Ετικέτες

Πέμπτη 26 Ιανουαρίου 2017

Developing a dedicated Dermatology Service for allogeneic bone marrow transplant recipients

Following allogeneic stem cell transplantation, graft versus host disease (GVHD) is a major cause of morbidity and mortality with the commonest organs affected being the skin and oral mucosa. Clinical presentation of cutaneous GVHD is widely variable and 13/30 patients attending a dedicated GVHD clinic were referred to Dermatologists with a specialist interest in GVHD (1). The British Committee for Standards in Haematology GVHD guidelines recommend organ-specific management and supportive care (2) recognising that early input from a Dermatologist is likely to improve clinical outcomes (3). JACIE 6th Edition standards also recommend access to certified specialist trained Dermatologists (4).

This article is protected by copyright. All rights reserved.



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De Novo Reconstruction of a Hybrid Patella by Staged Fabrication of a Microvascular Bone Transplant with an Osteointegrated Prosthetic Socket

imageSummary: Total patellectomy is sometimes unavoidable but usually results in severely impaired function, pain, and instability in the affected knee. Any patellar prosthetic solutions rely on a certain amount of remaining bone and therefore are not applicable after total patellectomy. Traditionally, reconstruction of a neopatella by avascular or allogeneic bone grafts is hampered by mechanical failure, resorption, or infection. We developed a new, 3-stage approach to reconstruct a hybrid patella composed of a revascularized scapula tip transplant fabricated with a prosthetic socket. The procedure is safe and provides optimal healing and prosthetic osteointegration through viable bone and dynamic stability to the considerable load a patella has to bear in unrestricted mobility. The technique also demonstrates successful integration of orthopedic prosthetic devices into current flap fabrication concepts.

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Oral health: OHRQoL in systemic sclerosis



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New year, new resolution



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Health impacts of Facebook usage and mobile texting among undergraduate dental students: it's time to understand the difference between usage and an excessive use



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Pharmacology: Discontinuation of bisphosphonates



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Focusing on the keystones of modern dentistry



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Oral surgery: Mutilation following MDMA



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The perceptions of dental practitioners of their role as clinical teachers in a UK outreach dental clinic



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Oral medicine: A waste of paper



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Protecting your toothbrush from contamination



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Social media: Professionalism



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Change



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Law and ethics: Out of context



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Laypeople's perceptions of frontal smile esthetics: a systematic review



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Dental education: Unimaginable opportunities



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Awareness of medication related osteonecrosis of the jaws (MRONJ) amongst general dental practitioners



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Dental pathology: Early identification



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Enlightened dentistry



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BAOMS launches enhanced website



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Digitally take control of your surgery



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Honours, awards, appointments



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Accuracy, Yield and Clinical Impact of a Low-Cost HRME in the Early Diagnosis of Esophageal Adenocarcinoma

Condition:   Barrett's Esophagus
Intervention:   Drug: Proflavine, high resolution imaging
Sponsors:   Anandasabapathy, Sharmila, M.D.;   William Marsh Rice University
Recruiting - verified January 2017

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Early Hospice and Palliative Care.

Author: Avanzato, Angela BS, RN
Page: 11


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Mitigating the Effects of Moral Distress.

Author: Kennedy, Maureen Shawn MA, RN, FAAN
Page: 7


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Suicide Awareness.

Author: Cazarian, Stella RN
Page: 11


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Saying Yes.

Author: , Gertha
Page: 11


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Infant Safe Sleep.

Author: M, Lisa-Dawn
Page: 11


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Infant Safe Sleep.

Author: L., Monica
Page: 11


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Proposed Regulations for Long-Term Care Omit Nurse Staffing Mandates.

Author: Sofer, Dalia
Page: 12


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Bipartisan Bills Propose Assistance for Caregivers.

Author: Potera, Carol
Page: 13


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NewsCAP: The emergence of Candida auris in the United States causes concern.

Author:
Page: 13


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NewsCAP: New consensus recommendations issued for enteral nutrition.

Author:
Page: 13


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Nurse Perception of Workplace Safety Affects Patient Care.

Author: Zolot, Joan PA
Page: 14


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NewsCAP: Updated list of known or potential carcinogens includes five viruses.

Author:
Page: 14


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Updated Recommendations for Preventing CVD with Statins.

Author: Zolot, Joan PA
Page: 15


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From the Agencies.

Author:
Page: 16


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Discussing Death over Coffee and Cake: The Emergence of the Death Cafe.

Author: Nelson, Roxanne
Page: 18-19


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NewsCAP: Nurses participated last November in protesting the Dakota Access Pipeline project.

Author:
Page: 15


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AJN On the Cover.

Author: Szulecki, Diane Associate Editor
Page: 17


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AJN On the Web.

Author:
Page: 17


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New Treatment for Soft Tissue Sarcoma.

Author: Aschenbrenner, Diane S. MS, RN
Page: 20


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Serious Adverse Effects of Testosterone Abuse.

Author: Aschenbrenner, Diane S. MS, RN
Page: 20,21


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A photoresponsive and rod-shape nanocarrier: Single wavelength of light triggered photothermal and photodynamic therapy based on AuNRs-capped & Ce6-doped mesoporous silica nanorods

Publication date: April 2017
Source:Biomaterials, Volume 122
Author(s): Qi Sun, Qing You, Xiaojuan Pang, Xiaoxiao Tan, Jinping Wang, Li Liu, Fang Guo, Fengping Tan, Nan Li
Rod-shape nanocarriers have attracted great interest because of their better cell internalization capacity and higher drug loading properties. Besides, the combination of photodynamic therapy (PDT) and photothermal therapy (PTT) holds great promise to overcome respective limitations of the anti-cancer treatment. In this work, we first report Au nanorods-capped and Ce6-doped mesoporous silica nanorods (AuNRs-Ce6-MSNRs) for the single wavelength of near infrared (NIR) light triggered combined phototherapy. AuNRs-Ce6-MSNRs are not only able to generate hyperthermia to perform PTT effect based on the AuNRs, but also can produce singlet oxygen (1O2) for PDT effect based on Ce6 after uncapping of AuNRs under the single NIR wavelength irradiation. In addition, the combined therapy can be dual-imaging guided by taking the photoacoustic (PA) and NIR fluorescence (NIRF) imaging of AuNRs and Ce6, respectively. What's more, by utilizing the special structure of MSNRs, this nanocarrier can serve as a drug delivery platform with high drug loading capacity and enhanced cellular uptake efficiency. The multi-functional nanocomposite is designed to integrate photothermal and photodynamic therapy, in vivo dual-imaging into one system, achieving synergistic anti-tumor effects both in vitro and in vivo.



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Memory and Traumatic Brain Injury

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2
Author(s): Tessa Hart, Angelle Sander




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Editorial Board

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2





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Table of Contents

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2





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Editors' Selections From This Issue: Volume 98 / Number 2 / February 2017

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2





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Relationship between pedometer-based physical activity and physical function in patients with osteoarthritis of the knee: a cross-sectional study

Publication date: Available online 26 January 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Hirotaka Iijima, Naoto Fukutani, Takuya Isho, Yuko Yamamoto, Masakazu Hiraoka, Kazuyuki Miyanobu, Masashi Jinnouchi, Eishi Kaneda, Tomoki Aoyama, Hiroshi Kuroki, Shuichi Matsuda
ObjectiveTo examine the association between pedometer-based ambulatory physical activity (PA) and physical function in patients with knee osteoarthritis (OA).DesignCross-sectional observational study.SettingInstitutional practice.ParticipantsParticipants in orthopaedic clinics (n = 207; age, 56–90 years; 71.5% female) diagnosed with radiographic knee OA (Kellgren/Lawrence [K/L] grade ≥1).InterventionsNot applicable.Main outcome measureAmbulatory PA was objectively measured as steps/day. Physical function was assessed using the Japanese Knee Osteoarthritis Measure (JKOM) functional subcategory, 10-meter walk, timed up and go (TUG), and five-repetition chair stand (5CS) tests.ResultsPatients walking <2500 steps/day had a low level of physical function with a slower gait speed, longer TUG time, and worse JKOM functional score compared with those who walk 2500–4999, 5000–7499, and ≥7500 steps/day adjusted for age, sex, body mass index [BMI], and K/L grade. Ordinal logistic regression analysis revealed that steps/day (continuous) was associated with better physical function adjusted for age, sex, BMI, and K/L grade. These relationships were still robust in sensitivity analyses that included patients with K/L grades ≥2 (n = 140).ConclusionsAlthough increased ambulatory PA had a positive relationship with better physical function, walking <2500 steps/day may be a simple indicator for a decrease in physical function in patients with knee OA among standard PA category. Our findings might be a basis for counseling patients with knee OA about their ambulatory PA and for developing better strategies for improving physical function in sedentary patients with knee OA.



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Masthead

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2





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Longer Versus Shorter Duration of Supervised Rehabilitation After Lung Transplantation: A Randomized Trial

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2
Author(s): Louise M. Fuller, Brenda Button, Ben Tarrant, Ranjana Steward, Lisa Bennett, Greg Snell, Anne E. Holland
ObjectiveTo investigate the effects of a supervised longer- (14wk) versus shorter-duration (7wk) rehabilitation program after lung transplantation (LTX).DesignRandomized controlled trial.SettingOutpatient rehabilitation gym setting.ParticipantsPost-LTX patients aged ≥18 years (N=66; 33 women; mean age, 51±13y) who had undergone either single LTX or bilateral LTX.InterventionOutpatient rehabilitation program consisting of thrice-weekly sessions with cardiovascular training on bike ergometer and treadmill plus upper and lower limb strength training.Main Outcome MeasuresMeasures were taken at baseline, 7 weeks, 14 weeks, and 6 months by assessors who were blinded to group allocation. Functional exercise capacity was measured by the 6-minute walk test (6MWT). Strength of quadriceps and hamstrings was measured on an isokinetic dynamometer and recorded as average peak torque of 6 repetitions for both muscles. Quality of life (QOL) was assessed with the Medical Outcomes Study 36-Item Short-Form Health Survey.ResultsOf the participants, 86% had bilateral LTX and 41% had primary diagnosis of chronic obstructive pulmonary disease. The 6MWT increased in both groups with no significant difference between groups at any time point (mean 6mo 6MWD: short, 590±85m vs long, 568±127m; P=0.5). Similarly, at 6 months, there was no difference between groups in quadriceps average peak torque (mean, 115±38Nm vs 114±40Nm, respectively; P=.59), hamstring average peak torque (57±18Nm vs 52±19Nm, respectively; P=.36), or mental or physical health domains of quality of life.ConclusionsShorter duration (7wk) of rehabilitation achieves comparable outcomes with 14 weeks of supervised rehabilitation for functional exercise capacity, lower limb strength, and quality of life at 6 months after LTX.



