OtoRhinoLaryngology News: 08/30/17

Τετάρτη 30 Αυγούστου 2017

Determination of ochratoxin A in tissues of wild boar ( Sus scrofa L.) by enzymatic digestion (ED) coupled to high-performance liquid chromatography with a fluorescence detector (HPLC-FLD)

Abstract

Ochratoxin A (OTA) is a secondary toxic metabolite synthesized by Aspergillus or Penicillium species, which can contaminate various crops. The International Agency for Research on Cancer (IARC) classified OTA as a group 2B possible human carcinogen. The aim of the present study was to assess OTA concentrations in tissues of wild boar (Sus scrofa L.) from Tuscany (Italy). Over a period of 2 years, samples of muscle, liver, and kidney from 48 wild boars were collected and concentrations of OTA were determined by enzymatic digestion (ED) coupled to high-performance liquid chromatography with a fluorescence detector (HPLC-FLD). The highest concentrations of OTA were found in the kidneys of the 48 wild boars analyzed. No difference in concentrations was found based on years of collection and sex while a significantly higher OTA concentration was found in the kidney of the young wild boars with respect to the adult one. Monitoring the quality of meat destined for transformation is a priority in order to decrease the possibility of toxin carry-over to humans. The present study showed that contamination of wild boar meat products by OTA represents a potential emerging source of OTA.

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Anaesthetic depth control using closed loop anaesthesia delivery system vs. target controlled infusion in patients with moderate to severe left ventricular systolic dysfunction

To compare the efficacy of anaesthetic depth control using Closed Loop Anaesthesia Delivery System (CLADS) and Target Controlled Infusion (TCI) in patients with moderate to severe left ventricular dysfunction (LVSD).

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Gardasil Vaccination for Recurrent Laryngeal Papillomatosis in Adult Men Second Report: Negative Conversion of HPV in Laryngeal Secretions

In our first report on antibody levels in middle-aged and older men with recurrent laryngeal papillomatosis (RLP), we reported increases in human papillomavirus (HPV) antibody levels similar to those seen in adult women and young men. We posited that HPV antibodies produced in laryngeal mucus by Gardasil would prevent postoperative reinfection in patients with RLP.

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Carotid atherosclerotic plaques standardized uptake values: methodological issues on reproducibility and accuracy

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Evaluation of periprocedural hypersensitivity reactions

Identifying the cause of periprocedural hypersensitivity reactions (HSRs) remains challenging because of the multitude of medications involved. Antibiotics are the most common cause in the United States, whereas neuromuscular blocking agents are most common in Europe.

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Unique heterozygous presentation in an infant with DNA ligase IV syndrome

DNA ligase IV deficiency, or ligase 4 (LIG4) syndrome, is a rare autosomal recessive disorder associated with impaired DNA damage-repair mechanisms, resulting in different clinical presentations. The repair of DNA double-stranded breaks through the nonhomologous end-joining pathway is essential in the early stages of B- and T-cell differentiation as they undergo recombination of variable, diverse, and joining gene segments to generate antigen-specific cell receptors.1 Defects in this pathway, as seen in ligase IV deficiency, lead to an extreme form of severe combined immunodeficiency disease with a lymphocyte phenotype described as T-cell negative, B-cell negative, and natural killer cell positive (T−B−NK+).

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Parental perception of anxiety in children with eosinophilic esophagitis in a tertiary care center

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated, atopic disease characterized by eosinophil infiltration into the esophageal epithelium, resulting in fibrosis and dysfunction.1 During the past 20 years, its prevalence has increased exponentially in children in Western countries up to 50.5 in 10,000, which is similar to that of pediatric inflammatory bowel disease.1 The pediatric population presents with a broad spectrum of symptoms that vary with age. These, in ascending order of age, include feeding difficulty, failure to thrive, acid reflux, vomiting, abdominal pain, dysphagia, and food impaction; in contrast, adults primarily present with dysphagia and food impaction.

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Filaggrin mutations and Molluscum contagiosum skin infection in patients with atopic dermatitis

Although mutations in the filaggrin (FLG) gene have been reported to predispose patients with atopic dermatitis (AD) skin infection susceptibility, to date, the data reported in the literature are still controversial.

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Management around invasive procedures in mastocytosis

Mastocytosis is a chronic hematologic disorder that is characterized by the accumulation of aberrant mast cells and typically involves the skin and/or bone marrow. Patients with mastocytosis are at increased risk of anaphylaxis. Based on theoretical assumptions, medical procedures requiring general anesthesia or radiocontrast media are deemed hazardous for patients with mastocytosis. The objective of this article is to provide a comprehensive overview of the actual risk of iatrogenic anaphylaxis and provide recommendations for daily practice.

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Identification and validation of asthma phenotypes in Chinese population using cluster analysis

Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management.

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Eosinophil-derived neurotoxin as a biomarker for disease severity and relapse in recalcitrant atopic dermatitis

Eosinophils are encountered in many skin diseases, but the role of eosinophils in atopic dermatitis (AD) remains uncertain.

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Clinical and biological response to rituximab treatment in 3 patients with acquired C1-inhibitor deficiency

Acquired C1 inhibitor (C1-INH) deficiency (ACID) is a rare cause of recurrent subcutaneous and submucosal edema without urticaria. The mechanisms of ACID include excessive C1-INH consumption because of an underlying lymphoid malignant tumors (often undiagnosed) or the presence of anti–C1-INH autoantibodies, often with an isolated monoclonal gammopathy or a lymphoproliferative disorder.1–3 The primary therapy for ACID is treatment of the underlying condition; however, management is complex, and all patients must have a medication for acute angioedema.

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Should Oral Corticosteroids Be Used to Treat Demyelinating Optic Neuritis?.

No abstract available

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Surgical Residents Vulnerable to Malpractice Claims

Malpractice claims involving surgical residents during a 10-year period were frequently decided in favor of the plaintiff and associated with a median $900,000 payout.
Medscape Medical News

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Should Oral Corticosteroids Be Used to Treat Demyelinating Optic Neuritis?.

No abstract available

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The Effect of Atorvastatin on Vascular Function and Structure in Young Adult Survivors of Childhood Cancer: A Randomized, Placebo-Controlled Pilot Clinical Trial

Journal of Adolescent and Young Adult Oncology , Vol. 0, No. 0.

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Robot-Assisted Training of Arm and Hand Movement Shows Functional Improvements for Incomplete Cervical Spinal Cord Injury.

Objective: The aim of the study was to demonstrate the feasibility, tolerability, and effectiveness of robotic-assisted arm training in incomplete chronic tetraplegia. Design: Pretest/posttest/follow-up was conducted. Ten individuals with chronic cervical spinal cord injury were enrolled. Participants performed single degree-of-freedom exercise of upper limbs at an intensity of 3-hr per session for 3 times a week for 4 wks with MAHI Exo-II. Arm and hand function tests (Jebsen-Taylor Hand Function Test, Action Research Arm Test), strength of upper limb (upper limb motor score, grip, and pinch strength), and independence in daily living activities (Spinal Cord Independence Measure II) were performed at baseline, end of training, and 6 mos later. Results: After 12 sessions of training, improvements in arm and hand functions were observed. Jebsen-Taylor Hand Function Test (0.14 [0.04]-0.21 [0.07] items/sec, P = 0.04), Action Research Arm Test (30.7 [3.8]-34.3 [4], P = 0.02), American Spinal Injury Association upper limb motor score (31.5 [2.3]-34 [2.3], P = 0.04) grip (9.7 [3.8]-12 [4.3] lb, P = 0.02), and pinch strength (4.5 [1.1]-5.7 [1.2] lb, P = 0.01) resulted in significant increases. Some gains were maintained at 6 mos. No change in Spinal Cord Independence Measure II scores and no adverse events were observed. Conclusions: Results from this pilot study suggest that repetitive training of arm movements with MAHI Exo-II exoskeleton is safe and has potential to be an adjunct treatment modality in rehabilitation of persons with spinal cord injury with mild to moderate impaired arm functions. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Effectiveness of a Group Physiotherapy Intervention in Nontraumatic, Inoperable Painful Shoulder: A Randomized Clinical Trial.

Purpose: The aim of the study was to assess the effectiveness of a group intervention in painful shoulder. Design: This was a two-arm controlled clinical trial with a 5-wk follow-up and 1:1 allocation ratio with pretreatment and posttreatment assessments in a Spanish hospital in 2015-2016. This study comprised 74 patients with nontraumatic, inoperable painful shoulder. Patients were randomized into two groups: (1) in intervention, patients underwent group rehabilitation exercises supervised by a physical therapist and (2) in control, patients performed the same exercises as the intervention group but in their own home. The main variables were the differences preintervention and postintervention between scores on the visual analog scale, Constant-Murley scale, and Disabilities of the Arm, Shoulder and Hand scale. The mean differences in the main variables were compared between the two interventions (t test). Registration code is NCT02541279 ( clinicaltrials.gov). Results: Differences were found in favor of the intervention group: (1) visual analog scale = -0.1 (P = 0.723), (2) Constant-Murley = 4.1 (P = 0.085), and (3) Disabilities of the Arm, Shoulder and Hand = 14.7 (P

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On ciprofloxacin concentration in chronic rhinosinusitis

Publication date: Available online 30 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): José Gameiro dos Santos, Rosário Figueirinhas, José P. Liberal, João C. Almeida, Joana Sousa, Amílcar Falcão, Corália Vicente, João Paço, Cecília A. Sousa
ObjectiveConsidering that all the evidence indicates that chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are distinct entities, the aim of this study was to compare the concentrations obtained in plasma and in sinonasal mucosa with oral and nasal topical ciprofloxacin, in patients with and without nasal polyps, without evaluating the effectiveness of the use of an antibiotic.MethodsProspective clinical study with single-blind randomization. The population consisted of patients with chronic rhinosinusitis with eligible for endonasal surgery, over 18 years old. It took place between January 2010 and December 2014. A single preoperative dose of ciprofloxacin (oral or nasal topic- spray, gel or drops) was given and samples of plasma and nasal mucosa (inferior turbinate, middle turbinate, ethmoid and maxillary sinus) were collected prior to surgery. The plasma and mucosal ciprofloxacin concentrations were assayed with high performance liquid chromatography (HPLC) with fluorescence detection (FD).ResultsThe oral ciprofloxacin achieved better mucosal concentrations but had a significant plasmatic expression in all patients. None of the topical formulations achieved measurable ciprofloxacin plasmatic levels. Among the topical formulations, the gel had the best mucosal results, despite the existence of polyposis.

