Medicine by Sfakianakis Alexandros: 11/23/17

Πέμπτη 23 Νοεμβρίου 2017

Regulation of cell proliferation in the retinal pigment epithelium: differential regulation of the death associated protein like-1 DAPL1 by alternative MITF splice forms

Summary

Vertebrate eye development and homoeostasis critically depend on the regulation of proliferation of cells forming the retinal pigment epithelium (RPE). Previous results indicated that the death associated protein like-1 DAPL1 cell-autonomously suppresses RPE proliferation in vivo and in vitro. Here we show in human RPE cell lines that the pigment cell transcription factor MITF regulates RPE cell proliferation by upregulating DAPL1 expression. DAPL1 regulation by MITF is, however, mediated predominantly by (-) MITF, one of two alternative splice isoforms of MITF that lacks six residues located upstream of the DNA binding basic domain. Furthermore, we find that the regulation of DAPL1 by MITF is indirect in that (-) MITF stimulates the transcription of Musashi-homolog-2 (MSI2), which negatively regulates the processing of the anti-DAPL1 microRNA miR-7. Our results provide molecular insights into the regulation of RPE cell proliferation and quiescence and may help us understand the mechanisms of normal RPE maintenance and of eye diseases associated with either RPE hyperproliferation or the lack of regenerative proliferation.

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Metastasis-specific patterns of response and progression with anti-PD-1 treatment in metastatic melanoma

Summary

This study evaluated patterns of response as discerned by comprehensive metastasis-specific analysis in metastatic melanoma patients receiving anti-PD-1 antibodies. Bi-dimensional measurements of every metastasis in patients enrolled in the KEYNOTE-001 trial at a single institution were obtained at baseline and throughout treatment. Twenty-seven evaluable patients had 399 baseline metastases measurable on CT imaging. Complete response (CR) which occurred in 52.6% of metastases was smaller (mean 223mm² vs. 760mm², p < 0.01) and occurred more frequently in the lungs (65% vs 39.4%, p < 0.01). Response was heterogenous (new/progressing metastases alongside CR metastases) at first assessment in 4/14 patients with objective response (OR) as opposed to 7/13 patients with non-OR. CR of individual metastases is common and influenced by site and size. Most patients with OR demonstrate homogenous regression in all metastases at the first assessment. In contrast, patients with early heterogeneity had a poor outcome.

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Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia

Abstract

Schizophrenia is a complex neuropsychiatric disorder characterized by hallucinations, delusions, anhedonia, flat affect and cognitive impairments. The aim of this study was to propose a prenatal treatment with ketamine, a psychedelic drug that acts as a non-competitive inhibitor of glutamate NMDA receptors, as a neurodevelopmental animal model of schizophrenia. The drug was applied (i.m. 60 mg.kg⁻¹ h⁻¹) in pregnant Sprague–Dawley rats on gestational Day 14. Offspring behavior was studied on pubertal (4 weeks old) and adult (10 weeks old) stages. Also, hippocampal CA1-CA3 morphology was assessed in adult animals through a Nissl stain. Results showed a disinhibition and hyperactive behavior in pubertal animals exposed to ketamine, followed in adulthood with cognitive impairments, social withdrawal, anxiety, depression, and aggressive-like behaviors. In the hippocampus, a reduction of the CA3 layer thickness was observed, without changes in cell density. These results strongly suggest a robust link between prenatal pharmacologic manipulation of NMDA receptors and schizophrenia.

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Children's anxiety symptoms and salivary immunoglobulin A: A mutual regulatory system?

Abstract

Anxiety can impact the immune system resulting in negative health outcomes. Salivary immunoglobulin A (sIgA) is a first line of defense against foreign antigens, with lowered levels indicative of weakened mucosal immunity. Little is known about how anxiety symptoms affect the diurnal rhythm of sIgA secretion, or the longitudinal transactional sequence between the two in children and adolescents. The goals of the two studies were to: (i) explore the concurrent associations between self-reported anxiety symptoms and diurnal variations of sIgA across the day using repeated daily samples of sIgA; and (ii) examine transactional relations between children's anxiety and aggregated total amount of sIgA levels across successive periods from middle childhood (Wave 1; ages 9–12) to early adolescence (Wave 2; ages 12–15), and from early to mid- adolescence (Wave 3; ages 15–18). Concurrent results showed a steeper (positive) rise in diurnal slope of sIgA from awakening to 5 hr post-awakening in children with higher anxiety. Longitudinally, higher levels of total anxiety, and specifically, worries at Wave 1 significantly predicted lower cumulative daily levels of sIgA 3 years later at Wave 2. Lowered sIgA levels at Wave 2 in turn predicted higher anxiety at Wave 3, illustrating a "vicious cycle" feedback loop. These findings broaden our understanding of the developmental links between anxiety symptoms, the immune system, and health.

