Myxoma of the mandibular condyle: Report of a rare case and review of the literature

Publication date: Available online 9 March 2018
Source:Oral Oncology
Author(s): Everaldo Pinheiro de Andrade Lima, Flávia Maria de Moraes Ramos-Perez, Rômulo Oliveira de Hollanda Valente, Jorge Esquiche León, Paulo Rogério Ferreti Bonan, Danyel Elias da Cruz Perez
This report describes an extremely rare case of myxoma of the mandibular condyle. The tumor occurred in the left mandibular condyle of a 42-year-old woman, which was identified in a routine radiographic examination. The clinico-radiographic and histopathological features, and histogenesis of the lesion are discussed. A review of the literature and differential diagnosis of radiolucent condylar lesions are also presented.



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Treatment and frequency of follow-up of BCC patients in the Netherlands

Abstract

The incidence of Basal Cell Carcinoma (BCC) rises by 5% per decade in the Netherlands (1), representing an important burden on the health care system and dermatologists' workload (2,3). There is no evidence that intensive follow-up results in better outcomes (burden of disease, cosmetic results) in patients with low risk BCCs (4–6). According to the Dutch BCC guideline, follow-up after treatment is not indicated for patients with a low risk BCC (7), but patients may come for follow-up more frequently for various reasons (4,7,8). Considering the enormous amount of patients, extra follow-up visits represent a substantial workload and healthcare costs. Therefore, we studied follow-up of 482 BCC patients, diagnosed in 2010 from general hospitals (N=291 – random sample from a population-based cancer registry) and academic hospitals (N=191), who had a total of 578 BCC diagnosed in 2010. Information on medical history, tumor characteristics and the treatment and follow-up of all diagnosed BCCs was retrieved from the patient files until April 2015.

This article is protected by copyright. All rights reserved.

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Immunohistochemical identification of nail matrix melanocytes

Abstract

Background

No previous studies have been conducted to determine the normal number of nail matrix melanocytes in Latin American individuals. The objective of this work was to determine the number of melanocytes per linear millimeter present in the nail matrix and the nail bed in samples obtained from Colombian individuals.

Methods

Twenty-six unilateral biopsies were taken from 19 cadavers subjected to clinical and medico-legal autopsies. These biopsy samples were processed with conventional histotechnology and immunohistochemistry (IHC) with anti-HMB-45 and anti-MiTF. Three sets of photographs (HE, HMB-45 and MiTF) were taken of each biopsy sample and independently assessed by three pathologists. Each observer counted the number of melanocytes present in 1 linear mm of the nail matrix or bed.

Results

We found an average of 4.6 melanocytes x linear mm with H & E staining, 9.8 with HMB-45 and 12.4 with MiTF.

Conclusions

The use of IHC significantly increases and facilitates the identification of melanocytes in unilateral biopsies. Our IHC counts exceed the averages found in the literature. This finding warrants new studies to verify whether the Colombian population presents higher numbers of melanocytes in the nail matrix than other populations or whether the observed increase is a result of the use of MiTF.

This article is protected by copyright. All rights reserved.

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A case of subepidermal autoimmune bullous disease with autoantibodies against 200-kDa and 290-kDa antigens

Abstract

Epidermolysis bullosa acquisita (EBA) and anti-p200 pemphigoid are uncommon subepidermal autoimmune bullous diseases caused by autoantibodies against the 200-kDa protein and 290-kDa type VII collagen, respectively. Here we describe a patient with autoantibodies against both 200-kDa and 290-kDa antigens.A 63-year-old-man had itchy tense blisters and edematous erythemas scattered on his trunk, buttocks, extremities and soles (Fig. 1a). There were no ocular or mucosal lesions. Psoriatic skin lesions were not observed. There was no personal or family history of serious diseases.

This article is protected by copyright. All rights reserved.

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Patch Testing in Gastrointestinal Diseases – A Systematic Review of the Patch Test (PT) and Atopy Patch Test (APT)

Abstract

Food allergy is common and the prevalence is increasing. The pathogenesis of food allergy has been extensively reviewed. Immunologic and clinical tolerance to food requires production of regulatory T cells that are food-antigen specific. Loss of tolerance to food can lead to IgE-mediated reactions and non-IgE-mediated reactions.

This article is protected by copyright. All rights reserved.

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Contact hypersensitivity in rosacea – a report on 143 cases

Abstract

Rosacea is a chronic skin disease characterized by inflammatory processes affecting mainly the center of the face. The pathophysiology is complex, environmental factors seem to play an important role in the exacerbation and worsening of the lesions. The barrier-dysfunction theory in atopic dermatitis has been well described in the literature.

This article is protected by copyright. All rights reserved.

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Reply to: Kubiak K. And al. Endosymbiosis and its significance in dermatology

Abstract

We would like to begin by congratulating Kubiak K et al on their work[1], which has the potential to contribute to review the question of endosymbiosis and its significance.We would like to add some new data, notes and comments. Some data regarding viral endosymbiosis other than those discussed by the authors, showed the transmission of a Gemycircularvirus - Sclerotinia sclerotiorum hypovirulence-associated DNA1- like virus (SsHADV-1–LV)- via insect vectors - Lycoriella ingenua.

This article is protected by copyright. All rights reserved.

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The iris signal: blue periphery, tan collaret and freckles pattern – strong indicators for epidermal skin cancer in South-Eastern Europe

Abstract

Background

Eye and skin share the embryological origin. Both are established risk factors in epidermal skin cancer. There are few reports using iris colour classification scales, most of them analyse colour in general or are too complex to use in daily practice.

Objectives

To investigate which iris colour pattern is associated with epidermal skin cancer in a S-E European Caucasian population.

Methods

A case control study was conducted on 480 patients: 229 skin cancers patients and 251 controls (dermatological patients free of skin cancers), admitted in two medical clinics of Dermatology in Bucharest, between October 2011 and May 2014. High resolution iris photos were taken for each patient. Three parameters of the iris were analysed individually and in association for each patient: periphery, collaret and freckles.

Results

The most frequent iris colour pattern associated with epidermal skin cancer was blue periphery with light brown collaret and freckles present. In terms of individual parameters, the strongest indicators for skin cancer patients were blue periphery and blue collaret.

Conclusions

The results of this study sustain the hypothesis that blue periphery with light brown collaret and freckles iris pattern is a reliable phenotypic marker for epidermal skin cancer. The results of this study differ from previous reports in which skin cancer risk was associated with a homogenous blue iris. We account these differences to the characteristics of the recruited patients (S-E European, skin type II and III). The assessment of iris colour patterns is an easy and inexpensive detection tool in skin cancer risk assessment.

This article is protected by copyright. All rights reserved.

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5 alpha-reductase inhibitor treatment for frontal fibrosing alopecia: An evidence-based treatment update

Abstract

Background

Treatment for frontal fibrosing alopecia (FFA) is challenging and its treatment regimen often mirrors other lymphocytic-predominant cicatricial alopecia. 5 alpha-reductase inhibitor (5ARI) has been reported with some treatment success in severe cases of FFA.

Objective

To carry out evidence-based analysis of articles published on treatment efficacy and safety of 5 alpha-reductase inhibitor for the treatment of FFA.

Methods

Articles published on the use of 5ARI to treat FFA between 2005 to 2017 were reviewed, analysed and graded according to the American College of Physicians outcome study grading system.

Results

There were two studies with moderate-level of evidence that described the efficacy of 5ARI for treatment of FFA. 5ARI was commonly used as adjunctive therapy with positive results in recalcitrant disease. Mild to moderate hair regrowth was reported in one grade 2 and three lower grade (one grade 3 and two grade 4) studies. There is limited evidence on the safety aspects of this medication in most studies that were analysed.

Limitations

Database studies might not fully account for confounders and is subjected to variations in methodology and data collection.

Conclusion

This review demonstrated that FFA patients treated with 5ARI could achieve either disease stability or reduction in the rate of progression in selected cases. A well designed randomised, double-blind, controlled study would strengthen the role of 5ARI as part of treatment armamentarium for FFA.

This article is protected by copyright. All rights reserved.

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Rapid fully automatic segmentation of subcortical brain structures by shape-constrained surface adaptation

Publication date: Available online 9 March 2018
Source:Medical Image Analysis
Author(s): Fabian Wenzel, Carsten Meyer, Thomas Stehle, Jochen Peters, Susanne Siemonsen, Christian Thaler, Lyubomir Zagorchev
This work presents a novel approach for the rapid segmentation of clinically relevant subcortical brain structures in T1-weighted MRI by utilizing a shape-constrained deformable surface model. In contrast to other approaches for segmenting brain structures, its design allows for parallel segmentation of individual brain structures within a flexible and robust hierarchical framework such that accurate adaptation and volume computation can be achieved within a minute of processing time. Furthermore, adaptation is driven by local and not global contrast, potentially relaxing requirements with respect to preprocessing steps such as bias-field correction. Detailed evaluation experiments on more than 1000 subjects, including comparisons to FSL FIRST and FreeSurfer as well as a clinical assessment, demonstrate high accuracy and test-retest consistency of the presented segmentation approach, leading, for example, to an average segmentation error of less than 0.5 mm. The presented approach might be useful in both, research as well as clinical routine, for automated segmentation and volume quantification of subcortical brain structures in order to increase confidence in the diagnosis of neuro-degenerative disorders, such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, or clinical applications for other neurologic and psychiatric diseases.

Graphical abstract

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Estimating fiber orientation distribution from diffusion MRI with spherical needlets

Publication date: Available online 8 February 2018
Source:Medical Image Analysis
Author(s): Hao Yan, Owen Carmichael, Debashis Paul, Jie Peng
We present a novel method for estimation of the fiber orientation distribution (FOD) function based on diffusion-weighted magnetic resonance imaging (D-MRI) data. We formulate the problem of FOD estimation as a regression problem through spherical deconvolution and a sparse representation of the FOD by a spherical needlets basis that forms a multi-resolution tight frame for spherical functions. This sparse representation allows us to estimate the FOD by ℓ1-penalized regression under a non-negativity constraint on the estimated FOD. The resulting convex optimization problem is solved by an alternating direction method of multipliers (ADMM) algorithm. The proposed method leads to a reconstruction of the FOD that is accurate, has low variability and preserves sharp features. Through extensive experiments, we demonstrate the effectiveness and favorable performance of the proposed method compared to three existing methods. Specifically, we demonstrate that the proposed method is able to successfully resolve fiber crossings at small angles and automatically identify isotropic diffusion. We also apply the proposed method to real 3T D-MRI data sets of healthy individuals. The results show realistic depictions of crossing fibers that are more accurate, less noisy, and lead to superior tractography results compared to competing methods.