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Broadening the Conceptualization of Participation of Persons With Physical Disabilities: A Configurative Review and Recommendations

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2
Author(s): Kathleen A. Martin Ginis, M. Blair Evans, W. Ben Mortenson, Luc Noreau
Within the context of physical disability, participation has typically been conceptualized in terms of one's performance of different roles and activities. This perspective, however, ignores the meanings and satisfactions that a person derives from participating. Without an accepted conceptualization of participation that accounts for people's subjective perceptions and experiences, it is challenging for decision-makers and service providers to design meaningful participation-enhancing services, programs, and policies. Accordingly, our objectives were (1) to conduct a review of definitions and conceptualizations of participation that extend beyond performance and capture people's subjective experiences of participating and (2) to identify key experiential aspects of participation that can be used as a basis for conceptualizing and operationalizing the concept more broadly. The project involved a systematic, configurative review of relevant literature. Ten relevant articles were identified. Information on characteristics associated with experiential aspects of participation was extracted and subjected to a thematic analysis. The following 6 themes emerged: autonomy, belongingness, challenge, engagement, mastery, and meaning. Drawing on these findings, it is recommended that the individual's subjective perceptions of autonomy, belongingness, challenge, engagement, mastery, and meaning associated with participating be incorporated into conceptualizations and operationalizations of the participation construct. This recommendation provides a starting point for clinicians, researchers, and policymakers to conceptualize and measure the participation concept more consistently and more broadly.



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Call for Papers

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2





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Wisdom from a Chair: Thirty Years of Quadriplegia

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2
Author(s): Ruth W. Brannon




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Measurement Characteristics and Clinical Utility of the Urinary Incontinence Quality of Life Scale in People With Incontinence and Multiple Sclerosis

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2
Author(s): Jordan Keller, Lindsay Long, Kristian Nitsch, Jill Smiley




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Information/Education Pages (I/EPs)

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Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2





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Rehabilitation in Multiple Sclerosis: A Systematic Review of Systematic Reviews

Publication date: February 2017
Source:Archives of Physical Medicine and Rehabilitation, Volume 98, Issue 2
Author(s): Fary Khan, Bhasker Amatya
ObjectivesTo systematically evaluate existing evidence from published systematic reviews of clinical trials for the effectiveness of rehabilitation for improving function and participation in persons with multiple sclerosis (MS).Data SourcesA literature search was conducted using medical and health science electronic databases (MEDLINE, EMBASE, CINAHL, PubMed, Cochrane Library) up to January 31, 2016.Study SelectionTwo reviewers independently applied inclusion criteria to select potential systematic reviews assessing the effectiveness of organized rehabilitation for persons with MS. Data were summarized for type of interventions, type of study designs included, outcome domains, method of data synthesis, and findings.Data ExtractionData were extracted by 2 reviewers independently for methodological quality using the Assessment of Multiple Systematic Reviews. Quality of evidence was critically appraised with the Grades of Recommendation, Assessment, Development, and Evaluation.Data SynthesisThirty-nine systematic reviews (one with 2 reports) evaluated best evidence to date. There is "strong" evidence for physical therapy for improved activity and participation, and for exercise-based educational programs for the reduction of patient-reported fatigue. There is "moderate" evidence for multidisciplinary rehabilitation for longer-term gains at the levels of activity (disability) and participation, for cognitive-behavior therapy for the treatment of depression, and for information-provision interventions for improved patient knowledge. There is "limited" evidence for better patient outcomes using psychological and symptom management programs (fatigue, spasticity). For other rehabilitation interventions, the evidence is inconclusive because of limited methodologically robust studies.ConclusionsDespite the range of rehabilitative treatments available for MS, there is a lack of high-quality evidence for many modalities. Further research is needed for effective rehabilitation approaches with appropriate study design, outcome measurement, type and intensity of modalities, and cost-effectiveness of these interventions.



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Implicit activation of the aging stereotype influences effort-related cardiovascular response: The role of incentive

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Publication date: Available online 26 January 2017
Source:International Journal of Psychophysiology
Author(s): Athina Zafeiriou, Guido H.E. Gendolla
Based on previous research on implicit effects on effort-related cardiovascular response and evidence that aging is associated with cognitive difficulties, we tested whether the mere activation of the aging stereotype can systematically influence young individuals' effort-mobilization during cognitive performance. Young participants performed an objectively difficult short-term memory task during which they processed elderly vs. youth primes and expected low vs. high incentive for success. When participants processed elderly primes during the task, we expected cardiovascular response to be weak in the low-incentive condition and strong in the high-incentive condition. Unaffected by incentive, effort in the youth-prime condition should fall in between the two elderly-prime cells. Effects on cardiac pre-ejection period (PEP) and heart rate (HR) largely supported these predictions. The present findings show for the first time that the mere activation of the aging stereotype can systematically influence effort mobilization during cognitive performance—even in young adults.



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New bismuth-containing quadruple therapy in patients infected with Helicobacter pylori: A first Italian experience in clinical practice

Abstract

Background

Rising antibiotic resistance requires the evaluation of new and effective therapies.

Aims

To test the efficacy and safety of the new bismuth-containing quadruple therapy in patients infected with Helicobacter pylori.

Material and Methods

Consecutive H. pylori-positive dyspeptic patients were enrolled, either naïve or with previous failure treatment. Patients were treated with Pylera® (three-in-one capsules containing bismuth subcitrate potassium 140 mg, metronidazole 125 mg, and tetracycline 125 mg) three capsules q.i.d. plus omeprazole 20 mg or esomeprazole 40 mg b.i.d. for 10 days. Eradication was confirmed using an urea breath test (at least 30 days after the end of treatment). Efficacy was assessed by UBT and safety by means of treatment-emergent adverse events.

Results

One hundred and thirty-one patients were included in the study: 42% of patients were naïve, and 58%, with previous failure treatment. H. pylori eradication was achieved in 124 patients (94.7%, 95% confidence intervals (CIs) 89.3-97.8) in ITT population. In the PP population, the percentage was 97.6% (95%, CIs 93.3-99.2). No difference in eradication rate was found either between naïve and previously treated patients (92.7% vs 96.0%, P=.383), or smoking and nonsmoking ones, or in patients taking omeprazole or esomeprazole.

Treatment-emergent adverse events occurred in 35 patients (26.7%, 95% CIs 19.9-34.9). They were mild in all cases except in four, who discontinued the study due to diarrhea (three patients) and diffuse urticarial rush (one patient).

Conclusions

Pylera® achieved a remarkable eradication rate in clinical practice, irrespective if it was used as first treatment or as a rescue therapy. Treatment-emergent adverse events were uncommon generally mild.



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Insights from Ultrahigh Field Imaging in Multiple Sclerosis

Publication date: Available online 26 January 2017
Source:Neuroimaging Clinics of North America
Author(s): Matthew K. Schindler, Pascal Sati, Daniel S. Reich

Teaser

Ultrahigh-field (≥7 T) magnetic resonance (MR) imaging is being used at many leading academic medical centers to study neurologic disorders. The improved spatial resolution and anatomic detail are due to the increase in signal-to-noise and contrast-to-noise ratio at higher magnetic field strengths. Ultrahigh-field MR imaging improves multiple sclerosis (MS) lesion detection, with particular sensitivity to detect cortical lesions. The increase in magnetic susceptibility effects inherent to ultrahigh field can be used to detect pathologic features of MS lesions, including a central vein, potentially useful for diagnostic considerations, and heterogeneity among MS lesions, potentially useful in determining lesion outcomes.


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Signaling of Noncomprehension in Communication Breakdowns in Fragile X Syndrome, Down Syndrome, and Autism Spectrum Disorder

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Publication date: Available online 26 January 2017
Source:Journal of Communication Disorders
Author(s): Gary E. Martin, Jamie Barstein, Jane Hornickel, Sara Matherly, Genna Durante, Molly Losh
The ability to indicate a failure to understand a message is a critical pragmatic (social) language skill for managing communication breakdowns and supporting successful communicative exchanges. The current study examined the ability to signal noncomprehension across different types of confusing message conditions in children and adolescents with fragile X syndrome (FXS), Down syndrome (DS), autism spectrum disorder (ASD), and typical development (TD). Controlling for nonverbal mental age and receptive vocabulary skills, youth with comorbid FXS and ASD and those with DS were less likely than TD controls to signal noncomprehension of confusing messages. Youth with FXS without ASD and those with idiopathic ASD did not differ from controls. No sex differences were detected in any group. Findings contribute to current knowledge of pragmatic profiles in different forms of genetically-based neurodevelopmental disorders associated with intellectual disability, and the role of sex in the expression of such profiles.Learning OutcomesUpon completion of this article, readers will have learned about: (1) the social-communicative profiles of youth with FXS, DS, and ASD, (2) the importance of signaling noncomprehension in response to a confusing message, and (3) the similarities and differences in noncomprehension signaling in youth with FXS (with and without ASD), DS, idiopathic ASD, and TD.



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Merging video coaching and an anthropologic approach to understand health care provider behavior toward hand hygiene protocols

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Publication date: Available online 26 January 2017
Source:American Journal of Infection Control
Author(s): Sophia Boudjema, Clément Tarantini, Patrick Peretti-Watel, Philippe Brouqui
BackgroundWe used videorecordings of routine care to analyze health care providers' deviance from protocols and organized follow-up interviews that were conducted by an anthropologist and a nurse.MethodsAfter consent, health care workers were recorded during routine care by an automatic video remote control. Each participant was invited to watch her or his recorded behaviors on 2 different videos showing routine practices and her or his deviance from protocols, and to comment on them. After this step an in-depth interview based on preestablished guidelines was organized and explanations regarding the observed deviance was discussed. This design was intended to reveal the HCWs' subjectivity; that is, how they perceive hand hygiene issues in their daily routine, what concrete difficulties they face, and how they try to resolve them.ResultsWe selected 43 of 250 videorecordings created during the study, which allowed us to study 15 out of 20 health care professionals. Twenty out of 43 videos showed 1 or more breaches in the hand hygiene protocol. The breaches were frequently linked to glove abuse. Deviance from protocols was explained by the health care workers as the result of an adaptive behavior; that is, facing work constraints that were disconnected from infection control protocols. Professional practices and protocols should be revisited to create simple messages that are adapted to the mandatory needs in a real life clinic environment.