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Cortisol profiles differentiated in adolescents and young adult males with fragile X syndrome versus autism spectrum disorder

Background

Fragile X syndrome (FXS) and non-syndromic autism spectrum disorder (ASD) are distinct disorders with overlapping behavioral features. Both disorders are also highly associated with anxiety with abnormal physiological regulation implied mechanistically. Some reports suggest atypical hypothalamus-pituitary-adrenal (HPA) axis function, indexed via aberrant cortisol reactivity, in both FXS and non-syndromic ASD. However, no study has compared cortisol reactivity across these two disorders, or its relationship to ASD symptom severity.

Methods

Cortisol reactivity (prior to and following a day of assessments) was measured in 54 adolescent/young adult males with FXS contrasted to 15 males with non-syndromic ASD who had low cognitive abilities.

Results

Greater ASD symptom severity was related to increased cortisol reactivity and higher levels at the end of the day, but only in the non-syndromic ASD group. Elevated anxiety was associated with increased HPA activation in the group with FXS alone.

Conclusions

Taken together, findings suggest a unique neuroendocrine profile that distinguishes adolescent/young adult males with FXS from those with non-syndromic ASD. Severity of ASD symptoms appears to be related to cortisol reactivity in the non-syndromic ASD sample, but not in FXS; while anxiety symptoms are associated with HPA activation in the FXS sample, but not in ASD despite a high prevalence of ASD, anxiety and physiological dysregulation characteristic in both populations.

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Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitisation to cat and dog allergens in early childhood: a Finnish population-based study

Abstract

Background

Children whose 11^th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitisation to food allergens. No such finding has been reported for pet allergens.

Objective

The aim of the study was to 1) evaluate the incidence of pet (dog and cat) sensitisation according to the season of the 11^th fetal week and 2) whether the association between pet exposure and respective sensitisation is modified by the coincidence of the 11^th fetal week with pollen season.

Methods

The study population comprised all children (born between 2001 and 2006) in the province of South Karelia, Finland (N=5920). Their data of IgE and skin prick tests to pet allergens (N=538) were collected from patient records and linked with questionnaire data on pet exposure.

Results

The seasonal incidence peak of cat sensitisation was observed in children whose 11^th fetal week occurred in June (7.4%) and that of dog sensitisation in April (3.8%) and June (4.7%). The relative rate (RR) for cat sensitisation was 2.92 (95% CI 1.40-6.08) in children with cat exposure alone, 8.53 (4.07−17.86) in children with cat and fetal pollen exposures, and 0.61 (0.20−1.83) in children exposed to pollen alone, compared with children without these exposures. The respective RRs for dog sensitisation were 2.17 (1.13-4.19), 4.40 (2.19−8.83) and 1.65 (0.77−3.53).

Conclusions and clinical relevance

Coincidence of the first fetal trimester with pollen season strengthens the association between pet exposure and respective sensitisation. Pollen exposure at early pregnancy may deviate immune system towards Th2 type reactivity promoting development of specific allergy in case allergen exposure occurred. Therefore, primary prevention of allergic diseases may need to begin during early pregnancy.

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Coincidence of pollen season with the first fetal trimester together with early pet exposure is associated with sensitisation to cat and dog allergens in early childhood: a Finnish population-based study

Abstract

Background

Children whose 11^th fetal week falls in pollen season (spring) reportedly have an increased risk of sensitisation to food allergens. No such finding has been reported for pet allergens.

