Exhibition of stochastic resonance in vestibular tilt motion perception

Publication date: Available online 3 April 2018
Source:Brain Stimulation
Author(s): R.C. Galvan-Garza, T.K. Clark, A.P. Mulavara, C.M. Oman
BackgroundStochastic Resonance (SR) is a phenomenon broadly described as "noise benefit". The application of subsensory electrical Stochastic Vestibular Stimulation (SVS) via electrodes behind each ear has been used to improve human balance and gait, but its effect on motion perception thresholds has not been examined.ObjectiveThis study investigated the capability of subsensory SVS to reduce vestibular motion perception thresholds in a manner consistent with a characteristic bell-shaped SR curve.MethodsWe measured upright, head-centered, roll tilt Direction Recognition (DR) thresholds in the dark in 12 human subjects with the application of wideband 0–30 Hz SVS ranging from ±0–700 μA. To conservatively assess if SR was exhibited, we compared the proportions of both subjective and statistical SR exhibition in our experimental data to proportions of SR exhibition in multiple simulation cases with varying underlying SR behavior. Analysis included individual and group statistics.ResultsAs there is not an established mathematical definition, three humans subjectively judged that SR was exhibited in 78% of subjects. "Statistically significant SR exhibition", which additionally required that a subject's DR threshold with SVS be significantly lower than baseline (no SVS), was present in 50% of subjects. Both percentages were higher than simulations suggested could occur simply by chance. For SR exhibitors, defined by subjective or statistically significant criteria, the mean DR threshold improved by −30% and −39%, respectively. The largest individual improvement was −47%.ConclusionAt least half of the subjects were better able to perceive passive body motion with the application of subsensory SVS. This study presents the first conclusive demonstration of SR in vestibular motion perception.



https://ift.tt/2GVxSLZ

Characteristics and sources of nitrous acid in an urban atmosphere of northern China: Results from 1-yr continuous observations

Publication date: June 2018
Source:Atmospheric Environment, Volume 182
Author(s): Dandan Li, Likun Xue, Liang Wen, Xinfeng Wang, Tianshu Chen, Abdelwahid Mellouki, Jianmin Chen, Wenxing Wang
Nitrous acid (HONO) is a key reservoir of the hydroxyl radical (OH) and plays a central role in the atmospheric chemistry. To understand the sources and impact of HONO in the polluted atmosphere of northern China, continuous measurements of HONO and related parameters were conducted from September 2015 to August 2016 at an urban site in Ji'nan, the capital city of Shandong province. HONO showed well-defined seasonal and diurnal variation patterns with clear wintertime and nighttime concentration peaks. Elevated HONO concentrations (e.g., over 5 ppbv) were frequently observed with a maximum value of 8.36 ppbv. The HONO/NOX ratios of direct vehicle emissions varied in the range of 0.29%–0.87%, with a mean value of 0.53%. An average NO2-to-HONO nighttime conversion frequency (khet) was derived to be 0.0068 ± 0.0045 h⁻¹ from 107 HONO formation cases. A detailed HONO budget analysis suggests an unexplained daytime missing source of 2.95 ppb h⁻¹ in summer, which is about seven times larger than the homogeneous reaction of NO with OH. The effect of HONO on OH production was also quantified. HONO photolysis was the uppermost source of local OH radical throughout the daytime. This study provides the year-round continuous record of ambient HONO in the North China Plain, and offers some insights into the characteristics, sources and impacts of HONO in the polluted atmospheres of China.



https://ift.tt/2GAfqoZ

Lower expression of bone marrow miR-122 is an independent risk factor for overall survival in cytogenetically normal acute myeloid leukemia

Publication date: Available online 3 April 2018
Source:Pathology - Research and Practice
Author(s): Ting-juan Zhang, Zhen Qian, Xiang-mei Wen, Jing-dong Zhou, Xi-xi Li, Zi-jun Xu, Ji-chun Ma, Zhi-hui Zhang, Jiang Lin, Jun Qian
BackgroundThe liver-enriched microRNA-122 (miR-122) plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) with prognostic value. Recently, miR-122 was also found to be related to many other cancers besides HCC. However, less study determined miR-122 expression and its clinical significance in acute myeloid leukemia (AML).MethodsReal-time quantitative PCR was performed to detect the level of bone marrow (BM) miR-122 in de novo AML patients. The clinical significance of miR-122 expression in AML was further investigated.ResultsAmong whole-cohort AML, lower expression of BM miR-122 was associated with male patients, higher hemoglobin and favorable-karyotypes (P = 0.038, 0.006, and 0.038, respectively). Among cytogenetically normal AML (CN-AML), lower expression of BM miR-122 was correlated with DNMT3A wild type (P = 0.043). Moreover, patients with lower expression of BM miR-122 presented lower complete remission (CR) rate and shorter overall survival (OS) than those with higher expression of BM miR-122 in CN-AML (P = 0.025 and 0.013, respectively). Cox regression analyses further confirmed the prognostic value of BM miR-122 expression in CN-AML (P = 0.024). In follow-up patients, BM miR-122 expression level in CR time was increased compared to diagnosis time, and was returned to primary level when in relapse time again (P = 0.062 and 0.049, respectively).ConclusionsOur findings indicated that lower expression of BM miR-122 acted as an independent risk factor for OS in CN-AML.



https://ift.tt/2GUVwZ8

Histopathology of Locally Advanced Colorectal Carcinoma, With Emphasis on Tumor Invasion of Adherent Peritoneal Membranes

Publication date: Available online 3 April 2018
Source:Pathology - Research and Practice
Author(s): Jey-Hsin Chen
Locally advanced colorectal carcinomas are characterized by neoplastic cells that invade beyond the colon and directly into surrounding organs and structures that include the retroperitoneum and abdominopelvic sidewall. These aggressive tumors are prognostically adverse and are categorized with highest possible tumor stage in current cancer staging systems. Recognizing colorectal carcinoma with extensive locoregional invasion is typically straightforward, but some cases can be diagnostically challenging. These include tumors with limited invasion of extracolonic tissue such as the subserosa in which there are no cells or structures that are histologically or architecturally distinct from the colonic primary. Tumor-associated injury of the colonic peritoneum often precedes invasion by the neoplastic cells and can cause the peritoneal membrane of the colon to adhere and subsequently fuse to the peritoneal membrane of a neighboring organ or structure, thereby creating a trans-peritoneal bridge through which a tumor can directly invade the adherent extracolonic tissue. Hence, locally advanced colorectal carcinoma can be narrowly defined by neoplastic cells that completely invade through the fused peritoneal membrane and into the subserosa of the adherent extracolonic tissue. The evaluation of tumor invasion of the fused peritoneal membrane, which is enhanced by the combined use of an elastic stain and an immunostain for pan-keratin, is essential for the proper staging of locally advanced colorectal carcinoma and its clinical management.



https://ift.tt/2GznDd1

Editorial Board

Publication date: April 2018
Source:Pathology - Research and Practice, Volume 214, Issue 4





https://ift.tt/2GMr5nZ

Peroxiredoxin 1 promoted tumor metastasis and angiogenesis in colorectal cancer

Publication date: Available online 3 April 2018
Source:Pathology - Research and Practice
Author(s): Huan-Xi Li, Xiang-Yu Sun, Shi-Ming Yang, Qing Wang, Zhen-Yu Wang
Peroxiredoxin1 (Prdx1) is a member of the PrdxS family, and it regulates cellular signaling and differentiation. The role of Prdx1in colorectal cancer (CRC) remains unclear. In this study, we investigated the relevance of Prdx1 in the metastasis and angiogenesis of CRC. The expression of Prdx1 in 60 cases human CRC tissues was detected through immunohistochemistry. The tumors that highly expressed Prdx1 (42/60) exhibited higher tumor grade and lymph node metastasis than those with low expression of Prdx1 (18/60) (p < 0.05). Kaplan–Meier survival analysis showed that the survival time of thePrdx1-positive group was shorter than that of thePrdx1-negative group (p = 0.046).Moreover, a statistically significant correlation was observed between the Prdx1 expression and microvessel density (p = 0.004). Transwell migration assay revealed that Prdx1 was down-regulated in the CRC cell line HCT116, thereby suppressing the invasion and migration capacities of tumor cells, whereas Prdx1was up-regulated in HT29 cells, thereby increasing the invasion and migration capacities of tumor cells. The tube formation capacity of human umbilical vein endothelial cells cultured in 3D medium was increased after conditioned medium from overexpressed Prdx1cancer cells was added relative to that when down-regulated Prdx1 cell medium was added(p < 0.05). In addition, up-regulated Prdx1 increased the protein expression of MMP2, MMP9, and VEGFA. These data suggested that Prdx1 expression predicted poor prognosis by regulating the tumor metastasis and angiogenesis of CRC. Therefore, Prdx1 may serve as a potential therapeutic target.



https://ift.tt/2GAX72R

Green synthesis of carbon dots functionalized silver nanoparticles for the colorimetric detection of phoxim

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Mingda Zheng, Chenge Wang, Yingying Wang, Wei Wei, Shuang Ma, Xiaohan Sun, Jiang He
In this work, Lycii Fructus as raw materials for green synthesis of fluorescent carbon dots (CDs) reduce AgNO3. The CDs-AgNPs were synthesized by one-step method. CDs were applied to stabilize AgNPs due to abundant functional groups on the surface of CDs. In presence of phoxim, the dispersed CDs-AgNPs get aggregated and the absorption peak with red shift from 400 nm to 525 nm, resulting in the color changed from yellow to red. Under optimized conditions, the absorbance ratio at A525 nm/A400 nm was related linearly to the concentrations of phoxim in the range of 0.1–100 μM. The detection limit was calculated to 0.04 μM, which is lower than maximum residue limits of phoxim in samples in China. The colorimetric sensor was successfully utilized to monitoring phoxim in environmental and fruit samples with good recoveries ranges from 87% to 110.0%. These results showed the sensor had a promising application prospect in real samples.



https://ift.tt/2uNalbn

Specific detection of stable single nucleobase mismatch using SU-8 coated silicon nanowires platform

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Melania Banu, Monica Simion, Marian C. Popescu, Pericle Varasteanu, Mihaela Kusko, Ileana C. Farcasanu
Novel microarray platform for single nucleotide polymorphisms (SNPs) detection has been developed using silicon nanowires (SiNWs) as support and two different surface modification methods for attaining the necessary functional groups. Accordingly, we compared the detection specificity and stability over time of the probes printed on SiNWs modified with (3-aminopropyl)triethoxysilane (APTES) and glutaraldehyde (GAD), or coated with a simpler procedure using epoxy-based SU-8 photoresist.Scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) were used for comparative characterization of the unmodified and coated SiNWs. The hybridization efficiency was assessed by comprehensive statistical analysis of the acquired data from confocal fluorescence scanning of the manufactured biochips.The high detection specificity between the hybridized probes containing different mismatch types was demonstrated on SU-8 coating by one way ANOVA test (adjusted p value *** < .0001). The stability over time of the probes tethered on SiNWs coated with SU-8 was evaluated after 1, 4, 8 and 21 days of probe incubation, revealing values for coefficient of variation (CV) between 2.4% and 5.6%. The signal-to-both-standard-deviations ratio measured for SU-8 coated SiNWs platform was similar to the commercial support, while the APTES-GAD coated SiNWs exhibited the highest values.

