terms of anesthesia, concurrent use of iMRI for awake craniotomy is clinically acceptable providing potential intraoperative complications can be controlled. Further, the configuration of the iMRI scanner as well as the reduced exposure from the lower magnetic field strength was found to impact patient safety management. Therefore when a conscious patient is left in the gantry without airway support, it is advisable that levels of oxygenation and ventilation should be monitored at all times.

https://ift.tt/2Bc9DV2

The role of the skin microbiome in atopic dermatitis

Atopic dermatitis (AD) is a common inflammatory skin disease associated with significant medical burden, affecting 15-20% of children and 1-3% of adults worldwide.1 The prevalence of AD has increased by 2-3 folds during the past decade in Western countries. While the cause of this increase remains unknown, meta-analyses have indicated that the risk of AD is lower when associated with potentially protective environmental factors during childhood such as three or more siblings, day care, pet ownership and farm residence.

https://ift.tt/2rtUaes

The Asthma Controller Step-down Yardstick

Guidelines for asthma recommend a series of treatment steps (Figure 1) as a framework for disease management.1,2 The steps allow individualized adjustments in controller therapy in an upward or downward manner in response to a patient's level of asthma control over a period of time. For patients with inadequately controlled asthma, a step-up is recommended.1,2 Strategies for stepping up controller therapy are described in detail in the adult and pediatric Asthma Yardsticks.3,4 For patients whose asthma has been well controlled for at least 3 months (or longer for the highest risk patients), controller treatment may be stepped down.

https://ift.tt/2G8qmOv

Basic chemical peeling—superficial and medium-depth peels

Chemical peeling, or chemexfoliation, has been used for centuries to improve signs of ultraviolet light-induced sun damage. Over the last 30 years, the science behind chemical peeling has evolved, increasing our understanding of the role of peeling ingredients and treatment indications. The depth of peels is directly related to improved results and to the number of complications that can occur. Key principles for superficial and medium depth peeling are discussed, as well as appropriate indications for these treatments.

https://ift.tt/2En8TjK

Advanced chemical peels: phenol-croton oil peel

Once considered the gold standard for deep facial resurfacing, the classical Baker-Gordon phenol-croton oil peel has largely been replaced by formulas with lower concentrations of phenol and croton oil. The improved safety profile of deep peels has ushered in a new era in chemical peeling. Wrinkles can be improved and skin tightened with more subtle and natural results. No longer does a deep peel denote "alabaster white" facial depigmentation with complete effacement of wrinkles. The research of Dr.

https://ift.tt/2EcFx6K

Access to Dermatology Services at Free Medical Clinics, A Nationwide Cross-sectional Survey

https://ift.tt/2EsRgis

Tezepelumab, an anti-TSLP monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial

•Thymic stromal lymphopoietin may initiate inflammation and therefore be a key target for atopic dermatitis treatmentHere, thymic stromal lymphopoietin blockade shows limited efficacy after 12 weeks' treatment; findings at later time points suggest that future clinical trials may require longer treatment periods to determine a significant treatment effect

https://ift.tt/2Ee387e

Epithelioid cell granuloma with caseating necrosis possibly caused by periapical periodontitis: a case report

Epithelioid cell granuloma with caseating necrosis is a typical pathological finding in tuberculosis. While specific inflammation, including that related to tuberculosis, can induce caseating granuloma formati...

https://ift.tt/2QT3U0l

Correction for Yoon et al., Control of movement vigor and decision making during foraging [Corrections]

NEUROSCIENCE, PSYCHOLOGICAL AND COGNITIVE SCIENCES Correction for "Control of movement vigor and decision making during foraging," by Tehrim Yoon, Robert B. Geary, Alaa A. Ahmed, and Reza Shadmehr, which was first published October 15, 2018; 10.1073/pnas.1812979115 (Proc Natl Acad Sci USA 115:E10476–E10485). The authors note that, due to a printer's...

https://ift.tt/2PwRWon

PYL8 mediates ABA perception in the root through non-cell-autonomous and ligand-stabilization-based mechanisms [Plant Biology]

The phytohormone abscisic acid (ABA) plays a key role regulating root growth, root system architecture, and root adaptive responses, such as hydrotropism. The molecular and cellular mechanisms that regulate the action of core ABA signaling components in roots are not fully understood. ABA is perceived through receptors from the PYR/PYL/RCAR...

https://ift.tt/2zU7eyh

Retraction for Baradaran-Heravi et al., Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity [Retractions]

GENETICS Retraction for "Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity," by Alireza Baradaran-Heravi, Jürgen Niesser, Aruna D. Balgi, Kunho Choi, Carla Zimmerman, Andrew P. South, Hilary J. Anderson, Natalie C. Strynadka, Marcel B. Bally, and Michel Roberge, which was first published March 13, 2017;...

https://ift.tt/2zURriH

Metabolic network-based stratification of hepatocellular carcinoma reveals three distinct tumor subtypes [Systems Biology]

Hepatocellular carcinoma (HCC) is one of the most frequent forms of liver cancer, and effective treatment methods are limited due to tumor heterogeneity. There is a great need for comprehensive approaches to stratify HCC patients, gain biological insights into subtypes, and ultimately identify effective therapeutic targets. We stratified HCC patients...

https://ift.tt/2zUUdom

Hinge region of Arabidopsis phyA plays an important role in regulating phyA function [Plant Biology]

Phytochrome A (phyA) is the only plant photoreceptor that perceives far-red light and then mediates various responses to this signal. Phosphorylation and dephosphorylation of oat phyA have been extensively studied, and it was shown that phosphorylation of a serine residue in the hinge region of oat phyA could regulate the...

https://ift.tt/2PvErFf

Role of human Hv1 channels in sperm capacitation and white blood cell respiratory burst established by a designed peptide inhibitor [Physiology]

Using a de novo peptide inhibitor, Corza6 (C6), we demonstrate that the human voltage-gated proton channel (hHv1) is the main pathway for H+ efflux that allows capacitation in sperm and permits sustained reactive oxygen species (ROS) production in white blood cells (WBCs). C6 was identified by a phage-display strategy whereby...

https://ift.tt/2PvEsJj

TRPV1 pore turret dictates distinct DkTx and capsaicin gating [Pharmacology]

Many neurotoxins inflict pain by targeting receptors expressed on nociceptors, such as the polymodal cationic channel TRPV1. The tarantula double-knot toxin (DkTx) is a peptide with an atypical bivalent structure, providing it with the unique capability to lock TRPV1 in its open state and evoke an irreversible channel activation. Here,...

https://ift.tt/2zQR4G0

Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance [Neuroscience]

β-Catenin signaling controls the development and maintenance of the blood–brain barrier (BBB) and the blood–retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand–receptor systems—the Norrin and Wnt7a/Wnt7b systems—are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB...

https://ift.tt/2PzCwPY

Quantifying the role of mineral bridges on the fracture resistance of nacre-like composites [Engineering]

The nacreous layer of mollusk shells holds design concepts that can effectively enhance the fracture resistance of lightweight brittle materials. Mineral bridges are known to increase the fracture resistance of nacre-inspired materials, but their role is difficult to quantify due to the lack of experimental systems where only this parameter...

https://ift.tt/2G9tQAE

Photoreceptive retinal ganglion cells control the information rate of the optic nerve [Neuroscience]

Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information...

https://ift.tt/2zVAFQw

Intrinsically ultrastrong plasmon-exciton interactions in crystallized films of carbon nanotubes [Applied Physical Sciences]

In cavity quantum electrodynamics, optical emitters that are strongly coupled to cavities give rise to polaritons with characteristics of both the emitters and the cavity excitations. We show that carbon nanotubes can be crystallized into chip-scale, two-dimensionally ordered films and that this material enables intrinsically ultrastrong emitter–cavity interactions: Rather than...

https://ift.tt/2Puip5S

Individual synaptic vesicles mediate stimulated exocytosis from cochlear inner hair cells [Neuroscience]

Spontaneous excitatory postsynaptic currents (sEPSCs) measured from the first synapse in the mammalian auditory pathway reach a large mean amplitude with a high level of variance (CV between 0.3 and 1). This has led some to propose that each inner hair cell (IHC) ribbon-type active zone (AZ), on average, releases...

