Head and Neck Diseases by Alexandros G.Sfakianakis: 01/07/18

Κυριακή 7 Ιανουαρίου 2018

Tumour necrosis factor-α-inhibitor-induced neutrophilic folliculitis presenting with strong lesional expression of interleukin-36γ

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Depression- and anxiety-like behaviour is related to BDNF/TrkB signalling in a mouse model of psoriasis

Summary

Background

The prevalence of anxiety and depression is significantly higher in individuals with psoriasis than in the general population. Clinical data also show that anti-anxiety and antidepression drugs can reduce skin lesions in patients with psoriasis, but the actual mechanism is still poorly understood.

Aim

To investigate whether brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrKB) signalling plays a role in the mechanism underlying psoriasis with depression and anxiety behaviours.

Methods

Expression of BDNF and tropomyosin receptor kinase B (TrKB) in the K5.Stat3C mouse, an animal model of psoriasis, were investigated by reverse transcription PCR and Western blotting. Anxiety-like behaviours in the elevated-plus maze test and changes in BDNF/TrkB that have been implicated in depression and anxiety behaviours were measured. Skin lesions induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) were also measured when the mice were administered fluoxetine and K252a, an antagonist of TrkB.

Results

The antidepression and anti-anxiety drug fluoxetine reduced TPA-induced skin lesions and increased expression of BDNF and TrkB in K5.Stat3C mice. More importantly, the effects of fluoxetine were reversed by the TrkB antagonist K252a.

Conclusions

BDNF/TrkB signalling participates in the pathological mechanism of depression and anxiety behaviours in psoriasis. Our findings provide a new therapeutic strategy for the treatment of skin lesions in psoriasis.

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The incidence, mutational status, risk classification and referral pattern of gastro-intestinal stromal tumours in the Netherlands: a nationwide pathology registry (PALGA) study

Abstract

Symptomatic gastrointestinal stromal tumours (GIST) are infrequent with an incidence of 12.7 per million inhabitants in the western population. We studied whether the incidence of GIST has further increased between 2003 and 2012 and assessed the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. From PALGA, the nationwide Dutch Pathology Registry, pathology excerpts from all patients with a GIST or GIST-like tumour between 2003 and 2012 were retrieved to calculate incidence rates. Full pathology reports were retrieved of resections in 2011 and 2012 to study the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. The incidence of GIST increased to 17.7 per million inhabitants in 2012 with a median age of 67 years. Mutational analysis was performed in 33.9% of patients with a resection between 2011 and 2012 (KIT mutation 67.5%, PDGFRA 16.3%, wild-type 11.4%). The percentage of high risk patients in the different risk classifications varied from 19.9% to 38.0% depending on the used classification. Only 35.9% of patients had diagnosis or revision of pathology diagnosis within three months in a designated GIST referral centre. No increase in proportion of central pathology reviews was found. Proportion of patients with mutational analysis increased over the years. The registered incidence of GIST, 17.7 per million inhabitants in 2012 in the Netherlands, is still rising. Despite incorporation in the ESMO GIST guidelines since 2008 for mutational testing and since 2010 for central review of pathology, both are performed in a minority of patients.

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Short course of cyclosporin A as a treatment option for drug-induced hypersensitivity syndrome: Case reports and review of the published work

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Clinical and immunohistochemical comparative study of the efficacy of carboxytherapy vs platelet-rich plasma in treatment of stretch marks

Summary

Background

Striae distensae are dermal scars with a linear atrophic depression. The exact origin of striae distensae remains unrevealed, but low expression of collagen and fibronectin genes in the affected tissue was found. Several treatment modalities have been proposed, yet no consistent modality is available.

Aim of the work

To evaluate and compare the efficacy and safety of carboxytherapy vs platelet-rich plasma (PRP) in treatment of stretch marks.

Patients and methods

This study included 20 patients with striae alba. Every patient received treatment in the form of PRP injection in their right side (group A) and carboxytherapy session in their left side (group B) every 3-4 weeks for 4 sessions. Skin biopsies were taken before and after treatment, and they were subjected to fibronectin immunohistochemical stain.

Results

There was a significant improvement in striae alba in both groups after than before treatment. There was no significant difference between both groups as regards either percentage of improvement, response (grading scale), or patient satisfaction. The fibronectin-stained area was significantly higher in both groups after than before treatment, and it was significantly higher after treatment in group (B) than group (A).

Conclusions

Both methods were safe and effective with minimal side effects. There was no significant difference between both methods of treatments. This was confirmed histopathologically by fibronectin expression which is found to be low in striae and increased significantly after treatment. But fibronectin expression was higher in group (B) than (A).

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Filler migration and extensive lesions after lip augmentation: Adverse effects of polydimethylsiloxane filler

Summary

Polydimethylsiloxane (PDMS), also called liquid silicone, belongs to a group of polymeric compounds that are commonly referred to as silicones. These filling agents have been used as injectable filler for soft tissue augmentation. There are limited experiences about management of the severe complications related to filler migration associated with PDMS injection. We present a 35-year-old female with severe erythema, edema over her cheeks and neck, and multiple irregularities following cosmetic lip augmentation with PDMS. Further studies are required for management of this complicated case of PDMS injection.

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Protective effect of conditioner agents on hair treated with oxidative hair dye

Summary

Background

Hair coloring is broadly used by women and men either to change their natural hair color or to delay the onset of gray hair. Oxidative dyes may damage the hair, as chemical and physical processes are required to convert the fiber structure and, consequently, alterations in its mechanical and surface properties.

Objectives

The aim of this study was to evaluate the protective effect of silanetriol (and) Panthenol, PEG-12 dimethicone, and hydrolyzed silk (and) hydrolyzed milk protein (and) lactose as conditioner agents on hair treated with oxidative hair dye by protein loss, combability, and breaking strength.

Methods

In this research, we analyzed the untreated hair (sample I) and the effect of oxidative hair dye emulsions, with or without conditioner agents (sample II) silanetriol (and) Panthenol (sample III), PEG-12 dimethicone (sample IV), and hydrolyzed silk (and) hydrolyzed milk protein (and) lactose (sample V) on Caucasian hair. The hair samples were submitted to protein loss quantification, breaking strength, and combing analysis.

Results

For protein loss, the results were: II^a = V^a > IV^b > III^c > I^d. For the breaking strength: I^e = II^e= III^e= IV^e = V^e. For the combing analysis for wet and dry hair, the results were, respectively: II^a > III^b = IV^b > V^c > I^d and II^A > III^b = V^b > IV ^c= I^c. Data classified by different letters presented statistically significant alterations, α = 5, P ≤ . 05, n = 15.

Conclusions

Based on these results, the incorporation of conditioner agents into emulsion blond color decreased the damage caused by the coloring process.

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Thyroid Top-Read Articles of 2017

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FREE ACCESS through January 16, 2018.
Read now:

Latest Impact Factor: 5.515
The Official Journal of: American Thyroid Association

The 2017 Bethesda System for Reporting Thyroid Cytopathology
Edmund S. Cibas, Syed Z. Ali

Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis
Spyridoula Maraka, Naykky M. Singh Ospina, Derek T. O'Keeffe, Ana E. Espinosa De Ycaza, Michael R. Gionfriddo, Patricia J. Erwin, Charles C. Coddington III, Marius N. Stan, M. Hassan Murad, Victor M. Montori

Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology
Yuri E. Nikiforov, Sally E. Carty, Simon I. Chiosea, Christopher Coyne, Umamaheswar Duvvuri, Robert L. Ferris, William E. Gooding, Shane O. LeBeau, N. Paul Ohori, Raja R. Seethala, Mitchell E. Tublin, Linwah Yip, Marina N. Nikiforova

Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery
Hitomi Oda, Akira Miyauchi, Yasuhiro Ito, Kana Yoshioka, Ayako Nakayama, Hisanori Sasai, Hiroo Masuoka, Tomonori Yabuta, Mitsuhiro Fukushima, Takuya Higashiyama, Minoru Kihara, Kaoru Kobayashi, Akihiro Miya

Thyroid Ultrasound Features and Risk of Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies
Luciana Reck Remonti, Caroline Kaercher Kramer, Cristiane Bauermann Leitão, Lana Catani F. Pinto, Jorge Luiz Gross

The post <i>Thyroid</i> Top-Read Articles of 2017 appeared first on American Thyroid Association.

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Contact heat evoked potentials: reliable acquisition from lower extremities

Publication date: Available online 7 January 2018
Source:Clinical Neurophysiology
Author(s): J Rosner, M Hubli, P Hostettler, PS Scheuren, J Rinert, JLK Kramer, M Hupp, A Curt, CR Jutzeler
ObjectiveTo investigate test-retest reliability of contact heat evoked potentials (CHEPs) from lower extremities using two different stimulation protocols, i.e., normal and increased baseline temperature.MethodsA total of 32 able-bodied subjects were included and a subset (N=22) was retested. CHEPs were recorded from three different dermatomes of the lower extremity (i.e., L2, L5, and S2). Test-retest reliability of CHEPs acquisition after simulation in various lower limb dermatomes using different stimulation protocolswas analyzed.ResultsThe study revealed an improved acquisition of CHEPS employing the increased baseline protocol, particularly when stimulating more distal sites, i.e., dermatome L5 and S2. Based on repeatability coefficients, CHEP latency (N2 potential) emerged as the most robust CHEP parameter. Although CHEP amplitudes (N2P2 complex) and pain ratings were decreased in the retest, amplitudes still showed fair to excellent intraclass correlation coefficients (ICCs) using normal baseline or increased baseline temperature, respectively.ConclusionsThis is the first study to demonstrate that CHEPs acquisition from the lower extremities is improved by increasing the baseline temperature of the thermode.SignificanceThis study highlights the usability of CHEPs as a viable diagnostic method to study small fiber integrity.