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Editorial Board and Contents

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Publication date: February 2017
Source:Trends in Immunology, Volume 38, Issue 2





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Dapagliflozin, a selective SGLT2 Inhibitor, attenuated cardiac fibrosis by regulating the macrophage polarization via STAT3 signaling in infarcted rat hearts

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Publication date: Available online 26 January 2017
Source:Free Radical Biology and Medicine
Author(s): Tsung-Ming Lee, Nen-Chung Chang, Shinn-Zong Lin
During myocardial infarction, infiltrated macrophages have pivotal roles in cardiac remodeling and delayed M1 toward M2 macrophage phenotype transition is considered one of the major factors for adverse ventricular remodeling. We investigated whether dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, attenuates cardiac fibrosis via regulating macrophage phenotype by a reactive oxygen and nitrogen species (RONS)/STAT3-dependent pathway in postinfarcted rats. Normoglycemic male Wistar rats were subjected to coronary ligation and then randomized to either saline, dapagliflozin (a specific SGLT2 inhibitor), phlorizin (a nonspecific SGLT1/2 inhibitor), dapagliflozin + S3I-201 (a STAT3 inhibitor), or phlorizin + S3I-201 for 4 weeks. There were similar infarct sizes among the infarcted groups at the acute and chronic stages of infarction. At day 3 after infarction, post-infarction was associated with increased levels of superoxide and nitrotyrosine, which can be inhibited by administering either dapagliflozin or phlorizin. SGLT2 inhibitors significantly increased STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels and the percentage of M2 macrophage infiltration. At day 28 after infarction, SGLT2 inhibitors were associated with attenuated myofibroblast infiltration and cardiac fibrosis. Although phlorizin decreased myofibroblast infiltration, the effect of dapagliflozin on attenuated myofibroblast infiltration was significantly higher than phlorizin. The effects of SGLT2 inhibitors on cardiac fibrosis were nullified by adding S3I-201. Furthermore, the effects of dapagliflozin on STAT3 activity and myocardial IL-10 levels can be reversed by 3-morpholinosydnonimine, a peroxynitrite generator. Taken together, these observations provide a novel mechanism of SGLT2 inhibitors-mediated M2 polarization through a RONS-dependent STAT3-mediated pathway and selective SGLT2 inhibitors are more effective in attenuating myofibroblast infiltration during postinfarction remodeling.



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Combined NADPH and the NOX inhibitor apocynin provides greater anti-inflammatory and neuroprotective effects in a mouse model of stroke

Publication date: Available online 26 January 2017
Source:Free Radical Biology and Medicine
Author(s): Yuan-Yuan Qin, Mei Li, Xing Feng, Jian Wang, Lijuan Cao, Xi-Kui Shen, Jieyu Chen, Meiling Sun, Rui Sheng, Feng Han, Zheng-Hong Qin
Our previous study has reported that the pentose phosphate pathway product nicotinamide adenine dinucleotide phosphate (NADPH) protected neurons against ischemia/reperfusion-induced brain injury. NADPH can either act as a co-enzyme to produce GSH or a substrate of NADPH oxidase (NOX) to generate ROS. This study was designed to elucidate the effects of co-treatment with NADPH and NOX inhibitor apocynin on ischemia/reperfusion-induced brain inflammation and neuronal injury. The results showed that both NADPH and apocynin markedly attenuated ischemia/reperfusion-induced increases in the levels of NOX2, NOX4 and ROS. NADPH and apocynin significantly inhibited the phosphorylation and degradation of IκBα, NF-κBp65 nuclear localization, and the expression of NF-κB target gene cyclooxygenase (COX2) and inducible nitric oxide synthase (iNOS). Furthermore, both NADPH and apocynin suppressed the expression of inflammasome proteins including NLRP3 ASC, caspase-1, interleukin (IL)−1β and IL-18 in the ischemic cortex as revealed by Western blot analysis and immunofluorescence. Moreover, all these effects were greatly amplified by combination of NADPH and apocynin. Both NADPH and apocynin significantly reduced infarct volume, improved post-stroke survival, and recovery of neurological functions in mouse model of stroke. Consistently, the combination of NADPH and apocynin produced greater beneficial effects in against ischemic brain damage. These studies suggest that, beyond anti-oxidative effects, NADPH may also have anti-inflammatory effects and combination of NADPH and NOX inhibitors could produce a greater neuroprotective effect in ischemic stroke.

Graphical abstract

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Heme Oxygenase 2 Binds Myristate to Regulate Retrovirus Assembly and TLR4 Signaling

Publication date: Available online 26 January 2017
Source:Cell Host & Microbe
Author(s): Yiping Zhu, Shukun Luo, Yosef Sabo, Cheng Wang, Liang Tong, Stephen P. Goff
N-myristoylation is the covalent attachment of myristic acid to the N terminus of proteins in eukaryotic cells. The matrix domain (MA) of HIV-1 Gag protein is N-myristoylated and plays an important role in virus budding. In screening for host factors that interact with HIV-1 MA, we found that heme oxygenase (HO-2) specifically binds the myristate moiety of Gag. HO-2 was also found to bind TRAM, an adaptor protein for Toll-like receptor 4 (TLR4), and thereby impact both virus replication and cellular inflammatory responses. A crystal structure revealed that HO-2 binds myristate via a hydrophobic channel adjacent to the heme-binding pocket. Inhibiting HO-2 expression, or blocking myristate binding with a heme analog, led to marked increases in virus production. HO-2 deficiency caused hyperresponsive TRAM-dependent TLR4 signaling and hypersensitivity to the TLR4 ligand lipopolysaccharide. Thus, HO-2 is a cellular myristate-binding protein that negatively regulates both virus replication and host inflammatory responses.

Graphical abstract

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Teaser

Zhu et al. identify heme oxygenase 2 (HO-2) as a myristate-binding protein that interacts with an array of myristoylated proteins to negatively regulate their function. HO-2 binds HIV-1 Gag, which inhibits virion production, and TRAM, a key molecule in the LPS-TLR4 signaling pathway, to downregulate inflammatory responses.


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Human Cytomegalovirus Tegument Protein UL82 Inhibits STING-Mediated Signaling to Evade Antiviral Immunity

Publication date: Available online 26 January 2017
Source:Cell Host & Microbe
Author(s): Yu-Zhi Fu, Shan Su, Yi-Qun Gao, Pei-Pei Wang, Zhe-Fu Huang, Ming-Ming Hu, Wei-Wei Luo, Shu Li, Min-Hua Luo, Yan-Yi Wang, Hong-Bing Shu
Recognition of human cytomegalovirus (HCMV) DNA by the cytosolic sensor cGAS initiates STING-dependent innate antiviral responses. HCMV can antagonize host immune responses to promote latency infection. However, it is unknown whether and how HCMV targets the cGAS-STING axis for immune evasion. Here we identified the HCMV tegument protein UL82 as a negative regulator of STING-dependent antiviral responses. UL82 interacted with STING and impaired STING-mediated signaling via two mechanisms. UL82 inhibited the translocation of STING from the ER to perinuclear microsomes by disrupting the STING-iRhom2-TRAPβ translocation complex. UL82 also impaired the recruitment of TBK1 and IRF3 to the STING complex. The levels of downstream antiviral genes induced by UL82-deficient HCMV were higher than those induced by wild-type HCMV. Conversely, wild-type HCMV replicated more efficiently than the UL82-deficient mutant. These findings reveal an important mechanism of immune evasion by HCMV.

Graphical abstract

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Teaser

Whether and how HCMV proteins target the host immune system for evasion is enigmatic. Fu et al. found that HCMV protein UL82 inhibits STING-mediated signaling by impairing its cellular trafficking and complex formation, leading to inhibition of innate antiviral response and immune evasion by HCMV.


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Pseudomonas syringae Type III Effector HopBB1 Promotes Host Transcriptional Repressor Degradation to Regulate Phytohormone Responses and Virulence

Publication date: Available online 26 January 2017
Source:Cell Host & Microbe
Author(s): Li Yang, Paulo José Pereira Lima Teixeira, Surojit Biswas, Omri M. Finkel, Yijian He, Isai Salas-Gonzalez, Marie E. English, Petra Epple, Piotr Mieczkowski, Jeffery L. Dangl
Independently evolved pathogen effectors from three branches of life (ascomycete, eubacteria, and oomycete) converge onto the Arabidopsis TCP14 transcription factor to manipulate host defense. However, the mechanistic basis for defense control via TCP14 regulation is unknown. We demonstrate that TCP14 regulates the plant immune system by transcriptionally repressing a subset of the jasmonic acid (JA) hormone signaling outputs. A previously unstudied Pseudomonas syringae (Psy) type III effector, HopBB1, interacts with TCP14 and targets it to the SCFCOI1 degradation complex by connecting it to the JA signaling repressor JAZ3. Consequently, HopBB1 de-represses the TCP14-regulated subset of JA response genes and promotes pathogen virulence. Thus, HopBB1 fine-tunes host phytohormone crosstalk by precisely manipulating part of the JA regulon to avoid pleiotropic host responses while promoting pathogen proliferation.

Graphical abstract

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Teaser

Yang et al. demonstrate that the Pseudomonas syringae type III effector HopBB1 modulates two negative regulators of plant jasmonic acid (JA) signaling, TCP14 and JAZ3, and "glues" them together for degradation, resulting in precise activation of a subset of JA output responses that promote bacterial virulence.


