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Πέμπτη 26 Οκτωβρίου 2017

Denosumab-induced cutaneous hypersensitivity reaction with distinct clinical and histopathologic findings

Targeted biologic agents are increasingly approved for the treatment of a wide range of medical conditions. Cutaneous drug reactions are seen to varying degrees with these agents, and postmarketing surveillance is critical to identifying adverse and uncommon events. Denosumab is a monoclonal antibody to receptor activator of nuclear factor kappa-B ligand (RANKL) that results in decreased osteoclast activation.



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Copyright

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6





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Contributors

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6





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Contents

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6





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Forthcoming Issues

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6





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Hematology/Oncology Emergencies

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): John C. Perkins, Jonathan E. Davis




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Hematology/Oncology Emergencies

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): John C. Perkins, Jonathan E. Davis




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Oncologic Mechanical Emergencies

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Umar A. Khan, Carl B. Shanholtz, Michael T. McCurdy

Teaser

Prevalence of cancer and its various related complications continues to rise. Increasingly these life-threatening complications are initially managed in the emergency department, making a prompt and accurate diagnosis crucial to effectively institute the proper treatment and establish goals of care. The following oncologic emergencies are reviewed in this article: pericardial tamponade, superior vena cava syndrome, brain metastasis, malignant spinal cord compression, and hyperviscosity syndrome.


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Oncologic Metabolic Emergencies

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Jonathan Wagner, Sanjay Arora

Teaser

Cancer and its therapies may lead to several metabolic emergencies that emergency providers (EPs) should be well-versed in identifying and managing. With prompt recognition and treatment initiation in the emergency department, lives can be saved and quality of life maintained. Most oncologic metabolic emergencies occur in advanced cancer states, but some follow initiation of treatment or may be the presenting syndrome that leads to the cancer diagnosis. This article reviews the 2 most emergent oncologic metabolic diagnoses: tumor lysis syndrome and hypercalcemia of malignancy. A discussion on associated cancers and conditions, pathogenesis and pathophysiology, and management recommendations is included.


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Pediatric Oncologic Emergencies

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Melanie K. Prusakowski, Daniel Cannone

Teaser

The overall prognosis for most pediatric cancers is good. Mortality for all childhood cancers combined is approximately half what it was in 1975, and the survival rates of many malignancies continue to improve. However, the incidence of childhood cancer is significant and the related emergencies that develop acutely carry significant morbidity and mortality. Emergency providers who can identify and manage oncologic emergencies can contribute significantly to an improved prognosis. Effective care of pediatric malignancies requires an age-appropriate approach to patients and compassionate understanding of family dynamics.


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Neutropenic Fever

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Lindsey White, Michael Ybarra

Teaser

Fever is a common presenting complaint among adult or pediatric patients in the emergency department setting. Although fever in healthy individuals does not necessarily indicate severe illness, fever in patients with neutropenia may herald a life-threatening infection. Therefore, prompt recognition of patients with neutropenic fever is imperative. Serious bacterial illness is a significant cause of morbidity and mortality for neutropenic patients. Neutropenic fever should trigger the initiation of a rapid work-up and the administration of empiric systemic antibiotic therapy to attenuate or avoid the progression along the spectrum of sepsis, severe sepsis, septic shock syndrome, and death.


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Chemotherapeutic Medications and Their Emergent Complications

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Janet S. Young, Jennifer W. Simmons

Teaser

Patients with complications of chemotherapy, either acute or chronic, are frequently encountered in the emergency department (ED). Some patients present with complaints immediately after chemotherapy administration, whereas others may show subtle, secondary signs or may have no signs or symptoms of chemotoxicity. An increased index of suspicion prompts early recognition, diagnosis, and prevention of further iatrogenic injury. This article reviews characteristic hypersensitivity reactions, typical organ system dysfunction, and treatment strategies for adult patients who present to the ED with complications after chemotherapy.


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Acute Leukemia

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Hayley Rose-Inman, Damon Kuehl

Teaser

Although great progress has been made in the understanding and treatment of acute leukemia, this disease has not been conquered. For emergency providers (EPs), the presentation of these patients to an emergency department presents a host of challenges. A patient may present with a new diagnosis of leukemia or with complications of the disease process or associated chemotherapy. It is incumbent on EPs to be familiar with the manifestations of leukemia in its various stages and maintain some suspicion for this diagnosis, given the nebulous and insidious manner in which leukemia can present.


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Myeloproliferative Disorders

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Brian Meier, John H. Burton

Teaser

The emergency providers generally encounters myeloproliferative disorders (MPNs) in 1 of 2 ways: as striking laboratory abnormalities of seeming unknown consequence, or in previously diagnosed patients presenting with complications. The course of patients with MPNs is highly variable, but major complications can arise. Emergent conditions related to hyperviscosity need to be recognized early and treated aggressively. Rapid hydration, transfusion, cytoreduction, and early hematology consultation can be lifesaving. Likewise, although management is not altered, a high index of suspicion for thrombotic complications is required in patients with known MPNs as these are a significant cause of morbidity and mortality.


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Anemia

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Julie T. Vieth, David R. Lane

Teaser

Patients with anemia are frequently encountered in the emergency department (ED); emergency physicians (EPs) often play an important role in the evaluation and management of anemia. Although many patients have findings consistent with anemia on routine laboratory tests, only a small percentage will require acute intervention. An understanding of the broader types of anemia and how to manage such patients is important in the practice of an EP, as the presence of anemia will impact treatment plans for a variety of other disorders. This article reviews the evaluation and management of adult patients presenting to the ED with anemia.


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Sickle Cell Disease in the Emergency Department

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Paris B. Lovett, Harsh P. Sule, Bernard L. Lopez

Teaser

Acute painful episodes are the most common reason for emergency department visits among patients with sickle cell disease (SCD). Early and aggressive pain management is a priority. Emergency providers (EPs) must also diagnose other emergent diagnoses in patients with SCD and differentiate them from vaso-occlusive crisis. EPs should be aware of cognitive biases that may misdirect the diagnostic process. Administration of intravenous fluids should be used judiciously. Blood transfusion may be considered. Coordination of care with hematology is an important part of the effective emergency department and long-term management of patients with SCD.


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Thrombotic Microangiopathies (TTP, HUS, HELLP)

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Shane Kappler, Sarah Ronan-Bentle, Autumn Graham

Teaser

Thrombocytopenia, strictly defined as a platelet count less than 150,000, is common in the emergency department. Recognition, diagnostic investigation, and proper disposition of a thrombocytopenic patient are imperative. One group of disorders leading to thrombocytopenia is the thrombotic microangiopathies, hallmarked by platelet destruction. These thrombotic microangiopathies include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and hemolysis, elevated liver enzyme levels, low platelet count (HELLP), which should be distinguished from similar disease processes such as immune thrombocytopenia (ITP), disseminated intravascular coagulation (DIC) and heparin induced thrombocytopenia (HIT). In this article, clinical presentations, pathophysiology, diagnostic workup, management plans, complications, and dispositions are addressed for this complex group of platelet disorders.


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Evaluation and Management of Congenital Bleeding Disorders

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Rahul Bhat, Whitney Cabey

Teaser

Patients presenting to the emergency department with acute bleeding and a history of clotting or platelet disorder present a unique challenge to the emergency physician. The severity of bleeding presentation is based on mechanism as well as factor levels: patients with factor levels greater than 5% can respond to most minor hemostatic challenges, whereas those with factor levels less than 1% bleed with minor trauma or even spontaneously. Treatment should be initiated in consultation with the patient's hematologist using medications and specific factor replacement, except in rare, life-threatening, resource-poor situations, when cryoprecipitate or activated prothrombin complex may be considerations.


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Acquired Bleeding Disorders

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Alisheba Hurwitz, Richard Massone, Bernard L. Lopez

Teaser

Emergency medicine practitioners treat bleeding patients on a regular basis. Disorders of hemostasis are an additional challenge in these patients but can be assessed and managed in a systematic fashion. Of particular importance to the emergency clinician are the iatrogenic causes of abnormal hemostasis. Other acquired causes of abnormal hemostasis include renal disease, immune thrombocytopenia, thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, acquired coagulation factor inhibitors, acute traumatic coagulopathy, liver disease, and disseminated intravascular coagulopathy.


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Antithrombotic Reversal Agents

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Matthew D. Wilson, Jonathan E. Davis

Teaser

The actively bleeding anticoagulated patient presenting to the emergency department requires rapid evaluation and treatment, which is made increasingly complicated by the ever-evolving antithrombotic treatment options used in medicine. Even with excellent supportive care, the timeliness with which reversal decisions need to be made continues to demand of the emergency practitioner a familiarity with the properties and general characteristics of a variety of antithrombotic agents. Reversal options vary and may include vitamin K, FFP, PCC, rFVIIa, platelets, and desmopressin, among others.


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Blood Product Transfusions and Reactions

Publication date: December 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 6
Author(s): Jessica L. Osterman, Sanjay Arora

Teaser

Blood product transfusions are an essential component of the practice of emergency medicine. From acute traumatic hemorrhage to chronic blood loss necessitating transfusion for symptomatic anemia, familiarity with individual blood products and their indications for transfusion is an essential tool for every emergency physician (EP). Although the focus of this article is primarily on the transfusion of red blood cells, many of the concepts are applicable to the transfusion of all blood products. EPs must be fully familiar with both the individual blood components and the potential reactions and complications of these transfusions.


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Adolescent Tuning of Association Cortex in Human Structural Brain Networks

Abstract
Motivated by prior data on local cortical shrinkage and intracortical myelination, we predicted age-related changes in topological organization of cortical structural networks during adolescence. We estimated structural correlation from magnetic resonance imaging measures of cortical thickness at 308 regions in a sample of N = 297 healthy participants, aged 14–24 years. We used a novel sliding-window analysis to measure age-related changes in network attributes globally, locally and in the context of several community partitions of the network. We found that the strength of structural correlation generally decreased as a function of age. Association cortical regions demonstrated a sharp decrease in nodal degree (hubness) from 14 years, reaching a minimum at approximately 19 years, and then levelling off or even slightly increasing until 24 years. Greater and more prolonged age-related changes in degree of cortical regions within the brain network were associated with faster rates of adolescent cortical myelination and shrinkage. The brain regions that demonstrated the greatest age-related changes were concentrated within prefrontal modules. We conclude that human adolescence is associated with biologically plausible changes in structural imaging markers of brain network organization, consistent with the concept of tuning or consolidating anatomical connectivity between frontal cortex and the rest of the connectome.