Graphical abstract

http://ift.tt/2FrQgMN

Focal immune-related pancreatitis occurring after treatment with programmed cell death 1 inhibitors: a distinct form of autoimmune pancreatitis?

Publication date: Available online 9 March 2018
Source:European Journal of Cancer
Author(s): Gabriele Capurso, Livia Archibugi, Laura Tessieri, Maria Chiara Petrone, Andrea Laghi, Paolo Giorgio Arcidiacono




http://ift.tt/2IeudGS

Immune checkpoint therapy in proteinuric kidney disease

Publication date: Available online 9 March 2018
Source:European Journal of Cancer
Author(s): Tsuneo Takenaka, Yohko Kawai, Takahiro Amano




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(Meth)acrylate allergy: frequently missed?

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(Meth)acrylate allergy: frequently missed?

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Mutilating male genital Crohn's without gastrointestinal involvement

Abstract

A 58 year old gentleman developed multiple fissures and discharging sinuses in the groin and perineum. Skin biopsies showed non-caseating granulomas suggestive of Crohn's disease. The patient had no gastrointestinal symptoms and a radio-labelled white cell scan demonstrated no bowel involvement.

This article is protected by copyright. All rights reserved.

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Long-Term Optimization of Outcomes With Flexible Adalimumab Dosing in Patients With Moderate to Severe Plaque Psoriasis

Abstract

Background

The recently updated dosing recommendation for adalimumab for moderate to severe plaque psoriasis states that patients with inadequate response to adalimumab every other week (EOW) after 16 weeks may benefit from an increase in dosing frequency to 40 mg every week (EW).

Objective

To determine the long-term efficacy of adalimumab in patients with psoriasis with flexibility to escalate and de-escalate between EOW and EW dosing.

Methods

Data from an open-label study in patients with psoriasis who had received adalimumab in phase 2/3 studies and their extensions were included. Patients initially received 40 mg adalimumab EOW for 24 weeks. From weeks 24 to 252, patients whose Psoriasis Area and Severity Index response was <50% (PASI 50) could be dose-escalated to 40 mg EW and were re-evaluated at 6 and 12 weeks and then every 12 weeks thereafter. Patients who dose-escalated and achieved a PASI 75 response were de-escalated to EOW and could re-escalate to EW if response fell below PASI 50 again; no further de-escalation was allowed. Changes in PASI scores were reported at the last visit before dose escalation or de-escalation.

Results

By week 24, 64.1% of patients in the overall population (n=1256) achieved ≥PASI 75 response, 40.3% ≥PASI 90 response, and 21.7% PASI 100 response. Patients who had a <PASI 50 during weeks 24 to 252 (349/1256, 27.8%) were dose-escalated to EW; 182 (52.1%) remained on EW dosing and 167 (47.9%) achieved a PASI 75 response and were de-escalated to EOW; 83 patients were later re-escalated to EW dosing owing to a <PASI 50 response. Dose escalation was not associated with additional safety concerns.

Conclusion

Optimizing therapy by temporarily increasing the dosing of adalimumab to EW in patients with psoriasis and an inadequate response to adalimumab 40 mg EOW permitted the achievement and long-term maintenance of clinical improvement.

This article is protected by copyright. All rights reserved.

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Whole genome sequence and phenotypic characterization of a Cbm+ serotype e strain of Streptococcus mutans

Abstract

We report the whole genome sequence (WGS) of the serotype e Cbm⁺ strain LAR01 of Streptococcus mutans, a dental pathogen frequently associated with extra-oral infections. The LAR01 genome is a single circular chromosome of 2.1 Mb with a GC content of 36.96%. The genome contains 15 PTS gene clusters, 7 cell wall-anchored (LPxTG) proteins, all genes required for the development of natural competence and genes coding for mutacins VI and K8. Interestingly, the cbm gene is genetically linked to a putative type VII secretion system that has been found in Mycobacteria and few other gram-positive bacteria. When compared to the UA159 type strain, phenotypic characterization of LAR01 revealed increased biofilm formation in the presence of either glucose or sucrose but similar abilities to withstand acid and oxidative stresses. LAR01 was unable to inhibit the growth of S. gordonii, which is consistent with the genomic data that indicates absence of mutacins that can kill mitis streptococci. On the other hand, LAR01 effectively inhibited growth of other S. mutans strains suggesting that it may be specialized to outcompete strains from its own species. In vitro and in vivo studies using mutational and heterologous expression approaches revealed that Cbm is a virulence factor of S. mutans by mediating binding to extracellular matrix proteins and intracellular invasion. Collectively, the WGS analysis and phenotypic characterization of LAR01 provides new insights on the virulence properties of S. mutans and grants further opportunities to understand the genomic fluidity of this important human pathogen.

This article is protected by copyright. All rights reserved

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Blunt cannula subcision is more effective than Nokor needle subcision for acne scars treatment

Summary

Background and aim

A comprehensive study comparing two different modalities, Nokor needle subcision (NNS) and blunt cannula subcision (BCS), for treatment of acne scars, has not been reported previously. The aim was to compare the effectiveness of these two methods based on patient's and doctor's satisfaction measures, in addition to the late complications 3 months postsubcision.

Method of intervention

Patients had 18-65 years old, with acne scars on both malar sides. They were treated at one malar side with NNS and with BCS at another side. They were monitored during the first week, at one and 3 months postintervention. Patient's and two dermatologist's satisfactions were compared during 3 months, for each modality and between modalities.

Results

From 34 patients, 29.4%, 55.9%, and 14.7% had mild, moderate, and severe acne scars, respectively. Ecchymosis, nodule formation post-NNS, and edema after BCS were the complications. Patients were satisfied with BCS during 3-month monitoring (P = .021), but not with NNS (P = .353). Physician-1 was satisfied from the outcome of both BCS and NNS procedures (P = .044 and .006, respectively). However, physician-2 was only satisfied with NNS at the month 3 than the month 1 (P = .002). All patients and physicians were significantly more satisfied with BCS than NNS (P = .000). Anyway, at the month 3, physician-2 had no significant different points of view about applied methods (P = .25).

Discussion

Considering the complications and satisfaction rates, BCS was more efficient than NNS for acne scar treatment. Then, we suggest BCS as a good replacement for NNS.

http://ift.tt/2G9y2MR

Clinical evaluation of simultaneously applied monopolar radiofrequency and targeted pressure energy as a new method for noninvasive treatment of cellulite in postpubertal women

Summary

Introduction

This study investigates noninvasive cellulite treatments based on simultaneous application of monopolar radiofrequency (RF) and targeted pressure energy to evaluate efficacy and safety and to see whether simultaneous application has any benefits in noninvasive cellulite treatments.

Methods

Thirty women with cellulite (fibrous/adipose/aqueous types) received 4 gluteofemoral treatments (~24 minutes; ~1000 cm²) using a simultaneous application of RF and targeted pressure energy. Clinical improvement was assessed using a pentile grading scale and satisfaction questionnaires. Hip/thigh circumference was measured. Ultrasonography and thermography observed changes in dermal/subcutaneous tissue composition and in gluteofemoral thermal profile. Evaluation at 3 months posttreatment was compared against the baseline.

Results

The clinical improvement averaged 2.17 ± 0.95 (54% improvement). Cellulite was reduced in 93% of cases, while 73% of patients showed good/very good/excellent improvement, with most significant improvement seen in patients with moderately severe cellulite. Hips and thigh circumference decreased on average by 2.31 cm and 2.13 cm, respectively (P < .001). Patient satisfaction was very high, averaging 4.47 ± 0.57 points (1-5 scale). Ultrasonography revealed smoothing and thickening (+0.28 ± 0.15 mm) of the dermis and an average reduction of 1.96 ± 1.60 mm in fat thickness (P < .05). Subjects with significant cellulite reduction had a more homogenous thermal profile at follow-up as a result of therapy-induced diminution of topographic skin defects. No adverse events were recorded.

Conclusion

The application is effective and safe for treating cellulite. The level of clinical improvement after 4 sessions is comparable to results reported after 6-20 sessions in studies on stand-alone RF/laser/targeted pressure energy devices. The technology is promising and deserves further attention and research.

http://ift.tt/2p2030X

Antiaging and antioxidant effects of topical autophagy activator: A randomized, placebo-controlled, double-blinded study

Summary

Background

Recently, potential roles of autophagy in skin homeostasis received many interests. But, little has been reported for the potential antiaging effects of autophagy activator.

Objective

With the newly synthesized autophagy activator, heptasodium hexacarboxymethyl dipeptide-12 (Aquatide™) in vitro and clinical efficacy of the topical autophagy activator as an antiaging cosmeceutical ingredient was evaluated.

Methods

Antioxidant effect of Aquatide™ was evaluated by radical scavenging assay. In vitro effect was assessed by measuring the cytotoxicity of hydrogen peroxide in cultured normal human epidermal keratinocytes. Clinical evaluation was performed by a randomized, placebo-controlled, double-blinded study. Antioxidant efficacy was observed by measuring the carbonylated proteins in stratum corneum (SC) by fluorescein-5-thiosemicarbazide (FTZ) staining.

Results

Radical scavenging effects of Aquatide were observed with the ABTS assay, and significant reduction in hydrogen peroxide-induced cytotoxicity was observed in Aquatide™-treated cells. Autophagy inhibitor treatment abrogated cytoprotective effects of Aquatide™. In a clinical study, statistically significant increase in skin elasticity was observed after 4 and 8 weeks. Quantitative analysis of carbonylated proteins in SC also showed significant reduction in Aquatide™-treated group, which is consistent with the in vitro data.

Conclusion

These results suggest that autophagy plays important roles in antioxidant system and aging process in skin, and topical autophagy activators can be potential cosmeceutical ingredients for skin antiaging.

http://ift.tt/2FFCB3C

Blunt cannula subcision is more effective than Nokor needle subcision for acne scars treatment

Summary

Background and aim

A comprehensive study comparing two different modalities, Nokor needle subcision (NNS) and blunt cannula subcision (BCS), for treatment of acne scars, has not been reported previously. The aim was to compare the effectiveness of these two methods based on patient's and doctor's satisfaction measures, in addition to the late complications 3 months postsubcision.