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New methods for automatic quantification of microstructural features using digital image processing

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Andrew Campbell, Paul Murray, Evgenia Yakushina, Stephen Marshall, William Ion
Thermal and mechanical processes alter the microstructure of materials, which determines their mechanical properties. This makes reliable microstructural analysis important to the design and manufacture of components. However, the analysis of complex microstructures, such as Ti6Al4V, is difficult and typically requires expert materials scientists to manually identify and measure microstructural features. This process is often slow, labour intensive and suffers from poor repeatability. This paper overcomes these challenges by proposing a new set of automated techniques for 2D microstructural analysis. Digital image processing algorithms are developed to isolate individual microstructural features, such as grains and alpha lath colonies. A segmentation of the image is produced, where regions represent grains and colonies, from which morphological features such as; grain size, volume fraction of globular alpha grains and alpha colony size can be measured. The proposed measurement techniques are shown to obtain similar results to existing manual methods while drastically improving speed and repeatability. The benefits of the proposed approach when measuring complex microstructures are demonstrated by comparing it with existing analysis software. Using a few parameter changes, the proposed techniques are effective on a variety of microstructure types and both SEM and optical microscopy images.

Graphical abstract

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The value of detection of S100A8 and ASAH1 in predicting the chemotherapy response for breast cancer patients

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Yu-hong Li, Hai-ting Liu, Jing Xu, Ai-yan Xing, Jie Zhang, Ya-wen Wang, Gang Yin, Peng Gao
Chemotherapy plays an important role in the treatment of breast cancer. However, chemoresistance remains the main obstacle for effective treatment, leading to poor prognosis. This study aims to investigate the value of detection of S100A8 and ASAH1 in predicting the chemotherapy response. Miller and Payne grades were used to assess the chemotherapy response in breast cancers. The expression of S100A8 and ASAH1, as well as ER, PR, HER-2 and Ki-67 were assessed by immunohistochemical staining in 120 cases of non-special type invasive ductal carcinoma (IDC-NOS). S100A8 expression was higher in chemosensitive breast cancers than chemoresistant ones. Moreover, S100A8 expression was significantly correlated with the molecular subtypes and histological grade, but not with patients' age, tumor size and lymph nodes status. However, there was no significant difference in ASAH1 expression between chemoresistant and chemosensitive group. We also found that higher ASAH1 expression was correlated with positive lymph nodes status, but not with age, tumor size, molecular subtypes and histological grade. S100A8 was valuable in predicting chemotherapy response in breast cancers. The expression of ASAH1 was associated significantly with lymph nodes metastasis, indicating that ASAH1 may serve as a biomarker to predict patients' lymph nodes status in breast cancers.

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Atypical multivacuolated lipoblasts and atypical mitoses are not compatible with the diagnosis of spindle cell/pleomorphic lipoma—reply

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Michael Michal, Dmitry V. Kazakov, Kvetoslava Michalova, Michal Michal

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Characteristics of cribriform morular variant of papillary thyroid carcinoma in post-Chernobyl affected region

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Alfred King-yin Lam, Mikhail Fridman
The aim is to study the characteristics of cribriform morular variant of papillary thyroid carcinoma (CMV-PTC) in patients living in radiation-affected area of Belarus. The clinical and pathological features of 35 patients with CMV-PTC from Belarus were studied and compared with those of conventional papillary thyroid carcinoma diagnosed in the same period. The patients with CMV-PTC were all females and were younger at presentation (mean age = 24) than those with conventional papillary thyroid carcinoma. Familial adenomatous polyposis (FAP) was identified in 20% of the patients with CMV-PTC. The majority of the CMV-PTCs (29/35; 83%) were staged as pT1 and were less advanced than conventional papillary thyroid carcinoma. There was no evidence of lymph node metastases or distant metastases. CMV-PTCs were positive for beta-catenin, APC (adenomatous polyposis coli) and p53 proteins. No psammoma bodies were identified on microscopic examination. Over a median follow-up of 9 years, all the patients were alive, there were no cancer recurrence or mortality related to the thyroid cancer. To conclude, patients with CMV-PTC in radiation-affected region behave in an indolent fashion. They had distinctive features that are different from patients with conventional papillary thyroid carcinoma living in the same region.

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Downregulated SASH1 Expression Indicates Poor Clinical Prognosis in Gastric Cancer

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Nan Zhou, Can Liu, Xudong Wang, Qinsheng Mao, Qin Jin, Peng Li
SASH1 (SAM- and SH3-domain containing 1), a novel candidate tumor suppressor, has attracted attention due to its role in intracellular signal transduction and its tumor prognostic value in diverse cancers. Reports have demonstrated that reduced SASH1 expression correlates with tumor proliferation, invasion, and metastasis. However, the expression and prognostic significance of SASH1 in gastric cancer (GC) remain unclear. In this study, 8 paired fresh-frozen GC tissues and corresponding gastric mucosal tissues were examined by Western blot to analyze the protein expression of SASH1. 726 formalin-fixed, paraffin-embedded (FFPE) gastric tissue samples were evaluated by immunohistochemical (IHC) to determine the correlations of SASH1 expression with clinicopathological factors and prognosis. Compared with adjacent noncancerous tissues, SASH1 was significantly downregulated in GC specimens. Analysis using the χ test revealed that low SASH1 expression was significantly associated with advanced TNM stage (P<0.001) in GC. Cox regression multivariable analyses demonstrated that SASH1 expression (P<0.001), TNM stage (P<0.001), preoperative CEA level (P=0.003) and preoperative CA19-9 level (P=0.002) were independent prognostic factors. Our clinical findings suggest that downregulated SASH1 expression could be used as an independent biomarker for poor prognosis in GC.

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Prognostic significance of S100A16 sub-cellular localization in lung adenocarcinoma

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Makoto Kobayashi, Ryo Nagashio, Keita Saito, Clemente Aguilar-Bonavides, Shinichiro Ryuge, Ken Katono, Satoshi Igawa, Benio Tsuchiya, Shi-Xu Jiang, Masaaki Ichinoe, Yoshiki Murakumo, Makoto Saegusa, Yukitoshi Satoh, Yuichi Sato
To discover novel tumor markers for lung adenocarcinoma (AC), we performed proteomics analysis and reported a correlation between S100A16 membranous expression in AC tissues and a poor prognosis. However, some patients with a good prognosis also showed S100A16 membranous staining. We re-evaluated immunohistochemically stained tissues, and found membrane-positive and nucleus- negative expressions to be significantly higher in the presence of the following: male, smoker, positive nodal metastasis, higher p-TNM stage, larger tumor, poorer differentiation, positive for lymphatic invasion, positive for vascular invasion, and positive for pleural invasion (all factors P < 0.05). This pattern of staining was also an independent prognostic factor. Furthermore, we analyzed S100A16 mRNA expression using TCGA and Kaplan-Meier plotter databases, and found that higher S100A16 mRNA expression in AC was significantly correlated with poorer survival. To our knowledge, there has been no comprehensive study focused on both S100A16 protein and mRNA expression levels in AC patients. Our results suggest that the sub-cellular localization of S100A16 and S100A16 mRNA expression levels are promising prognostic markers for AC.

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Uterine Rhabdomyosarcoma in Adults

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Andre Pinto, Ryan M. Kahn, Andrew E. Rosenberg, Brian Slomovitz, Charles Matthew Quick, Michella K. Whisman, Marilyn Huang
Rhabdomyosarcoma (RMS) is an aggressive mesenchymal tumor most commonly diagnosed in the pediatric population, and when occurring in adults, tends to develop in the deep soft tissue of the limbs. Primary uterine RMS comprises an even more restricted subset, with little known or reported when compared to most other gynecologic sarcomas. Our goal with this study was to retrospectively evaluate cases from two academic institutions and describe the main histopathologic findings of this rare gynecologic malignancy. A total of eight cases were identified, consisting of four pleomorphic rhabdomyosarcomas (PRMS), two alveolar rhabdomyosarcomas (ARMS), and two embryonal rhabdomyosarcomas (ERMS). They occurred in patients ranging from 22 to 70 years old, and the most common presenting symptom was vaginal bleeding. Most patients presented with advanced stage at diagnosis, including metastatic disease to lymph nodes and to distant sites. The masses were mostly (6/8) centered in the myometrium, while two cases arose in the cervix (2/8). Histologic characteristics of the tumors were dependent of the RMS subtype, although all cases demonstrated a similar immunohistochemical profile regardless of their subclassification. RMS of the uterus has a very poor prognosis, and data regarding treatment of this rare malignancy is limited, and usually extrapolated from non-uterine sites.

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The Many Faces of Intestinal Tract Gastric Heterotopia; A Series of Four Cases Highlighting Clinical and Pathological Heterogeneity

Publication date: Available online 7 January 2018
Source:Human Pathology
Author(s): Aqsa Nasir, Stuart K. Amateau, Sabina Khan, Ross W. Simpson, Dale C. Snover, Khalid Amin
Gastric heterotopia of the intestinal tract can have a diverse clinicopathologic presentation, resulting in a diagnostic dilemma. We present a series of four cases, two male and two female patients with age range of 31-82 year, found in the duodenum, jejunum, and transverse colon. The most common and rather unusual clinical presentation was iron deficiency anemia, seen in three cases, while one patient presented with abdominal pain. Endoscopically two cases were visualized as pedunculated polyps and two as sessile/plaques like lesions. Polypectomy was performed in three patients and one patient underwent biopsy followed by resection. Two cases showed oxyntic-type epithelium and two cases exhibited pylorictype gastric epithelium. Three patients were relieved of their presenting symptoms after therapeutic procedure with no evidence of recurrence noted on follow-up. Follow-up was not available on one patient. This case series highlights diverse clinicopathologic spectrum of gastric heterotopia. Accurate diagnosis is essential for proper management.