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Network Structure and Function in Parkinson’s Disease

Abstract
Little is known of the structural and functional properties of abnormal brain networks associated with neurological disorders. We used a social network approach to characterize the properties of the Parkinson's disease (PD) metabolic topography in 4 independent patient samples and in an experimental non-human primate model. The PD network exhibited distinct features. Dense, mutually facilitating functional connections linked the putamen, globus pallidus, and thalamus to form a metabolically active core. The periphery was formed by weaker connections linking less active cortical regions. Notably, the network contained a separate module defined by interconnected, metabolically active nodes in the cerebellum, pons, frontal cortex, and limbic regions. Exaggeration of the small-world property was a consistent feature of disease networks in parkinsonian humans and in the non-human primate model; this abnormality was only partly corrected by dopaminergic treatment. The findings point to disease-related alterations in network structure and function as the basis for faulty information processing in this disorder.

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Neural Encoding of Auditory Features during Music Perception and Imagery

Abstract
Despite many behavioral and neuroimaging investigations, it remains unclear how the human cortex represents spectrotemporal sound features during auditory imagery, and how this representation compares to auditory perception. To assess this, we recorded electrocorticographic signals from an epileptic patient with proficient music ability in 2 conditions. First, the participant played 2 piano pieces on an electronic piano with the sound volume of the digital keyboard on. Second, the participant replayed the same piano pieces, but without auditory feedback, and the participant was asked to imagine hearing the music in his mind. In both conditions, the sound output of the keyboard was recorded, thus allowing precise time-locking between the neural activity and the spectrotemporal content of the music imagery. This novel task design provided a unique opportunity to apply receptive field modeling techniques to quantitatively study neural encoding during auditory mental imagery. In both conditions, we built encoding models to predict high gamma neural activity (70–150 Hz) from the spectrogram representation of the recorded sound. We found robust spectrotemporal receptive fields during auditory imagery with substantial, but not complete overlap in frequency tuning and cortical location compared to receptive fields measured during auditory perception.

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Large-Scale Network Topology Reveals Heterogeneity in Individuals With at Risk Mental State for Psychosis: Findings From the Longitudinal Youth-at-Risk Study

Abstract
Emerging evidence demonstrates heterogeneity in clinical outcomes of prodromal psychosis that only a small percentage of at-risk individuals eventually progress to full-blown psychosis. To examine the neurobiological underpinnings of this heterogeneity from a network perspective, we tested whether the early patterns of large-scale brain network topology were associated with risk of developing clinical psychosis. Task-free functional MRI data were acquired from subjects with At Risk Mental State (ARMS) for psychosis and healthy controls (HC). All individuals had no history of drug abuse and were not on antipsychotics. We performed functional connectomics analysis to identify patterns of system-level functional brain dysconnectivity associated with ARMS individuals with different outcomes. In comparison to HC and ARMS who did not transition to psychosis at follow-up (ARMS-NT), ARMS individuals who did (ARMS-T) showed marked brain functional dysconnectivity, characterized by loss of network segregation and disruption of network communities, especially the salience, default, dorsal attention, sensorimotor and limbic networks (P < 0.05 FWE-corrected, Cohen's d > 1.00), and was associated with baseline symptom severity. In contrast, we did not observe connectivity differences between ARMS-NT and HC individuals. Taken together, these results suggest a possible large-scale functional brain network topology phenotype related to risk of psychosis transition in ARMS individuals.

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The Arthur Prophet Memorial Lecture



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Reflection



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Paediatric dentistry: A multidisciplinary approach



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Stress and burnout research project



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Dental notation: Mental gymnastics



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Fracture resistance of zirconia-based all-ceramic crowns after bur adjustment



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Identifying teeth correctly



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Community dental team screen factory workers for mouth cancer



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Dental education: A gentle touch



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Interview: Say no more... An insight into the Behavioural Insights Team



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Patient benefits: Incorrect advice



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Oral surgery II: Part 3. Cysts of the mouth and jaws and their management



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From the archive: Sydney turns 100



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An estimated carbon footprint of NHS primary dental care within England. How can dentistry be more environmentally sustainable?



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Primary dental care: You're not serious



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Eavesdroppers and nosey neighbours required



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Alternative sugars: Syrup

Elaine Gardner, British Dietetic Association (BDA) Spokesperson, discusses the sugar content in syrup and provides related oral health advice.

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Is it time to digitally enable dentistry with the rest of healthcare?



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Spreading the word about a devastating disease



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BDA AGM



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Editorial Board

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Publication date: October 2017
Source:Artificial Intelligence in Medicine, Volume 82





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A matched-filter algorithm to detect amperometric spikes resulting from quantal secretion

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Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Supriya Balaji Ramachandran, Kevin D. Gillis
BackgroundElectrochemical microelectrodes located immediately adjacent to the cell surface can detect spikes of amperometric current during exocytosis as the transmitter released from a single vesicle is oxidized on the electrode surface. Automated techniques to detect spikes are needed in order to quantify the spike rate as a measure of the rate of exocytosis.New methodWe have developed a Matched Filter (MF) detection algorithm that scans the data set with a library of prototype spike templates while performing a least-squares fit to determine the amplitude and standard error. The ratio of the fit amplitude to the standard error constitutes a criterion score that is assigned for each time point and for each template. A spike is detected when the criterion score exceeds a threshold and the highest-scoring template and the time of peak score is identified. The search for the next spike commences only after the score falls below a second, lower threshold to reduce false positives. The approach was extended to detect spikes with double-exponential decays with the sum of two templates.ResultsReceiver Operating Characteristic plots (ROCs) demonstrate that the algorithm detects >95% of manually identified spikes with a false-positive rate of ∼2%.Comparison with existing methodsROCs demonstrate that the MF algorithm performs better than algorithms that detect spikes based on a derivative-threshold approach.ConclusionsThe MF approach performs well and leads into approaches to identify spike parameters.



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Widespread optogenetic expression in macaque cortex obtained with MR-guided, convection enhanced delivery (CED) of AAV vector to the thalamus

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Publication date: 1 January 2018
Source:Journal of Neuroscience Methods, Volume 293
Author(s): Azadeh Yazdan-Shahmorad, Nan Tian, Viktor Kharazia, Lluis Samaranch, Adrian Kells, John Bringas, Jiwei He, Krystof Bankiewicz, Philip N. Sabes
BackgroundIn non-human primate (NHP) optogenetics, infecting large cortical areas with viral vectors is often a difficult and time-consuming task. Previous work has shown that parenchymal delivery of adeno-associated virus (AAV) in the thalamus by convection-enhanced delivery (CED) can lead to large-scale transduction via axonal transport in distal areas including cortex. We used this approach to obtain widespread cortical expression of light-sensitive ion channels.New methodAAV vectors co-expressing channelrhodopsin-2 (ChR2) and yellow fluorescent protein (YFP) genes were infused into thalamus of three rhesus macaques under MR-guided CED. After six to twelve weeks recovery, in vivo optical stimulation and single cell recording in the cortex was carried out using an optrode in anesthetized animals. Post-mortem immunostaining against YFP was used to estimate the distribution and level of expression of ChR2 in thalamus and cortex.ResultsHistological analysis revealed high levels of transduction in cortical layers. The patterns of expression were consistent with known thalamo-cortico-thalamic circuits. Dense expression was seen in thalamocortiocal axonal fibers in layers III, IV and VI and in pyramidal neurons in layers V and VI, presumably corticothalamic neurons. In addition we obtained reliable in vivo light-evoked responses in cortical areas with high levels of expression.Comparison with existing methodsThalamic CED is very efficient in achieving large expressing areas in comparison to convectional techniques both in minimizing infusion time and in minimizing damage to the brain.ConclusionMR-guided CED infusion into thalamus provides a simplified approach to transduce large cortical areas by thalamo-cortico-thalamic projections in primate brain.



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The effect of plasma rich in growth factors combined with follicular unit extraction surgery for the treatment of hair loss: A pilot study

Summary

Background

Hair transplant surgery using follicular unit extraction technique (FUE) is a common surgical procedure for the treatment of severe hair loss. Blood-derived autologous growth factors have also proved to promote hair regeneration in patients with different types of alopecia.

Aims

The aim of this study was to evaluate the safety and clinical efficacy of plasma rich in growth factors (PRGF) technology as an adjuvant therapy for FUE surgery in hair loss affected patients.

Methods

The biologic potential of PRGF was firstly in vitro evaluated over follicular germinal matrix and dermal papilla cells. Afterward, fifteen patients were subjected to routine FUE procedure while 15 patients underwent FUE+PRGF therapy. PRGF group included intradermal injections of growth factors and follicular transfer unit (FTU) preservation in an autologous fibrin clot. Postsurgical patient satisfaction and clinical improvement were evaluated, and PRGF or saline-preserved hair grafts were histomorphometrically analyzed.

Results

Follicular cell proliferation and migration was induced after autologous growth factors treatment. PRGF-preserved FTUs presented higher bioactivity signals and improved integrity of perifollicular structures and extracellular matrix proteins such as collagen and elastic fibers. PRGF not only reduced the postsurgical crust healing and hair fixation period, but also decreased the inflammatory pain and itching sensation.

Conclusions

This preliminary data demonstrate that PRGF is able to minimize the postsurgical follicle loss and potentiate the performance of grafted hairs. The fibrin clot not only acts as a protective barrier against environmental factors, but also provides a biologically active scaffold that induces resident cell proliferation and maintains an optimal integrity of the grafted hair.