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Encuesta sobre el conocimiento en la indicación de implantes cocleares para el tratamiento de la hipoacusia en España

Publication date: Available online 30 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Manuel Manrique, Ángel Ramos, Beatriz Pradel, Carlos Cenjor, Diego Calavia, Constantino Morera
IntroducciónEste trabajo pretende analizar el conocimiento del especialista en Otorrinolaringología en España sobre los criterios de indicación de los implantes cocleares (IC) y, según los resultados, considerar si es necesario implementar medidas de formación dirigidas a mejorar el conocimiento en esta área.Material y métodosSe diseña un cuestionario dirigido a conocer el nivel de conocimiento sobre la indicación de IC en personas con hipoacusia. Este cuestionario recogía información demográfica de los encuestados y conocimientos sobre aspectos como indicaciones convencionales y emergentes de los IC, características técnicas de los IC y resultados en la población implantada.ResultadosUn total de 222 especialistas españoles en Otorrinolaringología respondieron el cuestionario (10,29% de la muestra encuestada).ConclusionesUn 50% de los encuestados mostraron unos conocimientos medios-altos sobre IC. Datos epidemiológicos sugieren que un alto porcentaje de adultos con sorderas poslocutivas candidatos a un IC no son referidos para tratamiento. El desconocimiento de los criterios para la indicación de IC por parte de los especialistas en Otorrinolaringología puede contribuir a una inadecuada orientación de los pacientes potencialmente candidatos a un IC. Las mayores deficiencias se encontraron en las indicaciones más emergentes de un IC. Dentro de los profesionales de la Otorrinolaringología los mayores conocimientos sobre IC se concentraron en aquellos que trabajaban en hospitales terciarios, especializados en Otología y Otoneurología, y desempeñaban su actividad laboral en el sector público y privado. Este estudio sugiere la conveniencia de incrementar acciones formativas sobre IC en los profesionales de la Otorrinolaringología, especialmente para otorrinolaringólogos generales.IntroductionThis study aims to analyse the knowledge of cochlear implant (CI) candidacy criteria of otorhinolaryngology specialists in Spain, and from the results, consider whether it is necessary to implement training measures aimed at improving knowledge in this area.Material and methodsA questionnaire was designed for measuring the level of knowledge of cochlear implant candidacy criteria (CI) in people with hearing loss. The questionnaire collected the demographic data of the respondents and their knowledge on the conventional and emergency indications for CI, technical characteristics of CI and results in the implanted population.ResultsA total of 222 Spanish specialists in otorhinolaryngology answered the questionnaire (10.29% of the sample surveyed).ConclusionsThe 50% of all respondents showed a medium-high knowledge about CI. Epidemiological data suggest that a high percentage of adults with postlocutive deafness and candidates for a CI are not referred for treatment. The lack of knowledge about the criteria for the indication of CI by otorhinolaryngology specialists may contribute to inadequate guidance of patients who are potential candidates for CI. The greatest shortcomings are found in the most emergency indications for a CI. Among otorhinolaryngology professionals, the greatest knowledge about CI is found in those who work in tertiary hospitals in the areas of otology and otoneurology, either in the public or private sector. This study suggests that training on CI should be increased for otorhinolaryngology professionals, especially for general otorhinolaryngologists.

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Maxillary hydatid cyst

Publication date: Available online 30 August 2017
Source:Acta Otorrinolaringológica Española
Author(s): Satvinder Singh Bakshi, Roopa Urs

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Squamoid Morules in the Pseudoinvasive Foci of Colonic Polyp Morphologically Mimic Invasive Carcinoma

Publication date: Available online 30 August 2017
Source:Human Pathology
Author(s): Hee Eun Lee, Vishal S. Chandan, Chung-Ta Lee, Tsung-Teh Wu
Colorectal adenomas can show focal squamous differentiation or squamoid morules. We describe histologic findings of squamoid morules in the pseudoinvasive foci of colorectal polyps mimicking invasive carcinoma. Five colonic polyps with squamoid morules in the pseudoinvasive foci were collected. Histologic review and immunostains for cytokeratin (CK) 5/6, p63, synaptophysin, and chromogranin were performed on cases with squamoid morules. Forty-seven consecutive colorectal polyps with pseudoinvasion, none of which showed squamoid morules by histology review, and their clinicopathologic features were compared with the cases containing squamoid morules. Cases with squamoid morules more frequently occurred in younger patients (P=.047) and located in right colon (P=.027) than those without squamoid morules. Diagnosis of the polyps included tubular/tubulovillous adenoma with low-grade (with squamoid morules, n=3; vs without squamoid morules, n=29) or high-grade dysplasia (n=2 vs n=15) and sessile serrated adenoma (none vs n=3). Squamoid morules formed nodules protruding into the lumen of glandular structure or partially replaced adenomatous glands without forming a discrete nodule. They also presented as solid nests showing a well-formed morular structure around the bottom of adenomatous glands or myxoinflammatory stroma. Importantly, squamoid morules often formed a pseudocribriform or solid nest sitting in the stroma of pseudoinvasive foci. All cases (n=4) showed CK5/6 positivity and p63 negativity in squamoid morules. Three and 1 of 4 cases showed focal positivity for synaptophysin and chromogranin, respectively, in squamoid morules. Squamoid morules in colonic adenomatous polyps can mimic invasive carcinoma when present in the pseudoinvasive foci. Pathologists should be aware of its presence.

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Multicentric visceral epithelioid hemangioendothelioma, with extremity dermal deposits, unusual late recurrence on the nasal bridge and TFE3 gene rearrangement

Publication date: Available online 30 August 2017
Source:Human Pathology
Author(s): Khin Thway, Thomas Mentzel, Conal M Perrett, Eduardo Calonje
Epithelioid hemangioendothelioma (EHE) is a malignant neoplasm with vascular differentiation that most frequently occurs within soft tissues, bone, lung and liver. It is histologically typified by epithelioid or spindle cells present singly or in cords or clusters, many with cytoplasmic vacuoles that can contain intraluminal erythrocytes (in keeping with primitive vascular differentiation), within myxohyaline or sclerotic matrix. Up to 50% present with synchronous lesions as multifocal disease. The WWTR1–CAMTA1 fusion has been demonstrated in EHEs at a variety of sites and is considered to represent its genetic hallmark. We describe a case of EHE in a patient who initially presented with multiple liver and pulmonary deposits, was found to have a soft tissue lesion in the foot, and then presented with further lesions on the nasal bridge and the arm approximately six years after initial presentation. Interestingly, the case showed diffuse CAMTA1 expression but negative TFE3 immunohistochemically, but in contrast showed TFE3 gene rearrangement with fluorescence in situ hybridization but no evidence of WWTR1-CAMTA1 translocation. The clinical behavior of EHE is unpredictable, and this case highlights unusual anatomic, immunohistochemical and molecular cytogenetic findings. Characterization of the genetics of EHE is important as targeted therapies towards products of the specific WWTR1–CAMTA1 gene fusion may have an impact in the near future.

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Interleukin-8 and nuclear factor kappa B are increased and positively correlated in myelodysplastic syndrome

Abstract

The pathogenesis of myelodysplastic syndromes (MDS) is complex and depends on the interaction between aberrant hematopoietic cells and their microenvironment, probably including aberrations in cytokines and their signaling pathways. To evaluate interleukin-8 (IL-8) plasma levels and nuclear factor kappa B (NF-kB) in patients with MDS and to test possible correlation between IL-8 and NF-Kb, a total of 45 individuals were analyzed: 25 consecutive adult de novo MDS patients and 20 sex and age-matched healthy elderly volunteers. IL-8 analysis was performed by ELISA and activity of NF-kB by chemiluminescent assay. MDS patients showed higher level of IL-8 when compared to controls (p = 0.006). Patients aged 75 and above showed even higher levels (p = 0.035). NF-kB activity was significantly elevated in MDS patients when compared to controls (p < 0.0001) and higher in patients older than 75 years (p = 0.047). NF-kB activity was associated with higher serum ferritin (p = 0.042) and higher percentage of blasts (p = 0.028). A significant positive correlation between IL-8 and NF-kB was demonstrated (r = 0.480; p = 0.015). Many pathways involved in pathophysiology of MDS have been recently described, suggesting that an inflammatory process may act as a pathogenic driver. In this study, significantly elevated levels of IL-8 and NF-kB were demonstrated in MDS patients, with positive association of NF-kB with some markers of poor prognosis. A positive correlation between IL-8 and NF-kB suggests they cooperate as part of a complex networking of immune and inflammatory factors involved in MDS.