https://ift.tt/2C5IHIc

Single-atomic cobalt sites embedded in hierarchically ordered porous nitrogen-doped carbon as a superior bifunctional electrocatalyst [Chemistry]

Exploring efficient and cost-effective catalysts to replace precious metal catalysts, such as Pt, for electrocatalytic oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) holds great promise for renewable energy technologies. Herein, we prepare a type of Co catalyst with single-atomic Co sites embedded in hierarchically ordered porous N-doped carbon...

https://ift.tt/2ryqbSy

Strong impact of wildfires on the abundance and aging of black carbon in the lowermost stratosphere [Environmental Sciences]

Wildfires inject large amounts of black carbon (BC) particles into the atmosphere, which can reach the lowermost stratosphere (LMS) and cause strong radiative forcing. During a 14-month period of observations on board a passenger aircraft flying between Europe and North America, we found frequent and widespread biomass burning (BB) plumes,...

https://ift.tt/2zWORJ7

Eurasian river spring flood observations support net Arctic Ocean mercury export to the atmosphere and Atlantic Ocean [Earth, Atmospheric, and Planetary Sciences]

Midlatitude anthropogenic mercury (Hg) emissions and discharge reach the Arctic Ocean (AO) by atmospheric and oceanic transport. Recent studies suggest that Arctic river Hg inputs have been a potentially overlooked source of Hg to the AO. Observations on Hg in Eurasian rivers, which represent 80% of freshwater inputs to the...

https://ift.tt/2PBL1KE

Mechanism of the E2 to E1 transition in Ca2+ pump revealed by crystal structures of gating residue mutants [Biochemistry]

Ca2+-ATPase of sarcoplasmic reticulum (SERCA1a) pumps two Ca2+ per ATP hydrolyzed from the cytoplasm and two or three protons in the opposite direction. In the E2 state, after transferring Ca2+ into the lumen of sarcoplasmic reticulum, all of the acidic residues that coordinate Ca2+ are thought to be protonated, including...

https://ift.tt/2PwowXq

The calculation of transcript flux ratios reveals single regulatory mechanisms capable of activation and repression [Biochemistry]

The regulation of transcription allows cells to adjust the rate of RNA polymerases (RNAPs) initiated in a promoter-specific manner. Classically, transcription factors are directed to a subset of promoters via the recognition of DNA sequence motifs. However, a unique class of regulators is recruited directly through interactions with RNAP. Surprisingly,...

https://ift.tt/2C3JUzI

Phage Mu Gam protein promotes NHEJ in concert with Escherichia coli ligase [Biochemistry]

The Gam protein of transposable phage Mu is an ortholog of eukaryotic and bacterial Ku proteins, which carry out nonhomologous DNA end joining (NHEJ) with the help of dedicated ATP-dependent ligases. Many bacteria carry Gam homologs associated with either complete or defective Mu-like prophages, but the role of Gam in...

https://ift.tt/2PzgexU

Benefits of phenotypic plasticity for population growth in varying environments [Biophysics and Computational Biology]

Phenotypic plasticity refers to the capacity of the same organisms to exhibit different characteristics under varied environmental conditions. A plastic developmental program allows organisms to sense environmental cues in early stages of life and express phenotypes that are better fitted to environments encountered later in life. This is often considered...

https://ift.tt/2C60XRQ

Structural snapshots of OxyR reveal the peroxidatic mechanism of H2O2 sensing [Biochemistry]

Hydrogen peroxide (H2O2) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward H2O2. One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces H2O2. In this study, we...

https://ift.tt/2zVAFju

Isotretinoin and Candida immunotherapy for recalcitrant warts in solid organ transplant recipients

Abstract

Treatment of recalcitrant warts in solid organ transplant recipients (SOTR) can pose a therapeutic challenge for dermatologists. Successful treatment of recalcitrant warts can serve as secondary prevention for skin cancer in those with chronic immunosuppression. Given the heterogeneity of associated comorbid conditions in SOTR, clinical trials are difficult to conduct in this high‐risk population, therefore, our clinical practice is mostly driven by observed responses from studies in immunocompetent patients or from case reports of immunocompromised patients. The combination of systemic retinoids and candida immunotherapy likely provide the most effective treatment for recalcitrant warts in SOTR. However, many SOTR have chronic renal insufficiency and are not candidates for Acitretin therapy. We provide two cases of recalcitrant warts in SOTR successfully treated with Isotretinoin in the setting of impaired renal function.

This article is protected by copyright. All rights reserved.

https://ift.tt/2SFMils

Otopathology in Angiosarcoma of the Temporal Bone

Objectives/Hypothesis

Investigate the otopathology of angiosarcoma of the temporal bone, which has not been previously described in the literature.

Study Design

Postmortem evaluation and literature review.

Methods

Postmortem histological evaluation of the temporal bones and review of the literature for the treatment and prognosis of this rare disease were performed.

Results

A 50‐year‐old male with right chronic otitis media presented with progressive hearing loss, disequilibrium, otalgia, and acute facial paresis. Biopsy of the external auditory canal was unrevealing, but specimens from a canal wall down tympanomastoidectomy later showed high‐grade angiosarcoma. Magnetic resonance imaging demonstrated an unresectable middle ear and mastoid mass extending superiorly into the temporal lobe. The patient received induction chemotherapy followed by proton beam radiation therapy and concurrent paclitaxel and bevacizumab. His course was complicated by a cerebrospinal fluid leak and cauda equina syndrome from leptomeningeal sarcomatosis. The patient died after developing meningitis and a temporal lobe abscess. Postmortem otopathology revealed persistent angiosarcoma in the internal auditory canal, although none was found in the middle ear or mastoid. There was inflammatory infiltrate throughout the mastoid, with direct extension of neutrophils and bacteria into the cochlea and through the tegmen into the middle cranial fossa.

Conclusions

Angiosarcoma of the temporal bone can arise in the setting of chronic otitis media. In this case, postmortem temporal bone sections demonstrated viable cancer despite chemoradiation. Inflammatory infiltrates crossing from the middle ear/mastoid into the labyrinth and central nervous system illustrate pathways for the development of otogenic meningitis.

Level of Evidence

4 Laryngoscope, 2018

https://ift.tt/2QpX7f8

In Response to Altered Molecular Profile in Thyroid Cancers From Patients Affected by Three Mile Island Nuclear Accident

https://ift.tt/2RWPXvC

Osteitis is associated with dysregulated pro‐osteoblastic activity in patients with nasal polyps

Objectives/Hypothesis

The overlying inflammatory mucosa plays a crucial role in the initiation of osteitis; however, the molecular mechanism is unclear. The objective of this study was to explore the bone morphogenetic protein (BMP) pathway and to correlate the expression of key signaling molecules with the degree of osteitis in patients with chronic rhinosinusitis with nasal polyps (CRSwNP).

Study Design

Prospective experimental analysis.

Methods

This was an institutional review board–approved study in which mucosal samples were obtained from sites of osteitis in CRSwNP and compared to nonosteitic healthy controls (n = 10/group). Protein expression of key BMP pathway was quantified by aptamer‐based protein array and confirmed by a set of selected mRNA analyses. Degree of osteitis was assessed using both Kennedy Osteitis Score and Global Osteitis Score (GOS).

Results

Pro‐osteoblastic expression of BMP7 (fold change [FC] = −1.18, P = .017) and BMP9 (FC = −1.32, P = .023), their receptors, BMP receptor type‐1A (BMPR1A) (FC = −2.56, P = .005) and BMP receptor type‐2 (FC = −1.28, P = .022), and two enhancers of BMP signaling pathway, the repulsive guidance molecule domain family member B (FC = −1.13, P = .008) and the chordin‐like protein 1 (FC = −1.18, P = .027), were all significantly downregulated in CRSwNP. Conversely, the pro‐osteoclastic factor, tartrate‐resistant acid phosphatase type 5 (ACP5) (FC = 2.36, P = .001), was significantly increased in CRSwNP. GOS was inversely correlated with levels of BMP7 (r = −0.684, P =  .005) and BMPR1A (r = −0.864, P =  .005) and positively correlated with levels of ACP5 (r = 0.815, P =  .004). The FCs among the proteins studied significantly and positively correlated with the FCs of their mRNA expression (r = 0.908, P =  .002).