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Exogenous pigmentation of skin and nail caused by a millipede in a patient with plantar psoriasis



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Colonic strictures in children and young adults with Crohn's disease: Recognition on MR enterography

Publication date: March–April 2018
Source:Clinical Imaging, Volume 48
Author(s): David M. Biko, Petar Mamula, Nancy A. Chauvin, Sudha A. Anupindi
ObjectivesIdentify MRE features of colonic strictures in children/young adults with Crohn's disease.MethodsIncluded are patients with colonic strictures on colonoscopy imaged with MRE. Bowel wall thickening (BWT) with luminal narrowing, pre-stenotic dilatation (PSD), bowel wall enhancement, and diffusion restriction were evaluated.ResultsAll potential strictures (n=12) had BWT with luminal narrowing on MRE. 8/12 had PSD, meeting our MRE stricture criteria. MRE diagnosed 8/12 colonic strictures compared to colonoscopy but was concordant with findings in all surgical patients.ConclusionStrictures on MRE did not always agree with colonoscopy, but when correlating with surgery, MRE findings were all concordant.



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Intertwined control of the cell cycle and nucleocytoplasmic transport by the cyclin-dependent kinase Pho85 and RanGTPase Gsp1 in Saccharomyces cerevisiae

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Publication date: Available online 26 October 2017
Source:Microbiological Research
Author(s): Oriol Mirallas, Elisabet Ballega, Bàrbara Samper-Martín, Sergio García-Márquez, Reyes Carballar, Natalia Ricco, Javier Jiménez, Josep Clotet
Deciphering the molecular mechanisms that connect cell cycle progression and nucleocytoplasmic transport is of particular interest: this intertwined relationship, once understood, may provide useful insight on the diseases resulting from the malfunction of these processes. In the present study we report on findings that indicate a biochemical connection between the cell cycle regulator CDK Pho85 and Ran-GTPase Gsp1, an essential nucleocytoplasmic transport component. When Gsp1 cannot be phosphorylated by Pho85, the cell cycle progression is impaired. Accordingly, a nonphosphorylatable version of Gsp1 abnormally localizes to the nucleus, which impairs the nuclear transport of molecules, including key components of cell cycle progression. Furthermore, our results suggest that the physical interaction of Gsp1 and the Kap95 karyopherin, essential to the release of nuclear cargoes, is altered. Altogether, the present findings point to the involvement of a biochemical mechanism in the interlocked regulation of the cell cycle and nuclear transport.



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Isolation, purification, structural elucidation and antimicrobial activities of kocumarin, a novel antibiotic isolated from actinobacterium Kocuria marina CMG S2 associated with the brown seaweed Pelvetia canaliculata

Publication date: Available online 26 October 2017
Source:Microbiological Research
Author(s): Bushra Uzair, Farid Menaa, Barkat Ali Khan, Faryal Vali Mohammad, Viqar Uddin Ahmad, Ryad Djeribi, Bouzid Menaa
AimsScreening of seaweed-associated bacteria capable of producing antimicrobials.Methods and resultsFifteen microbial strains, associated to the brown seaweed Pelvetia canaliculata (Linnaeus) attached to the rocks of Sonmiani Beach (Karachi, Pakistan), were screened. Crude extract filtrates of CMG S2 strain grew on Zobell marine agar (ZMA) had the most remarkable antimicrobial activity. Based on its phenotypic aspects (e.g. Gram-positive, microccoid form), biochemical characteristics (e.g. halotolerance) and genetic analyses, CMG S2 is identified as a putatively new Kocuria marina type strain belonging to the actinobacteria's class and micrococcaceae family. Thereby, the nucleotide sequence analysis of its full-length 16S ribosomal ribonucleic acid (rRNA) gene (GenBank accession number EU073966.1) displayed highest identity (i.e. 99%) and score (2630) with K. marina KMM 3905. Phylogenic trees analysis using the neighbor-joining method showed closest evolutionary distance of CMG S2 with KMM 3905 strain and K. carniphila (DC2201) specie. Interestingly, a unique ultraviolet (UV)-bioactive compound was purified from CMG S2 crude extracts by flash silica gel column and thin-layer chromatography techniques (TLC). Its chemical structure was unraveled as 4-[(Z)-2 phenyl ethenyl] benzoic acid (PEBA, later named kocumarin) by nuclear magnetic resonance (NMR) spectroscopy techniques. Importantly, kocumarin demonstrated prominent and rapid growth inhibition against all tested fungi and pathogenic bacteria including methicillin-resistant Staphylococcus aureus (MRSA), with a minimal fungal inhibitory concentration (MFC) of 15–25μg/mL and a minimal (bacterial) inhibitory concentration (MIC) of 10–15μg/mL.Significance and impact of the studyKocumarin represents a new promising natural antibiotic for in vivo and environmental applications.

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Cover 2 -- Editorial Board

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Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44





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fm iii and iv -- Contents/Barcode

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Publication date: December 2017
Source:Magnetic Resonance Imaging, Volume 44





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A review of electrocatalyst characterization by transmission electron microscopy

Publication date: Available online 26 October 2017
Source:Journal of Energy Chemistry
Author(s): Liyun Zhang, Wen Shi, Bingsen Zhang
At present, the development of highly efficient electrocatalysts with more rational control of microstructures (e.g. particle size, morphology, surface structure, and electronic structure) and chemical composition is needed and remained great challenges. Transmission electron microscopy (TEM) can offer the information about the microstructures and chemical compositions of the electrocatalysts on nano and atomic scale, which enables us to establish the synthesis-structure-performance relationship and further direct the design of new electrocatalysts with high performance. In this minireview paper, a brief introduction on the basic characterization of electrocatalysts with TEM, followed by the studying of dynamic evolution of the electrocatalysts in electrochemical reactions with identical location-TEM, is discussed.

Graphical abstract

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Degradation of Diphenhydramine by the Photocatalysts of ZnO/Fe2O3 and TiO2/Fe2O3 Based on Clinoptilolite: Structural and Operational Comparison

Publication date: Available online 26 October 2017
Source:Journal of Environmental Chemical Engineering
Author(s): Nila Davari, Mehrdad Farhadian, Ali Reza Solaimany Nazar, Maryam Homayoonfal
The photocatalysts of TiO2/Fe2O3 and ZnO/Fe2O3 based on clinoptilolite natural zeolite were synthesized by impregnation route and sol-gel methods The synthesized photocatalysts were characterized by XRD, XRF, EDX, FE-SEM, FT-IR, BET and UV–vis DRS analyses. The results of XRD, FT-IR, and EDX confirmed the presence of Fe2O3, TiO2, and ZnO nanoparticles on the surface of clinoptilolite. The FE-SEM results confirmed deposition of TiO2/Fe2O3 and ZnO/Fe2O3 on the surface of zeolite. The approximate particle size of TiO2/Fe2O3 and ZnO/Fe2O3 was 47 and 34nm, respectively. According to the XRF results, the synthesized nanoparticles had Fe3+/TiO2 and Fe3+/ZnO molar ratios of 0.06 in TiO2/Fe2O3/Zeolite and ZnO/Fe2O3/Zeolite, respectively. Based on BET analysis, the surface area of TiO2/Fe2O3/Zeolite and ZnO/Fe2O3/Zeolite was about 112 and 289m2/g, respectively. UV–vis DRS analysis confirmed that both TiO2/Fe2O3/Zeolite and ZnO/Fe2O3/Zeolite have high absorbtion capacity at visible light region. The performance of these two photocatalysts in degradation of diphenhydramine (DPH) from contaminated water was evaluated by investigating the effects of operational factors such as concentration of the contaminant (1–100mg/l), photocatalysts (0.5–2g/l), irradiation time (45–180min), and pH (4-10). The results of the photocatalytic experiments revealed that the ZnO/Fe2O3/Zeolite had a more effective performance in degrading DPH, compared to TiO2/Fe2O3/Zeolite. Under the optimal conditions, the efficiency of DPH degradation with TiO2/Fe2O3/Zeolite (DPH: 50mg/l, hydrogen peroxide: 50mg/l, irradiation time: 120min, photocatalyst: 0.5g/l, pH=5) and ZnO/Fe2O3/Zeolite (DPH: 50mg/l, hydrogen peroxide: 50mg/l, irradiation time: 100min, photocatalyst: 0.5g/l, pH=10) was 80 and 95%, respectively.

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Book review: beyond a shadow of a diet



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Cardiovascular Effects Of Oral Appliance Therapy In Obstructive Sleep Apnea: A Systematic Review And Meta-Analysis

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. This study systematically reviews the effects of oral appliance therapy (OAT) on a broad spectrum of cardiovascular outcomes.A literature search was performed up to December 31st 2016. Twenty-five relevant full-text articles were retrieved. Sixteen articles were considered methodologically sufficient, including 11 randomized controlled trials.Pooled data of the RCTs showed significant reductions in daytime systolic and diastolic blood pressure compared to baseline, but no significant reductions in heart rate, except for daytime heart rate when compared to inactive/placebo OAT.

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Women’s Perceptions of Usefulness and Ease of Use of Four Healthy Eating Blog Characteristics: A Qualitative Study of 33 French-Canadian Women

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Publication date: Available online 26 October 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Véronique Bissonnette-Maheux, Audrée-Anne Dumas, Véronique Provencher, Annie Lapointe, Marilyn Dugrenier, Sharon Straus, Marie-Pierre Gagnon, Sophie Desroches
BackgroundHealthy eating blogs are knowledge translation tools used by nutrition and dietetics practitioners for helping people improve their health behaviors and food choices.ObjectiveOur aim was to explore women's perceptions of the usefulness and ease of use of healthy eating blog (HEB) characteristics that might increase potential users' intention to use them as tools to improve their dietary habits.DesignWe conducted qualitative research using semi-structured individual interviews.ParticipantsThirty-three women (mean age of 44 years; range=27 to 61 years) living in the Quebec City, Canada, metropolitan area were studied.InterventionFour existing HEBs, written by French-Canadian registered dietitians (RDs) whose main objective was the promotion of a healthy diet, were explored by women during individual interviews. A standardized open-ended interview questionnaire based on the Technology Acceptance Model was used to identify women's perceptions about characteristics of type of blog content delivery, RD blogger's delivery of information, blog layout, and blog design.Main outcome measuresWomen's perceptions toward the contribution of HEB characteristics to the usefulness and ease of use of those tools to improve their dietary habits were measured.Analyses performedInterviews were audiorecorded, transcribed verbatim, coded, and analyzed through an inductive content analysis using NVivo software.ResultsThe most useful characteristics of type of blog content delivery identified by women were recipes, hyperlinks, and references. Among characteristics of RD blogger's delivery of information, most women reported that interaction between blog readers and the RD blogger created a sense of proximity and of connection that was helpful for improving their dietary behaviors. Women's perceptions toward various characteristics of blog layout and design were also discussed.ConclusionsIncorporating specific characteristics when designing HEBs should be considered by RDs and future research to promote the use of those tools to support dietary behavior change efforts of internet users.