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Diversity and functional evolution of the plasminogen activator system

Publication date: February 2018
Source:Biomedicine & Pharmacotherapy, Volume 98
Author(s): Rishi Kumar Jaiswal, Akhil Kumar Varshney, Pramod Kumar Yadava
The urokinase plasminogen activator system is a family of serine proteases which consists of uPA (urokinase plasminogen activator), uPAR (urokinase type plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1). In addition to their significant roles in activation, these proteases act as key regulators of the tumor microenvironment and are involved in the metastatic process in many cancers. High levels of uPA system proteases in many human cancer predicts poor patient prognosis and strongly indicated a key role of uPA system in cancer metastasis. Individual components of uPA system are found to be differentially expressed in cancer cells compared to normal cells and therefore are potential therapeutic targets. In this review, we present the molecular and cellular mechanisms underlying the role of uPA system in cancer progression. Epithelial to mesenchymal transitions (EMT) is the main cause of the cancer cell metastasis. We have also attempted to relate the role of uPA signaling in EMT of cancer cells.

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Effects of Rhinovirus (RV) 39 Infection on Airway Hyper-responsiveness (AHR) to Carbachol in Human Airways Precision Cut Lung Slices (PCLS)

Publication date: Available online 6 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Joshua L. Kennedy, Cynthia J. Koziol-White, Susanne Jeffus, Mallikarjuna R. Rettiganti, Paige Fisher, Megan Kurten, Anthony Eze, Suzanne House, James D. Sikes, Emily Askew, Claire Putt, Reynold A. Panettieri, Stacie M. Jones, Richard C. Kurten

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Cluster Analysis of Vulnerable Groups in Acute TBI Rehabilitation

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Erkut N. Kucukboyaci, Coralynn Long, Michelle Smith, Joseph F. Rath, Tamara Bushnik
ObjectiveTo analyze the complex relationship between various social indicators that contribute to socioeconomic status and healthcare barriers.DesignCluster analysis of historical patient data obtained from inpatient visits.SettingSetting: Inpatient rehabilitation unit in a large, urban university hospitalParticipantsAdult patients receiving acute inpatient care, predominantly for closed head injury.InterventionsNot applicableMain outcome measuresWe examined the membership of TBI patients in various "vulnerable group" (VG) clusters (e.g., homeless, unemployed, racial/ethnic minority) and characterized the rehabilitation outcomes of the patients (e.g., duration of stay, changes in Functional Independence Measure [FIM] scores between admission to inpatient stay and discharge).ResultsAnalysis revealed four major clusters (i.e., Clusters A-D) separated by VG memberships, with distinct durations of stay and FIM gains during their stay. Cluster B, the largest cluster and also consisting of mostly racial/ethnic minorities, had the shortest duration of hospital stay and one of the lowest FIM improvements among the four clusters despite higher FIM scores at admission. In cluster C, also consisting of mostly ethnic minorities with multiple SES vulnerabilities, patients were characterized by low cognitive FIM scores at admission and the longest duration of stay, and they showed good improvement in FIM scores.ConclusionsApplication of clustering techniques to inpatient data identified distinct clusters of patients who may experience differences in their rehabilitation outcome due to their membership in various "at-risk" groups. Results identified patients (i.e., cluster B, with minority patients and Cluster D, with elderly patients) who attain below-average gains in brain injury rehabilitation. Results also suggested that systemic (e.g., duration of stay) or clinical service improvements (e.g., staff's language skills, ability to offer substance abuse therapy, provide appropriate referrals or liaise with intensive social work services or plan subacute rehabilitation phase) could be beneficial for acute settings. Stronger recruitment, training and retention initiatives for bilingual and multiethnic professionals may also be considered to optimize gains from acute inpatient rehabilitation following traumatic brain injury.

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Determining Reliability of a Dual-task Functional Mobility Protocol for Individuals with Lower Extremity Amputations

Publication date: Available online 6 January 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Courtney Frengopoulos, Michael WC. Payne, Jeffrey Holmes, Ricardo Viana, Susan W. Hunter
ObjectivesTo determine the relative and absolute reliability of a dual-task functional mobility assessment.DesignCross-sectional study.SettingAcademic Rehabilitation Hospital.ParticipantsSixty individuals with lower extremity amputation (LEA) attending an outpatient amputee clinic (age= 58.21±12.59; 80.0% male). Subjects were stratified into three groups: 1) transtibial amputations of vascular etiology (TTA-vas), transtibial amputations of non-vascular etiology (TTA-nonvas); transfemoral or bilateral amputees (TFA/bilat) of any etiology.InterventionsN/AMain Outcome MeasuresTime to complete the L Test measured functional mobility under single- and dual-task conditions. Addition of a cognitive task (serial subtractions by 3s) created dual-task conditions. Single task performance on the cognitive task was also reported. Intra-class correlation coefficients (ICC) measured relative reliability; standard error of measurement (SEM) and minimal detectable change with a 95% confidence interval (MDC95) measured absolute reliability. Bland and Altman plots measured agreement between assessments.ResultsRelative reliability results were excellent for all three groups. Values for the dual-task L Test for those with TTA-vas (n=20, age=60.36±7.84, 90.0% male) were ICC=0.98 (95% CI, 0.94-0.99), with SEM=1.36s and MDC95 of 3.76s; for those with TTA-nonvas (n=20, age=55.85±14.08, 85.0% male), were ICC=0.93 (95% CI, 0.80-0.98), SEM=1.34s and MDC95 of 3.71s; and for those with TFA/bilat group (n=20, age=58.21±14.88, 65.0% male) were ICC=0.998 (95% CI, 0.996-0.999), SEM=1.03s and an MDC95 of 2.85s. Bland-Altman plots indicated that assessments did not vary systematically for each group.ConclusionsThis dual-task assessment protocol achieved approved levels of relative reliability values for the three groups tested. This protocol may be used clinically or in research settings to assess the interaction between cognition and functional mobility in the LEA population.

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Design, synthesis and evaluation against Chikungunya virus of novel small-molecule antiviral agents

Publication date: Available online 6 January 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Roberta Tardugno, Gilda Giancotti, Tine De Burghgraeve, Leen Delang, Johan Neyts, Pieter Leyssen, Andrea Brancale, Marcella Bassetto
Chikungunya virus is a re-emerging arbovirus transmitted to humans by mosquitoes, responsible for an acute flu-like illness associated with debilitating arthralgia, which can persist for several months or become chronic. In recent years, this viral infection has spread worldwide with a previously unknown virulence. To date, no specific antivirals treatments nor vaccines are available against this important pathogen. Starting from the structures of two antiviral hits previously identified in our research group with in silico techniques, this work describes the design and preparation of 31 novel structural analogues, with which different pharmacophoric features of the two hits have been explored and correlated with the inhibition of Chikungunya virus replication in cells. Structure-activity relationships were elucidated for the original scaffolds, and different novel antiviral compounds with EC50 values in the low micromolar range were identified. This work provides the foundation for further investigation of these promising novel structures as antiviral agents against Chikungunya virus.

Graphical abstract

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Amoebal endosymbiont Neochlamydia protects host amoebae against Legionella pneumophila infection by preventing Legionella entry

Publication date: Available online 6 January 2018
Source:Microbes and Infection
Author(s): Chinatsu Maita, Mizue Matsushita, Masahiro Miyoshi, Torahiko Okubo, Shinji Nakamura, Junji Matsuo, Masaharu Takemura, Masaki Miyake, Hiroki Nagai, Hiroyuki Yamaguchi
Acanthamoeba isolated from environmental soil harbors the obligate intracellular symbiont Neochlamydia, which has a critical role in host amoebal defense against Legionella pneumophila infection. Here, by using morphological analysis with confocal laser scanning fluorescence microscopy and transmission electron microscopy, proteome analyses with two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and liquid chromatography–mass spectrometry (LC/MS), and transcriptome analysis with DNA microarray, we explored the mechanism by which the Neochlamydia effected this defense. We observed that when rare uptake did occur, the symbiotic amoebae allowed Legionella to grow normally. However, the symbiotic amoebae had severely reduced uptake of Legionella when compared with the aposymbiotic amoebae. Also, in contrast to amoebae carrying the endosymbiont, the actin cytoskeleton was significantly disrupted by Legionella infection in aposymbiotic amoebae. Furthermore, despite Legionella exposure, there was little change in Neochlamydia gene expression. Taken together, we concluded that the endosymbiont, Neochlamydia prevents Legionella entry to the host amoeba, resulting in the host defense against Legionella infection.

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Development of stereotaxic recording system for awake marmosets (Callithrix jacchus)

Publication date: Available online 6 January 2018
Source:Neuroscience Research
Author(s): Masahiro Wakabayashi, Daisuke Koketsu, Hideki Kondo, Shigeki Sato, Kiichi Ohara, Zlata Polyakova, Satomi Chiken, Nobuhiko Hatanaka, Atsushi Nambu
The common marmoset has been proposed as a potential alternative to macaque monkey as a primate model for neuroscience and medical research. Here, we have newly developed a stereotaxic neuronal recording system for awake marmosets under the head-fixed condition by modifying that for macaque monkeys. Using this system, we recorded neuronal activity in the cerebral cortex of awake marmosets and successfully identified the primary motor cortex by intracortical microstimulation. Neuronal activities of deep brain structures, such as the basal ganglia, thalamus, and cerebellum, in awake marmosets were also successfully recorded referring to magnetic resonance images. Our system is suitable for functional mapping of the brain, since the large recording chamber allows access to arbitrary regions over almost the entire brain, and the recording electrode can be easily moved stereotaxically from one site to another. In addition, our system is desirable for neuronal recording during task performance to assess motor skills and cognitive function, as the marmoset sits in the marmoset chair and can freely use its hands. Moreover, our system can be used in combination with cutting-edge techniques, such as two-photon imaging and optogenetic manipulation. This recording system will contribute to boosting neuroscience and medical research using marmosets.

