European S3-Guideline on the systemic treatment of psoriasis vulgaris – Update Apremilast and Secukinumab – EDF in cooperation with EADV and IPC

http://ift.tt/2wX74Fq

Microstructure-informed slow diffusion tractography in humans enhances visualisation of fibre pathways

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): Farida Grinberg, Ivan I. Maximov, Ezequiel Farrher, N. Jon Shah
Conventional fibre tractography methods based on diffusion tensor imaging exploit diffusion anisotropy and directionality in the range of low diffusion weightings (b-values). High b-value Biexponential Diffusion Tensor Analysis reported previously has demonstrated that fractional anisotropy of the slow diffusion component is essentially higher than that of conventional diffusion tensor imaging whereas popular compartment models associate this slow diffusion component with axonal water fraction. One of the primary aims of this study is to elucidate the feasibility and potential benefits of "microstructure-informed" whole-brain slow-diffusion fibre tracking (SDIFT) in humans. In vivo diffusion-weighted images in humans were acquired in the extended range of diffusion weightings≤6000smm⁻² at 3T. Fast and slow diffusion tensors were reconstructed using the bi-exponential tensor decomposition, and a detailed statistical analysis of the relevant whole-brain tensor metrics was performed. We visualised three-dimensional fibre tracts in in vivo human brains using deterministic streamlining via the major eigenvector of the slow diffusion tensor. In particular, we demonstrated that slow-diffusion fibre tracking provided considerably higher fibre counts of long association fibres and allowed one to reconstruct more short association fibres than conventional diffusion tensor imaging. SDIFT is suggested to be useful as a complimentary method capable to enhance reliability and visualisation of the evaluated fibre pathways. It is especially informative in precortical areas where the uncertainty of the mono-exponential tensor evaluation becomes too high due to decreased anisotropy of low b-value diffusion in these areas. Benefits can be expected in assessment of the residual axonal integrity in tissues affected by various pathological conditions, in surgical planning, and in evaluation of cortical connectivity, in particular, between Brodmann's areas.



http://ift.tt/2wWYfeQ

A new RF transmit coil for foot and ankle imaging at 7T MRI

Publication date: January 2018
Source:Magnetic Resonance Imaging, Volume 45
Author(s): Tales Santini, Junghwan Kim, Sossena Wood, Narayanan Krishnamurthy, Nadim Farhat, Carlos Maciel, Shailesh Raval, Tiejun Zhao, Tamer Ibrahim
A four-channel Tic-Tac-Toe (TTT) transmit RF coil was designed and constructed for foot and ankle imaging at 7T MRI. Numerical simulations using an in-house developed FDTD package and experimental analyses using a homogenous phantom show an excellent agreement in terms of B1⁺ field distribution and s-parameters. Simulations performed on an anatomically detailed human lower leg model demonstrated an B1⁺ field distribution with a coefficient of variation (CV) of 23.9%/15.6%/28.8% and average B1⁺ of 0.33μT/0.56μT/0.43μT for 1W input power (i.e., 0.25W per channel) in the ankle/calcaneus/mid foot respectively. In-vivo B1⁺ mapping shows an average B1⁺ of 0.29μT over the entire foot/ankle. This newly developed RF coil also presents acceptable levels of average SAR (0.07W/kg for 10g per 1W of input power) and peak SAR (0.34W/kg for 10g per 1W of input power) over the whole lower leg. Preliminary in-vivo images in the foot/ankle were acquired using the T2-DESS MRI sequence.



http://ift.tt/2wmnhQJ

Endocrine Mucin-Producing Sweat Gland Carcinoma of the Eyelid Associated With Mucinous Adenocarcinoma.

Endocrine mucin-producing sweat gland carcinoma, a rare, low-grade neoplasm with predilection for the eyelids, has been posited as a precursor to invasive mucinous adenocarcinoma. Endocrine mucin-producing sweat gland carcinoma and its concurrence with mucinous adenocarcinoma have received little attention in the ophthalmic literature. The combination of the 2 histologic patterns parallels endocrine ductal carcinoma in situ of the breast and its transition to Type B invasive mucinous carcinoma. The authors describe a 59-year-old man who developed a tumor of the right upper eyelid showing endocrine mucin-producing sweat gland carcinoma in the outer dermis and extensive mucinous carcinoma in the deeper tissue. Immunohistochemical analysis showed positivity for endocrine markers chromogranin, synaptophysin, CD56, estrogen, and progesterone in each histologic component of the tumor. This research was conducted in conformity with the Helsinki Declaration and HIPPA regulations. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

http://ift.tt/2wWgKyf

Keyword index

Publication date: June 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism, Volume 31, Issue 3





http://ift.tt/2vQKxqS

Supraventricular tachycardia diagnosed by smartphone ECG

Diagnosis of paroxysmal supraventricular tachycardia (PSVT) may be difficult due to its episodic nature, which can be brief and self-limited, limiting the ability for clinicians to diagnose the specific rhythm disorder in a timely manner. We present a case of PSVT, which was unable to be diagnosed through typical evaluation with an event monitor despite several years of symptoms. The patient was ultimately diagnosed using the AliveCor Mobile ECG, a smartphone-based ECG device and application, which he purchased himself and captured a typical atrioventricular node re-entrant tachycardia. The patient was then able to email his cardiologist the tracing, which led to an electrophysiology study and successful slow pathway ablation procedure. Smartphone-based technology has the potential to push diagnostic evaluations outside of the healthcare system and empower patients.

http://ift.tt/2wWZhaH

Dilation of epidural space and posterior soft tissue veins in Hirayama disease

Description

An 18-year-old man presented with distal weakness and amyotrophy of the right hand for a few months. He had no familial or personal medical history. Clinical examination showed atrophy and a marked weakness of right hypothenar and interossei muscles (grade 1/5 on Medical Research Council scale) and a mild weakness of right thumb abduction and wrist extension (4/5). Biceps, brachioradial and triceps tendon reflexes were normal and symmetric. There were no fasciculation, sensory abnormality or pain. Motor nerve conduction studies showed a reduced amplitude of compound muscle action potential of the right ulnar nerve but normal parameters of left ulnar and two median nerves. No focal slowing or conduction block was found. Studies of bilateral median, ulnar and right medial antebrachial cutaneous sensory nerves were normal. Electromyographic examination found active denervation (fibrillation potentials and neurogenic recruitment) in right C8-T1 innervated muscles (abductor pollicis brevis, first dorsal interosseus, extensor...

http://ift.tt/2wmhScv

Brainstem encephalitis and acute polyneuropathy associated with hepatitis E infection

A 59-year-old man presented with feverish illness. His Glasgow Coma Scale was 15, had reduced visual acuity in the left eye with partial left ptosis and mild left hemiparesis with an extensor left plantar. Over 48 hours, he accrued multiple cranial nerves palsies and progressed to a flaccid paralysis necessitating admission to an intensive care unit.

Cerebrospinal fluid (CSF) study showed 20 lymphocytes and raised protein. Viral and bacterial PCRs were negative. Samples for Lyme, blood-borne viruses, syphilis and autoantibodies were also negative. MRI brain showed T2 abnormalities within the brainstem. Nerve conduction studies revealed an acute motor and sensory axonal neuropathy pattern of Guillian Barre Syndrome (GBS). The patient was treated for both infective and inflammatory causes of brainstem encephalitis and GBS.

Retrospective studies confirmed the presence of hepatitis E virus (HEV) RNA in CSF and serum studies showed positive HEV IgG and IgM prior to intravenous infusion. After 3 months of intensive rehabilitation, the patient was discharged home walking with a frame.

http://ift.tt/2wWTjXm

Issue Information - TOC

http://ift.tt/2wXGHzb

Updated view on epidemiology and clinical aspects of pilomatricoma in adults

Abstract

Background

Clinically, pilomatricoma offers potential for a wide spectrum of differential diagnoses. It typically occurs in pediatric patients with the head being the most common location. A second peak of clinical presentation occurs in adults at age 50–65 years, suggesting a bimodal pattern of occurrence.

Objective

To investigate the clinical and epidemiological features of pilomatricoma in adults over 20 years old, as it is a common and frequently misdiagnosed tumor.

Methods

This was a retrospective study of pilomatricomas surgically removed at a tertiary hospital between January 1994 and December 2014. A search of the all-pathological database of patients aged over 20 years old with a pathological diagnosis of pilomatricoma was carried out.

Results

The clinical preoperative diagnosis of pilomatricoma was made in 34.0% of cases. Tumor location showed a predilection to the head and neck. Of the reported concomitant neoplasm, a majority had accompanying skin tumors.

Conclusion

We conclude that clinical features in adults were similar to those of children. This study outlines clinical presentations that should help to guide differential diagnoses. Additionally, because of similarities between the distribution and depth of vellus hair follicles and pilomatricomas, it is probable that vellus hair bulbs may be the origin of this tumor.

http://ift.tt/2wmHyG4

MTA1 expression in human cancers – Clinical and pharmacological significance

Publication date: November 2017
Source:Biomedicine & Pharmacotherapy, Volume 95
Author(s): Vijaya Lakshmi Malisetty, Vasudevarao Penugurti, Prashanth Panta, Suresh Kumar Chitta, Bramanandam Manavathi
Remarkably, majority of the cancer deaths are due to metastasis, not because of primary tumors. Metastasis is one of the important hallmarks of cancer. During metastasis invasion of primary tumor cells from the site of origin to a new organ occurs. Metastasis associated proteins (MTAs) are a small family of transcriptional coregulators that are closely associated with tumor metastasis. These proteins are integral components of nuclear remodeling and deacetylation complex (NuRD). By virtue of being integral components of NuRD, these proteins regulate the gene expression by altering the epigenetic changes such as acetylation and methylation on the target gene chromatin. Among the MTA proteins, MTA1 expression is very closely correlated with the aggressiveness of several cancers that includes breast, liver, colon, pancreas, prostate, blood, esophageal, gastro-intestinal etc. Considering its close association with aggressiveness in human cancers, MTA1 may be considered as a potential therapeutic target for cancer treatment. The recent developments in its crystal structure further strengthened the idea of developing small molecule inhibitors for MTA1. In this review, we discuss the recent trends on the diverse functions of MTA1 and its role in various cancers, with the focus to consider MTA1 as a 'druggable' target in the control of human cancers.



http://ift.tt/2wX6IhZ

Radiographic evaluation of condylar positioning in patients undergoing orthognathic surgery

Abstract

Objective

The aim of this study was to evaluate alterations in condylar positioning through submentovertex projection (Hirtz Radiographic Technique) in patients who underwent orthognathic surgery for maxillary advancement and mandibular setback with stable internal fixation.

Methods

A prospective longitudinal clinical study of 40 surgical patients presenting dentofacial deformity admitted in the Oral and Maxillofacial Surgery Department of Federal University of Paraná (UFPR) in the period between March 2013 and December 2015. We performed two submentovertex digital radiographs, one 7 days before surgery and the other one 30 days after the procedure. Cephalometric tracings were made using Radiocef® Studio 2 Software and measured the intercondylar and condylar angles (right and left).

Results

There was a decrease in the intercondylar angle (p < 0.001) and an increase in condylar angles both the right and the left side (p < 0.001) when compared with the pre and postoperative period. There was a larger increase in condylar angle on the right side in males (p = 0.007).