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Adult hippocampal neurogenesis in neuropathic pain and alkyl glycerol ethers treatment

Publication date: Available online 26 October 2017
Source:Acta Histochemica
Author(s): Anna A. Tyrtyshnaia, Igor V. Manzhulo, Ruslan M. Sultanov, Ekaterina V. Ermolenko
Neuropathic pain manifested by a number of sensory symptoms is often accompanied by disorders of higher nervous activity, such as memory impairment, depression, anxiety, anhedonia, etc. This emphasizes the involvement of supraspinal structures including the hippocampus in neuropathic pain pathogenesis. In the present study, we focused on the impact of chronic neuropathic pain on hippocampal neurogenesis and microglial state. In addition, we test the effect of alkyl glycerol ethers on hippocampal neuronal and microglial plasticity as well as behavioral parameters. Neuropathic pain was induced using the model of sciatic nerve chronic constriction injury. We found an impairment of working memory and locomotor activity in animals with neuropathic pain, which was prevented by alkyl glycerol ethers treatment. Sciatic nerve ligation in mice contributed to the decrease in hippocampal neurogenesis intensity. Alkyl glycerol ethers administration significantly reduced this effect. Neuropathic pain-associated neurogenesis reduction was accompanied by an increased percentage of Iba1-labeled area in the CA1 hippocampal region on the 14th and 28th days after surgery. In addition, we observed a decrease in hippocampal pro-inflammatory microglia marker CD86 immunostaining on day 28 after surgery in alkyl glycerol ethers-treated mice with sciatic nerve ligation. These results are consistent with data on pro- and anti-inflammatory cytokines expression in the hippocampus. Alkyl glycerol ethers administration increased IL-10 and decreased IL-1β hippocampal expression in animals with neuropathic pain. Taken together, these data suggest that neuropathic pain-behavior in rodents is accompanied by changes in microglia polarization, thereby contributing to neurogenesis impairment and cognitive disturbances. Alkyl glycerol ethers prevented M1 microglial activation, contributing to the maintenance of normal neurogenesis levels within the hippocampus and normalizing working memory.

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Inside Front Cover - Editorial Board Page

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179





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Nuclear weapons produced 236U, 239Pu and 240Pu archived in a Porites Lutea coral from Enewetak Atoll

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): M.B. Froehlich, S.G. Tims, S.J. Fallon, A. Wallner, L.K. Fifield
A slice from a Porites Lutea coral core collected inside the Enewetak Atoll lagoon, within 15 km of all major nuclear tests conducted at the atoll, was analysed for 236U, 239Pu and 240Pu over the time interval 1952-1964 using a higher time resolution than previously reported for a parallel slice from the same core. In addition two sediment samples from the Koa and Oak craters were analysed. The strong peaks in the concentrations of 236U and 239Pu in the testing years are confirmed to be considerably wider than the flushing time of the lagoon. This is likely due to the growth mechanism of the coral. Following the last test in 1958 atom concentrations of both 236U and 239Pu decreased from their peak values by more than 95% and showed a seasonal signal thereafter. Between 1959 and 1964 the weighted average of the 240Pu/239Pu atom ratio is 0.124 ± 0.008 which is similar to that in the lagoon sediments (0.129 ± 0.006) but quite distinct from the global fallout value of ∼0.18. This, and the high 239,240Pu and 236U concentrations in the sediments, provides clear evidence that the post-testing signal in the coral is dominated by remobilisation of the isotopes from the lagoon sediments rather than from global fallout.



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The 137Cs activity concentration of suspended and dissolved fractions in irrigation waters collected from the 80 km zone around TEPCO's Fukushima Daiichi Nuclear Power Station

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Hirofumi Tsukada, Satoshi Nihira, Takashi Watanabe, Satoru Takeda
Fifty-four samples of irrigation water were collected in 2014 from agricultural ponds, rivers, and dams within the 80 km zone around TEPCO's Fukushima Daiichi Nuclear Power Station (FDNPS). The samples were filtered with a 0.45 μm pore-size membrane filter to produce suspended and dissolved fractions. The 137Cs activity concentration of the suspended fraction varied from 1.5 to 300 Bq g−1 dry weight and was significantly higher than that in the soil around each sampling site. The range of 137Cs activity concentrations in the dissolved fraction varied over three orders of magnitude at 0.0075–6.7 Bq l−1, which was a larger range than that of the suspended fraction; the higher values for samples were from within the 20 km zone. In the dissolved fraction 87 ± 9% of the 137Cs (n = 37) was in a monovalent cationic form (Cs+) and therefore potentially mobile. The distribution coefficient (Kd) ranged from 4100 to 2,100,000; the geometric mean value (110,000) was higher than that reported by the IAEA (2010). The geometric mean Kd of samples collected from the 20 km zone was 61,000 (n = 27), which was significantly lower than that collected from 20 to 80 km zone (200,000, n = 27). The Kd-value was negative correlated with the concentration of stable 133Cs and the electric conductivity in the dissolved fraction. This shows relatively higher mobility of radiocaesium in irrigation waters may occur when there are higher contents of cations present.



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Effects of bark washing and epiphytic moss on 137Cs activity concentration in bark and stemflow in Japanese persimmon (Diospyros kaki Thunb.)

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Mamoru Sato, Tsugiko Takase, Katsuhiko Yamaguchi
The effects of bark washing, and of epiphytic moss growing on the bark surfaces, on the 137Cs activity concentrations in bark and stemflow samples were evaluated at two Japanese persimmon orchards located in Fukushima City and Date City, both approximately 60–65 km northwest of the Fukushima Dai-ichi nuclear power plant. The means of 137Cs in stemflow captured by 1 g of sphagnum placed on the main trunks of washed and unwashed trees, and on sites with moss and with no moss growing on bark of the non-washed trees in Date City, were 0.37 Bq, 1.08Bq, 0.77 Bq and 0.52 Bq respectively. The 137Cs was significantly lower in the washed bark and in the absence of moss at p = 0.00031 and p = 0.0443 by t-test respectively. The 137Cs in directly-collected stemflow on the main trunks was significantly higher for the unwashed tree at 6.0 Bq L−1 compared with the washed tree at 1.1 Bq L−1 (p = 0.017 by Tukey's test). The extraction rate of dissolved 137Cs with deionized water was 7.3% even after stirring for 40 h. These results indicate that the moss acts as reservoir of 137Cs, and that bark-washing decontamination can reduce the additional 137Cs supply from moss in subsequent years following the radioactive fallout.



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Behavior of 137Cs in ponds in the vicinity of the Fukushima Dai-ichi nuclear power plant

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Yoshifumi Wakiyama, Alexei Konoplev, Toshihiro Wada, Tsugiko Takase, Ian Byrnes, Matthew Carradine, Kenji Nanba
137Cs activity concentration in the water of four ponds, Suzuuchi (SU), Funasawa (FS), Inkyozaka (IZ), and Kashiramori (KM), that are within 10 km of the Fukushima Dai-ichi nuclear power plant were observed from April 2015 to August 2016. 137Cs inventories in soils surrounding SU, FS, IZ, and KM were 6.4, 2.9, 2.1, and 0.9 MBq m−2, respectively. 137Cs inventories in the bottom sediments of SU, FS, IZ, and KM were 13, 8.9, 1.6, and 1.1 MBq m−2, respectively. Higher 137Cs inventories in bottom sediment than those of soil in SU and FS suggest that 137Cs was delivered to and accumulated in these ponds. Mean total 137Cs activity concentrations in SU, FS, IZ, and KM were 41, 13, 9.5, and 1.4 Bq L−1, respectively. Particulate 137Cs concentration accounted for 71–90% of total 137Cs in the water samples, on average. The mean distribution coefficient, Kd, in SU, FS, IZ, and KM was 1.3 × 105, 2.1 × 105, 1.7 × 105, and 6.2 × 105 L kg−1, respectively. These Kd values were higher than the Kd values observed in the Chernobyl area by 1–2 orders of magnitude. Although no significant decreasing trends were found, dissolved 137Cs activity concentration tended to be low during winter in all four ponds. Dissolved 137Cs activity concentrations were proportional to K+ and DOC concentrations in all the ponds. The results from principal component analysis performed for 137Cs activity concentration and water chemistry data sets suggested that there were different mechanisms behind variability of dissolved 137Cs activity concentrations for each pond. Continuous monitoring is required to reveal temporal trends in 137Cs activity concentrations of these waters and controlling factors of such in closed water systems in Fukushima.