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Presynaptic Calcium Channels

Publication date: Available online 6 January 2018
Source:Neuroscience Research
Author(s): Sumiko Mochida
At the presynaptic terminal, neuronal firing activity induces membrane depolarization and subsequent Ca²⁺ entry through voltage-gated Ca²⁺ (CaV) channels triggers neurotransmitter release from the active zone. Presynaptic Ca²⁺ channels form a large signaling complex, which targets synaptic vesicles to Ca²⁺ channels for efficient release and mediates Ca²⁺ channel regulation. The presynaptic CaV2 channel family (comprising CaV2.1, CaV2.2 and CaV2.3 isoforms) encode the pore-forming α1 subunit. The cytoplasmic regions are the target of regulatory proteins for channel modulation. Modulation of presynaptic Ca²⁺ channels has a powerful influence on synaptic transmission. This article overviews spatial and temporal regulation of Ca²⁺ channels by effectors and sensors of Ca²⁺ signaling, and describes the emerging evidence for a critical role of Ca²⁺ channel regulation in control of synaptic transmission and presynaptic plasticity. Sympathetic superior cervical ganglion neurons in culture expressing CaV2.2 channels represent a well-characterized system for investigating synaptic transmission. The exogenously expressed α1 subunit of the CaV2.1 as well as endogenous CaV2.2 was examined for modulation of channel activity, and thereby regulation of synaptic transmission. The constitutive and Ca²⁺-dependent modulation of CaV2.1 channels coordinately act as spatial and temporal molecular switches to control synaptic efficacy.

http://ift.tt/2FbRqIm

Exposure- and flux-based assessment of ozone risk to sugarcane plants

Publication date: March 2018
Source:Atmospheric Environment, Volume 176
Author(s): Bárbara Baêsso Moura, Yasutomo Hoshika, Rafael Vasconcelos Ribeiro, Elena Paoletti
Ozone (O3) is a toxic oxidative air pollutant, with significant detrimental effects on crops. Sugarcane (Saccharum spp.) is an important crop with no O3 risk assessment performed so far. This study aimed to assess O3 risk to sugarcane plants by using exposure-based indices (AOT40 and W126) based on O3 concentrations in the air, and the flux-based index (PODy, where y is a threshold of uptake) that considers leaf O3 uptake and the influence of environmental conditions on stomatal conductance (gsto). Two sugarcane genotypes (IACSP94-2094 and IACSP95-5000) were subjected to a 90-day Free-Air Controlled Experiment (FACE) exposure at three levels of O3 concentrations: ambient (Amb); Amb x1.2; and Amb x1.4. Total above-ground biomass (AGB), stalk biomass (SB) and leaf biomass (LB) were evaluated and the potential biomass production in a clean air was estimated by assuming a theoretical clean atmosphere at 10 ppb as 24 h O3 average. The Jarvis-type multiplicative algorithm was used to parametrize gsto including environmental factors i.e. air temperature, light intensity, air vapor pressure deficit, and minimum night-time temperature. Ozone exposure caused a negative impact on AGB, SB and LB. The O3 sensitivity of sugarcane may be related to its high gsto (∼535 mmol H2O m⁻² s⁻¹). As sugarcane is adapted to hot climate conditions, gsto was restricted when the current minimum air temperature (Tmin) was below ∼14 °C and the minimum night-time air temperature of the previous day (Tnmin) was below ∼7.5 °C. The flux-based index (PODy) performed better than the exposure-based indices in estimating O3 effect on biomass losses. We recommend a y threshold of 2 nmol m⁻² s⁻¹ to incorporate O3 effects on both AGB and SB and 1 nmol m⁻² s⁻¹ on LB. In order not to exceed 4% reduction in the growth of these two sugarcane genotypes, we recommend the following critical levels: 1.09 and 1.04 mmol m⁻² POD2 for AGB, 0.91 and 0.96 mmol m⁻² POD2 for SB, and 3.00 and 2.36 mmol m⁻² POD1 for LB of IACSP95-5000 and IACSP94-2094, respectively.

http://ift.tt/2CQtzAe

Editorial Board

Publication date: January 2018
Source:Biological Psychology, Volume 131

http://ift.tt/2m4tqxX

Using c-Jun to identify fear extinction learning-specific patterns of neural activity that are affected by single prolonged stress

Publication date: 2 April 2018
Source:Behavioural Brain Research, Volume 341
Author(s): Dayan Knox, Briana R. Stanfield, Jennifer M. Staib, Nina P. David, Thomas DePietro, Marisa Chamness, Elizabeth K. Schneider, Samantha M. Keller, Caroline Lawless
Neural circuits via which stress leads to disruptions in fear extinction is often explored in animal stress models. Using the single prolonged stress (SPS) model of post traumatic stress disorder and the immediate early gene (IEG) c-Fos as a measure of neural activity, we previously identified patterns of neural activity through which SPS disrupts extinction retention. However, none of these stress effects were specific to fear or extinction learning and memory. C-Jun is another IEG that is sometimes regulated in a different manner to c-Fos and could be used to identify emotional learning/memory specific patterns of neural activity that are sensitive to SPS. Animals were either fear conditioned (CS-fear) or presented with CSs only (CS-only) then subjected to extinction training and testing. C-Jun was then assayed within neural substrates critical for extinction memory. Inhibited c-Jun levels in the hippocampus (Hipp) and enhanced functional connectivity between the ventromedial prefrontal cortex (vmPFC) and basolateral amygdala (BLA) during extinction training was disrupted by SPS in the CS-fear group only. As a result, these effects were specific to emotional learning/memory. SPS also disrupted inhibited Hipp c-Jun levels, enhanced BLA c-Jun levels, and altered functional connectivity among the vmPFC, BLA, and Hipp during extinction testing in SPS rats in the CS-fear and CS-only groups. As a result, these effects were not specific to emotional learning/memory. Our findings suggest that SPS disrupts neural activity specific to extinction memory, but may also disrupt the retention of fear extinction by mechanisms that do not involve emotional learning/memory.

http://ift.tt/2CzOlA2

Creation of Dystrophin Expressing Chimeric Cells of Myoblast Origin as a Novel Stem Cell Based Therapy for Duchenne Muscular Dystrophy.

Creation of Dystrophin Expressing Chimeric Cells of Myoblast Origin as a Novel Stem Cell Based Therapy for Duchenne Muscular Dystrophy.

Stem Cell Rev. 2018 Jan 05;:

Authors: Siemionow M, Cwykiel J, Heydemann A, Garcia-Martinez J, Siemionow K, Szilagyi E

Abstract
Over the past decade different stem cell (SC) based approaches were tested to treat Duchenne Muscular Dystrophy (DMD), a lethal X-linked disorder caused by mutations in dystrophin gene. Despite research efforts, there is no curative therapy for DMD. Allogeneic SC therapies aim to restore dystrophin in the affected muscles; however, they are challenged by rejection and limited engraftment. Thus, there is a need to develop new more efficacious SC therapies. Chimeric Cells (CC), created via ex vivo fusion of donor and recipient cells, represent a promising therapeutic option for tissue regeneration and Vascularized Composite Allotransplantation (VCA) due to tolerogenic properties that eliminate the need for lifelong immunosuppression. This proof of concept study tested feasibility of myoblast fusion for Dystrophin Expressing. Chimeric Cell (DEC) therapy through in vitro characterization and in vivo assessment of engraftment, survival, and efficacy in the mdx mouse model of DMD. Murine DEC were created via ex vivo fusion of normal (snj) and dystrophin-deficient (mdx) myoblasts using polyethylene glycol. Efficacy of myoblast fusion was confirmed by flow cytometry and dystrophin immunostaining, while proliferative and myogenic differentiation capacity of DEC were assessed in vitro. Therapeutic effect after DEC transplant (0.5 × 106) into the gastrocnemius muscle (GM) of mdx mice was assessed by muscle functional tests. At 30 days post-transplant dystrophin expression in GM of injected mdx mice increased to 37.27 ± 12.1% and correlated with improvement of muscle strength and function. Our study confirmed feasibility and efficacy of DEC therapy and represents a novel SC based approach for treatment of muscular dystrophies.

PMID: 29305755 [PubMed - as supplied by publisher]

http://ift.tt/2D3iglq

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

http://ift.tt/2m6vwxc

Hearing impairment and hearing aid usage in Singapore.

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

Abstract
OBJECTIVE: To examine the epidemiological and audiological profile, pattern of hearing aid (HA) fitting and usage among HA users in Singapore.
DESIGN: Retrospective cross-sectional study.
STUDY SAMPLE: Cohort of 1068 subjects issued with HAs at a tertiary hospital between 2001 and 2013.
RESULTS: Mean age was 70 years with 50.8% male. Mean hearing loss (HL) was 63.1 dB and 69.5% had at least moderate-severe HL. Sensorineural HL was present in 66.4% and 69.8% had symmetrical HL. "Behind-the-Ear" HAs were cheaper than "In-Ear" HAs. Standard "Behind-The-Ear" HAs were also cheaper than "Receiver-in-Canal" HAs. Among In-Ear HAs, "In-the-Canal" and "Completely-in-Canal" were more popular than "In-the-Ear" HAs despite costing more. HA was used ≥4 days/week by 85.6% but >7 h per day by only 35.7%. Only 18% received bilateral first HA fitting. In multivariate analysis, younger age and symmetrical HL were predictors of bilateral HA uptake while better Pure-Tone-Audiometry of aided ear and >7 h of daily HA usage were predictors of successive HA fitting.
CONCLUSIONS: HA users in Singapore were elderly and presented with advanced HL. Bilateral HA adoption and average daily use were low compared to other developed countries. Future research on understanding the suboptimal HA usage should explore patients motivation, hearing disability, and HA effectiveness.