Conclusion

There is a tendency of decreasing of the intercondylar angle after orthognathic surgery, regardless of the alteration in the condylar angles, creating a new position of the condyle in the glenoid fossa. Patients with asymmetry may present greater alterations in the positioning of the opposite condylar to the deviation of the mandibular midline.

http://ift.tt/2xsfPZn

Shrinkage in oral squamous cell carcinoma: An analysis of tumor and margin measurements in vivo, post-resection, and post-formalin fixation

To quantify changes in tumor size and tumor-free margins following surgical resection and formalin fixation of oral cavity squamous cell carcinoma.

http://ift.tt/2wTLvGn

Shrinkage in oral squamous cell carcinoma: An analysis of tumor and margin measurements in vivo, post-resection, and post-formalin fixation

To quantify changes in tumor size and tumor-free margins following surgical resection and formalin fixation of oral cavity squamous cell carcinoma.

http://ift.tt/2wTLvGn

Intussusception caused by heterotopic gastric mucosa in small intestine: a case report

Intestinal intussusception is the most frequent cause of small bowel obstruction in children between the ages of 2 months and 5 years and often remains idiopathic in etiology, even after surgery. On microscopi...

http://ift.tt/2xh5SNN

Stem Cells and Other Emerging Agents as Innovative “Drugs” in Neurodegenerative Diseases: Benefits and Limitations

Rejuvenation Research , Vol. 0, No. 0.


http://ift.tt/2wX3qLR

Mesenchymal stem cells alleviate oxidative stress-induced mitochondrial dysfunction in the airways

iPSC-MSCs protect against oxidative stress-induced mitochondrial dysfunction, apoptosis, hyper-responsiveness and inflammation in the airways. These findings highlight the potential use of iPSC-MScs as a novel cell-based therapy for COPD.

http://ift.tt/2w3bifY

The effects of house dust mite sublingual immunotherapy (SLIT)-tablet effects on immunological biomarkers and nasal allergen challenge symptoms

SQ HDM SLIT-tablet significantly increased serum HDM-specific IgG4 and IgE blocking factor, and significantly decreased early phase nasal symptoms after nasal allergen challenge. No significant effects on cytokines or gene expression in nasal mucosa were observed.

http://ift.tt/2y1aa9L

Outpatient management of pediatric acute mastoiditis

Evaluate the Montreal Children's Hospital experience with outpatient management of uncomplicated acute mastoiditis with parenteral antibiotic therapy alone and determine if it is a safe alternative to inpatient management.

http://ift.tt/2wVxbe7

Practice patterns in the management of post-tonsillectomy hemorrhage: An American Society of Pediatric Otolaryngology survey

To evaluate practice patterns amongst pediatric otolaryngologists in the management of post-tonsillectomy hemorrhage.

http://ift.tt/2xWJ96q

Intermittent hypoxia caused cognitive dysfunction relate to miRNAs dysregulation in hippocampus

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Huabin Gao, Zhaoli Han, Shan Huang, Ruojing Bai, Xintong Ge, Fanglian Chen, Ping Lei
Intermittent hypoxia (IH) is a characteristic pathophysiological change of obstructive sleep apnea (OSA), a commonly diagnosed chronic sleep disorder. With the process of OSA, patients will suffer from the nervous system damage and appear to multiple cognitive dysfunction. The mechanism that how IH causes cognitive impairment is still unknown. Both control and experimental rats were placed in conditions absence and presence of intermittent hypoxia (IH) for 8h a day for a week, two weeks and four weeks, and then followed by behavioral assessments with Morris Water Maze (MWM) test. The results showed that the escape latency of the tested animals to IH significantly increased the escape latency on the last four training days in comparison to the control group. Consistent with this, the expressions of apoptosis/anti-apoptosis proteins were both changed in the hippocampus. Then we utilized the miRNA microarray assay to investigate the level of miRNA expression in rat hippocampus which suffered from intermittent hypoxia. It is noteworthy that the expressions of miR-26b and miR-207 were consistently dysregulated in all the experimental groups post IH. And we utilized qRT-PCR methods to verify the microarray results. Our results showed that microarray based analysis of microRNA expression in rat hippocampus after IH has shown that some microRNAs such as miR-26b and miR-207 could be involved in the OSA-induced cognitive impairments.



http://ift.tt/2vQZuJg

Environmental enrichment protects spatial learning and hippocampal neurons from the long-lasting effects of protein malnutrition early in life

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Roberto O. Soares, Everton Horiquini-Barbosa, Sebastião S. Almeida, João-José Lachat
As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development.



http://ift.tt/2gXgVFy

May the use of different background strains ‘strain’ the stress-related phenotype of GR+/− mice?

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Miriam A. Vogt, Natascha Pfeiffer, Anne Marie Le Guisquet, Christiane Brandwein, Bruno Brizard, Peter Gass, Catherine Belzung, Sabine Chourbaji
Genetically altered mice are available on different background strains. While respective backcrosses are often performed for pragmatic reasons, e.g. references, comparability, or existing protocols, the interaction between the mutations per se and the background strain often remains a neglected factor.The heterozygous mutation of the glucocorticoid receptor gene (GR) represents a well-examined model for depressive-like behavior in mice. To address the question in how far a robust depressive-like phenotype on a distinct background strain may allow a generalized conclusion, we analyzed respective phenotypes in two commonly used inbred strains: i.) C57BL/6N and ii.) BALB/c.Beside the use of different genetic models, we also extended our approach by applying two alternative paradigms to induce a depressive-like phenotype. Our study therefore comprised the model of 'unpredictable chronic mild stress' (UCMS) for four weeks and 'learned helplessness' (LH), which were used to study the role of GR, a key player in the development of depression.In the course of the experiment two cohorts of male GR^+/− mice on either C57BL/6N or BALB/c background strain underwent a behavioral test battery to assess basal and depressive-like features.While both stress paradigms were functional in inducing depressive-like changes, the results were strictly strain-dependent. The genetic consequences became even more obvious under non-stress conditions with significant effects detected in BALB/c mice, which indicates a different basal stress predisposition due to differences in the genetic background.



http://ift.tt/2vQSqfW

Full title with Editorial board members

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335





http://ift.tt/2vQh4x5

Corrigendum to “Ephrin-A5 regulates inter-male aggression in mice” [Behav. Brain Res. 286 (June) (2015) 300–307]

Publication date: 29 September 2017
Source:Behavioural Brain Research, Volume 335
Author(s): Michal Sheleg, Carrie L. Yochum, Jason R. Richardson, George C. Wagner, Renping Zhou




http://ift.tt/2gZIi1L

ATX-101 (Deoxycholic Acid Injection) Treatment in Men: Insights From Our Clinical Experience.

BACKGROUND: Excess submental fat (SMF), also called as a double chin, is an area of concern for men that can be addressed clinically. ATX-101 (deoxycholic acid injection; Kybella in the United States and Belkyra in Canada, Australia, and various European countries) is the first injectable approved for reduction of SMF. OBJECTIVE: To share the authors' clinical experience using ATX-101 in men with submental fullness and offer insights regarding how this treatment may be presented to men as an option to improve their submental profile. METHODS: Retrospective review of the authors' medical records for male patients treated with ATX-101. RESULTS: To allow for fewer ATX-101 treatments, it is recommended that a large surface area be treated at the first session. The positive changes and outcomes achieved with ATX-101 build confidence between the physician and patient, which often leads to male patients seeking other aesthetic treatments to improve their overall appearance. CONCLUSION: ATX-101 treatment is often an effective introduction to aesthetic medicine for men. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2gZ1mgt

Association of Socioeconomic and Geographic Factors With Google Trends for Tanning and Sunscreen.

BACKGROUND: Internet search trends are used to track both infectious diseases and noncommunicable conditions. OBJECTIVE: The authors sought to characterize Google Trends search volume index (SVI) for the terms "sunscreen" and tanning ("tanning salon" and "tanning bed") in the United States from 2010 to 2015 and analyze association with educational attainment, average income, and percent white data by state. METHODS: SVI is search frequency data relative to total search volume. Analysis of variance, univariate, and multivariate analyses were performed to assess seasonal variations in SVI and the association of state-level SVI with state latitudes and census data. RESULTS: Hawaii had the highest SVI for sunscreen searches, whereas Alaska had the lowest. West Virginia had the highest SVI for tanning searches, whereas Hawaii had the lowest. There were significant differences between seasonal SVI for sunscreen and tanning searches (p

http://ift.tt/2vQJ2c5

Clinical Outcomes of Radiofrequency Ablation for Unilateral and Bilateral Varicose Veins.

BACKGROUND: Approximately 20% of varicose vein are bilateral. Patients prefer a simultaneous bilateral procedure instead of 2 separate unilateral procedures. There is currently little evidence comparing bilateral and unilateral varicose vein surgeries. OBJECTIVE: To report the clinical outcomes of unilateral and bilateral radiofrequency ablation (RFA) for varicose veins. MATERIALS AND METHODS: The authors retrospectively collected data on clinical outcomes of patients who underwent RFA. They investigated clinical, etiologic, anatomic, and pathophysiologic (CEAP) score, venous clinical severity score (VCSS), and quality of life (QoL) score. RESULTS: Radiofrequency ablation was performed in 546 limbs in 385 patients. Women comprised 60.4% of the patients. The mean age was 52.3 +/- 11.6 years (range, 19-84). The occlusion rate after 2 years was 94.5%. Clinical outcomes of CEAP score, VCSS, and QoL scores improved significantly from 2.15 +/- 0.45, 2.70 +/- 2.04, and 6.91 +/- 6.69 at baseline to 2.10 +/- 0.32, 0.63 +/- 0.04, and 3.38 +/- 4.74 at the study end, respectively. The preoperative and postoperative differences in CEAP score for unilateral and bilateral RFA were 0.02 +/- 0.21 and 0.13 +/- 0.49, respectively (p = .073). Those of VCSS for unilateral and bilateral RFA were 1.87 +/- 1.50 and 4.01 +/- 2.93, respectively (p

http://ift.tt/2vQHxux

A-101, a Proprietary Topical Formulation of High-Concentration Hydrogen Peroxide Solution: A Randomized, Double-Blind, Vehicle-Controlled, Parallel Group Study of the Dose-Response Profile in Subjects With Seborrheic Keratosis of the Face.

BACKGROUND: Seborrheic keratosis (SK) is a common benign skin tumor, yet no topical treatments are approved in the United States. OBJECTIVE: To evaluate the proprietary, stabilized, high-concentration hydrogen peroxide-based topical solution A-101 (32.5% and 40% concentrations) for treatment of facial SK lesions. MATERIALS AND METHODS: In this multicenter, double-blind, vehicle-controlled study, eligible subjects were randomly assigned to receive up to 2 treatments of A-101 40%, A-101 32.5%, or vehicle solution applied to a single facial SK lesion. The primary efficacy assessment was the Physician's Lesion Assessment (PLA), a validated 4-ordinal scale. RESULTS: The primary end point, the mean reduction in PLA grade from baseline to Day 106 was 1.7 for A-101 40%, 1.4 for A-101 32.5%, and 0.1 for vehicle (p

http://ift.tt/2gXE7DB

Shave Versus Elliptical Biopsy for Melanoma Substantially Increases Re-excision Area and Length.

