Synthesis of chondroitin sulfate CC and DD tetrasaccharides and interactions with 2H6 and LY111

Publication date: Available online 3 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Kenya Matsushita, Tomomi Nakata, Naoko Takeda-Okuda, Satomi Nadanaka, Hiroshi Kitagawa, Jun-ichi Tamura
We synthesized the biotinylated chondroitin sulfate tetrasaccharides CS-CC [-3)βGalNAc6S(1–4)βGlcA(1-]2 and CS-DD [-3)βGalNAc6S(1–4)βGlcA2S(1-]2 which possess sulfate groups at O-6 of GalNAc and an additional sulfate group at O-2 of GlcA, respectively. We also analyzed interactions among CS-CC and CS-DD and the antibodies 2H6 and LY111, both of which are known to bind with CS-A, while CS-DD was shown for the first time to bind with both antibodies.

Graphical abstract

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Design, synthesis and evaluation of 4′-OH-flurbiprofen-chalcone hybrids as potential multifunctional agents for Alzheimer’s disease treatment

Publication date: Available online 2 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Zhongcheng Cao, Jie Yang, Rui Xu, Qin Song, Xiaoyu Zhang, Hongyan Liu, Xiaoming Qiang, Yan Li, Zhenghuai Tan, Yong Deng
A series of 4′-OH-flurbiprofen-chalcone hybrids were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease. The biological screening results indicated that most of these hybrids exhibited good multifunctional activities. Among them, compounds 7k and 7m demonstrated the best inhibitory effects on self-induced Aβ1-42 aggregation (60.0% and 78.2%, respectively) and Cu²⁺-induced Aβ1-42 aggregation (52.4% and 95.0%, respectively). Moreover, these two representative compounds also exhibited good antioxidant activities, MAO inhibitions, biometal chelating abilities and anti-neuroinflammatory activities in vitro. Furthermore, compound 7m displayed appropriate blood-brain barrier permeability. These multifunctional properties highlight compound 7k and 7m as promising candidates for further development of multi-functional drugs against AD.

Graphical abstract

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Synthesis and biological evaluation of aminothiazoles against Histoplasma capsulatum and Cryptococcus neoformans

Publication date: Available online 2 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Keisuke Ishita, Stavros Stefanopoulos, Ahmed Khalil, Xiaolin Cheng, Werner Tjarks, Chad Rappleye
The design and synthesis of a library of forty novel 2-aminoazole analogues as well as their evaluation as antifungal compounds against Histoplasma capsulatum and Cryptococcus neoformans is described. These structures were derived from N-[5-(1-naphthalenylmethyl)-2-thiazolyl]cyclohexanecarboxamide (41F5), a fungistatic agent previously identified through phenotypic screening (Antimicrob Agents Chemother. 2013; 57:4349). Modifications to improve potency and water-solubility of 41F5 focused primarily on the 5-naphthalenyl group, the thiazole core, and the methylene linker between these two structural elements. In general, compounds with lipophilic [5+6] bicyclics ring systems, such as the 7-benzothiophenyl- and 4-indanyl groups, at the 5-position were 2-3 times more active against both fungal species as compard to 41F5. Also, introduction of a carbonyl group at the methylene linker of 41F5 resulted in a 2-3 fold increase in potency. These highly active compounds also showed generally low toxicities against murine P388D1 macrophages resulting in selectivity indices ranging from 63 to >200. Compounds that were highly active against fluconazole-sensitive C. neoformans strains had almost identical activity against fluconazole-resistant variants of this fungus indicating that 14α-demethylase is not their molecular target. Highly active compounds also retained activity against H. capsulatum phagocytosed into P388D1 macrophages.

Graphical abstract

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Development of selective inhibitors for the treatment of rheumatoid arthritis: (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile as a JAK1-selective inhibitor

Publication date: Available online 3 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Chieyeon Chough, Misuk Joung, Sunmin Lee, Jaemin Lee, Jong Hoon Kim, B. Moon Kim
A series of 3(R)-aminopyrrolidine derivatives were designed and synthesized for JAK1-selective inhibitors through the modification of tofacitinib's core structure, (3R,4R)-3-amino-4-methylpiperidine. From the new core structures, we selected (R)-N-methyl-N-(pyrrolidin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine as a scaffold for further SAR studies. From biochemical enzyme assays and liver microsomal stability tests, (R)-3-(3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)pyrrolidin-1-yl)-3-oxopropanenitrile (6) was chosen for further in vivo test through oral administration. Compound 6 showed improved selectivity for JAK1 compared to that of tofacitinib (IC50 11, 2.4x10², 2.8x10³, and 1.1x10² nM for JAK1, JAK2, JAK3, and TYK2, respectively). In CIA and AIA model tests, compound 6 exhibited similar efficacy to tofacitinib citrate.

Graphical abstract

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Hepatic NAD+ levels and NAMPT abundance are unaffected during prolonged high-fat diet consumption in C57BL/6JBomTac mice

Publication date: Available online 2 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Morten Dall, Melanie Penke, Karolina Sulek, Madlen Matz-Soja, Birgitte Holst, Antje Garten, Wieland Kiess, Jonas T. Treebak
Dietary supplementation of nicotinamide adenine dinucleotide (NAD⁺) precursors has been suggested as a treatment for non-alcoholic fatty liver disease and obesity. In the liver, NAD⁺ is primarily generated by nicotinamide phosphoribosyltransferase (NAMPT), and hepatic levels of NAMPT and NAD⁺ have been reported to be dependent on age and body composition. The aim of the present study was to identify time-course-dependent changes in hepatic NAD content and NAD⁺ salvage capacity in mice challenged with a high-fat diet (HFD). We fed 7-week-old C57BL/6JBomTac male mice either regular chow or a 60% HFD for 6, 12, 24, and 48 weeks, and we evaluated time course-dependent changes in whole body metabolism, liver steatosis, and abundance of hepatic NAD-associated metabolites and enzymes. Mice fed a 60% HFD rapidly accumulated fat and hepatic triglycerides, with associated changes in respiratory exchange ratio (RER) and a disruption of the circadian feeding pattern. The HFD did not alter hepatic NAD⁺ levels, but caused a decrease in NADP⁺ and NADPH levels. Decreased NADP⁺ content was not accompanied by alterations in NAD kinase (NADK) abundance in HFD-fed mice, but NADK levels increased with age regardless of diet. NAMPT protein abundance did not change with age or diet. HFD consumption caused a severe decrease in protein lysine malonylation after six weeks, which persisted throughout the experiment. This decrease was not associated with changes in SIRT5 abundance. In conclusion, hepatic NAD⁺ salvage capacity is resistant to long-term HFD feeding, and hepatic lipid accumulation does not compromise the hepatic NAD⁺ pool in HFD-challenged C57BL/6JBomTac male mice.



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Epigenetic regulation of male fate commitment from an initially bipotential system

Publication date: Available online 2 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): S. Alexandra Garcia-Moreno, Michael P. Plebanek, Blanche Capel
A fundamental goal in biology is to understand how distinct cell types containing the same genetic information arise from a single stem cell throughout development. Sex determination is a key developmental process that requires a unidirectional commitment of an initially bipotential gonad towards either the male or female fate. This makes sex determination a unique model to study cell fate commitment and differentiation in vivo. We have focused this review on the accumulating evidence that epigenetic mechanisms contribute to the bipotential state of the fetal gonad and to the regulation of chromatin accessibility during and immediately downstream of the primary sex-determining switch that establishes the male fate.



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Partial growth hormone insensitivity and dysregulatory immune disease associated with de novo germline activating STAT3 mutations

Publication date: Available online 3 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Mariana Gutiérrez, Paula Scaglia, Ana Keselman, Lucía Martucci, Liliana Karabatas, Sabina Domené, Ayelen Martin, Patricia Pennisi, Miguel Blanco, Nora Sanguineti, Liliana Bezrodnik, Daniela Di Giovanni, María Soledad Caldirola, María Esnaola Azcoiti, María Isabel Gaillard, Lee A. Denson, Kejian Zhang, Ammar Husami, Nana-Hawa Yayah Jones, Vivian Hwa, Santiago Revale, Martín Vázquez, Héctor Jasper, Ashish Kumar, Horacio Domené
Germinal heterozygous activating STAT3 mutations represent a novel monogenic defect associated with multi-organ autoimmune disease and, in some cases, severe growth retardation. By using whole-exome sequencing, we identified two novel STAT3 mutations, p.E616del and p.C426R, in two unrelated pediatric patients with IGF-I deficiency and immune dysregulation. The functional analyses showed that both variants were gain-of-function (GOF), although they were not constitutively phosphorylated. They presented differences in their dephosphorylation kinetics and transcriptional activities under interleukin-6 stimulation. Both variants increased their transcriptional activities in response to growth hormone (GH) treatment. Nonetheless, STAT5b transcriptional activity was diminished in the presence of STAT3 GOF variants, suggesting a disruptive role of STAT3 GOF variants in the GH signaling pathway. This study highlights the broad clinical spectrum of patients presenting activating STAT3 mutations and explores the underlying molecular pathway responsible for this condition, suggesting that different mutations may drive increased activity by slightly different mechanisms.



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Prostaglandin E2 (PGE2) is a testicular peritubular cell-derived factor involved in human testicular homeostasis

Publication date: Available online 2 February 2018
Source:Molecular and Cellular Endocrinology
Author(s): Verónica Rey-Ares, Soledad Paola Rossi, Kim-Gwendolyn Dietrich, Frank-Michael Köhn, J. Ulrich Schwarzer, Harald Welter, Mónica Beatriz Frungieri, Artur Mayerhofer
In man, blockage of prostaglandin (PG)-production e.g. by non-steroidal anti-inflammatory drug (NSAIDs) may have negative testicular side effects, implying beneficial actions of PGs in the testis. We examined human testicular samples and isolated human testicular peritubular cells (HTPCs) to explore sites of PG-synthesis and targets. HTPCs express cyclooxygenase 1 (COX1) and secrete PGE2. Receptors (EP1, 2, 4) were specifically identified in peritubular cells. In HTPCs PGE2 significantly increased mRNA levels of the contractility protein calponin, but did not induce contractions. PGE2, as well as EP1 and EP4 receptor agonists, significantly increased glia cell line derived neurotrophic factor (GDNF) mRNA and/or protein levels. Importantly, the NSAID ibuprofen reduced PGE2 and this action also lowered SMA and calponin mRNA levels and levels of secreted GDNF protein. The results reveal an unknown PGE2 system in the human testis, in involving peritubular cells, which may be prone to interference by NSAIDs.