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Efficacy of a Surfactant-based Wound Dressing on Biofilm Control

Abstract

The aim of this study was to evaluate the efficacy of both a non-antimicrobial and antimicrobial (1% silver sulfadiazine - SSD) surfactant-based wound dressing in the control of Pseudomonas aeruginosa, Enterococcus sp, Staphylococcus epidermidis, Staphylococcus aureus and meticillin-resistant S. aureus (MRSA) biofilms. Anti-biofilm efficacy was evaluated in numerous adapted American Standards for Testing and Materials (ASTM) standard biofilm models and other bespoke biofilm models. The ASTM standard models employed included the MBEC biofilm model (ASTM E2799) and the CDC biofilm reactor model (ASTM 2871). Such bespoke biofilm models included the filter biofilm model and the chamberslide biofilm model. Results showed complete kill of microorganisms within a biofilm using the antimicrobial surfactant-based wound dressing. Interestingly, the non-antimicrobial surfactant-based dressing could disrupt existing biofilms by causing biofilm detachment. Prior to biofilm detachment, we demonstrated, using confocal laser scanning microscopy (CLSM), the dispersive effect of the non-antimicrobial surfactant-based wound dressing on the biofilm within 10 minutes of treatment. Furthermore, the non-antimicrobial surfactant-based wound dressing caused an increase in microbial flocculation/aggregation, important for microbial concentration. In conclusion, this non-antimicrobial surfactant-based wound dressing leads to the effective detachment and dispersion of in vitro biofilms. The use of surfactant-based wound dressings in a clinical setting may help to disrupt existing biofilm from wound tissue and may increase the action of antimicrobial treatment. This article is protected by copyright. All rights reserved.

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The Wound-QoL Questionnaire on Quality of Life in Chronic Wounds is Highly Reliable

Abstract

The Wound-QoL questionnaire has been tested in a previous study, indicating that the instrument is a reliable and valid measurement for the assessment of HRQoL in chronic wounds. The aim of this study was to examine the test-retest reliability of the Wound-QoL. Patients were asked to complete the Wound-QoL twice within 3-7 days. Next to descriptive statistics, internal consistency was determined. Test re-test reliability was calculated with the intraclass correlation coefficient. The data showed ICCs between 0.79 and 0.86, which can be considered evidence of excellent reliability. Another indicator of very good reliability, high internal consistency of both global score and subscale scores were found. The availability of the Wound-QoL provides a step forward in allowing measurement of the HRQoL in chronic wounds. The instrument is fit for use to measure outcomes in clinical trials and as well to assess treatment outcomes in routine practice. This article is protected by copyright. All rights reserved.

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Status of Wound Management in Korea

Abstract

In spite of a period of intense economic, social, and political hardship following the Korean War, the Republic of Korea has made great strides in economic growth over the past half century, and also remarkable progress in the medical field. However, wound research has been slow to take off in South Korea. Meanwhile, as is the case in many countries in Western Europe and North America, South Korea is seeing a steady increase in its aged population. The growth in the geriatric population has in turn brought on more cases of chronic wounds. Though South Korea only began to recognize the importance of wound management in the early 2000s, it was fortunate enough to have sophisticated related industries, such as biotechnology and information technology, and brilliant, industrious, and eager wound researchers, contributing to rapid development of the field. The country has particular strengths in research for innovative cell-based treatments and products for managing wounds. Notwithstanding government policy ill-equipped to sufficiently support such advancement, better communication between experts and public officials will no doubt bring forth even more achievements in this very promising field. It is in this context that this article aims to summarize current wound management practices, research, training, product development, and government policies regarding wound management in South Korea as of the year 2017. This article is protected by copyright. All rights reserved.

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Galectin-1 from conditioned medium of three-dimensional culture of adipose-derived stem cells accelerates migration and proliferation of human keratinocytes and fibroblasts

ABSTRACT

Keratinocytes and fibroblasts cells play important roles in the skin-wound healing process and are the cell types activated by trauma. Activated cells participate in epithelialization, granulation, scar-tissue formation, wound remodeling, and angiogenesis via a series of cellular activities including migration and proliferation. Previous studies reported that the conditioned medium (CM) of adipose-derived stem cells (ADSCs) stimulated the migration and proliferation of cell types involved in the skin-wound healing process; however, these studies only show ADSC-CM effects that were obtained using 2-dimensional (2D) culture. Recently, 3-dimensional (3D) culture has been considered as a more physiologically appropriate system than 2D culture for ADSC cultures; therefore, ADSC-CM was collected from 3D culture (ADSC-CM-3D) and compared with ADSC-CM from 2D culture (ADSC-CM-2D) to investigate the effects on the migration and proliferation of human keratinocytes (HaCaTs) and fibroblasts. The migrations of the HaCaT cells and fibroblasts were significantly higher with ADSC-CM-3D compared with the 2D culture; similarly, the proliferation of HaCaT cells was also highly stimulated by ADSC-CM-3D. Proteomic analyses of the ADSC-CM revealed that collagens and actins were highly expressed in the 3D-culture system. Chitinase 3-like 1 (CHI3L1), tissue inhibitor of metalloproteinases (TIMP), and galectin-1 were specifically expressed only in ADSC-CM-3D. Especially, through antibody neutralization, galectin-1 in ADSC-CM-3D was found to be an important factor for the migration of human keratinocytes. Therefore, these results suggest that ADSC-CM-3D was more effective in the wound healing than ADSC-CM-2D, and galectin-1 in ADSC-CM-3D was could be a promising option for skin-wound healing. Furthermore, the differential expressions of several ADSC-CM proteins between the 2D- and 3D-culture systems may be used as basic information for the development of efficient wound-healing strategies. This article is protected by copyright. All rights reserved.

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Evidence-based injury prediction data for the water temperature and duration of exposure for clinically relevant deep dermal scald injuries

Abstract

Deep dermal burn injuries require extensive medical care, however, the water temperatures and durations of exposure that result in a severe scald injury are unknown. This study used a porcine burn model to investigate the time and temperature threshold for clinically relevant deep dermal injuries for both immersion (long duration) and spill/splash (short duration) scald events. Scald wounds were created on the flanks of anaesthetised juvenile Large White pigs (27kgs). Acute tissue injury evaluations performed at 1 hour and days 1, 3 and 7 post-burn (16 pigs) included: wound examination, biopsies and Laser Doppler Imaging. Up to 20 burn combinations were tested including: 50 to 60°C water for 1 to 10 minutes (immersion); and 60 to 90°C water for 5 seconds (spill/splash). Burn conditions demonstrating mid-to-deep dermal damage histologically were followed for 21 days to assess time to re-epithelialize (8 pigs). Histologically, depth of damage increased until day 3 post-burn. Damage to ≥ 75% of the depth of dermis was associated with burns taking longer than 3 weeks to fully re-epithelialize. For spill/splash (5 second) scalds, water at ≥ 75°C showed damage to mid-dermis or deeper by day 3, however only burns from water ≥ 85°C were not re-epithelialized by day 21. For immersion scalds of equivalent duration, water at 55°C caused significantly deeper dermal damage than 50°C (p<0.05) at day 3. Immersion scalds which were not fully re-epithelialized by day 21 included: 50°C for > 10 minutes; 55°C for 5 minutes; 60°C for 60 seconds; 70°C for > 15 seconds. This research provides valuable evidence-based injury prediction data which can be used to inform future burn injury prevention guidelines/legislation to reduce the risk of severe scald injuries and support medicolegal opinions for cases where an inflicted mechanism of injury is alleged. This article is protected by copyright. All rights reserved.

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Profiling of Glycan Alterations in Regrowing Limb Tissues of Cynops orientalis

Abstract

Glycans are known to play important roles in molecular recognition, cell-cell adhesion, molecular trafficking, receptor activation and signal transduction during development and regeneration. Despite numerous investigations of regenerating salamander limbs, global analysis of the precise variation of glycans during the limb regeneration process has received little attention. Here, we have used lectin microarrays and lectin histochemistry to analyze the alterations and distribution of glycans during the early stages leading to blastema formation during Cynops orientalis limb regeneration in response to limb amputation. Compared with the control group, analysis at several time points (3, 7, and 14 days post-amputation) using microarrays containing 37 lectins showed that limb tissues expressed significantly different complements of glycans recognized by 9 different lectins. Post-amputation limb tissues showed higher expression of two glycan structures recognized by the lectins STL and LTL and lower expression of seven glycan structures recognized by PHA-E, MAL-I, SNA, UEA-I, PHA-E+L, VVA and GNA. We also observed significant changes in glycans specifically at 7 days post-amputation, including higher binding capacity by WFA, GSL-I and NPA and lower binding capacity by PNA, HHL, ConA, LCA, GSL-II, and PWM. Next, we validated our lectin microarray data by using lectin histochemistry in limb tissues. Glycans recognized by STL and GNA showed similar changes in signal intensity to those found in the lectin microarrays, with STL staining in the cytoplasm and GNA in the cytoplasm and nucleus. Our findings are the first report of significant post-amputation changes in glycans in limb tissues and suggest that those glycans perform potentially important functions during the early stages of C. orientalis limb regeneration. This article is protected by copyright. All rights reserved.

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Understanding Hearing and Hearing Loss in Children With Down Syndrome

Purpose

This study evaluated the prevalence of permanent and transient hearing loss, the use of hearing aids as a recommendation, and middle ear dysfunction in children with Down syndrome (DS) through a large multiage and ethnically diverse sample, using current audiologic testing practices.

Method

Retrospective analysis of data collected on 308 children with DS (168 boys, 140 girls; average age = 5.99 ± 4.88 years) who received an audiological evaluation during 2013 as part of their medical care at a large pediatric hospital.

Results

Permanent hearing loss was identified in 24.9% of the children, among whom bilateral (75.4%) and conductive (33.3%) hearing losses occurred most often. Of children with DS, 22%–30% experienced a transient hearing loss, with a high incidence of middle ear pathologies from infancy until early adulthood. There were no statistical differences between ethnicity and permanent/transient hearing loss diagnosis. Twenty-three percent were current hearing aid users or had them recommended in a treatment plan.