No abstract available

http://ift.tt/2vQVdFH

Multimodal Approach for Treating Horizontal Neck Wrinkles Using Intensity Focused Ultrasound, Cohesive Polydensified Matrix Hyaluronic Acid, and IncobotulinumtoxinA.

BACKGROUND: For the restoration of horizontal neck wrinkles, multimodal approaches using neuromodulators, intensity focused ultrasound (IFU), and fine line fillers are recommended. OBJECTIVE: To evaluate the efficacy and safety of a 1-day, multimodal approach for horizontal neck wrinkles. METHODS: Twelve female patients with horizontal neck wrinkles were treated with a combined treatment of IFU, cohesive polydensified matrix hyaluronic acid (CPMHA), and incobotulinumtoxinA. Therapeutic outcomes were assessed on Day 0 and 1, 2, 3, and 6 months thereafter. RESULTS: Horizontal neck wrinkles decreased significantly in length from a median at baseline of 269.75 mm (interquatile range [IQR], 235.35-302.94 mm) to 91.5 mm (IQR, 51.4-108.61 mm) at 1 month, 92.3 mm (IQR, 69.66-132.07 mm) at 2 months, 101.88 mm (IQR, 86-146.77 mm) at 3 months, and 109.48 mm (IQR, 85.06-148.17 mm) at 6 months after the combined treatment. The median global aesthetic improvement scale scores were 3.5 (IQR, 2-4) at 1 month, 3 (IQR, 3-3.5) at 2 months, 3 (IQR, 2-4) at 3 months, and 3 (IQR, 3-3) at 6 months. Post-treatment petechiae resolved completely within 7 days, and CPMHA-induced lumps disappeared within 1 month. CONCLUSION: The present data demonstrated that the multimodal, combined treatment used in the present study provides satisfactory and long-lasting therapeutic outcomes by targeting different pathogenetic factors of horizontal neck wrinkles. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2vQyHwZ

Commentary on The Nasal Tip Rotation Flap for Reconstruction of the Lateral Nasal Tip, Anterior Ala, and Soft Triangle.

No abstract available

http://ift.tt/2gY4s4A

Repair of Defects of the Central Forehead With a Modified Banner Transposition Flap.

No abstract available

http://ift.tt/2vQy2ve

Reactive Eccrine Syringofibroadenoma Associated With Basal Cell Carcinoma: A Histologic Mimicker of Fibroepithelioma of Pinkus.

No abstract available

http://ift.tt/2gXfGGo

Safety and Efficacy of a Noninvasive 1,060-nm Diode Laser for Fat Reduction of the Flanks.

BACKGROUND: Preliminary reports indicate a hyperthermic diode laser treatment could be a safe and effective method for noninvasive fat reduction using the 1,060-nm wavelength. This wavelength penetrates the skin to heat subcutaneous adipocytes causing cellular disruption, leaving extracellular lipids, and cellular debris to be evacuated naturally by the body. OBJECTIVE: To evaluate the safety and effectiveness of this modality for noninvasive fat reduction of the flanks. MATERIALS AND METHODS: Forty-nine subjects received single laser treatment to 1 flank. Ultrasound images were taken at baseline, follow-up at 6 and 12 weeks after treatment. High-resolution photographs were taken at baseline and 12 weeks after treatment and then evaluated by independent reviewers. Adverse events recorded at all visits. Subjects completed a satisfaction questionnaire at the conclusion of the trial. RESULTS: Ultrasound images showed statistically significant (p

http://ift.tt/2vQxW6Q

Small-Particle Hyaluronic Acid Gel Treatment of Photoaged Hands.

BACKGROUND: Aging hands tend to lose subcutaneous volume resulting in prominence of the underlying vessels, tendons, and bone contributing to an aged appearance. Dermal fillers have been successfully used to improve the appearance of the aging dorsal hand. OBJECTIVE: The objective is to evaluate the safety and efficacy of a small-particle hyaluronic acid (SPHA) injectable gel for the treatment of photoaged volume loss of the hands. MATERIALS AND METHODS: This is an open-label, prospective, randomized, interventional, study. Twenty-five healthy female volunteer subjects aged 40 to 70 years with photoaged thinning of the hands received an injection of an SPHA gel to the dorsal aspect of 1 hand. Subjects were followed up for 6 months. The hands were evaluated at regular intervals according to a 5-point validated hand grading scale. RESULTS: The average hand grading scores demonstrated statistically significant improvement at all time points compared with baseline. Eighty-eight percent to 100% of subjects achieved improvement at 1 month after treatment, and 50% to 83% maintained at least 1 point improvement at 6 months. There were no adverse events reported. CONCLUSION: The investigated SPHA is a safe and effective method for improving the thinned and photoaged appearance of the hands. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2gXDfPl

Clinical and Histological Evaluations of Enlarged Facial Skin Pores After Low Energy Level Treatments With Fractional Carbon Dioxide Laser in Korean Patients.

BACKGROUND: Enlarged facial pores can be an early manifestation of skin aging and they are a common aesthetic concern for Asians. However, studies of improving the appearance of enlarged pores have been limited. OBJECTIVE: The authors aimed to study the application of CO2 fractional laser treatment in patients with enlarged facial pores. METHODS: A total of 32 patients with dilated facial pores completed 3 consecutive sessions of low energy level treatments with a fractional CO2 laser at 4-week intervals. Image analysis was performed to calculate the number of enlarged pores before each treatment session and 12 weeks after the final treatment. RESULTS: After application of laser treatments, there was a significant decrease in the number of enlarged pores. The mean number of enlarged pores was decreased by 28.8% after the second session and by 54.5% at post-treatment evaluation. Post-treatment side effects were mild and transitory. Histological and immunohistochemical analyses demonstrated clear increases in the number of collagen fibers and the expression of transforming growth factor-[beta]1. CONCLUSION: The short-term results showed that treatment with low energy level CO2 fractional laser therapy could be a safe and effective option for patients with Fitzpatrick skin Types III and IV who are concerned with enlarged pores. (C) 2017 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2vQRQPi

Mutation-Based Therapy for Duchenne Muscular Dystrophy: Antisense Treatment Arrives in the Clinic.

Author: McNally, Elizabeth M. MD, PhD; Wyatt, Eugene J. PhD

Page: 979-981

http://ift.tt/2y0Y7JN

Physical Activity and Prognosis in the TOPCAT Trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist).

Author: Hegde, Sheila M. MD, MPH; Claggett, Brian PhD; Shah, Amil M. MD, MPH; Lewis, Eldrin F. MD, MPH; Anand, Inder MD, PhD; Shah, Sanjiv J. MD; Sweitzer, Nancy K. MD, PhD; Fang, James C. MD; Pitt, Bertram MD; Pfeffer, Marc A. MD, PhD; Solomon, Scott D. MD

Page: 982-992

http://ift.tt/2w2z0J3

Physical Activity in Heart Failure With Preserved Ejection Fraction: Moving Toward a Newer Treatment Paradigm.

Author: Pandey, Ambarish MD; Berry, Jarett D. MD, MS

Page: 993-995

http://ift.tt/2y17qsY

Pericarditis as a Marker of Occult Cancer and a Prognostic Factor for Cancer Mortality.

Author: Sogaard, Kirstine Kobberoe PhD; Farkas, Dora Kormendine MSc; Ehrenstein, Vera DSc; Bhaskaran, Krishnan PhD; Botker, Hans Erik DMSc; Sorensen, Henrik Toft DMSc

Page: 996-1006

http://ift.tt/2w2E3cC

Optical Coherence Tomography Findings in Patients With Coronary Stent Thrombosis: A Report of the PRESTIGE Consortium (Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort).

Author: Adriaenssens, Tom MD, PhD *; Joner, Michael MD *; Godschalk, Thea C. MSc; Malik, Nikesh MD; Alfonso, Fernando MD, PhD; Xhepa, Erion MD; De Cock, Dries MD; Komukai, Kenichi MD; Tada, Tomohisa MD; Cuesta, Javier MD; Sirbu, Vasile MD; Feldman, Laurent J. MD, PhD; Neumann, Franz-Josef MD; Goodall, Alison H. PhD; Heestermans, Ton MD; Buysschaert, Ian MD, PhD; Hlinomaz, Ota MD; Belmans, Ann MSc; Desmet, Walter MD; ten Berg, Jurrien M. MD, PhD; Gershlick, Anthony H. MD; Massberg, Steffen MD; Kastrati, Adnan MD; Guagliumi, Giulio MD +; Byrne, Robert A. MB, BCh, PhD +; on behalf of the Prevention of Late Stent Thrombosis by an Interdisciplinary Global European Effort (PRESTIGE) Investigators

Page: 1007-1021

http://ift.tt/2y0Y00P

A Cytokine-Like Protein Dickkopf-Related Protein 3 Is Atheroprotective.

Author: Yu, Baoqi PhD *; Kiechl, Stefan MD *; Qi, Dan MB; Wang, Xiaocong PhD; Song, Yanting MB; Weger, Siegfried MD; Mayr, Agnes MD; Le Bras, Alexandra PhD; Karamariti, Eirini PhD; Zhang, Zhongyi MSc; Barco Barrantes, Ivan del PhD; Niehrs, Christof PhD; Schett, Georg MD; Hu, Yanhua MD; Wang, Wen PhD; Willeit, Johann MD; Qu, Aijuan PhD; Xu, Qingbo MD, PhD

Page: 1022-1036

http://ift.tt/2w3iUiv

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

Author: Amyere, Mustapha PhD *; Revencu, Nicole MD, PhD *; Helaers, Raphael PhD; Pairet, Eleonore BSC; Baselga, Eulalia MD; Cordisco, Maria MD; Chung, Wendy MD, PhD; Dubois, Josee MD; Lacour, Jean-Philippe MD; Martorell, Loreto MD; Mazereeuw-Hautier, Juliette MD, PhD; Pyeritz, Reed E. MD, PhD; Amor, David J. MD; Bisdorff, Annouk MD; Blei, Francine MD; Bombei, Hannah MSc; Dompmartin, Anne MD, PhD; Brooks, David MD; Dupont, Juliette MD; Gonzalez-Ensenat, Maria Antonia MD; Frieden, Ilona MD; Gerard, Marion MD; Kvarnung, Malin MD; Hanson-Kahn, Andrea Kwan MSc; Hudgins, Louanne MD; Leaute-Labreze, Christine MD; McCuaig, Catherine MD; Metry, Denise MD; Parent, Philippe MD; Paul, Carle MD, PhD; Petit, Florence MD; Phan, Alice MD; Quere, Isabelle MD; Salhi, Aicha MD; Turner, Anne MD; Vabres, Pierre MD; Vicente, Asuncion MD; Wargon, Orli MD; Watanabe, Shoji MD, PhD; Weibel, Lisa MD; Wilson, Ashley MSc; Willing, Marcia MD; Mulliken, John B. MD; Boon, Laurence M. MD, PhD; Vikkula, Miikka MD, PhD

Page: 1037-1048

http://ift.tt/2y17iK0

Conduction Disturbances After Transcatheter Aortic Valve Replacement: Current Status and Future Perspectives.

Author: Auffret, Vincent MD, MSc; Puri, Rishi MBBS, PhD; Urena, Marina MD, PhD; Chamandi, Chekrallah MD; Rodriguez-Gabella, Tania MD; Philippon, Francois MD; Rodes-Cabau, Josep MD

Page: 1049-1069

http://ift.tt/2w3a7wM

Irregular Narrow Complex Tachycardia in a 29-Year-Old Woman.