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Intramuscular granular cell tumor of the gluteal region

Abstract

Granular cell tumors are uncommon, usually benign neoplasms, mainly observed in the head and neck region, chest wall and upper extremities. These tumors account for ~0.5% of all soft-tissue tumors. Less than 2% are malignant. These are associated with poor prognosis. Clinical signs suspicious for malignancy are large size, rapid growth, invasion, recurrence and metastasis. Malignancy is confirmed by histological examination. We present the case of a 79-year-old patient with a 6-month history of a rapidly growing mass in the left gluteal region giving the clinical impression of a malignant tumor. The patient underwent surgical excision of the tumor and the pathology report revealed a granular cell tumor. In difficult cases, multidisciplinary approach is necessary for appropriate diagnosis and management.

http://ift.tt/2DZ84Ou

A rare case of massive lower gastrointestinal bleeding from a ruptured splenic artery aneurysm

Abstract

Splenic artery aneurysms (SAAs) are an extremely rare cause of asymptomatic massive lower gastrointestinal bleeding with less than a handful of patients surviving such a presentation. A 24-year-old female presented in shock after multiple episodes of massive rectal bleeding. Imaging revealed a heterogeneous mass arising from the tail of the pancreas eroding into the splenic flexure of the colon. Further episodes of bleeding led to an exploratory laparotomy. Intraoperatively, a suspected neoplastic process arising from the tail of the pancreas with contiguous involvement of the splenic flexure of the colon and the greater curvature of the stomach was noted. Distal pancreaticosplenectomy, gastric wedge resection with segmental colectomy and primary anastomosis were performed. Histology revealed a SAA with rupture into the colon. This case report shows that en-bloc resection of a ruptured SAA can be performed with success in the emergency setting.

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A rare case of spinal cord compression due to cervical spine metastases from paraganglioma of the jugular foramen—how should it be treated?

Abstract

Paragangliomas are benign neoplasms that arise from the autonomic nervous system and the associated paraganglia. Although benign, they have been shown to possess metastatic potential. Involvement of the spine is rare. Even rarer is considered the involvement of the cervical spine. We report a case of a patient with a history of an extra-adrenal non-functional paraganglioma of the jugular foramen which was initially treated with intra-arterial embolization. After a 3-year disease-free follow-up, the patient was presented with symptoms of spinal cord compression due to spinal metastases in C2 and C3 vertebrae. The patient was then treated with surgical decompression and external beam radiation. Therapeutic management with additional treatment options is now under discussion by a multidisciplinary team. Paraganglioma of the jugular foramen with spinal metastasis is an uncommon presentation where increased physician awareness and long-term follow-up are mandatory for all patients with history of paraganglioma.

http://ift.tt/2DWqzTu

Electrodiagnostic applications of somatosensory evoked high-frequency EEG oscillations: Technical considerations

Publication date: March 2018
Source:Brain Research Bulletin, Volume 137
Author(s): A.J. Simpson, M.O. Cunningham, M.R. Baker
IntroductionHigh frequency oscillations (HFOs) embedded within the somatosensory evoked potential (SEP) are not routinely recorded/measured as part of standard clinical SEPs. However, HFOs could provide important additional diagnostic/prognostic information in various patient groups in whom SEPs are tested routinely. One area is the management of patients with hypoxic ischaemic encephalopathy (HIE) in the intensive care unit (ICU). However, the sensitivity of standard clinical SEP recording techniques for detecting HFOs is unknown.MethodsSEPs were recorded using routine clinical methods in 17 healthy subjects (median nerve stimulation; 0.5 ms pulse width; 5 Hz; maximum 4000 stimuli) in an unshielded laboratory. Bipolar EEG recordings were acquired (gain 50 k; bandpass 3Hz–2 kHz; sampling rate 5 kHz; non-inverting electrode 2 cm anterior to C3/C4; inverting electrode 2 cm posterior to C3/C4). Data analysis was performed in MATLAB.ResultsSEP-HFOs were detected in 65% of controls using standard clinical recording techniques. In 3 controls without significant HFOs, experiments were repeated using a linear electrode array with higher spatial sampling frequency. SEP-HFOs were observed in all 3 subjects.ConclusionsCurrently standard clinical methods of recording SEPs are not sufficiently sensitive to permit the inclusion of SEP-HFOs in routine clinical diagnostic/prognostic assessments. Whilst an increase in the number/density of EEG electrodes should improve the sensitivity for detecting SEP-HFOs, this requires confirmation. By improving and standardising clinical SEP recording protocols to permit the acquisition/analysis of SEP-HFOs, it should be possible to gain important insights into the pathophysiology of neurological disorders and refine the management of conditions such as HIE.



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Ensemble support vector machine classification of dementia using structural MRI and mini-mental state examination

Publication date: Available online 3 February 2018
Source:Journal of Neuroscience Methods
Author(s): Lauge Sørensen, Mads Nielsen
BackgroundThe International Challenge for Automated Prediction of MCI from MRI data offered independent, standardized comparison of machine learning algorithms for multi-class classification of normal control (NC), mild cognitive impairment (MCI), converting MCI (cMCI), and Alzheimer's disease (AD) using brain imaging and general cognition.New methodWe proposed to use an ensemble of support vector machines (SVMs) that combined bagging without replacement and feature selection. SVM is the most commonly used algorithm in multivariate classification of dementia, and it was therefore valuable to evaluate the potential benefit of ensembling this type of classifier.ResultsThe ensemble SVM, using either a linear or a radial basis function (RBF) kernel, achieved multi-class classification accuracies of 55.6% and 55.0% in the challenge test set (60 NC, 60 MCI, 60 cMCI, 60 AD), resulting in a third place in the challenge. Similar feature subset sizes were obtained for both kernels, and the most frequently selected MRI features were the volumes of the two hippocampal subregions left presubiculum and right subiculum. Post-challenge analysis revealed that enforcing a minimum number of selected features and increasing the number of ensemble classifiers improved classification accuracy up to 59.1%.Comparison with existing method(s)The ensemble SVM outperformed single SVM classifications consistently in the challenge test set.ConclusionsEnsemble methods using bagging and feature selection can improve the performance of the commonly applied SVM classifier in dementia classification. This resulted in competitive classification accuracies in the International Challenge for Automated Prediction of MCI from MRI data.



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Editorial Board

Publication date: 1 February 2018
Source:Journal of Neuroscience Methods, Volume 295





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In This Issue

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TcR-α recombinations in renal cell carcinoma exome files correlate with an intermediate level of T-cell exhaustion biomarkers

Abstract

Renal cell carcinoma exome-derived, V(D)J recombination reads had an elevated presence and variability, for both TcR-α and -β, when compared to marginal tissue, reflecting an opportunity to assess tumor immunogenicity by comparison with marginal tissue T cells. PD-1, PD-L2, CTLA4 and FOXP3, all of which are implicated in the evasion of an anti-tumor immune response, had a significantly higher expression for samples representing co-detection of productive TcR-α and -β recombination reads. Samples representing tumors with productive TcR-α recombination reads but no detectable, productive TcR-β recombination reads, reflected a 20% survival advantage, and RNASeq data indicated an intermediate level of immune checkpoint gene expression for those samples. These results raise the question of whether relatively high levels of detection of productive TcR-α recombination reads, in comparison with detection of reads representing the TcR-β gene, identify a microenvironment that has not yet entered a T-cell exhaustion phase and may thereby represent conditions for immune enhancements that do not require anti-immune checkpoint therapies.

http://ift.tt/2E9D2Tc

Rapid immunosurveillance by recirculating lymphocytes in the rat intestine: critical role of unsulfated sialyl-Lewis X on high endothelial venules of the Peyer’s patches

Abstract

Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection. Immunohistochemistry showed that donor TDLs predominantly transmigrated across high endothelial venules (HEVs) at the interfollicular area of the Peyer's patches (PPs), then exited into the LYVE-1⁺ efferent lymphatics, that were close to the venules. The rapid recirculation depended largely on the local expression of unsulfated sialyl-Lewis X on these venules where putative dendritic cells (DCs) were associated underneath. Recruited naive T cells briefly made contact with resident DCs before exiting to the lymphatics in the steady state. In some transplant settings, however, the T cells retained contact with DCs and were sensitized and differentiated into activated T cells. In conclusion, we directly demonstrated that lymphocyte recirculation within the gut is a very rapid process. The interfollicular area of PPs functions as a strategically central site for rapid immunosurveillance where HEVs, efferent lymphatics and resident DCs converge. PPs can, however, generate alloreactive T cells, leading to exacerbation of graft-versus-host disease or gut allograft rejection.

http://ift.tt/2FHrBzj

Clinical response to PD-1 blockade correlates with a sub-fraction of peripheral central memory CD4+ T cells in patients with malignant melanoma

Abstract

Cancer immunotherapy that blocks immune checkpoint molecules, such as PD-1/PD-L1, unleashes dysfunctional antitumor T-cell responses and has durable clinical benefits in various types of cancers. Yet its clinical efficacy is limited to a small proportion of patients, highlighting the need for identifying biomarkers that can predict the clinical response by exploring antitumor responses crucial for tumor regression. Here, we explored comprehensive immune-cell responses associated with clinical benefits using PBMCs from patients with malignant melanoma treated with anti-PD-1 monoclonal antibody. Pre- and post-treatment samples were collected from two different cohorts (discovery set and validation set) and subjected to mass cytometry assays that measured the expression levels of 35 proteins. Screening by high dimensional clustering in the discovery set identified increases in three micro-clusters of CD4⁺ T cells, a subset of central memory CD4⁺ T cells harboring the CD27⁺FAS⁻CD45RA⁻CCR7⁺ phenotype, after treatment in long-term survivors, but not in non-responders. The same increase was also observed in clinical responders in the validation set. We propose that increases in this subset of central memory CD4⁺ T cells in peripheral blood can be potentially used as a predictor of clinical response to PD-1 blockade therapy in patients with malignant melanoma.

http://ift.tt/2E9CX1Q

The immune checkpoint molecule VISTA regulates allergen-specific Th2-mediated immune responses

Abstract

V-domain immunoglobulin suppressor of T-cell activation (VISTA) is a novel immune checkpoint receptor and ligand that regulates T-cell activation. We investigated the functional involvement of VISTA in T_h2 cell-mediated immune responses using an ovalbumin (OVA)-induced allergic asthma model. Treatment with an anti-VISTA monoclonal antibody (mAb) during allergen sensitization increased the production of antibodies, including total IgE, OVA-specific IgG1 and IgG2a and allergen-specific IL-5 and IL-13; it also increased the expression of IL-13 by splenic CD4⁺ T cells. However, treatment with the anti-VISTA mAb during sensitization did not accelerate asthmatic responses, including airway hyper-responsiveness (AHR) or the number of eosinophils in bronchoalveolar lavage (BAL) fluid. In contrast, treatment with the anti-VISTA mAb during allergen challenge significantly augmented AHR and BAL fluid eosinophilia. This treatment also increased the production of IL-5 and IL-13 in BAL fluid and the expression of IL-13 by CD4⁺ T cells in draining lymph nodes. These results suggest that VISTA is involved in the regulation of T_h2 cell generation and T_h2 cell-mediated antibody production and regulates asthmatic responses, especially in the effector phase.