Conclusions

Downregulated pro‐osteoblastic mucosal BMP signaling is strongly and significantly associated with increased osteitis in CRSwNP.

Level of Evidence

NA Laryngoscope, 2018

https://ift.tt/2Qve3ks

Supraglottic Squamous Cell Carcinoma: A Population‐Based Study of 22,675 Cases

Objectives/Hypothesis

The authors used the Surveillance, Epidemiology, and End Results (SEER) database to analyze epidemiological features of patients presenting with supraglottic squamous cell carcinoma (SCCa) and to evaluate treatment trends and outcomes.

Methods

The SEER database was queried for patients with supraglottic SCCa from 1973 to 2013. Information on demographics; tumor size; histologic grade; American Joint Committee on Cancer (AJCC) stage; SEER local, regional, distant stage; and treatment modality were analyzed.

Results

There were 22,675 cases of primary supraglottic SCCa identified. The mean age at diagnosis was 62.3 years, with males accounting for 70.3% of all cases. A high percentage of patients presented with stage IV disease (44.9%). The most common treatment modality was radiotherapy (46.6%), followed by combination of surgery and radiotherapy (29.2%) and surgery alone (15.0%). Overall 5‐year disease‐specific survival (DSS) for all cases was 54.0%. When stratified by treatment modality, 5‐year DSS was best for patients receiving surgery alone (64.2%). However, for patients with AJCC stage IV disease, survival was significantly better with combined surgery and radiotherapy (52.5%).

Conclusion

In general, supraglottic SCCa is treated most commonly with radiotherapy, followed by surgery and radiotherapy. Patients managed surgically had better 5‐year DSS when compared to patients treated by other modalities. However, when stratified by stage, patients with AJCC stage IV disease had significantly better survival with combined surgery and radiotherapy. Of patients receiving surgery, supraglottic laryngectomy was found to have a significantly better 5‐year DSS when compared to both total laryngectomy and laryngectomy, not otherwise specified.

Level of Evidence

NA. Laryngoscope, 2018

https://ift.tt/2RLmG6O

Ocular Complications from Retained Intraocular Ointment Discovered 33 Months after Cataract Surgery

Topical antibiotic and steroid ointments are sometimes used topically at the conclusion of intraocular surgery, and inadvertent entry into the eye has been reported. Dispersed ointment droplets or consolidated globules in the anterior chamber (AC) can sometimes be visualized on exam. Occasionally, intraocular ointment is found incidentally without apparent toxic effect, but retained ointment usually presents with early or delayed intraocular inflammation, pressure rise, macular edema, or corneal edema. The usual treatment for toxicity from retained ointment is removal of the ointment. While the complication of ointment-induced cystoid macular edema has been reported, there is paucity of literature on the anatomical response and eventual visual outcome of patients who have been treated for long-standing edema from retained ointment. We present a case of a patient who presented with history of poor vision since the time of cataract surgery 33 months prior, who had cystoid macular edema, reduced endothelial cell count, and apparent Maxitrol ointment (neomycin, polymyxin B sulfate, and dexamethasone in paraffin vehicle; Novartis Pharmaceuticals UK) floating in the AC. The patient was treated with AC washout and sub-Tenon injection of triamcinolone. His vision, retinal architecture by optical coherence tomography, endothelial cell count, and pachymetry has been followed for 9 months following this treatment.
Case Rep Ophthalmol 2018;9:493–498

https://ift.tt/2RPoGed

Extensive Paneth cell metaplasia in an ovarian Krukenberg tumor: report of an unusual case and literature review

Abstract

Paneth cells are classified as secretory cells which are normally found in the cecum and ascending colon. Their presence in other parts of the gastrointestinal tract is regarded as abnormal and indicates metaplasia. Paneth cells may also be rarely found in gastrointestinal, biliary and prostatic tumors. The presence of Paneth cells in ovarian Krukenberg tumors is rare and to the best of our knowledge is restricted to metastatic appendiceal goblet cells tumors. We report a rare case of unilateral metastatic gastric carcinoma to the ovary in a 23-year-old female. This tumor showed unusual extensive Paneth cells metaplasia with classical signet ring cell morphology.

https://ift.tt/2C52Ttu

A case series on the conservative management of the bony skull in patients with aggressive skin carcinomas of the scalp

Abstract

Few studies examine techniques of surgical resection for scalp malignancies to ensure clear margins. We present a case series utilizing outer cortex removal in patients without evidence of bony or pericranial invasion. A retrospective casenote review is presented of three cases treated in a tertiary Head and Neck Cancer Centre. An outer table removal approach was utilized based on the absence of bony involvement either on pre-operative imaging or from intra-operative findings. All cases underwent an outer table drilldown procedure. Tumour histology included high grade carcinoma of unknown origin, malignant cylindroma and squamous cell carcinoma. Complete excisions with adequate deep margins were achieved in 100% cases. Overall disease-free survival was 66.6% and local control rate was 100%. This technique allows a high degree of local control, notably at the deep margin. There is little morbidity and it avoids the complications associated with full thickness calvarial resection.

https://ift.tt/2LcRtqw

Internal hernia through the foramen of Winslow

Abstract

Foramen of Winslow hernias are one of the most uncommon types of internal hernias that a surgeon will encounter. They are often initially indolent with vague symptoms that present over an extended period of time. Unfortunately, these hernias are not often diagnosed prior to requiring emergent operative intervention. This case report describes a patient who had a long history of vague abdominal pain and radiographic evidence of a foramen of Winslow hernia 4 years prior to presenting with acute obstructive symptoms. This raises the question: Should foramen of Winslow hernias, if diagnosed early, be repaired on an elective basis?

https://ift.tt/2LaM6Z4

Radiation therapy quality assurance in head and neck radiotherapy – Moving forward

Publication date: January 2019

Source: Oral Oncology, Volume 88

Author(s): Lachlan McDowell, June Corry

Abstract

Head and Neck Cancer (HNC) radiation oncologists (ROs) enjoy the immense pleasure of curing patients, working within a large multidisciplinary team to effectively deliver curative intent treatment whilst also aiming to minimise late treatment toxicity.

Secondary analyses of large-scale HNC clinical trials have shown the critical impact of the quality of radiotherapy plans, where protocol non-compliant plans have yielded inferior survival rates approximating 20%. The peer review process in routine day-to-day HNC practice shows that even in major academic centers a significant proportion of RT plans may require changes to the radiotherapy planning volume.

Optimising the therapeutic ratio in HNC has been dramatically facilitated by intensity modulated radiotherapy (IMRT), but that technology has also increased the complexity of HNC radiotherapy treatment and high-volume centers with experienced clinicians may be best placed to deliver this most accurately. International consensus guidelines to standardise or benchmark best practice with respect to the RT-QA process in HNC are needed.

The aim of this paper is to highlight the importance of the RT-QA process in the HNC treatment process and to make some recommendations for its inclusion in both clinical trials and routine clinical practice.

https://ift.tt/2QtEJ57

Pediatric malignancies presenting in the head and neck

Publication date: Available online 11 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Jacob Kinggaard Lilja-Fischer, Henrik Schrøder, Viveque E. Nielsen

Abstract

Objectives

Childhood cancer is rare and often difficult to diagnose. In the head and neck region, benign diseases are much more common. The aim of this study was to estimate the proportion of childhood cancer cases with a primary head and neck presentation, to describe symptoms, physical findings, diagnostic interval and tentative diagnoses.

Methods

Registry-based retrospective cohort study, with patients identified in the Danish Childhood Cancer Registry. Review of medical records, imaging reports and pathology reports.

Tertiary care center

All childhood cancer patients less than 15 years of age with primary disease presentation in the head and neck region from the Central Danish Region in the years 2003 – 2013.

Proportion of patients with a primary head and neck presentation; frequency of physical findings; diagnostic intervals; and frequency of tentative diagnoses.