Author: Naksuk, Niyada MD; Schleifer, J. William MD; Deshmukh, Abhishek J. MBBS; Madhavan, Malini MBBS

Page: 1070-1072

http://ift.tt/2y0XQXh

Origin of Cardiac Troponin T Elevations in Chronic Kidney Disease.

Author: van der Linden, Noreen MD; Cornelis, Tom PhD; Kimenai, Dorien M. MSc; Klinkenberg, Lieke J.J. PhD; Hilderink, Judith M. MD; Luck, Sarah MSc; Litjens, Elisabeth J. R. MD; Peeters, Frederique E.C.M. MD; Streng, Alexander S. PhD; Breidthardt, Tobias MD; van Loon, Luc J.C. PhD; Bekers, Otto PhD; Kooman, Jeroen P. PhD; Westermark, Pal O. PhD; Mueller, Christian MD; Meex, Steven J.R. PhD

Page: 1073-1075

http://ift.tt/2w2YSV2

Letter by Ferrero et al Regarding Article, "Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome: A Multicenter Study".

Author: Ferrero, Paolo MD; D'Elia, Emilia MD, PhD; Ciuffreda, Matteo MD

Page: 1076-1077

http://ift.tt/2y0XKin

Response by Kempny et al to Letter Regarding Article, "Predictors of Death in Contemporary Adult Patients With Eisenmenger Syndrome: A Multicenter Study".

Author: Kempny, Aleksander MD; Sorensen Hjortshoj, Cristel; Li, Wei MD, PhD; Schophuus Jensen, Annette PhD; Sondergaard, Lars MD, DMSc; Diller, Gerhard-Paul MD, PhD, MSc; Dimopoulos, Konstantinos MD, PhD, MSc; Wort, Stephen J. MA, MBBS, PhD; Gatzoulis, Michael A. MD, PhD

Page: 1078-1079

http://ift.tt/2w2yXwR

Letter by Ciliberti and Capucci Regarding Article, "Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease".

Author: Ciliberti, Giuseppe MD; Capucci, Alessandro MD

Page: 1080-1081

http://ift.tt/2y1m0AW

Response by Lindahl et al to Letter Regarding Article, "Medical Therapy for Secondary Prevention and Long-Term Outcome in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease".

Author: Lindahl, Bertil MD, PhD; Baron, Tomasz MD, PhD; Erlinge, David MD, PhD; Hadziosmanovic, Nermin MSc; Nordenskjold, Anna MD, PhD; Gard, Anton MD; Jernberg, Tomas MD, PhD

Page: 1082-1083

http://ift.tt/2w2J84w

Correction to: When Lightning Strikes: Fulminant Myocarditis in the Realm of Inflammatory Cardiomyopathies.

Author:

Page: e198

http://ift.tt/2w2XZw2

Correction to: Particulate Matter Exposure and Stress Hormone Levels: A Randomized, Double-Blind, Crossover Trial of Air Purification.

Author:

Page: e199

http://ift.tt/2y0LnCV

Effects of Early Integrated Palliative Care on Caregivers of Patients with Lung and Gastrointestinal Cancer: A Randomized Clinical Trial

AbstractBackground.The family and friends (caregivers) of patients with advanced cancer often experience tremendous distress. Although early integrated palliative care (PC) has been shown to improve patient‐reported quality of life (QOL) and mood, its effects on caregivers' outcomes is currently unknown.Materials and Methods.We conducted a randomized trial of early PC integrated with oncology care versus oncology care alone for patients who were newly diagnosed with incurable lung and noncolorectal gastrointestinal cancers and their caregivers. The early PC intervention focused on addressing the needs of both patients and their caregivers. Eligible caregivers were family or friends who would likely accompany patients to clinic visits. The intervention entailed at least monthly patient visits with PC from the time of diagnosis. Caregivers were encouraged, but not required, to attend the palliative care visits. We used the Hospital Anxiety and Depression Scale (HADS) and Medical Health Outcomes Survey Short‐Form to assess caregiver mood and QOL.Results.Two hundred seventy‐five caregivers (intervention n = 137; control n = 138) of the 350 patients participated. The intervention led to improvement in caregivers' total distress (HADS‐total adjusted mean difference = −1.45, 95% confidence interval [CI] −2.76 to −0.15, p = .029), depression subscale (HADS‐depression adjusted mean difference = −0.71, 95% CI −1.38 to −0.05, p = .036), but not anxiety subscale or QOL at week 12. There were no differences in caregivers' outcomes at week 24. A terminal decline analysis showed significant intervention effects on caregivers' total distress (HADS‐total), with effects on both the anxiety and depression subscales at 3 and 6 months before patient death.Conclusion.Early involvement of PC for patients with newly diagnosed lung and gastrointestinal cancers leads to improvement in caregivers' psychological symptoms. This work demonstrates that the benefits of early, integrated PC models in oncology care extend beyond patient outcomes and positively impact the experience of caregivers.Implications for Practice.Early involvement of palliative care for patients with newly diagnosed lung and gastrointestinal cancers leads to improvement in caregivers' psychological symptoms. The findings of this trial demonstrate that the benefits of the early, integrated palliative care model in oncology care extend beyond patient outcomes and positively impact the experience of caregivers. These findings contribute novel data to the growing evidence base supporting the benefits of integrating palliative care earlier in the course of disease for patients with advanced cancer and their caregivers.

http://ift.tt/2xgZoOL

In Reply

http://ift.tt/2eRpVYN

The Issue of Tissue in Molecular Stratification

http://ift.tt/2xheq73

Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS): A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study

AbstractBackground.This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment.Materials and Methods.The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug‐naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics.Results.A total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8–9.2) in the regorafenib group and 7.4 months (95% CI, 6.6–8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78–1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98–1.69), whereas TFTD was favored in patients aged ≥65 years (HR, 0.78; 95% CI, 0.59–1.03).Conclusion.No significant difference in OS between regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies.Implications for Practice.Previous studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there is no head‐to‐head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged ≥65 years in the subgroup analysis.

http://ift.tt/2eS1nik

Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma

Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.

http://ift.tt/2wlFMVq

Immunologic Response Elicited in Breast Cancer Patients Receiving a NeuGcGM3-based Vaccine as Adjuvant Therapy

This study aimed to investigate the immunogenicity of a cancer vaccine consisting of the NeuGcGM3 ganglioside combined with the outer membrane protein complex of Neisseria meningitides to form very small size particles. The vaccine is administered together with Montanide ISA51, as adjuvant treatment for breast cancer patients. After surgical resection and standard first-line chemo/radiotherapy, breast cancer patients in stage II–III were enrolled in a phase III clinical trial and allocated into 2 strata, according to the number of positive lymph nodes [stratum I (0–3); stratum II (≥4)]. Subsequently, patients were randomly assigned to receive the vaccine or placebo. The treatment consisted of 5 vaccine doses (200 μg) every 2 weeks and thereafter monthly reimmunizations to complete 15 doses. The vaccine was well-tolerated and high titers of immunoglobulin M and immunoglobulin G anti-NeuGcGM3 antibodies were similarly detected in each stratum. Hyperimmune sera were able to specifically recognize and kill the NeuGcGM3-expressing L1210 tumor cell line, and these functional capacities were significantly associated with a better clinical outcome in patients of stratum II. Besides, postimmune sera had the capacity to revert in vitro the immunosuppression induced by NeuGcGM3, as measured by the prevention of CD4 downmodulation on human T lymphocytes. Vaccination had no impact on the frequency of regulatory T cells or circulating NK cells. This study demonstrated, for the first time, the immunogenicity of the NeuGcGM3/VSSP/Montanide ISA 51 vaccine in the adjuvant setting and describes the functionality of induced anti-NeuGcGM3 antibodies as potential surrogate biomarkers of clinical benefit.

http://ift.tt/2wm2EnT

First-in-Human Treatment With a Dendritic Cell-targeting Lentiviral Vector-expressing NY-ESO-1, LV305, Induces Deep, Durable Response in Refractory Metastatic Synovial Sarcoma Patient

Effective induction of antitumor T cells is a pivotal goal of cancer immunotherapy. To this end, lentiviral vectors (LV) are uniquely poised to directly prime CD8 T-cell responses via transduction of dendritic cells in vivo and have shown promise as active cancer therapeutics in preclinical tumor models. However, until now, significant barriers related to production and regulation have prevented their widespread use in the clinic. We developed LV305, a dendritic cell-targeting, integration-deficient, replication incompetent LV from the ZVex platform, encoding the full-length cancer-testis antigen NY-ESO-1. LV305 is currently being evaluated in phase 1 and 2 trials in metastatic recurrent cancer patients with NY-ESO-1 positive solid tumors as a single agent and in combination with anti-PD-L1. Here we report on the first patient treated with LV305, a young woman with metastatic, recurrent, therapy-refractive NY-ESO-1+ synovial sarcoma. The patient developed a robust NY-ESO-1-specific CD4+ and CD8+ T-cell response after 3 intradermal injections with LV305, and subsequently over 85% disease regression that is continuing for >2.5 years posttherapy. No adverse events >grade 2 occurred. This case demonstrates that LV305 can be safely administered and has the potential to induce a significant clinical benefit and immunologic response in a patient with advanced stage cancer.

http://ift.tt/2wlvuoq

Two Cases of Sinusitis Induced by Immune Checkpoint Inhibition

We report the acute onset of aseptic sinusitis in 2 patients receiving the immune checkpoint inhibitors, ipilimumab and nivolumab, for treatment of metastatic melanoma. Ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte antigen-4, and nivolumab, targeting programmed cell death-1, have been associated with numerous immune-related adverse events. To the authors' knowledge, this is the first report of aseptic sinusitis as a consequence of immune checkpoint inhibition therapy.

http://ift.tt/2wmtDji

The TAF10-containing TFIID and SAGA transcriptional complexes are dispensable for early somitogenesis in the mouse embryo [RESEARCH ARTICLE]

Paul Bardot, Stephane D. Vincent, Marjorie Fournier, Alexis Hubaud, Mathilde Joint, Laszlo Tora, and Olivier Pourquie

During development, tightly regulated gene expression programs control cell fate and patterning. A key regulatory step in eukaryotic transcription is the assembly of the pre-initiation complex (PIC) at promoters. The PIC assembly has mainly been studied in vitro, and little is known about its composition during development. In vitro data suggests that TFIID is the general transcription factor that nucleates PIC formation at promoters. Here we show that TAF10, a subunit of TFIID and of the transcriptional co-activator SAGA, is required for the assembly of these complexes in the mouse embryo. We performed Taf10 conditional deletions during mesoderm development and show that Taf10 loss in the presomitic mesoderm (PSM) does not prevent cyclic gene transcription or PSM segmental patterning, while lateral plate differentiation is profoundly altered. During this period, global mRNA levels are unchanged in the PSM, with only a minor subset of genes dysregulated. Together, our data strongly suggest that the TAF10-containing canonical TFIID and SAGA complexes, are dispensable for early paraxial mesoderm development, arguing against the generic role in transcription proposed for these fully assembled holo complexes.

http://ift.tt/2ffcxya

Timing of adrenal regression controlled by synergistic interaction between Sf1 SUMOylation and Dax1 [RESEARCH ARTICLE]