Method of intervention

Patients had 18-65 years old, with acne scars on both malar sides. They were treated at one malar side with NNS and with BCS at another side. They were monitored during the first week, at one and 3 months postintervention. Patient's and two dermatologist's satisfactions were compared during 3 months, for each modality and between modalities.

Results

From 34 patients, 29.4%, 55.9%, and 14.7% had mild, moderate, and severe acne scars, respectively. Ecchymosis, nodule formation post-NNS, and edema after BCS were the complications. Patients were satisfied with BCS during 3-month monitoring (P = .021), but not with NNS (P = .353). Physician-1 was satisfied from the outcome of both BCS and NNS procedures (P = .044 and .006, respectively). However, physician-2 was only satisfied with NNS at the month 3 than the month 1 (P = .002). All patients and physicians were significantly more satisfied with BCS than NNS (P = .000). Anyway, at the month 3, physician-2 had no significant different points of view about applied methods (P = .25).

Discussion

Considering the complications and satisfaction rates, BCS was more efficient than NNS for acne scar treatment. Then, we suggest BCS as a good replacement for NNS.

http://ift.tt/2G9y2MR

Clinical evaluation of simultaneously applied monopolar radiofrequency and targeted pressure energy as a new method for noninvasive treatment of cellulite in postpubertal women

Summary

Introduction

This study investigates noninvasive cellulite treatments based on simultaneous application of monopolar radiofrequency (RF) and targeted pressure energy to evaluate efficacy and safety and to see whether simultaneous application has any benefits in noninvasive cellulite treatments.

Methods

Thirty women with cellulite (fibrous/adipose/aqueous types) received 4 gluteofemoral treatments (~24 minutes; ~1000 cm²) using a simultaneous application of RF and targeted pressure energy. Clinical improvement was assessed using a pentile grading scale and satisfaction questionnaires. Hip/thigh circumference was measured. Ultrasonography and thermography observed changes in dermal/subcutaneous tissue composition and in gluteofemoral thermal profile. Evaluation at 3 months posttreatment was compared against the baseline.

Results

The clinical improvement averaged 2.17 ± 0.95 (54% improvement). Cellulite was reduced in 93% of cases, while 73% of patients showed good/very good/excellent improvement, with most significant improvement seen in patients with moderately severe cellulite. Hips and thigh circumference decreased on average by 2.31 cm and 2.13 cm, respectively (P < .001). Patient satisfaction was very high, averaging 4.47 ± 0.57 points (1-5 scale). Ultrasonography revealed smoothing and thickening (+0.28 ± 0.15 mm) of the dermis and an average reduction of 1.96 ± 1.60 mm in fat thickness (P < .05). Subjects with significant cellulite reduction had a more homogenous thermal profile at follow-up as a result of therapy-induced diminution of topographic skin defects. No adverse events were recorded.

Conclusion

The application is effective and safe for treating cellulite. The level of clinical improvement after 4 sessions is comparable to results reported after 6-20 sessions in studies on stand-alone RF/laser/targeted pressure energy devices. The technology is promising and deserves further attention and research.

http://ift.tt/2p2030X

Antiaging and antioxidant effects of topical autophagy activator: A randomized, placebo-controlled, double-blinded study

Summary

Background

Recently, potential roles of autophagy in skin homeostasis received many interests. But, little has been reported for the potential antiaging effects of autophagy activator.

Objective

With the newly synthesized autophagy activator, heptasodium hexacarboxymethyl dipeptide-12 (Aquatide™) in vitro and clinical efficacy of the topical autophagy activator as an antiaging cosmeceutical ingredient was evaluated.

Methods

Antioxidant effect of Aquatide™ was evaluated by radical scavenging assay. In vitro effect was assessed by measuring the cytotoxicity of hydrogen peroxide in cultured normal human epidermal keratinocytes. Clinical evaluation was performed by a randomized, placebo-controlled, double-blinded study. Antioxidant efficacy was observed by measuring the carbonylated proteins in stratum corneum (SC) by fluorescein-5-thiosemicarbazide (FTZ) staining.

Results

Radical scavenging effects of Aquatide were observed with the ABTS assay, and significant reduction in hydrogen peroxide-induced cytotoxicity was observed in Aquatide™-treated cells. Autophagy inhibitor treatment abrogated cytoprotective effects of Aquatide™. In a clinical study, statistically significant increase in skin elasticity was observed after 4 and 8 weeks. Quantitative analysis of carbonylated proteins in SC also showed significant reduction in Aquatide™-treated group, which is consistent with the in vitro data.

Conclusion

These results suggest that autophagy plays important roles in antioxidant system and aging process in skin, and topical autophagy activators can be potential cosmeceutical ingredients for skin antiaging.

http://ift.tt/2FFCB3C

Design and characterization of silicone micromaterials: A systematic study

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Joanna Lewandowska-Łańcucka, Magdalena Staszewska, Michał Szuwarzyński, Szczepan Zapotoczny, Mariusz Kepczynski, Zbigniew Olejniczak, Bogdan Sulikowski, Maria Nowakowska
Silicone micromaterials were synthesized using two surfactant-free methods: the Stöber synthesis or solidification in spontaneously formed emulsions (the Ouzo effect) and their physicochemical properties were evaluated. The effect of the chemical structure of a silicone precursor on the morphology of formed microstructures was considered. For that purpose, various organosilicon compounds containing in their structure T-units and D-units, methyl groups, ethylene linkages, and cyclotetrasiloxane rings were used as silicone precursors. All materials existed as sub-micron sized particles, although they differed considerably in morphology and dispersity (spherical particles with a diameter of about 490 and 740nm, cauliflower-like structures, large rough-surfaced aggregates). The chemical composition of the microstructure surface was examined using XPS. The porosity of silicone materials was assessed on the basis of nitrogen adsorption isotherms. The specific surface area (SBET) varied substantially and ranged from 5 to 379m²/g. For the first time the microelastic modulus of the silicone materials was determined using AFM measurements. We found that the structure of the organic part had a large impact on the microelasticity of the material. The microelastic modulus of the silicone materials (11–33GPa) was significantly lower compared to silica (59GPa).

Graphical abstract

http://ift.tt/2FvKKoa

Meta-Analysis: Contrast-Enhanced Ultrasound Versus Conventional Ultrasound for Differentiation of Benign and Malignant Breast Lesions

Publication date: Available online 9 March 2018
Source:Ultrasound in Medicine & Biology
Author(s): Qian Li, Min Hu, Zhikui Chen, Changtian Li, Xi Zhang, Yiqing Song, Feixiang Xiang
This meta-analysis aimed to compare the diagnostic performance of contrast-enhanced ultrasound (CEUS), conventional ultrasound (US) combined with CEUS (US + CEUS) and US for distinguishing breast lesions. From thorough literature research, studies that compared the diagnostic performance of CEUS versus US or US + CEUS versus US, using pathology results as the gold standard, were included. A total of 10 studies were included, of which 9 compared the diagnostic performance of CEUS and US, and 5 studies compared US + CEUS and US. In those comparing CEUS versus US, the pooled sensitivity was 0.93 (95% CI: 0.91–0.95) versus 0.87 (95% CI: 0.85–0.90) and pooled specificity was 0.86 (95% CI: 0.84–0.88) versus 0.72 (95% CI: 0.69–0.75). In studies comparing US + CEUS versus US, the pooled sensitivity was 0.94 (95% CI: 0.92–0.96) versus 0.87 (95% CI: 0.84–0.90) and pooled specificity was 0.86 (95% CI: 0.82–0.89) versus 0.80 (95% CI: 0.76–0.84). In terms of diagnosing breast malignancy, areas under the curve of the summary receiver operating characteristic (of both CEUS (p = 0.003) and US + CEUS (p = 0.000) were statistically higher than that of US. Both CEUS alone and US + CEUS had better diagnostic performance than US in differentiation of breast lesions, and US + CEUS also had low negative likelihood ratio.



http://ift.tt/2DfmEfs

In situ DSC investigation into the kinetics and microstructure of dispersoid formation in Al-Mn-Fe-Si(-Mg) alloys

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Richard H. Kemsies, Benjamin Milkereit, Sigurd Wenner, Randi Holmestad, Olaf Kessler
Dispersoid strengthening in Al-Mn-Fe-Si(-Mg) aluminum wrought alloys can play an important role in applications at elevated temperatures. Fine and evenly distributed dispersoids are needed to increase alloy strength, which can be achieved by conducting an adapted homogenization heat treatment. In this work for the first time, the precipitation behavior of dispersoids in direct chill casted Al-Mn-Fe-Si(-Mg) alloys was systematically investigated in situ during heating by means of differential scanning calorimetry. In situ analysis of the phase transformation kinetics during heating and homogenization was complemented by ex situ testing of the electrical conductivity and Vickers hardness, as well as micro- and nano-structural analyses by optical light and transmission electron microscopy. The influence of the heating rate on precipitation behavior was determined by calorimetric in situ experiments, covering a wide heating rate, ranging from 0.003 to 2K/s. The influence of 400 and 550°C homogenization temperatures and soaking durations on hardness and electrical conductivity was also investigated. The highest dispersoid strengthening was obtained after heat treating the as-cast Mg-containing alloy at 400°C for 3 to 10h. Furthermore, the Mg content heavily influenced the precipitation behavior by forming β-Mg2Si precursor phases, which can act as nucleation sites for dispersoid precipitation.

Graphical abstract

http://ift.tt/2FoOv2I

Slip transfer across γ-TiAl lamellae in tension

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Alberto Jesús Palomares-García, María Teresa Pérez-Prado, Jon Mikel Molina-Aldareguia
This work identifies the mechanisms governing dislocation transmission across lamellar interfaces in a Ti-45Al-2Nb-2Mn (at.%) + 0.8(vol%) TiB2 (Ti4522XD) alloy. With this aim, a microgrip and a microtensile specimen were designed and fabricated using a focused ion beam (FIB), to test micrometer-sized specimens in tension. The deformation mechanisms acting in a microtensile specimen of a Ti4522XD alloy were investigated through electron backscatter diffraction (EBSD) and transmission electron microscopy (TEM). The results revealed that domain boundaries (order variant) and lamellar interfaces (order variant, true twin and pseudo-twin) are relatively transparent to dislocation propagation, but they present significant differences in the geometrical alignment between the incoming and outgoing slip systems. While for order variant interfaces, the incoming and outgoing slip systems are perfectly aligned, true twin and pseudo twin interfaces require a change in slip plane and direction, which leaves residual dislocations with Burgers vectors lying on the interface plane. The analysis of the slip transfer mechanisms revealed that the outgoing slip system is governed more by the maximum geometrical alignment, than the applied resolved shear stress.