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Sweet syndrome associated with ipilimumab in a patient with metastatic melanoma

http://ift.tt/2DUKguW

Use of a novel 1-hour protocol for rapid frozen section immunocytochemistry, in a case of squamous cell carcinoma treated with Mohs micrographic surgery

Summary

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue.

http://ift.tt/2nEGXgv

Sweet syndrome associated with ipilimumab in a patient with metastatic melanoma

http://ift.tt/2DUKguW

Use of a novel 1-hour protocol for rapid frozen section immunocytochemistry, in a case of squamous cell carcinoma treated with Mohs micrographic surgery

Summary

For squamous cell carcinoma (SCC) treated using Mohs micrographic surgery (MMS), interpretation of haematoxylin and eosin-stained frozen sections can be challenging. In these situations, ancillary use of immunostaining is a useful tool for the Mohs surgeon. However, use of immunostaining in MMS laboratories is limited, mainly because current manual immunostaining platforms are subject to operator error, and automated immunostaining, albeit accurate, is too slow for inclusion in MMS. In this report, we describe a novel 1-hour protocol for rapid frozen section immunocytochemistry, using the pancytokeratin markers AE1/AE3. This protocol has been specifically designed to integrate the speed of manual techniques and the accuracy of automated platforms, making it a valuable addition to the MMS laboratory. We propose that in selected or histologically challenging cases, there is a role for the use of this novel protocol, allowing the Mohs surgeon to more confidently declare tumour clearance, thus preventing further unnecessary surgery and preserving healthy tissue.

http://ift.tt/2nEGXgv

A new discussion of the cutaneous vascular reactivity in sensitive skin: A sub-group of SS?

Abstract

Background

Sensitive skin (SS) seems not to be a one-dimensional condition and many scholars concentrate on skin barrier disruption or sensorineural change, but few focus on its increased vascular reactivity. This study explored the possibility of using the different selection methods and measurement methods to verify a high vascular reactivity in SS without an impaired cutaneous barrier function.

Methods

Sixty "self-perceived sensitive skin" volunteers were enlisted and each one completed three kinds of screening tests: assess cutaneous sensory using questionnaire survey and Lactic Acid Sting Test (LAST); assess barrier function using Sodium lauryl sulphate (SLS) skin irritation test and assess cutaneous vascular reactivity using 98% DMSO test and non-invasive measurement. Volunteers were divided into different groups based on response to SLS. The DMSO clinical score and the biophysical parameters obtained by non-invasive measurement were subsequently analysed.

Results

(1) The positive correlations could be seen between sum LAST score and sum DMSO score regardless of the observation time; (2) The biological parameters (CBF、a*values and L* values) are all keeping with DMSO score; (3) If the participants were divided into SLS reactors and non-reactors, a composition ratio of DMSO score was significant difference in these two groups and in SLS non-reactors, there were still seven participants showed high reaction to DMSO.

Conclusions

There is a sub-group of SS for characteristics of a high vascular reactivity without an impaired cutaneous barrier function. The DMSO test and novel non-invasive measurements which are conducive to assess cutaneous vascular reactivity, combined with SLS skin irritation test could help us to screen this kind of SS.

http://ift.tt/2nFMNhB

An innovative method to quantitate tissue integration of hyaluronic acid-based dermal fillers

Abstract

Background/purpose

Following intradermal injection, hyaluronic acid (HA)-based fillers tend to spread within the reticular dermis and to distribute between the dermal fibers. This biointegration is commonly measured qualitatively using histological methods. We developed a "toolbox" consisting of a visual scoring and a semi-automatic image analysis method using internal developed algorithm to quantitate the biointegration of Restylane® in histological sections.

Methods

Restylane^® was injected intradermally in the abdominal skin of 10 healthy human subjects scheduled for abdominoplasty. The injections were performed either in vivo before surgery or ex vivo on samples taken post-surgery at different time points. The samples were processed for histology by visual scoring and image analysis using algorithms developed in Definiens to assess biointegration.

Results

The image analysis segmentation was accurate with <5% manual changes. Furthermore, the results calculated with the semi-automatic method were consistent with the visual scores obtained on injected human skin samples by means of a 5-grade photographic scale. A modified hematoxylin-eosin staining was found adequate to visualize both, the filler and the general morphology, on the same section. An excellent correlation was observed between the integration results obtained with PAS/Alcian Blue and HE-stained slides, allowing for a single staining in future studies.

Conclusion

We developed a modified HE staining histological method and a new histomorphometric image analysis tool to quantitate biointegration of HA-based fillers in human skin. The results obtained in this study confirmed the known intermediate biointegration properties of Restylane®, thus validating these innovative methods.

http://ift.tt/2DZNJbS

First data from a population based cancer registry in Ethiopia

Publication date: April 2018
Source:Cancer Epidemiology, Volume 53
Author(s): Genebo Timotewos, Asmare Solomon, Assefa Mathewos, Adamu Addissie, Solomon Bogale, Tigeneh Wondemagegnehu, Abraha Aynalem, Bekele Ayalnesh, Hailemariam Dagnechew, Wondatir Bireda, Eric Sven Kroeber, Rafael Mikolajczyk, Freddie Bray, Ahmedin Jemal, Eva Johanna Kantelhardt
BackgroundThe Addis Ababa City Cancer Registry, established in September 2011, is the only population-based cancer registry in Ethiopia, covering a catchment population of just over three million habitants. Herein, we report incidence data based on the first two years of registration, 2012–2013.MethodsNewly-diagnosed cancer cases in the capital city were actively collected from 22 hospitals, clinics, and diagnostic facilities.ResultsDuring 2012–2013, a total of 4139 newly diagnosed cases were recorded, with the majority (67%) occurring in females. Cancers of the breast (31.5%) and cervix (14.1%) were the two most common cancers among females, while colorectal cancers (10.6%) and non-Hodgkin lymphomas (10.2%) were the most common cancers among males. The average annual age-standardized rate for all sites 2012–13 were 136.2 (per 100,000) and 70.7 in females and males, respectively. Female age-standardized rates were 40.6 for breast cancer and 21.5 for cervix, while equivalent rates in males were 7.6 per 100,000 for colorectal cancer and 6.8 per 100,000 for non-Hodgkin lymphoma.ConclusionIn general, these incidence patterns were similar to those reported in neighboring countries, which suggests that the majority of cancer cases occurring in Addis Ababa are captured within this starting phase of the registry. However, our finding of colorectal cancer as the most commonly-diagnosed cancer in males is novel and requires further investigation.



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A highly efficient polymer non-fullerene organic solar cell enhanced by introducing a small molecule as a crystallizing-agent

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): Yifan Zheng, Jiang Huang, Gang Wang, Jaemin Kong, Di Huang, Megan Mohadjer Beromi, Nilay Hazari, André D. Taylor, Junsheng Yu
Non-fullerene organic solar cells (OSCs) have attracted tremendous interest because of their potential to replace traditional expensive fullerene-based OSCs. To further increase the power conversion efficiency (PCE), it is necessary to offset the narrow absorption of the non-fullerene materials, which is often achieved by adding an additive (>10 wt%) to form a ternary blend. However, a high ratio of the third component can often be detrimental to the active layer morphology and can increase the complexity in understanding the device physics toward rationally designed improvements. In this work, we introduce 2,4-bis-[(N,N-diisobutylamino)-2,6-dihydroxyphenyl]-4-(4-diphenyliminio) squaraine (ASSQ) in the poly [(2,6-(4,8-bis(5-(2-ethylhexyl)thiophen-2-yl) benzo [1,2-b:4,5-b′] dithiophene)-co-(1,3-di(5-thiophene-2-yl)-5,7-bis(2-ethylhexyl) benzo [1,2-c:4,5-c′] dithiophene-4,8-dione)] (PBDB-T): 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-indanone))-5,5,11,11-tetrakis(4-hexylphenyl)-dithieno [2,3-d:2′,3′-d′]-s-indaceno [1,2-b:5,6-b′] dithiophene (ITIC) as an active layer "crystallizing-agent". Through detailed morphology characterization, we find that the addition of 4 wt% ASSQ assists ITIC organization order and promotes PDBD-T:ITIC aggregation in the preferential face-on orientation. In addition, we demonstrate that the ASSQ and PBDB-T show efficient exciton dissociation in the ternary blend over Förster resonance energy transfer (FRET). We reveal using surface potential and solubility measurements that a ASSQ-ITIC co-crystalline structure forms which facilitates a significant improvement in the device PCE, from 8.98% to 10.86%.

Graphical abstract

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From biomaterial-based data storage to bio-inspired artificial synapse

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): Ziyu Lv, Ye Zhou, Su-Ting Han, V.A.L. Roy
The implementation of biocompatible and biodegradable information storage would be a significant step toward next-generation green electronics. On the other hand, benefiting from high density, multifunction, low power consumption and multilevel data storage, artificial synapses exhibit attractive future for built-in nonvolatile memories and reconstructed logic operations. Here, we provide a comprehensive and critical review on the developments of bio-memories with a view to inspire more intriguing ideas on this area that may finally open up a new chapter in next-generation consumer electronics. We will discuss that biomolecule-based memory employed evolutionary natural biomaterials as data storage node and artificial synapse emulated biological synapse function, which is expected to conquer the bottleneck of the traditional von Neumann architecture. Finally, challenges and opportunities in the aforementioned bio-memory area are presented.