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Copyright

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1





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Processing of Egomotion-Consistent Optic Flow in the Rhesus Macaque Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The cortical network that processes visual cues to self-motion was characterized with functional magnetic resonance imaging in 3 awake behaving macaques. The experimental protocol was similar to previous human studies in which the responses to a single large optic flow patch were contrasted with responses to an array of 9 similar flow patches. This distinguishes cortical regions where neurons respond to flow in their receptive fields regardless of surrounding motion from those that are sensitive to whether the overall image arises from self-motion. In all 3 animals, significant selectivity for egomotion-consistent flow was found in several areas previously associated with optic flow processing, and notably dorsal middle superior temporal area, ventral intra-parietal area, and VPS. It was also seen in areas 7a (Opt), STPm, FEFsem, FEFsac and in a region of the cingulate sulcus that may be homologous with human area CSv. Selectivity for egomotion-compatible flow was never total but was particularly strong in VPS and putative macaque CSv. Direct comparison of results with the equivalent human studies reveals several commonalities but also some differences.</span>

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Contributors

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1





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Stimulus-Tuned Structure of Correlated fMRI Activity in Human Visual Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Processing units are interconnected in the visual system, where a sensory organ and downstream cortical regions communicate through hierarchical connections, and local sites within the regions communicate through horizontal connections. In such networks, neural activities at local sites are likely to influence one another in complex ways and thus are intricately correlated. Recognizing the functional importance of correlated activity in sensory representation, spontaneous activities have been studied via diverse local or global measures in various time scales. Here, measuring functional magnetic resonance imaging (fMRI) signals in human early visual cortex, we explored systematic patterns that govern the correlated activities arising spontaneously. Specifically, guided by previously identified biases in anatomical connection patterns, we characterized all possible pairs of gray matter sites in 3 relational factors: "retinotopic distance," "cortical distance," and "stimulus tuning similarity." By evaluating and comparing the unique contributions of these factors to the correlated activity, we found that tuning similarity factors overrode distance factors in accounting for the structure of correlated fMRI activity both within and between V1, V2, and V3, irrespective of the presence or degree of visual stimulation. Our findings indicate that the early human visual cortex is intrinsically organized as a network tuned to the stimulus features.</span>

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Contents

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1





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mGluR2 versus mGluR3 Metabotropic Glutamate Receptors in Primate Dorsolateral Prefrontal Cortex: Postsynaptic mGluR3 Strengthen Working Memory Networks

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The newly evolved circuits in layer III of primate dorsolateral prefrontal cortex (dlPFC) generate the neural representations that subserve working memory. These circuits are weakened by increased cAMP-K<sup>+</sup> channel signaling, and are a focus of pathology in schizophrenia, aging, and Alzheimer's disease. Cognitive deficits in these disorders are increasingly associated with insults to mGluR3 metabotropic glutamate receptors, while reductions in mGluR2 appear protective. This has been perplexing, as mGluR3 has been considered glial receptors, and mGluR2 and mGluR3 have been thought to have similar functions, reducing glutamate transmission. We have discovered that, in addition to their astrocytic expression, mGluR3 is concentrated postsynaptically in spine synapses of layer III dlPFC, positioned to strengthen connectivity by inhibiting postsynaptic cAMP-K<sup>+</sup> channel actions. In contrast, mGluR2 is principally presynaptic as expected, with only a minor postsynaptic component. Functionally, increase in the endogenous mGluR3 agonist, N-acetylaspartylglutamate, markedly enhanced dlPFC Delay cell firing during a working memory task via inhibition of cAMP signaling, while the mGluR2 positive allosteric modulator, BINA, produced an inverted-U dose–response on dlPFC Delay cell firing and working memory performance. These data illuminate why insults to mGluR3 would erode cognitive abilities, and support mGluR3 as a novel therapeutic target for higher cognitive disorders.</span>

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Forthcoming Issues

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1





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Connectivity of the Cingulate Sulcus Visual Area (CSv) in the Human Cerebral Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The human cingulate sulcus visual area (CSv) responds selectively to visual and vestibular cues to self-motion. Although it is more selective for visual self-motion cues than any other brain region studied, it is not known whether CSv mediates perception of self-motion. An alternative hypothesis, based on its location, is that it provides sensory information to the motor system for use in guiding locomotion. To evaluate this hypothesis we studied the connectivity pattern of CSv, which is completely unknown, with a combination of diffusion MRI and resting-state functional MRI. Converging results from the 2 approaches suggest that visual drive is provided primarily by areas hV6, pVIP (putative intraparietal cortex) and PIC (posterior insular cortex). A strong connection with the medial portion of the somatosensory cortex, which represents the legs and feet, suggests that CSv may receive locomotion-relevant proprioceptive information as well as visual and vestibular signals. However, the dominant connections of CSv are with specific components of the motor system, in particular the cingulate motor areas and the supplementary motor area. We propose that CSv may provide a previously unknown link between perception and action that serves the online control of locomotion.</span>

http://ift.tt/2jCB8gs

Anesthesiologists in Obstetric Care: Beyond Labor Epidurals and C-Section Care

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Lee A. Fleisher




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Task Context Overrules Object- and Category-Related Representational Content in the Human Parietal Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The dorsal, parietal visual stream is activated when seeing objects, but the exact nature of parietal object representations is still under discussion. Here we test 2 specific hypotheses. First, parietal cortex is biased to host some representations more than others, with a different bias compared with ventral areas. A prime example would be object action representations. Second, parietal cortex forms a general multiple-demand network with frontal areas, showing similar task effects and representational content compared with frontal areas. To differentiate between these hypotheses, we implemented a human neuroimaging study with a stimulus set that dissociates associated object action from object category while manipulating task context to be either action- or category-related. Representations in parietal as well as prefrontal areas represented task-relevant object properties (action representations in the action task), with no sign of the irrelevant object property (category representations in the action task). In contrast, irrelevant object properties were represented in ventral areas. These findings emphasize that human parietal cortex does not preferentially represent particular object properties irrespective of task, but together with frontal areas is part of a multiple-demand and content-rich cortical network representing task-relevant object properties.</span>

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Obstetric Anesthesia

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Onyi C. Onuoha, Robert R. Gaiser




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Transcriptome Analysis Identifies Multifaceted Regulatory Mechanisms Dictating a Genetic Switch from Neuronal Network Establishment to Maintenance During Postnatal Prefrontal Cortex Development

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The prefrontal cortex (PFC) is one of the latest brain regions to mature, which allows the acquisition of complex cognitive abilities through experience. To unravel the underlying gene expression changes during postnatal development, we performed RNA-sequencing (RNA-seq) in the rat medial PFC (mPFC) at five developmental time points from infancy to adulthood, and analyzed the differential expression of protein-coding genes, long intergenic noncoding RNAs (lincRNAs), and alternative exons. We showed that most expression changes occur in infancy, and that the number of differentially expressed genes reduces toward adulthood. We observed 137 differentially expressed lincRNAs and 796 genes showing alternative exon usage during postnatal development. Importantly, we detected a genetic switch from neuronal network establishment in infancy to maintenance of neural networks in adulthood based on gene expression dynamics, involving changes in protein-coding and lincRNA gene expression as well as alternative exon usage. Our gene expression datasets provide insights into the multifaceted transcriptional regulation of the developing PFC. They can be used to study the basic developmental processes of the mPFC and to understand the mechanisms of neurodevelopmental and neuropsychiatric disorders. Our study provides an important contribution to the ongoing efforts to complete the "brain map", and to the understanding of PFC development.</span>

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Embracing the Next Phase in Obstetric Anesthesiology

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Onyi C. Onuoha, Robert R. Gaiser




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Cortical Thickness and Local Gyrification in Children with Developmental Dyslexia

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Developmental dyslexia is frequently associated with atypical brain structure and function within regions of the left hemisphere reading network. To date, few studies have employed surface-based techniques to evaluate cortical thickness and local gyrification in dyslexia. Of the existing cortical thickness studies in children, many are limited by small sample size, variability in dyslexia identification, and the recruitment of prereaders who may or may not develop reading impairment. Further, no known study has assessed local gyrification index (LGI) in dyslexia, which may serve as a sensitive indicator of atypical neurodevelopment. In this study, children with dyslexia (<span style="font-style:italic;">n</span> = 31) and typically decoding peers (<span style="font-style:italic;">n</span> = 45) underwent structural magnetic resonance imaging to assess whole-brain vertex-wise cortical thickness and LGI. Children with dyslexia demonstrated reduced cortical thickness compared with controls within previously identified reading areas including bilateral occipitotemporal and occipitoparietal regions. Compared with controls, children with dyslexia also showed increased gyrification in left occipitotemporal and right superior frontal cortices. The convergence of thinner and more gyrified cortex within the left occipitotemporal region among children with dyslexia may reflect its early temporal role in processing word forms, and highlights the importance of the ventral stream for successful word reading.</span>

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Identification and Management of Obstetric Hemorrhage

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Emily J. Baird

Teaser

Obstetric hemorrhage remains the leading cause of maternal death and severe morbidity worldwide. Although uterine atony is the most common cause of peripartum bleeding, abnormal placentation, coagulation disorders, and genital tract trauma contribute to adverse maternal outcomes. Given the inability to reliably predict patients at high risk for obstetric hemorrhage, all parturients should be considered susceptible, and extreme vigilance must be exercised in the assessment of blood loss and hemodynamic stability during the peripartum period. Obstetric-specific hemorrhage protocols, facilitating the integration and timely escalation of pharmacologic, radiological, surgical, and transfusion interventions, are critical to the successful management of peripartum bleeding.


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MRI Shows that Exhaustion Syndrome Due to Chronic Occupational Stress is Associated with Partially Reversible Cerebral Changes

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The present study investigates the cerebral effects of chronic occupational stress and its possible reversibility. Forty-eight patients with occupational exhaustion syndrome (29 women) and 80 controls (47 women) underwent structural magnetic resonance imaging (MRI) and neuropsychological testing. Forty-four participants (25 patients, 19 controls) also completed a second MRI scan after 1–2 years. Only patients received cognitive therapy. The stressed group at intake had reduced thickness in the right prefrontal cortex (PFC) and left superior temporal gyrus (STG), enlarged amygdala volumes, and reduced caudate volumes. Except for the caudate volume, these abnormalities were more pronounced in females. They were all related to perceived stress, which was similar for both genders. Thickness of the PFC also correlated with an impaired ability to down-modulate negative emotions. Thinning of PFC and reduction of caudate volume normalized in the follow-up. The amygdala enlargement and the left STG thinning remained. Longitudinal changes were not detected among controls. Chronic occupational stress was associated with partially reversible structural abnormalities in key regions for stress processing. These changes were dynamically correlated with the degree of perceived stress, highlighting a possible causal link. They seem more pronounced in women, and could be a substrate for an increased cerebral vulnerability to stress-related psychiatric disorders.</span>

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The Use of Ultrasonography in Obstetric Anesthesia

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Chiraag Talati, Cristian Arzola, Jose C.A. Carvalho

Teaser

This article provides an overview of the use of ultrasonography in obstetric anesthesia. It discusses the indications, benefits, and techniques of using ultrasonography to optimize the delivery of anesthesia and provide safe and efficacious clinical care. More specifically, it discusses the use of ultrasonography to facilitate neuraxial anesthesia, abdominal field blocks, central and peripheral vascular access, as well as the assessment of the lung fields and gastric contents, and identification of the cricothyroid membrane.