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Measurement of tributyl phosphate (TBP) in groundwater at a legacy radioactive waste site and its possible role in contaminant mobilisation

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Brett Rowling, Andrew S. Kinsela, M. Josick Comarmond, Catherine E. Hughes, Jennifer J. Harrison, Mathew P. Johansen, Timothy E. Payne
At many legacy radioactive waste sites, organic compounds have been co-disposed, which may be a factor in mobilisation of radionuclides at these sites. Tri-butyl phosphate (TBP) is a component of waste streams from the nuclear fuel cycle, where it has been used in separating actinides during processing of nuclear fuels. Analyses of ground waters from the Little Forest Legacy Site (LFLS) in eastern Australia were undertaken using solid-phase extraction (SPE) followed by gas chromatographic mass spectrometry (GCMS). The results indicate the presence of TBP several decades after waste disposal, with TBP only being detected in the immediate vicinity of the main disposal area. TBP is generally considered to degrade in the environment relatively rapidly. Therefore, it is likely that its presence is due to relatively recent releases of TBP, possibly stemming from leakage due to container degradation. The ongoing presence and solubility of TBP has the potential to provide a mechanism for nuclide mobilisation, with implications for long term management of LFLS and similar legacy waste sites.

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Whole-organism concentration ratios in wildlife inhabiting Australian uranium mining environments

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Gillian A. Hirth, Mathew P. Johansen, Julia G. Carpenter, Andreas Bollhöfer, Nicholas A. Beresford
Wildlife concentration ratios for 226Ra, 210Pb, 210Po and isotopes of Th and U from soil, water, and sediments were evaluated for a range of Australian uranium mining environments. Whole-organism concentration ratios (CRwo-media) were developed for 271 radionuclide-organism pairs within the terrestrial and freshwater wildlife groups. Australian wildlife often has distinct physiological attributes, such as the lower metabolic rates of macropod marsupials as compared with placental mammals. In addition, the Australian CRswo-media originate from tropical and semi-arid climates, rather than from the temperate-dominated climates of Europe and North America from which most (>90%) of internationally available CRwo-media values originate. When compared, the Australian and non-Australian CRs are significantly different for some wildlife categories (e.g. grasses, mammals) but not others (e.g. shrubs). Where differences exist, the Australian values were higher, suggesting that site-, or region-specific CRswo-media should be used in detailed Australian assessments. However, in screening studies, use of the international mean values in the Wildlife Transfer Database (WTD) appears to be appropriate, as long as the values used encompass the Australian 95th percentile values. Gaps in the Australian datasets include a lack of marine parameters, and no CR data are available for freshwater phytoplankton, zooplankton, insects, insect larvae or amphibians; for terrestrial environments, there are no data for amphibians, annelids, ferns, fungi or lichens & bryophytes. The new Australian specific parameters will aide in evaluating remediation plans and ongoing operations at mining and waste sites within Australia. They have also substantially bolstered the body of U- and Th-series CRwo-media data for use internationally.



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239Pu fallout across continental Australia: Implications on 239Pu use as a soil tracer

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): R. Lal, L.K. Fifield, S.G. Tims, R.J. Wasson
At present there is a need for the development of new radioisotopes for soil erosion and sediment tracing especially as fallout 137Cs levels become depleted. Recent studies have shown that 239Pu can be a useful new soil erosion and sediment radioisotope tracer. 239Pu was released in the major atmospheric nuclear weapons tests of 1950's and 1960's. However 239Pu has a half-life of 24110 years and more than 99% of this isotope is still present in the environment today. In contrast 137Cs with a half-life of 30.07 year has decayed to <35% of initially deposited activities and this isotope will become increasingly difficult to measure in the coming decades especially in the southern hemisphere, which received only about a third of the total global fallout from the atmospheric tests (UNSCEAR, 2000).In this study an assessment of the 239Pu fallout in Australia was carried out from comparison of measured 239Pu inventories with expected 239Pu inventories from fallout models. 239Pu inventories were also compared with rainfall and measured 240Pu/239Pu ratios across Australia.239Pu fallout inventories ranged from 430 to 1461 μB/cm2. Central Australia, with fallout 107% in excess of expected values, seems to be strongly impacted by local fallout deposition. In comparison other sites typically show 5–40% variation between expected and measured fallout values.The fallout inventories were found to weakly correlate (using power functions, y = axb) with rainfall with r2 = 0.50 across the southern catchments (25–40°S latitude band). Across the northern catchments (10–25°S latitude band) fallout showed greater variability with rainfall with r2 = 0.24. Central Australia and Alice Springs which seem to be strongly impacted by local fallout are excluded from the rainfall correlation data (with these sites included r2 = 0.08 and r2 < 0.01 respectively).240Pu/239Pu atom ratios range from 0.045 to 0.197, with averages of 0.139(0.017), 0.111(0.052) and 0.160(0.027) in the 10–20°S, 20–30°S and 30–40°S latitude bands respectively. The 240Pu/239Pu atom ratios in Central Australia (0.069) likely represent fallout from the Australian tests which also have low 240Pu/239Pu atom ratios i.e., Maralinga (0.113) and Montebello (0.045). The average ratios in the 20–30°S and 30–40° bands are closer to the global average (0.139 and 0.177 respectively when not including the close-in fallout data from the nuclear test sites) if the Australian test sites and Central Australian sites are neglected as they clearly represent the effects of close in fallout.



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Natural radionuclides and stable elements in weaver ants (Oecophylla smaragdina) from tropical northern Australia

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Peter Medley, Che Doering, Fiona Evans, Andreas Bollhöfer
Natural radionuclides and stable elements were measured in weaver ants, leaves and soils collected from three sites in tropical northern Australia. Radionuclide concentration ratios for ants relative to soil were derived from the measurements and used to refine the current environmental radiological assessment for remediation of Ranger uranium mine. Use of site-specific concentration ratios for weaver ants gave a more conservative estimate of environmental exposure to the arthropod wildlife group than use of default concentration ratios in the ERICA Tool. This was primarily because the 226Ra concentration ratio for weaver ants was more than 7 times greater than for generic arthropods.



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Comparison of radium-228 determination in water among Australian laboratories

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Atun Zawadzki, Megan Cook, Brodie Cutmore, Fiona Evans, Daniela Fierro, Alicea Gedz, Jennifer J. Harrison, Tom Loosz, Peter Medley, Lida Mokhber-Shahin, Sarah Mullins, Sandra Sdraulig
The National Health and Medical Research Council and Natural Resource Management Ministerial Council of Australia developed the current Australian Drinking Water Guidelines which recommend an annual radiation dose value of 1 mSv year−1. One of the potential major contributors to the radiation dose from drinking water is radium-228, a naturally occurring radionuclide arising from the thorium decay series. Various methods of analysing for radium-228 in water have been established and adapted by analytical radiochemistry laboratories. Seven laboratories in Australia participated in analysing radium-228 spiked water samples with activity concentrations ranging from 6 mBq L−1 to 20 Bq L−1. The aim of the exercise was to compare and evaluate radium-228 results reported by the participating laboratories, the methods used and the detection limits. This paper presents the outcome of the exercise.



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7Be and 210Pb wet/dry deposition in Melbourne, Australia and the development of deployable units for radiological emergency monitoring

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Jane Courtier, Sandra Sdraulig, Gillian Hirth
A large stainless-steel collection tray (with a surface area of one square metre) was purpose built and mounted on the roof of the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) building at Yallambie, Victoria, Australia. Using this system two years' worth of wet/dry deposition samples have been collected and analysed. Smaller portable units were also developed for deployment in an emergency and/or for environmental monitoring. The cosmogenic radionuclide 7Be and the naturally occurring terrestrial radionuclide 210Pb have been used to validate the systems. The data from the smaller units was successfully compared to the larger permanent collection unit for validation, thus finding the portable units fit for purpose.Monitoring of wet and dry fallout deposition is an important response to radiological emergencies. It can provide useful information in verifying predictive models of radionuclide atmospheric transport and dispersion, in addition to providing local deposition data.



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Robustness testing of an in-situ caesium extraction unit

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Ilonka Bokor, Sandra Sdraulig, Masoumeh Sanagou
Following on from the successful development and validation of a prototype automated unit for the extraction of radiocaesium from seawater, the unit was redesigned to be smaller, easier to transport and better suited for field work. An extension of the validation process was undertaken to include robustness testing. Robustness testing evaluates the behaviour of a procedure when deliberate small changes are made. This requires the identification and testing of experimental factors which could have an impact on the results. The Plackett-Burman approach was adopted to minimise the number of experiments needed for testing. The study showed that the analytical method was not sensitive to any of the factors tested, indicating that the method is robust.



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Experimental comparison of the bioaccumulation of anthropogenic radionuclides by egg and juvenile life stages of a small shark

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Ross A. Jeffree, Mathew P. Johansen
This study compared the bioaccumulation of anthropogenic nuclides (65Zn, 134Cs, 60Co and 241Am) between the egg and juvenile life stages of a small shark (Scyliorhinus canicula), based on previously published experimental data. Rates of accumulation over 15 days were derived and summed for the transfer pathways which were specific to these two life stages. Radionuclide transfers to the egg and its embryo & yolk were quantified for i) the maternal pathway following her uptake of radionuclides via food and seawater and ii) from seawater following its oviposition. For the juvenile, the transfer of radionuclides were measured for aqueous & dietary pathways. The results show that, compared to juveniles, eggs have equivalent rates of accumulation of 65Zn and 134Cs but enhanced accumulation of 241Am by a factor of five and of 60Co by two orders of magnitude. The radiological exposure of the embryo due to radionuclides maternally transferred to the embryo & yolk is also enhanced for the alpha-emitting 241Am. This enhanced accumulation of 241Am and 60Co, as well as the equivalent accumulation of 65Zn and 134Cs, suggest greater likely vulnerability to radiation damage in eggs as compared to juveniles. Radiological dose assessment confirmed highest doses to the egg which is predominantly due to accumulated 241Am.