Graphical abstract

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Superconducting stacks

Publication date: Available online 1 February 2018
Source:Materials Today
Author(s): M.A. Torres, Sh. Rasekh, M.A. Madre, J.C. Diez, A. Sotelo




http://ift.tt/2FFj6oj

Lithium-ion conductive ceramic textile: A new architecture for flexible solid-state lithium metal batteries

Publication date: Available online 2 February 2018
Source:Materials Today
Author(s): Yunhui Gong, Kun Fu, Shaomao Xu, Jiaqi Dai, Tanner R. Hamann, Lei Zhang, Gregory T. Hitz, Zhezhen Fu, Zhaohui Ma, Dennis W. McOwen, Xiaogang Han, Liangbing Hu, Eric D. Wachsman
Designing solid-state lithium metal batteries requires fast lithium-ion conductors, good electrochemical stability, and scalable processing approaches to device integration. In this work, we demonstrate a unique design for a flexible lithium-ion conducting ceramic textile with the above features for use in solid-state batteries. The ceramic textile was based on the garnet-type conductor Li7La3Zr2O12 and exhibited a range of desirable chemical and structural properties, including: lithium-ion conducting cubic structure, low density, multi-scale porosity, high surface area/volume ratio, and good flexibility. The solid garnet textile enabled reinforcement of a solid polymer electrolyte to achieve high lithium-ion conductivity and stable long-term Li cycling over 500 h without failure. The textile also provided an electrolyte framework when designing a 3D electrode to realize ultrahigh cathode loading (10.8 g/cm² sulfur) for high-performance Li-metal batteries.

Graphical abstract

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RHOA G17V Induces T Follicular Helper Cell Specification and Promotes Lymphomagenesis

Publication date: Available online 2 February 2018
Source:Cancer Cell
Author(s): Jose R. Cortes, Alberto Ambesi-Impiombato, Lucile Couronné, S. Aidan Quinn, Christine S. Kim, Ana C. da Silva Almeida, Zachary West, Laura Belver, Marta Sanchez Martin, Laurianne Scourzic, Govind Bhagat, Olivier A. Bernard, Adolfo A. Ferrando, Teresa Palomero
Angioimmunoblastic T cell lymphoma (AITL) is an aggressive tumor derived from malignant transformation of T follicular helper (Tfh) cells. AITL is characterized by loss-of-function mutations in Ten-Eleven Translocation 2 (TET2) epigenetic tumor suppressor and a highly recurrent mutation (p.Gly17Val) in the RHOA small GTPase. Yet, the specific role of RHOA G17V in AITL remains unknown. Expression of Rhoa G17V in CD4⁺ T cells induces Tfh cell specification; increased proliferation associated with inducible co-stimulator (ICOS) upregulation and increased phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase signaling. Moreover, RHOA G17V expression together with Tet2 loss resulted in development of AITL in mice. Importantly, Tet2^−/−RHOA G17V tumor proliferation in vivo can be inhibited by ICOS/PI3K-specific blockade, supporting a driving role for ICOS signaling in Tfh cell transformation.

Graphical abstract

Teaser

Cortes et al. show that expression of Rhoa G17V in CD4⁺ T cells drives proliferation and Tfh polarization, and they develop an angioimmunoblastic T cell lymphoma model by combining Rhoa G17V expression and Tet2 loss. These tumors show increased ICOS and PI3K/MAPK signaling and are sensitive to pathway inhibition.


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Plasticizers used in food-contact materials affect adipogenesis in 3T3-L1 cells

Publication date: Available online 2 February 2018
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Valentina Pomatto, Erika Cottone, Paolo Cocci, Matteo Mozzicafreddo, Gilberto Mosconi, Erik Russel Nelson, Francesco Alessandro Palermo, Patrizia Bovolin
Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.01-25 µM) of DiNP (Di-iso-nonyl-phthalate), DiDP (Di-iso-decyl-phthalate), DEGDB (Diethylene glycol dibenzoate), or TMCP (Tri-m-cresyl phosphate). Rosiglitazone, a well-known pro-adipogenic peroxisome proliferator activated receptor gamma (PPARγ) agonist, and the plasticizer BPA were included as reference compounds. All concentrations of plasticizers were able to enhance lipid accumulation, with TMCP being the most effective one. Accordingly, when comparing in silico the ligand binding efficiencies to the nuclear receptors PPARγ and retinoid-X-receptor-alpha (RXRα), TMPC displayed the highest affinity to both receptors. Differently from BPA, the four plasticizers were most effective in enhancing lipid accumulation when added in the mid-late phase of differentiation, thus suggesting the involvement of different intracellular signalling pathways. In line with this, TMCP, DiDP, DiNP and DEGDB were able to activate PPARγ in transient transfection assays, while previous studies demonstrated that BPA acts mainly through other nuclear receptors. qRT-PCR studies showed that all plasticizers were able to increase the expression of CCAAT/enhancer binding protein β (Cebpβ) in the early steps of adipogenesis, and the adipogenesis master gene Pparγ2 in the middle phase, with very similar efficacy to that of Rosiglitazone. In addition, TMCP was able to modulate the expression of both Fatty Acid Binding Protein 4/Adipocyte Protein 2 (Fabp4/Ap2) and Lipoprotein Lipase (Lpl) transcripts in the late phase of adipogenesis. DEGDB increased the expression of Lpl only, while the phthalate DiDP did not change the expression of either late-phase marker genes Fabp4 and Lpl. Taken together, our results suggest that exposure to low, environmentally relevant doses of the plasticizers DiNP, DiDP DEGDB and TMCP increase lipid accumulation in 3T3-L1 adipocytes, an effect likely mediated through activation of PPARγ and interference at different levels with the transcriptional cascade driving adipogenesis.



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Pendant/bridged/mesoporous silsesquioxane nanoparticles: Versatile and biocompatible platforms for smart delivery of therapeutics

Publication date: Available online 2 February 2018
Source:Chemical Engineering Journal
Author(s): Achraf Noureddine, C. Jeffrey Brinker
Silsesquioxane nanoparticles are composed of repetitive organosilica fragments in their frameworks and are now recognized to have outstanding functional fertility. Depending on the organosilane and the synthetic pathways, silsesquioxane NPs can be pendant, bridged, dense or porous. Recently the diverse functionalities of mesoporous silsesquioxane nanoparticles have been exploited for the sake of drug-related biomedicine. Fine-tuning the silsesquioxane nanoparticles characteristics allow not only a superior retention capacity of therapeutics without the need of any further modification, but also a controlled release through various environmentally-stimulated triggers. The main focus of the present review is to highlight the different types of silsesquioxane nanoparticles and their exceptional features focused on controlled delivery of drugs, proteins, antibodies and DNA through pH, redox or light stimuli.

Graphical abstract

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Efficient chlorine atom functionalization at nanodiamond surfaces by electron beam irradiation

Publication date: February 2018
Source:Diamond and Related Materials, Volume 82
Author(s): Jieying Zhou, Christian Laube, Wolfgang Knolle, Sergej Naumov, Andrea Prager, Frank-Dieter Kopinke, Bernd Abel
Surface functionality of nanodiamonds is of crucial importance for their desired chemical, optical and electromagnetic properties. Chlorinated surfaces are expected to enable an easy further modification of diamond surfaces via various substitution reactions for targeted molecule grafting, particularly interesting for biochemical applications. Previously reported chlorination approaches of diamonds required troublesome handling of hazardous chemicals, such as chlorine gas, and long chlorination time or high temperature. Here, we describe a radiation chemistry approach using electron beam irradiation for efficient surface chlorination of nanodiamonds (with averaged diameter of ca. 30 nm) at ambient temperature. Nanodiamonds with hydrogenated and graphitized surfaces were used for chlorination in CCl4, CHCl3 and CH2Cl2 at increasing radiation doses. A comprehensive set of measurements, including XPS, ATR-FTIR and in-source thermal desorption mass spectrometry (IS-TD-MS) was applied to characterize the chlorinated products. Density functional theory (DFT) calculations were performed to assist the discussion of reaction mechanisms. It is confirmed that remarkable covalently chlorine-covered surfaces bearing adequate stability against air and water were achieved for hydrogenated nanodiamonds in CCl4 by applying doses ≥500 kGy.

Graphical abstract

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Epitope Mapping of Monoclonal Antibody PMab-52 Against Cat Podoplanin

Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.


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Knowledge of self-myofascial release among allied health students in the United States: A descriptive comparison survey

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Scott W. Cheatham, Kyle R. Stull
BackgroundUniversity and collegiate education of the human myofascial system is commonly taught in basic science courses such as anatomy. Allied health programs may expand upon these concepts by teaching interventions such as myofascial release in clinical education courses. Self-myofascial release (SMR) with a device such as a foam roller is an emerging intervention that has become popular among clinicians and active individuals. Currently, it's unknown if allied health programs provide SMR education.PurposeThe purpose of this study was to survey and document responses in the knowledge of SMR among allied health students.Methods12 undergraduate and graduate allied health programs in the United States were sent a 12-question electronic survey that represented three areas: 1) respondent demographics and beliefs, 2) experience with SMR, 3) future practice and education. Descriptive data including response frequency and percentage was calculated and reported for the 12 questions.ResultsA total of 502 students from the different allied health programs completed the survey which represented a 33.00% response rate (502/1521). Approximately, half of respondents (49.6%, N = 249) reported learning about SMR in their degree program and the other half (50.40%, N = 253) report receiving no education. Most respondents (>50%) currently use or have used an SMR device and believe that SMR produces therapeutic benefits. Furthermore, most respondents (≥50%) had an idea of how they would integrate SMR into their future practice and where to purchase an SMR device.ConclusionA more global consensus on education for emerging therapeutic intervention such as SMR is needed in order to standardize and develop best teaching practices in allied health. This study highlighted the difference among allied health programs in the United States. This research should be a starting point for future survey research on this topic.