Yewei Xing, Ken-ichirou Morohashi, Holly A. Ingraham, and Gary D. Hammer

The nuclear receptor steroidogenic factor 1 (Sf1, Nr5a1, Ad4bp) is critical for formation, development and function of steroidogenic tissues. A fetal adrenal enhancer (FAdE) in the Sf1 gene was previously identified to direct Sf1 expression exclusively in the fetal adrenal cortex and is bound by both Sf-1 and Dax1. Here, we examined the function of Sf1 SUMOylation and its interaction with Dax1 on FAdE function. A diffused prolonged pattern of FAdE expression and delayed regression of the postnatal fetal cortex (X-zone) were detected in both the SUMOylation deficient-Sf1^2KR/2KR and Dax1 knockout mouse lines, with FAdE expression/activity retained in the postnatal 20αHSD positive postnatal X-zone cells. In vitro studies indicated that Sf1 SUMOylation, while not directly influencing DNA binding, actually increased binding of Dax1 to Sf1 to further enhance transcriptional repression of FAdE. Taken together, these studies define a critical repressor function of Sf1 SUMOylation and Dax1 in the physiologic cessation of FAdE mediated Sf1 expression and the resultant regression of the postnatal fetal cortex(X-zone).

http://ift.tt/2wT2ZTo

An X-ray shielded irradiation assay reveals EMT transcription factors control pluripotent adult stem cell migration in vivo in planarians [RESEARCH ARTICLE]

Prasad Abnave, Ellen Aboukhatwa, Nobuyoshi Kosaka, James Thompson, Mark A. Hill, and A. Aziz Aboobaker

Migration of stem cells underpins the physiology of metazoan animals. For tissues to be maintained, stem cells and their progeny must migrate and differentiate in the correct positions. This need is even more acute after tissue damage by wounding or pathogenic infections. Inappropriate migration also underpins the formation of metastasis. Despite this, few mechanistic studies address stem cell migration during repair or homeostasis in adult tissues. Here, we present a shielded X-ray irradiation assay that allows us to follow stem cell migration in planarians. We demonstrate that we can use this system to study the molecular control of stem cell migration and show that snail-1, snail-2 and zeb-1 EMT transcription factor homologs are necessary for cell migration to wound sites and for the establishment of migratory cell morphology. We also observed that stem cells undergo homeostatic migration to anterior regions without local stem cells, in the absence of injury, maintaining tissue homeostasis. This requires the polarity determinant notum. Our work establishes planarians as a suitable model for further in depth study of the processes controlling stem cell migration in vivo.

http://ift.tt/2fevCR0

Small-molecule Wnt agonists correct cleft palates in Pax9 mutant mice in utero [RESEARCH ARTICLE]

Shihai Jia, Jing Zhou, Christopher Fanelli, Yinshen Wee, John Bonds, Pascal Schneider, Gabriele Mues, and Rena N. D'Souza

Clefts of the palate and/or lip are the most common among human craniofacial malformations and involve multiple genetic and environmental factors. Defects can only be corrected surgically and require complex life-long treatments. Our studies utilized the well-characterized Pax9^–/– mouse model with a consistent cleft palate phenotype to test small-molecule Wnt agonist therapies. We first show that the absence of Pax9 alters the expression of Wnt pathway genes including Dkk1 and Dkk2, proven antagonists of Wnt signaling. The functional interactions between Pax9 and Dkk1 is shown by the genetic rescue of secondary palate clefts in Pax9^–/–Dkk1^f/+;Wnt1Cre embryos. The controlled intravenous delivery of small-molecule Wnt agonists (Dkk inhibitors) into pregnant Pax9^+/– mice restored Wnt signaling and led to the growth and fusion of palatal shelves as marked by an increase in cell proliferation and osteogenesis in-utero while other organ defects were not corrected. This work underscores the importance of Pax9-dependent Wnt signaling in palatogenesis and suggests that such a functional upstream molecular relationship can be exploited for the development of therapies for human cleft palates that arise from single gene disorders.

http://ift.tt/2wTQ1VA

A radial axis defined by Semaphorin to Neuropilin signaling controls pancreatic islet morphogenesis [RESEARCH ARTICLE]

Philip T. Pauerstein, Krissie Tellez, Kirk B. Willmarth, Keon Min Park, Brian Hsueh, H. Efsun Arda, Xueying Gu, Haig Aghajanian, Karl Deisseroth, Jonathan A. Epstein, and Seung K. Kim

The islets of Langerhans are endocrine organs characteristically dispersed throughout the pancreas. During development, endocrine progenitors delaminate, migrate radially, and cluster to form islets. Despite the distinctive distribution of islets, spatially localized signals that control islet morphogenesis have not been discovered. Here we identify a radial signaling axis that instructs developing islet cells to disperse throughout the pancreas. A screen of pancreatic extracellular signals identified factors that stimulated islet cell development. These included Semaphorin3a, a guidance cue in neural development without known functions in the pancreas. In the fetal pancreas, peripheral mesenchymal cells expressed Sema3a, while central nascent islet cells produced the Semaphorin receptor Neuropilin2 (Nrp2). Nrp2 mutant islet cells developed in proper numbers, but had defects in migration and were unresponsive to purified Sema3a. Mutant Nrp2 islets aggregated centrally and failed to disperse radially. Thus, Sema3a-Nrp2 signaling along an unrecognized pancreatic developmental axis constitutes a chemoattractant system essential for generating the hallmark morphogenetic properties of pancreatic islets. Unexpectedly, Sema3a-Nrp2 control of islet morphogenesis is strikingly homologous to signals regulating radial neuronal migration and cortical lamination in the developing mammalian brain.

http://ift.tt/2feLqmJ

Zfp423/ZNF423 regulates cell cycle progression, the mode of cell division and the DNA damage response in Purkinje neuron progenitors [RESEARCH ARTICLE]

Filippo Casoni, Laura Croci, Camilla Bosone, Roberta D'Ambrosio, Aurora Badaloni, Davide Gaudesi, Valeria Barili, Justyna R. Sarna, Lino Tessarollo, Ottavio Cremona, Richard Hawkes, Soren Warming, and G. Giacomo Consalez

The Zfp423/ZNF423 gene encodes a 30-Zn-finger transcription factor involved in key developmental pathways. While null Zfp423 mutants develop cerebellar malformations, the underlying mechanism remains unknown. ZNF423 mutations have been associated to Joubert Syndrome, a ciliopathy causing cerebellar vermis hypoplasia and ataxia. ZNF423 participates in the DNA damage response, raising questions regarding its role as a regulator of neural progenitor cell cycle progression in cerebellar development. To characterize in vivo the function of ZFP423 in neurogenesis, we analyzed allelic murine mutants in which distinct functional domains are deleted. One deletion impairs mitotic spindle orientation, leading to premature cell cycle exit and Purkinje cell (PC) progenitor pool deletion. The other one impairs PC differentiation. In both mutants, cell cycle progression is remarkably delayed and DNA-damage response markers are upregulated in cerebellar ventricular zone progenitors. Our in vivo evidence sheds light on the domain-specific roles played by ZFP423 in different aspects of PC progenitor development, and at the same time strengthens the emerging notion that an impaired DNA damage response may be a key factor in the pathogenesis of JS and other ciliopathies.

http://ift.tt/2wSq3lg

Modular flow chamber for engineering bone marrow architecture and function

Publication date: November 2017
Source:Biomaterials, Volume 146
Author(s): Christian A. Di Buduo, Paolo M. Soprano, Lorenzo Tozzi, Stefania Marconi, Ferdinando Auricchio, David L. Kaplan, Alessandra Balduini
The bone marrow is a soft, spongy, gelatinous tissue found in the hollow cavities of flat and long bones that support hematopoiesis in order to maintain the physiologic turnover of all blood cells. Silk fibroin, derived from Bombyx mori silkworm cocoons, is a promising biomaterial for bone marrow engineering, because of its tunable architecture and mechanical properties, the capacity of incorporating labile compounds without loss of bioactivity and demonstrated ability to support blood cell formation. In this study, we developed a bone marrow scaffold consisting of a modular flow chamber made of polydimethylsiloxane, holding a silk sponge, prepared with salt leaching methods and functionalized with extracellular matrix components. The silk sponge was able to support efficient platelet formation when megakaryocytes were seeded in the system. Perfusion of the chamber allowed the recovery of functional platelets based on multiple activation tests. Further, inhibition of AKT signaling molecule, which has been shown to be crucial in regulating physiologic platelet formation, significantly reduced the number of collected platelets, suggesting the applicability of this tissue model for evaluation of the effects of bone marrow exposure to compounds that may affect platelet formation. In conclusion, we have bioengineered a novel modular system that, along with multi-porous silk sponges, can provide a useful technology for reproducing a simplified bone marrow scaffold for blood cell production ex vivo.



http://ift.tt/2wTxgBo

Live cell imaging of mouse intestinal organoids reveals heterogeneity in their oxygenation

Publication date: November 2017
Source:Biomaterials, Volume 146
Author(s): Irina A. Okkelman, Tara Foley, Dmitri B. Papkovsky, Ruslan I. Dmitriev
Intestinal organoids are widely applied in stem cell research, regenerative medicine, toxicology, pharmacology, and host-microbe interactions research. The variability of oxidative metabolism for stem and differentiated cell types constituting organoid is known to be important but so far it has not been studied in details. Here, we report the use of live cell microscopy of oxygen via the phosphorescence lifetime imaging microscopy (PLIM) method to address the oxygenation and variability of aerobic metabolism of individual organoids in the culture. Using the cell-penetrating phosphorescent O2-sensitive probe, we found inhomogeneous O2 distribution in live organoids, with areas of relatively high oxygenation (up to 73 μM in organoid compared to an average 40 μM O2) and trans-epithelial O2 microgradients (up to 0.6–0.83 μM/μm). We also demonstrated that intestinal organoid culture consists of units with different respiration activity and oxygenation (from 27 to 92 μM, equal to 2.8–9.7% O2), depending on age of the culture and drug treatment. Collectively, our results indicate that ignoring the metabolic heterogeneity of organoid culture can be critical for proper data interpretation. The live cell imaging PLIM method demonstrates a clear advantage of using individual organoids as separate experimental units rather than 'bulk' organoid cultures.

Graphical abstract

http://ift.tt/2fe89PE

Cuprous oxide nanoparticles trigger ER stress-induced apoptosis by regulating copper trafficking and overcoming resistance to sunitinib therapy in renal cancer

Publication date: November 2017
Source:Biomaterials, Volume 146
Author(s): Qiwei Yang, Ye Wang, Qing Yang, Yi Gao, Xiaopeng Duan, Qingcheng Fu, Chuanmin Chu, Xiuwu Pan, Xingang Cui, Yinghao Sun
While the current standard first-line treatment for advanced renal cell carcinoma (RCC) is sunitinib, patients inevitably develop resistance to this drug. However, the rapid development of nanotechnology has provided emerging techniques for the treatment of advanced tumours, including RCC. In our previous research, cuprous oxide nanoparticles (CONPs) showed ideal anti-tumour effects and low systemic toxicity. While many inorganic nanomedicines, including CONPs, have similar pharmacological effects, their detailed mechanisms remain unknown. Copper chaperone proteins, which regulate the endocellular dosage and transport of copper, also play crucial roles in the progression of cancer. In this research, we discovered that CONPs can disrupt copper transportation by regulating the copper chaperone proteins ATOX1 and CCS in RCC cells and induce endoplasmic reticulum (ER) stress in vitro and in vivo by promoting the accumulation of intracellular calcium and reactive oxygen species (ROS). Furthermore, CONPs can initiate ER- and mitochondrial-dependent apoptosis by activating caspase-3, caspase-9 and caspase-12. In addition, CONPs downregulate the expression of AXL, MET, AKT, and ERK to recover sunitinib responsiveness in RCC cells with sunitinib resistance (SR) and may therefore facilitate the development of promising new pathways to treat patients with acquired SRRCC.