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The Swedish radiological environmental protection regulations applied in a review of a license application for a geological repository for spent nuclear fuel

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Pål Andersson, Karolina Stark, Shulan Xu, Maria Nordén, Björn Dverstorp
For the first time, a system for specific consideration of radiological environmental protection has been applied in a major license application in Sweden. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a license application for construction of a geological repository for spent nuclear fuel at the Forsmark site. The license application is supported by a post-closure safety assessment, which in accordance with regulatory requirements includes an assessment of environmental consequences. SKB's environmental risk assessment uses the freely available ERICA Tool. Environmental media activity concentrations needed as input to the tool are calculated by means of complex biosphere modelling based on site-specific information gathered from site investigations, as well as from supporting modelling studies and projections of future biosphere conditions in response to climate change and land rise due to glacial rebound. SKB's application is currently being reviewed by the Swedish Radiation Safety Authority (SSM). In addition to a traditional document review with an aim to determine whether SKB's models are relevant, correctly implemented and adequately parametrized, SSM has performed independent modelling in order to gain confidence in the robustness of SKB's assessment. Thus, SSM has used alternative stylized reference biosphere models to calculate environmental activity concentrations for use in subsequent exposure calculations. Secondly, an alternative dose model (RESRAD-BIOTA) is used to calculate doses to biota that are compared with SKB's calculations with the ERICA tool. SSM's experience from this review is that existing tools for environmental dose assessment are possible to use in order to show compliance with Swedish legislation. However, care is needed when site representative species are assessed with the aim to contrast them to generic reference organism. The alternative modelling of environmental concentrations resulted in much lower concentrations compared to SKB's results. However, SSM judges that SKB's in this part conservative approach is relevant for a screening assessment. SSM also concludes that there are big differences in dose rates calculated to different organisms depending on which tool that is used, although not systematically higher for either of them. Finally, independent regulatory modelling has proven valuable for SSM's review in gaining understanding and confidence in SKB's assessment presented in the license application.



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A method for independent modelling in support of regulatory review of dose assessments

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Björn Dverstorp, Shulan Xu
Several countries consider geological disposal facilities as the preferred option for spent nuclear fuel due to their potential to provide isolation from the surface environment on very long timescales. In 2011 the Swedish Nuclear Fuel & Waste Management Co. (SKB) submitted a license application for construction of a spent nuclear fuel repository. The disposal method involves disposing spent fuel in copper canisters with a cast iron insert at about 500 m depth in crystalline basement rock, and each canister is surrounded by a buffer of swelling bentonite clay. SKB's license application is supported by a post-closure safety assessment, SR-Site. SR-Site has been reviewed by the Swedish Radiation Safety Authority (SSM) for five years. The main method for review of SKB's license application is document review, which is carried out by SSM's staff and supported by SSM's external experts. The review has proven a challenging task due to its broad scope, complexity and multidisciplinary nature. SSM and its predecessors have, for several decades, been developing independent models to support regulatory reviews of post-closure safety assessments for geological repositories. For the review of SR-Site, SSM has developed a modelling approach with a structured application of independent modelling activities, including replication modelling, use of alternative conceptual models and bounding calculations, to complement the traditional document review. This paper describes this scheme and its application to biosphere and dose assessment modelling. SSM's independent modelling has provided important insights regarding quality and reasonableness of SKB's rather complex biosphere modelling and has helped quantifying conservatisms and highlighting conceptual uncertainty.



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Aquatic live animal radiotracing studies for ecotoxicological applications: Addressing fundamental methodological deficiencies

Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Tom Cresswell, Marc Metian, Lisa A. Golding, Mike D. Wood
The use of live animal gamma radioisotope tracer techniques in the field of ecotoxicology allows laboratory studies to accurately monitor contaminant biokinetics in real time for an individual organism. However, methods used in published studies for aquatic organisms are rarely described in sufficient detail to allow for study replication or an assessment of the errors associated with live animal radioanalysis to be identified. We evaluate the influence of some important methodological deficiencies through an overview of the literature on live aquatic animal radiotracer techniques and through the results obtained from our radiotracer studies on four aquatic invertebrate species. The main factors discussed are animal rinsing, radioanalysis and geometry corrections. We provide examples of three main techniques in live aquatic animal radiotracer studies to improve data quality control and demonstrate why each technique is crucial in interpreting the data from such studies. The animal rinsing technique is also relevant to non-radioisotope tracer studies, especially those involving nanoparticles. We present clear guidance on how to perform each technique and explain the importance of proper reporting of the validation of each technique for individual studies. In this paper we describe methods that are often used in lab-based radioecology studies but are rarely described in great detail. We hope that this paper will act as the basis for standard operating procedures for future radioecology studies to improve study replication and data quality control.

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Editorial Board

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Publication date: November 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 11





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Longitudinal recovery and reduced costs after 120 sessions of locomotor training for motor incomplete spinal cord injury

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Publication date: Available online 26 October 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Sarah A. Morrison, Douglas Lorenz, Carol P. Eskay, Gail F. Forrest, D. Michele Basso
ObjectiveTo determine the impact of long term, body weight supported locomotor training (BWSLT) after chronic, incomplete spinal cord injury (SCI). Also, health care costs were estimated related to lost recovery potential and preventable secondary complications that may have occurred due to visit limits imposed by insurers.DesignProspective observational cohort with longitudinal follow up.SettingEight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network® (NRN).ParticipantsIndividuals with motor incomplete chronic SCI (Asia Impairment Scale C or D; n=69; 0.1-45 yr after SCI), who completed at least 120 NRN physical therapy sessions.InterventionsManually-assisted locomotor training in a body weight supported treadmill environment, overground standing and stepping activities, and community integration tasks.Main Outcome Measure(s)International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, SCI-FAI, Berg Balance Scale, Modified Functional Reach, 10-meter walk test and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6-12 month follow-up after discharge from therapy.ResultsSignificant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6-12 months after treatment.ConclusionsDelivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20 session insurance limit can reduce rehospitalizations and long term health costs.



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Table of Contents

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Publication date: November 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 11





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Editors' Selections From This Issue: Volume 98 / Number 11 / November 2017

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Publication date: November 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 11





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IFC (editorial board)

Publication date: November 2017
Source:Peptides, Volume 97





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The International Neuropeptide society pages

Publication date: November 2017
Source:Peptides, Volume 97





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Gayle & Richard Olson prize pages

Publication date: November 2017
Source:Peptides, Volume 97





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Orexins/hypocretins and sex

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Publication date: Available online 26 October 2017
Source:Peptides
Author(s): Olaf Jöhren




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Intranasal administration of neuromedin U derivatives containing cell-penetrating peptides and a penetration-accelerating sequence induced memory improvements in mice

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Publication date: Available online 25 October 2017
Source:Peptides
Author(s): Sachie Sasaki-Hamada, Taichi Funane, Yusuke Nakao, Rie Sasaki, Mio Nagai, Yudai Ueta, Kazumi Yoshizawa, Michiko Horiguchi, Chikamasa Yamashita, Jun-Ichiro Oka
Neuromedin U (NMU) is a neuropeptide that is expressed and secreted in the brain and gut. We previously demonstrated that the intracerebroventricular (i.c.v.) administration of NMU inhibited inflammation-mediated memory impairment in mice. In order to utilize NMU as a clinical treatment tool for inflammation-mediated amnesia, we herein focused on non-invasive intranasal delivery because the i.c.v. administration route is invasive and impractical. In the present study, we prepared two NMU derivatives containing cell-penetrating peptides (CPPs), octaarginine (R8), and each penetration-accelerating sequence, namely FFLIPKG (PASR8-NMU) and FFFFG (F4R8-NMU), for intranasal (i.n.) administration. In the Y-maze test, the i.c.v. administration of lipopolysaccharide (LPS) (10μg/mouse) significantly decreased spontaneous alternation behavior, and this was prevented by the prior administration of PASR8-NMU or F4R8-NMU (5.6μg/mouse, i.n.). Moreover, the administration of PASR8-NMU or F4R8-NMU (5.6μg/mouse, i.n.) just before the Y-maze test also improved LPS-induced memory impairment. Indocyanine green (ICG)-labeled PASR8-NMU (i.n.) was significantly observed in the hippocampus and paraventricular hypothalamic nucleus 30min after its i.n. administration. PASR8-NMU, but not F4R8-NMU guaranteed the stability of the administration liquid for 24h. These results suggest that PASR8-NMU is effective for i.n. delivery to the brain, and may be useful in the clinical treatment of inflammation-mediated amnesia.



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The neuropeptides and protein hormones of the agricultural pest fruit fly Bactrocera dorsalis: what do we learn from the genome sequencing and tissue-specific transcriptomes?

Publication date: Available online 20 October 2017
Source:Peptides
Author(s): Shun-Hua Gui, Hong-Bo Jiang, Guy Smagghe, Jin-Jun Wang
Neuropeptides and protein hormones are very important signaling molecules, and are involved in the regulation and coordination of various physiological processes in invertebrates and vertebrates. Using a bioinformatics approach, we screened the recently sequenced genome and six tissue-specific transcriptome databases (central nervous system, fat body, ovary, testes, male accessory glands, antennae) of the oriental fruit fly (Bactrocera dorsalis) that is economically one of the most important pest insects of tropical and subtropical fruit. Thirty-nine candidate genes were found to encode neuropeptides or protein hormones. These include most of the known insect neuropeptides and protein hormones, with the exception of adipokinetic hormone-corazonin-related peptide, allatropin, diuretic hormone 34, diuretic hormone 45, IMFamide, inotocin, and sex peptide. Our results showed the neuropeptides and protein hormones of Diptera insects appear to have a reduced repertoire compared to some other insects. Moreover, there are also differences between B. dorsalis and the super-model of Drosophila melanogaster. Interesting features of the oriental fruit fly are the absence of genes coding for sex peptide and the presence of neuroparsin and two genes coding neuropeptide F. The majority of the identified neuropeptides and protein hormones is present in the central nervous system, with only a limited number of these in the other tissues. Moreover, we predicted their physiological functions via comparing with data of FlyBase and FlyAtlas. Taken together, owing to the large number of identified peptides, this study can be used as a reference about structure, tissue distribution and physiological functions for comparative studies in other model and important pest insects.