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Therapeutic heat and cold around the elbow on the response of median neurodynamic test 1

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Winora Conchita Gomes, Kavitha Vishal, Ganesh Balthillaya
ObjectiveTo compare the effects of the application of therapeutic heat and cold on the mechanical response of the median nerve neurodynamic testing.DesignSingle-blinded randomized crossover trial.Methodology56 asymptomatic university students (mean age = 21.82 ± 1.64 years) of either gender with a limited elbow extension range of motion during a Median Neurodynamic Test 1 were recruited. Each subject was administered 3 testing conditions on separate days with a 24-hr washout period. The interventions included 1) therapeutic moist heat around the elbow, 2) therapeutic cold around the elbow and 3) no thermal agent as a controlled condition. Outcome measure of elbow extension range of motion at the Onset of pain and Submaximal pain was recorded before the intervention, immediately after the removal of the thermal agents and at 2 subsequent readings of 30min and 1 h after the removal of the thermal agent.Resultsthere was a significant effect of using a thermal agent with time on the elbow range of motion at the onset of pain [F(2,165) = 3.622, p = 0.029] and submaximal pain[F(2,165) = 3.841, p = 0.023] at the 20th min. A posthoc comparison indicated that at the 20th min the mean elbow range at the onset of pain and submaximal pain for the therapeutic heat condition (m = 33.5, S.D = 13.37 and m = 16.80, S.D = 12.99 respectively) was significantly different than the no thermal agent condition (m = 40.17, S.D = 12.34 and m = 23.4, S.D = 13.82 respectively). However. Therapeutic cold condition did not significantly differ from both the other conditions.ConclusionTherapeutic heat causes an immediate increase in elbow extension range of motion during a Median Neurodynamic Test1 and testing post the application of thermal agents can alter the test response.



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Dry needling in chronic abdominal wall pain of uncertain origin

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Rajkannan Pandurangan, Rajagopalan Vijayaraghavan
BackgroundAbdominal wall pain is considered as pain that arises from the abdominal muscles rather than the underlying viscera or the spine. It is frequently overlooked and is often misdiagnosed, as these patients continue to suffer with pain. Many such patients would have even been subjected to a psychiatric evaluation in view of the absence of any ostensible clinical cause for the pain. In this study, we describe the role of myofascial trigger points in the abdominal wall pain that could be a cause of chronic pain and present our findings of pain relief by dry needling technique.ObjectivesTo report the effect of dry needling treatment for patients who suffer from chronic abdominal wall pain of uncertain etiology and in whom specific myofascial trigger points were identified.MethodsTwelve patients diagnosed with chronic abdominal wall pain were included in the study. All patients were clinically evaluated and subjected to a combination of imaging techniques. Once categorized as patients suffering from chronic abdominal wall pain, they were subjected to a thorough palpation of the abdominal wall to identify the presence of myofascial trigger points (MTrPs) over the abdominal muscles. All had MTrPs over one or more abdominal muscles either unilaterally or bilaterally. Dry Needling using a standard technique was done based on the side and localization of the myofascial trigger points. Numerical pain rating scale (NPRS) was used to measure pain before and after treatment and at the end of four months. All patients were then seen by the primary clinician and re-evaluated.ResultsEleven out of twelve patients had significant reduction with a mean difference 5.95 in NPRS in their pain levels at four months follow up. Seven patients had complete resolution of the pain. Some patients had improvement in complaints such as Dysmenorrhea, Urinary Frequency and constipation.ConclusionDry Needling can be a useful adjunct in treating chronic abdominal wall pain especially in those patients in whom Myofascial Trigger Points in the muscles of abdomen are identified by palpation.Level of evidenceLevel 4.



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Comparison of muscular activities between subjects with and without scapular downward rotation impairment during diagonal pattern of exercises

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Se-Yeon Park, Du-Jin Park
BackgroundsOne form of abnormal scapular alignment is scapular downward rotation (SDR). Changes in muscle function in SDR have not been clearly identified, and SDR exercises also require investigation. Although a diagonal pattern of exercise is commonly used as part of the exercise protocol, a direct comparison of shoulder and scapular diagonal exercises has not yet been conducted. The objectives of this study were to determine the altered activation of the scapular musculature in the SDR group and to investigate which diagonal pattern of exercise effectively activates the scapular musculature.MethodsThirty-two participants (18 in the control group and 14 in the SDR group) volunteered to participate in this study. Electromyographic signals were collected from four muscles, the upper trapezius (UT), lower trapezius (LT), serratus anterior (SA), and anterior deltoid (AD), during standing performance of diagonal shoulder and scapular exercises.ResultsThe control group showed significantly lower UT activity, UT/LT ratio, and UT/SA values than the SDR group (p < .05). Activation of the AD was significantly higher in the SDR than in the control group (p < .05). SA and AD activation were significantly higher in shoulder diagonal pattern exercises than in scapular diagonal pattern exercises (p < .05). The scapular posterior elevation pattern exercise showed significantly higher UT and LT activities than anterior elevation and shoulder diagonal pattern exercises (p < .05).ConclusionOur findings suggest that reduced activation of the UT could lead to greater activation in the AD in SDR. Scapular posterior elevation exercise is advantageous as selectively activates the trapezius musculature, and shoulder diagonal pattern exercise is advantageous in activating the SA and AD.



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Immediate effects and one-week follow-up after neuromuscular electric stimulation alone or combined with stretching on hamstrings extensibility in healthy football players with hamstring shortening

Publication date: Available online 2 February 2018
Source:Journal of Bodywork and Movement Therapies
Author(s): Luis Espejo-Antúnez, María Carracedo-Rodríguez, Fernando Ribeiro, João Venâncio, Blanca De la Cruz-Torres, Manuel Albornoz-Cabello
ObjectiveTo assess the immediate and mid-term (after 7 days) effects of electric current combined with simultaneous muscle stretching (EME technique) per comparison to the isolated use of the same current (without applying simultaneous muscle stretching), over the hamstring extensibility in football players with hamstring shortening, and to estimate the clinical benefit of the interventions according to the muscular extensibility.MethodsForty-eight participants were randomized to receive one session of EME technique (n = 26) or one session of the electrical current (EC) alone (n = 22). The measurement of the hamstrings extensibility through the active knee test was carried out before and immediately after each intervention and one week later.ResultsA significant interaction group x time was observed (F2,84 = 7.112, p = 0.001; partial eta squared = 0.145). The hamstrings extensibility changed significantly immediately after the EME technique (147.3° ± 16.4° to 153.5° ± 14.2°, p < 0.05), but not after the EC only (144.2 ± 10.2° to 141.7 ± 7.8°, p > 0.05). One week after the intervention no significant differences were found to the baseline values in both groups. The number needed to treat to prevent one new case of hamstring shortening was 3.ConclusionThe combination of electric current with simultaneous stretching is an effective technique to acutely increase the hamstring extensibility of football players with hamstring shortness.



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The Impact of Ethnicity on the Prevalence and Severity of Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a common disorder associated with multiple adverse health consequences and its prevalence is increasing in parallel with rising obesity trends. Early support for ethnic differences in OSA prevalence and severity has been derived from studies of relatively homogenous ethnic groups. However, between-study comparisons are problematic given differing methodologies. Recent large inter-ethnic studies examining different ethnic populations using standardized protocols support the notion that Chinese have an increased OSA prevalence and severity compared to those of European descent.

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Characterization of Cervical Neuromuscular Response to Head-neck Perturbation in Active Young Adults

Publication date: Available online 2 February 2018
Source:Journal of Electromyography and Kinesiology
Author(s): Bara Alsalaheen, Ryan Bean, Andrea Almeida, James Eckner, Matthew Lorincz
BackgroundThe majority of studies examining the role of cervical muscles on head-neck kinematics focused on musculoskeletal attributes (e.g. strength). Cervical neuromuscular response to perturbation may represent a divergent construct that has not been examined under various perturbation conditions. This study examined the association between cervical musculoskeletal attributes and cervical neuromuscular response of the sternocleidomastoid (SCM) to perturbation. Furthermore, this study examined the effect of anticipation and preload on the SCM neuromuscular response.MethodsNineteen participants completed measurement of SCM muscle size, cervical flexion maximal voluntary isometric contraction, and the neuromuscular response of the SCM to cervical perturbation. Cervical perturbation was delivered by dropping a 1.59 kg mass from a loading apparatus. The impulsive load was delivered under four conditions: 1) Anticipated perturbation with no preload (A-NP), 2) Unanticipated perturbation with no preload (U-NP), 3) Anticipated perturbation with preload (A-P), and 4) Unanticipated perturbation with preload (U-P).ResultsNone of the cervical musculoskeletal attributes were correlated with the SCM cervical neuromuscular response. This study demonstrated significant effect of preloading and anticipation on baseline EMG amplitude and EMG onset latency for the SCM. Furthermore, there was a significant effect of preloading on average EMG response amplitude for the SCM.DiscussionThe findings of this study indicate that cervical neuromuscular response of the SCM is different from musculoskeletal attributes and is influenced by perturbation conditions. These findings provide conceptual support to examine the neuromuscular response of the SCM in mitigating head-neck kinematics.



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If John Is Taller Than Jake, Where Is John? Spatial Inference From Magnitude Comparison.

Author: Skylark, William J.

DOI: 10.1037/xlm0000505

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BQIchC

Phonologically-Based Priming in the Same-Different Task With L1 Readers.

Author: Lupker, Stephen J.; Nakayama, Mariko; Yoshihara, Masahiro

DOI: 10.1037/xlm0000515

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nyJVnL

The Effect of Feedback Delay on Perceptual Category Learning and Item Memory: Further Limits of Multiple Systems.

Author: Stephens, Rachel G.; Kalish, Michael L.

DOI: 10.1037/xlm0000528

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BQtabR

Distinctiveness and the Attentional Boost Effect.

Author: Smith, S. Adam; Mulligan, Neil W.

DOI: 10.1037/xlm0000531

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BRJlp9

Imagining Counterfactual Worlds in Autism Spectrum Disorder.

Author: Black, Jo; Williams, David; Ferguson, Heather J.

DOI: 10.1037/xlm0000500

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nxbSw6

Context Specificity of Automatic Influences of Memory.

Author: Smith, Steven M.; Handy, Justin D.; Hernandez, Alan; Jacoby, Larry L.

DOI: 10.1037/xlm0000523

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BQ1pAc

Gender Congruency From a Neutral Point of View: The Roles of Gender Classes and Conceptual Connotations.

Author: Bender, Andrea; Beller, Sieghard; Klauer, Karl Christoph

DOI: 10.1037/xlm0000534

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

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The Sandwich Priming Paradigm Does Not Reduce Lexical Competitor Effects.

Author: Trifonova, Iliyana V.; Adelman, James S.

DOI: 10.1037/xlm0000542

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

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Best, Second-Best, and Good-Enough Explanations: How They Matter to Reasoning.

Author: Douven, Igor; Mirabile, Patricia

DOI: 10.1037/xlm0000545

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nxbT38

Explaining Recollection Without Remembering.