Results

85 patients (15% of all childhood cancers) had primary disease presentation in the head & neck region (95% confidence interval [CI]: 12 – 18%). A total of 24% (CI: 21 - 28%) of patients had any symptoms or findings from the head and neck region at presentation. Most common symptoms and findings were a swelling or a tumor, and possibly general symptoms. Diagnostic interval was more than three weeks in three out of four of patients. Primary suspicion was most commonly an infectious disease.

Conclusions

A substantial proportion of patients with childhood cancer have disease presentation in the head and neck. Worth noting is, that symptoms and findings are easily mistaken for an infectious disease, which probably explains the significant diagnostic interval.

https://ift.tt/2UBmOI3

Clinical Analysis of Pediatric Primary External Auditory Canal Cholesteatoma

Publication date: Available online 11 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Guanwen He, Yangbin Xu, Zhongshou Zhu

Abstract

Objective

Pediatric primary external auditory canal cholesteatoma (EACC) is a rare disease. The present study aimed to explore the clinical features and prognosis of this disease.

Methods

Clinical data of 41 ears with pediatric primary EACC were collected, and the clinical characteristics and prognosis were analyzed in this retrospective study.

Results

A total of 35 patients (median age of 13 years) were recruited in this study. Of these, 13 suffered on the left side and 16 on the other side, while 6 suffered on the bilateral ears. A total of 30 ears had hearing loss, 21 had otalgia, 14 had otorrhea, 9 had tinnitus, and 2 had pruritus. The median course of the disease was 1 month. The bone destruction of the external auditory canal (EAC) was located on the inferior wall of 20 ears, the posterior wall of 22 ears, the superior wall of 15 ears, and the anterior wall of 15 ears. According to Shin's stages, 24 ears were in stage I, 2 in stage II, 15 in stage III. A total of 40 ears underwent transcanal cholesteatoma removal (TCR) and 1 underwent both TCR and tympanoplasty. Finally, 33 ears were followed up postoperatively, and only 1 ear presented recurrence.

Conclusion

The posterior wall of the EAC is the most commonly affected wall, and the involvement of multiple walls is common. Due to the remodeling of the EAC bone in pediatric patients, the high stage lesions can be treated by minimally invasive surgical debridement combined with a close follow-up postoperatively.

https://ift.tt/2BataVD

Portable, non-powered, suction-generating device for management of life-threatening aerodigestive tract foreign bodies: Novel prototype and literature review

Publication date: Available online 11 December 2018

Source: International Journal of Pediatric Otorhinolaryngology

Author(s): Pratik B. Patel, Nina L. Shapiro

Abstract

Objective

To present a novel approach for the emergent, pre-hospital management of life-threatening aerodigestive tract foreign body aspiration using a portable, non-powered, suction-generating device (PNSD), in the context of a literature review of emergent pre-hospital management of patients with foreign body airway obstruction.

Methods

The PubMed and MEDLINE databases were comprehensively screened using broad search terms. A literature review of pre-hospital management and resuscitative techniques of foreign body airway obstruction was performed. Further, independent measurements of PNSD pressure generation were obtained. Application of a PNSD in cadaveric and simulation models were reviewed. A comparative analysis between a PNSD and other resuscitative techniques was performed.

Results

Physiologic data from adult and pediatric human, non-human, and simulation studies show pressure generation ranging from 5.4 to 179 cm H₂O using well-established resuscitative maneuvers. Laboratory testing demonstrated that a protypic PNSD demonstrated peak airway pressures of 434.23 ± 12.35 cm H₂O. A simulation study of a PNSD demonstrated 94% reliability in retrieving airway foreign body, while a similar cadaveric study demonstrated 98% reliability, with both studies approaching 100% success rate after multiple attempts. Several case reports have also shown successful application of PNSD in the emergent management of airway foreign body in elderly and disabled patients.

Conclusion

PNSDs may play an important role in the emergent, non-operative, pre-hospital management of upper aerodigestive tract foreign body aspiration, particularly in settings and populations with high choking risk. Further characterization of effectiveness and safety in larger cadaveric or simulation studies mimicking physiologic conditions is indicated.

https://ift.tt/2UB97J2

Citizen Science for Observing and Understanding the Earth

Haklay, M; Mazumdar, S; Wardlaw, J; (2018) Citizen Science for Observing and Understanding the Earth. In: Mathieu, PP and Aubrecht, C, (eds.) Earth Observation Open Science and Innovation. (pp. 69-88). Springer: Cham, Switzerland. Green open access

https://ift.tt/2Bb9jpy

Fluctuation identities with continuous monitoring and their application to the pricing of barrier options

Phelan, CE; Marazzina, D; Fusai, G; Germano, G; (2018) Fluctuation identities with continuous monitoring and their application to the pricing of barrier options. European Journal of Operational Research , 271 (1) pp. 210-223. 10.1016/j.ejor.2018.04.016 . Green open access

https://ift.tt/2B9qAzl

Filamin A (FLNA) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification

Shelmerdine, SC; Semple, T; Wallis, C; Aurora, P; Moledina, S; Ashworth, MT; Owens, CM; (2017) Filamin A (FLNA) mutation—A newcomer to the childhood interstitial lung disease (ChILD) classification. Pediatric Pulmonology , 52 (10) pp. 1306-1315. 10.1002/ppul.23695 . Green open access

https://ift.tt/2UCT3X5

Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up

Hirji, N; Georgiou, M; Kalitzeos, A; Bainbridge, JW; Kumaran, N; Aboshiha, J; Carroll, J; Hirji, N; Georgiou, M; Kalitzeos, A; Bainbridge, JW; Kumaran, N; Aboshiha, J; Carroll, J; Michaelides, M; - view fewer (2018) Longitudinal Assessment of Retinal Structure in Achromatopsia Patients With Long-Term Follow-up. Investigative Ophthalmology & Visual Science , 59 (15) pp. 5735-5744. 10.1167/iovs.18-25452 . Green open access

https://ift.tt/2B8QTpi

Pearls and Pitfalls in Diagnosing Pediatric Urinary Bladder Masses

Shelmerdine, SC; Lorenzo, AJ; Gupta, AA; Chavhan, GB; (2017) Pearls and Pitfalls in Diagnosing Pediatric Urinary Bladder Masses. RadioGraphics , 37 (6) pp. 1872-1891. 10.1148/rg.2017170031 . Green open access

https://ift.tt/2UC7QBi

On the Front Line of Community-Led Air Quality Monitoring

Haklay, M; Eleta, I; (2018) On the Front Line of Community-Led Air Quality Monitoring. In: Nieuwenhuijsen, M and Khreis, H, (eds.) Integrating Human Health into Urban and Transport Planning: A Framework. (pp. 563-580). Springer: Cham, Switzerland. Green open access

https://ift.tt/2BdqSVJ

Rapid antiretroviral therapy initiation in low and middle-income countries: A resource-based approach

Tenforde, MW; Walker, AS; Gibb, DM; Manabe, YC; (2019) Rapid antiretroviral therapy initiation in low and middle-income countries: A resource-based approach. PLoS Medicine (In press).

https://ift.tt/2BjXcGT

Hubris: A doença do poder [Hubris: The disease of power]

Rego, A; Cunha, M; Guinote, A; (2017) Hubris: A doença do poder [Hubris: The disease of power]. RH Magazine , J/F 17 (108) pp. 38-41.

https://ift.tt/2UxXF0I

The Un(solv)able Problem

Cubitt, TS; Perez-Garcia, D; Wolf, M; (2018) The Un(solv)able Problem. Scientific American , 319 (4) pp. 29-37. 10.1038/scientificamerican1018-28 .

https://ift.tt/2Uunejc

How Should We Evaluate and Use Evidence to Improve Population Oral Health?