Graphical abstract

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Molecular forms of C-type natriuretic peptide in cerebrospinal fluid and plasma reflect differential processing in brain and pituitary tissues

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Publication date: Available online 19 October 2017
Source:Peptides
Author(s): Michele O. Wilson, Graham K. Barrell, Timothy C.R. Prickett, Eric A. Espiner
C-type natriuretic peptide (CNP) is a paracrine growth factor widely expressed within tissues of the central nervous system. Consistent with this is the high concentration of CNP in cerebrospinal fluid (CSF), exceeding levels in the systemic circulation. CNP abundance is high in hypothalamus and especially enriched in pituitary tissue where − in contrast to hypothalamus − processing to CNP-22 is minimal. Recently we have shown that dexamethasone acutely raises CNP peptides throughout the brain as well as in CSF and plasma. Postulating that molecular forms of CNP would differ in central tissues compared to forms in pituitary and plasma, we have characterized the molecular forms of CNP in tissues (hypothalamus, anterior and posterior pituitary gland) and associated fluids (CSF and plasma) using size-exclusion high performance liquid chromatography (SE-HPLC) and radioimmunoassay in control (saline-treated) and dexamethasone-treated adult sheep. Three immunoreactive-CNP components were identified which were consistent with proCNP (1-103), CNP-53 and CNP-22, but the presence and proportions of these different fragments differed among tissues. Peaks consistent with CNP-53 were the dominant form in all tissues and fluids. Peaks consistent with proCNP, conspicuous in hypothalamic extracts, were negligible in CSF whereas proportions of low molecular weight immunoreactivity (IR) consistent with CNP-22 were similar in hypothalamus, posterior pituitary gland and CSF. In contrast, in both plasma and the anterior pituitary gland, proportions of higher molecular weight IR, consistent with CNP-53 and proCNP, predominated, and low molecular weight IR consistent with CNP-22 was very low. After dexamethasone, proCNP like material − but not other forms − was increased in all samples except CSF, consistent with increased synthesis and secretion. In conclusion, immunoreactive forms of CNP in central tissues differ from those identified in anterior pituitary tissue and plasma − suggesting that the anterior pituitary gland may contribute to systemic levels of CNP in some physiological settings.



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Transcriptomic discovery and comparative analysis of neuropeptide precursors in sea cucumbers (Holothuroidea)

Publication date: Available online 18 October 2017
Source:Peptides
Author(s): Saowaros Suwansa-ard, Arada Chaiyamoon, Alzbeta Talarovicova, Ruchanok Tinikul, Yotsawan Tinikul, Tanes Poomtong, Maurice R. Elphick, Scott F. Cummins, Prasert Sobhon
Neuropeptides synthesized and released by neuronal cells play important roles in the regulation of many processes, e.g. growth, feeding, reproduction, and behavior. In the past decade, next-generation sequencing technologies have helped to facilitate the identification of multiple neuropeptide genes in a variety of taxa, including arthropods, molluscs and echinoderms. In this study, we extend these studies to Holothuria scabra, a sea cucumber species that is widely cultured for human consumption. In silico analysis of H. scabra neural and gonadal transcriptomes enabled the identification of 28 transcripts that encode a total of 26 bilaterian and echinoderm-specific neuropeptide precursors. Furthermore, publicly available sequence data from another sea cucumber, Holothuria glaberrima, allowed a more in-depth comparative investigation. Interestingly, two isoforms of a calcitonin-type peptide precursor (CTPP) were deduced from the H. scabra transcriptome − HscCTPP-long and HscCTPP-short, likely the result of alternative splicing. We also identified a sea cucumber relaxin-type type peptide precursor, which is of interest because relaxin-type peptides have been shown to act as gonadotropic hormones in starfish. Two neuropeptides that appear to be holothurian-specific are GLRFA, and GN-19. In H. scabra, the expression of GLRFA was restricted to neural tissues, while GN-19 expression was additionally found in the longitudinal muscle and intestinal tissues. In conclusion, we have obtained new insights into the neuropeptide signaling systems of holothurians, which will facilitate physiological studies that may enable advances in the aquaculture of sea cucumbers.



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Blockade of the orexin receptors in the CA1 region of hippocampus decreased the lateral hypothalamic-induced antinociceptive responses in the model of orofacial formalin test in the rats

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Publication date: Available online 16 October 2017
Source:Peptides
Author(s): Amir Haghparast, Iman Shafiei, Amir-Mohammad Alizadeh, Somayeh Ezzatpanah, Abbas Haghparast
The role of hippocampus and lateral hypothalamus (LH) in modulation of formalin-induced nociception has been established. The present study aims to examine the role of orexin receptors in the Cornu Ammonis 1 (CA1) region of hippocampus in modulation of the LH-induced antinociception in the orofacial formalin test. Male Wistar rats were unilaterally implanted with two cannulae into the LH and CA1. Intra-LH microinjection of carbachol was done 5min after intra-CA1 administration of SB-334867 (OX1R antagonist) or TCS OX2 29 (OX2R antagonist). After 5min, 50μl of 1% formalin was subcutaneously injected into the upper lip for inducing the nociceptive behaviors. Solely intra-LH administration of carbachol reduced early and late phases of formalin-induced orofacial nociception in a dose-dependent manner. The antinociception evoked by intra-LH injection of carbachol (0.5μl of 250nM carbachol) was antagonized by intra-CA1 administration of 0.5μl of 3, 10 and 30nM solutions of SB-334867 or TCS OX2 29 during the early and late phases of orofacial formalin test. This effect was more remarkable during the late phase in comparison to the early phase. In addition, anti-analgesic effect of SB-334867 was more than TCS OX2 29 during the early and late phases. The results suggest the interpretation that a neural pathway from the LH to the CA1 probably contributes to the modulation of formalin-induced orofacial nociception through recruitment of both CA1 orexin receptors. Clinical studies are recommended to study the probable effectiveness of orexinergic system in modulation of the orofacial nociceptive responses.



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Specific plasma amino acid disturbances associated with metabolic syndrome

Abstract

Purpose

The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process.

Methods

Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(−): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed. The ability of the BCAA and AAA to discriminate subjects with MS and insulin resistance was tested. Based on logistic discrimination, a multivariate early MS diagnostic model was built, and its discrimination properties were evaluated.

Results

Two functionally independent amino acid clusters were identified. BCAA and phenylalanine differed significantly between MS(+) and MS(−) participants (P = 0.003). These factors were also found to be indicators of MS(+) individuals (AUC: 0.66; 95% CI: 0.5757–0.7469), and correlated with cardiometabolic factors. No statistically significant differences in amino acid concentrations between those with and without insulin resistance were noted, and none of the amino groups were indicators of insulin resistance. The proposed MS multivariate diagnostic model consisted of phenylalanine, insulin, leptin, and adiponectin, and had good discrimination properties [AUC 0.79; 95% CI: 0.7239–0.8646].

Conclusions

MS is associated with selective BCAA and AAA profile disturbances, which could be part of cardiometabolic disease pathogenesis and derive neither directly from insulin sensitivity impairment, nor obesity or muscle mass. The MS diagnostic model developed and described herein should be validated in future studies.



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Specific plasma amino acid disturbances associated with metabolic syndrome

Abstract

Purpose

The primary objective of the present study was to examine the association between branched chain and aromatic amino acid profiles (BCAA and AAA respectively) and the metabolic syndrome (MS), and to evaluate the clinical utility of these associations in the diagnostic process.

Methods

Two hundred and sixty three healthy men with MS [MS(+): n = 165] and without MS [MS(−): n = 98] were enrolled in the observational study. Anthropometrical, biochemical, and amino acid measurements were performed. The ability of the BCAA and AAA to discriminate subjects with MS and insulin resistance was tested. Based on logistic discrimination, a multivariate early MS diagnostic model was built, and its discrimination properties were evaluated.

Results

Two functionally independent amino acid clusters were identified. BCAA and phenylalanine differed significantly between MS(+) and MS(−) participants (P = 0.003). These factors were also found to be indicators of MS(+) individuals (AUC: 0.66; 95% CI: 0.5757–0.7469), and correlated with cardiometabolic factors. No statistically significant differences in amino acid concentrations between those with and without insulin resistance were noted, and none of the amino groups were indicators of insulin resistance. The proposed MS multivariate diagnostic model consisted of phenylalanine, insulin, leptin, and adiponectin, and had good discrimination properties [AUC 0.79; 95% CI: 0.7239–0.8646].

Conclusions

MS is associated with selective BCAA and AAA profile disturbances, which could be part of cardiometabolic disease pathogenesis and derive neither directly from insulin sensitivity impairment, nor obesity or muscle mass. The MS diagnostic model developed and described herein should be validated in future studies.



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Common and Uncommon Benign Pancreatic Lesions Mimicking Malignancy: Imaging Update and Review

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Publication date: Available online 26 October 2017
Source:Seminars in Ultrasound, CT and MRI
Author(s): Ulysses S. Torres, Carlos Matsumoto, Augusto Cesar de Macedo Neto, Rogério Pedreschi Caldana, Ângela Hissae Motoyama Caiado, Dario Ariel Tiferes, Gisele Warmbrand, Laiz Laura de Godoy, Giuseppe D′Ippolito
There is a broad range of inflammatory, pseudotumoral and benign lesions that may masquerade as pancreatic malignancies, often representing a challenge to the radiologist. Unawareness of these entities can lead to inadequate differential diagnoses or misdiagnosis, with important prognostic and therapeutic consequences. The purpose of this article is to revisit a spectrum of lesions, varying from common to exceedingly rare non-malignant, that may mimic malignant pancreatic neoplasms on imaging, identifying relevant features that may contribute to reaching the correct diagnosis. Representative cases include focal fatty replacement, intrapancreatic accessory spleen, pancreatic lobulation, lipoma, autoimmune pancreatitis, focal pancreatitis, eosinophilic pancreatitis, groove pancreatitis, hemangioma, intrapancreatic aneurysm, tuberculosis and Castleman′s disease.