Conclusions

The prevalence of hearing loss and abnormal middle ear status is high in the pediatric population with DS. Audiologic evaluations should follow the American Academy of Pediatrics practice guidelines to monitor this high-risk population, and amplification should be considered as an appropriate intervention option if repeated audiologic examinations reveal hearing loss.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_AJA-17-0010/2653279/Understanding-Hearing-and-Hearing-Loss-in-Children

Factors related with colorectal and stomach cancer screening practice among disease-free lung cancer survivors in Korea

Abstract

Background

Lung cancer survivors are more likely to develop colorectal and stomach cancer than the general population. However, little is known about the current status of gastrointestinal cancer screening practices and related factors among lung cancer survivors.

Methods

We enrolled 829 disease-free lung cancer survivors ≥40 years of age, who had been treated at two hospitals from 2001 to 2006. The patients completed a questionnaire that included stomach and colorectal cancer screening after lung cancer treatment, as well as other sociodemographic variables.

Results

Among lung cancer survivors, correlations with stomach and colorectal screening recommendations were 22.7 and 25.8%, respectively. Of these, 40.7% reported receiving physician advice to screen for second primary cancer (SPC). Those who were recommended for further screening for other cancers were more likely to receive stomach cancer screening [adjusted odds ratios (aOR) = 1.63, 95% confidence interval (CI), 1.16–2.30] and colorectal cancer screening [aOR = 1.37, 95% CI, 0.99–1.90]. Less-educated lung cancer survivors were less likely to have stomach and colorectal cancer screenings.

Conclusions

Lack of a physician's advice for SPC screening and lower educational status had negative impact on the gastrointestinal cancer screening rates of lung cancer survivors.

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Spatial and temporal epithelial ovarian cancer cell heterogeneity impacts Maraba virus oncolytic potential

Abstract

Background

Epithelial ovarian cancer exhibits extensive interpatient and intratumoral heterogeneity, which can hinder successful treatment strategies. Herein, we investigated the efficacy of an emerging oncolytic, Maraba virus (MRBV), in an in vitro model of ovarian tumour heterogeneity.

Methods

Four ovarian high-grade serous cancer (HGSC) cell lines were isolated and established from a single patient at four points during disease progression. Limiting-dilution subcloning generated seven additional subclone lines to assess intratumoral heterogeneity. MRBV entry and oncolytic efficacy were assessed among all 11 cell lines. Low-density receptor (LDLR) expression, conditioned media treatments and co-cultures were performed to determine factors impacting MRBV oncolysis.

Results

Temporal and intratumoral heterogeneity identified two subpopulations of cells: one that was highly sensitive to MRBV, and another set which exhibited 1000-fold reduced susceptibility to MRBV-mediated oncolysis. We explored both intracellular and extracellular mechanisms influencing sensitivity to MRBV and identified that LDLR can partially mediate MRBV infection. LDLR expression, however, was not the singular determinant of sensitivity to MRBV among the HGSC cell lines and subclones. We verified that there were no apparent extracellular factors, such as type I interferon responses, contributing to MRBV resistance. However, direct cell-cell contact by co-culture of MRBV-resistant subclones with sensitive cells restored virus infection and oncolytic killing of mixed population.

Conclusions

Our data is the first to demonstrate differential efficacy of an oncolytic virus in the context of both spatial and temporal heterogeneity of HGSC cells and to evaluate whether it will constitute a barrier to effective viral oncolytic therapy.

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LINE-1 hypermethylation in white blood cell DNA is associated with high-grade cervical intraepithelial neoplasia

Abstract

Background

Long Interspersed Nuclear Elements-1 (LINEs-1) methylation from white blood cells (WBCs) DNA has been proposed as biomarker associated with different types of cancer. The aim of the present study was to investigate the degree of WBCs LINE-1 methylation, according to high-risk Human Papilloma Virus (hrHPV) status in a healthy population, and the association with high-grade Cervical Intraepithelial Neoplasia (CIN2+) in hrHPV positive women.

Methods

Women with abnormal cervical cells were enrolled and classified by histological diagnosis and hrHPV infection. A structured questionnaire was used to obtain information on socio-demographic variables and lifestyle factors. LINE-1 methylation level in WBCs was measured by pyrosequencing-based methylation analysis after bisulfite conversion.

Results

Among 252 women diagnosed with normal cervical epithelium, with regard to LINE-1 methylation level no significant difference was observed between hrHPV positive and hrHPV negative women, also adjusting for known risk factors of infection. The association between WBCs LINE-1 methylation and CIN2+ status was analyzed in hrHPV positive women. The median value of LINE-1 methylation levels was higher in cases (CIN2+) than in controls (75.00% versus 73.17%; p = 0.002). For a one-unit increase in LINE-1 methylation level, the odds of being diagnosed with CIN2+ increased by 10%, adjusting for known factors related to LINE-1 methylation (adjOR: 1.10; 95% CI:1.01–1.20; p = 0.032). The Receiver-Operating Characteristic (ROC) curve analysis identified the cut-off value of 73.8% as the best threshold to separate cases from controls (sensitivity: 63.4% and specificity: 61.8%).

Conclusions

LINE-1 methylation status in WBCs DNA may represent a cost-effective and tissue-accessible biomarker for high-grade CIN in hrHPV positive women. However, LINE-1 hypermethylation cannot be considered specific for cervical cancer (CC) and a model based solely on LINE-1 methylation levels has limited performance. Further investigations are necessary to propose and validate a novel methylation biomarker panel, based on LINE-1 methylation and other differentially methylated regions, for the screening of women at risk of CC.

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Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy

Abstract

Background

Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.

Methods

Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.

Results

A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease.

Conclusions

CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT.

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A cross-cultural convergent parallel mixed methods study of what makes a cancer-related symptom or functional health problem clinically important

Abstract

Objective

In this study we investigated what makes a symptom or functional impairment clinically important, that is, relevant for a patient to discuss with a health care professional (HCP). This is the first part of an EORTC Quality of Life Group project focusing on the development of thresholds for clinical importance for the EORTC QLQ-C30 questionnaire and its corresponding computer-adaptive version.

Methods

We conducted interviews with cancer patients and HCPs in six European countries. Participants were asked to name aspects of a symptom or problem that make it clinically important, and to provide importance ratings for a predefined set of aspects (e.g. need for help, limitations of daily functioning).

Results

We conducted interviews with 83 cancer patients (mean age: 60.3y; 50.6% men) and 67 HCPs. Participants related clinical importance to limitations of everyday life (patients: 65.1%, HCPs: 77.6%), the emotional impact of a symptom/problem (patients: 53.0%, HCPs 64.2%), and duration/frequency (patients: 51.8%, HCPs: 49.3%). In the patient sample, importance ratings were highest for worries by partner or family, limitations in everyday life and need for help from the medical staff. HCPs rated limitations in everyday life and need for help from the medical staff to be most important.

Conclusions

Limitations in everyday life, need for (medical) help, and emotional impact on the patient or family/partner were found to be relevant aspects of clinical importance. Based on these findings we will define anchor items for the development of thresholds for clinical importance for the EORTC measures in a Europe-wide field study.

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Frontmatter

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: i-iii

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Standard body mass index reference data of prepubescent diabetic Egyptian children

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 909-915

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Frequency and risk factors of depression in type 1 diabetes in a developing country

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 917-922

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Association of obesity and health related quality of life in Iranian children and adolescents: the Weight Disorders Survey of the CASPIAN-IV study

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 923-929

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Association between urinary phthalates and metabolic abnormalities in obese Thai children and adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 931-938

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A pilot study of the effect of human breast milk on urinary metabolome analysis in infants

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 939-946

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Assessment of the correlation between the atherogenic index of plasma and cardiometabolic risk factors in children and adolescents: might it be superior to the TG/HDL-C ratio?

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 947-955

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Cardiovascular and metabolic risk in pediatric patients with congenital adrenal hyperplasia due to 21 hydroxylase deficiency

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 957-966

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Application of povidone-iodine at delivery significantly increases maternal urinary iodine but not neonatal thyrotropin in an area with iodine sufficiency

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 967-972

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Influence of topical iodine-containing antiseptics used during delivery on recall rate of congenital hypothyroidism screening program

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 973-978

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Applying targeted next generation sequencing to dried blood spot specimens from suspicious cases identified by tandem mass spectrometry-based newborn screening

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 979-988

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Initial patient choice of a growth hormone device improves child and adolescent adherence to and therapeutic effects of growth hormone replacement therapy

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 989-993

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An occult ectopic parathyroid adenoma in a pediatric patient: a case report and management algorithm

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 995-999

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Fetal goitrous hypothyroidism treated by intra-amniotic levothyroxine administration: case report and review of the literature

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 1001-1005

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Carotid intima media thickness in a girl with sitosterolemia carrying a homozygous mutation in the ABCG5 gene

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 1007-1011

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Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 9
Pages: 1013-1017

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Modified Stem Cells Deliver Chemotherapy to Metastatic Tumors

Researchers have used modified stem cells to deliver a cancer drug selectively to metastatic breast cancer tumors in mice. The stem cells target metastatic tumors by homing in on the stiff environment that typically surrounds them.

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Use of low-dose radioiodine ablation for Graves’ orbitopathy: results of a pilot, perspective study in a small series of patients

Abstract

Objective

Elimination of thyroid antigens by total thyroid ablation (TTA), namely, thyroidectomy followed by radioiodine, may be beneficial for Graves' Orbitopathy (GO). TTA is usually performed with a ¹³¹I dose of 30 mCi. In Italy, this dose must be followed by a 24-h protected hospitalization, with increase in the waiting lists. In contrast, a 15 mCi dose can be given without hospitalization and with lower costs. Here, we investigated whether a lower dose of radioiodine can be used to ablate thyroid remnants in patients with GO, after thyroidectomy.