Brocklehurst, PR; Baker, SR; Listl, S; Peres, MA; Tsakos, G; Rycroft-Malone, J; (2019) How Should We Evaluate and Use Evidence to Improve Population Oral Health? Dental Clinics of North America , 63 (1) pp. 145-156. 10.1016/j.cden.2018.08.009 .

https://ift.tt/2UC0WfI

Post-mortem magnetic resonance (PMMR) imaging of the brain in fetuses and children with histopathological correlation

Shelmerdine, SC; Hutchinson, JC; Sebire, NJ; Jacques, TS; Arthurs, OJ; (2017) Post-mortem magnetic resonance (PMMR) imaging of the brain in fetuses and children with histopathological correlation. Clinical Radiology , 72 (12) pp. 1025-1037. 10.1016/j.crad.2017.07.015 . Green open access

https://ift.tt/2BcvZ8T

Investigating equalisation of health inequalities during adolescence in four low-income and middle-income countries: an analysis of the Young Lives cohort study

Ward, JL; Viner, RM; (2018) Investigating equalisation of health inequalities during adolescence in four low-income and middle-income countries: an analysis of the Young Lives cohort study. BMJ Open , 8 (9) , Article 022114. 10.1136/bmjopen-2018-022114 . Green open access

https://ift.tt/2UA84ZV

Sex differences in children's toy preferences: A systematic review, meta-regression, and meta-analysis

Todd, BK; Fischer, RA; Di Costa, S; Roestorf, A; Harbour, K; Hardiman, P; Barry, JA; (2018) Sex differences in children's toy preferences: A systematic review, meta-regression, and meta-analysis. Infant and Child Development , 27 (2) , Article e2064. 10.1002/icd.2064 . Green open access

https://ift.tt/2UusR0Z

Journey history reconstruction from the soils and sediments on footwear: An empirical approach

Morgan, RM; Scott, KR; Ainley, J; Bull, PA; (2018) Journey history reconstruction from the soils and sediments on footwear: An empirical approach. Science and Justice 10.1016/j.scijus.2018.11.002 . (In press). Green open access

https://ift.tt/2UEeh7h

Imaging of late complications of cancer therapy in children

Shelmerdine, SC; Chavhan, GB; Babyn, PS; Nathan, PC; Kaste, SC; (2017) Imaging of late complications of cancer therapy in children. Pediatric Radiology , 47 (3) pp. 254-266. 10.1007/s00247-016-3708-6 . Green open access

https://ift.tt/2B9qA2j

Effect of electric field on migration of defects in oxides: Vacancies and interstitials in bulk MgO

El-Sayed, A; Watkins, MB; Grasser, T; Shluger, AL; (2018) Effect of electric field on migration of defects in oxides: Vacancies and interstitials in bulk MgO. Physical Review B , 98 (6) , Article 064102. 10.1103/PhysRevB.98.064102 . Green open access

https://ift.tt/2BaqO9f

Presentation to publication: proportion of abstracts published for ESPR, SPR and IPR

Shelmerdine, SC; Lynch, JO; Langan, D; Arthurs, OJ; (2016) Presentation to publication: proportion of abstracts published for ESPR, SPR and IPR. Pediatric Radiology , 46 (10) pp. 1371-1377. 10.1007/s00247-016-3653-4 . Green open access

https://ift.tt/2Uuswvf

Service Design and Knowledge Management in the Construction Supply Chain for an Infrastructure Programme

Duryan, M; Smyth, H; (2019) Service Design and Knowledge Management in the Construction Supply Chain for an Infrastructure Programme. Built Environment Project and Asset Management 10.1108/BEPAM-04-2018-0060 . (In press).

https://ift.tt/2B6dMtw

Mission-orientated innovation policy and dynamic capabilities in the public sector

Mazzucato, M; Kattel, R; (2018) Mission-orientated innovation policy and dynamic capabilities in the public sector. Industrial and Corporate Change , 27 (5) pp. 787-801. 10.1093/icc/dty032 .

https://ift.tt/2BaqMy9

Age-Related Deficits in Memory Encoding and Retrieval in Word List Free Recall

Cadar, D; Usher, M; Davelaar, EJ; (2018) Age-Related Deficits in Memory Encoding and Retrieval in Word List Free Recall. Brain Sciences , 8 (12) , Article 211. 10.3390/brainsci8120211 . Green open access

https://ift.tt/2UA0Ghe

Diagnostic Significance of CTCs in Patients With Thyroid Nodules (Circulating Tumor Cells)

Conditions:   Thyroid Nodule;   Diagnoses Disease
Intervention:   Diagnostic Test: circulating tumor cells test
Sponsors:   Cancer Institute and Hospital, Chinese Academy of Medical Sciences;   China-Japan Friendship Hospital;   Chinese PLA General Hospital;   Beijing Chao Yang Hospital
Recruiting

https://ift.tt/2Px398q

Combination Therapy With NC-6004 and Pembrolizumab in Head and Neck Cancer Subjects Who Have Failed Platinum Regimen

Condition:   SCCHN
Interventions:   Drug: NC-6004;   Drug: Pembrolizumab
Sponsors:   NanoCarrier Co., Ltd.;   Orient Europharma Co., Ltd.
Not yet recruiting

https://ift.tt/2zQW0e8

Siglec-8 in eosinophilic disorders: receptor expression and targeting using chimeric antibodies

Publication date: Available online 10 December 2018

Source: Journal of Allergy and Clinical Immunology

Author(s): Fanny Legrand, Yun Cao, Joshua Wechsler, Xiang Zhu, Nives Zimmermann, Shakuntala Rampertaap, Joseph Monsale, Kimberly Romito, Bradford A. Youngblood, Emily C. Brock, Michelle Makiya, Nenad Tomasevic, Christopher Bebbington, Irina Maric, Dean D. Metcalfe, Bruce S. Bochner, Amy D. Klion

Abstract

Background

Sialic acid–binding immunoglobulin-like lectin (Siglec)-8 is selectively expressed on eosinophils, mast cells and basophils, and, when engaged on eosinophils, can cause cell death.

Objective

To characterize surface and soluble Siglec-8 levels in normal (ND) and eosinophilic (EO) subjects and assess the efficacy of anti-Siglec-8 antibodies in inducing eosinophil cell death in vitro.

Methods

Eosinophil expression of Siglec-8 was assessed using flow cytometry and quantitative PCR. Serum soluble Siglec-8 levels were measured by ELISA. Induction of eosinophil death by IgG4 (c2E2 IgG4) and afucosylated IgG1 (c2E2 IgG1) anti-Siglec-8 antibodies was evaluated in vitro by flow cytometry and in vivo in humanized mice.

Results

Siglec-8 was consistently expressed on eosinophils from ND and EO and did not correlate with absolute eosinophil count (AEC) or disease activity. Soluble Siglec-8 levels were measurable in serum from most donors, unrelated to AEC or Siglec-8 surface expression. c2E2 IgG1 and c2E2 IgG4 were equally effective at inducing cell death (Annexin-V positivity) of purified eosinophils from ND and EO after overnight IL-5 priming. In contrast, killing of purified eosinophils without IL-5 was only seen in EO subjects, and NK-mediated eosinophil killing was seen only with c2E2 IgG1. Finally, treatment of humanized mice with anti-Siglec antibody led to robust depletion of IL-5-induced eosinophilia in vivo.

Conclusions

Siglec-8 is highly expressed on blood eosinophils from EO and ND and represents a potential therapeutic target for eosinophilic disorders. Enhanced killing of eosinophils in the presence of IL-5 may lead to increased efficacy in patients with IL-5-driven eosinophilia.

Graphical abstract

https://ift.tt/2QmtMSF

Polysomnographic and pulmonary function changes in patients with sleep problems after septoplasty with turbinectomy

Publication date: Available online 11 December 2018

Source: American Journal of Otolaryngology

Author(s): Yasser Mohammad Hassan Mandour, Shimaa Magdy Abo Youssef, Hany Hussein Moussa

Abstract

Object

To compare Polysomnography and Pulmonary function tests before and after Septoplasty with Turbinectomy in patients complaining of nasal obstruction and sleep problems due to deviated septum with hypertrophic inferior turbinate.

Methods

90 patients underwent Septoplasty with Turbinectomy due to nasal obstruction and sleep problems involved in this study, their sleep quality evaluated by polysomnography before and after the surgery, their pulmonary functions assessed by spirometry before and after the operation.