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Commentary to ‘Safety and efficacy of the new micromesh-covered stent CGuard™ in patients undergoing carotid artery stenting: early experience from a single centre’

Publication date: Available online 26 October 2017
Source:European Journal of Vascular and Endovascular Surgery
Author(s): Gert J. de Borst




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Response to Dixon et al “Foam soap is not as effective as liquid soap in eliminating hand microbial flora”

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Publication date: Available online 26 October 2017
Source:American Journal of Infection Control
Author(s): John D. Hines, Paul Alper




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Crisaborole Ointment 2%: A Review in Mild to Moderate Atopic Dermatitis

Abstract

Crisaborole ointment 2% (Eucrisa™) is a novel, anti-inflammatory inhibitor of phosphodiesterase 4 (PDE4) that is available in the USA for the topical treatment of mild to moderate atopic dermatitis in patients aged ≥ 2 years. In two short-term (28 days), identically designed, multicentre, phase III studies in this patient population, topical therapy with crisaborole ointment 2% reduced disease severity and pruritus severity compared with vehicle, with the effect established early and sustained over the course of treatment. Improvements in the other signs of atopic dermatitis (erythema, exudation, excoriation, induration/papulation, and lichenification) were also seen. Crisaborole ointment 2% was generally well tolerated in the short-term studies, with its favorable safety profile maintained over the longer term (up to 52 weeks) in a multicentre, extension study. Most treatment-emergent adverse events (TEAEs) were of mild to moderate severity and considered unrelated to the study medication. Moreover, the incidence of application-site pain following short- and longer-term topical therapy with crisaborole ointment 2% was low. In conclusion, crisaborole ointment 2% is an effective and generally well tolerated new topical option for the management of mild to moderate atopic dermatitis in patients aged ≥ 2 years, with the potential to effectively treat this patient population over the longer term without the safety concerns associated with other current topical anti-inflammatory agents.



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CD209 -336A/G Promotor Polymorphism and its Clinical Associations in Sickle cell disease Egyptian Pediatric Patients

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Publication date: Available online 26 October 2017
Source:Hematology/Oncology and Stem Cell Therapy
Author(s): Rasha Abdel-Raouf Afifi, Dina Kamal, Riham El. Sayed, Sherif M.M. Ekladious, Gehan H. Shaheen, Sherif M. Yousry, Rania Elsayed Hussein
ObjectivesTo detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity.MethodsA total of 100 Egyptian children with SCD and 100 Egyptian controls were tested for CD209 A>G polymorphism and were followed up prospectively between June 2012 and December 2014.ResultsComparison of CD209 A>G polymorphism among cases and controls did not show statistically significant difference (p = .742). In addition, comparison of the allelic frequency did not show statistically significant difference (p = .738). Infections occurred more frequently among the heterozygous genotype (AG; 60.5%) and homozygous genotype (GG; 75%) patients than among the wild (AA) genotype (24.1%; p < .001). The use of hydroxyurea treatment was significantly higher among the wild (AA) genotype (47%) than the heterozygous (AG; 21%) and homozygous (GG; 5%) genotypes (p = .003).ConclusionWe found no significant difference between our population of Egyptian SCD cases and controls regarding CD209 A>G polymorphism. Infections occurred more frequently among the heterozygous genotype (AG) and homozygous genotype (GG) patients.



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Cardiac Vagal Control as a Marker of Emotion Regulation in Healthy Adults: A Review

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Publication date: Available online 25 October 2017
Source:Biological Psychology
Author(s): S. Balzarotti, F. Biassoni, B. Colombo, M.R. Ciceri
In the last two decades, a growing body of theory and research has targeted the role of cardiac vagal control (CVC) in emotional responding. This research has either focused on resting CVC (also denoted as cardiac vagal tone) or phasic changes in CVC (also denoted as vagal reactivity) in response to affective stimuli. The present paper is aimed at reporting a review of the papers published between 1996 and 2016, and focused on the results of 135 papers examining cardiac vagal control as a physiological marker of emotion regulation in healthy adults. The review shows that studies have employed a wide array of methodologies and measures, often leading to conflicting results. High resting CVC has been associated with better down-regulation of negative affect, use of adaptive regulatory strategies, and more flexible emotional responding. Concerning phasic changes, research has consistently found decreased CVC in response to stress, while CVC increases have been shown to reflect either self-regulatory efforts or recovery from stress. Despite conflicting results, we conclude that existing literature supports the use of CVC as a noninvasive, objective marker of emotion regulation.



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Psychophysiology of Proactive and Reactive Relational Aggression

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Publication date: Available online 18 October 2017
Source:Biological Psychology
Author(s): Dianna Murray-Close, Leigh Ann Holterman, Nicole L. Breslend, Alexandra Sullivan
This study investigated the joint effects of parasympathetic and sympathetic nervous system reactivity to social and non-social stressors on proactive (i.e., goal-directed, unemotional) and reactive (i.e., emotional, impulsive) functions of relational aggression. Two hundred and forty-seven (Mage=18.77years) participants completed a series of stressor tasks while their sympathetic arousal (i.e., skin conductance) and parasympathetic arousal (i.e., respiratory sinus arrhythmia) were assessed. Participants also provided self-reports of their aggressive behavior. In the standardized social stressor only, physiological reactivity was related to aggression, such that respiratory sinus arrhythmia augmentation predicted proactive relational aggression whereas heightened skin conductance reactivity predicted reactive relational aggression. Finally, in the context of low skin conductance reactivity, respiratory sinus arrhythmia augmentation was related to heightened proactive and reactive aggression, whereas respiratory sinus arrhythmia withdrawal was protective. Results suggest that the benefits hypothesized to accompany respiratory sinus arrhythmia withdrawal may only occur among individuals with low "fight or flight" stress responses. Findings extend research on the physiological indicators of aggression to relational aggression, and highlight the importance of assessing functions of aggression, as well as physiological reactivity to multiple stressors.



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Attend or Defend? Sex Differences in Behavioral, Autonomic, and Respiratory Response Patterns to Emotion-Eliciting Films

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Publication date: Available online 18 October 2017
Source:Biological Psychology
Author(s): Frank H. Wilhelm, Julina A. Rattel, Melanie Wegerer, Michael Liedlgruber, Simon Schweighofer, Sylvia D. Kreibig, Vitaliy Kolodyazhniy, Jens Blechert
Sex differences in emotional reactivity have been studied primarily for negative but less so for positive stimuli; likewise, sex differences in the psychophysiological response-patterning during such stimuli are poorly understood. Thus, the present study examined sex differences in response to negative/positive and high/low arousing films (classified as threat-, loss-, achievement-, and recreation-related, vs. neutral films), while measuring 18 muscular, autonomic, and respiratory parameters. Sex differences emerged for all films, but were most prominent for threat-related films: Despite equivalent valence and arousal ratings, women displayed more facial-muscular and respiratory responding than men and pronounced sympathetic activation (preejection period, other cardiovascular and electrodermal measures), while men showed coactivated sympathetic/parasympathetic responding (including increased respiratory sinus arrhythmia). This indicates a prototypical threat-related defense response in women, while men showed a pattern of sustained orienting, which can be understood as a shift toward less threat proximity in the defense cascade model.



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Parental Perception of Child Weight and Inflammation: Perceived Overweight Is Associated with Higher Child C-Reactive Protein

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Publication date: Available online 17 October 2017
Source:Biological Psychology
Author(s): Angelina R. Sutin, George Rust, Eric Robinson, Michael Daly, Antonio Terracciano
Self-perceived overweight and weight discrimination are associated with inflammation in adulthood. We test whether there is an intergenerational association of parent perception of child overweight on higher levels of child c-reactive protein (CRP), a marker of inflammation implicated in stress. Data were from the National Health and Nutrition Examination Survey 2005-2014 (N=4,988). Parents reported their perception of their child's weight; CRP was assayed from children's blood samples. Children whose parents perceived them as overweight had higher CRP levels than children who were perceived about the right weight; perceived underweight was also associated with higher CRP (F(2,4977)=9.23, p<.001). These associations were independent of the child's objective weight status and waist circumference and held when the sample was limited to children with objective overweight and obesity. These results suggest an intergenerational transfer of the psychological perception of body weight from parents to the inflammatory health of their child.



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Effects of GABA active steroids in the female brain with focus on the premenstrual dysphoric disorder

Abstract

PMDD (premenstrual dysphoric disorder) afflicts 3-5% of women of childbearing age, and is characterized by recurrent negative mood symptoms, e.g. irritability, depression, anxiety and emotional lability during the luteal phase of the menstrual cycle. The etiology of PMDD is unknown, but a temporal association with circulating ovarian steroids, in particular progesterone and its metabolite allopregnanolone, during the luteal phase has been established.

Allopregnanolone is a positive modulator of the GABAA receptor: it is sedative in high concentrations, but may precipitate paradoxical adverse effects on mood at levels corresponding to luteal phase concentrations in susceptible women. Saccadic eye velocity (SEV) is a measure of GABAA receptor sensitivity; in experimental studies of healthy women, intravenous allopregnanolone decreases SEV. Women with PMDD display an altered sensitivity to an intravenous injection of allopregnanolone in comparison with healthy controls in this model.

In fMRI studies, women with PMDD react differently to emotional stimuli in contrast with controls. A consistent finding in PMDD patients is increased amygdala reactivity during the luteal phase. Post-mortem studies in humans have revealed that allopregnanolone concentrations vary across different brain regions, but mean levels in the brain also reflect variations in peripheral serum concentrations. The amygdala processes emotions such as anxiety and aggression, which is interesting since allopregnanolone is detected at high concentrations within the region into which marked increases in blood flow are measured with fMRI following progesterone/allopregnanolone administration.

Allopregnanolone effects are antagonized by its isomer isoallopregnanolone (UC1010), which significantly reduces negative mood symptoms in women with PMDD when administered subcutaneously in the premenstrual phase. This was shown in a randomized, placebo-controlled clinical trial in which the primary outcome was change in symptom scoring on the DRSP (Daily Rating of Severity of Problems): the treatment reduced negative mood scores (p<0.005) as well as total DRSP scores (p<0.01) compared to placebo in women with PMDD.

In conclusion, the underlying studies of this review provide evidence that allopregnanolone is the provoking factor behind the negative mood symptoms in PMDD and that isoallopregnanolone could ameliorate the symptoms due to its ability to antagonize the allopregnanolone effect on the GABAA receptor.

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