Methods

The study was performed in two small groups of consecutive thyroidectomized patients (six patients per group) with Graves' hyperthyroidism and GO. Patients underwent ablation with either 15 or 30 mCi of ¹³¹I following treatment with recombinant human TSH (rhTSH). The primary outcome was rhTSH-stimulated serum thyroglobulin (Tg) at 6 months. The secondary outcome was baseline Tg at 6 months.

Results

Baseline Tg and rhTSH-stimulated Tg after at 6 months did not differ between two groups, suggesting a similar extent of ablation. rhTSH-stimulated Tg was reduced significantly compared with rhTSH-stimulated Tg at ablation in both groups. GO outcome following treatment with intravenous glucocorticoids did not differ between the two groups.

Conclusions

Our findings may provide a preliminary basis for the use of a 15 mCi dose of radioiodine upon rhTSH stimulation in thyroidectomized patients with Graves' hyperthyroidism and GO.

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Use of low-dose radioiodine ablation for Graves’ orbitopathy: results of a pilot, perspective study in a small series of patients

Abstract

Objective

Methods

Results

Conclusions

Our findings may provide a preliminary basis for the use of a 15 mCi dose of radioiodine upon rhTSH stimulation in thyroidectomized patients with Graves' hyperthyroidism and GO.

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Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients

Abstract

A large subset of oropharyngeal squamous cell carcinomas (OPSCCs) is associated with HPV infection and has better outcome than non-viral-related tumors. Various malignancies also carry a role for TLRs, key activators of inflammation and innate immunity. We examined the expression of TLRs in OPSCC, and their association with HPV status and treatment outcome. TLR 5, 7, 9, and p16 were studied by immunohistochemistry and HPV status was detected with in situ hybridization in 202 tumors of consecutively treated OPSCC patients using tissue microarray method. The relations between TLR expression and HPV status, p16 expression, clinicopathological factors, and survival were analyzed. TLR 5, 7, and 9 expression patterns differed between HPV-positive and -negative tumors, and they were statistically significantly associated with history of smoking, heavy drinking, tumor site, grade, size (T), metastasis (N), and stage. Moreover, in HPV-positive tumors the expression of TLR 5 and 7 correlated with tumor recurrence. After adjustment, among HPV-positive OPSCC patients, high TLR 5 and low TLR 7 expression were associated with poor disease-specific survival. Our results indicate that TLR 5 and 7 may have a role in the prognostication of HPV-positive OPSCC, however, further studies are needed to clarify the comprehensive role of these TLRs in OPSCC.

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Three-dimensional CT angiography of anatomic variations in the pulmonary arterial tree

Abstract

Purpose

Anatomic variations of the pulmonary arterial tree can cause technical difficulties during pulmonary lobectomy in general and video-assisted thoracic surgery (VATS). Using CT angiography and 3D reconstruction, we sought to identify anatomic variations of the pulmonary arterial tree and assess their respective frequencies.

Methods

We retrospectively studied 88 pulmonary arterial trees in 44 patients having undergone VATS lobectomy for lung cancer over an 18-month period in Amiens University Hospital's Department of Thoracic Surgery. Each CT angiography with 3D reconstruction of the pulmonary arterial tree was performed by two experienced operators, according to a standardized procedure.

Results

On the right side, the upper lobe was supplied with blood by a mediastinal artery in 100% of cases and by one or more fissural arteries in 88.6%. The middle lobe was usually supplied by two arteries (54.5%). The upper segment of the right lower lobe was usually supplied by a single artery (90.9%). We identified 11 variations in the vasculature of the basal segments. On the left side, the upper lobe was supplied by four arteries in 50% of cases, three culminal arteries (50%), and a fissural lingular artery (77.3%). The upper segment of the left lower lobe was usually supplied by a single artery (65.9%). We identified 15 anatomic variations in the vasculature of the basal segments. We observed that the origin of the apical artery of the right lower lobe was proximal to the origin of the middle lobe artery in 38.6% of cases. The origin of the apical artery of the left lower lobe artery was proximal to the origin of the lingular fissural artery in 65.9% of cases.

Conclusion

The findings of the present CT angiography/3D reconstruction study agreed with the reference works on the anatomy of the pulmonary arterial tree and defined the frequency of anatomic variations. It is essential to assess the anatomy of the pulmonary arterial tree before VATS lobectomy.

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3D printing the pterygopalatine fossa: a negative space model of a complex structure

Abstract

Purpose

The pterygopalatine fossa is one of the most complex anatomical regions to understand. It is poorly visualized in cadaveric dissection and most textbooks rely on schematic depictions. We describe our approach to creating a low-cost, 3D model of the pterygopalatine fossa, including its associated canals and foramina, using an affordable "desktop" 3D printer.

Methods

We used open source software to create a volume render of the pterygopalatine fossa from axial slices of a head computerised tomography scan. These data were then exported to a 3D printer to produce an anatomically accurate model.

Results

The resulting 'negative space' model of the pterygopalatine fossa provides a useful and innovative aid for understanding the complex anatomical relationships of the pterygopalatine fossa.

Conclusion

This model was designed primarily for medical students; however, it will also be of interest to postgraduates in ENT, ophthalmology, neurosurgery, and radiology. The technical process described may be replicated by other departments wishing to develop their own anatomical models whilst incurring minimal costs.

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Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients

Abstract

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Effects of capacity limits, memory loss, and sound type in change deafness

Abstract

Change deafness, the inability to notice changes to auditory scenes, has the potential to provide insights about sound perception in busy situations typical of everyday life. We determined the extent to which change deafness to sounds is due to the capacity of processing multiple sounds and the loss of memory for sounds over time. We also determined whether these processing limitations work differently for varying types of sounds within a scene. Auditory scenes composed of naturalistic sounds, spectrally dynamic unrecognizable sounds, tones, and noise rhythms were presented in a change-detection task. On each trial, two scenes were presented that were same or different. We manipulated the number of sounds within each scene to measure memory capacity and the silent interval between scenes to measure memory loss. For all sounds, change detection was worse as scene size increased, demonstrating the importance of capacity limits. Change detection to the natural sounds did not deteriorate much as the interval between scenes increased up to 2,000 ms, but it did deteriorate substantially with longer intervals. For artificial sounds, in contrast, change-detection performance suffered even for very short intervals. The results suggest that change detection is generally limited by capacity, regardless of sound type, but that auditory memory is more enduring for sounds with naturalistic acoustic structures.

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How humans react to changing rewards during visual foraging

Abstract

Much is known about the speed and accuracy of search in single-target search tasks, but less attention has been devoted to understanding search in multiple-target foraging tasks. These tasks raise and answer important questions about how individuals decide to terminate searches in cases in which the number of targets in each display is unknown. Even when asked to find every target, individuals quit before exhaustively searching a display. Because a failure to notice targets can have profound effects (e.g., missing a malignant tumor in an X-ray), it is important to develop strategies that could limit such errors. Here, we explored the impact of different reward patterns on these failures. In the Neutral condition, reward for finding a target was constant over time. In the Increasing condition, reward increased for each successive target in a display, penalizing early departure from a display. In the Decreasing condition, reward decreased for each successive target in a display. The experimental results demonstrate that observers will forage for longer (and find more targets) when the value of successive targets increases (and the opposite when value decreases). The data indicate that observers were learning to utilize knowledge of the reward pattern and to forage optimally over the course of the experiment. Simulation results further revealed that human behavior could be modeled with a variant of Charnov's Marginal Value Theorem (MVT) (Charnov, 1976) that includes roles for reward and learning.

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Toll-like receptor 5 and 7 expression may impact prognosis of HPV-positive oropharyngeal squamous cell carcinoma patients

Abstract

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Training Peer Partners to Use a Speech-Generating Device With Classmates With Autism Spectrum Disorder: Exploring Communication Outcomes Across Preschool Contexts

Purpose

This study examined effects of a peer-mediated intervention that provided training on the use of a speech-generating device for preschoolers with severe autism spectrum disorder (ASD) and peer partners.

Method

Effects were examined using a multiple probe design across 3 children with ASD and limited to no verbal skills. Three peers without disabilities were taught to Stay, Play, and Talk using a GoTalk 4+ (Attainment Company) and were then paired up with a classmate with ASD in classroom social activities. Measures included rates of communication acts, communication mode and function, reciprocity, and engagement with peers.

Results

Following peer training, intervention effects were replicated across 3 peers, who all demonstrated an increased level and upward trend in communication acts to their classmates with ASD. Outcomes also revealed moderate intervention effects and increased levels of peer-directed communication for 3 children with ASD in classroom centers. Additional analyses revealed higher rates of communication in the added context of preferred toys and snack. The children with ASD also demonstrated improved communication reciprocity and peer engagement.

Conclusions

Results provide preliminary evidence on the benefits of combining peer-mediated and speech-generating device interventions to improve children's communication. Furthermore, it appears that preferred contexts are likely to facilitate greater communication and social engagement with peers.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-L-17-0049/2653179/Training-Peer-Partners-to-Use-a-SpeechGenerating

Distributed Training Enhances Implicit Sequence Acquisition in Children With Specific Language Impairment

Purpose

This study explored the effects of 2 different training structures on the implicit acquisition of a sequence in a serial reaction time (SRT) task in children with and without specific language impairment (SLI).

Method

All of the children underwent 3 training sessions, followed by a retention session 2 weeks after the last session. In the massed-training condition, the 3 training sessions were in immediate succession on 1 day, whereas in the distributed-training condition, the 3 training sessions were spread over a 1-week period in an expanding schedule format.

Results

Statistical analyses showed that the children with normal language were unaffected by the training conditions, performing the SRT task similarly in both training conditions. The children with SLI, however, were affected by the training structure, performing the SRT task better when the training sessions were spaced over time rather than clustered on 1 day.