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Fine Motor Skill Mediates Visual Memory Ability with Microstructural Neuro-correlates in Cerebellar Peduncles in Prematurely Born Adolescents

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Adolescents born preterm (PT) with no evidence of neonatal brain injury are at risk of deficits in visual memory and fine motor skills that diminish academic performance. The association between these deficits and white matter microstructure is relatively unexplored. We studied 190 PTs with no brain injury and 92 term controls at age 16 years. The Rey–Osterrieth Complex Figure Test (ROCF), the Beery visual-motor integration (VMI), and the Grooved Pegboard Test (GPT) were collected for all participants, while a subset (40 PTs and 40 terms) underwent diffusion-weighted magnetic resonance imaging. PTs performed more poorly than terms on ROCF, VMI, and GPT (all <span style="font-style:italic;">P</span> < 0.01). Mediation analysis showed fine motor skill (GPT score) significantly mediates group difference in ROCF and VMI (all <span style="font-style:italic;">P</span> < 0.001). PTs showed a negative correlation (<span style="font-style:italic;">P</span> < 0.05, corrected) between fractional anisotropy (FA) in the bilateral middle cerebellar peduncles and GPT score, with higher FA correlating to lower (faster task completion) GPT scores, and between FA in the right superior cerebellar peduncle and ROCF scores. PTs also had a positive correlation (<span style="font-style:italic;">P</span> < 0.05, corrected) between VMI and left middle cerebellar peduncle FA. Novel strategies to target fine motor skills and the cerebellum may help PTs reach their full academic potential.</span>

http://ift.tt/2juGmNM

The Rich-Club Organization in Rat Functional Brain Network to Balance Between Communication Cost and Efficiency

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Network analyses of structural connectivity in the brain have highlighted a set of highly connected hubs that are densely interconnected, forming a "rich-club" substrate in diverse species. Here, we demonstrate the existence of rich-club organization in functional brain networks of rats. Densely interconnected rich-club regions are found to be distributed in multiple brain modules, with the majority located within the putative default mode network. Rich-club members exhibit high wiring cost (as measured by connection distance) and high metabolic running cost (as surrogated by cerebral blood flow), which may have evolved to achieve high network communications to support efficient brain functions. Furthermore, by adopting a forepaw electrical stimulation paradigm, we find that the rich-club organization of the rat functional network remains almost the same as in the resting state, whereas path motif analysis reveals significant differences, suggesting the rat brain reorganizes its topological routes by increasing locally oriented shortcuts but reducing rich-club member-involved paths to conserve metabolic running cost during unimodal stimulation. Together, our results suggest that the neuronal system is organized and dynamically operated in an economic way to balance between cost minimization and topological/functional efficiency.</span>

http://ift.tt/2jCF8xh

Obstetric and Anesthetic Approaches to External Cephalic Version

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Stephanie Lim, Jennifer Lucero

Teaser

Breech presentation is the most common abnormal fetal presentation and complicates approximately 3% to 4% of all pregnancies. External cephalic version (ECV) should be recommended to women with a breech singleton pregnancy, if there is no maternal or fetal contraindication. ECV increases the chance of cephalic presentation at the onset of labor and decreases the rate of cesarean delivery by almost 40%. The success rate of ECV is approximately 60%. Review of the risks and benefits for performing an ECV and for both the timing of ECV and the number of attempts should be should be discussed with the patient.


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Cognitive Control Structures in the Imitation Learning of Spatial Sequences and Rhythms—An fMRI Study

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Imitation learning involves the acquisition of novel motor patterns based on action observation (AO). We used event-related functional magnetic resonance imaging to study the imitation learning of spatial sequences and rhythms during AO, motor imagery (MI), and imitative execution in nonmusicians and musicians. While both tasks engaged the fronto-parietal mirror circuit, the spatial sequence task recruited posterior parietal and dorsal premotor regions more strongly. The rhythm task involved an additional network for auditory working memory. This partial dissociation supports the concept of task-specific mirror mechanisms. Two regions of cognitive control were identified: 1) dorsolateral prefrontal cortex (DLPFC) was found to be more strongly activated during MI of novel spatial sequences, which allowed us to extend the 2-level model of imitation learning by Buccino et al. (2004) to spatial sequences. 2) During imitative execution of both tasks, the posterior medial frontal cortex was robustly activated, along with the DLPFC, which suggests that both regions are involved in the cognitive control of imitation learning. The musicians' selective behavioral advantage for rhythm imitation was reflected cortically in enhanced sensory-motor processing during AO and by the absence of practice-related activation differences in DLPFC during rhythm execution.</span>

http://ift.tt/2juGmxg

Should Nitrous Oxide Be Used for Laboring Patients?

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Michael G. Richardson, Brandon M. Lopez, Curtis L. Baysinger

Teaser

Nitrous oxide, long used during labor in Europe, is gaining popularity in the United States. It offers many beneficial attributes, with few drawbacks. Cost, safety, and side effect profiles are favorable. Analgesic effectiveness is highly variable, yet maternal satisfaction is often high among the women who choose to use it. Despite being less effective in treating labor pain than neuraxial analgesic modalities, nitrous oxide serves the needs and preferences of a subset of laboring parturients. Nitrous oxide should, therefore, be considered for inclusion in the repertoire of modalities used to alleviate pain and facilitate effective coping during labor.


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Medial Prefrontal Cortex–Pontine Nuclei Projections Modulate Suboptimal Cue-Induced Associative Motor Learning

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Diverse and powerful mechanisms have evolved to enable organisms to modulate learning and memory under a variety of survival conditions. Cumulative evidence has shown that the prefrontal cortex (PFC) is closely involved in many higher-order cognitive functions. However, when and how the medial PFC (mPFC) modulates associative motor learning remains largely unknown. Here, we show that delay eyeblink conditioning (DEC) with the weak conditioned stimulus (wCS) but not the strong CS (sCS) elicited a significant increase in the levels of c-Fos expression in caudal mPFC. Both optogenetic inhibition and activation of the bilateral caudal mPFC, or its axon terminals at the pontine nucleus (PN) contralateral to the training eye, significantly impaired the acquisition, recent and remote retrieval of DEC with the wCS but not the sCS. However, direct optogenetic activation of the contralateral PN had no significant effect on the acquisition, recent and remote retrieval of DEC. These results are of great importance in understanding the elusive role of the mPFC and its projection to PN in subserving the associative motor learning under suboptimal learning cue.</span>

http://ift.tt/2jCRUfx

Postdural Puncture Headache

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1
Author(s): Robert R. Gaiser

Teaser

Headache after dural puncture is a common complication accompanying neuraxial anesthesia. The proposed cause is loss of cerebrospinal fluid through the puncture into the epidural space. Although obstetric patients are at risk for the development of this headache because of female gender and young age, there is a difference in the obstetric population. Women who deliver by cesarean delivery have a lower incidence of headache after dural puncture compared with those who deliver vaginally. Treatment of postdural puncture headache is an epidural blood patch. Departments should develop protocols for management of accidental dural puncture, including appropriate follow-up and indications for further management.


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Altered Connectivity and Synapse Maturation of the Hippocampal Mossy Fiber Pathway in a Mouse Model of the Fragile X Syndrome

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The Fragile X syndrome (FXS) as the most common monogenetic cause of cognitive impairment and autism indicates how tightly the dysregulation of synapse development is linked to cognitive deficits. Symptoms of FXS include excessive adherence to patterns that point to compromised hippocampal network formation. Surprisingly, one of the most complex hippocampal synapses connecting the dentate gyrus (DG) to CA3 pyramidal neurons has not been analyzed in FXS yet. Intriguingly, we found altered synaptic function between DG and CA3 in a mouse model of FXS (<span style="font-style:italic;">fmr1</span> knockout [KO]) demonstrated by increased mossy fiber-dependent miniature excitatory postsynaptic current (mEPSC) frequency at CA3 pyramidal neurons together with increased connectivity between granule cells and CA3 neurons. This phenotype is accompanied by increased activity of <span style="font-style:italic;">fmr1</span> KO animals in the marble burying task, detecting repetitive and obsessive compulsive behavior. Spine apparatus development and insertion of AMPA receptors is enhanced at postsynaptic thorny excrescences (TEs) in <span style="font-style:italic;">fmr1</span> KO mice. We report age-dependent alterations in TE morphology and in the underlying actin dynamics possibly linked to a dysregulation in profilin1 expression. TEs form detonator synapses guiding CA3 network activity. Thus, alterations described here are likely to contribute substantially to the impairment in hippocampal function and therefore to the pathogenesis of FXS.</span>

http://ift.tt/2juMBB2

Differential Contribution of Low- and High-level Image Content to Eye Movements in Monkeys and Humans