Graphical abstract

https://ift.tt/2q3ivY7

Stability of proton-bound clusters of alkyl alcohols, aldehydes and ketones in Ion Mobility Spectrometry

Publication date: 1 August 2018
Source:Talanta, Volume 185
Author(s): Natividad Jurado-Campos, Rocío Garrido-Delgado, Bruno Martínez-Haya, Gary A. Eiceman, Lourdes Arce
Significant substances in emerging applications of ion mobility spectrometry such as breath analysis for clinical diagnostics and headspace analysis for food purity include low molar mass alcohols, ketones, aldehydes and esters which produce mobility spectra containing protonated monomers and proton-bound dimers. Spectra for all n- alcohols, aldehydes and ketones from carbon number three to eight exhibited protonated monomers and proton-bound dimers with ion drift times of 6.5–13.3 ms at ambient pressure and from 35° to 80 °C in nitrogen. Only n-alcohols from 1-pentanol to 1-octanol produced proton-bound trimers which were sufficiently stable to be observed at these temperatures and drift times of 12.8–16.3 ms. Polar functional groups were protected in compact structures in ab initio models for proton-bound dimers of alcohols, ketones and aldehydes. Only alcohols formed a V-shaped arrangement for proton-bound trimers strengthening ion stability and lifetime. In contrast, models for proton-bound trimers of aldehydes and ketones showed association of the third neutral through weak, non-specific, long-range interactions consistent with ion dissociation in the ion mobility drift tube before arriving at the detector. Collision cross sections derived from reduced mobility coefficients in nitrogen gas atmosphere support the predicted ion structures and approximate degrees of hydration.

Graphical abstract

https://ift.tt/2uJ7f89

High dose rate brachytherapy for prostate cancer: A prospective toxicity evaluation of a one day schedule including two 13.5 Gy fractions

Publication date: Available online 3 April 2018
Source:Radiotherapy and Oncology
Author(s): Gorka Nagore, Jose Luis Lopez Guerra, Evita Krumina, Mark Lagos, Beatriz Ovalles, Antonio Miró, Lourdes Beltran, Emilia Gómez, Juan Manuel Praena-Fernandez, Eleonor Rivin del Campo, Ignacio Azinovic, Alfonso Gomez-Iturriaga
Background and purposeHigh dose-rate (HDR) brachytherapy (BT) provides a highly conformal method of dose delivery to the prostate. The purpose of this study is to prospectively determine the toxicity of the treatment protocol of 13.5 Gy × 2 fractions.Materials and methodsFrom 2010 through 2017, 119 patients with low (71%) or intermediate-risk prostate cancer were prospectively treated in a single institute with HDR-BT at 13.5 Gy × 2 fractions within one day. Median follow-up time was 4.4 years.ResultsActuarial rates of no biochemical evidence of disease, overall survival and metastasis-free survival for all patients were 96%,98% and 98%, respectively. The cumulative incidence of acute grade 2 and 3 genitourinary (GU) toxicity was 9% and 2%, respectively. The corresponding incidences of late GU toxicity were 18% and 1%. No grade ≥4 of either type of toxicity was detected. Multivariate analysis showed that having higher international prostate symptom score (IPSS; P = 0.041) or higher V200 (P = 0.013) was associated with a higher risk of experiencing any grade of acute GU toxicity. In addition, patients having a higher IPSS (P = 0.019) or a higher V150 (P = 0.033) were associated with a higher grade >1 acute GU toxicity.ConclusionsThe findings of this study show that HDR-BT 13.5 Gy × 2 as monotherapy was safe and effective for prostate cancer patients with low-intermediate risk.



https://ift.tt/2JiDGxl

ENLIGHT: European network for Light ion hadron therapy

Publication date: Available online 3 April 2018
Source:Radiotherapy and Oncology
Author(s): Manjit Dosanjh, Ugo Amaldi, Ramona Mayer, Richard Poetter
The European Network for Light Ion Hadron Therapy (ENLIGHT) was established in 2002 following various European particle therapy network initiatives during the 1980s and 1990s (e.g. EORTC task group, EULIMA/PIMMS accelerator design). ENLIGHT started its work on major topics related to hadron therapy (HT), such as patient selection, clinical trials, technology, radiobiology, imaging and health economics. It was initiated through CERN and ESTRO and dealt with various disciplines such as (medical) physics and engineering, radiation biology and radiation oncology. ENLIGHT was funded until 2005 through the EC FP5 programme. A regular annual meeting structure was started in 2002 and continues until today bringing together the various disciplines and projects and institutions in the field of HT at different European places for regular exchange of information on best practices and research and development. Starting in 2006 ENLIGHT coordination was continued through CERN in collaboration with ESTRO and other partners involved in HT. Major projects within the EC FP7 programme (2008–2014) were launched for R&D and transnational access (ULICE, ENVISION) and education and training networks (Marie Curie ITNs: PARTNER, ENTERVISION). These projects were instrumental for the strengthening of the field of hadron therapy.With the start of 4 European carbon ion and proton centres and the upcoming numerous European proton therapy centres, the future scope of ENLIGHT will focus on strengthening current and developing European particle therapy research, multidisciplinary education and training and general R&D in technology and biology with annual meetings and a continuously strong CERN support. Collaboration with the European Particle Therapy Network (EPTN) and other similar networks will be pursued.



https://ift.tt/2q4VZNL

PROGRAD – An observational study of the prognosis of inpatients evaluated for palliative radiotherapy

Publication date: Available online 3 April 2018
Source:Radiotherapy and Oncology
Author(s): Andre Tsin Chih Chen, Geovanne Pedro Mauro, Flavia Gabrielli, Cristiane de Lacerda Gonçalves Chaves, Igor Castro, Karina Moutinho Vasconcelos, Milena Reis, Thalita Saraiva, Heloisa Andrade de Carvalho
Background and purposeLow-and-middle-income countries have resource constraints and waiting lists for radiotherapy (RT). In this context, we sought to determine the survival of inpatients evaluated for palliative RT in a large referral cancer center in Brazil.Material and methodsFrom November 2014 through December 2015, we enrolled 333 inpatients with palliative RT evaluation requests in this prospective observational study. We applied Palliative Prognostic Index (PPI) and Survival Prediction Score using Number of Risk Factors (NRF). Primary endpoint was overall survival. Secondary endpoints were survival by PPI and NRF. (ClinicalTrials.gov number, NCT02312791).ResultsMedian survival (MS) for the entire cohort was 73 days. PPI ≤2 had MS of 120 days; PPI 2.5–4 had MS of 55 days (HR 1.84; 95% CI, 1.07–3.16); PPI >4 had MS of 39 days (HR 3.45; 95% CI, 2.07–5.74) (p < .0001). NRF 0–1 had MS of 129 days; NRF 2 had MS of 73 days (HR 1.74; 95% CI 0.89–3.38); NRF 3 had MS of 40 days (HR 2.95; 95% CI, 1.50–5.78) (p < .0001).ConclusionInpatients with palliative RT requests seem to have an overall poor survival. PPI and NRF can define subgroups with different prognosis. This could help hospitals and healthcare systems to standardize criteria for prioritization and contribute for fairness.



https://ift.tt/2q2IU7G

Survey data from 38 integrated crop-livestock farming systems in Western France

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Matthieu Carof, Olivier Godinot
This paper presents data collected from 38 integrated crop-livestock farming systems in Ille-et-Vilaine, Brittany, France, during face-to-face surveys. Surveys were conducted using a quantitative questionnaire to collect information about farm management practices that affect nitrogen (N) inputs, N outputs, and internal N flows. The data were used to develop new indicators of N efficiency (SyNE, System N Efficiency) and of N balance (SyNB, System N Balance), as described in "SyNE: An improved indicator to assess nitrogen efficiency of farming systems" [1]. Also, the data were used to test an online tool developed to calculate these indicators, as described in "A free online tool to calculate three nitrogen-related indicators for farming systems" [2]. The data are provided with this article.



https://ift.tt/2GzDDPW

Effect of traditional plants in Sri Lanka on skin keratinocyte count

Publication date: June 2018
Source:Data in Brief, Volume 18
Author(s): Katsura Sano, Takao Someya, Kotaro Hara, Yoshimasa Sagane, Toshihiro Watanabe, R.G.S. Wijesekara
This article describes the effects of extracts of several plants collected in Sri Lanka on the number of human skin keratinocytes. This study especially focuses on the plants traditionally used in indigenous systems of medicine in Sri Lanka, such as Ayurveda, as described below (English name, "local name in Sri Lanka," scientific name). Neem plant,"kohomba," Azadirachta indica (Sujarwo et al., 2016; Nature's Beauty Creations Ltd., 2014) [1,2], emblic myrobalan plant, "nelli," Phyllanthus emblica (Singh et al., 2011; Nature's Beauty Creations Ltd., 2014) [3,4], malabar nut plant, "adhatoda," Justicia adhatoda (Claeson et al., 2000; Nature's Beauty Creations Ltd., 2014) [5,6], holy basil plant, "maduruthala," Ocimum tenuiflorum ( Cohen et al., 2014; Nature's Beauty Creations Ltd., 2014) [7,8]. The expression profiles are provided as line graphs.



https://ift.tt/2uJgkOm

MNE Scan: Software for Real-Time Processing of Electrophysiological Data

Publication date: Available online 3 April 2018
Source:Journal of Neuroscience Methods
Author(s): Lorenz Esch, Limin Sun, Viktor Klüber, Seok Lew, Daniel Baumgarten, P. Ellen Grant, Yoshio Okada, Jens Haueisen, Matti S Hämäläinen, Christoph Dinh
BackgroundMagnetoencephalography (MEG) and Electroencephalography (EEG) are noninvasive techniques to study the electrophysiological activity of the human brain. Thus, they are well suited for real-time monitoring and analysis of neuronal activity. Real-time MEG/EEG data processing allows adjustment of the stimuli to the subject's responses for optimizing the acquired information especially by providing dynamically changing displays to enable neurofeedback.New MethodWe introduce MNE Scan, an acquisition and real-time analysis software based on the multipurpose software library MNE-CPP. MNE Scan allows the development and application of acquisition and novel real-time processing methods in both research and clinical studies. The MNE Scan development follows a strict software engineering process to enable approvals required for clinical software.ResultsWe tested the performance of MNE Scan in several device-independent use cases, including, a clinical epilepsy study, real-time source estimation, and Brain Computer Interface (BCI) application.Comparison with Existing Method(s)Compared to existing tools we propose a modular software considering clinical software requirements expected by certification authorities. At the same time the software is extendable and freely accessible.ConclusionWe conclude that MNE Scan is the first step in creating a device-independent open-source software to facilitate the transition from basic neuroscience research to both applied sciences and clinical applications.



https://ift.tt/2GyhHAN

The role of the water footprint in the context of green marketing

Abstract

The environmental degradation, because of various factors, such as climate change, human activities, increase of population globally, etc. have brought on pressures on the fresh water supplies that vary on time and space. Consequently, economic, environmental, and social tools have emerged known as footprints, in an effort to examine and measure the needs and consequences of humanity on the Earth's life support systems and take measures towards sustainable development. Furthermore, the constantly worsening environmental conditions have resulted in the cultivation of a green culture among society stakeholders that brought on terms such as green marketing and green products. This paper deals with the water footprint (WF) concept and an effort is performed, to explore through a literature review, in which ways it can contribute to the sustainable development of water use, in the context of green marketing (GM) strategies. The approach of the analysis is based on the discrimination to the following aspects: international scale, national and subnational scale, farmers, business, and consumers, in order to track the affection of each part in water issues. The main findings of the literature review showed that the aforementioned factors are playing a key role in protecting water recourses, by the way they formulate their water use and they are interrelated and interdependent. WFs can be useful in the context of GM, by providing helpful information about direct and indirect water consumption, to every contributor factor in supply chains, to consumers, governments, and water managers.

https://ift.tt/2GWoeIS

The rolling stones: an inappropriate surrogate for upper-abdominal image-guided radiotherapy

Publication date: Available online 3 April 2018
Source:Practical Radiation Oncology
Author(s): Jasmine Chen, Louise Murray, Laura A. Dawson, Michael Velec




https://ift.tt/2GT4yG0

Radiation retinopathy after external-beam irradiation for nasopharyngeal carcinoma: a case report and review of the literature.