Conclusion

This study demonstrated that although intensive training does not increase learning in children with SLI, distributing training sessions over time does increase learning. The implications of these results on the learning abilities of children with SLI are discussed, as are the mechanisms involved in massed versus distributed learning.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://article/doi/10.1044/2017_JSLHR-L-16-0146/2653205/Distributed-Training-Enhances-Implicit-Sequence

Cancer-related risk factors and incidence of major cancers by race, gender and region; analysis of the NIH-AARP diet and health study

Abstract

Background

Racial disparities in the incidence of major cancers may be attributed to differences in the prevalence of established, modifiable risk factors such as obesity, smoking, physical activity and diet.

Methods

Data from a prospective cohort of 566,398 adults aged 50–71 years, 19,677 African-American and 450,623 Whites, was analyzed. Baseline data on cancer-related risk factors such as smoking, alcohol, physical activity and dietary patterns were used to create an individual adherence score. Differences in adherence by race, gender and geographic region were assessed using descriptive statistics, and Cox proportional hazards models were used to determine the association between adherence and cancer incidence.

Results

Only 1.5% of study participants were adherent to all five cancer-related risk factor guidelines, with marked race-, gender- and regional differences in adherence overall. Compared with participants who were fully adherent to all five cancer risk factor criteria, those adherent to one or less had a 76% increased risk of any cancer incidence (HR: 1.76, 95% CI: 1.70 – 1.82), 38% increased risk of breast cancer (HR: 1.38, 95% CI: 1.25 – 1.52), and doubled the risk of colorectal cancer (HR: 2.06, 95% CI: 1.84 – 2.29). However, risk of prostate cancer was lower among participants adherent to one or less compared with those who were fully adherent (HR: 0.79, 95% CI: 0.75 – 0.85). The proportion of cancer incident cases attributable to low adherence was higher among African-Americans compared with Whites for all cancers (21% vs. 19%), and highest for colorectal cancer (25%) regardless of race.

Conclusion

Racial differences in the proportion of cancer incidence attributable to low adherence suggests unique opportunities for targeted cancer prevention strategies that may help eliminate racial disparities in cancer burden among older US adults.

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Chemoradiotherapy versus surgery followed by postoperative radiotherapy in tonsil cancer: Korean Radiation Oncology Group (KROG) study

Abstract

Background

Treatment of tonsil cancer, a subset of oropahryngeal cancer, varies between surgery and radiotherapy. Well-designed studies in tonsil cancer have been rare and it is still controversial which treatment is optimal. This study aimed to assess the outcome and failure patterns in tonsil cancer patients treated with either approaches.

Methods

We retrospectively reviewed medical records of 586 patients with tonsil cancer, treated between 1998 and 2010 at 16 hospitals in Korea. Two hundred and one patients received radiotherapy and chemotherapy (CRT), while 385 patients received surgery followed by radiotherapy and/or chemotherapy (SRT). Compared with the SRT group, patients receiving CRT were older, with more advanced T stage and received higher radiotherapy dose given by intensity modulation techniques. Overall survival (OS), disease-free survival (DFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and clinicopathologic factors were analyzed.

Results

At follow-up, the 5-year OS, DFS, LRRFS and DMFS rates in the CRT group were 82, 78, 89, and 94%, respectively, and in the SRT group were 81, 73, 87, and 89%, respectively. Old age, current smoking, poor performance status, advanced T stage, nodal involvement, and induction chemotherapy were associated with poor OS. Induction chemotherapy had a negative prognostic impact on OS in both treatment groups (p = 0.001 and p = 0.033 in the CRT and SRT groups, respectively).

Conclusions

In our multicenter, retrospective study of tonsil cancer patients, the combined use of radiotherapy and chemotherapy resulted in comparable oncologic outcome to surgery followed by postoperative radiotherapy, despite higher-risk patients having been treated with the definitive radiotherapy. Induction chemotherapy approaches combined with either surgery or definitive radiotherapy were associated with unfavorable outcomes.

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Self-reported sexual health: Breast cancer survivors compared to women from the general population – an observational study

Abstract

Background

Cancer survivorship is of increasing importance in post-treatment care. Sexual health (SH) and femininity can be crucial issues for women surviving cancer. We aimed to determine a more complete understanding of the contribution that a breast cancer (BC) diagnosis and its treatment exert on patients' follow-up SH. For this purpose, self-reported levels and predictors of SH in breast cancer survivors (BCS) were compared with those of women with no previous or current BC (WNBC).

Methods

BCS and WNBC underwent a comprehensive, cross-sectional patient-reported outcome (PRO) assessment. Validated PRO instruments were used to measure SH, body image, anxiety and depression and menopausal symptoms. Assessments were performed within the routine clinical setting.

Instruments used were the Sexual Interest and Desire Inventory - Female, Sexual Activity Questionnaire, Body Image Scale, Hospital Anxiety and Depression Scale and the Menopause-Specific Quality of Life Questionnaire.

Results

One hundred five BCS (average time since diagnosis of 3 years) and 97 WNBC with a mean age of 49 years completed the assessment. SH was significantly worse in BCS compared to WNBC (p = 0.005; BCS SIDI-F mean = 24.9 vs. WNBC mean = 29.8). 68.8% of BCS and 58.8% of WNBC met criteria of a hypo-active sexual desire disorder. Higher depressive symptoms, higher age and lower partnership satisfaction were predictive for poorer SH in BCS.

Conclusion

SH problems are apparent in BCS and differ significantly from those seen in the general population. Consequently, BC survivorship care should include interventions to ameliorate sexual dysfunction and provide help with depressive symptoms and partnership problems, which are associated with poor BCS SH.

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Innovative dressing and securement of tunneled central venous access devices in pediatrics: a pilot randomized controlled trial

Abstract

Background

Central venous access device (CVAD) associated complications are a preventable source of patient harm, frequently resulting in morbidity and delays to vital treatment. Dressing and securement products are used to prevent infectious and mechanical complications, however current complication rates suggest customary practices are inadequate. The aim of this study was to evaluate the feasibility of launching a full-scale randomized controlled efficacy trial of innovative dressing and securement products for pediatric tunneled CVAD to prevent complication and failure.

Methods

An external, pilot, four-group randomized controlled trial of standard care (bordered polyurethane dressing and suture), in comparison to integrated securement-dressing, suture-less securement device, and tissue adhesive was undertaken across two large, tertiary referral pediatric hospitals in Australia. Forty-eight pediatric participants with newly inserted tunneled CVADs were consecutively recruited. The primary outcome of study feasibility was established by elements of eligibility, recruitment, attrition, protocol adherence, missing data, parent and healthcare staff satisfaction and acceptability, and effect size estimates for CVAD failure (cessation of function prior to completion of treatment) and complication (associated bloodstream infection, thrombosis, breakage, dislodgement or occlusion). Dressing integrity, product costs and site complications were also examined.

Results

Protocol feasibility was established. CVAD failure was: 17% (2/12) integrated securement-dressing; 8% (1/13) suture-less securement device; 0% tissue adhesive (0/12); and, 0% standard care (0/11). CVAD complications were: 15% (2/13) suture-less securement device (CVAD associated bloodstream infection, and occlusion and partial dislodgement); 8% (1/12) integrated securement-dressing (partial dislodgement); 0% tissue adhesive (0/12); and, 0% standard care (0/11). One CVAD-associated bloodstream infection occurred, within the suture-less securement device group. Overall satisfaction was highest in the integrated securement-dressing (mean 8.5/10; standard deviation 1.2). Improved dressing integrity was evident in the intervention arms, with the integrated securement-dressing associated with prolonged time to first dressing change (mean days 3.5).

Conclusions

Improving the security and dressing integrity of tunneled CVADs is likely to improve outcomes for pediatric patients. Further research is necessary to identify novel, effective CVAD securement to reduce complications, and provide reliable vascular access for children.

Trial registration

ACTRN12614000280606; prospectively registered on 17/03/2014.

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Demographic and clinicopathological characteristics of nasopharyngeal carcinoma and survival outcomes according to age at diagnosis: A population-based analysis

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): San-Gang Wu, Xu-Lin Liao, Zhen-Yu He, Li-Ying Tang, Xue-Ting Chen, Yan Wang, Qin Lin
ObjectiveTo investigate the demographic features, clinicopathological characteristics and treatment outcomes of patients with nasopharyngeal carcinoma (NPC) according to age at diagnosis.MethodsWe assessed demographic and clinicopathological variables extracted from the Surveillance, Epidemiology, and End Results database (2004–2014). The Cox proportional hazards regression model was used to perform univariate and multivariate analyses of NPC-related mortality (cause-specific survival).ResultsA total of 3880 patients were analyzed. Median age was 55-years-old; 108 (2.8%), 508 (13.1%), 1876 (48.4%), 1240 (32.0%), and 148 (3.8%) patients were aged 1–19, 20–39, 40–59, 60–79, and 80–99-years-old, respectively. Younger patients tended to be black and present with poorly/undifferentiated disease and advanced tumor and nodal category compared to older patients. Younger patients were more likely to receive chemotherapy than older patients. In multivariate analyses, age at diagnosis was an independent prognostic factor for cause-specific survival. Increasing age at diagnosis was associated with a significantly higher risk of NPC-related mortality. Compared to patients aged 1–19-years-old, the hazard ratios for patients aged 20–39, 40–59, 60–79, and 80–99-years-old were 2.030 (95% confidence interval 1.004–4.104), 2.871 (1.474–5.590), 4.443 (2.273–8.683), and 12.024 (5.855–24.695), respectively. With the exception of black patients (P=0.100), older age was associated with poor survival in all demographic and clinical subgroups.ConclusionAlthough younger patients tended to have advanced disease at diagnosis, older age at diagnosis was associated with a higher risk of NPC-related mortality.