PMID: 29304553 [PubMed - as supplied by publisher]

http://ift.tt/2m9mArQ

Mitochondrial Network Responses in Oxidative Physiology and Disease

Publication date: Available online 6 January 2018
Source:Free Radical Biology and Medicine
Author(s): Young-Mi Go, Jolyn Fernandes, Xin Hu, Karan Uppal, Dean P. Jones
Mitochondrial activities are linked directly or indirectly to all cellular functions in aerobic eukaryotes. Omics methods enable new approaches to study functional organization of mitochondria and their adaptive and maladaptive network responses to bioenergetic fuels, physiologic demands, environmental challenges and aging. In this review, we consider mitochondria collectively within a multicellular organism as a macroscale "mitochondriome", functioning to organize bioenergetics and metabolism as an organism utilizes environmental resources and protects against environmental threats. We address complexities of knowledgebase-driven functional mapping of mitochondrial systems and then consider data-driven network mapping using omics methods. Transcriptome-metabolome-wide association study (TMWAS) shows connectivity and organization of nuclear transcription with mitochondrial transport systems in cellular responses to mitochondria-mediated toxicity. Integration of redox and respiratory measures with TMWAS shows central redox hubs separating systems linked to oxygen consumption rate and H2O2 production. Combined redox proteomics, metabolomics and transcriptomics further shows that physiologic network structures can be visualized separately from toxicologic networks. These data-driven integrated omics methods create new opportunities for mitochondrial systems biology.

Graphical abstract

http://ift.tt/2qBSYrO

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

http://ift.tt/2m6vwxc

Hearing impairment and hearing aid usage in Singapore.

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

PMID: 29304553 [PubMed - as supplied by publisher]

http://ift.tt/2m9mArQ

Vestibulo-cochlear function in inflammatory neuropathies.

Vestibulo-cochlear function in inflammatory neuropathies.

Clin Neurophysiol. 2017 Dec 20;:

Authors: Blanquet M, Petersen JA, Palla A, Veraguth D, Weber KP, Straumann D, Tarnutzer AA, Jung HH

Abstract
OBJECTIVE: We aimed to quantify peripheral-vestibular deficits that may contribute to imbalanced stance/gait in patients with inflammatory neuropathies.
METHODS: Twenty-one patients (58 ± 15 y [mean age ± 1SD]; chronic-inflammatory-demyelinating-polyneuropathy = 10, Guillain-Barré Syndrome = 5, Anti-MAG peripheral neuropathy = 2, multifocal-motor-neuropathy = 4) were compared with 26 healthy controls. All subjects received video-head-impulse testing (vHIT), caloric irrigation and cervical/ocular vestibular-evoked myogenic-potentials (VEMPs). The Yardley vertigo-symptom-scale (VSS) was used to rate vertigo/dizziness. Postural stability was assessed using the functional gait-assessment (FGA). Pure-tone audiograms (n = 18), otoacoustic emissions (n = 12) and auditory brainstem responses were obtained (n = 12).
RESULTS: Semicircular-canal hypofunction was noted in 9/21 (43%) patients (vHIT = 6; caloric irrigation = 5), whereas otolith function was impaired in 12/21 (57%) (oVEMPs = 8; cVEMPs = 5), resulting in vestibular impairment of at least one sensor in 13/21 (62%). On average, 2.4 ± 1.1 vestibular end organs (each side: anterior/posterior/horizontal canal, utriculus, sacculus; total = 10) were affected. The VSS-scores were higher in patients (16.8 ± 8.6 vs. 9.5 ± 6.2, p = 0.002) but did not correlate with the number of affected organs. Auditory neuropathy was found in 1/12 (8%) patients.
CONCLUSION: Impairment of one or more vestibular end organs was frequent, but usually mild, possibly contributing to imbalance of stance/gait in inflammatory neuropathies.
SIGNIFICANCE: While our data does not support routine vestibular testing in inflammatory neuropathies, this may be considered in selected cases.

PMID: 29305208 [PubMed - as supplied by publisher]

http://ift.tt/2CJWeq7

Analysis of the spectrum and antibiotic resistance of uropathogens in outpatients at a tertiary hospital.

Analysis of the spectrum and antibiotic resistance of uropathogens in outpatients at a tertiary hospital.

J Chemother. 2018 Jan 05;:1-5

Authors: Yang B, Yang F, Wang S, Wang Q, Liu Z, Feng W, Sun F, Xia P

Abstract
The objective of this study was to analyse the distribution and antimicrobial resistance of bacterial uropathogens isolated from outpatients at Henan Provincial People's Hospital. A total of 1419 samples from 823 newly diagnosed and 596 recurrent UTI outpatients culture positive. Escherichia coli was the most common uropathogen. Compared with the recurrent group, the newly diagnosed group had a higher isolation rate of E. coli and Enterobacter cloacae but a lower isolation rate of Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. Except for P. aeruginosa, the resistance of Gram-negative bacteria to most antibiotics was less than 30%. All Enterococcus and Staphylococcus spp. were sensitive to linezolid, vancomycin and teicoplanin. Both Gram-negative and -positive bacteria exhibited high susceptibility to fosfomycin. Uropathogens isolated from recurrent outpatients had higher resistance rates than did those isolated from newly diagnosed outpatients. Our study indicated that fosfomycin might be an excellent treatment option for outpatients with UTIs.

PMID: 29304717 [PubMed - as supplied by publisher]

http://ift.tt/2m9u6Tt

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

The River of Aural Serenity: selected papers from the 2017 Annual Conference of the National Hearing Conservation Association.

Int J Audiol. 2018 Jan 05;:1-2

Authors: Tufts JB, Giguère C

PMID: 29304562 [PubMed - as supplied by publisher]

http://ift.tt/2m6vwxc

Hearing impairment and hearing aid usage in Singapore.

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

PMID: 29304553 [PubMed - as supplied by publisher]

http://ift.tt/2m9mArQ

Evaluation of truncated G protein delivered by live attenuated Salmonella as a vaccine against respiratory syncytial virus.

Evaluation of truncated G protein delivered by live attenuated Salmonella as a vaccine against respiratory syncytial virus.

Microb Pathog. 2018 Jan 03;:

Authors: Tian P, Xu D, Huang Z, Meng F, Fu J, Wei H, Chen T

Abstract
Human respiratory syncytial virus (RSV) can cause severe acute lower respiratory tract disease leading to numerous hospitalizations and deaths in the infant and elderly populations worldwide, while no vaccine or effective drug is available for RSV infections. In the present study, truncated G protein was successfully expressed both in prokaryotic and eukaryotic system, and high levels of serum IgG in response to truncated G protein were observed both in GD-protein group (intramuscularly with purified GD protein) and GD-VNP20009 group (challenged via the oral route with 1 × 109 CFU of pLIVE-RSV-GD-VNP20009 strains) since 21th day, and GD-VNP20009 significantly reduced the productions of IL-1β, IL-6, and TNF-α, histamine and pathological features caused by the RSV Long strain (P < .01). Our data indicated that Salmonella typhimurium can be used to deliver truncated G DNA vaccine and represents a promising effect to protect host against RSV.

PMID: 29306006 [PubMed - as supplied by publisher]

http://ift.tt/2m8A3QH

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

Blood. 2018 Jan 05;:

Authors: Coutre S, Choi M, Furman RR, Eradat H, Heffner L, Jones JA, Chyla B, Zhou L, Agarwal S, Waskiewicz T, Verdugo M, Humerickhouse RA, Potluri J, Wierda WG, Davids MS

Abstract
B-cell receptor pathway inhibitors (BCRi) have transformed treatment for chronic lymphocytic leukemia (CLL); however, efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRi is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi prior to enrollment. Venetoclax was initiated at 20mg daily followed by intra-patient ramp up to 400mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib, with ORR of 67% (24/36); two patients achieved complete remission and one had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached and estimated 12-month PFS was 79%. The most common AEs (all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy.
TRIAL REGISTRATION: clinicaltrials.gov #NCT02141282.

PMID: 29305552 [PubMed - as supplied by publisher]

http://ift.tt/2qEtRF0

A multi-center study on the risk factors of infection caused by multi-drug resistant Acinetobacter baumannii.

A multi-center study on the risk factors of infection caused by multi-drug resistant Acinetobacter baumannii.

BMC Infect Dis. 2018 Jan 05;18(1):11

Authors: Huang H, Chen B, Liu G, Ran J, Lian X, Huang X, Wang N, Huang Z

Abstract
BACKGROUND: Acinetobacter baumannii (AB) is critical for healthcare-associated infections (HAI) with significant regional differences in the resistance rate, but its risk factors and infection trends has not been well studied. We aimed to explore the risk factors, epidemiological characteristics and resistance of multidrug-resistant Acinetobacter baumannii (MDR-AB) in intensive care unit inpatients.
METHODS: Data of patients with MDR-AB (195 cases), and with antibiotic-sensitive AB infection (294 cases, control) during January to December, 2015 in three medical centers in Xiamen, China were conducted and analyzed in the present retrospective study.
RESULTS: Lower respiratory tract infection with AB accounted for 68.71%. MDR-AB was detected in 39.88% of all cases. Univariate analysis suggested that mechanical ventilation, indwelling catheter, cancer patients, length of hospitalization in intensive care unit (ICU) ≥15 d, Acute Physiology and Chronic Health Evaluation (APACHE) II score, combined using antibiotic before isolation of AB and use of third-lines cephalosporins were associated with the development of MDR-AB healthcare-associated infections. Dose-response relationship analysis suggested that the age and the days of mechanical ventilation were associated with increased infection with MDR-AB. Logistic regression analysis suggested that, mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter, were associated with MDR-AB infection, with odds ratios (OR) and 95% confidence intervals (CI) of 3.93 (1.52-10.14), 4.11 (1.58-10.73), and 4.15 (1.32-12.99), respectively.
CONCLUSIONS: MDR-AB infection was associated with mechanical ventilation, combined using antibiotic before isolation of AB, and indwelling catheter. Furthermore, the age and the days of mechanical ventilation were associated with increased infection with MDR-AB.