Graphical abstract

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Fatigue driven matrix crack propagation in laminated composites

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): Bijan Mohammadi, Hamed Pakdel
An energy based evolution rule is developed to predict the propagation of mid and outer-ply matrix cracks in laminates with the layups of [0n/θm] s and [θm/0n] s subject to tensile fatigue loading from initiation up to saturation. A unit cell based variational approach is developed to model the damage state considering both crack density and distribution pattern. Crack densities for different layups are then predicted using only two unit effective material properties which are independent from geometry of laminate. Numerous specimens with 8 different layups are tested and during tensile fatigue loading, matrix cracks multiplication is monitored on site using an appropriate optical microscopy setup. Both material properties of Paris like evolution equation are derived based on experimental observations of crack density in two general layups. Analytically predicted crack densities of tested specimens are shown to be in agreement with experimental observations which confirms empirical parameters to be independent from layup in the tested carbon-epoxy specimens. The independence of the empirical parameters from layup and loading must be validated using extensive experimental results of different layups and materials considering different modes of damage.

Graphical abstract

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Effect of particle shape and size on the morphology and optical properties of zinc oxide synthesized by the polyol method

Publication date: 15 May 2018
Source:Materials & Design, Volume 146
Author(s): T.E.P. Alves, C. Kolodziej, C. Burda, A. Franco
In this study we prepared zinc oxide (ZnO) nanoparticles using the polyol method with zinc acetate and/or sodium acetate in a propylene glycol medium with varied hydrolysis reaction time (10, 60 and 300 min). It was observed that the hydrolysis reaction time and the concentration of acetate ions had a strong effect on the morphology and size of ZnO nanoparticles (NPs). X-ray diffraction (XRD) patterns revealed that all samples crystalized in the typical ZnO wurtzite structure and Rietveld refinement was used to characterize the structure and to suggest a preferential growth. Fourier transformed infrared spectroscopy (FTIR) was performed and showed the typical ZnO band, no impurity signals, as well as differences in A1 and E1 vibration modes due to different crystal growth in the structure. Raman scattering was carried out to determine the defects in the structure of ZnO, such as interstitial oxygen and oxygen vacancies. Transmission electron microscope (TEM) images revealed that ZnO NPs size and shape are strongly dependent on the hydrolysis reaction time and addition of acetate counter ions, respectively. The change in shape and size has also affected the optical properties, such as the optical bandgap (Eg) of ZnO NPs and their florescence.

Graphical abstract

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Comparison of complications in midlines versus central venous catheters: Are midlines safer than central venous lines?

Publication date: Available online 7 March 2018
Source:American Journal of Infection Control
Author(s): Ammara Mushtaq, Bhagyashri Navalkele, Maninder Kaur, Amar Krishna, Aleena Saleem, Natasha Rana, Sonia Gera, Suganya Chandramohan, Malini Surapaneni, Teena Chopra
BackgroundWith the rising use of midline catheters (MCs), validation of their safety is essential. Our study aimed to evaluate the incidence of bloodstream infections (BSIs) and other complications related to the use of MCs and central venous catheters (CVCs).MethodsA retrospective cohort study was performed at a tertiary care hospital in Detroit, Michigan, from March-September 2016. Adult patients with either MC or CVC were included. Outcomes assessed were catheter-related BSI (CRBSI), mechanical complications, hospital length of stay, readmission within 90 days of discharge (RA), and mortality. Statistical analysis was performed using SAS software.ResultsA total of 411 patients with MC and 282 patients with CVC were analyzed. More CRBSIs were seen in patients with CVC (10/282) than MC (1/411) (3.5% vs 0.2%, respectively; P = .0008). More mechanical complications were seen in patients with MC (2.6%) than CVC (0.3%; P = .03). Patients with CVC had a higher crude mortality (17.3% vs 5.3%; P < .0001), RA (58% vs 35%; P ≤ .0001), line-related RA (2.8% vs 0.2%; P = .0041), and transfer to intensive care unit after line placement (9% vs 5%; P = .01). CVC was a significant exposure for a composite of mortality, CRBSI, mechanical issues, thrombosis, and readmission because of a line-related complication (odds ratio, 3.2; 95% confidence interval, 1.8-5.8).ConclusionsOur findings show use of MC is safer than CVC, but larger studies are needed to confirm our findings.



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Determinants of urinary catheter removal practices in the pediatric intensive care unit: A survey

Publication date: Available online 5 March 2018
Source:American Journal of Infection Control
Author(s): Karen Trudel, Samara Zavalkoff, Nicholas Winters, Caroline Quach, Jacques Lacroix, Patricia S. Fontela
BackgroundProlonged use of indwelling catheters is associated with hospital-acquired urinary tract infections (UTIs). Literature is scarce about the factors influencing urinary catheter removal and maintenance in children. This study aims to describe the determinants of urinary catheter removal in pediatric intensive care unit (PICU) patients.MethodsCross-sectional survey of 171 physicians and nurses working at 2 tertiary PICUs in Montreal, Canada. We used focus groups and literature review to design the survey questions and 3 clinical scenarios. We analyzed our results using descriptive statistics and multivariate multinomial regression.ResultsThere were 131 (77%) participants who answered the survey. Factors prompting urinary catheter removal (P < .01) included recent extubation, superficial sedation level, fever, and history of previous UTI. Presence of shock (P < .01) and fluid overload (P < .05) were associated with maintenance of catheters. Physicians were more likely to remove urinary catheters than nurses in all scenarios.ConclusionsWe identified a consistent set of variables that drive the removal of indwelling catheters in PICUs. Studies are needed to determine whether incorporating these determinants into infection control interventions will reduce urinary catheter use and catheter-associated UTIs in critically ill children.



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Safe removal of gloves from contact precautions: The role of hand hygiene

Publication date: Available online 5 March 2018
Source:American Journal of Infection Control
Author(s): Susan Jain, Kate Clezy, Mary-Louise McLaws
BackgroundRoutine hand hygiene effectively removes methicillin-resistant Staphylococcus aureus (MRSA) and/or vancomycin resistant Enterococcus (VRE) from the ungloved hands of healthcare workers (HCWs) who are caring for patients under contact precautions, when exposure to bodily fluids is not expected.MethodsHCWs' ungloved hands were cultured after hand hygiene with alcohol-based hand rub (ABHR) or soap-and-water wash after routine clinical care of patients known to be colonized or infected with MRSA or VRE.ResultsTwo hundred forty samples from 40 HCWs were tested and found to be culture negative for either MRSA or VRE after contact with patients when 3 pumps of ABHR (0/80) or plain soap-and-water wash (0/80) were used. No VRE was observed in any of the 120 samples collected. Two plates (2/40) grew 1 colony-forming unit of MRSA after 2 pumps of ABHR. Two HCWs with positive plates were cultured negative on retesting.ConclusionWe showed that appropriate hand hygiene was effective in removing MRSA and VRE even when gloves were not used for routine clinical care, despite contact with patients known to be colonized with MRSA or VRE. A modified approach to glove use for dry contact with patients on contact precautions might improve patient safety within healthcare settings.



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Nurses' experiences of care for patients with Middle East respiratory syndrome-coronavirus in South Korea

Publication date: Available online 1 March 2018
Source:American Journal of Infection Control
Author(s): Yujeong Kim
BackgroundThis study aimed to identify nurses' experiences of care for patients with Middle East respiratory syndrome-coronavirus (MERS-CoV). Their experiences can be useful to establish a safer healthcare system in preparation for infectious disease outbreaks.MethodsData were collected through in-depth individual interviews and analyzed using Colaizzi's phenomenological method. Participants were 12 nurses.ResultsNurses' experiences of care for patients with MERS-CoV were categorized as follows: "Going into a dangerous field," "Strong pressure because of MERS-CoV," "The strength that make me endure," "Growth as a nurse," and "Remaining task."ConclusionsIt is necessary to examine the difficulties and demands of healthcare providers for establishing a safe healthcare system to respond effectively when national disasters occur. In addition, it is necessary to develop strategies to protect healthcare providers from severe physical and psychological stress.



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Editorial Board

Publication date: March 2018
Source:American Journal of Infection Control, Volume 46, Issue 3





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Journal club: A pilot gap analysis survey of US emergency medical services practitioners to determine training and education needs pertaining to highly infectious disease preparedness and response

Publication date: March 2018
Source:American Journal of Infection Control, Volume 46, Issue 3
Author(s): Sara M. Reese




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Information for Readers

Publication date: March 2018
Source:American Journal of Infection Control, Volume 46, Issue 3





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Use of a verbal electronic audio reminder with a patient hand hygiene bundle to increase independent patient hand hygiene practices of older adults in an acute care setting

Publication date: Available online 1 March 2018
Source:American Journal of Infection Control
Author(s): Shanina C. Knighton, Mary Dolansky, Curtis Donskey, Camille Warner, Herleen Rai, Patricia A. Higgins
BackgroundWe hypothesized that the addition of a novel verbal electronic audio reminder to an educational patient hand hygiene bundle would increase performance of self-managed patient hand hygiene.MethodsWe conducted a 2-group comparative effectiveness study randomly assigning participants to patient hand hygiene bundle 1 (n = 41), which included a video, a handout, and a personalized verbal electronic audio reminder (EAR) that prompted hand cleansing at 3 meal times, or patient hand hygiene bundle 2 (n = 34), which included the identical video and handout, but not the EAR. The primary outcome was alcohol-based hand sanitizer use based on weighing bottles of hand sanitizer.ResultsParticipants that received the EAR averaged significantly more use of hand sanitizer product over the 3 days of the study (mean ± SD, 29.97 ± 17.13 g) than participants with no EAR (mean ± SD, 10.88 ± 9.27 g; t73 = 5.822; P ≤ .001).ConclusionsThe addition of a novel verbal EAR to a patient hand hygiene bundle resulted in a significant increase in patient hand hygiene performance. Our results suggest that simple audio technology can be used to improve patient self-management of hand hygiene. Future research is needed to determine if the technology can be used to promote other healthy behaviors, reduce infections, and improve patient-centered care without increasing the workload of health care workers.