Results

The postoperative pulmonary function values; FVC, FEV1, PEFR and postoperative polysomonographic values; AHI, Snoring index/hour, SpaO2 were higher than the preoperative values, and the results were statistically significant (p-values <0.001).

Conclusion

Septoplasty with partial inferior turbinectomy might be a useful operation in the management of nasal obstruction and sleep problems that caused by a deviated nasal septum and hypertrophied inferior turbinate.

https://ift.tt/2C5mrhI

Buccal Fat Pad: Report of 24 Cases and Literature Review of 1,635 Cases of Oral Defect Reconstruction

Objective: The buccal fat pad (BFP) has been progressively introduced into clinical practice for oral defect reconstruction. This study describes our experience with this technique and compares indications in the literature and outcomes. Methods: We prospectively enrolled 24 patients presenting oral surgical defects and treated between January 2012 and January 2015 at our institution. They all were eligible for BFP defect reconstruction. A comprehensive literature review was performed from 1977 onwards and surgical indications and results were compared. Results: All 24 BFP procedures showed excellent recovery and uneventful follow-up. Literature review confirmed a global success rate of 96.2% for a reported number of 1,635 patients with multiple surgical indications. BFP showed very low morbidity and failure rates in accordance with the outcomes reported in the literature, and the high patient compliance together with the easy harvesting of this surgical technique make it a good reconstructive option in cases of small-to-medium size oral defects in patients with a high rate of comorbidities or as salvage/second option. Conclusion: The BFP is worthy of consideration for the reconstruction of selected mouth defects, due to its easy mobilization, excellent blood supply, and minimal donor-site morbidity, where shape and size represent its main limitations, and a defect's location influences its pliability.
ORL 2019;81:24–35

https://ift.tt/2SFl3HT

Transoral Robotic Surgery (TORS) for Bilateral Eagle Syndrome

Eagle syndrome is a rare and poorly understood clinical condition caused by an elongated or disfigured styloid process. The possible managements of Eagle syndrome include conservative medical treatment or surgical intervention. The surgical removal of the elongated styloid process may be efficiently achieved either by an intraoral or a transcervical approach. An effective styloidectomy may be either total or partial, provided the bony residue's length is within the range of normality. Here, we report our experience with a bilateral robotic-assisted styloidectomy in a young female patient. Our experience showed that this procedure is a safe alternative to traditional surgical approaches, granting an excellent view and a safe manipulation by robotic arms, and, thereby, avoiding iatrogenic damage to neurovascular structures. Moreover, transoral robotic surgery could represent the gold standard for the treatment of bilateral Eagle syndrome cases allowing a quick and safe single-time surgery.
ORL 2019;81:36–40

https://ift.tt/2QJG8ne

Gene Expression Profiles of Tumor Necrosis Factor-α and Endothelin-1 in Obstructive Sleep Apnea

Background/Aims: The aim of this study was to observe the relationship between the gene expression profiles of tumor necrosis factor (TNF)-α and endothelin (EDN)-1 and obstructive sleep apnea (OSA). Methods: A prospective, cross-sectional study performed at a tertiary-care academic center; 108 patients with snoring and day-time sleeplessness were included in this study carried out in the Otolaryngology Department. All patients were evaluated with 1-night polysomnography (PSG). There were 63 patients with OSA and 45 patients without OSA. In the OSA group, the median apnea hypopnea index (AHI) was 29.1; in the non-OSA group, the median AHI was 2.1. Blood samples were obtained from all 108 patients for the genetic analysis of the expression of TNF-α and EDN-1. PSG findings and gene expression levels were evaluated in both groups. Results: The median (range) age was 46 (20–81) years, BMI 24.9 (15–49), EDN-1 gene expression 0.45 (0.02–67.88) pg/µL, and TNF-α gene expression 1.71 (0.08–59.52) pg/µL. We found that EDN-1 and TNF-α gene expression levels were significantly higher in the OSA group than in the control group (p = 0.009 vs. p #x3c; 0.001). Conclusion: EDN-1 and TNF-α gene expression levels were associated with the occurrence of OSA.
ORL 2019;81:16–23

https://ift.tt/2QJG46Y

Perioperative Care of the Trauma Patient: New Concepts Since Wartime Learning

Publication date: Available online 10 December 2018

Source: Anesthesiology Clinics

Author(s): Lee A. Fleisher

https://ift.tt/2L8z3aJ

Modern Day Trauma Care for the Anesthesiologist

Publication date: Available online 10 December 2018

Source: Anesthesiology Clinics

Author(s): Maureen McCunn, Mohammed Iqbal Ahmed, Catherine M. Kuza

https://ift.tt/2C3uOKD

Propionibacterium ( Cutibacterium ) acnes Bacteriophage Therapy in Acne: Current Evidence and Future Perspectives

Abstract

Acne vulgaris is the most common dermatological disorder worldwide. It is a multifactorial disease that involves increased sebum production, hyperkeratinization of the pilosebaceous unit, Propionibacterium acnes (Cutibacterium acnes) colonization, and inflammation. The human skin microbiome hosts a wide variety of microorganisms, including bacteria, viruses, and fungi. A delicate balance of these microorganisms is essential for the barrier function of the skin. Propionibacterium acnes represents nearly 90% of the human skin microbiome of healthy adults. Acne is a chronic recurrent disease that requires long-lasting treatment, which has led to the emergence of antibiotic resistance. New alternatives to traditional therapy are emerging, including antimicrobial peptides, natural engineered antibodies, and bacteriophages. Bacteriophages have been shown to play a role in human skin health and disease. There is evidence supporting phage therapy in many types of skin infections. P. acnes bacteriophages have been isolated and characterized. However, only a few in vitro studies have tested the ability of bacteriophages to kill P. acnes. Furthermore, there is no evidence on bacteriophage therapy in the treatment of acne in humans. In this review, we summarize the most recent evidence regarding P. acnes bacteriophages and the potential role of these bacteriophages in the treatment of acne. Further research on this field will provide the evidence to use phage therapy to decrease rates of antibiotic resistance and restore antibiotic susceptibility of P. acnes.

https://ift.tt/2QGU9Cf

Microbial transglutaminase: A new potential player in celiac disease

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Lerner Aaron, Matthias Torsten

Abstract

Microbial transglutaminase is heavily used in the food processing industries to improve food qualities. Being a protein's glue, by cross-linking it creates neoepitope complexes that are immunogenic and potentially pathogenic in celiac disease. Despite low sequence identity, it imitates functionally its family member, the endogenous tissue transglutaminase, which is the autoantigen of celiac disease. The present comprehensive review highlights the enzyme characteristics, endogenous and exogenous intestinal sources, its cross-talks with gluten and gliadin, its immunogenicity and potential pathogenicity and risks for the gluten induced conditions. If substantiated, it might represent a new environmental inducer of celiac disease. The present findings might affect nutritional product labeling, processed food additive policies and consumer health education.

https://ift.tt/2Px54cW

The long-term prognostic significance of sarcoidosis-associated pulmonary hypertension – A cohort study

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Shmuel Tiosano, Mathilde Versini, Lior Dar Antaki, Liron Spitzer, Yarden Yavne, Abdulla Watad, Omer Gendelman, Doron Comaneshter, Arnon D. Cohen, Howard Amital

Abstract

Background

Sarcoidosis is a multisystem, chronic, progressive, granulomatous disease. Sarcoidosis-associated pulmonary hypertension is a well described, but not common, complication of sarcoidosis. In small scale studies, it has been previously described as manifestation of advanced disease and was found to be associated increased morbidity and mortality. This study sought to assess the long-term prognostic significance of sarcoidosis-associated pulmonary hypertension (SAPH) by using data obtained from a large population-based registry which contains longitudinal follow-up data.

Methods

Utilizing the records of the largest healthcare provider in Israel, we extracted a cohort consisting of sarcoidosis patients and age-and-sex matched controls. Dates of sarcoidosis registration, pulmonary hypertension and death, as well as anthropometric information and medical comorbidities, were extracted from the database. A multivariate logistic regression model was used to find variables associated with pulmonary hypertension. Cox proportional hazards method and log-rank test were used for survival analysis.