PMID: 29304746 [PubMed - in process]

http://ift.tt/2CBN8Z4

Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI.

Transauricular vagus nerve stimulation at auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) can induce auditory and limbic cortices activation measured by fMRI.

Hear Res. 2017 Dec 24;:

Authors: Peng L, Mu K, Liu A, Zhou L, Gao Y, Shenoy IT, Mei Z, Chen Q

Abstract
The purpose of this study was to explore the central mechanism of transauricular vagus nerve stimulation (taVNS) to human by fMRI and to find a suitable taVNS site for potential tinnitus treatment. 24 healthy subjects aged between 28 and 38 years were enrolled in the experiment. 8 subjects were stimulated in the auricular acupoints Kindey (CO10), Yidan (CO11), Liver (CO12) and Shenmen (TF4) in the left ear, 8 subjects were stimulated at the anterior wall of the auditory canal and left lower limb as an anterior stimulation group; 8 persons who were arranged in a sham group received taVNS at the left ear lobe and tail of the helix. Functional magnetic resonance imaging (fMRI) data from the cortices was collected and an Alphasim analysis was performed. We found that taVNS at auricular acupoints CO10-12, TF4 can instantly and effectively generate blood oxygenation level dependent (BOLD) signal changes in the prefrontal, auditory and limbic cortices of healthy subjects by fMRI. When comparing the acupoints group and the sham group in the left brain, the signals from the prefrontal cortex, the auditory ascending pathway including superior temporal gyrus, middle temporal gyrus, thalamus and limbic system regions such as putamen, caudate, posterior cingulate cortex, amygdala and parahippocampal gyrus were increased under our stimulation. The difference of the BOLD signal in the left brain between acupoints group and anterior group was in the superior temporal gyrus. We could also find signal differences in several regions of right brain among the groups. In conclusion, taVNS at acupoints CO10-12, TF4 could activate the prefrontal, auditory and limbic cortices of healthy brain and this scheme could be a promising tool for tinnitus treatment.

PMID: 29305037 [PubMed - as supplied by publisher]

http://ift.tt/2ABpHxh

Persistent postural-perceptual dizziness: a useful new syndrome.

Persistent postural-perceptual dizziness: a useful new syndrome.

Pract Neurol. 2018 Jan 04;:

Authors: Seemungal BM, Passamonti L

PMID: 29305493 [PubMed - as supplied by publisher]

http://ift.tt/2EfFuUM

Soluble protein fraction of human seminal plasma

Publication date: 1 March 2018
Source:Journal of Proteomics, Volume 174
Author(s): Laura Bianchi, Chiara Carnemolla, Viola Viviani, Claudia Landi, Valentina Pavone, Alice Luddi, Paola Piomboni, Luca Bini

Graphical abstract

http://ift.tt/2AB6HyO

Transcriptional retargeting of herpes simplex virus for cell-specific replication to control cancer.

Transcriptional retargeting of herpes simplex virus for cell-specific replication to control cancer.

J Cancer Res Clin Oncol. 2018 Jan 05;:

Authors: Lou W, Ji F, Fu J, Han Z, Di W, Zhang N

Abstract
INTRODUCTION: Oncolytic virotherapy has emerged as a novel frontier in the treatment of cancer. Among the viruses that entered clinical trials are the oncolytic herpes simplex virus-1 (HSV-1). Current oncolytic HSV-1 approved for clinical practice, and those in clinical trials are attenuated viruses, often deleted in the neurovirulence gene γ134.5, and in additional genes, which may result in a much more attenuated virus with reduced replication efficiency. Therefore, the transcriptional retargeting strategy by modifying the regulator elements flanking essential viral genes to achieve tumor-specific replication while maintaining as much of the viral genome has been representing alternative promising oncolytic virotherapy modality.
MATERIALS AND METHODS: In this communication, we aimed to review extensive studies on transcriptional retargeting strategy with HSV-1 genome engineered on immediate-early ICP4 gene, late γ134.5 gene or early ICP6 gene as well as multiple-regulated oncolytic HSV1 through combining transcriptional retargeting and translational control. Design modality based on differential cellular background, advantage, and potential clinic limitation of the innovative oncolytic HSV-1 was described, and prospective and challenge of transcriptional retargeting strategy were collectively summarized.
CONCLUSION: Transcriptional retargeting strategy holds great promise in retaining tumor specificity as well as full replication capacity of oncolytic virus in the target cell as urgently required by clinical trials. Future efforts should be aimed toward the development of multiple-component targeted oncolytic virus such as combing the transcriptional retargeting strategy and genetically attenuated modulation or post-transcriptional control that will be the most effective at generating truly tumor selective vectors.

PMID: 29305707 [PubMed - as supplied by publisher]

http://ift.tt/2D57smD

Patient Reported Outcomes: Recent Successes and Future Opportunities.

Patient Reported Outcomes: Recent Successes and Future Opportunities.

Gynecol Oncol. 2018 Jan;148(1):1-2

Authors: Melamed A, Wright AA

PMID: 29304953 [PubMed - in process]

http://ift.tt/2CDDyoI

GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

Respir Res. 2018 Jan 05;19(1):3

Authors: Halstead ES, Umstead TM, Davies ML, Kawasawa YI, Silveyra P, Howyrlak J, Yang L, Guo W, Hu S, Hewage EK, Chroneos ZC

Abstract
BACKGROUND: Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established.
METHODS: Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi.
RESULTS: Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ).
CONCLUSIONS: Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

PMID: 29304863 [PubMed - in process]

http://ift.tt/2CAo3Og

Patient-specific estimation of detailed cochlear shape from clinical CT images.

Patient-specific estimation of detailed cochlear shape from clinical CT images.

Int J Comput Assist Radiol Surg. 2018 Jan 06;:

Authors: Kjer HM, Fagertun J, Wimmer W, Gerber N, Vera S, Barazzetti L, Mangado N, Ceresa M, Piella G, Stark T, Stauber M, Reyes M, Weber S, Caversaccio M, González Ballester MÁ, Paulsen RR

Abstract
PURPOSE: A personalized estimation of the cochlear shape can be used to create computational anatomical models to aid cochlear implant (CI) surgery and CI audio processor programming ultimately resulting in improved hearing restoration. The purpose of this work is to develop and test a method for estimation of the detailed patient-specific cochlear shape from CT images.
METHODS: From a collection of temporal bone [Formula: see text]CT images, we build a cochlear statistical deformation model (SDM), which is a description of how a human cochlea deforms to represent the observed anatomical variability. The model is used for regularization of a non-rigid image registration procedure between a patient CT scan and a [Formula: see text]CT image, allowing us to estimate the detailed patient-specific cochlear shape.
RESULTS: We test the accuracy and precision of the predicted cochlear shape using both [Formula: see text]CT and CT images. The evaluation is based on classic generic metrics, where we achieve competitive accuracy with the state-of-the-art methods for the task. Additionally, we expand the evaluation with a few anatomically specific scores.
CONCLUSIONS: The paper presents the process of building and using the SDM of the cochlea. Compared to current best practice, we demonstrate competitive performance and some useful properties of our method.

PMID: 29305790 [PubMed - as supplied by publisher]

http://ift.tt/2qDBw6p

Central Lymph Node Metastasis in Papillary Thyroid Carcinoma.

Central Lymph Node Metastasis in Papillary Thyroid Carcinoma.

World J Surg. 2018 Jan 05;:

Authors: Shaha AR

PMID: 29305712 [PubMed - as supplied by publisher]

http://ift.tt/2EiwttM

Mal de Debarquement Syndrome: a survey on subtypes, misdiagnoses, onset and associated psychological features.

Mal de Debarquement Syndrome: a survey on subtypes, misdiagnoses, onset and associated psychological features.

J Neurol. 2018 Jan 05;:

Authors: Mucci V, Canceri JM, Brown R, Dai M, Yakushin S, Watson S, Van Ombergen A, Topsakal V, Van de Heyning PH, Wuyts FL, Browne CJ

Abstract
INTRODUCTION: Mal de Debarquement Syndrome (MdDS) is a neurological condition typically characterized by a sensation of motion, that persists longer than a month following exposure to passive motion (e.g., cruise, flight, etc.). The most common form of MdDS is motion triggered (MT). However, recently it has been acknowledged that some patients develop typical MdDS symptoms without an apparent motion trigger. These cases are identified here as spontaneous or other onset (SO) MdDS. This study aimed to address similarities and differences between the MdDS subtypes. Diagnostic procedures were compared and extensive diagnostic guidelines were proposed. Second, potential triggers and associated psychological components of MdDS were revealed.
METHODS: This was a retrospective online survey study for MT and SO MdDS patients. Participants were required to respond to a set of comprehensive questions regarding epidemiological details, as well as the diagnostic procedures and onset triggers.
RESULTS: There were 370 patients who participated in the surveys. It is indicated that MdDS is often misdiagnosed; more so for the SO group. In addition to the apparent self-motion, both groups reported associated levels of stress, anxiety and depression.
DISCUSSION: It appears at present that both MdDS subtypes are still poorly recognised. This was the first attempt to evaluate the diagnostic differences between MdDS subtypes and to propose a set of comprehensive diagnostic guidelines for both MdDS subtypes. In addition, the current research addressed that associated symptoms such as stress, anxiety and depression should also be considered when treating patients. We hope this study will help the medical community to broaden their awareness and diagnostic knowledge of this condition.