Graphical abstract

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You have questions…APIC Text Online has the answers!

Publication date: March 2018
Source:American Journal of Infection Control, Volume 46, Issue 3





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Adherence to surgical hand antisepsis: Barriers and facilitators in a tertiary care hospital

Publication date: Available online 22 February 2018
Source:American Journal of Infection Control
Author(s): Xavier Schwartz, Michelle Schmitz, Nasia Safdar, Aurora Pop-Vicas
Although surgical hand antisepsis is paramount to surgical infection prevention, adherence to correct technique may be suboptimal. We conducted direct observations and semistructured interviews to identify barriers and facilitators to appropriate surgical hand antisepsis in a tertiary care hospital. Only 18% (9 out of 50) surgical hand antisepsis observations were fully compliant with the recommended application techniques. Most surgical staff members considered lack of organizational oversight, monitoring, and direct hands-on training as important barriers to adherence.



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Correlation between hospital-level antibiotic consumption and incident health care facility-onset Clostridium difficile infection

Publication date: March 2018
Source:American Journal of Infection Control, Volume 46, Issue 3
Author(s): Page E. Crew, Nathaniel J. Rhodes, J. Nicholas O'Donnell, Cristina Miglis, Elise M. Gilbert, Teresa R. Zembower, Chao Qi, Christina Silkaitis, Sarah H. Sutton, Marc H. Scheetz
BackgroundThe purpose of this single-center, ecologic study is to characterize the relationship between facility-wide (FacWide) antibiotic consumption and incident health care facility-onset Clostridium difficile infection (HO-CDI).MethodsFacWide antibiotic consumption and incident HO-CDI were tallied on a monthly basis and standardized, from January 2013 through April 2015. Spearman rank-order correlation coefficients were calculated using matched-months analysis and a 1-month delay. Regression analyses were performed, with P < .05 considered statistically significant.ResultsFacWide analysis identified a matched-months correlation between ceftriaxone and HO-CDI (ρ = 0.44, P = .018). A unit of stem cell transplant recipients did not have significant correlation between carbapenems and HO-CDI in matched months (ρ = 0.37, P = .098), but a significant correlation was observed when a 1-month lag was applied (ρ = 0.54, P = .014).DiscussionThree statistically significant lag associations were observed between FacWide/unit-level antibiotic consumption and HO-CDI, and 1 statistically significant nonlagged association was observed FacWide. Antibiotic consumption may convey extended ward-level risk for incident CDI.ConclusionsConsumption of antibiotic agents may have immediate and prolonged influence on incident CDI. Additional studies are needed to investigate the immediate and delayed associations between antibiotic consumption and C difficile colonization, infection, and transmission at the hospital level.



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TMS over the supramarginal gyrus delays selection of appropriate grasp orientation during reaching and grasping tools for use

Publication date: Available online 9 March 2018
Source:Cortex
Author(s): Tomás McDowell, Nicholas P. Holmes, Alan Sunderland, Martin Schürmann
Tool use, a ubiquitous part of human behaviour, requires manipulation control and knowledge of tool purpose. Neuroimaging and neuropsychological research posit that these two processes are supported by separate brain regions, ventral premotor and inferior parietal for manipulation control, and posterior middle temporal cortex for tool knowledge, lateralised to the left hemisphere. Action plans for tool use need to integrate these two separate processes, which is likely supported by the left supramarginal gyrus (SMG). However, whether this integration occurs during action execution is not known. To clarify the role of the SMG we conducted two experiments in which healthy participants reached to grasp everyday tools with the explicit instruction to use them directly following their grasp. To study the integration of manipulation control and tool knowledge within a narrow time window we mechanically perturbed the orientation of the tool to force participants to correct grasp orientation 'on-line' during the reaching movement. In experiment 1, twenty healthy participants reached with their left hand to grasp a tool. Double-pulse transcranial magnetic stimulation (TMS) was applied, in different blocks over left or right SMG at the onset of perturbation. Kinematic data revealed delayed and erroneous online correction after TMS over left and right SMG. In Experiment 2 twelve participants reached, in different blocks, with their left or right hand and TMS was applied over SMG ipsilateral to the reaching hand. A similar effect on correction was observed for ipsilateral stimulation when reaching with the left and right hands, and no effect of or interaction with hemisphere was observed. Our findings implicate a bilateral role of the SMG in correcting movements and selection of appropriate grasp orientation during reaching to grasp tools for use.



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Phase of beta-frequency tACS over primary motor cortex modulates corticospinal excitability

Publication date: Available online 9 March 2018
Source:Cortex
Author(s): Lukas Schilberg, Tahnée Engelen, Sanne ten Oever, Teresa Schuhmann, Beatrice de Gelder, Tom A. de Graaf, Alexander T. Sack
The assessment of corticospinal excitability by means of TMS-induced MEPs is an established diagnostic tool in neurophysiology and a widely used procedure in fundamental brain research. However, concern about low reliability of these measures has grown recently. One possible cause of high variability of MEPs under identical acquisition conditions could be the influence of oscillatory neuronal activity on corticospinal excitability. Based on research showing that tACS can entrain neuronal oscillations we here test whether alpha or beta frequency tACS can influence corticospinal excitability in a phase-dependent manner. We applied tACS at individually calibrated alpha- and beta-band oscillation frequencies, or we applied sham tACS. Simultaneous single TMS pulses time locked to eight equidistant phases of the ongoing tACS signal evoked MEPs. To evaluate offline effects of stimulation frequency, MEP amplitudes were measured before and after tACS. To evaluate whether tACS influences MEP amplitude, we fitted one-cycle sinusoids to the average MEPs elicited at the different phase conditions of each tACS frequency. We found no frequency-specific offline effects of tACS. However, beta-frequency tACS modulation of MEPs was phase-dependent. Post hoc analyses suggested that this effect was specific to participants with low (<19Hz) intrinsic beta frequency. In conclusion, by showing that beta tACS influences MEP amplitude in a phase-dependent manner, our results support a potential role attributed to neuronal oscillations in regulating corticospinal excitability. Moreover, our findings may be useful for the development of TMS protocols that improve the reliability of MEPs as a meaningful tool for research applications or for clinical monitoring and diagnosis.



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Sounds from seeing silent motion: Who hears them, and what looks loudest?

Publication date: Available online 9 March 2018
Source:Cortex
Author(s): Christopher J. Fassnidge, Elliot D. Freeman
Some people hear what they see: car indicator lights, flashing neon shop signs, and people's movements as they walk may all trigger an auditory sensation, which we call the visual-evoked auditory response (vEAR or 'visual ear'). We have conducted the first large-scale online survey (N>4000) of this little-known phenomenon. We analysed the prevalence of vEAR, what induces it, and what other traits are associated with it.We asked respondents if they had previously experienced vEAR. Participants then rated silent videos for vividness of evoked auditory sensations, and answered additional questions.Prevalence appeared higher relative to other typical synaesthesias. Prior awareness and video ratings were associated with greater frequency of other synaesthesias, including flashes evoked by sounds, and musical imagery. Higher-rated videos often depicted meaningful events that predicted sounds (e.g. collisions). However, ratings were also driven by the low-level 'motion energy' of non-predictive flashing or moving patterns, specifically in respondents who had previous awareness of vEAR.Our motion energy analysis suggests that signals from visual motion processing may affect audition relatively directly, without requiring higher-level interpretative processes. While some popular explanations of synaesthesia assume rare and specific patterns of brain hyper-connectivity, the apparently high prevalence of vEAR, and its broad association with other synaesthesias and traits, are consistent with a common dependence on normal variations in physiological mechanisms of disinhibition or excitability of sensory brain areas and their functional connectivity, rather than just on specific patterns of hyper-connectivity. The prevalence of vEAR makes it easier to test such hypotheses further, and makes the results more relevant to understanding not only synaesthetic anomalies but also normal perception.



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Controlled semantic cognition relies upon dynamic and flexible interactions between the executive ‘semantic control’ and hub-and-spoke ‘semantic representation’ systems

Publication date: Available online 9 March 2018
Source:Cortex
Author(s): Rocco Chiou, Gina F. Humphreys, JeYoung Jung, Matthew A. Lambon Ralph
Built upon a wealth of neuroimaging, neurostimulation, and neuropsychology data, a recent proposal set forth a framework termed controlled semantic cognition (CSC) to account for how the brain underpins the ability to flexibly use semantic knowledge (Lambon Ralph et al., 2017, Nature Reviews Neuroscience). In CSC, the 'semantic control' system, underpinned predominantly by the prefrontal cortex, dynamically monitors and modulates the 'semantic representation' system that consists of a 'hub' (anterior temporal lobe, ATL) and multiple 'spokes' (modality-specific areas). CSC predicts that unfamiliar and exacting semantic tasks should intensify communication between the 'control' and 'representation' systems, relative to familiar and less taxing tasks. In the present study, we used fMRI to test this hypothesis. Participants paired unrelated concepts by canonical colours (a less accustomed task – e.g., pairing ketchup with fire-extinguishers due to both being red) or paired well-related concepts by semantic relationship (a typical task – e.g., ketchup is related to mustard). We found the 'control' system was more engaged by atypical than typical pairing. While both tasks activated the ATL 'hub', colour pairing additionally involved occipitotemporal 'spoke' regions abutting areas of hue perception. Furthermore, we uncovered a gradient along the ventral temporal cortex, transitioning from the caudal 'spoke' zones preferring canonical colour processing to the rostral 'hub' zones preferring semantic relationship. Functional connectivity also differed between the tasks: Compared with semantic pairing, colour pairing relied more upon the inferior frontal gyrus, a key node of the control system, driving enhanced connectivity with occipitotempral 'spoke'. Together, our findings characterise the interaction within the neural architecture of semantic cognition – the control system dynamically heightens its connectivity with relevant components of the representation system, in response to different semantic contents and difficulty levels.