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Oculomotor selection exerts a fundamental impact on our experience of the environment. To better understand the underlying principles, researchers typically rely on behavioral data from humans, and electrophysiological recordings in macaque monkeys. This approach rests on the assumption that the same selection processes are at play in both species. To test this assumption, we compared the viewing behavior of 106 humans and 11 macaques in an unconstrained free-viewing task. Our data-driven clustering analyses revealed distinct human and macaque clusters, indicating species-specific selection strategies. Yet, cross-species predictions were found to be above chance, indicating some level of shared behavior. Analyses relying on computational models of visual saliency indicate that such cross-species commonalities in free viewing are largely due to similar low-level selection mechanisms, with only a small contribution by shared higher level selection mechanisms and with consistent viewing behavior of monkeys being a subset of the consistent viewing behavior of humans.</span>

http://ift.tt/2jCOnO0

Index

Publication date: March 2017
Source:Anesthesiology Clinics, Volume 35, Issue 1





http://ift.tt/2k8QIEb

Representational Similarity Mapping of Distributional Semantics in Left Inferior Frontal, Middle Temporal, and Motor Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Language comprehension engages a distributed network of frontotemporal, parietal, and sensorimotor regions, but it is still unclear how meaning of words and their semantic relationships are represented and processed within these regions and to which degrees lexico-semantic representations differ between regions and semantic types. We used fMRI and representational similarity analysis to relate word-elicited multivoxel patterns to semantic similarity between action and object words. In left inferior frontal (BA 44-45-47), left posterior middle temporal and left precentral cortex, the similarity of brain response patterns reflected semantic similarity among action-related verbs, as well as across lexical classes-between action verbs and tool-related nouns and, to a degree, between action verbs and food nouns, but not between action verbs and animal nouns. Instead, posterior inferior temporal cortex exhibited a reverse response pattern, which reflected the semantic similarity among object-related nouns, but not action-related words. These results show that semantic similarity is encoded by a range of cortical areas, including multimodal association (e.g., anterior inferior frontal, posterior middle temporal) and modality-preferential (premotor) cortex and that the representational geometries in these regions are partly dependent on semantic type, with semantic similarity among action-related words crossing lexical-semantic category boundaries.</span>

http://ift.tt/2juNFos

Proteomic and peptidomic analysis of human sweat with emphasis on proteolysis

Publication date: 23 February 2017
Source:Journal of Proteomics, Volume 155
Author(s): Yijing Yu, Ioannis Prassas, Carla M.J. Muytjens, Eleftherios P. Diamandis
Sweat is produced by eccrine and apocrine glands and represents a biological fluid with established roles in thermo-regulation and host infection defense. The composition of sweat is highly dynamic and alters significantly in various skin and other disorders. Therefore, in-depth profiling of sweat protein composition is expected to augment our understanding of the pathobiology of several skin diseases and may lead to the identification of useful sweat-based disease biomarkers. We here reported an in-depth analysis of the human sweat proteome and peptidome. Sweat was collected from healthy males and healthy females of ages 20–60years, following strenuous exercise. Two sweat pools were prepared (1 for males and 1 for females) and were subjected to sample preparation for mass spectrometric analysis. We identified a total of 861 unique proteins during our proteomic analysis and 32,818 endogenous peptides (corresponding to additional 1067 proteins) from our peptidomics workflow. As expected, the human skin was identified as the most abundant source of sweat proteins and peptides. Several skin proteases and protease inhibitors were identified in human sweat, highlighting the intense proteolytic activity of human skin. The presence of several antimicrobial peptides supports the functional roles of sweat in host defense and innate immunity.SignificanceSweat is a skin-associated biological fluid, secreted by eccrine and apocrine glands, with essential function in body thermo-regulation and host infection defense. In the present study, we performed in-depth profiling of both sweat proteome and peptidome composition. Our data provide the most in-depth characterization of the skin's catalytic network present in sweat. For the first time, we brought to light novel peptides in human sweat that potentially have antimicrobial activity, which highlight the important role of this fluid in innate immunity. All these findings allow us to have a better understanding of the complex web of proteases in skin and may act as a platform for the future discovery of novel skin biomarkers.

Graphical abstract

image


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Editorial Board

Publication date: 10 February 2017
Source:Journal of Proteomics, Volume 154





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Distinct Corticostriatal and Intracortical Pathways Mediate Bilateral Sensory Responses in the Striatum

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Individual striatal neurons integrate somatosensory information from both sides of the body, however, the afferent pathways mediating these bilateral responses are unclear. Whereas ipsilateral corticostriatal projections are prevalent throughout the neocortex, contralateral projections provide sparse input from primary sensory cortices, in contrast to the dense innervation from motor and frontal regions. There is, therefore, an apparent discrepancy between the observed anatomical pathways and the recorded striatal responses. We used simultaneous in vivo whole-cell and extracellular recordings combined with focal cortical silencing, to dissect the afferent pathways underlying bilateral sensory integration in the mouse striatum. We show that unlike direct corticostriatal projections mediating responses to contralateral whisker deflection, responses to ipsilateral stimuli are mediated mainly by intracortical projections from the contralateral somatosensory cortex (S1). The dominant pathway is the callosal projection from contralateral to ipsilateral S1. Our results suggest a functional difference between the cortico-basal ganglia pathways underlying bilateral sensory and motor processes.</span>

http://ift.tt/2kywVyz

An Electrophysiological Index of Perceptual Goodness

<span class="paragraphSection"><div class="boxTitle">Abstract</div>A traditional line of work starting with the Gestalt school has shown that patterns vary in strength and salience; a difference in "Perceptual goodness." The Holographic weight of evidence model quantifies goodness of visual regularities. The key formula states that <span style="font-style:italic;">W = E/N</span>, where <span style="font-style:italic;">E</span> is number of holographic identities in a pattern and <span style="font-style:italic;">N</span> is number of elements. We tested whether <span style="font-style:italic;">W</span> predicts the amplitude of the neural response to regularity in an extrastriate symmetry-sensitive network. We recorded an Event Related Potential (ERP) generated by symmetry called the Sustained Posterior Negativity (SPN). First, we reanalyzed the published work and found that <span style="font-style:italic;">W</span> explained most variance in SPN amplitude. Then in four new studies, we confirmed specific predictions of the holographic model regarding 1) the differential effects of numerosity on reflection and repetition, 2) the similarity between reflection and Glass patterns, 3) multiple symmetries, and 4) symmetry and anti-symmetry. In all cases, the holographic approach predicted SPN amplitude remarkably well; particularly in an early window around 300–400 ms post stimulus onset. Although the holographic model was not conceived as a model of neural processing, it captures many details of the brain response to symmetry.</span>

http://ift.tt/2jkdRir

Developmental Expression Patterns of KCC2 and Functionally Associated Molecules in the Human Brain

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Work on rodents demonstrated that steep upregulation of KCC2, a neuron-specific Cl<sup>−</sup> extruder of cation-chloride cotransporter (CCC) family, commences in supraspinal structures at around birth, leading to establishment of hyperpolarizing GABAergic responses. We describe spatiotemporal expression profiles of the entire CCC family in human brain. KCC2 mRNA was observed already at 10th postconceptional week (PCW) in amygdala, cerebellum, and thalamus. KCC2-immunoreactive (KCC2-ir) neurons were abundant in subplate at 18 PCW. By 25 PCW, numerous subplate and cortical plate neurons became KCC2-ir. The mRNA expression profiles of α- and β-isoforms of Na-K ATPase, which fuels cation-chloride cotransport, as well of tropomyosin receptor kinase B (TrkB), which promotes developmental upregulation of KCC2, were consistent with data from studies on rodents about their interactions with KCC2. Thus, in human brain, expression of KCC2 and its functionally associated proteins begins in early fetal period. Our work facilitates translation of results on CCC functions from animal studies to human and refutes the view that poor efficacy of anticonvulsants in the term human neonate is attributable to the lack of KCC2. We propose that perinatally low threshold for activation of Ca<sup>2+</sup>-dependent protease calpain renders neonates susceptible to downregulation of KCC2 by traumatic events, such as perinatal hypoxia ischemia.</span>

http://ift.tt/2kyyfRS

Extending the Cortical Grasping Network: Pre-supplementary Motor Neuron Activity During Vision and Grasping of Objects

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Grasping relies on a network of parieto-frontal areas lying on the dorsolateral and dorsomedial parts of the hemispheres. However, the initiation and sequencing of voluntary actions also requires the contribution of mesial premotor regions, particularly the pre-supplementary motor area F6. We recorded 233 F6 neurons from 2 monkeys with chronic linear multishank neural probes during reaching–grasping visuomotor tasks. We showed that F6 neurons play a role in the control of forelimb movements and some of them (26%) exhibit visual and/or motor specificity for the target object. Interestingly, area F6 neurons form 2 functionally distinct populations, showing either visually-triggered or movement-related bursts of activity, in contrast to the sustained visual-to-motor activity displayed by ventral premotor area F5 neurons recorded in the same animals and with the same task during previous studies. These findings suggest that F6 plays a role in object grasping and extend existing models of the cortical grasping network.</span>

http://ift.tt/2jkeaKa

The Response of the Left Ventral Attentional System to Invalid Targets and its Implication for the Spatial Neglect Syndrome: a Multivariate fMRI Investigation

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In humans, invalid visual targets that mismatch spatial expectations induced by attentional cues are considered to selectively engage a right hemispheric "reorienting" network that includes the temporal parietal junction (TPJ), the inferior frontal gyrus (IFG), and the medial frontal gyrus (MFG). However, recent findings suggest that this hemispheric dominance is not absolute and that it is rather observed because the TPJ and IFG areas in the left hemisphere are engaged both by invalid and valid cued targets. Because of this, the BOLD response of the left hemisphere to invalid targets is usually cancelled out by the standard "invalid versus valid" contrast used in functional magnetic resonance imaging investigations of spatial attention. Here, we used multivariate pattern recognition analysis (MVPA) to gain finer insight into the role played by the left TPJ and IFG in reorienting to invalid targets. We found that in left TPJ and IFG blood oxygen level-dependent (BOLD) responses to invalid and valid targets were associated to different patterns of neural activity, possibly reflecting the presence of functionally distinct neuronal populations. Pattern segregation was significant at group level, it was present in almost all of the participants to the study and was observed both for targets in the left and right side of space. A control whole-brain MVPA ("Searchlight" analysis) confirmed the results obtained in predefined regions of interest and highlighted that also other areas, that is, superior parietal and frontal-polar cortex, show different patterns of BOLD response to valid and invalid targets. These results confirm and expand previous evidence highlighting the involvement of the left hemisphere in reorienting of visual attention (<a href="#bhv208C11" class="reflinks">Doricchi et al. 2010</a>; <a href="#bhv208C14" class="reflinks">Dragone et al. 2015</a>). These findings suggest that asymmetrical reorienting deficits suffered by right brain damaged patients with left spatial neglect, who have severe impairments in contralesional reorienting and less severe impairments in ipsilesional reorienting, are due to preserved reorienting abilities in the intact left hemisphere.</span>

http://ift.tt/2kyAxQP

Illusory Obesity Triggers Body Dissatisfaction Responses in the Insula and Anterior Cingulate Cortex