Graphical abstract

http://ift.tt/2feg13R

State of diagnosing infectious pathogens using colloidal nanomaterials

Publication date: November 2017
Source:Biomaterials, Volume 146
Author(s): Jisung Kim, Mohamed A. Abdou Mohamed, Kyryl Zagorovsky, Warren C.W. Chan
Infectious diseases are a major global threat that accounts for one of the leading causes of global mortality and morbidity. Prompt diagnosis is a crucial first step in the management of infectious threats, which aims to quarantine infected patients to avoid contacts with healthy individuals and deliver effective treatments prior to further spread of diseases. This review article discusses current advances of diagnostic systems using colloidal nanomaterials (e.g., gold nanoparticles, quantum dots, magnetic nanoparticles) for identifying and differentiating infectious pathogens. The challenges involved in the clinical translation of these emerging nanotechnology based diagnostic devices will also be discussed.



http://ift.tt/2fejvDo

Immune monitoring for precision medicine in allergy and asthma

Scott Dexter Boyd | Ramona Amy Hoh | Kari Christine Nadeau | Stephen Joseph Galli

http://ift.tt/2xt1qfL

Immune mechanisms of food allergy and its prevention by early intervention

Victor Turcanu | Helen A Brough | George Du Toit | Ru-Xin Foong | Tom Marrs | Alexandra F Santos | Gideon Lack

http://ift.tt/2h0vZyv

Regulation of body growth by microRNAs

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): Julian C. Lui
Regulation of body growth remains a fascinating and unresolved biological mystery. One key component of body growth is skeletal and longitudinal bone growth. Children grow taller because their bones grew longer, and the predominant driver of longitudinal bone growth is a cartilaginous structure found near the ends of long bone named the growth plate. Numerous recent studies have started to unveil the importance of microRNAs in regulation of growth plate functions, therefore contributing to regulation of linear growth. In addition to longitudinal growth, other organs in our body need to increase in size and cell number as we grow, and the regulation of organ growth involves both systemic factors like hormones; and other intrinsic mechanisms, which we are just beginning to understand. This review aims to summarize some recent important findings on how microRNAs are involved in both of these processes: the regulation of longitudinal bone growth, and the regulation of organs and overall body growth.



http://ift.tt/2wlaUVm

MicroRNAs in parathyroid physiopathology

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): V. Vaira, C. Verdelli, I. Forno, S. Corbetta
Parathyroid glands regulate calcium homeostasis through synthesis and secretion of parathormone (PTH). They sense the extracellular calcium concentration through the G-protein coupled calcium sensing receptor (CASR) and release PTH in order to preserve calcium concentration in the physiological range. Tumors of the parathyroid glands are common endocrine neoplasia associated with primary or secondary/tertiary hyperparathyroidisms. Small non-coding RNAs are regulators of gene expression able to modulate hormone synthesis, hormone release and endocrine cell proliferation. In this scenario, microRNA (miRNA) expression profiles have been investigated in parathyroid tumors, while miRNAs are involved in hypocalcemia and uremia-induced PTH release from normal parathyroid cells. Here we reviewed data about the role of miRNAs in the regulation of: 1) PTH synthesis and secretion; 2) CASR expression; 3) parathyroid cell tumorigenesis. Though studies about miRNAs in parathyroid gland pathophysiology are limited, they contribute in elucidating regulatory pathways involved in PTH release and parathyroid cell tumorigenesis.



http://ift.tt/2wWnRZ3

Small non-coding RNAs-based bone regulation and targeting therapeutic strategies

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): Ying Yang, Sijie Fang
Small non-coding RNAs, which are 20–25 nucleotide ribonucleic acids, have emerged as an important transformation in the biological evolution over almost three decades. microRNAs (miRNAs) and short interfering RNAs (siRNAs) are two significant categories of the small RNAs that exert important effects on bone endocrinology and skeletology. Therefore, clarifying the expression and function of these important molecules in bone endocrine physiology and pathology is of great significance for improving their potential therapeutic value for metabolism-associated bone diseases. In the present review, we highlight the recent advances made in understanding the function and molecular mechanism of these small non-coding RNAs in bone metabolism, especially their potentially therapeutic values in bone-related diseases.



http://ift.tt/2wlECt6

The role of microRNAs in the pathophysiology of adrenal tumors

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): Nunki Hassan, Jing Ting Zhao, Stan B. Sidhu
MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression in a sequence-specific manner. Due to its association with an assortment of diseases, miRNAs have been extensively studied in the last decade. In this review, the current understanding of the role of miRNAs in the pathophysiology of adrenal tumors is discussed. The recent contributions of high-throughput miRNA profiling studies have identified miRNAs that have functional and molecular roles in adrenal tumorigenesis. With respect to the biological heterogeneity of adrenal tumors and the limitations of the current treatments, an improved understanding of miRNAs may hold potential diagnostic and therapeutic value to facilitate better clinical management.



http://ift.tt/2wWF0SC

MicroRNAs in thyroid development, function and tumorigenesis

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): Cesar Seigi Fuziwara, Edna Teruko Kimura
MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression that modulate the vast majority of cellular processes. During development, the correct timing and expression of miRNAs in the tissue differentiation is essential for organogenesis and functionality. In thyroid gland, DICER and miRNAs are necessary for accurately establishing thyroid follicles and hormone synthesis. Moreover, DICER1 mutations and miRNA deregulation observed in human goiter influence thyroid tumorigenesis. The thyroid malignant transformation by MAPK oncogenes is accompanied by global miRNA changes, with a marked reduction of "tumor-suppressor" miRNAs and activation of oncogenic miRNAs. Loss of thyroid cell differentiation/function, and consequently iodine trapping impairment, is an important clinical characteristic of radioiodine-refractory thyroid cancer. However, few studies have addressed the direct role of miRNAs in thyroid gland physiology. Here, we focus on what we have learned in the thyroid follicular cell differentiation and function as revealed by cell and animal models and miRNA modulation in thyroid tumorigenesis.

Graphical abstract

http://ift.tt/2wlYo7L

Small non-coding RNAs in endocrinology

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): Enzo Lalli




http://ift.tt/2wlkQhB

MicroRNAs in pituitary tumors

Publication date: 15 November 2017
Source:Molecular and Cellular Endocrinology, Volume 456
Author(s): Anne Wierinckx, Magali Roche, Catherine Legras-Lachuer, Jacqueline Trouillas, Gérald Raverot, Joël Lachuer
Since the presence of microRNAs was first observed in normal pituitary, the majority of scientific publications addressing their role and the function of microRNAs in the pituitary have been based on pituitary tumor studies. In this review, we briefly describe the involvement of microRNAs in the synthesis of pituitary hormones and we present a comprehensive inventory of microRNA suppressors and inducers of pituitary tumors. Finally, we summarize the functional role of microRNAs in tumorigenesis, progression and aggressiveness of pituitary tumors, mechanisms contributing to the regulation (transcription factors, genomic modifications or epigenetic) or modulation (pharmacological treatment) of microRNAs in these tumors, and the interest of thoroughly studying the expression of miRNAs in body fluids.



http://ift.tt/2wWWa2y

ETS transcription factor family member GABPA contributes to vitamin D receptor target gene regulation

Publication date: Available online 11 September 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Sabine Seuter, Antonio Neme, Carsten Carlberg
Binding motifs of the ETS-domain transcription factor GABPA are found with high significance below the summits of the vitamin D receptor (VDR) cistrome. VDR is the nuclear receptor for the biologically most active vitamin D metabolite 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3). In this study, we determined the GABPA cistrome in THP-1 human monocytes and found that it is comprised of 3822 genomic loci, some 20% of which were modulated by 1,25(OH)2D3. The GABPA cistrome showed a high overlap rate with accessible chromatin and the pioneer transcription factor PU.1. Interestingly, 23 and 12% of persistent and transient VDR binding sites, respectively, co-localized with GABPA, which is clearly higher than the rate of secondary VDR loci (4%). Some 40% of GABPA binding sites were found at transcription start sites, nearly 100 of which are of 1,25(OH)2D3 target genes. On 593 genomic loci VDR and GABPA co-localized with PU.1, while only 175 VDR sites bound GABPA in the absence of PU.1. In total, VDR sites with GABPA co-localization may control some 450 vitamin D target genes. Those genes that are co-controlled by PU.1 preferentially participate in cellular and immune signaling processes, while the remaining genes are involved in cellular metabolism pathways. In conclusion, GABPA may contribute to differential VDR target gene regulation.



http://ift.tt/2wlj8gb

Promotional effect of rare earth-doped manganese oxides supported on activated semi-coke for selective catalytic reduction of NO with NH 3

Abstract

A composite catalyst for the selective catalytic reduction (SCR) of NO_x with NH₃ is investigated, in which the rare earth (RE, including La, Ce, Pr, and Nd) is doped into manganese oxides supported on activated semi-coke (MnO_x/ASC) via hydrothermal method at the molar ratio of Mn:RE = 1:5. It is evidenced that the addition of RE at a rather low molar ratio can enhance the catalytic activity of MnO_x/ASC. The catalyst with a Mn:Ce molar ratio of 10:1 yields an over 90% NO_x removal efficiency in the temperature range of 150–250 °C. An approximate 100% NO conversion and 95% N₂ selectivity are achieved at about 200 °C. The catalysts are characterized by N₂ physisorption, X-ray powder diffraction (XRD), scanning electron microscope (SEM), hydrogen temperature-programmed reduction (H₂-TPR) and X-ray photoelectron spectroscopy (XPS). The results indicated that the Ce additive is conducive to the NO_x adsorption and then accelerates the SCR reaction due to the formation of more chemisorbed oxygen (O_β), which is favored during the oxidation of NH₃ and NO. Moreover, the in situ diffused reflectance infrared Fourier transform spectroscopy (DRIFTS) results confirm that the Ce additive on MnO_x/ASC catalyst could provide more active Brønsted acid sites, which eventually contributes to the SCR reaction. The generation of ad-NH₄⁺ and nitrite species is proved to play the crucial role in the promotional effect of RE addition.

http://ift.tt/2gXia7J

IOP-details

Publication date: October 2017
Source:International Journal of Psychophysiology, Volume 120





http://ift.tt/2y1j3Af

Full title with Editorial board members

Publication date: October 2017
Source:International Journal of Psychophysiology, Volume 120





http://ift.tt/2w2VY2N

Instructions to Authors

Publication date: October 2017
Source:International Journal of Psychophysiology, Volume 120





http://ift.tt/2y1C4SX

Childhood adversity predicts reduced physiological flexibility during the processing of negative affect among adolescents with major depression histories