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Early and long term anamnestic response to HBV booster dose among fully vaccinated Egyptian children during infancy

Publication date: Available online 9 March 2018
Source:Vaccine
Author(s): Iman I. Salama, Samia M. Sami, Zeinab N. Said, Somaia I. Salama, Thanaa M. Rabah, Ghada A. Abdel-Latif, Dalia M. Elmosalami, Rehan M. Saleh, Aida M. Abdel Mohsin, Ammal M. Metwally, Amal I. Hassanin, Hanaa M. Emam, Samia A. Hemida, Safaa M. Elserougy, Fatma A. Shaaban, Walaa A. Fouad, Amira Mohsen, Manal H. El-Sayed
ObjectiveTo evaluate early and long term anamnestic response to a booster dose of HBV vaccine among non-seroprotected children.Subjects and methodA national community based project was carried out on 3600 children aged 9 months to 16 years, fully vaccinated during infancy. They were recruited from 6 governorates representing Egypt. It revealed that 1535 children (42.8%) had non sero-protective anti-HBs (<10 IU/L) and were HBsAg or anti-HBc negative. A challenging dose of 10 μg of mono-valent Euvax HBV vaccine was given to 1121/1535 children. Quantitative assessment of anti-HBs was performed to detect early (2–4 weeks) and long term (one year) anamnestic responses.ResultsEarly anamnestic response developed among 967/1070 children (90.3%).Children having detectable anti-HBs (1–9 IU/L) significantly developed early anamnestic response (90%) compared to 85% with undetectable anti-HBs (<1 IU/L), P < 0.001. Multiple logistic analysis revealed that undetectable anti-HBs, living in rural residence and children aged 15–16 years were the most significant predicting risk factors for the absence of early anamnestic response (<10 IU/L), with AOR 2.7, 2.7 & 4.7 respectively. After one year, long term anamnestic response was absent among 15% of children who previously showed early response. Poor early anamnestic response and undetectable pre-booster anti-HBs were the significant predicting risk factors for absent long term anamnestic response, with AOR 18.7 & 2.7 respectively.ConclusionImmunological memory for HBV vaccine outlasts the presence of anti- HBs and HBV vaccination program provides effective long term protection even in children showing waning or undetectable concentrations of anti-HBs. This signifies no need for a booster dose especially to healthy children.



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Chicken immune response following in ovo delivery of bacterial flagellin

Publication date: Available online 9 March 2018
Source:Vaccine
Author(s): M.M. Vaezirad, M.G. Koene, J.A. Wagenaar, J.P.M. van Putten
In ovo immunization of chicken embryos with live vaccines is an effective strategy to protect chickens against several viral pathogens. We investigated the immune response of chicken embryos to purified recombinant protein. In ovo delivery of Salmonella flagellin to 18-day old embryonated eggs resulted in elevated pro-inflammatory chIL-6 and chIL-8 (CXCL8-CXCLi2) cytokine transcript levels in the intestine but not in the spleen at 24 h post-injection. Analysis of the chicken Toll-like receptor (TLR) repertoire in 19-day old embryos revealed gene transcripts in intestinal and spleen tissue for most chicken TLRs, including TLR5 which recognizes Salmonella flagellin (FliC). The in ovo administration of FliC did not alter TLR transcript levels, except for an increase in intestinal chTLR15 expression. Measurement of the antibody response in sera collected at day 11 and day 21 post-hatch demonstrated high titers of FliC-specific antibodies for the animals immunized at the late-embryonic stage in contrast to the mock-treated controls. The successful in ovo immunization with purified bacterial antigen indicates that the immune system of the chicken embryo is sufficiently mature to yield a strong humoral immune response after single exposure to purified protein. This finding strengthens the basis for the development of in ovo protein-based subunit vaccines.



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Post stem cell transplantation revaccination: A survey of the current practices in India

Publication date: Available online 9 March 2018
Source:Vaccine
Author(s): M. Joseph John, Amrith Mathew, Sunil Bhat, Anushree Prabhakaran, Biju George, Jacob John
BackgroundHematopoietic stem cell transplant (HSCT) recipients are more susceptible to infections from vaccine preventable diseases (VPDs) than the general population. Indian stem cell transplant registry (ISCTR) post-BMT vaccination guidelines were formulated in 2015. The objective of the survey was to assess the compliance to these guidelines among transplant physicians in India.Materials and methodsThis is a cross-sectional survey executed as the quantitative research strategy to explore the various aspects of vaccination practices among transplant physicians in India. The 'data collection tool' included 36 predetermined questions related to vaccination of the patients and their close contacts. Theoretical construct of the questionnaire was face-validated and questionnaire survey forms were emailed individually as attachments or by google forms. This study is being reported based on the checklist for reporting results of internet e-surveys statement guidelines.ResultsSurvey forms were sent to 105 transplant physicians in India, 62% of whom responded representing 78.8% of transplant centers in India. More than 90% of allogeneic transplant physicians and 64% of autologous transplant physicians offered vaccination. Over two third of the physicians responded that they would discontinue vaccination at the onset of cGVHD. Fewer than one third physicians offered vaccination against Hepatitis A, Typhoid or Meningococcal infections. Forty two percent of respondents were unaware of the ISCTR post-BMT vaccination protocol. Only 47% of respondents reported complete adherence to any of the protocols they were following. Immune reconstitution to guide vaccination was available only to 13.3 percent of respondents.ConclusionThere is a need to improve the implementation strategies of vaccination in HSCT recipients to increase the adherence and continuation of it even in the presence of GVHD. There is also a need to extend the vaccination among VPDs especially prevalent in India.



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Phase II Study of Preoperative Treatment with External Radiotherapy Plus Panitumumab in Low‐Risk, Locally Advanced Rectal Cancer (RaP Study/STAR‐03)

AbstractBackground.Treatment with fluoropyrimidines and concomitant long‐course external radiotherapy (RTE) is the standard of care in locally advanced rectal cancer (LARC) preoperative chemoradiation. A randomized phase II study (RaP/STAR‐03) was conducted that aimed to evaluate the activity and safety of the monoclonal antibody anti‐epidermal growth factor receptor panitumumab as a single agent in combination with radiotherapy in low‐risk LARC preoperative treatment.Materials and Methods.Patients had adenocarcinoma of the mid‐low rectum, cT3N− or cT2–T3N+, KRAS wild‐type status, and negative circumferential radial margin. Panitumumab was administered concomitant to RTE. Rectal surgery was performed 6–8 weeks after the end of preoperative treatment. The adjuvant chemotherapy regimen was FOLFOX. The primary endpoint was the pathologic complete response (pCR) rate. The sample size was calculated using Simon's two‐stage design. A pCR of 16% was considered to qualify the experimental treatment for further testing.Results.Ninety‐eight patients were enrolled in 13 Italian centers from October 2012 to October 2015. Three panitumumab infusions were administered in 92 (93.4%) patients. The RTE compliance was median dose 50.4 Gy; ≥28 fractions in 82 (83.7%) patients. Surgical treatment was performed in 92 (93.9%) patients, and no severe intraoperative complications were observed. A pCR was observed in 10 (10.9%) patients (95% confidence interval, 4.72%–17.07%). Pathological downstaging occurred in 45 (45.9%) patients. Grade 3 toxicities were observed in 22 (22.3%) patients, and the common adverse events were skin rash in 16 (16.3%) patients. No grade 4 toxicities were reported.Conclusion.The pCR rate (our primary endpoint), at only 10.9%, did not reach the specified level considered suitable for further testing. However, the analysis showed a good toxicity profile and compliance to concomitant administration of panitumumab and RTE in preoperative treatment of LARC. The pCR evaluation in all wild‐type RAS is ongoing.Implications for Practice.The aim of the RaP/STAR‐03 study was to evaluate the activity and safety of monoclonal antibody anti‐epidermal growth factor receptor (EGFR) panitumumab as a single agent without chemotherapy in low‐risk, locally advanced rectal cancer (LARC) preoperative treatment. Nevertheless, the use of panitumumab in combination with radiotherapy in preoperative treatment in patients with KRAS wild type and low‐risk LARC did not reach the pathologic complete response primary endpoint. This study showed a good toxicity profile and compliance to combination treatment. Further analysis of NRAS and BRAF on tissue and circulating levels of the EGFR ligands and vascular factors (soluble vascular endothelial growth factor, E‐selectin) may provide insight on the potential molecular pathways involved in the anti‐EGFR response.

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Implementing Keytruda/Pembrolizumab Testing in Clinical Practice

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The Use of Virtual Technology as an Intervention for Wheelchair Skills Training: A Systematic Review

Publication date: Available online 10 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Jean-François Lam, Laurent Gosselin, Paula W. Rushton
ObjectiveTo provide a comprehensive description of the current state of knowledge regarding the use of virtual technology (VT) for wheelchair skills training.Data sourcesThe Cochrane Library, MEDLINE, CINAHL, EMBASE, ACM, IEEE Xplore, Inspec, and Web of Science databases were searched for relevant articles from 1990 to February 2016.Study selectionWe included peer-reviewed studies or long conference proceedings that examined the use of VT as a medium to provide a wheelchair skills training intervention for any population with any diagnosis using any research design. One investigator screened the titles and abstracts, then 2 investigators independently reviewed the full-text articles. Disagreements regarding inclusion were resolved by consensus or a third reviewer. Ten studies were included out of 4994 initially identified.Data extractionTwo investigators extracted data to systematically assess the studies' findings into 6 tables (study design and participant characteristics, equipment and technology used, intervention characteristics, outcome measures, and outcomes).Data synthesisMost studies demonstrated that VT wheelchair skills training showed improved outcomes such as simulation score, completion time, and number of collisions in the virtual environment and/or in real world. However, subject characteristics, equipment, virtual environment, intervention tasks, and outcome measures varied across the studies.ConclusionsThere exists a variety of studies using VT as an intervention for wheelchair skills training. Given the positive outcomes for most of the studies, it appears as though VT may indeed be a solution that can help to alleviate barriers to wheelchair skills training and subsequently improve wheelchair user skill.