<span class="paragraphSection"><div class="boxTitle">Abstract</div>In today's Western society, concerns regarding body size and negative feelings toward one's body are all too common. However, little is known about the neural mechanisms underlying negative feelings toward the body and how they relate to body perception and eating-disorder pathology. Here, we used multisensory illusions to elicit illusory ownership of obese and slim bodies during functional magnetic resonance imaging. The results implicate the anterior insula and the anterior cingulate cortex in the development of negative feelings toward the body through functional interactions with the posterior parietal cortex, which mediates perceived obesity. Moreover, cingulate neural responses were modulated by nonclinical eating-disorder psychopathology and were attenuated in females. These results reveal how perceptual and affective body representations interact in the human brain and may help explain the neurobiological underpinnings of eating-disorder vulnerability in women.</span>

http://ift.tt/2jkiwRv

Evidence and Counterevidence in Motion Perception

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Sensory neurons gather evidence in favor of the specific stimuli to which they are tuned, but they could improve their sensitivity by also taking counterevidence into account. The Bours–Lankheet model for motion detection uses counterevidence that relies on a specific combination of the ON and OFF channels in the early visual system. Specifically, the model detects pairs of flashes that occur separated in space and time. If the flashes have the same contrast polarity, they are interpreted as evidence in favor of the corresponding motion. But if they have opposite contrasts, they are interpreted as evidence against it. This mechanism provides an explanation for reverse-phi (the perceived reversal of an apparent motion stimulus due to periodic contrast-inversions) that is a conceptual departure from the standard explanations of the effect. Here, we investigate this counterevidence mechanism by measuring directional tuning curves of neurons in the primary visual and middle temporal cortex areas of awake, behaving macaques using constant-contrast and inverting-contrast moving dot stimuli. Our electrophysiological data support the Bours–Lankheet model and suggest that the counterevidence computation occurs at an early stage of neural processing not captured by the standard models.</span>

http://ift.tt/2kyIG8f

Hybrid Scheme for Modeling Local Field Potentials from Point-Neuron Networks

<span class="paragraphSection"><div class="boxTitle">Abstract</div>With rapidly advancing multi-electrode recording technology, the local field potential (LFP) has again become a popular measure of neuronal activity in both research and clinical applications. Proper understanding of the LFP requires detailed mathematical modeling incorporating the anatomical and electrophysiological features of neurons near the recording electrode, as well as synaptic inputs from the entire network. Here we propose a hybrid modeling scheme combining efficient point-neuron network models with biophysical principles underlying LFP generation by real neurons. The LFP predictions rely on populations of network-equivalent multicompartment neuron models with layer-specific synaptic connectivity, can be used with an arbitrary number of point-neuron network populations, and allows for a full separation of simulated network dynamics and LFPs. We apply the scheme to a full-scale cortical network model for a ∼1 mm<sup>2</sup> patch of primary visual cortex, predict laminar LFPs for different network states, assess the relative LFP contribution from different laminar populations, and investigate effects of input correlations and neuron density on the LFP. The generic nature of the hybrid scheme and its public implementation in hybridLFPy form the basis for LFP predictions from other and larger point-neuron network models, as well as extensions of the current application with additional biological detail.</span>

http://ift.tt/2jk8PSW

Functional Brain Connectivity Develops Rapidly Around Term Age and Changes Between Vigilance States in the Human Newborn

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Large-scale coupling in neuronal activity is essential in all cognitive functions, but its emergence and functional correlates are poorly known in the human newborn. This study aimed to characterize functional connectivity in the healthy human newborn, and to identify the changes in connectivity related to vigilance states and to maturation during the early postnatal weeks. We recorded active and quiet sleep of 38 sleeping newborn babies using multichannel electroencephalography (EEG) at 2 neonatal time points. Functional connectivity between brain areas was quantified with 3 different metrics: phase–phase correlations, amplitude–amplitude correlations (AACs), and phase–amplitude correlations. All functional connectivity measures changed significantly between vigilance states and matured rapidly after normal birth. The observed changes were frequency-specific, most salient in AAC coupling, and their development was compatible with the known development of structural cortico-cortical connectivity. The present findings support the view that emerging functional connectivity exhibits fundamental differences between sleep states months before the onset of genuine EEG signatures of sleep states. Moreover, our findings also support the idea that early cortical events entail different mechanisms of functional coupling needed to provide endogenous guidance for early activity-dependent development of brain networks.</span>

http://ift.tt/2kyu9cy

The Organization of Mouse and Human Cortico-Hippocampal Networks Estimated by Intrinsic Functional Connectivity

<span class="paragraphSection"><div class="boxTitle">Abstract</div>While the hippocampal memory system has been relatively conserved across mammals, the cerebral cortex has undergone massive expansion. A central question in brain evolution is how cortical development affected the nature of cortical inputs to the hippocampus. To address this question, we compared cortico-hippocampal connectivity using intrinsic functional connectivity MRI (fcMRI) in awake mice and humans. We found that fcMRI recapitulates anatomical connectivity, demonstrating sensory mapping within the mouse parahippocampal region. Moreover, we identified a similar topographical modality-specific organization along the longitudinal axis of the mouse hippocampus, indicating that sensory information arriving at the hippocampus is only partly integrated. Finally, comparing cortico-hippocampal connectivity across species, we discovered preferential hippocampal connectivity of sensory cortical networks in mice compared with preferential connectivity of association cortical networks in humans. Supporting this observation in humans but not in mice, sensory and association cortical networks are connected to spatially distinct subregions within the parahippocampal region. Collectively, these findings indicate that sensory cortical networks are coupled to the mouse but not the human hippocampal memory system, suggesting that the emergence of expanded and new association areas in humans resulted in the rerouting of cortical information flow and dissociation of primary sensory cortices from the hippocampus.</span>

http://ift.tt/2jk8LCN

Enhancement of Working Memory and Task-Related Oscillatory Activity Following Intermittent Theta Burst Stimulation in Healthy Controls

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Noninvasive brain stimulation is increasingly being investigated for the enhancement of cognition, yet current approaches appear to be limited in their degree and duration of effects. The majority of studies to date have delivered stimulation in "standard" ways (i.e., anodal transcranial direct current stimulation or high-frequency transcranial magnetic stimulation). Specialized forms of stimulation, such as theta burst stimulation (TBS), which more closely mimic the brains natural firing patterns may have greater effects on cognitive performance. We report here the findings from the first-ever investigation into the persistent cognitive and electrophysiological effects of intermittent TBS (iTBS) delivered to the left dorsolateral prefrontal cortex. In 19 healthy controls, active iTBS significantly improved performance on an assessment of working memory when compared with sham stimulation across a period of 40 min post stimulation. The behavioral findings were accompanied by increases in task-related fronto-parietal theta sychronization and parietal gamma band power. These results have implications for the role of more specialized stimulation approaches in neuromodulation.</span>

http://ift.tt/2k75iLQ

The Development of Nociceptive Network Activity in the Somatosensory Cortex of Freely Moving Rat Pups

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Cortical perception of noxious stimulation is an essential component of pain experience but it is not known how cortical nociceptive activity emerges during brain development. Here we use continuous telemetric electrocorticogram (ECoG) recording from the primary somatosensory cortex (S1) of awake active rat pups to map functional nociceptive processing in the developing brain over the first 4 weeks of life. Cross-sectional and longitudinal recordings show that baseline S1 ECoG energy increases steadily with age, with a distinctive beta component replaced by a distinctive theta component in week 3. Event-related potentials were evoked by brief noxious hindpaw skin stimulation at all ages tested, confirming the presence of functional nociceptive spinothalamic inputs in S1. However, hindpaw incision, which increases pain sensitivity at all ages, did not increase S1 ECoG energy until week 3. A significant increase in gamma (20–50 Hz) energy occurred in the presence of skin incision at week 3 accompanied by a longer-lasting increase in theta (4–8 Hz) energy at week 4. Continuous ECoG recording demonstrates specific postnatal functional stages in the maturation of S1 cortical nociception. Somatosensory cortical coding of an ongoing pain "state" in awake rat pups becomes apparent between 2 and 4 weeks of age.</span>

http://ift.tt/2jCMmRW

Memory, Decision-Making, and the Ventromedial Prefrontal Cortex (vmPFC): The Roles of Subcallosal and Posterior Orbitofrontal Cortices in Monitoring and Control Processes

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The ventromedial prefrontal cortex (vmPFC) prominently and separately features in neurobiological models of decision-making (e.g., value-encoding) and of memory (e.g., automatic veracity-monitoring). Recent decision-making models propose value judgments that inherently comprise of second-order confidence estimates. These demonstrate quadratic relationships with first-order judgments and are automatically encoded in vmPFC activity. Memory studies use Quantity–Accuracy Profiles to capture similar first-order and second-order meta-mnemonic processes, suggesting convergence across domains. Patients with PFC damage answered general knowledge questionnaires under 2 conditions. During forced report, they chose an answer and rated the probability of it being correct (first-order "monitoring"). During free report, they could choose to volunteer or withhold their previous answers (second-order "control") to maximize performance. We found quadratic relationships between first-order and second-order meta-mnemonic processes; voxel-based lesion-symptom mapping demonstrated that vmPFC damage diminished that relationship. Furthermore, damage to subcallosal vmPFC was specifically associated with impaired monitoring and additional damage to posterior orbitofrontal cortex led to deficient control. In decision-making, these regions typically support valuation and choice, respectively. Persistent spontaneous confabulation (false memory production) confirmed the clinical relevance of these dissociations. Compared with patients with no confabulation history, patients who currently confabulate were impaired on both monitoring and control, whereas former confabulators demonstrated impaired monitoring but intact control.</span>

http://ift.tt/2k6Z4eZ

Age-Dependent D1–D2 Receptor Coactivation in the Lateral Orbitofrontal Cortex Potentiates NMDA Receptors and Facilitates Cognitive Flexibility

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The orbitofrontal cortex (OFC) integrates information about the environment to guide decision-making. Glutamatergic synaptic transmission mediated through <span style="font-style:italic;">N</span>-methyl-<span style="text-transform:lowercase;font-variant:small-caps;">d</span>-aspartate receptors is required for optimal functioning of the OFC. Additionally, abnormal dopamine signaling in this region has been implicated in impulsive behavior and poor cognitive flexibility. Yet, despite the high prevalence of psychostimulants prescribed for attention deficit/hyperactivity disorder, there is little information on how dopamine modulates synaptic transmission in the juvenile or the adult OFC. Using whole-cell patch-clamp recordings in OFC pyramidal neurons, we demonstrated that while dopamine or selective D2-like receptor (D2R) agonists suppress excitatory synaptic transmission of juvenile or adult lateral OFC neurons; in juvenile lateral OFC neurons, higher concentrations of dopamine can target dopamine receptors that couple to a phospholipase C (PLC) signaling pathway to enhance excitatory synaptic transmission. Interfering with the formation of a putative D1R–D2R interaction blocked the potentiation of excitatory synaptic transmission. Furthermore, targeting the putative D1R–D2R complex with a biased agonist, SKF83959, not only enhanced excitatory synaptic transmission in a PLC-dependent manner, but also improved the performance of juvenile rats on a reversal-learning task. Our results demonstrate that dopamine signaling in the lateral OFC differs between juveniles and adults, through potential crosstalk between dopamine receptor subtypes.</span>

http://ift.tt/2jCMkti

Neural Encoding of Self and Another Agent's Goal in the Primate Prefrontal Cortex: Human–Monkey Interactions