PMID: 29305644 [PubMed - as supplied by publisher]

http://ift.tt/2qw8IfU

Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma.

Anti-Trop2 blockade enhances the therapeutic efficacy of ErbB3 inhibition in head and neck squamous cell carcinoma.

Cell Death Dis. 2018 Jan 05;9(1):5

Authors: Redlich N, Robinson AM, Nickel KP, Stein AP, Wheeler DL, Adkins DR, Uppaluri R, Kimple RJ, Van Tine BA, Michel LS

Abstract
ErbB3 has been widely implicated in treatment resistance, but its role as a primary treatment target is less clear. Canonically ErbB3 requires EGFR or ErbB2 for activation, whereas these two established treatment targets are thought to signal independently of ErbB3. In this study, we show that ErbB3 is essential for tumor growth of treatment-naive HNSCC patient-derived xenografts. This ErbB3 dependency occurs via ErbB3-mediated control of EGFR activation and HIF1α stabilization, which require ErbB3 and its ligand neuregulin-1. Here, we show that ErbB3 antibody treatment selects for a population of ErbB3-persister cells that express high levels of the transmembrane protein Trop2 that we previously identified as an inhibitor of ErbB3. Co-treatment with anti-ErbB3 and anti-Trop2 antibodies is synergistic and produces a greater anti-tumor response than either antibody alone. Collectively, these data both compel a revision of ErbB-family signaling and delineate a strategy for its effective inhibition in HNSCC.

PMID: 29305574 [PubMed - in process]

http://ift.tt/2qBFbS4

Hearing impairment and hearing aid usage in Singapore.

Hearing impairment and hearing aid usage in Singapore.

Int J Audiol. 2018 Jan 05;:1-11

Authors: Ho EC, Zhang H, Ong WMW, Li K, Bei YTE, Medapati SVR, Seneviratna A

PMID: 29304553 [PubMed - as supplied by publisher]

http://ift.tt/2m9mArQ

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

Hum Genet. 2018 Jan 05;:

Authors: Tranebjærg L, Strenzke N, Lindholm S, Rendtorff ND, Poulsen H, Khandelia H, Kopec W, Lyngbye TJB, Hamel C, Delettre C, Bocquet B, Bille M, Owen HH, Bek T, Jensen H, Østergaard K, Möller C, Luxon L, Carr L, Wilson L, Rajput K, Sirimanna T, Harrop-Griffiths K, Rahman S, Vona B, Doll J, Haaf T, Bartsch O, Rosewich H, Moser T, Bitner-Glindzicz M

Abstract
Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patients suggests that cochlear implantation may be effective in CAPOS patients.

PMID: 29305691 [PubMed - as supplied by publisher]

http://ift.tt/2ma3uli

Comment on "Sensitivity of the Speech Intelligibility Index to the Assumed Dynamic Range," by Jin et al. (2017).

Comment on "Sensitivity of the Speech Intelligibility Index to the Assumed Dynamic Range," by Jin et al. (2017).

J Speech Lang Hear Res. 2018 Jan 05;:1-3

Authors: Smits C, Theo Goverts S, Versfeld NJ

Abstract
Purpose: This letter to the editor is in response to a research note by Jin, Kates, and Arehart (2017), "Sensitivity of the Speech Intelligibility Index to the Assumed Dynamic Range," published in June 2017 by the Journal of Speech, Language, and Hearing Research.
Conclusion: The authors argue that the approach and line of reasoning in the Jin et al. (2017) research note suggest new findings but do not lead to essentially new insights.

PMID: 29305602 [PubMed - as supplied by publisher]

http://ift.tt/2m8AtGF

Food and drug administration approval process for dermatology drugs in the United States.

Food and drug administration approval process for dermatology drugs in the United States.

J Dermatolog Treat. 2018 Jan 05;:1-16

Authors: Boozalis E, Semenov YR, Kwatra SG

Abstract
The process by which dermatology drugs are approved in the United States is not well understood by many clinicians. In general, new dermatology drugs must undergo pre-clinical studies on non-human subjects and three phases of clinical trials in humans before undergoing review by the Food and Drug Administration (FDA). This review process involves an interdisciplinary team of scientists that determines if the drug should be brought to market based on its efficacy, risk-to-benefit ratio, and ability to be labeled. The team that specifically reviews dermatology drugs within the Center for Drug Evaluation and Research (CDER) at the FDA is the Division of Dermatologic and Dental Drug Products. The purpose of this review is to elucidate the steps involved in the FDA's approval of new dermatology drugs. To help illustrate this process, we use examples from the recent approval of dupilumab (REGN668; Regeneron Pharmaceuticals).

PMID: 29304565 [PubMed - as supplied by publisher]

http://ift.tt/2m84uGO

Intraventricular hemorrhage due to subarachnoid hemorrhage: Does the severity matter?

Intraventricular hemorrhage due to subarachnoid hemorrhage: Does the severity matter?

World Neurosurg. 2018 Jan 03;:

Authors: Oppong MD, Gembruch O, Herten A, Frantsev R, Chihi M, Dammann P, El Hindy N, Forsting M, Sure U, Jabbarli R

Abstract
OBJECT: Aneurysm rupture might be accompanied by intraventricular hemorrhage (IVH) that is associated with poor outcome of subarachnoid hemorrhage (SAH). The aim of this study was to analyze risk factors and clinical impact of IVH severity.
MATERIAL AND METHODS: 995 consecutive SAH patients treated at our institution between January 2003 and June 2016 were eligible for this study. Clinical and radiological findings were correlated with the presence and severity of IVH assessed with the original Graeb score.
RESULTS: Four hundred and eighty seven SAH patients (48.9%) presented with IVH (mean IVH severity: 5.48 points [± 3.5]). IVH severity correlated with poorer initial clinical condition (WFNS grade > 3, p < 0.001), acute hydrocephalus (p = 0.001) and poor outcome at 6 months (modified Rankin scale > 2, p < 0.001). Location of the ruptured aneurysm in anterior cerebral artery independently predicted the occurrence (p = 0.007) and severity of IVH (p < 0.001). In turn, aneurysm size impacted only the severity of IVH (p = 0.001), but not its occurrence (p = 0.153). Early complications of SAH occurring within 72 hours after the bleeding event: cerebral infarction (p = 0.043), early mortality (p = 0.001) and primary craniectomy (p = 0.043) were independently associated with the severity of IVH.
CONCLUSION: Severity of aneurysmal IVH is a strong contributor to initial severity and early complications of SAH. Patients with larger aneurysms, especially located in the anterior cerebral artery are at particular risk of severe IVH in case of aneurysm rupture.

PMID: 29305915 [PubMed - as supplied by publisher]

http://ift.tt/2mccTsX

The Comparison of Monitoring of Cerebral Blood Flow by c-FLOW and Transcranial Doppler in Carotid Endarterectomy.

The Comparison of Monitoring of Cerebral Blood Flow by c-FLOW and Transcranial Doppler in Carotid Endarterectomy.

World Neurosurg. 2018 Jan 03;:

Authors: Wang X, Yang B, Ma Y, Gao P, Wang Y, Chen Y, Jiao L, Ling F, Zhao G

Abstract
OBJECTIVE: To prospectively compare the use of the c-FLOW (cerebral blood flow monitor) and transcranial Doppler (TCD) as two techniques for assessing brain perfusion during carotid endarterectomy (CEA).
METHODS: This was a prospective, single center, observational study. All patients were monitored using c-FLOW and TCD during the operation. Changes from baseline values of cerebral blood flow index (CFI) and blood flow velocity of middle cerebral artery (V-MCA) were recorded following carotid artery clamping and unclamping. The correlation analysis was conducted for c-FLOW and TCD monitoring values.
RESULTS: 73 consecutive patients were enrolled from August 2015 to March 2016. No dearth or stroke occurred during the postoperative hospitalization. Fresh infarction was identified on magnetic resonance imaging (MRI) in 17 patients. 10 patients showed significant decrease of V-MCA following carotid clamping, a shunt was placed for only 4. The Pearson correlation index between CFI and V-MCA was 0.647 (P<0.001). A cut-off of 21% decrease of CFI was proposed as optimal to detect intraoperative hypoperfusion. 7 patients were diagnosed as hyperperfusion by TCD monitoring. The Pearson correlation index between CFI and V-MCA was 0.286 (P=0.014). A cut-off of 15% increase of CFI following carotid unclamping was suggested as optimal to detect the postoperative hyperperfusion.
CONCLUSIONS: c-FLOW could continuously and non-invasively monitor the cerebral blood flow (CBF) in real-time during CEA, and effectively detect the intraoperative hypoperfusion and postoperative hyperperfusion as defined by TCD, so it may serve as a favorable modality in future intraoperative monitoring.

PMID: 29305914 [PubMed - as supplied by publisher]

http://ift.tt/2qyPs1r

Endoscope holders in Cranial Neurosurgery: Part 2 - An international survey.

Endoscope holders in Cranial Neurosurgery: Part 2 - An international survey.