Results

The cohort included 3993 sarcoidosis patients and 19,856 controls. Pulmonary hypertension was observed among 269 sarcoidosis patients (6.74%) vs. 400 controls (2.01%). Sarcoidosis was found as independently associated with pulmonary hypertension (OR 3.17). After a mean follow-up of 7.49 years (median 7.24, maximum 17.88 years), 710 (17.8%) of the sarcoidosis patients and 2121 (10.7%) of the controls had died. Both sarcoidosis and pulmonary hypertension were found to be significantly associated with an increased risk of all-cause mortality (HR 1.82 and HR 2.31, respectively).

Conclusions

SAPH is associated with a poor prognosis. Proper screening methods may assess whether early identification and treatment improve life expectancy.

https://ift.tt/2zTbi1H

Intravenous Immunoglobulin (IVIG) in the vanguard therapy of Systemic Sclerosis

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): João Pedro Gomes, Lèlita Santos, Yehuda Shoenfeld

Abstract

Systemic Sclerosis (SSc) is a rare autoimmune disease that is characterized by a progressive skin fibrosis, an obliteration of the microvasculature and an exaggerated extracellular matrix deposition, which lead to a multisystemic dysfunction. Various pathogenetic mechanisms were described. The lack of a successful therapy make SSc a disease with a poor prognosis. The intravenous immunoglobulin (IVIG) has been used for a long time in different autoimmune diseases, and firstly used in SSc patients in 2000. IVIG has multiple non-specific mechanisms of action and, beyond an impressive improvement in muscle symptoms, a French nationwide cohort demonstrated that IVIG ameliorates the skin disease and systemic inflammation, and helps the daily dose corticosteroid's tapering at the end of the treatment. The benefits on gastrointestinal symptoms of IVIG was reported by a recent English article, in which the patients consistently reported a decrease in the gastro-esophageal reflux disease symptoms and their frequencies. The impact on the lung involvement still remains unclear. One of the advantages of IVIG is its safe profile. Few adverse effects were reported and most of them are mild, and can be managed and usually they do not relapse. Harmful effects were described, but they can be avoid with cautious and judicious use of this therapy.

https://ift.tt/2zUjf70

The kaleidoscope of autoimmunity – From genes to microbiome

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Yehuda Shoenfeld, Michael Ehrenfeld, Ori Perry

Graphical abstract

https://ift.tt/2zW77Cp

The role of synthetic manufactured peptides containing common citrullinated epitopes in rheumatoid arthritis diagnosis

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Saeed Darawshe, Abdulla Watad, Nicola L. Bragazzi, Smadar Gertel, Howard Amital

Abstract

Background: Anti-citrullinated peptide antibodies (ACPA) play an important role in rheumatoid arthritis (RA) diagnosis. In our study, we sought to assess the potential diagnostic value of synthetically manufactured peptides that contain epitopes believed to have a pathogenic role in RA.

Methods: Serum samples from RA patients and healthy controls were obtained. Two synthetic peptides were manufactured containing the common epitopes considered to play a pivotal role in the RA pathogenesis including the antigenic epitopes of filaggrin, beta-fibrinogen, collagen, vimentin and enolase. Three different ELISA kits for citrullinated peptides (namely: CCP3, Cit-ME-Vim and Cit-ME-Eno) were tested and compared. To assess the diagnostic value of the three ELISA tests, for each test the optical densities (OD) were recorded. The statistical power of each test was calculated measuring the area under the curve (AUC) corresponding with each peptide.

Results: Serum levels of ACPA recognized by the commercial CCP3 in RA and healthy controls were 1.31 ± 0.88 optic density units (ODU) and 0.21 ± 0.11 ODU, respectively. Cit-ME-Vim levels were 0.55 ± 0.46 ODU in RA subjects and 0.17 ± 0.182 ODU in healthy controls whereas Cit-ME-Eno was 0.61 ± 0.65 ODU in RA subjects and 0.22 ± 0.20 ODU in healthy controls. AUC results were as follows: CCP3, 0.89 [95%CI 0.75–0.87]; Cit-ME-Vim, 0.76 [95%CI 0.69–0.82]; Cit-ME-Eno, 0.73 [95%CI 0.65–0.79]. Statistical significance for all results was achieved (p < .0001). Sensitivity values for each kit are as follow: CCP3 70.42%; Cit-ME-Vim 63.38%; Cit-ME-Eno 40.85%, and specificity 91% for all tests.

Conclusion: Our study supports the presence of an added value for the Cit-ME-Vim peptides in the diagnosis of RA. Further studies are needed to replicate such findings.

https://ift.tt/2Px4HPs

Autoimmune and angiogenic biomarkers in autoimmune atherosclerosis

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Emese Balogh, Anita Pusztai, Attila Hamar, Edit Végh, Szilvia Szamosi, György Kerekes, Jennifer McCormick, Monika Biniecka, Sándor Szántó, Gabriella Szűcs, Zoltán Nagy, Ursula Fearon, Douglas J. Veale, Zoltán Szekanecz

Abstract

Several inflammatory, proteolytic, angiogenic and bone-associated factors play a role in the development of autoimmune, accelerated atherosclerosis in rheumatic diseases. Some of these may serve as biomarkers of vascular pathology and may be useful in the follow-up of vascular damage and outcome. Multi-biomarker profiles rather than a single markers would likely be optimal in this respect.

https://ift.tt/2zSG0YM

Autoimmune interstitial lung disease in Latin-America

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): F. Vivero, F. Campins, D. Lancellotti, P. Malfante, S. Babini, J. Sebastiani, V. Basso, A. Gaser, J. Enghelmayer, E. Gandara, EPIMAR Group

Abstract

Information about the prognosis and natural history of autoimmune interstitial lung diseases (Ai-ILD) is limited. The aim of the study was to evaluate the characteristics of patients diagnosed with Ai-ILD in Latin-America. We conducted an ambispective multicenter cohort study in 25 centers of Argentina, Colombia, and Uruguay between January 2015 and April 2018. Participants were included in the study if they had diagnosis of Ai-ILD performed by a multidisciplinary team. Patients were classified into the following sub-groups: connective tissue disease-associated ILD (ILD-CTD), interstitial pneumonia with autoimmune features (IPAF), and positive antineutrophils cytoplasmatic antibodies associated ILD (ILD-ANCA). All images were reviewed by a blinded thoracic radiologist. Out of the 381 patients included during the study period, 282 (74%; 95% CI; 69.39–78.16) were women. Mean age was 58 years old (DS 16). Three-hundred and twenty-five (85.1%; 95% CI 81.39–88.5) patients were classified as ILD-CTD (rheumatoid arthritis 31%, systemic sclerosis 29%, dermatomyositis 15%). Thirty-six patients were classified as IPAF (9.5%; 95% CI 6.9–12.8), and 13 (3.5%; 95% CI 2–5.75) as ILD-ANCA. Fifty percent of patients (95% CI 45.12–55.43) had a mild decrease of the forced vital capacity at the time of diagnosis. The most common treatment strategy was the combination of steroids and cyclophosphamide (30.1%; 95% CI 25.32–35.34) followed by azathioprine (20,3%; 95% CI 16.32–25.14). In conclusion, to the best of our knowledge, this is the first study to evaluate the characteristics and treatment strategies used in patients affected by Ai-ILD in Latin-America. Future studies should to evaluate the prognosis and impact of current treatment strategies in patients with Ai-ILD.

https://ift.tt/2Pz6hRf

Relapsing Evans syndrome and systemic lupus erythematosus with antiphospholipid syndrome treated with Bortezomib in combination with plasma exchange

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Olga Tkachenko, Sergey Lapin, Alexey Maslyansky, Valentina Myachikova, Liya Mikhailova, Boris Gilburd