Author: Chen, X. R.; Gomes, C. F. A.; Brainerd, C. J.

DOI: 10.1037/xlm0000559

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

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Mood State Dissociates Conflict Adaptation Within Tasks and Across Tasks.

Author: Schuch, Stefanie; Putz, Sebastian

DOI: 10.1037/xlm0000530

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nxe5HW

The Dimensionality of Reasoning: Inductive and Deductive Inference can be Explained by a Single Process.

Author: Hayes, Brett K.; Stephens, Rachel G.; Ngo, Jeremy; Dunn, John C.

DOI: 10.1037/xlm0000527

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BPZpId

Fluctuation in Cognitive Engagement During Reading: Evidence From Concurrent Recordings of Postural and Eye Movements.

Author: Kaakinen, Johanna K.; Ballenghein, Ugo; Tissier, Geoffrey; Baccino, Thierry

DOI: 10.1037/xlm0000539

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nz8znZ

The Use of Phonological Representations in Guiding Eye Movements in the Visual World Paradigm.

Author: Gregg, Julie; Sajin, Stanislav

DOI: 10.1037/xlm0000541

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BQcNfu

How Listening to Music Affects Reading: Evidence From Eye Tracking.

Author: Zhang, Han; Miller, Kevin; Cleveland, Raymond; Cortina, Kai

DOI: 10.1037/xlm0000544

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nC8QH5

Explaining the Association Between Music Training and Reading in Adults.

Author: Swaminathan, Swathi; Schellenberg, E. Glenn; Venkatesan, Kirthika

DOI: 10.1037/xlm0000493

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BPibzt

Listeners and Readers Generalize Their Experience With Word Meanings Across Modalities.

Author: Gilbert, Rebecca A.; Davis, Matthew H.; Gaskell, M. Gareth; Rodd, Jennifer M.

DOI: 10.1037/xlm0000532

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2nzOlut

Postcategorical Auditory Distraction in Short-Term Memory: Insights From Increased Task Load and Task Type.

Author: Marsh, John E.; Yang, Jingqi; Qualter, Pamela; Richardson, Cassandra; Perham, Nick; Vachon, Francois; Hughes, Robert W.

DOI: 10.1037/xlm0000492

Publication Date: POST AUTHOR CORRECTIONS, 1 February 2018

http://ift.tt/2BPhWEz

Corrigendum to “miR-142-5p promotes development of colorectal cancer through targeting SDHB and facilitating generation of aerobic glycolysis” [Biomed. Pharmacother. 92 (2017) 1119–1127]

Publication date: Available online 2 February 2018
Source:Biomedicine & Pharmacotherapy
Author(s): Shaojun Liu, Zhiming Xiao, Feiyan Ai, Fen Liu, Xiong Chen, Ke Cao, Weiguo Ren, Xuemei Zhang, Peng Shu, Decai Zhang




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Snap, crackle and pop: when sneezing leads to crackling in the neck

Wanding Yang<br />Jan 15, 2018; 2018:bcr-2016-218906-bcr-2016-218906<br />Rare disease

http://ift.tt/2DWxIPU

Successful treatment of postural orthostatic tachycardia and mast cell activation syndromes using naltrexone, immunoglobulin and antibiotic treatment

Leonard B Weinstock<br />Jan 11, 2018; 2018:bcr-2017-221405-bcr-2017-221405<br />Novel treatment (new drug/intervention; established drug/procedure in new situation)

http://ift.tt/2Exc6KN

Non-replication of neurophysiological predictors of non-response to rTMS in depression and neurophysiological data-sharing proposal

Publication date: Available online 2 February 2018
Source:Brain Stimulation
Author(s): Noralie Krepel, Alexander T. Sack, Leon J. Kenemans, Paul B. Fitzgerald, Wilhelmus H. Drinkenburg, Martijn Arns




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Longitudinal study of radiation-induced brain microstructural alterations with S-index, a Diffusion MRI biomarker, and MR Spectroscopy

Publication date: Available online 2 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): E.A. Pérès, O. Etienne, A. Grigis, F. Boumezbeur, F.D. Boussin, D. Le Bihan
PurposeRadiotherapy is widely used for the treatment of brain tumors but it may lead to severe cognitive impairments. Previous studies have shown that ionizing radiation induces demyelination, blood-brain barrier alterations and impaired neurogenesis in animal models. Hence, non-invasive and sensitive biomarkers of radiation injury are needed to investigate these effects in patients and improve radiotherapy protocols.Methods and MaterialsThe heads of 3-months old male C57BL/6RJ mice (CTL: n=15; IR: n=15) were exposed to radiation doses of 3x5Gy from a ⁶⁰Co source with a medical irradiator. A longitudinal study was performed to investigate cranial radiation-induced (3x5Gy) microstructural tissue alterations using water diffusion MRI (dMRI) and MR Spectroscopy (MRS) in different areas of the mouse brain (cortex, thalamus, striatum, olfactory bulbs (OB), hippocampus and the subventricular zone (SVZ)). In addition to the quantification of standard non-Gaussian diffusion parameters, ADC0 (Apparent Diffusion Coefficient) and K (Kurtosis), we evaluated a new composite diffusion metric, designated as S-index.ResultsWe observed a significant decrease in S-index in the SVZ, from 1 month to 8 months after brain radiation (p<0.05). Interestingly, along with a decrease in Taurine (up to -15% at 2 months, p<0.01), a delayed S-index drop was also observed in the OB from 4 months after irradiation and maintained until the end of our experiment (p<0.0001). These observations suggest that S-index variations revealed the radiation-induced decline of neurogenesis that was further confirmed by a decrease of neural stem cells in the SVZ and of newborn neurons in the OB of irradiated animals.ConclusionsThis study demonstrates that dMRI, especially through the S-index approach, is a relevant imaging modality to monitor brain radiation injury and probe microstructural changes underlying radiation-induced cognitive deficits.

Teaser

Cancer patients frequently suffer from cognitive impairments following brain radiotherapy. To monitor radiation-induced microstructural tissue damage, especially in neurogenic areas, we have investigated the potential of diffusion MRI and MR spectroscopy. The diffusion S-index calculated from diffusion MRI signal acquired at two optimized values of diffusion-weighting appeared as the most sensitive biomarker revealing subtle brain tissue alterations induced by ionizing radiation.


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Bioluminescence Tomography Guided Small Animal Radiotherapy and Tumor Response Assessment

Publication date: Available online 2 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Junwei Shi, Thirupandiyur S. Udayakumar, Keying Xu, Nesrin Dogan, Alan Pollack, Yidong Yang
Purposes: The image-guided SMall Animal Arc Radiation Treatment platform (iSMAART) has adopted onboard cone beam computed tomography (CBCT) and bioluminescence tomography (BLT). In this study, we used BLT to guide radiation delivery and quantitatively assess radiation-induced tumor response.Methods and MaterialsBLT was first validated on a tissue-simulating phantom, where the internal chemiluminescent liquid had a constant volume while its luminescence intensity gradually decayed. Then, in vivo experiments were performed on BALB/c mice orthotopically inoculated with 4T1 breast carcinoma cells expressing luciferase. Animals received either radiation treatment (RT group, n=9) or not (Control group, n=9). BLT was used to guide delivery of a single fraction of 5 Gy radiation dose to the tumor, and to evaluate the treatment response. The terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was used to evaluate the radiation-induced DNA damage and cell apoptosis.ResultsPhantom results showed that BLT not only recovered the constant target volume with <2% deviation, but also accurately monitored the decay of the chemiluminescent molecules. For the RT animal group, there was significant reduction in both BLT-based tumor volume (21±10%, P=0.001) and bioluminescence intensity (48±17%, P=0.0008). For the control group, the significant increase was detected in the BLT tumor volume (35±12%, P<0.0001), but not in the BLT bioluminescence intensity (P=0.4). There was a significant difference in the BLT tumor volume between the RT and control group 7 days after radiation (P=0.03). Regression analysis suggests a strong correlation between the BLT and CBCT tumor volume (R²=0.93). The TUNEL staining analysis showed a significant difference in tumor cell apoptosis between the RT and control group (20.6±2.9% vs 3.2±1.7%, P<0.05).ConclusionBLT onboard the iSMAART can be used to accurately guide radiation delivery, and to quantitatively assess treatment response by simultaneously monitoring tumor volume and cancer cell population.



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IDEAL 2a phase-II study of ultra-focal brachytherapy for low and intermediate risk prostate cancer

Publication date: Available online 2 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Pierre Graff, Daniel Portalez, Amélie Lusque, Thomas Brun, Richard Aziza, Jonathan Khalifa, Mathieu Roumiguié, Marie-Laure Quintyn Ranty, Thomas Filleron, Jean-Marc Barchaud, Bernard Malavaud
PurposeFocal therapy of prostate cancer requires precise positioning of therapeutic agents within well-characterised index tumours (IT).We assessed the feasibility of low-dose-rate ultra-focal brachytherapy (UFB).Methods & MaterialsIRB-approved European Clinical Trials Database-registered phase II protocol. Patients referred (10/2013-8/2016) for active surveillance [PSA<10ng/mL, cT1c-cT2a, Gleason sum on referring biopsies ≤6(3+3), ≤3 positive biopsies, ≤50% of cancer] were pre-selected. Inclusion was confirmed when complementary image-guided biopsies informed a single PI-RADS.v1≥3 Gleason sum ≤7a(3+4) lesion.A single ultrasound-visible ancillary marker was positioned within the IT using 3D-TRUS/MRI elastic fusion registration (Koelis°). Ultra-focal transperineal delivery of I-125 seeds then used classical 2D-Transrectal ultrasonography (Bard-FlexFocus°) and dose-optimization (Variseed Treatment Planning System°).Following Simon's optimal design, 17 patients were required to assess the feasibility of delivering ≥95% of the prescribed dose (160Gy) to the IT (primary objective). Adverse-events (CTCAE) and quality-of-life (IIEF-5, IPSS) were recorded. 1-year control biopsies were obtained in IT and untreated segments.Results27/44 of pre-selected patients failed inclusion. 16/17 of UFB-treated patients met the primary objective (per-protocol success). Prescription dose was delivered to 14.5±6.4% of the prostate volume resulting in negligible urethral and rectal irradiations and toxicities. No recurrences were evidenced on 1-year control MRI and IT biopsies. Seven non-clinically significant cancers and one Gleason sum 7a(3+4) cancer (salvage prostatectomy) were observed in the untreated parenchyma.ConclusionsRecent technology allows selective and effective brachytherapy of small MRI targets.