Publication date: Available online 3 April 2018
Source:Practical Radiation Oncology
Author(s): Pritam Bawankar, Manabjyoti Barman, Harsha Bhattacharjee, Ronel Soibam, Vivek Paulbuddhe




https://ift.tt/2IqAheK

Contents

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3





https://ift.tt/2GztToQ

CME Accreditation Page

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3





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Imaging of Lung Cancer: Update on Staging and Therapy

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Jeremy J. Erasmus, Mylene T. Truong




https://ift.tt/2uPg4gQ

Imaging of Lung Cancer: Update on Screening, Staging, and Therapy

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Jeremy J. Erasmus, Mylene T. Truong




https://ift.tt/2Gw6Jjv

Pulmonary Nodule Management in Lung Cancer Screening

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Myrna C.B. Godoy, Erika G.L.C. Odisio, Mylene T. Truong, Patricia M. de Groot, Girish S. Shroff, Jeremy J. Erasmus

Teaser

The number of screening-detected lung nodules is expected to increase as low-dose computed tomography screening is implemented nationally. Standardized guidelines for image acquisition, interpretation, and screen-detected nodule workup are essential to ensure a high standard of medical care and that lung cancer screening is implemented safely and cost effectively. In this article, we review the current guidelines for pulmonary nodule management in the lung cancer screening setting.


https://ift.tt/2q1BQYQ

Tumor Staging of Lung Cancer

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Constantine A. Raptis, Caroline L. Robb, Sanjeev Bhalla

Teaser

Several important modifications have been proposed for the tumor (T) descriptor for lung cancers. New size cutoffs have been determined and there are new T descriptors for adenocarcinoma in situ, minimally invasive adenocarcinoma, and part-solid adenocarcinomas with a solid component > 0.5 cm to 3 cm (T1a, T1b, T1c). There are also recommendations for multifocal adenocarcinoma, which are classified by the lesion with the highest level T descriptor, and the number of lesions is indicated. Knowledge of these changes is important in the appropriate clinical staging of patients with lung cancer.


https://ift.tt/2Guhvq9

Staging Lung Cancer

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Ahmed H. El-Sherief, Charles T. Lau, Brett W. Carter, Carol C. Wu

Teaser

This article reviews regional lymph node assessment in lung cancer. In the absence of a distant metastasis, the absence or location of lung cancer spread to a regional mediastinal lymph node affects treatment options and prognosis. Regional lymph node maps have been created to standardize assessment of the N descriptor. The International Association for the Study of Lung Cancer lymph node map is used for the standardization of N descriptor assessment. CT, PET/CT with fluorodeoxyglucose, endobronchial ultrasound–guided and/or esophageal ultrasound–guided biopsy, and mediastinoscopy are common modalities used to determine the N descriptor.


https://ift.tt/2q1BGAI

Lung Cancer

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Marcelo F. Benveniste, James Welsh, Chitra Viswanathan, Girish S. Shroff, Sonia L. Betancourt Cuellar, Brett W. Carter, Edith M. Marom

Teaser

In this review, we discuss the different radiation delivery techniques available to treat non–small cell lung cancer, typical radiologic manifestations of conventional radiotherapy, and different patterns of lung injury and temporal evolution of the newer radiotherapy techniques. More sophisticated techniques include intensity-modulated radiotherapy, stereotactic body radiotherapy, proton therapy, and respiration-correlated computed tomography or 4-dimensional computed tomography for radiotherapy planning. Knowledge of the radiation treatment plan and technique, the completion date of radiotherapy, and the temporal evolution of radiation-induced lung injury is important to identify expected manifestations of radiation-induced lung injury and differentiate them from tumor recurrence or infection.


https://ift.tt/2GwOc6J

Targeted Therapy and Immunotherapy in the Treatment of Non–Small Cell Lung Cancer

Publication date: May 2018
Source:Radiologic Clinics of North America, Volume 56, Issue 3
Author(s): Girish S. Shroff, Patricia M. de Groot, Vassiliki A. Papadimitrakopoulou, Mylene T. Truong, Brett W. Carter

Teaser

The treatment strategy in advanced non–small cell lung cancer (NSCLC) has evolved from empirical chemotherapy to a personalized approach based on histology and molecular markers of primary tumors. Targeted therapies are directed at the products of oncogenic driver mutations. Immunotherapy facilitates the recognition of cancer as foreign by the host immune system, stimulates the immune system, and alleviates the inhibition that allows the growth and spread of cancer cells. The authors describes the role of targeted therapy and immunotherapy in the treatment of NSCLC, patterns of disease present on imaging studies, and immune-related adverse events encountered with immunotherapy.


https://ift.tt/2q6GOUa

Improving detection of patient deterioration in the general hospital ward environment

Patient monitoring on low acuity general hospital wards is currently based largely on intermittent observations and measurements of simple variables, such as blood pressure and temperature, by nursing staff. Often several hours can pass between such measurements and patient deterioration can go unnoticed. Moreover, the integration and interpretation of the information gleaned through these measurements remains highly dependent on clinical judgement. More intensive monitoring, which is commonly used in peri-operative and intensive care settings, is more likely to lead to the early identification of patients who are developing complications than is intermittent monitoring. Early identification can trigger appropriate management, thereby reducing the need for higher acuity care, reducing hospital lengths of stay and admission costs and even, at times, improving survival. However, this degree of monitoring has thus far been considered largely inappropriate for general hospital ward settings due to device costs and the need for staff expertise in data interpretation. In this review, we discuss some developing options to improve patient monitoring and thus detection of deterioration in low acuity general hospital wards.

https://ift.tt/2H5XkvO

Free pre-operative clear fluids before day-surgery?: Challenging the dogma

No abstract available

https://ift.tt/2EijWGq

Reply to: what is more important, cost or effectiveness?

No abstract available

https://journals.lww.com/ejanaesthesiology/Fulltext/2018/05000/Reply_to___what_is_more_important,_cost_or.12.aspx

Comparison of double intravenous vasopressor automated system using nexfin versus manual vasopressor bolus administration for maintenance of haemodynamic stability during spinal anaesthesia for caesarean delivery: A randomised double-blind controlled trial

BACKGROUND Hypotension is a common side effect of spinal anaesthesia during caesarean delivery and is associated with maternal and foetal adverse effects. We developed an updated double intravenous vasopressor automated (DIVA) system that administers phenylephrine or ephedrine based on continuous noninvasive haemodynamic monitoring using the Nexfin device. OBJECTIVE The aim of our present study is to compare the performance and reliability of the DIVA system against Manual Vasopressor Bolus administration. DESIGN A randomised, double-blind controlled trial. SETTING Single-centre, KK Women's and Children's Hospital, Singapore. PATIENTS Two hundred and thirty-six healthy women undergoing elective caesarean delivery under spinal anaesthesia. MAIN OUTCOME MEASURES The primary outcome was the incidence of maternal hypotension. The secondary outcome measures were reactive hypertension, total vasopressor requirement and maternal and neonatal outcomes. RESULTS The DIVA group had a significantly lower incidence of maternal hypotension, with 39.3% (46 of 117) patients having any SBP reading less than 80% of baseline compared with 57.5% (65 of 113) in the manual vasopressor bolus group (P = 0.008). The DIVA group also had fewer hypotensive episodes than the manual vasopressor bolus group (4.67 versus 7.77%; P 

https://ift.tt/2GOCV0N

The trapezius plane block: a technique for regional anaesthesia of the superficial posterior thorax

No abstract available

https://ift.tt/2GPZxhf

Oesophageal or transgastric views for estimating mean pulmonary artery pressure with transoesophageal echocardiography: A prospective observational study

BACKGROUND Recent data suggest that in cardiac surgical patients, the pulmonary artery acceleration time (PAT) is useful for estimating mean pulmonary artery pressure (MPAP) noninvasively with transoesophageal echocardiography (TOE). The pulmonary valve can be visualised from multiple echocardiographic windows, but it is unclear which, if any, view correlates best with MPAP. OBJECTIVE(S) To compare the PAT measured with TOE from oesophageal and transgastric views with MPAP obtained invasively with a pulmonary artery catheter. DESIGN A prospective observational study. SETTING St. Vincent's Hospital, Melbourne, a university tertiary referral centre in Australia. PATIENTS Sixty-three patients having cardiac surgery were included in our study. All patients had insertion of both a TOE probe and pulmonary artery catheter; this is the routine standard of care in our centre. INTERVENTION(S) Nil. MAIN OUTCOME MEASURES During a period of haemodynamic stability, the PAT was measured first from an oesophageal view and then immediately after from a transgastric view. The results were then compared with the invasively measured MPAP. RESULTS Simultaneous measurements of MPAP and PAT were taken in 63 patients. In two patients, these measurements were not possible in the transgastric position due to an inability to visualise the right ventricular outflow tract and pulmonary valve. A Bland–Altman analysis of the PAT measured from the upper oesophageal and transgastric views showed a mean difference of 1 ms and limits of agreement of −18 to 16 ms. The area under the receiver operating curves for predicting pulmonary hypertension with PAT were upper oesophageal view 0.99 [95% confidence interval (CI), 0.98 to 1.00] and transgastric view 0.99 (95% CI, 0.97 to 1.00). The agreement between the results from these two views in the diagnosis of pulmonary hypertension (defined as PAT  25 mmHg) with a sensitivity of 94.7% and specificity of 97.6%. The transgastric view predicted pulmonary hypertension with a sensitivity of 89.4% and specificity of 95.2%. CONCLUSION Oesophageal and transgastric measurements of PAT have close agreement and a similar high ability to discriminate between people with and without pulmonary hypertension. The transgastric measurement was unobtainable in a small percentage of patients and required more probe manipulation. We would recommend PAT measurement in the upper oesophageal view.