Abstract

Relapsing Evans syndrome (ES) and systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome (APS) is very rare association. Coexistence of these syndromes is potentially fatal and require high-dose combined immunosuppressive therapy. We describe a case of successful use of Bortezomib and plasma exchange in a patient with ES and APS refractory to standard therapy. Thirty-two-year-old male who presented episodes of relapsing hemolytic anemia, pancytopenia and multiple thrombosis with positive direct and indirect antiglobulin test result, lupus anticoagulant and medium titer of anti-beta-2-glycoprotein 1 and anti-cardiolipin antibodies was diagnosed with ES and SLE with secondary APS. High-dose therapy by steroids and Cyclosporin A were started with temporary improvement. There was also no stable improvement with Rituximab and Cyclophosphamide. Bortezomib in combination with cyclosporine A and plasma exchange was introduced. He had stable improvement in hematological parameters with no evidence of relapse of hemolytic crisis or thrombosis during a follow-up for 1 year.

https://ift.tt/2zONc8o

T cell receptor revision and immune repertoire changes in autoimmune diseases

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Xi Jia, Bing Wang, Tianyu Zhai, Qiuming Yao, Qian Li, Jin-an Zhang

Abstract

Autoimmune disease (AID) is a condition in which the immune system breaks down and starts to attack the body. Some common AIDs include rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes mellitus and so forth. The changes in T-cell receptor (TCR) repertoire have been found in several autoimmune diseases, and may be responsible for the breakdown of peripheral immune tolerance. In this review, we discussed the processes of TCR revision in peripheral immune environment, the changes in TCR repertoire that occurred in various AIDs, and the specifically expanded T cell clones. We hope our discussion can provide insights for the future studies, helping with the discovery of disease biomarkers and expanding the strategies of immune-targeted therapy.

https://ift.tt/2PxsezN

Insights from the 11th International Congress on Autoimmunity, Lisbon, Portugal, 2018.

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Abdulla Watad, Nicola Luigi Bragazzi, Yehuda Shoenfeld

https://ift.tt/2PtOlqR

The loss of tolerance to CHI3L1 – A putative role in inflammatory bowel disease?

Publication date: Available online 10 December 2018

Source: Clinical Immunology

Author(s): Claudia Deutschmann, Dirk Roggenbuck, Peter Schierack

Abstract

The incidence of inflammatory bowel disease (IBD) is steadily increasing. IBD is characterized by a chronic inflammation of the gastrointestinal tract and is classified into the two main groups Crohn's disease (CD) and ulcerative colitis (UC). Genetic predispositions, environmental factors and a dysregulated immune response are known to part take in the onset of IBD. However, their etiopathogenesis is still not fully understood. In the last decade, there is growing evidence of the involvement of the 18- glycosylhydrolase family member Chitinase-3-like protein 1 (CHI3L1) in IBD. CHI3L1 is associated with various diseases including cancer and chronic inflammatory conditions like rheumatoid arthritis, IBD and even neurological disorders where it can act as a chemotractant, mitogen or growth factor. In this review will focus on the role of autoimmunity to CHI3L1 in IBD in the context of its expression in inflamed colonic epithelia and interaction with intestinal microbiota. It will further provide insight into the interaction of CHI3L1 with different mechanisms of the innate and adaptive immune response in IBD.

https://ift.tt/2Px4EDg

Brand and generic use of inhalation medication and frequency of switching in children and adults : a population-based cohort study

BACKGROUND: The expiration of patents of brand inhalation medications and the ongoing pressure on healthcare budgets resulted in a growing market for generics. AIM: To study the use of brand and generic inhalation medication and the frequency of switching between brand and generic and between devices. In addition, we investigated whether switching affected adherence. METHODS: From dispensing data from the Dutch PHARMO Database Network a cohort aged ≥ 5 years, using ≥ 1 year of inhalation medication between 2003 and 2012 was selected. Switching was defined as changing from brand to generic or vice versa. In addition, we studied change in aerosol delivery device type (e.g., DPI, pMDI, and nebulizers). Adherence was calculated using the medication possession ratio (MPR). RESULTS: The total cohort comprised 70,053 patients with 1,604,488 dispensations. Per calendar year, 5% switched between brand and generic inhalation medication and 5% switched between devices. Median MPRs over the first 12 months ranged between 33 and 55%. Median MPR over the total period was lower after switch from brand to generic and vice versa for formoterol (44.5 vs. 42.1 and 63.5 vs. 53.8) and beclomethasone (93.8 vs. 59.8 and 81.3 vs. 55.9). CONCLUSION: Per year, switching between brand and generic inhalation medication was limited to 5% of the patients, switching between device types was observed in 5% as well. Adherence to both generic and brand inhalation medication was low. Effect of switching on adherence was contradictory; depending on time period, medication and type, and direction of switching. Further research on reasons for switching and potential impact on clinical outcomes is warranted.

https://ift.tt/2Eds1jj

Environmental factors influence the detection probability in acoustic telemetry in a marine environment : results from a new setup

https://ift.tt/2ErUSBi

Mapping synergies and trade-offs between urban ecosystems and the Sustainable Development Goals

Maes, M; Jones, KE; Toledano, M; Milligan, B; (2019) Mapping synergies and trade-offs between urban ecosystems and the Sustainable Development Goals. Environmental Science & Policy (In press).

https://ift.tt/2A2ywmr

Misconceptions on legislative quality: an enlightened approach to the drafting of legislation

Xanthaki, H; (2018) Misconceptions on legislative quality: an enlightened approach to the drafting of legislation. In: Oliver Lalana, D, (ed.) Conceptions and Misconceptions of Legislation. Springer: USA. (In press).

https://ift.tt/2zS9PsL

Neurocritical Care Management of Hepatic Encephalopathy and Coma in Liver Failure

Kerbert, AJ; Engelmann, C; Jalan, R; (2018) Neurocritical Care Management of Hepatic Encephalopathy and Coma in Liver Failure. Seminars in Respiratory and Critical Care Medicine , 39 (5) pp. 523-537. 10.1055/s-0038-1672180 .

https://ift.tt/2PuTZcl

Community-Led Social Housing Regeneration: From Government-Led Programmes to Community Initiatives

Sendra, P; (2018) Community-Led Social Housing Regeneration: From Government-Led Programmes to Community Initiatives. In: Clark, J and Wise, N, (eds.) Urban Renewal, Community and Participation: Theory, Policy and Practice. (pp. 71-87). Springer: Cham, Switzerland.

https://ift.tt/2PvW4Vx

Martin J. Finkelstein, Valerie Martin Conley and Jack H. Schuster the faculty factor: Reassessing the American Academy in a turbulent era

Marini, G; (2018) Martin J. Finkelstein, Valerie Martin Conley and Jack H. Schuster the faculty factor: Reassessing the American Academy in a turbulent era. [Review]. Higher Education , 75 (3) pp. 553-555. 10.1007/s10734-017-0144-y . Green open access

https://ift.tt/2Pw5WhP

The Genetic Legacy of State Centralization in the Kuba Kingdom of the Democratic Republic of the Congo

Hellenthal, GR; van Dorp, L; Thomas, M; Lopez, S; Mendoza-Revilla, J; (2019) The Genetic Legacy of State Centralization in the Kuba Kingdom of the Democratic Republic of the Congo. Proceedings of the National Academy of Sciences (In press).

https://ift.tt/2zSEDt6

Radical History Then and Now

Bressey, C; (2017) Radical History Then and Now. History Workshop Journal , 83 (1) pp. 217-222. 10.1093/hwj/dbx004 .

https://ift.tt/2Pz4iwh

Newborn screening for congenital hypothyroidism: performance and outcomes of the UK programme

Knowles, RL; (2017) Newborn screening for congenital hypothyroidism: performance and outcomes of the UK programme. Presented at: 45th Meeting of the British Society for Paediatric Endocrinology and Diabetes, Newcastle, UK. Green open access

https://ift.tt/2PuiwOM

Objectifying Micrognathia Using Three-Dimensional Photogrammetric Analysis

Basart, H; Suttie, M; Ibrahim, A; Ferretti, P; van der Horst, CMAM; Hennekam, RC; Hammond, P; (2018) Objectifying Micrognathia Using Three-Dimensional Photogrammetric Analysis. The Journal of Craniofacial Surgery , 29 (8) pp. 2106-2109. 10.1097/SCS.0000000000005056 .

https://ift.tt/2zS7xKe