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Epigenetic therapy regulates the expression of ALDH1 and immunologic response: Relevance to the prognosis of oral cancer

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Ming-Shao Tsai, Wen-Cheng Chen, Chia-Hsuan Lai, Yu-Yen Chen, Miao-Fen Chen
ObjectivesAldehyde dehydrogenase 1 (ALDH1) is associated with tumorigenesis, and shown to identify cancer stem cells (CSC)-like cells. We aimed to investigate the significance of ALDH1 in oral squamous cell carcinoma (OSCC) and its correlation with DNMT3b and immune evasion in the present study.MethodsWe retrospectively analyzed the clinical outcomes of OSCC patients and examined its correlation with the levels of ALDH1 in tumors and circulating myeloid-derived suppressor cells (MDSCs) in the peripheral blood. Furthermore, the relationships between the DNMT3b, ALDH1 expression, and immune response were examined via clinical specimens and cellular and animal experiments. We also investigated the therapeutic potential of DNA hypomethylating agents in OSCC.ResultsOur data revealed that the levels of ALDH1 expression were linked to treatment resistance, CSC-like properties, higher circulating MDSC and poor prognosis for OSCC. The radiation resistance noted in ALDH1-positive tumors was associated with augmented radiation-induced increases in the expression of programmed death ligand (PD-L1) and the activation of MDSCs. Furthermore, there was a positive link between ALDH1 and DNMT3b expression shown by clinical specimens and cellular experiments. DNA hypomethylating agents attenuated the radioresistance of ALDH1-positive cancer cells associated with the decreased ALDH1 and the increased DNA damages. In addition, the activation of MDSCs and the expression of PD-L1 were significantly attenuated by epigenetic therapy.ConclusionsOur findings suggested that ALDH1 played an important role in treatment response and the tumor-promoting microenvironment in OSCC. Moreover, epigenetic therapy could be a promising strategy for the treatment of OSCC.

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Incidence and dosimetric parameters for brainstem necrosis following intensity modulated radiation therapy in nasopharyngeal carcinoma

Publication date: October 2017
Source:Oral Oncology, Volume 73
Author(s): Yang-Chan Li, Fo-Ping Chen, Guan-Qun Zhou, Jin-Han Zhu, Jiang Hu, De-Hua Kang, Chen-Fei Wu, Li Lin, Xiao-Ju Wang, Jun Ma, Ying Sun
ObjectivesTo clarify the incidence of brainstem toxicity and perform a dose-volume analysis for the brainstem after long-term follow-up of a large cohort of nasopharyngeal carcinoma (NPC) patients who underwent intensity-modulated radiation therapy (IMRT).Materials and methodsAll patients with NPC treated with IMRT at Sun Yat-sen University Cancer Center between April 2009 and March 2012 were retrospectively reviewed. A total of 1544 patients with follow-up >12months and detailed treatment plan data were included. Radiotherapy was administered using the simultaneous integrated boost technique in 2.0–2.48Gy per fractions/28–33 fractions. Brainstem necrosis was defined as lesions with high signal intensity on T2-weighted images and low signal intensity on T1-weighted images, with or without enhancement after administration of contrast in follow-up MRI.ResultsAfter median follow-up of 79.7months (range, 12.2–85.6months), 2/1544 (0.13%) patients developed brainstem necrosis after intervals of 12.3 and 18.5months. Actuarial incidence of brainstem necrosis was 0.07%, 0.13%, 0.13% and 0.13% after 1, 2, 3 and 5years, respectively. Overall, 384 (24.9%), 153 (9.9%), 67 (4.3%), 39 (2.5%), 78 (5.1%), and 114 (7.4%) patients had excessive doses of Dmax≥64Gy, D1cc>59Gy, D2cc>59Gy, aV50>5.9cc, aV55>2.7cc and aV60>0.9cc respectively, of whom only two developed brainstem necrosis.ConclusionsBrainstem necrosis is rare in NPC. The definitive criteria based on conventional radiotherapy cannot accurately predict the occurrence of brainstem necrosis after IMRT, thus more flexible definitive criteria with strict restrictions need to be defined.

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3D printing the pterygopalatine fossa: a negative space model of a complex structure

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The resulting 'negative space' model of the pterygopalatine fossa provides a useful and innovative aid for understanding the complex anatomical relationships of the pterygopalatine fossa.

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Associations between reduced telomere length, depressed mood, anhedonia, and irritability in Prostate Cancer patients: Further evidence for the presence of ‘male depression’?

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Visual Perceptual Echo Reflects Learning of Regularities in Rapid Luminance Sequences

A novel neural signature of active visual processing has recently been described in the form of the "perceptual echo", in which the cross-correlation between a sequence of randomly fluctuating luminance values and occipital electrophysiological signals exhibits a long-lasting periodic (~100 ms cycle) reverberation of the input stimulus (VanRullen and Macdonald, 2012). As yet, however, the mechanisms underlying the perceptual echo and its function remain unknown. Reasoning that natural visual signals often contain temporally predictable, though nonperiodic features, we hypothesized that the perceptual echo may reflect a periodic process associated with regularity learning. To test this hypothesis, we presented subjects with successive repetitions of a rapid nonperiodic luminance sequence, and examined the effects on the perceptual echo, finding that echo amplitude linearly increased with the number of presentations of a given luminance sequence. These data suggest that the perceptual echo reflects a neural signature of regularity learning.

Furthermore, when a set of repeated sequences was followed by a sequence with inverted luminance polarities, the echo amplitude decreased to the same level evoked by a novel stimulus sequence. Crucially, when the original stimulus sequence was re-presented, the echo amplitude returned to a level consistent with the number of presentations of this sequence, indicating that the visual system retained sequence-specific information, for many seconds, even in the presence of intervening visual input. Altogether, our results reveal a previously undiscovered regularity learning mechanism within the human visual system, reflected by the perceptual echo.

SIGNIFICANCE STATEMENT How the brain encodes and learns fast-changing but nonperiodic visual input remains unknown, even though such visual input characterizes natural scenes. We investigated whether the phenomenon of "perceptual echo" might index such learning. The perceptual echo is a long-lasting reverberation between a rapidly changing visual input and evoked neural activity, apparent in cross-correlations between occipital EEG and stimulus sequences, peaking in the alpha (~10 Hz) range. We indeed found that perceptual echo is enhanced by repeatedly presenting the same visual sequence, indicating that the human visual system can rapidly and automatically learn regularities embedded within fast-changing dynamic sequences. These results point to a previously undiscovered regularity learning mechanism, operating at a rate defined by the alpha frequency.

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Working Memories Are Maintained in a Stable Code

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This Week in The Journal

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Advantages of Using the Dorsolateral versus the Dorsomedial Visual Stream for Decoding Hand Movements

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Selective Phosphorylation of AMPA Receptor Contributes to the Network of Long-Term Potentiation in the Anterior Cingulate Cortex

Phosphorylation of AMPA receptor GluA1 plays important roles in synaptic potentiation. Most previous studies have been performed in the hippocampus, while the roles of GluA1 phosphorylation in the cortex remain unknown. Here we investigated the involvement of the phosphorylation of GluA1 in the LTP in the anterior cingulate cortex (ACC) using mice with a GluA1 knock-in mutation at the PKA phosphorylation site serine 845 (s845A) or CaMKII/PKC phosphorylation site serine 831 (s831A). The network LTP, which is constructed by multiple recordings of LTP at different locations within the ACC, was also investigated. We found that the expression of LTP and network LTP was significantly impaired in the s845A mice, but not in the s831A mice. By contrast, basal synaptic transmission and NMDA receptor-mediated responses were not affected. Furthermore, to uncover potential information under the current acquired data, a new method for reconstruction and better visualization of the signals was developed to observe the spatial localizations and dynamic temporal changes of fEPSP signals and multiple LTP responses within the ACC circuit. Our results provide strong evidence that PKA phosphorylation of the GluA1 is important for the network LTP expression in the ACC.

SIGNIFICANCE STATEMENT Previous studies have shown that PKA and PKC phosphorylation of AMPA receptor GluA1 plays critical roles in LTP in the hippocampus, while the roles of GluA1 phosphorylation in the cortex remain unknown. In the present study, by combining a 64-channel multielectrode system and a novel analysis and visualization method, we observed the accurate spatial localization and dynamic temporal changes of network fEPSP signals and LTP responses within the ACC circuit and found that PKA phosphorylation, but not PKC phosphorylation, of the GluA1 is required for LTP in the ACC.

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Tonic or Phasic Stimulation of Dopaminergic Projections to Prefrontal Cortex Causes Mice to Maintain or Deviate from Previously Learned Behavioral Strategies

Dopamine neurons in the ventral tegmental area (VTA) encode reward prediction errors and can drive reinforcement learning through their projections to striatum, but much less is known about their projections to prefrontal cortex (PFC). Here, we studied these projections and observed phasic VTA–PFC fiber photometry signals after the delivery of rewards. Next, we studied how optogenetic stimulation of these projections affects behavior using conditioned place preference and a task in which mice learn associations between cues and food rewards and then use those associations to make choices. Neither phasic nor tonic stimulation of dopaminergic VTA–PFC projections elicited place preference. Furthermore, substituting phasic VTA–PFC stimulation for food rewards was not sufficient to reinforce new cue–reward associations nor maintain previously learned ones. However, the same patterns of stimulation that failed to reinforce place preference or cue–reward associations were able to modify behavior in other ways. First, continuous tonic stimulation maintained previously learned cue–reward associations even after they ceased being valid. Second, delivering phasic stimulation either continuously or after choices not previously associated with reward induced mice to make choices that deviated from previously learned associations. In summary, despite the fact that dopaminergic VTA–PFC projections exhibit phasic increases in activity that are time locked to the delivery of rewards, phasic activation of these projections does not necessarily reinforce specific actions. Rather, dopaminergic VTA–PFC activity can control whether mice maintain or deviate from previously learned cue–reward associations.