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Rhythm perception and production abilities and their relationship to gait after stroke

Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Kara K. Patterson, Jennifer S. Wong, Svetlana Knorr, Jessica A. Grahn
ObjectivesTo assess rhythm abilities, describe their relationship to clinical presentation, and to determine if rhythm production independently contributes to temporal gait asymmetry post-stroke.DesignCross-sectional.SettingLarge urban rehabilitation hospital and university.ParticipantsIndividuals with subacute and chronic stroke (n=39) and data for healthy adults extracted from a pre-existing database (n=21).InterventionNot applicable.Main outcome measuresStroke group: National Institutes of Health Stroke Scale (NIHSS), Chedoke-McMaster Stroke Assessment (CMSA) leg and foot scales, Montreal Cognitive Assessment (MoCA), rhythm perception and production (Beat Alignment Test; BAT) and spatiotemporal gait parameters were assessed. Temporal gait asymmetry (TGA) was quantified with the swing time symmetry ratio. Healthy group: age and beat perception scores assessed by BAT. Rhythm perception of the stroke group and healthy adults was compared with ANOVA. Spearman correlations quantified the relationship between rhythm perception and production abilities and clinical measures. Multiple linear regression assessed the contribution of rhythm production along with motor impairment and time post stroke to TGA.ResultsRhythm perception in the stroke group was worse than healthy adults (F(1,56) = 17.5, p=0.0001) Within the stroke group, rhythm perception was significantly correlated with CMSA leg (rs =0.33, p=0.04), and foot (rs =0.49, p=0.002) scores but not NIHSS or MOCA scores. The model for TGA was significant (F(3,35)=12.8, p<0.0001) with CMSA leg scores, time post-stroke and asynchrony of rhythm production explaining 52% of the variance.ConclusionsRhythm perception is impaired after stroke and temporal gait asymmetry relates to impairments in producing rhythmic movement. These results may have implications for the use of auditory rhythmic stimuli to cue motor responses post-stroke. Future work will explore brain responses to rhythm processing post-stroke.



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Self-regulatory strategies as correlates of physical activity behavior in persons with multiple sclerosis

Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Katie L. Cederberg, Julia M. Balto, Robert W. Motl
ObjectiveTo examine self-regulation strategies as correlates of physical activity in persons with multiple sclerosis (MS).DesignCross-sectional, or survey, study.SettingUniversity-based research laboratory.ParticipantsConvenience sample of 68 persons with MS.InterventionsNot applicable.Main Outcome MeasuresExercise Self-Efficacy Scale (EXSE), Physical Activity Self-Regulation Scale (PASR-12), and Godin Leisure-Time Exercise Questionnaire (GLTEQ).ResultsCorrelation analyses indicated that GLTEQ scores were positively and significantly associated with overall self-regulation (r=0.43), self-monitoring (r=0.45), goal-setting (r=0.27), reinforcement (r=0.30), time management (r=0.41), and relapse prevention (r=0.53) PASR-12 scores. Regression analyses indicated that relapse prevention (B=5.01; SE B=1.74; β=0.51) and self-monitoring (B=3.65; SE B=1.71; β=0.33) were unique predictors of physical activity behavior, and relapse prevention demonstrated a significant association with physical activity behavior that was accounted for by EXSE.ConclusionsOur results indicate that self-regulatory strategies, particularly relapse prevention, may be important correlates of physical activity behavior that can inform the design of future behavioral interventions in MS.



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Aerobic stimulus induced by virtual reality games in stroke survivors

Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Julio Cesar Silva de Sousa, Camila Torriani-Pasin, Amanda Barboza Tosi, Rafael Yokoyama Fecchio, Luiz Augusto Riani da Costa, Cláudia Lúcia de Moraes Forjaz
ObjectiveTo evaluate whether virtual reality games (VRG) in stroke survivors produce significant and reproducible heart rate (HR) and oxygen consumption (VO2) responses during their execution, corresponding to an intensity between the anaerobic threshold (AT) and the respiratory compensation point (RCP).DesignSingle subjects repeated measure designSettingStroke survivors registered from a rehabilitation programParticipantsTwelve chronic hemiparetic stroke survivors (10 men, 58 ± 12 years) rated at 3 or 4 in the Functional Ambulation Categories (FAC).InterventionsSubjects underwent, in a random order, two identical sessions of VRG (console Xbox360+Kinect) and one control session (CONT – 38 min watching a movie). The VRG sessions were composed by four sets of VRG (3 min of Boxing, 1 min for changing the game and 4 min of Tennis) interspaced by 2 min of rest.Main Outcome MeasuresHR and VO2 were measured during the experimental sessions and compared to HR and VO2 obtained at AT and RCP assessed in a maximal cardiopulmonary exercise test.ResultsHR and VO2 during VRG presented good reproducibility (intraclass correlation coefficient > 0.91 and > 0.85 and coefficient of variation < 6.7 and < 13.7%, respectively). HR during VRG was similar to AT and significantly lower than RCP (p<0.05), while VO2 was significantly lower than AT and RCP (p<0.05).ConclusionsAn acute session of VRG composed by Tennis and Boxing games of the console XBox360+Kinect promotes reproducible responses of HR and VO2 that corresponded, respectively, to AT and below AT, characterizing a low intensity aerobic stimulus.



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The Effects of Timing and Intensity of Neurorehabilitation on Functional Outcome after Traumatic Brain Injury: a Systematic Review & Meta-Analysis

Publication date: Available online 8 February 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Marsh Königs, Eva A. Beurskens, Lian Snoep, Erik J.A. Scherder, Jaap Oosterlaan
ObjectiveTo systematically review evidence on the effects of timing and intensity of neurorehabilitation on the functional recovery of patients with moderate to severe traumatic brain injury (TBI) and aggregate the available evidence using meta-analytic methods.Data sourcesPubmed, Embase, PsycINFO and Cochrane Database.Data selectionElectronic databases were searched for prospective controlled clinical trials assessing the effect of timing or intensity of multidisciplinary neurorehabilitation programs on functional outcome of patients with moderate or severe TBI. A total of 5,961 unique records were screened for relevance, of which 58 full-text articles were assessed for eligibility by two independent authors. Eleven articles were included for systematic review and meta-analysis.Data extractionTwo independent authors performed data extraction and risk of bias analysis using the Cochrane Collaboration Tool. Discrepancies between authors were resolved by consensus.Data synthesisSystematic review of a total of six randomized controlled trials, one quasi-randomized trails and four controlled trials revealed consistent evidence for a beneficial effect of early onset neurorehabilitation in the trauma center and intensive neurorehabilitation in the rehabilitation facility on functional outcome, as compared to usual care. Meta-analytic quantification revealed a large-sized positive effect for early onset rehabilitation programs (d = 1.02, p < .001, 95%-confidence interval [CI]: 0.56-1.47) and a medium-sized positive effect for intensive neurorehabilitation programs (d = 0.67, p < .001. 95%-CI: 0.38-0.97) as compared to usual care. These effects were replicated based on solely studies with a low overall risk of bias.ConclusionsThe available evidence indicates that early onset neurorehabilitation in the trauma center and more intensive neurorehabilitation in the rehabilitation facility promote functional recovery of patients with moderate to severe TBI as compared to usual care. These findings support the integration of early onset and more intensive neurorehabilitation in the chain of care for patients with TBI.



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Translational Control by Prion-like Proteins

Publication date: Available online 9 March 2018
Source:Trends in Cell Biology
Author(s): Liying Li, J.P. McGinnis, Kausik Si
Prion-like proteins overlap with intrinsically disordered and low-complexity sequence families. These proteins are widespread, especially among mRNA-binding proteins. A salient feature of these proteins is the ability to form protein assemblies with distinct biophysical and functional properties. While prion-like proteins are involved in myriad of cellular processes, we propose potential roles for protein assemblies in regulated protein synthesis. Since proteins are the ultimate functional output of gene expression, when, where, and how much of a particular protein is made dictates the functional state of a cell. Recent finding suggests that the prion-like proteins offer unique advantages in translation regulation and also raises questions regarding formation and regulation of protein assemblies.



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Interleukin-31 and interleukin-31 receptor–new therapeutic targets for atopic dermatitis

Abstract

Atopic dermatitis (AD) is characterized by chronic, eczematous, severe pruritic skin lesions caused by skin barrier dysfunction and T helper (Th)2 cell–mediated immunity. Interleukin (IL)-31 is a potent pruritogenic cytokine primarily produced by Th2 cells. Both IL-31 transgenic mice and wild-type mice treated with IL-31 exhibit AD-like skin lesions and scratching behaviour. IL-31 receptor α-chain (IL-31RA) are also expressed in peripheral nerves and epidermal keratinocytes, and the roles of IL-31 on pruritus and skin barrier have been investigated. Recently, an anti–IL-31 receptor antibody was shown to significantly improve pruritus in AD patients. This review focuses on IL-31 and IL-31RA in AD.

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High lymphocyte count during neoadjuvant chemoradiotherapy is associated with improved pathologic complete response in esophageal cancer

Publication date: Available online 9 March 2018
Source:Radiotherapy and Oncology
Author(s): Penny Fang, Wen Jiang, Rajayogesh Davuluri, Cai Xu, Sunil Krishnan, Radhe Mohan, Albert C. Koong, Charles C. Hsu, Steven H. Lin
Background and purposeNeoadjuvant chemoradiation (nCRT) can reduce tumor infiltrating lymphocytes. We examined absolute lymphocyte count (ALC) nadir during nCRT for esophageal cancer (EC) and pathologic complete response (pCR).Materials and methodsPatients with stage I–IVA EC (n = 313) treated 2007–2013 with nCRT followed by surgery were analyzed. ALC was obtained before, during/weekly, and one month after CRT. pCR was defined as no viable tumor cells at surgery. High ALC was defined as nadir of ≥0.35 × 10³/μL (highest tertile). Comparison of continuous and categorical variables by pCR was assessed by ANOVA and Pearson's chi-square. Univariate/multivariate logistic regression was used to assess predictors of pCR and high ALC nadir.ResultsEighty-nine patients (27.8%) achieved a complete pathological response (pCR). For patients with pCR, median ALC nadir was significantly higher than those without (0.35 × 10³/μL vs 0.29 × 10³/μL, p = 0.007). Patients maintaining high ALC nadir had a higher pCR rate (OR1.82, 95%CI 1.08–3.05, p = 0.024). Predictors of high ALC included treatment with proton therapy vs. IMRT (OR4.18, 95%CI 2.34–7.47, p < 0.001), smoking at diagnosis (OR2.80, 95%CI 1.49–5.25, p = 0.001), early stage I–II disease (OR2.33, 95%CI 1.32–4.17, p = 0.005), and SCC histology (OR3.70, 95%CI 1.01–14.29, p = 0.048). Mean body dose (MBD) was inversely related to high ALC nadir (OR0.77 per Gy, 95%CI 0.70–0.84, p < 0.001).ConclusionA higher ALC level during nCRT is associated with a higher rate of pCR for esophageal cancer patients undergoing trimodality therapy.