https://ift.tt/2EijVSS

Ultrasound examination of the antrum to predict gastric content volume in the third trimester of pregnancy as assessed by MRI: A prospective cohort study

BACKGROUND Ultrasound examination of the gastric antrum allows reliable pre-operative assessment of gastric contents and volume in adult patients. However, during pregnancy, the change in the anatomical position of the stomach due to the gravid uterus leads to a change in the measured value of the antral area. Therefore, current mathematical models predicting gastric content volume (GCV) in the adult may not apply in term pregnant women. OBJECTIVE To propose a mathematical model which is predictive of GCV in pregnant women and to assess the performance of an ultrasound qualitative grading scale (0 to 2) for the diagnosis of clear fluid volumes more than 0.8 and 1.5 ml kg−1. DESIGN Prospective cohort study. SETTING Hospices Civils de Lyon, Hôpital Femme Mère Enfant, Lyon and Assistance Publique – Hôpitaux de Marseille, Hôpital Nord, Marseille, France. PATIENTS Pregnant women in the third trimester of pregnancy. MAIN OUTCOME MEASURES Comparison of the GCV as measured by MRI and the ultrasound measured antral cross-sectional area, and an assessment of gastric contents according to a 0 to 2 qualitative grading scale. RESULTS Data from 34 women were analysed. A linear model predictive of GCV was constructed with a 95% agreement band of ±95 ml, with a mean polar angle of −8.7°. Performance of the qualitative grading scale to detect fluid volumes >0.8 and >1.5 ml kg−1 was improved when used in a composite scale including a 505 mm2 antral area cut-off value in the semirecumbent supine position. CONCLUSION We report a new mathematical model predictive of GCV in women in the third trimester of pregnancy. Furthermore, the combination of the qualitative and the quantitative ultrasound examination of the gastric antrum might be useful to assess gastric fluid volume in pregnant women. TRIAL REGISTRATION ANSM Register N°2015-A00800-49

https://ift.tt/2GVigIB

Microvascular reactivity, assessed by near-infrared spectroscopy and a vascular occlusion test, is associated with patient outcomes following cardiac surgery: A prospective observational study

BACKGROUND Microvascular dysfunction in patients admitted to the ICU following cardiac surgery may be related to perioperative complications and increased resource utilisation even in the presence of acceptable systemic haemodynamic variables. OBJECTIVES To assess the relationship between microvascular impairment using peripheral near-infrared spectroscopy at ICU admission and 6 h postadmission and the duration of mechanical ventilatory support, length of stay in ICU and in hospital. DESIGN Prospective, observational cohort study. SETTING Single-centre, tertiary-level cardiac ICU. PATIENTS Sixty-nine adult patients following elective cardiac surgery excluding patients with on-going extracorporeal support or in whom tissue haemoglobin oxygen saturation (StO2) measurements were not feasible. MAIN OUTCOME MEASURES Thenar and forearm StO2 in response to a vascular occlusion test to calculate desaturation and reperfusion slopes. A logistic regression model was used to ascertain the associations between StO2, desaturation and reperfusion slopes as well as cardiac index, mean arterial pressure, arterial lactate concentrations and prolonged (≥75th percentile) duration of mechanical ventilation, ICU length of stay and hospital length of stay. RESULTS A reduced reperfusion slope at ICU admission was associated independently with prolonged mechanical ventilation at thenar (OR 0.08; 95% CI [0.02 to 0.47], P = 0.003) and forearm [OR 0.2 (0.04 to 0.59), P = 0.006] sites. Similarly, a reduced Rres was associated with prolonged ICU LOS at both thenar [OR 0.3 (0.13 to 0.77), P = 0.007] and forearm [OR 0.2 (0.05 to 0.62), P = 0.007] sites at ICU0 h, as well as ICU6 h [OR 0.2 (0.05 to 0.66), P = 0.004 and OR 0.05 (0.008 to 0.34), P = 0.002]. An increased Rdes was associated with prolonged hospital LOS at the thenar eminence at ICU0 h [OR 1.9 (1.4 to 2.3), P = 0.004] and ICU6 h [OR 6.7 (2.0 to 23), P = 0.002] as well as the forearm at ICU0 h [OR 1.5 (1.3 to 1.9), P = 0.004] and ICU6 h [OR 1.6 (1.3 to 2.1), P = 0.004]. CONCLUSION In the early postoperative period following cardiac surgery, changes in thenar and forearm tissue oxygenation variables are associated with patient resource utilisation outcomes.

https://ift.tt/2EhOGr7

What is more important, cost or effectiveness?

No abstract available

https://ift.tt/2GQUBJ7

Prediction of bilateral cerebral oxygen desaturations from a single sensor in adult cardiac surgery: A prospective observational study

BACKGROUND Monitoring regional cerebral oxygen saturation (rcSO2) with near-infrared spectroscopy is increasingly being performed in patients scheduled for cardiac surgery. It is sometimes difficult to monitor both frontal lobes due to anatomical or space compromises. However, it remains unclear whether the use of only one lateral or medial probe can provide adequate bilateral monitoring. OBJECTIVE To evaluate the efficacy of using a single lateral or medial probe to detect substantial desaturations on both sides. DESIGN A prospective observational study. SETTING Tertiary university teaching hospital. PATIENTS Seventeen adult patients undergoing elective cardiac surgery monitored with three near-infrared spectroscopy probes (two lateral and one medial) using an INVOS 5100C monitor. INTERVENTIONS The value of rcSO2 was recorded up to 19 times during each procedure. Substantial desaturation was defined as an absolute rcSO2 value of 50% or less or a decrease of more than 20% compared with baseline values on spontaneous ventilation with 21% oxygen. MAIN OUTCOME MEASURES The level of agreement between the three pairs of probes using the Bland–Altman method for repeated measures, and the grade of concordant and discordant results between the three pairs of probes by means of contingency tables and the κ coefficient. RESULTS We obtained 244 records per probe. Greater agreement was observed between the two lateral probes (mean ± SD of the differences between recordings was -0.9 ± 5.5); mean difference between left and medial, and right and medial probes was 2.4 ± 7.3 and 3.3 ± 6.7, respectively. The rate of discordant results between the two lateral probes was 5.7%, κ coefficient of 0.6 with 95% confidence interval (95% CI 0.4 to 0.8), and between the left and medial, and right and medial of 8.2 and 7.4%, with κ coefficients of 0.57 (95% CI 0.38 to 0.76) and 0.5 (95% CI 0.29 to 0.71), respectively. CONCLUSION In cardiac surgery patients in whom there is difficulty in accommodating two rcSO2 probes, a single lateral probe can effectively measure bilateral rcSO2 in specific scenarios.

https://ift.tt/2EgusOD

Intubation with cervical spine immobilisation: a comparison between the KingVision videolaryngoscope and the Macintosh laryngoscopeA randomised controlled trial

No abstract available

https://ift.tt/2GRE4oc

Dexmedetomidine as a part of general anaesthesia for caesarean delivery in patients with pre-eclampsia: A randomised double-blinded trial

BACKGROUND During general anaesthesia, endotracheal intubation of patients with pre-eclampsia causes stimulation of the sympathetic nervous system and catecholamine release, which may lead to maternal and neonatal complications. OBJECTIVE To attenuate both the stress response and the haemodynamic response to tracheal intubation in patients with pre-eclampsia. DESIGN A randomised, double-blind, controlled study. SETTING Single University Hospital. PATIENTS Sixty patients aged 18 to 45 years with pre-eclampsia receiving general anaesthesia for caesarean section. INTERVENTIONS The patients were randomly allocated to three groups. Groups D1and D2 received an infusion of dexmedetomidine 1 μg kg−1 over the 10 min before induction of general anaesthesia, then 0.4 and 0.6 μg kg−1 h−1 dexmedetomidine, respectively. Group C received equivalent volumes of 0.9% saline. MAIN OUTCOME MEASURES The primary outcome was the effect of dexmedetomidine on mean arterial blood pressure measured before induction of general anaesthesia at 1 and 5 min after intubation, and then every 5 min until 10 min after extubation. The secondary outcomes were blood glucose and serum cortisol (measured before induction of general anaesthesia, and at 1 and 5 min after intubation), postoperative visual analogue pain scores, time to first request for analgesia, the total consumption of analgesia, Ramsay sedation score, maternal and placental vein blood serum levels of dexmedetomidine and neonatal Apgar score at 1 and 5 min. RESULTS At all assessment times, the mean arterial pressures were significantly lower in the dexmedetomidine groups than in the control group. Compared with group C, the heart rate was significantly lower in both groups D1 and D2. In group D2, the heart rate was lower than in group D1. Serum glucose and cortisol were significantly higher in the controls than in either group D1 or D2. Group D2 patients were significantly more sedated on arrival in the recovery room followed by D1. Time to first analgesia was significantly longer in groups D2 and D1 than in group C, and the visual analogue pain scores were significantly lower in groups D1 and D2 than in group C at 1, 2, 3 and 5 h. Total morphine consumption was significantly lower in groups D1 and D2 than in the control group. There was no difference in Apgar scores across the three groups despite significantly higher dexmedetomidine concentrations in group D2 (both maternal and placental vein) than in group D1. CONCLUSION Administration of dexmedetomidine in doses 0.4 and 0.6 μg kg−1 h−1 was associated with haemodynamic and hormonal stability, without causing significant adverse neonatal outcome. TRIAL REGISTRATION Pan African Clinical Trial Registry (PACTR201706002303170), (www.pactr.org).

https://ift.tt/2Egumqf

Economic evaluation of bilateral sternal local anaesthetic infusions via multi-hole catheters after cardiac surgery

No abstract available

https://ift.tt/2H6W0Jk

Official control of plant protection products in Poland: detection of illegal products

Abstract

Market presence of illegal and counterfeit pesticides is now a global problem. According to data published in 2012 by the European Crop Protection Association (ECPA), illegal products represent over 10% of the global market of plant protection products. Financial benefits are the main reason for the prevalence of this practice. Counterfeit and illegal pesticides may contain substances that may pose a threat to the environment, crops, animals, and humans, inconsistent with the label and registration dossier. In Poland, action against illegal and counterfeit plant protection products is undertaken by the Main Inspectorate of Plant Health and Seed Inspection (PIORiN), the police, the prosecution, and the pesticide producers. Results of chemical analyses carried out by the Institute of Plant Protection - National Research Institute Sośnicowice Branch, Pesticide Quality Testing Laboratory (PQTL IPP-NRI Sosnicowice Branch) indicate that a majority of illegal pesticides in Poland are detected in the group of herbicides. Products from parallel trade tend to have the most irregularities. This article describes the official quality control system of plant protection products in Poland and presents the analytical methods for testing pesticides suspected of adulteration and recent test results.

https://ift.tt/2GPD3gu

Correlation of neural activity with behavioral kinematics reveals distinct sensory encoding and evidence accumulation processes during active tactile sensing