Publication date: Available online 11 September 2017
Source:International Journal of Psychophysiology
Author(s): Shimrit Daches, Maria Kovacs, Charles George, Ilya Yaroslavsky, Eniko Kiss, Agnes Vetro, Roberta Dochnal, István Benak, Ildikó Baji, Kitti Halas, Attila Makai, Krisztina Kapornai, Jonathan Rottenberg
BackgroundAdversity during early development has been shown to have enduring negative physiological consequences. In turn, atypical physiological functioning has been associated with maladaptive processing of negative affect, including its regulation. The present study therefore explored whether exposure to adverse life events in childhood predicted maladaptive (less flexible) parasympathetic nervous system functioning during the processing of negative affect among adolescents with depression histories.MethodsAn initially clinic-referred, pediatric sample (N=189) was assessed at two time points. At Time 1, when subjects were 10.17years old (SD=1.42), on average, and were depressed, parents reported on adverse life events the offspring experienced up to that point. At Time 2, when subjects were 17.18years old (SD=1.28), and were remitted from depression, parents again reported on adverse life events in their offspring's lives for the interim period. At time 2, subjects' parasympathetic nervous system functioning (quantified as respiratory sinus arrhythmia) also was assessed at rest, during sad mood induction, and during instructed mood repair.ResultsExtent of adverse life events experienced by T1 (but not events occurring between T1 and T2) predicted less flexible RSA functioning 7years later during the processing of negative affect. Adolescents with more extensive early life adversities exhibited less vagal withdrawal following negative mood induction and tended to show less physiological recovery following mood repair.ConclusionsEarly adversities appear to be associated with less flexible physiological regulatory control during negative affect experience, when measured later in development. Stress-related autonomic dysfunction in vulnerable youths may contribute to the unfavorable clinical prognosis associated with juvenile-onset depression.



http://ift.tt/2w3usSF

Bloody Epiphora (Hemolacria) Years After Repair of Orbital Floor Fracture

Surgical repair of orbital fractures with implants is a widely used treatment modality. While a variety of established complications are associated with this technique, most are directly understood and treated. Bloody epiphora is a finding with potentially ominous causes. The authors present a unique case of bloody epiphora, accompanied by orbital hemorrhage arising several years after orbital floor fracture repair, due to erosion of the nasolacrimal drainage system by a displaced implant combined with anticoagulation. The collection and evaluation of all protected patient health information was compliant with the regulations and conditions set forth in the Health Insurance Portability and Availability Act of 1996.

http://ift.tt/2wWq1Io

Marcus Gunn Jaw-Winking Syndrome: A Comprehensive Review and Report of Four Novel Cases

Purpose: To report 4 cases of Marcus Gunn jaw-winking synkinesis (MGJWS) in the absence of ptosis. Methods: A retrospective review of patients with MGJWS and congenital ptosis was compiled from the public and private subspecialty adult and pediatric oculoplastic practices of the 2 senior authors (AAM, TGH). Clinical data collected on patients with MGJWS included visual acuity, stereopsis, ocular motility, side of jaw-wink, presence or absence of ptosis, levator function, clinical photographs and videos, and any management undertaken. Results: A total of 848 cases of congenital ptosis were seen. Of these, there were 72 consecutive patients with MGJWS, of which 4 cases (5.6%) had no ptosis. One patient had bilateral MGJWS, with ptosis on one side only. The authors found the incidence of MGJWS in our study population to be 8.5% of all congenital ptosis cases. When the authors excluded syndromic, neurogenic, and myopathic causes of congenital ptosis, the incidence was 12.1%. In addition, the authors found a trend toward females with simple congenital ptosis and MGJWS being affected on the left side, however this was not statistically significant. Conclusions: The authors report the first case series of MGJWS in the absence of ptosis within the second largest series ever reported. These findings may help further our understanding of the etiology behind MGJWS.

http://ift.tt/2wWJxV5

An Alternative for Permanent Punctal Occlusion: Labial Mucous Membrane Graft in the Management of Severe Dry Eye

No abstract available

http://ift.tt/2w2XnGs

A Single- Versus Double-Layered Closure Technique in Anophthalmic Surgery

Purpose: To compare the frequency of orbital implant exposure and extrusion following eye removal with a simplified closure technique, closing Tenon's capsule and conjunctiva in 1 layer versus the classic technique of closure in 2 separate layers. Methods: The authors conducted a retrospective case note review of patients who underwent evisceration or enucleation treated by 1 surgeon between 2001 and 2013. Between 2001 and 2004, Tenon's capsule and conjunctiva were closed in separate layers; after 2004, a simplified 1-layer closure following eye removal was used. The primary outcome parameters were presence or absence of implant exposure or extrusion. Results: One hundred fifty-seven patients who underwent evisceration and 172 patients who underwent enucleation were included. Following evisceration, 2.5% developed exposure or extrusion of the implant, this was 2.5% in the 1-layer closure technique and 2.7% in the 2-layer closure technique (p = 0.95). Following enucleation, 1.7% developed exposure or extrusion of the implant, this was 1.8% in the 1-layer closure technique and 1.7% in the 2-layer closure technique (p = 0.96). Overall implant exposure and extrusion was 2.1%, this was 2.2% in the 1-layer closure technique and 2.1% in the 2-layer closure technique (p = 0.96). Conclusions: No difference was found in the frequency of spheric acrylic implant exposure or extrusion in patients who underwent eye removal with single-layer closure of Tenon's capsule and conjunctiva compared with patients treated with separate closure of these layers.

http://ift.tt/2w2TFNj

Prognostic Value of the Staging System for Eyelid Tumors in the 7th Edition of the American Joint Committee on Cancer Staging Manual

Purpose: To determine the prognostic value of the staging criteria for eyelid tumors in the 7th edition of the American Joint Committee on Cancer (AJCC) staging manual and to determine, for each type of eyelid tumor, which AJCC T categories are associated with increased risk of nodal metastasis and thus potential usefulness of sentinel lymph node biopsy. Methods: Systematic review and analysis of articles found by searching PubMed and Google Scholar using the search terms "AJCC," "eyelid," "carcinoma," and "melanoma." Results: Rates of local recurrence, regional nodal metastasis, and distant metastasis were approximately 7% to 10%, 1% to 9%, and 0% to 0.8%, respectively, for eyelid squamous cell carcinoma; 5% to 6%, 8% to 23%, and 2% and 14%, respectively, for eyelid sebaceous carcinoma; 10%, 10% to 22%, and 19% to 22%, respectively, for eyelid Merkel cell carcinoma (when staged according to the criteria for eyelid carcinoma as opposed to Merkel cell carcinoma), 14%, 5%, and 0%, respectively, for eyelid sweat gland carcinoma; and 2%, 9%, and 6%, respectively, for eyelid melanoma. Overall, the risks of local recurrence and regional nodal and distant metastasis appeared to increase with increasing AJCC T category, although not statistically significant in all studies. Clinical T2b or greater T category was significantly associated with increased risk of nodal metastasis for eyelid squamous cell carcinomas, sebaceous carcinomas, Merkel cell carcinomas (staged with eyelid carcinoma criteria), sweat gland carcinomas, and melanomas. Clinical T3 or greater T category was significantly associated with distant metastasis for eyelid carcinomas and melanomas. Conclusion: For eyelid carcinomas and eyelid melanomas, AJCC 7th edition T category correlates with the risks of nodal and distant metastasis, with T2b and larger tumors associated with highest risk of nodal metastasis. Patients with T2b or larger tumors may be candidates for sentinel lymph node biopsy or close nodal surveillance.

http://ift.tt/2w32pTC

A Retrospective Review of Orbital Decompression for Thyroid Orbitopathy with Endoscopic Preservation of the Inferomedial Orbital Bone Strut

Purpose: To determine incidence of new-onset diplopia, resolution of preexisting diplopia, and impact on proptosis resulting from endoscopic orbital decompression with and without preservation of the inferomedial orbital strut for thyroid orbitopathy. Methods: Retrospective review of all patients undergoing endoscopic 2- or 3-wall decompression with or without preservation of the strut for thyroid orbitopathy from January 2012 to June 2015. Results: Twenty-six patients (45 orbits) were included and divided into 4 primary categories: 2-wall decompression with strut preservation (4 orbits, 8%), 2-wall decompression with strut removal (7 orbits, 16%), 3-wall decompression with strut preservation (27 orbits, 60%), and 3-wall decompression with strut removal (7 orbits, 16%). The incidence of new-onset diplopia was 20% (2/10 patients without preoperative diplopia) overall and 16% in the strut preservation group (1/6 patients without preoperative diplopia). Resolution of diplopia occurred in 4 of 16 patients (25%) with preoperative diplopia, and all 4 had been treated with a 3-wall decompression with strut preservation. Resolution of diplopia in the group treated with strut preservation was 36% (4/11 patients with preoperative diplopia), and 0% of the 5 diplopic patients treated without strut preservation. Reduction in proptosis was statistically greater in those treated with strut removal (p = 0.003). Conclusions: This study demonstrates that endoscopic orbital decompression with preservation of the inferomedial bone strut results in a comparable to lower rate of new-onset diplopia compared with other reported techniques. When combined with 3-wall balanced decompression, this technique demonstrates a high rate of resolution of preexisting diplopia.

http://ift.tt/2w2xcjt

Endovascular Management of a Traumatic Infraorbital Pseudoaneurysm Causing Orbital Compartment Syndrome

An 89-year-old woman presented after blunt injury to the left orbit from a fall. Examination findings were suggestive of left-sided orbital compartment syndrome, unresponsive to emergent lateral canthotomy and cantholysis. CT revealed a left-sided orbital floor blowout fracture involving the infraorbital canal, with a large maxillary and infraorbital hematoma. Angiography revealed a pseudoaneurysm supplied by the infraorbital artery. Interventional neuroradiology successfully achieved hemorrhage control by endovascular obliteration of the parent artery close to the pseudoaneurysm. To our knowledge, this is the first reported case of successfully managing active intraorbital hemorrhage causing orbital compartment syndrome by endovascular vessel sacrifice of an infraorbital artery pseudoaneurysm.

http://ift.tt/2w28JL3

Efficacy of Orbital Color Doppler Imaging and Neuroimaging in the Diagnosis of Carotid Cavernous Fistulas

Purpose: To evaluate the diagnostic sensitivity and specificity of orbital color Doppler imaging (CDI) and conventional neuroimaging (CT/MRI) compared with cerebral angiography in patients with carotid-cavernous fistulas (CCFs). Methods: The study design was a retrospective patient chart and imaging review. The authors reviewed 655 charts of all patients who underwent CDI and neuroimaging (CT/MRI) between 2006 and 2015 at one institution. Sixty patients had a presumptive diagnosis of CCF without thrombosis. Thirty-seven patients with 43 events met the inclusion criteria of the study. The diagnostic sensitivity of the 3 noninvasive imaging modalities (CDI, CT, MRI) for CCF was compared with the gold standard 6-vessel cerebral angiography. Significance testing was performed using the 2-tailed Fisher test. Results: Color Doppler imaging had high sensitivity (96.8%) but low specificity (41.7%) for the diagnosis of CCFs with anterior orbital findings. A negative CDI had more diagnostic value than a positive CDI. While an arterial wave form in the superior ophthalmic vein was the most common finding of CCF on CDI, enlargement of the superior ophthalmic vein was the only statistically significant finding. Posterior cortical venous drainage was noted in about 10% of the patients with indirect (low-flow) fistulas, who presented with unilateral orbital signs and symptoms, a finding not previously reported in the literature. Conclusion: Color Doppler imaging is a useful noninvasive, radiation-free modality for diagnosis of CCF with anterior drainage, with higher sensitivity than CT or MRI, but equivalent specificity. A significant limitation of CDI is the lack of usefulness in diagnosing fistulas with posterior cortical venous drainage, which carry a risk of intracerebral hemorrhage and stroke. In this series, 10% of unilateral CCFs with anterior orbital signs and symptoms showed angiographic evidence of posterior cortical venous drainage.