Objective

Methods

Results

Conclusions and clinical relevance

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Confirmed Ceylon krait (Bungarus ceylonicus) envenoming in Sri Lanka resulting in neuromuscular paralysis: a case report

Ceylon krait (Bungarus ceylonicus) is a venomous elapid snake endemic to Sri Lanka. It inhabits shaded home gardens and forests in the wet zone of Sri Lanka and might creep into houses in the night. Despite frequ...

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Facilitated acquisition of the classically conditioned eyeblink response in active duty military expressing posttraumatic stress disorder symptoms

Publication date: 26 February 2018
Source:Behavioural Brain Research, Volume 339
Author(s): Justin D. Handy, Pelin Avcu, Nora Ko, Alejandro Ortiz, Michael J. Doria, Richard J. Servatius
ObjectiveLearning diathesis models underscore the role of hyper-conditioning in the development of PTSD following trauma exposure. Eyeblink classical conditioning is one method of examining associative learning biases independent of fear and threat produced by trauma. Facilitated learning is apparent in individuals self-expressing PTSD symptoms, as well as behaviorally inhibited (BI) temperament, a vulnerability factor for PTSD. Here, we examine eyeblink conditioning in active duty military personnel and relate learning with PTSD symptomology.MethodVolunteers were 83 active duty United States Coast Guard personnel (18 females) recruited from small boat stations. Personnel were administered the PTSD Checklist (PCL) to assess current PTSD symptoms using DSM-IV criteria. BI temperament was assessed with the Adult Measure of Behavioural Inhibition (AMBI). Eyeblink conditioning was conducted using a partial reinforcement schedule, whereby paired trials (500-ms pure tone conditioned stimulus co-terminating with a 50-ms air-puff unconditional stimulus) were interpolated with 50% CS-alone trials.ResultsConsistent with previous work, there was a high degree of concordance between BI and incidence of PTSD. Further, PTSD was associated with faster learning during the acquisition period, with conditioned responding sustained through the extinction period.ConclusionsThese results reinforce the relationship between BI and PTSD in an active duty military sample, supporting previous observations in veteran and civilian samples. The conditioning data are consistent with predictions derived from a learning diathesis model of stress and anxiety, suggesting facilitated associative learning may represent an additional vulnerability for the development and maintenance of stress-related pathology.

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Structural malformations of the brain, eye, and pituitary gland in PHACE syndrome

PHACE syndrome is the association of segmental facial hemangiomas with congenital arterial, brain, cardiac, and ocular anomalies. Structural brain malformations affect 41–52% of PHACE patients and can be associated with focal neurologic deficits, developmental delays, and/or intellectual disability. To better characterize the spectrum of structural brain and other intracranial anomalies in PHACE syndrome, MRI scans of the head/neck were retrospectively reviewed in 55 patients from the PHACE Syndrome International Clinical Registry and Genetic Repository. All registry patients with a diagnosis of definite PHACE syndrome who had MRI scans of satisfactory quality were included. Of 55 patients, 34 (62%) demonstrated ≥1 non-vascular intracranial anomaly; structural brain malformations were present in 19 (35%). There was no difference in the prevalence of brain anomalies between genders. Brain anomalies were more likely in patients with S1 and/or S2 distribution of facial hemangioma. The most common structural brain defects were cerebellar hypoplasia (25%) and fourth ventricle abnormalities (13%). Dandy–Walker complex and malformations of cortical development were present in 9% and 7%, respectively. Extra-axial findings such as pituitary anomalies (18%) and intracranial hemangiomas (18%) were also observed. Six patients (11%) had anomalies of the globes or optic nerve/chiasm detectable on MRI. Brain malformations comprise a diverse group of structural developmental anomalies that are common in patients with PHACE syndrome. Along with brain malformations, numerous abnormalities of the pituitary, meninges, and globes were observed, highlighting the need for careful radiologic assessment of these structures in the neuroimaging workup for PHACE syndrome.

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Confirmed Ceylon krait (Bungarus ceylonicus) envenoming in Sri Lanka resulting in neuromuscular paralysis: a case report

Correction to: Long-term patient reported outcomes following radiation therapy for oropharyngeal cancer: cross-sectional assessment of a prospective symptom survey in patients ≥65 years old

In the original publication [1] the name of author Jeremy M. Aymard was spelled wrong. The original article was updated to rectify this error.