World Neurosurg. 2018 Jan 02;:

Authors: Paraskevopoulos D, Constantini S, Bal J, Roth J

Abstract
BACKGROUND: Following a prior systematic review of currently available endoscope holders (EH), we aspired to detect trends, task-specific preferences and pitfalls of EH in various cranial neuroendoscopic procedures.
METHODS: A questionnaire was disseminated to members of the International Federation of Neuroendoscopy (IFNE). The questionnaire evaluated indications and pitfalls of EH in different applications, in particular, differentiating between intraventricular and skull base endoscopy, as well as sub-categories of these two main fields. Furthermore, interest or involvement in research projects on EH was investigated.
RESULTS: Fifty two surgeons responded, with a broad geographic distribution. Most (54%) do not routinely use EH. Others utilize holders mainly for intraventricular rather than skull base procedures. Most surgeons (96%) regularly work with a co-surgeon. Reported weaknesses of EH included crude movements, downward drift, loss of depth perception, lack of flexibility, iatrogenic injury, cost and bulky construct. There is still a lack of consensus on surgical indications. Tumor resections in intraventricular and skull base regions (not small sellar tumors) seem to stand out as good, widely accepted indications.
CONCLUSION: Although EH have a role in cranial neuroendoscopy, their use seems limited and their technical features are regarded as suboptimal by most neuroendoscopists. Weaknesses and implications were detected in all application categories (skull base and intraventricular), but may vary slightly. Potentially, separate systems with distinct features may be required for skull base versus intraventricular surgery. There is a need for further evolution of EH, which could lead to a future paradigm shift in their use.

PMID: 29305118 [PubMed - as supplied by publisher]

http://ift.tt/2qBeayb

Conus medullaris arteriovenous malformation presenting with acute dysphagia and intractable hiccups.

Conus medullaris arteriovenous malformation presenting with acute dysphagia and intractable hiccups.

World Neurosurg. 2018 Jan 02;:

Authors: Jung J, Kailaya-Vasan A, Kellett C, Almahariq F, Grahovac G

PMID: 29305117 [PubMed - as supplied by publisher]

http://ift.tt/2m6A3Rq

Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

Paragangliomas arise through an autonomous vasculo-angio-neurogenic program inhibited by imatinib.

Acta Neuropathol. 2018 Jan 05;:

Authors: Verginelli F, Perconti S, Vespa S, Schiavi F, Prasat SC, Lanuti P, Cama A, Tramontana L, Esposito DL, Guarnieri S, Sheu A, Pantalone MR, Florio R, Morgano A, Rossi C, Bologna G, Marchisio M, D'Argenio A, Taschin E, Visone R, Opocher G, Veronese A, Paties CT, Rajasekhar VK, Söderberg-Nauclér C, Sanna M, Lotti LV, Mariani-Costantini R

Abstract
Tumours can be viewed as aberrant tissues or organs sustained by tumorigenic stem-like cells that engage into dysregulated histo/organogenetic processes. Paragangliomas, prototypical organoid tumours constituted by dysmorphic variants of the vascular and neural tissues found in normal paraganglia, provide a model to test this hypothesis. To understand the origin of paragangliomas, we built a biobank comprising 77 cases, 18 primary cultures, 4 derived cell lines, 80 patient-derived xenografts and 11 cell-derived xenografts. We comparatively investigated these unique complementary materials using morphofunctional, ultrastructural and flow cytometric assays accompanied by microRNA studies. We found that paragangliomas contain stem-like cells with hybrid mesenchymal/vasculoneural phenotype, stabilized and expanded in the derived cultures. The viability and growth of such cultures depended on the downregulation of the miR-200 and miR-34 families, which allowed high PDGFRA and ZEB1 protein expression levels. Both tumour tissue- and cell culture-derived xenografts recapitulated the vasculoneural paraganglioma structure and arose from mesenchymal-like cells through a fixed developmental sequence. First, vasculoangiogenesis organized the microenvironment, building a perivascular niche which in turn supported neurogenesis. Neuroepithelial differentiation was associated with severe mitochondrial dysfunction, not present in cultured paraganglioma cells, but acquired in vivo during xenograft formation. Vasculogenesis was the Achilles' heel of xenograft development. In fact, imatinib, that targets endothelial-mural signalling, blocked paraganglioma xenograft formation (11 xenografts from 12 cell transplants in the control group versus 2 out of 10 in the treated group, P = 0.0015). Overall our key results were unaffected by the SDHx gene carrier status of the patient, characterized for 70 out of 77 cases. In conclusion, we explain the biphasic vasculoneural structure of paragangliomas and identify an early and pharmacologically actionable phase of paraganglioma organization.

PMID: 29305721 [PubMed - as supplied by publisher]

http://ift.tt/2qBU32H

Endoscope holders in Cranial Neurosurgery: Part 2 - An international survey.

Endoscope holders in Cranial Neurosurgery: Part 2 - An international survey.

World Neurosurg. 2018 Jan 02;:

Authors: Paraskevopoulos D, Constantini S, Bal J, Roth J

PMID: 29305118 [PubMed - as supplied by publisher]

http://ift.tt/2qBeayb

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center.

Cranial Tumor Surgical Outcomes at a High-Volume Academic Referral Center.

Mayo Clin Proc. 2018 Jan;93(1):16-24

Authors: Brown DA, Himes BT, Major BT, Mundell BF, Kumar R, Kall B, Meyer FB, Link MJ, Pollock BE, Atkinson JD, Van Gompel JJ, Marsh WR, Lanzino G, Bydon M, Parney IF

Abstract
OBJECTIVE: To determine adverse event rates for adult cranial neuro-oncologic surgeries performed at a high-volume quaternary academic center and assess the impact of resident participation on perioperative complication rates.
PATIENTS AND METHODS: All adult patients undergoing neurosurgical intervention for an intracranial neoplastic lesion between January 1, 2009, and December 31, 2013, were included. Cases were categorized as biopsy, extra-axial/skull base, intra-axial, or transsphenoidal. Complications were categorized as neurologic, medical, wound, mortality, or none and compared for patients managed by a chief resident vs a consultant neurosurgeon.
RESULTS: A total of 6277 neurosurgical procedures for intracranial neoplasms were performed. After excluding radiosurgical procedures and pediatric patients, 4151 adult patients who underwent 4423 procedures were available for analysis. Complications were infrequent, with overall rates of 9.8% (435 of 4423 procedures), 1.7% (73 of 4423), and 1.4% (63 of 4423) for neurologic, medical, and wound complications, respectively. The rate of perioperative mortality was 0.3% (14 of 4423 procedures). Case performance and management by a chief resident did not negatively impact outcome.
CONCLUSION: In our large-volume brain tumor practice, rates of complications were low, and management of cases by chief residents in a semiautonomous manner did not negatively impact surgical outcomes.

PMID: 29304919 [PubMed - in process]

http://ift.tt/2F70QEO

The Benefit of Ultrasound in Deciding Between Tube Thoracostomy and Observative Management in Hemothorax Resulting from Blunt Chest Trauma.

The Benefit of Ultrasound in Deciding Between Tube Thoracostomy and Observative Management in Hemothorax Resulting from Blunt Chest Trauma.

World J Surg. 2018 Jan 05;:

Authors: Chung MH, Hsiao CY, Nian NS, Chen YC, Wang CY, Wen YS, Shih HC, Yen DH

Abstract
BACKGROUND: Hemothorax is most commonly resulted from a closed chest trauma, while a tube thoracostomy (TT) is usually the first procedure attempted to treat it. However, TT may lead to unexpected results and complications in some cases. The advantage of thoracic ultrasound (TUS) over a physical examination combined with chest radiograph (CXR) for diagnosing hemothorax1 has been proposed previously. However, its benefits in terms of avoiding non-therapeutic TT have not yet been confirmed. Therefore, this study is aimed to evaluate the severity of hemothorax in blunt chest trauma patients by using TUS in order to avoid non-therapeutic TT in stable cases.
METHODS: The data from 46,036 consecutive patient visits to our trauma center over a four-year period were collected, and those with blunt chest trauma were identified. Patients who met any of the following criteria were excluded: transferred from another facility, with an abbreviated injury scale (AIS) score ≥ 2 for any region except the chest region, with a documented finding of tension pneumothorax or pneumothorax >10%, younger than 16 years old and with indications requiring any non-thoracic major operation. The decision to perform TT for those patients in the non-TUS group was made on the basis of CXR findings and clinical symptoms. The continuous data were analyzed by using the two-tailed Student's t test, and the discrete data were analyzed by Chi-square test.
RESULTS: A total of 84 patients met the criteria for inclusion in the final analysis, with TT having been performed on 42 (50%) of those patients. The mean volume of the drainage amount was 860 ml after TT. The TT drainage was less than 500 ml in 12 patients in the non-TUS group (40%), while none was less than 500 ml in the TUS group (p = 0.036, Fisher's exact test). In terms of the positive rate of subsequent effective TT, the sensitivity of TUS was 90% and the specificity was 100%. There were 3 patients with delayed hemothorax: 2 of the 58 (3.6%) in the non-TUS group and 1 of 26 (4.5%) in the TUS group (p > 0.05, Fisher's exact test). The hospital length of stay in the non-TUS group with non-therapeutic TT was significantly longer than in the TUS group without TT (8.2 vs. 5.4 days, p = 0.018). There were no other major complications or deaths in either group during the 90-day follow-up period.
CONCLUSION: In the case of blunt trauma, TUS can rapidly and accurately evaluate hemothorax to avoid TT in patients who may not benefit much from it. As a result, the rate of non-therapeutic TT can be decreased, and the influence on shortening hospital length of stay may be further evaluated with prospective controlled study.

PMID: 29305713 [PubMed - as supplied by publisher]

http://ift.tt/2ma0cOY

Αρχειοθήκη ιστολογίου

! # Ola via Alexandros G.Sfakianakis on Inoreader

Η λίστα ιστολογίων μου

Κυριακή 7 Ιανουαρίου 2018

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