SIGNIFICANCE STATEMENT Dopaminergic inputs from ventral tegmental area (VTA) to striatum encode reward prediction errors and reinforce specific actions; however, it is currently unknown whether dopaminergic inputs to prefrontal cortex (PFC) play similar or distinct roles. Here, we used bulk Ca²⁺ imaging to show that unexpected rewards or reward-predicting cues elicit phasic increases in the activity of dopaminergic VTA–PFC fibers. However, in multiple behavioral paradigms, we failed to observe reinforcing effects after stimulation of these fibers. In these same experiments, we did find that tonic or phasic patterns of stimulation caused mice to maintain or deviate from previously learned cue–reward associations, respectively. Therefore, although they may exhibit similar patterns of activity, dopaminergic inputs to striatum and PFC can elicit divergent behavioral effects.

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Membrane-Associated Effects of Glucocorticoid on BACE1 Upregulation and A{beta} Generation: Involvement of Lipid Raft-Mediated CREB Activation

Glucocorticoid has been widely accepted to induce Alzheimer's disease, but the nongenomic effect of glucocorticoid on amyloid β (Aβ) generation has yet to be studied. Here, we investigated the effect of the nongenomic pathway induced by glucocorticoid on amyloid precursor protein processing enzymes as well as Aβ production using male ICR mice and human neuroblastoma SK-N-MC cells. Mice groups exposed to restraint stress or intracerebroventricular injection of Aβ showed impaired cognition, decreased intracellular glucocorticoid receptor (GR) level, but elevated level of membrane GR (mGR). In this respect, we identified the mGR-dependent pathway evoked by glucocorticoid using impermeable cortisol conjugated to BSA (cortisol-BSA) on SK-N-MC cells. Cortisol-BSA augmented the expression of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), the level of C-terminal fragment β of amyloid precursor protein (C99) and Aβ production, which were maintained even after blocking intracellular GR. We also found that cortisol-BSA enhanced the interaction between mGR and Gαs, which colocalized in the lipid raft. The subsequently activated CREB by cortisol-BSA bound to the CRE site of the BACE1 promoter increasing its expression, which was downregulated by inhibiting CBP. Consistently, blocking CBP attenuated cognitive impairment and Aβ production induced by corticosterone treatment or intracerebroventricular injection of Aβ more efficiently than inhibiting intracellular GR in mice. In conclusion, glucocorticoid couples mGR with Gαs and triggers cAMP-PKA-CREB axis dependent on the lipid raft to stimulate BACE1 upregulation and Aβ generation.

SIGNIFICANCE STATEMENT Patients with Alzheimer's disease (AD) have been growing sharply and stress is considered as the major environment factor of AD. Glucocorticoid is the primarily responsive factor to stress and is widely known to induce AD. However, most AD patients usually have impaired genomic pathway of glucocorticoid due to intracellular glucocorticoid receptor deficiency. In this respect, the genomic mechanism of glucocorticoid faces difficulties in explaining the consistent amyloid β (Aβ) production. Therefore, it is necessary to investigate the novel pathway of glucocorticoid on Aβ generation to find a more selective therapeutic approach to AD patients. In this study, we revealed the importance of nongenomic pathway induced by glucocorticoid where membrane glucocorticoid receptor plays an important role in Aβ formation.

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Optogenetic Central Amygdala Stimulation Intensifies and Narrows Motivation for Cocaine

Addiction is often characterized by intense motivation for a drug, which may be narrowly focused at the expense of other rewards. Here, we examined the role of amygdala-related circuitry in the amplification and narrowing of motivation focus for intravenous cocaine. We paired optogenetic channelrhodopsin (ChR2) stimulation in either central nucleus of amygdala (CeA) or basolateral amygdala (BLA) of female rats with one particular nose-poke porthole option for earning cocaine infusions (0.3 mg/kg, i.v.). A second alternative porthole earned identical cocaine but without ChR2 stimulation. Consequently, CeA rats quickly came to pursue their CeA ChR2-paired cocaine option intensely and exclusively, elevating cocaine intake while ignoring their alternative cocaine alone option. By comparison, BLA ChR2 pairing failed to enhance cocaine motivation. CeA rats also emitted consummatory bites toward their laser-paired porthole, suggesting that higher incentive salience made that cue more attractive. A separate progressive ratio test of incentive motivation confirmed that CeA ChR2 amplified rats' motivation, raising their breakpoint effort price for cocaine by 10-fold. However, CeA ChR2 laser on its own lacked any reinforcement value: laser by itself was never self-stimulated, not even by the same rats in which it amplified motivation for cocaine. Conversely, CeA inhibition by muscimol/baclofen microinjections prevented acquisition of cocaine self-administration and laser preference, whereas CeA inhibition by optogenetic halorhodopsin suppressed cocaine intake, indicating that CeA circuitry is needed for ordinary cocaine motivation. We conclude that CeA ChR2 excitation paired with a cocaine option specifically focuses and amplifies motivation to produce intense pursuit and consumption focused on that single target.

SIGNIFICANCE STATEMENT In addiction, intense incentive motivation often becomes narrowly focused on a particular drug of abuse. Here we show that pairing central nucleus of amygdala (CeA) optogenetic stimulation with one option for earning intravenous cocaine makes that option almost the exclusive focus of intense pursuit and consumption. CeA stimulation also elevated the effort cost rats were willing to pay for cocaine and made associated cues become intensely attractive. However, we also show that CeA laser had no reinforcing properties at all when given alone for the same rats. Therefore, CeA laser pairing makes its associated cocaine option and cues become powerfully attractive in a nearly addictive fashion.

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Feedback Inhibition Shapes Emergent Computational Properties of Cortical Microcircuit Motifs

Cortical microcircuits are very complex networks, but they are composed of a relatively small number of stereotypical motifs. Hence, one strategy for throwing light on the computational function of cortical microcircuits is to analyze emergent computational properties of these stereotypical microcircuit motifs. We are addressing here the question how spike timing-dependent plasticity shapes the computational properties of one motif that has frequently been studied experimentally: interconnected populations of pyramidal cells and parvalbumin-positive inhibitory cells in layer 2/3. Experimental studies suggest that these inhibitory neurons exert some form of divisive inhibition on the pyramidal cells. We show that this data-based form of feedback inhibition, which is softer than that of winner-take-all models that are commonly considered in theoretical analyses, contributes to the emergence of an important computational function through spike timing-dependent plasticity: The capability to disentangle superimposed firing patterns in upstream networks, and to represent their information content through a sparse assembly code.

SIGNIFICANCE STATEMENT We analyze emergent computational properties of a ubiquitous cortical microcircuit motif: populations of pyramidal cells that are densely interconnected with inhibitory neurons. Simulations of this model predict that sparse assembly codes emerge in this microcircuit motif under spike timing-dependent plasticity. Furthermore, we show that different assemblies will represent different hidden sources of upstream firing activity. Hence, we propose that spike timing-dependent plasticity enables this microcircuit motif to perform a fundamental computational operation on neural activity patterns.

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Intermittent Hypoxia Enhances Functional Connectivity of Midcervical Spinal Interneurons

Brief, intermittent oxygen reductions [acute intermittent hypoxia (AIH)] evokes spinal plasticity. Models of AIH-induced neuroplasticity have focused on motoneurons; however, most midcervical interneurons (C-INs) also respond to hypoxia. We hypothesized that AIH would alter the functional connectivity between C-INs and induce persistent changes in discharge. Bilateral phrenic nerve activity was recorded in anesthetized and ventilated adult male rats and a multielectrode array was used to record C4/5 spinal discharge before [baseline (BL)], during, and 15 min after three 5 min hypoxic episodes (11% O₂, H1–H3). Most C-INs (94%) responded to hypoxia by either increasing or decreasing firing rate. Functional connectivity was examined by cross-correlating C-IN discharge. Correlograms with a peak or trough were taken as evidence for excitatory or inhibitory connectivity between C-IN pairs. A subset of C-IN pairs had increased excitatory cross-correlations during hypoxic episodes (34%) compared with BL (19%; p < 0.0001). Another subset had a similar response following each episode (40%) compared with BL (19%; p < 0.0001). In the latter group, connectivity remained elevated 15 min post-AIH (30%; p = 0.0002). Inhibitory C-IN connectivity increased during H1–H3 (4.5%; p = 0.0160), but was reduced 15 min post-AIH (0.5%; p = 0.0439). Spike-triggered averaging indicated that a subset of C-INs is synaptically coupled to phrenic motoneurons and excitatory inputs to these "pre-phrenic" cells increased during AIH. We conclude that AIH alters connectivity of the midcervical spinal network. To our knowledge, this is the first demonstration that AIH induces plasticity within the propriospinal network.

SIGNIFICANCE STATEMENT Acute intermittent hypoxia (AIH) can trigger spinal plasticity associated with sustained increases in respiratory, somatic, and/or autonomic motor output. The impact of AIH on cervical spinal interneuron (C-IN) discharge and connectivity is unknown. Our results demonstrate that AIH recruits excitatory C-INs into the spinal respiratory (phrenic) network. AIH also enhances excitatory and reduces inhibitory connections among the C-IN network. We conclude that C-INs are part of the respiratory, somatic, and/or autonomic response to AIH, and that propriospinal plasticity may contribute to sustained increases in motor output after AIH.

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Αρχειοθήκη ιστολογίου

Τετάρτη 30 Αυγούστου 2017

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