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Ioannis Delis, Jacek P. Dmochowski, Paul Sajda, Qi Wang
Many real-world decisions rely on active sensing, a dynamic process for directing our sensors (e.g. eyes or fingers) across a stimulus to maximize information gain. Though ecologically pervasive, limited work has focused on identifying neural correlates of the active sensing process. In tactile perception, we often make decisions about an object/surface by actively exploring its shape/texture. Here we investigate the neural correlates of active tactile decision-making by simultaneously measuring electroencephalography (EEG) and finger kinematics while subjects interrogated a haptic surface to make perceptual judgments. Since sensorimotor behavior underlies decision formation in active sensing tasks, we hypothesized that the neural correlates of decision-related processes would be detectable by relating active sensing to neural activity. Novel brain-behavior correlation analysis revealed that three distinct EEG components, localizing to right-lateralized occipital cortex (LOC), middle frontal gyrus (MFG), and supplementary motor area (SMA), respectively, were coupled with active sensing as their activity significantly correlated with finger kinematics. To probe the functional role of these components, we fit their single-trial-couplings to decision-making performance using a hierarchical-drift-diffusion-model (HDDM), revealing that the LOC modulated the encoding of the tactile stimulus whereas the MFG predicted the rate of information integration towards a choice. Interestingly, the MFG disappeared from components uncovered from control subjects performing active sensing but not required to make perceptual decisions. By uncovering the neural correlates of distinct stimulus encoding and evidence accumulation processes, this study delineated, for the first time, the functional role of cortical areas in active tactile decision-making.



https://ift.tt/2q44zwm

Simultaneous scalp recorded EEG and local field potentials from monkey ventral premotor cortex during action observation and execution reveals the contribution of mirror and motor neurons to the mu-rhythm

Publication date: 15 July 2018
Source:NeuroImage, Volume 175
Author(s): Marco Bimbi, Fabrizia Festante, Gino Coudé, Ross E. Vanderwert, Nathan A. Fox, Pier Francesco Ferrari
The desynchronization of alpha and beta oscillations (mu rhythm) in the central scalp EEG during action observation and action execution is thought to reflect neural mirroring processes. However, the extent to which mirror neurons (MNs) or other populations of neurons contribute to such EEG desynchronization is still unknown. Here, we provide the first evidence that, in the monkey, the neuronal activity recorded from the ventral premotor cortex (PMv) strongly contributes to the EEG changes occurring in the beta band over central scalp electrodes, during executed and observed actions. We simultaneously recorded scalp EEG and extracellular activity, Multi Unit Activity (MUA) and Local Field Potentials (LFP), from area F5 of two macaques executing and observing grasping actions. We found that MUA highly correlates with an increase in high gamma LFP power and, interestingly, such LFP power increase also correlates to EEG beta – and in part also to alpha – desynchronization. In terms of timing of signal changes, the increase in high gamma LFP power precedes the EEG desynchronization, during both action observation and execution, thus suggesting a causal role of PMv neuronal activity in the modulation of the alpha and beta mu-rhythm. Lastly, neuronal signals from deeper layers of PMv exert a greater contribution than superficial layers to the EEG beta rhythm modulation, especially during the motor task. Our findings have clear implications for EEG studies in that they demonstrate that the activity of different populations of neurons in PMv contribute to the generation of the mu-rhythm.



https://ift.tt/2Jcry13

Fast and robust Block-Sparse Bayesian learning for EEG source imaging

Publication date: 1 July 2018
Source:NeuroImage, Volume 174
Author(s): Alejandro Ojeda, Kenneth Kreutz-Delgado, Tim Mullen
We propose a new Sparse Bayesian Learning (SBL) algorithm that can deliver fast, block-sparse, and robust solutions to the EEG source imaging (ESI) problem in the presence of noisy measurements. Current implementations of the SBL framework are computationally expensive and typically handle fluctuations in the measurement noise using different heuristics that are unsuitable for real-time imaging applications. We address these shortcomings by decoupling the estimation of the sensor noise covariance and the sparsity profile of the sources, thereby yielding an efficient two-stage algorithm. In the first stage, we optimize a simplified non-sparse generative model to get an estimate of the sensor noise covariance and a good initialization of the group-sparsity profile of the sources. Sources obtained at this stage are equivalent to those estimated with the popular inverse method LORETA. In the second stage, we apply a fast SBL algorithm with the noise covariance fixed to the value obtained in the first stage to efficiently shrink to zero groups of sources that are irrelevant for explaining the EEG measurements. In addition, we derive an initialization to the first stage of the algorithm that is optimal in the least squares sense, which prevents delays due to suboptimal initial conditions. We validate our method on both simulated and real EEG data. Simulations show that the method is robust to measurement noise and performs well in real-time, with faster performance than two state of the art SBL solvers. On real error-related negativity EEG data, we obtain source images in agreement with the experimental literature. The method shows promise for real-time neuroimaging and brain-machine interface applications.

Graphical abstract

https://ift.tt/2uOhjgm

A Circular RNA Protects Dormant Hematopoietic Stem Cells from DNA Sensor cGAS-Mediated Exhaustion

Publication date: Available online 3 April 2018
Source:Immunity
Author(s): Pengyan Xia, Shuo Wang, Buqing Ye, Ying Du, Chong Li, Zhen Xiong, Yuan Qu, Zusen Fan
Disrupting the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs) leads to bone marrow failure or hematologic malignancy. However, how HSCs sustain their quiescent state and avoid type I interferon (IFN)-mediated exhaustion remains elusive. Here we defined a circular RNA that we named cia-cGAS that was highly expressed in the nucleus of long-term (LT)-HSCs. Cia-cGAS deficiency in mice caused elevated expression of type I IFNs in bone marrow and led to decreased numbers of dormant LT-HSCs. Under homeostatic conditions, cia-cGAS bound DNA sensor cGAS in the nucleus to block its synthase activity, thereby protecting dormant LT-HSCs from cGAS-mediated exhaustion. Moreover, cia-cGAS harbored a stronger binding affinity to cGAS than self-DNA did and consequently suppressed cGAS-mediated production of type I IFNs in LT-HSCs. Our findings reveal a mechanism by which cia-cGAS inhibits nuclear cGAS by blocking its enzymatic activity and preventing cGAS from recognizing self-DNA to maintain host homeostasis.

Graphical abstract

Teaser

Disrupting the balance between self-renewal and differentiation of HSCs leads to severe pathologic consequences. Xia et al. identify a circular RNA cia-cGAS that is highly expressed in the nucleus of LT-HSCs. Under homeostatic conditions, cia-cGAS binds DNA sensor cGAS to block its synthase activity, protecting dormant LT-HSCs from cGAS-mediated exhaustion.


https://ift.tt/2IpNggB

Co-inhibitory Molecule B7 Superfamily Member 1 Expressed by Tumor-Infiltrating Myeloid Cells Induces Dysfunction of Anti-tumor CD8+ T Cells

Publication date: Available online 3 April 2018
Source:Immunity
Author(s): Jing Li, Younghee Lee, Yanjian Li, Yu Jiang, Huiping Lu, Wenjuan Zang, Xiaohong Zhao, Liguo Liu, Yang Chen, Haidong Tan, Zhiying Yang, Michael Q. Zhang, Tak W. Mak, Ling Ni, Chen Dong
The molecular mechanisms whereby CD8⁺ T cells become "exhausted" in the tumor microenvironment remain unclear. Programmed death ligand-1 (PD-L1) is upregulated on tumor cells and PD-1-PD-L1 blockade has significant efficacy in human tumors; however, most patients do not respond, suggesting additional mechanisms underlying T cell exhaustion. B7 superfamily member 1 (B7S1), also called B7-H4, B7x, or VTCN1, negatively regulates T cell activation. Here we show increased B7S1 expression on myeloid cells from human hepatocellular carcinoma correlated with CD8⁺ T cell dysfunction. B7S1 inhibition suppressed development of murine tumors. Putative B7S1 receptor was co-expressed with PD-1 but not T cell immunoglobulin and mucin-domain containing-3 (Tim-3) at an activated state of early tumor-infiltrating CD8⁺ T cells, and B7S1 promoted T cell exhaustion, possibly through Eomes overexpression. Combinatorial blockade of B7S1 and PD-1 synergistically enhanced anti-tumor immune responses. Collectively, B7S1 initiates dysfunction of tumor-infiltrating CD8⁺ T cells and may be targeted for cancer immunotherapy.

Graphical abstract

Teaser

Mechanisms driving T cell exhaustion have not been understood. Li et al. demonstrate that B7S1 on tumor-infiltrating myeloid cells initiates exhaustion of activated CD8⁺ TILs through upregulating Eomes, thus proposing B7S1 as a promising target to enhance the efficacy of anti-PD-1 therapy.


https://ift.tt/2Jg6gzx

Interleukin-15 Complex Treatment Protects Mice from Cerebral Malaria by Inducing Interleukin-10-Producing Natural Killer Cells

Publication date: Available online 3 April 2018
Source:Immunity
Author(s): Kristina S. Burrack, Matthew A. Huggins, Emily Taras, Philip Dougherty, Christine M. Henzler, Rendong Yang, Sarah Alter, Emily K. Jeng, Hing C. Wong, Martin Felices, Frank Cichocki, Jeffrey S. Miller, Geoffrey T. Hart, Aaron J. Johnson, Stephen C. Jameson, Sara E. Hamilton
Cerebral malaria is a deadly complication of Plasmodium infection and involves blood brain barrier (BBB) disruption following infiltration of white blood cells. During experimental cerebral malaria (ECM), mice inoculated with Plasmodium berghei ANKA-infected red blood cells develop a fatal CM-like disease caused by CD8⁺ T cell-mediated pathology. We found that treatment with interleukin-15 complex (IL-15C) prevented ECM, whereas IL-2C treatment had no effect. IL-15C-expanded natural killer (NK) cells were necessary and sufficient for protection against ECM. IL-15C treatment also decreased CD8⁺ T cell activation in the brain and prevented BBB breakdown without influencing parasite load. IL-15C induced NK cells to express IL-10, which was required for IL-15C-mediated protection against ECM. Finally, we show that ALT-803, a modified human IL-15C, mediates similar induction of IL-10 in NK cells and protection against ECM. These data identify a regulatory role for cytokine-stimulated NK cells in the prevention of a pathogenic immune response.