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Inter-institutional analysis demonstrates the importance of lower than previously anticipated dose regions to prevent late rectal bleeding following prostate radiotherapy

Publication date: Available online 9 March 2018
Source:Radiotherapy and Oncology
Author(s): Maria Thor, Andrew Jackson, Michael J. Zelefsky, Gunnar Steineck, Asa Karlsdòttir, Morten Høyer, Mitchell Liu, Nicola J. Nasser, Stine E. Petersen, Vitali Moiseenko, Joseph O. Deasy
PurposeTo investigate whether inter-institutional cohort analysis uncovers more reliable dose–response relationships exemplified for late rectal bleeding (LRB) following prostate radiotherapy.Material and methodsData from five institutions were used. Rectal dose–volume histograms (DVHs) for 989 patients treated with 3DCRT or IMRT to 70–86.4 Gy@1.8–2.0 Gy/fraction were obtained, and corrected for fractionation effects (α/β = 3 Gy). Cohorts with best-fit Lyman–Kutcher–Burman volume-effect parameter a were pooled after calibration adjustments of the available LRB definitions. In the pooled cohort, dose–response modeling (incorporating rectal dose and geometry, and patient characteristics) was conducted on a training cohort (70%) followed by final testing on the remaining 30%. Multivariate logistic regression was performed to build models with bootstrap stability.ResultsTwo cohorts with low bleeding rates (2%) were judged to be inconsistent with the remaining data, and were excluded. In the remaining pooled cohorts (n = 690; LRB rate = 12%), an optimal model was generated for 3DCRT using the minimum rectal dose and the absolute rectal volume receiving less than 55 Gy (AUC = 0.67; p = 0.0002; Hosmer–Lemeshow p-value, pHL = 0.59). The model performed nearly as well in the hold-out testing data (AUC = 0.71; p < 0.0001; pHL = 0.63), indicating a logistically shaped dose–response.ConclusionWe have demonstrated the importance of integrating datasets from multiple institutions, thereby reducing the impact of intra-institutional dose–volume parameters explicitly correlated with prescription dose levels. This uncovered an unexpected emphasis on sparing of the low to intermediate rectal dose range in the etiology of late rectal bleeding following prostate radiotherapy.



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Regulators of glucocorticoid receptor function in an animal model of depression and obesity

Abstract

Obesity is a disease that often co-occurs with depression, and some evidence indicates that chronic stress in the perinatal period, in association with overactive glucocorticoids, can cause permanent changes that increase the risk of the development of both depression and obesity later in life. However, the mechanism responsible for the overly potent action of glucocorticoids in both depression and obesity is not known. The aim of the present study was to determine the expression of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) and the factors that affect GR function (FKBP51, Bag-1 and HSP70) in a prenatal stress animal model of depression, a model of obesity and a model of both depression and obesity. Prenatal stress but not high-fat diet (HFD) was found to decrease the GR concentration in the frontal cortex. The level of the Bag-1M (46 kDa) isoform was also decreased in this structure but only in prenatal-stressed animals that did not show depression-like behaviour in the Porsolt test and were fed the standard diet (STD). In the model of depression employed here, decreases in MR expression and GR co-chaperone (FKBP51) levels in the hippocampus were also observed, and HFD intensified the prenatal stress-induced changes in MR expression. The obtained results indicated that prenatal stress affected the expression of GRs, MRs and their co-chaperones in the brain, but its effects were different in the frontal cortex and hippocampus. The decrease in MR density in the hippocampus and increased plasma insulin level seemed to be the most significant changes observed in the model of the co-occurrence of depression and obesity, which could limit the neuroprotective effects associated with the activation of MR and be a marker of peripheral insulin resistance, respectively.

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Pavlovian-to-instrumental transfer: A new paradigm to assess pathological mechanisms with regard to the use of Internet applications

Publication date: 16 July 2018
Source:Behavioural Brain Research, Volume 347
Author(s): Verena Vogel, Ines Kollei, Theodora Duka, Jan Snagowski, Matthias Brand, Astrid Müller, Sabine Loeber
At present, there is a considerable lack of human studies that investigated the impact of conditioned cues on instrumental responding although these processes are considered as core mechanisms contributing to the development and maintenance of addictive behaviours. No studies are available that assessed these processes with regard to Internet gaming or Internet shopping applications.We thus developed a Pavlovian-to-instrumental transfer (PIT)-Paradigm implementing appetitive stimuli related to Internet gaming and Internet shopping applications and investigated whether an outcome-specific PIT-Effect is observed. In addition, we assessed whether the problematic use of gaming or shopping applications, personality traits and stress would affect the acquisition of knowledge of the experimental contingencies during Pavlovian training and the impact of conditioned stimuli on instrumental responding.A PIT-Paradigm, screenings for Internet gaming disorder and Internet shopping disorder (s-IAT), and questionnaires on personality traits (NEO-FFI, BIS-15) and perceived stress (PSQ20) were administered to sixty-six participants.The PIT-Paradigm demonstrated the effects of stimuli conditioned to rewards related to Internet gaming and Internet shopping applications on instrumental responding to obtain such rewards. Findings also indicated that severity of problematic Internet gaming, but not Internet shopping, contributed to the acquisition of knowledge of the experimental contingencies. Stress, extraversion, neuroticism and gender emerged as further predictors. The strength of expectancy of the different reinforcers affected the 'gaming PIT'-Effect; however, none of the variables assessed in the present study showed any effect on the 'shopping PIT'-Effect. Future studies including participants with pathological use patterns that can be classified as internet use disorder are warranted to extend these findings.



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Excitatory repetitive transcranial magnetic stimulation applied to the right inferior frontal gyrus has no effect on motor or cognitive impulsivity in healthy adults

Publication date: 16 July 2018
Source:Behavioural Brain Research, Volume 347
Author(s): Cheng-Chang Yang, Najat Khalifa, Birgit Völlm
BackgroundImpulsivity is a multi-faceted concept. It is a crucial feature of many neuropsychiatric disorders. Three subtypes of impulsivity have been identified: motor, temporal, and cognitive impulsivity. Existing evidence suggests that the right inferior frontal gyrus (rIFG) plays a crucial role in impulsivity, and such a role has been elucidated using inhibitory repetitive transcranial magnetic stimulation (rTMS). There is a dearth of studies using excitatory rTMS at the rIFG, an important gap in the literature this study aimed to address.MethodsTwenty healthy male adults completed a single-blind sham-controlled randomised crossover study aimed at assessing the efficacy of rTMS in the neuromodulation of impulsivity. This involved delivering 10-Hz excitatory rTMS to the rIFG at the intensity of 100% motor threshold with 900 pulses per session. Trait impulsivity was measured at baseline using the Barrett Impulsiveness Scale and UPPS-P Impulsiveness Scale. The Stop Signal Task (SST) and Information Sampling Task (IST), administered before and after rTMS sessions, were used as behavioural measures of impulsivity.ResultsNo significant changes on any measures from either SST or IST after active rTMS at the rIFG compared to the sham-controlled condition were found.ConclusionsExcitatory rTMS applied to the rIFG did not have a statistically significant effect on response inhibition and reflective/cognitive impulsivity. Further research is required before drawing firm conclusions. This may involve a larger sample of highly impulsive individuals, a different stimulation site or a different TMS modality such as theta burst stimulation.



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Intestinal-type adenocarcinoma of the sinonasal tract: an update

Purpose of review Intestinal-type adenocarcinoma (ITAC) is one of the most frequent sinonasal tumors, especially in European countries. The purpose of this article is to review the most recent literature, with special emphasis on biological and genetic profile and treatment guidelines. Recent findings Results on large series support transnasal endoscopic surgery as the technique of choice in the large majority of patients with ITAC. Adjuvant radiotherapy is recommended in advanced-stage and high-grade lesions. More robust data are required to confirm that early-stage, low-grade lesions can be treated with exclusive surgery. The efficacy of new chemotherapy and biotherapy regimens and the added value of heavy particle radiotherapy are currently under evaluation. With a 5-year overall survival ranging between 53 and 83%, which is mainly impacted by local recurrences, ITAC requires a more detailed understanding of its biology. Genetic and biological studies have identified alterations in the molecular pathways of EGFR, MET, and H-RAS which might be considered as potential targets for biotherapy. Summary Surgery still plays a key role in the treatment of ITAC, but multidisciplinary management is mandatory. Although further validation is needed, the role of nonsurgical treatment strategies is rising, in agreement with the progresses made in the biological profiling of the disease.

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Salivary duct carcinoma

Purpose of review The review puts new information on geno- and phenotype of salivary duct carcinoma (SDC) in the perspective of the updated 2017 WHO classification. Recent findings The proportion of SDC is increasing. This may be because of a true rise in incidence, but certainly to better diagnostic tests and changed WHO definitions. In this light, a substantial proportion of carcinoma expleomorphic adenoma is now attributed to the category of SDC. 'Low-grade SDC' and 'SDC in-situ' of the former WHO classification, are now named low-grade and high-grade intraductal carcinoma (IDC), respectively. Recent series quantify biologic aggressiveness: perineural growth, vascular invasion, and extracapsular extension in lymph node metastasis are each observed in two out of three patients with SDC. Most patients die within 3 years, but once 5-year disease-free survival is reached, further disease activity is exceptional. The typical molecular biological profile with high human epidermal growth factor receptor 2 and androgen receptor expression is increasingly successfully exploited in clinical trials for advanced SDC. Summary The aggressive SDC is increasingly diagnosed. Despite intensive combined surgery and radiation therapy, many patients recur, for whom new bullets, targeting the molecular biological mechanisms, are the subject of ongoing clinical trials.

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Nature and role of surgical margins in transoral laser microsurgery for early and intermediate glottic cancer

Purpose of review Summarize recent findings regarding the impact of margin status on oncologic outcomes and organ preservation, as well as evaluate possible management policies of close and positive margins after transoral laser microsurgery (TLM) for Tis-T2 glottic carcinomas. Recent findings Impact of margin status on survival rates remains controversial, whereas some authors found close and positive margins to be independent risk factors for recurrence and poorer survival rates, others did not find any significant variations compared with negative ones. A common trend can be observed in performing a watchful waiting policy or second look TLM in patients with close-superficial and positive single-superficial margins. Further treatment seems preferable in case of deep and positive multiple superficial margins. Summary Positive margins are present in up to 50% of patients treated by TLM, even though a high rate of false positivity, reaching 80%, has been described. Close and positive single superficial margins seem to be linked to higher recurrence rates compared with negative margins, even though watchful wait and see policy, especially when performed by adjunctive visual aids like Narrow Band Imaging, maintains good final oncological and organ preservation outcomes. Further treatments are required in case of deep margin positivity.

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