http://ift.tt/2w2Wn5d

Lacrimal Drainage System Involvement in Linear Scleroderma

Linear scleroderma is a localized variety of scleroderma characterized by fibrotic areas of the dermis involving head region without systemic features. Ocular involvement has been sparsely reported in the form of episcleritis, dry eye, and uveitis. We describe a 42-year-old man with linear scleroderma, en coup de sabre type with associated nasolacrimal duct obstruction and prolonged dacryocystitis.

http://ift.tt/2feeuL4

Comparative Evaluation of the Ostium After External and Nonendoscopic Endonasal Dacryocystorhinostomy Using Image Processing (Matlabs and Image J) Softwares

Purpose: The purpose of this study was to compare the characteristics of the ostium after external dacryocystorhinostomy and nonendoscopic endonasal dacryocystorhinostomy (NEN-DCR). Methods: This cross-sectional study included patients who underwent a successful external dacryocystorhinostomy or NEN-DCR and had ≥1 month follow up. Pictures of the ostium were captured with a nasal endoscope (4 mm, 30°) after inserting a lacrimal probe premarked at 2 mm. Image analyses were performed using Image J and Contour softwares. Results: Of the 113 patients included, external dacryocystorhinostomy group had 53 patients and NEN-DCR group had 60 patients. The mean age of patients in the NEN-DCR group (38 years) was significantly (p 0.05) in mean follow up (6 vs. 4 months), maximum diameter of ostium (8 vs. 7 mm), perpendicular drawn to it (4 vs. 4 mm), area of ostium (43 vs. 36 mm2), and the minimum distance between common internal punctum and edge of the ostium (1 vs. 1 mm) between the external and NEN-DCR groups. Conclusions: Image processing softwares offer simple and objective method to measure the ostium. While ostia are comparable in size, their relative position differs with posteriorly placed ostia in external compared with inferior in NEN-DCR.

http://ift.tt/2fe20TV

Re: “Lateral Rectus and Medial Rectus Expansion Following Orbital Decompression”

No abstract available

http://ift.tt/2ffcVNb

A Novel One-Stage Obstruction-Based Endoscopic Approach to Congenital Nasolacrimal Duct Obstruction

Purpose: To report 10-year results of a 1-stage, obstruction-based, endoscopic approach in children with congenital nasolacrimal duct obstruction (CNLDO) with and without prior failed probing/intubation. Methods: In a retrospective study, children with primary CNLDO of >6 months old previously failed probing/intubation, acute dacryocystitis or dacryocele at any age, and at least 6 months follow up. Diagnosis was based on history of tearing and dye disappearance test. Excluded were patients with complete puncto-canalicular obstruction and craniofacial anomaly. Type of CNLDO was confirmed using endonasal endoscopic guided probing. An endoscopic probing was performed for membranous, intubation for incomplete complex, and dacryocystorhinostomy for complete complex CNLDO. They were followed at 1 week, 1, 3, and 6 months, and then after. Success was defined as no or occasional tearing related to noxious stimulus at least 6 months after the procedure. Results: There were 226 eyes (200 patients). Mean age was 26.72 months. Previous failed probing/intubation was in 34.1%. Inferior turbinate impaction in 73.5% and septal deviation in 2.7% were noted. Membranous CNLDO was found in 38.9%, incomplete complex in 57.9%, and complete complex in 3.1%. Mean time of tube removal was 11.9 weeks and last follow-up time was 24.3 months. There was no significant effect of any variables on the final success rates (probing: 96.5%, intubation: 95.4%, dacryocystorhinostomy: 100%). Conclusions: One-stage, obstruction-based endoscopic approach to CNLDO resulted in a high success rate for different types of CNLDO (membranous, incomplete complex, and complete complex). No variable significantly affected the success rates.

http://ift.tt/2fdPZ0C

Orbitocutaneous Fistula Secondary to Buried Polyethylene Mesh Implant 12 Years After Injury

Fabric monofilament polyethylene mesh is an implant primarily used in the repair of abdominal and chest walls. However, there have been isolated reports of using this implant in facial reconstruction. The authors describe a patient who underwent prior orbital floor fracture repair with polyethylene mesh and subsequently developed a recurrent orbital abscess 12 years later. Despite incorporation of the fabric monofilament polyethylene mesh within healed bone, an orbitocutaneous fistula developed after a secondary injury, causing hyperglobus and cicatricial lower eyelid retraction.

http://ift.tt/2ff5buy

Rates of Positive Findings on Positron Emission Tomography and Bone Marrow Biopsy in Patients With Ocular Adnexal Lymphoma

Purpose: The aim of this study was to determine rates of positive findings on positron emission tomography (PET) and bone marrow biopsy performed during staging workup for ocular adnexal lymphoma (OAL). Methods: A retrospective review of OAL patients was conducted. Demographics, primary versus secondary OAL, histologic subtype, and findings on PET and bone marrow biopsy performed as part of the initial staging workup for OAL were recorded. Results: The study included 119 patients with OAL. There were 85 primary and 34 secondary OALs. The main histologic subtypes of lymphoma were mucosa-associated lymphoid tissue (n = 61), follicular (n = 26), diffuse large B-cell (n = 17), and mantle cell (n = 10). Positive PET findings were seen in 42 of 68 patients (62%) with primary OAL and 19 of 24 (79%) with secondary OAL. Positive PET findings were seen in 24 of 47 patients (51%) with mucosa-associated lymphoid tissue, 13 of 17 (76%) with follicular, 14 of 15 (93%) with diffuse large B-cell, and 9 of 10 (90%) with mantle cell lymphoma. Positive findings on bone marrow biopsy were seen in 7 of 59 patients (12%) with mucosa-associated lymphoid tissue, 4 of 23 (17%) with follicular, 1 of 17 (6%) with diffuse large B-cell, and 2 of 9 (22%) with mantle cell lymphoma. Conclusions: Our findings suggest that a significant proportion of patients with primary and secondary OAL have positive findings on PET and bone marrow biopsy at initial diagnosis, suggesting a reasonable yield for these tests as part of the initial staging workup in patients with a new diagnosis of OAL.

http://ift.tt/2fdPTWO

Conjunctival Melanoma Responsive to Combined Systemic BRAF/MEK Inhibitors

This report demonstrates a unique case of conjunctival melanoma harboring a BRAF V600E mutation responsive to systemic therapy with BRAF and MEK inhibitors. While systemic therapy would not be appropriate in patients with local disease alone, it may act therapeutically in cases of higher stage ocular surface and eyelid melanoma.

http://ift.tt/2feoRP8

Periocular Breast Carcinoma Metastases: Predominant Origin From the Lobular Variant

Purpose: To further define the histopathologic features of breast carcinoma conducive to orbital metastasis. Methods: Ten new female patients with orbital or eyelid breast cancer metastases encountered between 2011 and 2016 had their medical records reviewed for determining their clinical characteristics. Microscopic glass slides from biopsies and immunohistochemical test results were also analyzed. Biomarkers studied included cytokeratin 7, nuclear estrogen and progesterone receptors, HER2, and E-cadherin. Results: All orbital metastatic lesions were lobular (nonductal) carcinomas that could arise as late as 24 years after the diagnosis of the primary breast tumors. The average age of patients at the time or orbital presentation was 64 years. Metastases were composed of small tumor cells with round, orthochromatic nuclei, and a small amount of cytoplasm. The cells were disposed in a variably fibrotic tumor-associated stroma. Two lesions were variants of lobular carcinoma—namely, alveolar and pleomorphic (the latter displaying cellular crowding, with some degree of nuclear atypia and less stroma). Three of the 9 orbital metastases presented with enophthalmos and 2 displayed euphthalmos despite variably sized orbital masses. In 2 cases, synchronous bilateral orbital metastases prevented any relative difference in globe position. Estrogen and progesterone receptors were usually detectable whereas E-cadherin could not be demonstrated. Conclusions: Breast pathologists no longer refer to primary breast carcinomas and their orbital metastases as "scirrhous." It has been determined that the majority of orbital breast metastases are lobular carcinomas. This may be due to their lack of intercellular cohesiveness and the absence of E-cadherin which normally is expressed in many neoplastic cell types including ductal breast carcinomas, limiting their dispersion. In contrast, the majority of primary breast carcinomas are ductal. The ubiquitous collagenous matrix in breast metastases retracts, partially accounting for enophthalmos. The presence of euphthalmos despite an orbital mass additionally suggests some retraction of fibrous tissue (with or without fat atrophy) that suppresses relative proptosis. Metastatic lobular breast carcinoma is further implicated if there is a concomitant limitation in extraocular motility or vision decline.

http://ift.tt/2fdPT9g

Amelanotic Cellular Blue Nevus of the Eyelid

The authors describe an isolated, yellowish papular lesion of the upper eyelid in a 63-year-old man. Following excision, histopathologic analysis showed the features of a benign hypopigmented cellular blue nevus, the first and only case involving the eyelid skin.

http://ift.tt/2feYN6g

An Anatomical Murine Model of Heterotopic Periorbital Subunit Transplantation

Background: Conventional reconstructive methods fail to achieve satisfactory results in total eyelid defect cases. Vascularized composite tissue allotransplantation might provide both good appearance and function for these patients. The structure of the eyelid is exceptional because it simultaneously consists of skin, connective tissue, the striated muscle, fiber structure, aponeuroses, and mucosa. Thus, before clinical application of eyelid allotransplantation, more experiments are needed to clarify the impact of ischemia, immunal suppressive agents, and deinnervation effects on these sophisticated structures. We developed an heterotopic periorbital transplantation model in rats to facilitate further experiment in this field. Methods: Twenty-five inbred male Lewis rats were used for anatomy study (n=10), and as donors or recipients of the operations (n=10). In the anatomy study, the vascular distribution and innervation to the periorbital unit was identified and recorded. Then, according to the anatomy study, 10 heterotopic transplantations and 2 transplantations with pedicle ligated were performed. The posterior facial vein and the external carotid artery are selected as the graft pedicle. All transplanted eyelids were assessed daily. Micro-CT scanning and hematoxylin and eosin staining of the grafts were performed 60 days after the operation. Results: All recipients tolerated the operation well. All grafts without pedicles ligated survived and new hair growth was observed. All of the transplanted eyelids were pink and pliable during the entire observation period, and we did not observe any signs of arterial or venous occlusion. In the recipients with graft pedicle ligated, the grafts were necrosed and mummified within 4 to 5 days. MicroCT of the survived grafts showed good blood supply and histologic staining revealed normal histologic morphologies. Conclusions: Our study proved the anatomical feasibility of periorbital transplantation by establishing a heterotopic transplantation model, which might facilitate future eyelid allotransplantation-related experiments.

http://ift.tt/2fenlg0