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Long-Term Outcomes and Prognostic Factors Following Pencil-Beam Scanning Proton Radiotherapy for Spinal Chordomas: A Large, Single-Institution Cohort

Publication date: Available online 2 February 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): J.W. Snider, Ralf A. Schneider, Davey Poelma-Tap, Sonja Stieb, Fritz R. Murray, Lorenzo Placidi, Francesca Albertini, Antony Lomax, Alessandra Bolsi, Ulrike Kliebsch, Robert Malyapa, Damien C. Weber
PurposeTo evaluate the efficacy and safety of high-dose pencil-beam scanning proton therapy (PBS-PT) in the adjuvant treatment of spinal chordomas.Methods and MaterialsBetween 1997 and 2015, 100 patients with spinal chordomas (median age, 56 years; range, 25–81 years) were treated with adjuvant PBS-PT at the XXXX: cervical (n=46), thoracic (n=4), lumbar (n=12), and sacral (n=38). The majority (88%) received PBS-PT alone rather than combined photon–proton therapy. The median radiotherapy dose prescribed was 74 Gy(RBE) (range, 59.4–77 Gy[RBE]). Thirty-nine (39%) patients had undergone surgical stabilization (SS), primarily with titanium hardware, prior to radiotherapy.ResultsWith a median follow-up of 65 months (range, 13–175 months), 5-year local control, disease control, and overall survival rates were 63% (95%CI: 57.7–68.7%; median, 103 months), 57% (95%CI: 50.9-62.1%; median, 82 months), and 81% (95%CI: 76.8-85.6%; median, 157 months), respectively. On univariate and multivariate analyses, the presence of SS was highly prognostic for worsened outcomes. Multivariate analysis also revealed the extent of treatment volumes and presence of gross residual disease to be important in predicting outcomes. High-grade (≥grade 3) toxicities were rare in both the acute (8%) and late (6%) settings.ConclusionFor spinal chordomas, PBS-PT remains a highly effective and safe method for delivery of dose-escalated adjuvant radiotherapy. The presence of metallic SS prognosticates for worsened outcomes. Further investigation is warranted to characterize ideal treatment volumes and effect of SS on therapy for these challenging tumors.



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Effet du port d’un masque de soins lors d’un test de marche de six minutes chez des sujets sains

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): E. Person, C. Lemercier, A. Royer, G. Reychler
IntroductionLe test de marche de six minutes (TM6) est fréquemment utilisé en pneumologie. Certains patients à risque d'infection croisée doivent porter un masque de soins pour se protéger et ce parfois pendant l'effort.But de l'étudeÉvaluer l'effet du port d'un masque de soins sur la distance parcourue lors du TM6 chez des sujets sains.Matériel et méthodeÉtude prospective portant sur 44 sujets sains. Après un TM6 de familiarisation, ils ont réalisé aléatoirement un TM6 avec et sans port d'un masque de soins. La distance et l'évolution de la dyspnée, de la fréquence cardiaque et de la saturation en oxygène ont été mesurées.RésultatsLa distance n'est pas influencée par le port du masque de soins (p=0,99). L'augmentation de la dyspnée est significativement plus élevée lors du port du masque de soins (+5,6 vs +4,6 ; p<0,001) et la différence est cliniquement significative. Par contre, il n'y a pas d'influence sur les autres paramètres.ConclusionLe port du masque de soins ne modifie pas la distance parcourue lors du TM6 mais augmente significativement et cliniquement la dyspnée.IntroductionSix minutes walking test (6MWT) is regularly used in pulmonology. To minimize the risk of cross-infection, some patients must wear surgical mask at rest and sometimes during exercise.Aim of the studyTo evaluate the effect of wearing a surgical mask during 6MWT in healthy subjects.Material and methodIt is a prospective study on 44 healthy subjects. After a first 6MWT for training, they performed randomly two 6MWT: with or without a surgical mask. Distance and dyspnea, heart rate and saturation variations were recorded.ResultsDistance was not modified by the mask (P=0.99). Dyspnea variation was significantly higher with surgical mask (+5.6 vs. +4.6; P<0.001) and the difference was clinically relevant. No difference was found for the variation of other parameters.ConclusionWearing a surgical mask modifies significantly and clinically dyspnea without influencing walked distance.



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Cohorte de patients nouvellement traités par ventilation non invasive à domicile. Étude observationnelle, prospective et multicentrique

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): C. Rabec, J. Gonzalez-Bermejo, A. Cuvelier, P. Cervantes, D. Foret, L. Mounier, B. Melloni, J.-F. Muir
Bien que l'efficacité clinique de la ventilation non invasive (VNI) soit clairement démontrée, aucune étude française récente n'indique les conditions de prescription et d'utilisation de celle-ci selon les pathologies respiratoires. La fédération ANTADIR avec l'appui et en partenariat avec le Groupe assistance ventilatoire de la SPLF, a mis en place une cohorte observationnelle, prospective et multicentrique, d'envergure nationale. L'objectif principal de cette étude est d'analyser les données cliniques justifiant la prescription conventionnelle d'une VNI à domicile chez des patients insuffisants respiratoires chroniques. Les objectifs secondaires seront : d'étudier l'évolution des comorbidités ou leur survenue, les hospitalisations, les échecs de traitement, la survie. La population concernée est celle des insuffisants respiratoires nouvellement mis sous VNI, autant à l'état stable que suite à une exacerbation respiratoire nécessitant la poursuite d'une VNI au long cours. Les données d'inclusion comprendront : diagnostic et comorbidités, données descriptives (âge, indice de masse corporelle, sexe) biologiques (hématocrite, gaz du sang, CO2 total), fonctionnelles (VEMS, CV, CPT), résultats nocturnes (SaO2, PtcCO2), type et paramètres du ventilateur et type de masque. Les données de suivi sont recueillies à 4 mois, 1 an et 2 ans et comporteront : hospitalisations, éventuelles modifications de prescription, observance, éventuel désappareillage ou décès. Ce travail permettra d'obtenir des informations scientifiques nouvelles sur la réalité de la VNI au long cours en France, un des pays européens à l'origine de l'essor de la VNI et où la prévalence des patients sous VNI au long cours a été signalée comme la plus importante du continent européen.Cohort of patients initiated to home ventilation. Observational and prospective study. The effectiveness of home noninvasive ventilation (NIV) for chronic respiratory failure (CRF) is well established. However, few data are available about home NIV prescription and utilization according to the different etiologies of respiratory failure. The ANTADIR Federation, in partnership with the Ventilatory Support Group of the French Speaking Pulmonary Society, has set up a national, observational and multicenter cohort study. The main goal of this study is to analyze the clinical data justifying home NIV prescription in patients with chronic respiratory insufficiency. The secondary objectives will be to assess: the evolution of comorbidities or their occurrence, hospitalizations, NIV compliance, dropout and survival. The population includes patients with chronic respiratory failure newly initiated onto NIV, both in a stable state and following an acute exacerbation who qualify for long-term NIV. Data collected include: diagnosis and comorbidities, age, sex, BMI, biomarkers (hematocrit, arterial blood gases, total CO2) and functional data (FEV1, VC, TLC), nocturnal results (SaO2, PtcCO2), type of ventilator used, ventilator parameters and mask type. Follow-up data will be collected at 4 months, 1 year and 2 years and will include: hospitalizations, changes in prescription, adherence, dropouts and deaths. This work will make it possible to obtain new scientific information on long-term NIV use in France.



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Bactériologie des exacerbations aiguës des bronchopneumopathies chroniques obstructives en Tunisie

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): S. Messous, M.H. Grissa, K. Beltaief, R. Boukef, S. Nouira, M. Mastouri
IntroductionLe rôle des bactéries, y compris les germes atypiques, dans les exacerbations aiguës de la bronchopneumopathie chronique obstructive (EABPCO) en Tunisie a été diversement apprécié.MéthodesÉtude descriptive et analytique incluant des patients d'âge moyen de 68,3±10,5 ans hospitalisés pour EABPCO. L'examen bactériologique comprend un examen cytobactériologique de crachat et une sérologie des germes atypiques incluant Mycoplasma pneumoniae, Coxiella burnetii, Chlamydophila pneumoniae et Legionella pneumophila selon les techniques standard.RésultatsSur les 240 patients inclus, 175 cultures de crachat (73 %) ont été considérées comme significatives. Vingt-neuf cultures étaient positives (16,5 %) et 31 germes ont été isolés dont les plus fréquents étaient P. aeruginosa (25,8 %), K. pneumoniae (16,2 %), H. influenzae (13 %) et S. pneumoniae (9,7 %). La prévalence de l'infection à C. pneumoniae, M. pneumoniae et C. burnetii était respectivement de 8,4 %, 9 % et 6,6 %. Aucune infection à L. pneumophila n'a été retrouvée. Les critères d'Anthonisen étaient associés à une culture positive (p=0,04). Près de la moitié (40,9 %) des souches isolées étaient résistantes aux antibiotiques classiques de première intention (43,7 % pour amoxicilline-acide clavulanique).ConclusionsLa faible positivité de la bactériologie quantitative des crachats et l'important pourcentage des souches résistantes avec une prédominance des Pseudomonas exclusivement multirésistantes peuvent aider dans la prise en charge des patients en EABPCO.IntroductionThe role of bacteria, including atypical organisms, in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) has been assessed in various ways in Tunisia.MethodsThis was a descriptive and analytical study of patients with a mean age of 68.3±10.5 years hospitalized for AECOPD. Bacteriological examination included a cytological sputum exam and serology for atypical organisms including Mycoplasma pneumoniae, Coxiella burnetii, Chlamydophila pneumoniae and Legionella pneumophila using standard techniques.ResultsOf the 240 patients enrolled, 175 sputum cultures (73%) were considered significant. Twenty-nine cultures were positive (16.5%) and 31 microorganisms were isolated of which the most frequent were P. aeruginosa (25.8%), K. pneumoniae (16.2%), H. influenzae (13%) and S. pneumoniae (9.7%). The prevalence of C. pneumoniae, M. pneumoniae and C. burnetii was 8.4%, 9% and 6.6%, respectively. No L. pneumophila infection was found. The Anthonisen criteria were associated with a positive culture (P=0.04). Almost half (40.9%) of the isolates were resistant to conventional first line antibiotics (43.7% to amoxicillin-clavulanic acid).ConclusionsAwareness of the low positivity of quantitative sputum bacteriology and the large percentage of resistant strains with a predominance of exclusively multi-resistant Pseudomonas should help in the management of patients with AECOPD.