<span class="paragraphSection"><div class="boxTitle">Abstract</div>The primate prefrontal cortex represents both past and future goals. To investigate its role in representing the goals of other agents, we designed a nonmatch-to-goal task that involved a human–monkey (H–M) interaction. During each trial, 2 of 4 potential goal objects were presented randomly to the left or right part of a display screen, and the monkey's (or human's) task was to choose the one that did not match the object goal previously chosen. Human and monkey trials were intermixed, and each agent, when acting as observer, was required to monitor the other actor's choice to switch the object goal choice in case it became the actor on the subsequent trial. We found neurons encoding the actor, either the monkey itself or the human, neurons encoding the agent future goal position and neurons encoding the agent previous goal position. In the category of neurons encoding the human future goal, we differentiated between those encoding the future goal of both agents and those encoding only the human agent future goal. While the first one might represent a covert mental simulation in the human trials, the other one could represent a prediction signal of the other's agent choice.</span>

http://ift.tt/2k78jMc

Evidence to Support Screening Women in Their 40s

Publication date: Available online 26 January 2017
Source:Radiologic Clinics of North America
Author(s): Kimberly M. Ray, Elissa R. Price, Bonnie N. Joe

Teaser

A large body of evidence demonstrates a 30% to 50% mortality benefit of screening mammography for women aged 40 to 49. Because of more rapid cancer growth rates in younger women, annual screening is more effective than biennial. Studies indicate that selective screening of women aged 40 to 49 would miss the majority of breast cancers. If implemented, recent US Preventive Services Task Force breast cancer screening guidelines, which recommend against routine screening of women in their 40s, could result in thousands of preventable breast cancer deaths per year. Vigilance is needed to safeguard younger women's access to screening mammography.


http://ift.tt/2jjVQki

Literature Commentary.

In this issue of Journal of Neuro-Ophthalmology, M. Tariq Bhatti, MD and Mark L. Moster, MD, will discuss the following 6 articles: 1. Lee YC, Wang JH, Huang TL, Tsai RK. Increased risk of stroke in patients with nonarteritic anterior ischemic optic neuropathy: a nationwide retrospective cohort study. Am J Ophthalmol. 2016;170:183-189. 2. Ray JG, Vermeulen MJ, Bharatha A, Montanera WJ, Park AL. Association between MRI exposure during pregnancy and fetal and childhood outcomes. JAMA. 2016;316:952-961. 3. Kilduff CL, Casswell EJ, Salam T, Hersh D, Ortiz-Perez S, Ezra D. Use of alleviating maneuvers for periocular facial dystonias. JAMA Ophthalmol. 2016;134:1247-1252. 4. Eklund A, Johannesson G, Johansson E, Holmlund P, Qvarlander S, Ambarki K, Wahlin A, Koskinen LO, Malm J. The pressure difference between eye and brain changes with posture. Ann Neurol. 2016;80:269-276. 5. Cortes-Vicente E, Gallardo E, Martinez MA, Diaz-Manera J, Querol L, Rojas-Garcia R, Illa I. Clinical characteristics of patients with double-seronegative myasthenia gravis and antibodies to cortactin. JAMA Neurology. 2016;73:1099-1104. 6. Kim SH, Zee DS, du Lac S, Kim HJ, Kim JS. Nucleus prepositus hypoglossi lesions produce a unique ocular motor syndrome. Neurology. 2016;87:2026-2033. (C) 2017 by North American Neuro-Ophthalmology Society

http://ift.tt/2juItAX

Pathways for Neuroimaging of Neonatal Stroke

Publication date: Available online 26 January 2017
Source:Pediatric Neurology
Author(s): S. Lee, D.M. Mirsky, L.A. Beslow, C. Amlie-Lefond, A.R. Danehy, L. Lehman, N.V. Stence, A. Vossough, M. Wintermark, M.J. Rivkin
PurposeTo provide consensus-based, suggested imaging protocols to facilitate the accurate and timely diagnosis of a neonate with symptoms concerning for stroke.MethodsThe Writing Group, an international collaboration of pediatric neurologists and neuroradiologists with expertise in perinatal and childhood stroke, participated in a series of pediatric stroke neuroimaging symposia. These discussions, in conjunction with extensive literature review, led to a consensus for imaging protocols to guide practitioners in the diagnosis of neonatal stroke subtypes as defined by the National Institute of Neurological Disorders and Stroke Common Data Elements. The epidemiology, clinical presentation, and associated risk factors for arterial ischemic stroke, cerebral sinovenous thrombosis, and hemorrhagic stroke are reviewed, with a focused discussion regarding the role of neuroimaging for each subtype.ResultsIn a neonate with suspected stroke, magnetic resonance imaging is the preferred modality, given the lack of X-irradiation, superior anatomic resolution, and sensitivity for acute ischemia. Core recommended sequences include diffusion-weighted imaging and apparent diffusion coefficient mapping to diagnose acute ischemia, gradient-recalled echo or susceptibility-weighted imaging to detect intracranial blood and its breakdown products, and T1- and T2- weighted imaging to assess for myelination, extra-axial blood and edema. Magnetic resonance angiography of the brain may be useful to detect vascular abnormalities, with venography if venous sinus thrombosis is suspected. The application of more novel sequences, as well as utility of follow up-imaging, is also discussed.



http://ift.tt/2k8QxbT

Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: the Canadian Pediatric Ischemic Stroke Registry

Publication date: Available online 26 January 2017
Source:Pediatric Neurology
Author(s): Gabrielle A. deVeber, Adam Kirton, Frances A. Booth, Jerome Y. Yager, Elaine C. Wirrell, Ellen Wood, Michael Shevell, Ann-Marie Surmava, Patricia McCusker, M. Patricia Massicotte, Daune MacGregor, E. Athen MacDonald, Brandon Meaney, Simon Levin, Bernard G. Lemieux, Lawrence Jardine, Peter Humphreys, Michèle David, Anthony K.C. Chan, David J. Buckley, Bruce H. Bjornson
BackgroundPediatric arterial ischemic stroke remains incompletely understood. Population-based epidemiological data inform clinical trial design but are scant in this condition. We aimed to determine age-specific epidemiological characteristics of arterial ischemic stroke in neonates (birth - 28 days) and older children (29 days - 18 years).MethodsWe conducted a 16-year, prospective, national population-based study, the Canadian Pediatric Ischemic Stroke Registry across all 16 Canadian acute children's hospitals. We prospectively enrolled children with arterial ischemic stroke from January 1992 - December 2001 and documented disease incidence, presentations, risk factors and treatments. Study outcomes were assessed throughout 2008 including abnormal clinical outcomes (stroke-related death or neurological deficit) and recurrent arterial ischemic stroke or transient ischemic attack.ResultsAmong 1,129 children enrolled with arterial ischemic stroke, stroke incidence was 1.72/100,000/year, (neonates 10.2/100,000 live births). Detailed clinical and radiological information were available for 933 children (232 neonates and 701 older children, 55% male). Predominant clinical presentations were seizures in neonates (88%), focal deficits in older children (77%), and diffuse neurological signs (54%) in both. Among neonates, 44% had no discernible risk factors. In older children, arteriopathy (49% of patients with vascular imaging), cardiac (28%) and prothrombotic disorders (35% of patients tested) predominated. Antithrombotic treatment increased during the study period (p<0.001). Stroke-specific mortality was 5%. Outcomes included neurological deficits in 60% of neonates and 70% of older children. Among neonates, deficits emerged during follow-up in 39%. Overall an initial decreased level of consciousness, non-specific systemic presentation and the presence of stroke risk factors predicted abnormal outcomes. For neonates, predictors were decreased level of consciousness, non-specific systemic presentation, and basal ganglia infarcts. For older children, predictors were initial seizures, non-specific systemic presentation, risk factors and lack of antithrombotic treatment. Recurrent arterial ischemic stroke or transient ischemic attack developed in 12% of older children and was predicted by arteriopathy, presentation without seizures, and lack of antithrombotic treatment. Emerging deficit was predicted by neonatal age at stroke and by cardiac disease.ConclusionsThis national data set provides a population-based disease incidence rate and demonstrates a protective effect of antithrombotic treatment in older children, and frequent long-term emerging deficits in neonates and in children with cardiac disorders. Further clinical trials are required to develop effective age-appropriate treatments for children with acute arterial ischemic stroke.



http://ift.tt/2jWvR46

Activated thrombin-activatable fibrinolysis inhibitor attenuates the angiogenic potential of endothelial cells: potential relevance to the breast tumour microenvironment

Abstract

Thrombin-activatable fibrinolysis inhibitor (TAFI) is a basic carboxypeptidase zymogen present in blood plasma. Proteolytic activation of TAFI by thrombin, thrombin in complex with the endothelial cell cofactor thrombomodulin, or plasmin results in an enzyme (TAFIa) that removes carboxyl-terminal lysine residues from protein and peptide substrates, including cell-surface plasminogen receptors. TAFIa is therefore capable of inhibiting plasminogen activation in the pericellular milieu. Since plasminogen activation has been linked to angiogenesis, TAFIa could therefore have anti-angiogenic properties, and indeed TAFIa has been shown to inhibit endothelial tube formation in a fibrin matrix. In this study, the TAFI pathway was manipulated by providing exogenous TAFI or TAFIa or by adding a potent and specific inhibitor of TAFIa. We found that TAFIa elicited a series of anti-angiogenic responses by endothelial cells, including decreased endothelial cell proliferation, cell invasion, cell migration, tube formation, and collagen degradation. Moreover, TAFIa decreased tube formation and proteolysis in endothelial cell culture grown alone and in co-culture with breast cancer cell lines. In accordance with these findings, inhibition of TAFIa increased secretion of matrix metalloprotease proenzymes by endothelial and breast cancer cells. Finally, treatment of endothelial cells with TAFIa significantly inhibited plasminogen activation. Taken together our results suggest a novel role for TAFI in inhibiting tumour angiogenic behaviors in breast cancer.



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