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Severe infantile onset developmental and epileptic encephalopathy caused by mutations in autophagy gene WDR45

Summary

Heterozygous de novo variants in the autophagy gene, WDR45, are found in beta-propeller protein-associated neurodegeneration (BPAN). BPAN is characterized by adolescent onset dementia and dystonia; 66% patients have seizures. We asked whether WDR45 was associated with developmental and epileptic encephalopathy (DEE). We performed next generation sequencing of WDR45 in 655 patients with developmental and epileptic encephalopathies. We identified 3/655 patients with DEE plus 4 additional patients with de novo WDR45 pathogenic variants (6 truncations, 1 missense); all were female. Six presented with DEE and 1 with early onset focal seizures and profound regression. Median seizure onset was 12 months, 6 had multiple seizure types, and 5/7 had focal seizures. Three patients had magnetic resonance susceptibility-weighted imaging; blooming was noted in the globus pallidi and substantia nigra in the 2 older children aged 4 and 9 years, consistent with iron accumulation. We show that de novo pathogenic variants are associated with a range of developmental and epileptic encephalopathies with profound developmental consequences.

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Inhibition of monoacylglycerol lipase terminates diazepam-resistant status epilepticus in mice and its effects are potentiated by a ketogenic diet

Summary

Objective

Status epilepticus (SE) is a life-threatening and commonly drug-refractory condition. Novel therapies are needed to rapidly terminate seizures to prevent mortality and morbidity. Monoacylglycerol lipase (MAGL) is the key enzyme responsible for the hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG) and a major contributor to the brain pool of arachidonic acid (AA). Inhibiting of monoacylglycerol lipase modulates synaptic activity and neuroinflammation, 2 mediators of excessive neuronal activation underlying seizures. We studied the effect of a potent and selective irreversible MAGL inhibitor, CPD-4645, on SE that was refractory to diazepam, its neuropathologic sequelae, and the mechanism underlying the drug's effects.

Methods

Diazepam-resistant SE was induced in adult mice fed with standard or ketogenic diet or in cannabinoid receptor type 1 (CB1) receptor knock-out mice. CPD-4645 (10 mg/kg, subcutaneously) or vehicle was dosed 1 and 7 h after status epilepticus onset in video–electroencephalography (EEG) recorded mice. At the end of SE, mice were examined in the novel object recognition test followed by neuronal cellloss analysis.

Results

CPD-4645 maximal plasma and brain concentrations were attained 0.5 h postinjection (half-life = 3.7 h) and elevated brain 2-AG levels by approximately 4-fold. CPD-4645 administered to standard diet–fed mice progressively reduced spike frequency during 3 h postinjection, thereby shortening SE duration by 47%. The drug immediately abrogated SE in ketogenic diet–fed mice. CPD-4645 rescued neuronal cell loss and cognitive deficit and reduced interleukin (IL)-1β and cyclooxygenase 2 (COX-2) brain expression resulting from SE. The CPD-4645 effect on SE was similar in mice lacking CB1 receptors.

Significance

MAGL represents a novel therapeutic target for treating status epilepticus and improving its sequelae. CPD-4645 therapeutic effects appear to be predominantly mediated by modulation of neuroinflammation.

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Oral keratinocytes synthesize CTACK: a new insight into the pathophysiology of the oral mucosa

Abstract

The skin-associated chemokine CTACK plays a key role in many inflammatory conditions and could be instrumental in the pathophysiology of tissue-specific immunological diseases such as oral lichen planus (OLP). In the present study, we investigated by RT-PCR, ELISA, chemotaxis assays, and fluorescence-activated cell sorting (FACS) the production of CTACK in oral keratinocytes, its expression in tissues from normal and OLP patients, and its role in T cell recruitment. CTACK was produced by the oral epithelium and it affects chemotaxis of memory CLA+ cells to the oral epithelium. CTACK mRNA was expressed constitutively in primary oral epithelium and was increased during pro-inflammatory IFN-γ treatment. We found a constitutive production of CTACK at a protein level in oral primary cells that increased after IFN-γ treatment. Moreover, we confirmed that CTACK attracts memory T cells and those T cells that express CLA above the level of basal migration.