Graphical abstract

Teaser

NK cells can display both pro-inflammatory and regulatory function, but their role in the pathogenesis of malaria is not fully understood. Burrack et al. demonstrate that IL-15 complex (IL-15C) therapy prevents mice from succumbing to experimental cerebral malaria (ECM). IL-15C treatment stimulates NK cells to produce IL-10, suppressing the pathogenic CD8⁺ T cell response during ECM.


https://ift.tt/2Iq5Y7Y

KLRG1+ Effector CD8+ T Cells Lose KLRG1, Differentiate into All Memory T Cell Lineages, and Convey Enhanced Protective Immunity

Publication date: Available online 3 April 2018
Source:Immunity
Author(s): Dietmar Herndler-Brandstetter, Harumichi Ishigame, Ryo Shinnakasu, Valerie Plajer, Carmen Stecher, Jun Zhao, Melanie Lietzenmayer, Lina Kroehling, Akiko Takumi, Kohei Kometani, Takeshi Inoue, Yuval Kluger, Susan M. Kaech, Tomohiro Kurosaki, Takaharu Okada, Richard A. Flavell
Protective immunity against pathogens depends on the efficient generation of functionally diverse effector and memory T lymphocytes. However, whether plasticity during effector-to-memory CD8⁺ T cell differentiation affects memory lineage specification and functional versatility remains unclear. Using genetic fate mapping analysis of highly cytotoxic KLRG1⁺ effector CD8⁺ T cells, we demonstrated that KLRG1⁺ cells receiving intermediate amounts of activating and inflammatory signals downregulated KLRG1 during the contraction phase in a Bach2-dependent manner and differentiated into all memory T cell linages, including CX3CR1^int peripheral memory cells and tissue-resident memory cells. "ExKLRG1" memory cells retained high cytotoxic and proliferative capacity distinct from other populations, which contributed to effective anti-influenza and anti-tumor immunity. Our work demonstrates that developmental plasticity of KLRG1⁺ effector CD8⁺ T cells is important in promoting functionally versatile memory cells and long-term protective immunity.

Graphical abstract

Teaser

Herndler-Brandstetter et al. demonstrate that KLRG1⁺IL-7Rα⁺ effector CD8⁺ T cells downregulate KLRG1 in a Bach2-dependent manner and differentiate into long-lived circulating and tissue-resident "exKLRG1" memory cells. Developmental plasticity of KLRG1⁺ effector cells therefore drives functional diversity within memory T cell lineages and promotes enhanced anti-influenza and anti-tumor immunity.


https://ift.tt/2GUyp0H

Toll-like Receptor 9 Contains Two DNA Binding Sites that Function Cooperatively to Promote Receptor Dimerization and Activation

Publication date: Available online 3 April 2018
Source:Immunity
Author(s): Umeharu Ohto, Hanako Ishida, Takuma Shibata, Ryota Sato, Kensuke Miyake, Toshiyuki Shimizu
Toll-like receptor 9 (TLR9) recognizes DNA containing CpG motifs derived from bacteria and viruses and activates the innate immune response to eliminate them. TLR9 is known to bind to CpG DNA, and here, we identified another DNA binding site in TLR9 that binds DNA containing cytosine at the second position from the 5′ end (5′-xCx DNA). 5′-xCx DNAs bound to TLR9 in the presence of CpG DNA and cooperatively promoted dimerization and activation of TLR9. Binding at both sites was important for efficient activation of TLR9. The 5′-xCx DNA bound the site corresponding to the nucleoside binding site in TLR7 and TLR8 as revealed by the structural analysis. This study revealed that TLR9 recognizes two types of DNA through its two binding sites for efficient activation. This information may contribute to the development of drugs that control the activity of TLR9.

Graphical abstract

Teaser

TLR9 recognizes DNAs with unmethylated CpG motifs and activates innate immune responses. Ohto et al. identify another TLR9 binding motif, the 5′-xCx DNA motif, and determine the tertiary structure of TLR9 in complex with CpG and 5′-xCx DNAs to reveal a cooperative activation mechanism of TLR9 by two types of DNAs.


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Further characterization of CAPOS/CAOS syndrome with the Glu818Lys mutation in the ATP1A3 gene: A case report

Publication date: Available online 3 April 2018
Source:Brain and Development
Author(s): Takuya Hayashida, Yoshiaki Saito, Atsushi Ishii, Shinichi Hirose, Rika Hiraiwa, Yoshihiro Maegaki, Kousaku Ohno
A 38-year-old female patient experienced recurrent episodes of neurological deterioration during febrile illness at the age of 7 and 8 months, and 2, 4, and 37 years. Acute symptoms comprised unconsciousness, headache, abnormal ocular movements, flaccid paralysis with areflexia, ataxia, dysphagia, and movement disorders. Each episode of neurological deterioration was followed by partial recovery with residual symptoms of progressive disturbance of visual acuity with optic atrophy and hearing loss, moderate intellectual disability, strabismus, ophthalmoplegia, as well as fluctuating degree of gait ataxia, chorea, tremor, and myoclonus. In addition, electrocardiography revealed incomplete right bundle branch block. The genetic testing revealed a de novo heterozygous mutation of c.2452G > A (p.Glu818Lys) in the ATP1A3 gene, which was compatible with the clinical phenotype of CAPOS (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss)/CAOS syndrome. Here we discuss the significance of clinical features of a patient, overlapping with those of alternating hemiplegia of childhood, along with a literature review.



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Effectiveness of total corpus callosotomy for diffuse bilateral polymicrogyria: Report of three pediatric cases

Publication date: Available online 3 April 2018
Source:Brain and Development
Author(s): Shimpei Baba, Tohru Okanishi, Mitsuyo Nishimura, Sotaro Kanai, Shinji Itamura, Takayuki Suzuki, Yosuke Masuda, Hideo Enoki, Ayataka Fujimoto
PurposePolymicrogyria, a malformation of the cerebral cortex, frequently causes epilepsy. Diffuse bilateral polymicrogyria (DBP) is related to poor epilepsy prognosis, but most patients with DBP are not good candidates for resective epilepsy surgery and effectiveness of corpus callosotomy (CC), a palliative surgery, for patients without resective epileptogenic cortices, has not been established in DBP. Because CC might be effective against DBP-related epilepsy, we conducted total CC in three pediatric DBP cases.MethodsCase 1. A girl developed epilepsy at 3 months of age, with focal versive seizures and epileptic spasms. The electroencephalogram (EEG) showed a suppression-burst pattern. Total CC was performed at 6 months of age.Case 2. A female infant developed epilepsy on the day of birth, exhibiting epileptic spasms, generalized tonic-clonic seizures, and eye-deviating seizures. She had a history of clusters of tonic seizures. Total CC was performed at 1 year and 2 months of age. After CC, the epileptic focus of the tonic seizures was identified; a secondary resective surgery was conducted.Case 3. A girl developed multiple types of seizures at 3 years of age. Frequent atypical absence status was refractory to antiepileptic drugs. Total CC was conducted at 8 years of age.ResultsCase 1: Frequencies of both seizure types decreased. The background EEG changed to continuous high-voltage slow waves.Case 2: Clusters of tonic seizures were well-controlled.Case 3: Atypical absence seizures completely disappeared.ConclusionCC could be effective for patients with DBP, whose habitual seizures include epileptic spasms and absence seizures.



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The Eyes Reveal Uncertainty about Object Distinctions in Semantic Variant Primary Progressive Aphasia

Publication date: Available online 3 April 2018
Source:Cortex
Author(s): Andreia V. Faria, David Race, Kevin Kim, Argye E. Hillis
At least three distinct variants of primary progressive aphasia (PPA) have been described, but they are difficult to distinguish early in the course, when individuals experience primarily anomia. People with svPPA are often the hardest to care for, because they have impaired comprehension of words and objects and often have negative changes in comportment. We sought to identify an early marker of semantic variant primary progressive aphasia (svPPA) and to enhance the understanding of the semantic deficit in svPPA. We hypothesized that the pattern of eye tracking in a word picture matching task can differentiate svPPA from other variants and can predict which participants with unclassifiable PPA will progress to svPPA. We tested 19 individuals with PPA on a word picture matching task with eye tracking. We found that individuals with svPPA were less accurate than other variants when the foils were semantic coordinates (horse-cow) or schematically related (horse-saddle), but not when they were thematically related (saw-horse) or unrelated. Moreover, even in the condition in which they were highly accurate (unrelated foils) they looked much more often to the foils and for longer, than other variants or controls. Unclassifiable PPA participants who eventually developed svPPA showed the same pattern. This abnormal pattern was associated with atrophy in bilateral temporal poles.



https://ift.tt/2H5mM4A

C5a receptor1 inhibition alleviates influenza virus-induced acute lung injury

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Nianping Song, Pei Li, Yuting Jiang, Hong Sun, Jing Cui, Guangyu Zhao, Dan Li, Yan Guo, Yuehong Chen, Jimin Gao, Shihui Sun, Yusen Zhou
Influenza A virus is an important human pathogen that causes 3 to 5 million severe cases of influenza worldwide each year. An aberrant innate immune response, particularly hypercytokinemia, is thought to play an important role in the disease, although the pathogenesis of severe influenza virus infection remains unclear and no specific and efficacious immunotherapy is available. This study reports dysregulated complement activation in mice after infection with A/Puerto Rico/8/34 (PR8). C5aR1-deficient mice and mice treated with an anti-C5aR1 antibody were used as models to study the C5a-C5aR1 axis during acute lung injury (ALI) induced by influenza virus infection. The results showed that blocking the C5a-C5aR1 axis alleviated ALI by inhibiting endothelial cell activation and dampening the host immune response (i.e., reduced TNF-α, IL-1β, IL-6, IP-10, MCP-1, IL-12p70, and IFN-γ concentrations in plasma), particularly CTL-mediated immunopathology. Furthermore, blockade of the C5a-C5aR1 axis inhibited viral replication in lung tissue. Taken together, the results indicate that the C5a-C5aR1 axis plays an important role in the outcome of ALI induced by influenza virus infection and that regulation of complement activation, particularly the C5aR1 inhibition, is a promising intervention and adjunctive treatment.



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20(R)-ginsenoside Rg3, a rare saponin from red ginseng, ameliorates acetaminophen-induced hepatotoxicity by suppressing PI3K/AKT pathway-mediated inflammation and apoptosis

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Yan-dan Zhou, Jin-gang Hou, Wei Liu, Shen Ren, Ying-ping Wang, Rui Zhang, Chen Chen, Zi Wang, Wei Li
Although ginsenoside Rg3 was isolated as a major component of Korea red ginseng and confirmed to exert potential hepatoprotective effect on acetaminophen (APAP)-induced liver injury via induction of glutathione S-transferase (GST) in vitro, thein vivo hepatoprotective effect of Rg3 and the underlying molecular mechanism of action remain unclear. The current study was aimed to explore whether 20(R)-Ginsenoside Rg3 (20(R)-Rg3) could alleviate acetaminophen-induced liver injury in mice and to determine the involvement of PI3K/AKT signaling pathway. Our findings demonstrated that a single injection of APAP (250 mg/kg) increased the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); such increases were attenuated by pretreatment of mice with 20(R)-Rg3 for seven days. The depletion of glutathione (GSH), generation of malondialdehyde (MDA) and the over expression of cytochrome P450 E1 (CYP2E1) and 4-hydroxynonenal (4-HNE) caused by APAP exposure were also inhibited by 20(R)-Rg3 pretreatment. Moreover, 20(R)-Rg3 pretreatment significantly alleviated APAP-induced apoptosis, necrosis, and inflammatory infiltration in liver tissues. Importantly, 20(R)-Rg3 effectively attenuated APAP-induced liver injury in part via activating PI3K/AKT signaling pathway. In summary, 20(R)-Rg3 exerted liver protection against APAP-caused hepatotoxicity evidenced by inhibition of oxidative stress and inflammatory response, alleviation of hepatocellular necrosis and apoptosis via activation of PI3K/AKT signaling pathway, showing potential as a novel therapeutic agent to prevent liver damage.