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Échobronchoscopie avec ponction transbronchique à l’aiguille : évaluation des pratiques

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): D. Basille, C. Hybiak, C. Dayen, B. Toublanc, Y. Douadi, G. Francois, I. Rault, C. Andrejak, P. Berna, V. Jounieaux
IntroductionL'échobronchoscopie linéaire avec ponction transbronchique à l'aiguille (EB-PTBA) connaît un développement considérable en France depuis 2007. L'objectif est d'évaluer l'évolution des différentes indications d'EB-PTBA entre 2008 et 2013 en Picardie.Matériels et méthodesNous avons mené une étude observationnelle rétrospective incluant les patients ayant bénéficié d'une EB-PTBA entre 2008 et 2013 en Picardie. L'évolution de la part respective de chaque indication d'EB-PTBA a été relevée.RésultatsSur la période considérée, 1036 examens ont été réalisés avec une augmentation constante du nombre d'EB-PTBA (86 en 2008 versus 275 en 2013). Nous avons observé une augmentation de la proportion d'EB-PTBA pour suspicion de sarcoïdose (OR=1,31 ; IC 95 % [1,09–1,58] ; p=0,005) ainsi que pour le diagnostic et la stadification simultanée d'un cancer bronchopulmonaire (OR=1,12 ; IC 95 % [1,02–1,24] ; p=0,022). Dans le cadre de la sarcoïdose, nous avons observé une augmentation du rendement diagnostique entre les périodes [2008–2010] et [2011–2013] (42,9 % versus 72,5 %).ConclusionUne augmentation constante du nombre d'échobronchoscopies a été observée durant la période 2008–2013. Cette augmentation s'associe à une modification des pratiques avec une augmentation de la proportion d'examens réalisés pour le diagnostic de sarcoïdose.IntroductionEndobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) has undergone a large increase in France since 2007. The aim is to study the evolution of the indications for EBUS-TBNA in our region during the period 2008–2013.Material and methodsWe conducted a retrospective observational study including all the patients who underwent an EBUS-TBNA procedure in Picardie from 2008 to 2013. The respective proportion for each indication was noted.ResultsDuring the study period, 1036 EBUS-TBNA procedures were performed with a continuous increase in number (86 in 2008 versus 275 in 2013). We observed an increase in the proportion of procedures performed for a suspected diagnosis of sarcoidosis (OR=1.31; IC 95% [1.09–1.58]; P=0.005) and for the simultaneous diagnosis and staging of lung cancer (OR=1.12; IC 95% [1.02–1.24]; P=0.022). For the diagnosis of sarcoidosis, we observed an improvement in the diagnostic yield between the periods [2008–2010] and [2011–2013] (42.9% versus 72.5%).ConclusionA continuous increase in the number of EBUS-TBNA procedures was observed during the period 2008–2013. It was associated with a modification in practice with an increased proportion of procedures performed for the diagnosis of sarcoidosis.



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Les inhibiteurs des freins immunitaires (anticorps anti-PD1 et anti-PD-L1), une nouvelle arme thérapeutique dans les cancers bronchiques non à petites cellules

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): T. Berghmans, B. Grigoriu, J.P. Sculier, A.P. Meert
IntroductionLa prise en charge classique des cancers bronchiques non à petites cellules de stade avancé ou métastatique reposait essentiellement sur la chimiothérapie cytotoxique pour les tumeurs sans mutation oncogénique ciblable avec des résultats modestes en termes de gain de survie.État des connaissancesLa compréhension de mécanismes impliqués dans le contrôle du système immunitaire a abouti au développement d'anticorps dirigés contre certains points de contrôle comme PD-L1. Les premiers résultats cliniques encourageants des anticorps monoclonaux dirigés contre PD1 ou PD-L1 objectivés en étude de phase I ont été confirmés dans plusieurs études randomisées de phase III.ConclusionCes nouveaux médicaments constituent maintenant un standard thérapeutique en seconde ligne métastatique et à l'avenir, à tout le moins pour le pembrolizumab, en 1^re ligne. Leur intérêt en adjuvant après un traitement locorégional à visée curative est en cours d'investigation.IntroductionClassical therapeutic strategy for advanced and metastatic non-small cell lung cancer, without activable oncogenic driver mutation, has been based mainly on cytotoxic chemotherapy with modest benefits in terms of increased survival.BackgroundA better understanding of the mechanisms involved in the regulation of the immune system led to the development of antibodies directed against immune checkpoints such as PD-L1. The first encouraging clinical data from phase I studies assessing anti-PD1 and anti-PD-L1 antibodies have been confirmed in randomised phase III trials.ConclusionsThese new drugs now constitute a standard second-line treatment for metastatic tumours and in the future, at least for pembrolizumab, in the first line. Their adjuvant role after locoregional treatment with curative intent is currently under investigation.



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Trachéotomie en réanimation : évaluation des pratiques professionnelles et devenir des patients

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): L. Martinez, J. Demanet, V. Mignaux, F. Dewavrin
IntroductionLe recours à la trachéotomie est fréquent. L'objectif de ce travail est de réaliser une évaluation des pratiques professionnelles, de décrire la population et d'étudier son devenir.MéthodesChaque patient présentant le code CCAM GEPA004 était rétrospectivement inclus.Résultats214 (7 %) patients sous ventilation mécanique invasive étaient trachéotomisés avec un délai médian de 22 (14–28) jours. 95,3 % des trachéotomies étaient chirurgicales. L'âge médian était de 58 (48–67) ans. 83 (38,8 %) trachéotomies étaient réalisées pour indication respiratoire. Le taux de mortalité à 28jours, 90jours et 1 an était respectivement de 4,2 %, 35,5 % et 52,4 %. Les patients trachéotomisés pour cause respiratoire avaient un taux de mortalité plus important. La mortalité en post-réanimation était de 29,8 % et était significativement plus élevée parmi les patients sortis de réanimation canulés. Les caractéristiques, les délais, les modalités de réalisation, l'indication et l'évolution des patients étaient stables au cours des six dernières années.ConclusionLes patients trachéotomisés étaient des patients jeunes principalement trachéotomisés pour sevrage ventilatoire. Plus de la moitié des patients trachéotomisés décédaient à 1 an avec une mortalité plus importante parmi les patients sortant de réanimation canulés.IntroductionTracheostomy is a commonly performed procedure. The aim of this study was to assess professional practice, describe patient characteristics and examine short and long-term outcomes.MethodsAll patients with CCAM GEPA004 code were retrospectively included.ResultsTwo hundred and fourteen (7%) patients who were mecanically ventilated had a tracheostomy performed in intensive care unit (ICU). Median time to tracheostomy was 22 (14–28) days. In total, 95.3% of tracheostomy procedures were surgical. Median age was 58 (48–67) years. Eighty-three (38.8%) tracheostomies were performed for respiratory reasons. Twenty-eight-day and 90-day mortality were 4.2% and 35.5%. One-year mortality was 52.4%. Patients with tracheostomies performed for weaning from mechanical ventilation had a higher mortality rate. After ICU discharge, mortality rate was 29.8% and was higher in non-decannulated patients. Patient characteristics, timing, technique, indication and outcomes were stable over the years.ConclusionYoung patients weaning from mechanical ventilation were more likely to receive a tracheostomy. More than half died during the first year. Patients discharged from ICU with a tracheostomy tube in place had higher mortality rate.



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La bronchoscopie rigide

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): A. Briault, H. Dutau




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Dyskinésie des cordes vocales et/ou asthme

Publication date: Available online 1 February 2018
Source:Revue des Maladies Respiratoires
Author(s): J.J. Braun, C. Delmas, A. Charloux, P. Schultz, F. de Blay
IntroductionLa dyskinésie des cordes vocales ou dysfonctionnement des cordes vocales (DCV) est caractérisée par une adduction paradoxale intermittente des cordes vocales à l'origine d'une obstruction fonctionnelle de la glotte, sans atteinte laryngée organique. Elle peut être isolée ou associée à un asthme. Sa physiopathologie complexe demeure mal connue et le diagnostic reste difficile.MéthodesÉtude rétrospective de 15 cas de DCV (8 cas de DCV isolée et 7 cas de DCV avec asthme associé) avec analyse de la symptomatologie clinique et de la méthodologie diagnostique.RésultatsLa symptomatologie associe de façon variable dyspnée laryngée avec stridor, sifflements laryngés, tirage et d'autres signes plus atypiques avec parfois perte de connaissance ou dyspnée aiguë nécessitant intubation, ventilation mécanique voire trachéotomie. Le gold standard diagnostique est l'examen ORL laryngé, tant pour le diagnostic différentiel que pour la mise en évidence de l'adduction paradoxale des cordes vocales lors de l'épisode aigu ou lors d'un test de provocation par exposition aux facteurs déclenchants habituels.ConclusionsLe diagnostic de DCV reste difficile et probablement sous-évalué. Il concerne les médecins urgentistes, les pneumologues et les ORL pour un diagnostic précoce limitant la morbidité et le coût liés aux traitements inutiles et à l'errance diagnostique fréquente.IntroductionVocal cord dyskinesia or vocal cord dysfunction (VCD) is characterized by intermittent abnormal adduction of the vocal cords leading to airflow limitation at the level of the larynx, in the absence of local organic disease. It may occur in isolation or in association with asthma. The pathophysiology is complex and poorly understood. Wheeze, stridor or apparent upper airway obstruction are the most common symptoms. It occurs in a wide age range, more commonly in women, and diagnosis is often delayed and leads to unnecessary treatments (intubation, tracheostomy and high dose steroids).MethodsA retrospective study of 15 cases of VCD (8 cases of isolated VCD and 7 cases of VCD with associated asthma) describing the main clinical features and the diagnosis strategy.ResultsApparent upper airway obstruction, with or without associated asthma, requires an ear nose and throat examination with laryngoscopy to confirm the paradoxical adduction of the vocal cords during an acute episode of dyspnoea or during a provocation test with triggers like exercise or exposure to irritants, and for the purpose of differential diagnosis.ConclusionsVCD remains under-appreciated and misdiagnosed, often by mimicking asthma with which it can be associated. A delayed diagnosis by emergency specialists, pulmonologists and ear nose and throat surgeons leads to unnecessary treatments and morbidity before specific therapy can be given.



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