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Personal history of non-melanoma skin cancer diagnosis and death from melanoma in women

Abstract

Melanoma incidence is increasing. We evaluated risk of melanoma death after diagnosis of non-melanoma skin cancer (NMSC).

We followed 77,288 female American nurses from the Nurses' Health Study from 1986 to 2012. We used Cox proportional hazards models to determine the hazard ratio (HR) of lethal and non-lethal melanoma diagnosis and melanoma death, according to personal NMSC history. Among melanoma cases, we examined the HR of melanoma death and the odds ratio (OR) of melanoma with a Breslow thickness ≥ 0.8mm or Clark's level of IV and V according to history of NMSC.

We documented 930 melanoma cases without NMSC history and 615 melanoma cases with NMSC history over 1.8 million person-years. The multivariate-adjusted HR (95% confidence interval) of melanoma death associated with personal history of NMSC was 2.89 (1.85-4.50). Women with history of NMSC were more likely to develop non-lethal melanoma than lethal melanoma (HR (95% CI): 2.31 (2.05–2.60) vs. 1.74 (1.05-2.87)). Among melanoma cases, women with history of NMSC had a non-significant decreased risk of melanoma deaths (0.87 (0.55-1.37)), Breslow thickness ≥0.8mm (0.85 (0.59-1.21)) and Clark's levels IV and V (0.81(0.52-1.24)).

Women with NMSC history were less likely to be diagnosed with a lethal melanoma than a non-lethal melanoma, but overall rate of melanoma diagnosis was increased in both subtypes, leading to the increased risk of subsequent melanoma death. Our findings suggest the continued need for dermatologic screening for patients after NMSC diagnosis, given increased melanoma risk. Early detection among NMSC patients may decrease deaths from subsequent melanoma. This article is protected by copyright. All rights reserved.

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Tank bromeliads capture Saharan dust in El Yunque National Forest, Puerto Rico

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Dana L. Royer, Kylen M. Moynihan, Carolyn Ariori, Gavin Bodkin, Gabriela Doria, Katherine Enright, Rémy Hatfield-Gardner, Emma Kravet, C. Miller Nuttle, Lisa Shepard, Timothy C.W. Ku, Suzanne O'Connell, Phillip G. Resor
Dust from Saharan Africa commonly blows across the Atlantic Ocean and into the Caribbean. Most methods for measuring this dust either are expensive if collected directly from the atmosphere, or depend on very small concentrations that may be chemically altered if collected from soil. Tank bromeliads in the dwarf forest of El Yunque National Forest, Puerto Rico, have a structure of overlapping leaves used to capture rainwater and other atmospheric inputs. Therefore, it is likely that these bromeliads are collecting in their tanks Saharan dust along with local inputs. Here we analyze the elemental chemistry, including rare earth elements (REEs), of tank contents in order to match their chemical fingerprint to a provenance of the Earth's crust. We find that the tank contents differ from the local soils and bedrock and are more similar to published values of Saharan dust. Our study confirms the feasibility of using bromeliad tanks to trace Saharan dust in the Caribbean.

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Changes in oxidative potential of soil and fly ash after reaction with gaseous nitric acid

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Ying Zhan, Matthew Ginder-Vogel, Martin M. Shafer, Yinon Rudich, Michal Pardo, Itzhak Katra, David Katoshevski, James J. Schauer
The goal of this study was to examine the impact of simulated atmospheric aging on the oxidative potential of inorganic aerosols comprised primarily of crustal materials. Four soil samples and one coal fly ash sample were artificially aged in the laboratory through exposure to the vapor from 15.8 M nitric acid solution for 24 h at room temperature. Native and acid-aged samples were analyzed with a cellular macrophage and acellular dithionthreitol assays to determine oxidative potential. Additionally, the samples were analyzed to determine the concentration of 50 elements, both total and the water-soluble fraction of these elements by Sector Field Inductively Coupled Plasma Mass Spectrometry (SF-ICMS) and crystalline mineral composition using X-ray Diffraction (XRD). The results show that reactions with gaseous nitric acid increase the water-soluble fraction of many elements, including calcium, iron, magnesium, zinc, and lead. The mineral composition analysis documented that calcium-rich minerals present in the soils (e.g., calcite) are converted into different chemical forms, such as calcium nitrate (Ca(NO3)2). The nitric acid aging process, which can occur in the atmosphere, leads to a 200–600% increase in oxidative potential, as measured by cellular and acellular assays. This laboratory study demonstrates that the toxic effects of aged versus freshly emitted atmospheric dust may be quite different. In addition, the results suggest that mineralogical analysis of atmospheric dust may be useful in understanding its degree of aging.