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Protective effect of pristimerin against LPS-induced acute lung injury in mice

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Ahmed A. Shaaban, Dalia H. El-Kashef, Mohamed F. Hamed, Dina S. El-Agamy
Pristimerin (Pris) is a triterpenoid derivative obtained from Celastraceae and Hippocrateaceae families. This compound has been extensively tested for its potent anti-cancer activity against different types of tumors. However, its effects against acute lung injury (ALI) remain to be investigated. This study explored the efficacy of Pris to protect against lipopolysaccharide (LPS)-induced ALI and its possible pathways. Results have shown that Pris possesses potent protective activity against LPS-induced acute lung damage. It significantly decreased pulmonary edema as presented by significant decrease in lung W/D ratio and in protein content. Pris attenuated LPS-induced inflammatory cell infiltration into the lung tissue and suppressed the activity of myeloperoxidase in lung. LPS-induced histopathological lesions were significantly improved via Pris pretreatment. Pris exhibited not only inhibition of LPS-induced oxidative stress, but also enhancement of the suppressed antioxidant capacity of the lung tissue. The anti-inflammatory activity of Pris against LPS-induced ALI was clearly evident via attenuation of the levels of pro-inflammatory cytokines namely, tumor necrosis factor-α and interleukin-6. Similarly, Pris inhibited LPS-induced elevation of pro-apoptotic protein, Bax, and caspase-3. Pris also increased the diminished level of Bcl2 induced by LPS. Collectively, Pris exerted protective activity against LPS-induced ALI via anti-oxidant, anti-inflammatory and anti-apoptotic pathways.



https://ift.tt/2GxkDOh

JMJD3 is involved in neutrophil membrane proteinase 3 overexpression during the hyperinflammatory response in early sepsis

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Yang Chen, Zhaojun Liu, Tingting Pan, Erzhen Chen, Enqiang Mao, Ying Chen, Ruoming Tan, Xiaoli Wang, Rui Tian, Jialin Liu, Hongping Qu
Excessive production of pro-inflammatory cytokines in early sepsis causes high early mortality rates. Membrane proteinase 3 (mPR3) expression on neutrophils plays a critical role in pro-inflammatory cytokine production. However, the mechanism underlying mPR3 overexpression in early sepsis is unknown. Here, we explored mPR3 expression in early sepsis and its regulatory mechanism. Thirty-two patients with sepsis and 20 healthy controls were prospectively enrolled. On day 1 after the onset of sepsis, mPR3 and jumonji domain-containing protein D3 (JMJD3) expression levels were measured in peripheral blood neutrophils. Lipopolysaccharide (LPS) was employed to induce JMJD3 expression in vitro, and GSK-J4 was used to inhibit JMJD3. Neutrophils were divided into four groups, control, LPS, LPS + GSK-J4, and GSK-J4, and cultured with THP-1 cells respectively. Plasma and culture supernatant cytokine levels were measured by enzyme-linked immunosorbent assays. Neutrophil mPR3 levels were significantly higher in patients with early sepsis than in healthy controls. Plasma cytokine (IL-1β and TNF-α) levels were increased in patients with sepsis exhibiting high mPR3 expression. Additionally, JMJD3 expression levels in neutrophils were increased in early sepsis. In vitro, both mPR3 on neutrophils and IL-1β in culture supernatants increased in response to LPS stimulation. Neutrophil mPR3 expression and IL-1β levels were significantly reduced by GSK-J4 in cells treated with LPS. IL-1β level was significantly higher in LPS-stimulated co-culture supernatants than in the corresponding individual cultured cells. Thus, our results suggest that JMJD3 contributes to the high expression of neutrophil mPR3, which promotes the production of proinflammatory IL-1β in early sepsis.



https://ift.tt/2Jftnu1

Antiviral activity of porcine interferon delta 8 against foot-and-mouth disease virus in vitro

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Shi-fang Li, Jun-jun Shao, Fu-rong Zhao, Mei-jiao Gong, Yin-li Xie, Hui-yun Chang, Yong-guang Zhang
Foot-and-mouth disease (FMD) is one of the most devastating diseases affecting livestock. Since vaccines fail to provide protection until seven days post-vaccination, the application of anti-viral molecules is imperative for suppressing the spread of FMDV prior to development of an adaptive immune response. Interferons (IFNs) are effective for the host to fight FMDV infections; however, a novel type I IFNs, interferon delta (IFN-δ), has not been investigated for their antiviral effects against this virus. Thus, this study investigated FMDV infection, upon pre- and post-treatment with PoIFN-δ8. Real-time quantitative PCR was used to quantify the expression levels of IFN-stimulated genes (ISGs), including ISG15, OAS1, PKR, and Mx1. Results showed the PoIFN-δ8 lacking its signal sequence was efficiently expressed in Escherichia coli, and the purified recombinant PoIFN-δ8 exerted a significantly protective effect against two different serotypes of FMDV in IBRS-2 cells. In addition, PoIFN-δ8 induced the expression of IFN-stimulated genes. These findings highlight the significance of PoIFN-δ might serve as an antiviral agent for the prevention of FMDV in pigs and will stimulate the study of exploiting the potential biological functions of IFN-δ in the future.



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Dysfunction of regulatory T cells in patients with ankylosing spondylitis is associated with a loss of Tim-3

Publication date: June 2018
Source:International Immunopharmacology, Volume 59
Author(s): Mingfei Wang, Chengyi Liu, Allen Bond, Jun Yang, Xu Zhou, Jian Wang, Bin Ji
An expansion of regulatory T cells (Tregs) in ankylosing spondylitis (AS) was observed. However, AS patients continue to exhibit aberrant inflammation. In this study, we collected PBMCs from 26 AS patients and 26 healthy controls, and investigated the functional capacity of Treg cells from these subjects. In AS patients, the frequency of CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was slightly increased compared to healthy controls, but the level of Foxp3 MFI in AS patient CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was significantly lower than that in healthy control CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells. Tim-3⁺ Treg cells were previously shown to present stronger suppressive capacity than Tim-3⁻ Treg cells. Here, we discovered that the Tim-3⁺ cell frequency in CD4⁺CD25⁺Foxp3⁺CD127⁻ Treg cells was significantly lower in AS patients. In both healthy volunteers and AS patients, Tim-3⁺ Treg cells demonstrated higher transcription of Foxp3, IL-10 and TGF-β, higher secretion of IL-10 and TGF-β, and stronger inhibition of conventional T cell inflammation, than Tim-3⁻ Treg cells. In some but not all functional aspects, the Tim-3⁺ Treg cells from healthy controls were more potent than the Tim-3⁺ Treg cells from AS patients. Collectively, these results demonstrated two Treg-related impairments in AS patients. First, the frequency of the more potent Tim-3⁺ Treg cells was lower in AS patients, and second, some of Tim-3⁺ Treg-mediated functions were less potent in AS patients. Interestingly, the ratio of Tim-3⁻/Tim-3⁺ Treg cells in AS patients was directly correlated with the Bath ankylosing spondylitis disease activity index (BASDAI) score, the C-reactive protein (CRP) level, and the erythrocyte sedimentation rate (ESR). Given the fact that Tim-3⁺ Treg cells presented potent suppressive functions, Tim-3⁺ Treg cells and Tim-3⁺ Treg-mediated mechanisms might be potential candidates for immunotherapies in AS patients.



https://ift.tt/2JizSvY

Targeting macrophage immunometabolism: Dawn in the darkness of sepsis

Publication date: May 2018
Source:International Immunopharmacology, Volume 58
Author(s): V. Kumar
Sepsis is known since the time (470 BC) of great Greek physician, Hippocrates. Advancement in modern medicine and establishment of separate branches of medical science dealing with sepsis research have improved its outcome. However, mortality associated with sepsis still remains higher (25–30%) that further increases to 40–50% in the presence of septic shock. For example, sepsis-associated deaths account more in comparison to deaths-associated with myocardial-infarction and certain cancers (i.e. breast and colorectal cancer). However, it is now well established that profound activation of innate immune cells including macrophages play a very important role in the immunopathogenesis of sepsis. Macrophages are sentinel cells of the innate immune system with their location varying from peripheral blood to various target organs including lungs, liver, brain, kidneys, skin, testes, vascular endothelium etc. Thus, profound and dysregulated activation of these cells during sepsis can directly impact the outcome of sepsis. However, the emergence of the concept of immunometabolism as a major controller of immune response has raised a new hope for identifying new targets for immunomodulatory therapeutic approaches. Thus this present review starts with an introduction of sepsis as a major medical problem worldwide and signifies the role of dysregulated innate immune response including macrophages in its immunopathogenesis. Thereafter, subsequent sections describe changes in immunometabolic stage of macrophages (both M1 and M2) during sepsis. The article ends with the discussion of novel macrophage-specific therapeutic targets targeting their immunometabolism during sepsis and epigenetic regulation of macrophage immunometabolism and vice versa.

Graphical abstract

https://ift.tt/2IqlAZe

Predictive Validity of the STarT Back Tool for Risk of Persistent Disabling Back Pain in a United States Primary Care Setting

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Pradeep Suri, Kristin Delaney, Sean D. Rundell, Daniel C. Cherkin
ObjectiveTo examine the predictive validity of the STarT Back tool for classifying people with back pain into categories of low, medium, and high risk of persistent disabling back pain, in US primary care.DesignSecondary analysis of data from participants receiving usual care in a randomized clinical trial.SettingPrimary care clinics.Participants1109 adults with back pain ≥18 years of age. Those with specific causes of back pain (pregnancy, disc herniation, vertebral fracture, spinal stenosis) and work-related injuries were not included.InterventionsN/AMain Outcome MeasuresThe original 9-item version of the STarT Back tool, administered at baseline, stratified patients by their risk (low, medium, high) of persistent disabling back pain ('STarT Back risk group'). Persistent disabling back pain was defined as Roland-Morris Disability Questionnaire scores of ≥7 at 6-month follow-up.ResultsSTarT Back risk group was a significant predictor of persistent disabling back pain (p<0.0001) at 6-month follow-up. The proportion of individuals with persistent disabling back pain at follow-up was 22% (95% confidence interval [CI] 18-25%) in the low risk group, 62% (95% CI 57-67%) in the medium-risk group, and 80% (95% CI 75-85%) in the high-risk group. The relative risk of persistent disabling back pain was 2.9 (95% CI 2.4-3.5) in the medium-risk group as compared to the low-risk group, and 3.7 (95% CI 3.1-4.4) in the high-risk group.ConclusionsWe found that the STarT Back risk groups successfully separated people with back pain into distinct categories of risk for persistent disabling back pain at 6-month follow-up in US primary care. These results were very similar to those seen in the original STarT Back validation study. This validation study is a necessary first step towards identifying whether the entire STarT Back approach, including matched/targeted treatment, can be effectively used for primary care in the US.



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Conceptual Underpinnings of the Quality of Life in Neurological Disorders (Neuro-QoL): Comparisons of Core Sets for Stroke, Multiple Sclerosis, Spinal Cord Injury, and Traumatic Brain Injury

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Alex W.K. Wong, Stephen C.L. Lau, Mandy W.M. Fong, David Cella, Jin-Shei Lai, Allen W. Heinemann
ObjectiveTo determine the extent to which the content of the Quality of Life in Neurological Disorders (Neuro-QoL) covers the ICF core sets for multiple sclerosis (MS), stroke, spinal cord injury (SCI), and traumatic brain injury (TBI) using summary linkage indicators.DesignContent analysis by linking content of the Neuro-QoL to corresponding ICF codes of each core set for MS, stroke, SCI, and TBI.SettingThree academic centersParticipantsNoneInterventionsNoneMain Outcome MeasureFour summary linkage indicators proposed by MacDermid and colleagues were estimated to compare the content coverage between Neuro-QoL and the ICF codes of core sets for MS, stroke, MS, and TBI.ResultsNeuro-QoL represented 20%-30% core set codes for different conditions in which more codes in core sets for MS (29%), stroke (28%), and TBI (28%) were covered than those for SCI in the LT (20%) and EPA (19%) contexts. Neuro-QoL represented nearly half of the unique Activity and Participation codes (43%–49%) and less than one-third of the unique Body Function codes (12%−32%). It represented fewer environmental codes (2%−6%) and no Body Structures codes. Absolute linkage indicators found that at least 60% of Neuro-QoL items were linked to core set codes (63%-95%) but many items covered same codes as revealed by unique linkage indicators (7%-13%), suggesting high concept redundancy among items.ConclusionThe Neuro-QoL links more closely to ICF core sets for stroke, MS, and TBI than to those for SCI, and primarily covers Activity and Participation ICF domains. Other instruments are needed to address concepts not measured by the Neuro-QoL when a comprehensive health assessment is needed.



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Measurement Characteristics and Clinical Utility of the Pediatric Evaluation of Disability Inventory in Children With Cerebral Palsy

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Sarah Brew, Erin Langan, Amanda Link-Dudek, Ryan Walsh, Linda Ehrlich-Jones




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Effectiveness of Client-Centered “Tune-Ups” on Community Reintegration, Mobility, and Quality of Life After Stroke: A Randomized Controlled Trial

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Brenda Brouwer, Dianne Bryant, S. Jayne Garland
ObjectiveTo explore the effectiveness of a 2-week client-centered rehabilitation intervention (tune-up) delivered 6 months after inpatient discharge on community reintegration at 1 year in people with stroke.DesignA multicenter randomized controlled trial with 2 groups: an intervention ("tune-up") group and a control group having the same exposure to assessment.SettingThree research laboratories.ParticipantsParticipants (N=103) with hemiparetic stroke recruited from inpatient rehabilitation units at the time of discharge.InterventionsParticipants randomized to the tune-up group received 1-hour therapy sessions in their home 3times/wk for 2 weeks at 6 months postdischarge focusing on identified mobility-related goals. A second tune-up was provided at 12 months.Main Outcome MeasuresCommunity reintegration measured by the Subjective Index of Physical and Social Outcome at 12 months and secondary outcomes included the Berg Balance Scale and measures of mobility and health-related quality of life up to 15 months.ResultsAt 12 months, both groups showed significant improvement in community reintegration (P<.05), a trend evident at all time points, with no difference between groups (mean difference, −0.5; 95% confidence interval, −1.8 to 2.7; P=.68). Similarly, a main effect of time reflected improvement in mobility-related and quality of life outcomes for both groups (P≤.0.5), but no group differences (P≥.30).ConclusionsAll participants in the tune-up group met or exceeded at least 1 mobility-related goal; however, the intervention did not differentially improve community reintegration. The improvements in mobility and quality of life over the 15-month postdischarge period may be secondary to high activity levels in both study groups and exposure to regular assessment.



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Is going beyond Rasch analysis necessary to assess the construct validity of a motor function scale?

Publication date: Available online 3 April 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Tiffanie Guillot, Sylvain Roche, Pascal Rippert, Dalil Hamroun, Jean Iwaz, René Ecochard, Carole Vuillerot
ObjectiveExamine whether a Rasch analysis is sufficient to establish the construct validity of the Motor Function Measure (MFM) and discuss whether weighting the MFM item scores would improve the MFM construct validity.DesignObservational cross-sectional multicenter study.Setting23 physical medicine departments, neurology departments, or reference centers for neuromuscular diseasesParticipants911 patients (aged 6 to 60 years) with Charcot-Marie-Tooth disease (CMT), facio-scapulo-humeral dystrophy (FSHD), or myotonic dystrophy type 1 (DM1)InterventionsNone.Main Outcome Measure(s)Comparison of the goodness-of-fit of the Confirmatory Factor Analysis (CFA) model vs. that of a modified multidimensional Rasch model on MFM item scores in each considered disease.ResultsCFA model showed good fit to the data and significantly better goodness-of-fit than the modified multidimensional Rasch model whatever the disease (P<0.001). Statistically significant differences in item standardized factor loadings were found between DM1, CMT, and FSHD in only 6 out of 32 items (Items 6, 27, 2, 7, 9 and 17).ConclusionIn the case of multidimensional scales designed to measure patient abilities in various diseases, a Rasch analysis might not be the most convenient whereas a CFA is able to establish the scale construct validity and provide weights to adapt the item scores to a specific disease.



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Contribution to the understanding of biologic concentrations of arsenic in children living in an urban area from Rio de Janeiro, Brazil

Abstract

There are few studies about children's environmental exposure to arsenic (As) in Brazil, most of them being in mining regions. The objective of this study was to contribute to the understanding of biologic concentrations of arsenic in children living in an urban area, in Brazil. A study of arsenic concentrations in capillary blood (n = 270), nail (n = 261), and urine (n = 99) samples, in male and female children, 8 to 10 years old, from two public schools in Rio de Janeiro, was conducted. Socio-economic and health data were obtained through questionnaires. The nail and capillary blood analysis were performed by inductively coupled plasma mass spectrometry (ICP-MS), while urine samples were analyzed using hydride generation atomic absorption spectrometry (HG-AAS). The median, geometric mean, and 95th percentiles of total arsenic concentrations were, respectively, 2.53, 2.40, and 3.58 μg/L in capillary blood; 0.09, 0.10, and 0.24 μg/g in nails; and 12.50, 10.97, and 39.45 μg/L in urine. The geometric mean of urinary arsenic level was above the values reported by international surveys for non-exposed populations. The arsenic concentrations in nails were compatible with the values found in national studies. These outcomes can contribute to the increase of knowledge on biologic concentrations of arsenic in children living in urban areas, in Brazil.

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Characterization of toluene metabolism by methanotroph and its effect on methane oxidation

Abstract

Methanotrophs not only oxidize CH₄, but also can oxidize a relatively broad range of other substrates, including trichloroethylene, alkanes, alkenes, and aromatic compounds. In this study, Methylosinus sporium was used as a model organism to characterize toluene metabolism by methanotrophs. Reverse transcription quantitative PCR analysis showed that toluene enhanced the mmoX expression of M. sporium. When the toluene concentration was below 2000 mg m⁻³, the kinetics of toluene metabolism by M. sporium conformed to the Michaelis-Menten equation (V_max = 0.238 g g_{dry weight}⁻¹ h⁻¹, K_m  = 545.2 mg m⁻³). The use of a solid-phase extraction technique followed by a gas chromatography-mass spectrometry analysis and molecular docking calculation showed that toluene was likely to primarily bind the di-iron center structural region of soluble methane monooxygenase (sMMO) hydroxylase and then be oxidized to o-cresol. Although M. sporium oxidized toluene, it did not incorporate toluene into its biomass. The coexistence of toluene and CH₄ could influence CH₄ oxidation, the growth of methanotrophs, and the distribution of CH₄-derived carbon, which were related to the ratio of the toluene concentration to biomass. These results would be helpful to understand the metabolism of CH₄ and non-methane volatile organic compounds in the environment.

https://ift.tt/2GQBM92

Politically-focused intrusive thoughts and associated ritualistic behaviors in a community sample

Publication date: Available online 31 March 2018
Source:Journal of Anxiety Disorders
Author(s): Sandra L. Cepeda, Dean McKay, Sophie C. Schneider, Valérie La Buissonnière-Ariza, Egberts Jolenthe T.N.E., Elizabeth McIngvale, Wayne K. Goodman, Eric A. Storch
A significant proportion of the U.S. population report increased stress attributed to the political climate following the controversial 2016 United States (U.S.) Presidential election. The political stressors paired with the growth in news consumption and social media-use could be a potential trigger for obsessive-compulsive-like symptoms specific to politics in some individuals. This study aimed to elucidate the rate of Politically-focused Intrusive Thoughts and associated Ritualistic Behaviors (PITRB), their demographic and clinical correlates, and the degree of association with political ideology. Survey data were collected using the crowdsourcing platform Mechanical Turk. A total of N = 484 individuals completed the survey. Measures of politically-focused intrusive thoughts and ritualistic behaviors, general obsessive-compulsive symptoms, depression, anxiety, anxiety control, worry, and disability were administered, as well as a measure of social and economic conservative affiliation. Results showed that a quarter of the sample (25.2%) had at least one PITRB more than once a day. PITRB was associated with all measures of psychopathology and disability. Finally, anxiety control moderated the relationship between PITRB and both anxiety and depression. No differences in psychopathology were found between major party affiliations. The findings suggest that politically-focused intrusive thoughts and ritualistic behaviors are associated with psychopathology domains in a manner comparable to general obsessive-compulsive symptoms.



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“Association Splitting” Versus Cognitive Remediation in Obsessive-Compulsive Disorder: A Randomized Controlled Trial

Publication date: Available online 31 March 2018
Source:Journal of Anxiety Disorders
Author(s): Lena Jelinek, Marit Hauschildt, Birgit Hottenrott, Michael Kellner, Steffen Moritz
Studies have confirmed the efficacy of the cognitive intervention Association Splitting (AS) in obsessive-compulsive disorder (OCD) when applied as a self-help technique. AS aims to alter symptom-provoking automated cognitive networks of OC-related stimuli by building new or strengthening established but weak neutral associations. The aim of this study was to investigate the acceptance and benefits of therapist-assisted AS as an add-on to cognitive behavioral therapy (CBT). One hundred and nine patients with OCD who were undergoing CBT were randomly assigned to either AS or cognitive remediation (CR). Both groups were assessed at baseline, 4 weeks and 6 months later. The primary measure was the Yale-Brown Obsessive Compulsive Scale. Although patients' acceptance of AS was good, there was no evidence for the superiority of AS over CR regarding overall symptom severity. A larger decrease was found from baseline to 6 months follow-up in AS regarding avoidance. Moreover, subsidiary analyses excluding control patients who had obtained information about AS indicated its superiority. Despite high acceptance, we found no clear additional effect of AS beyond CBT treatment. Because superiority of AS was found in post hoc analyses excluding control patients who had obtained information on AS, we suggest that contagion effects deserve consideration.



https://ift.tt/2GL8Z5N