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PAHs in Chinese atmosphere Part I: Concentration, source and temperature dependence

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Wan-Li Ma, Li-Yan Liu, Hong-Liang Jia, Meng Yang, Yi-Fan Li
The study on atmospheric polycyclic aromatic hydrocarbons (PAHs) in China has regional and global significance to understand the large scale atmospheric transport of PAHs. In this study, 16 US EPA priority PAHs were analyzed in more than 500 pairs of gas and particle phases samples, which were collected on the same schedule on a weekly basis from August 2008 to July 2009 at 11 urban sites (6 northern cities and 5 southern cities) across China. The average concentration was 239 ± 329 ng/m³ and 165 ± 164 ng/m³ for the northern cities and the southern cities, respectively. Different seasonal variations of atmospheric PAHs were observed between northern cities and southern cities, which were mainly caused by the different temperature effects in winter. Identified by principal component analysis, coal combustion and vehicle exhaust were the major sources of atmospheric PAHs in northern and southern cities of China, respectively. The temperature dependences of atmospheric PAHs were also different, which were caused by the different influences of temperature on identified sources. To our knowledge, this is the first comprehensive study to report the difference with concentrations, seasonal variations, sources and temperature dependences of atmospheric PAHs between northern cities and southern cities in China.

Graphical abstract

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The adverse effects of gas-burning CHP systems on the local air quality

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Javad Jazaeri, Mahdi Pahlevani
One of the benefits of the combined heat and power (CHP) systems is reducing greenhouse gases (GHG) in the national level. These systems are installed in the close vicinity of local communities and their pollution can directly affect the local environment. This paper studies the adverse environmental effects of a 2 MW gas-burning CHP (GB-CHP) system in a residential community in Mashhad, Iran. We compare the amount of CO2 and NOx emissions from the GB-CHP with the conventional choice of supplying electricity from the central power plants and heat from the locally installed boilers. The results show that the GB-CHP system increases local CO2 and NOx emissions by approximately two and six times, respectively. The NOx emission is increased from 3.1 tonnes to 18.7 tonnes. The CO2 emission increases from 3623 tonnes to 7238 tonnes. Furthermore, we use Gaussian Dispersion model to estimate the concentration of these emissions in the local area using the weather conditions of the most polluted times of the previous year. The results show that for a 3-meter stack, the maximum concentration of CO2 and NOx are 14.8 mg/m3 and 38.1 μg/m3, respectively. Our analysis shows that increasing the height of the GB-CHP stack from 3 meters to 10 meters reduces the concentration by 40%.

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Analysis of patterns in the concentrations of atmospheric greenhouse gases measured in two typical urban clusters in China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Lixin Liu, Pieter P. Tans, Lingjun Xia, Lingxi Zhou, Fang Zhang
China is the largest emitter of greenhouse gases, and urban clusters play an essential role in China's carbon emissions because of the country's unbalanced economic development. In this paper, the discrete air sample measurements of atmospheric CO2, CH4, and CO during the period between 2007 and 2013 from Shangdianzi (SDZ) station in Jing-Jin-Ji (JJJ) region and Linan (LAN) station in Yangtze River Delta (YRD) region, respectively, are presented and characterized. By backward trajectory cluster analysis, the low background CO2 mole fraction and similar long-term trends with Waliguan global station (WLG) were observed at SDZ because most of the air masses originate mostly from remote clean terrestrial areas in the north with limited information of anthropogenic emissions. But the background CH4 and CO are influenced mainly by ruminants and rice field emission from the surrounding regions and urban cluster emission in the JJJ region, which lead to the higher CH4 and CO in summer at SDZ. Whereas, the CO2, CH4 and CO background values observed at LAN are higher by the combined effects of long-distance atmospheric transportation from Northern and Central China and urban clusters emission from the YRD region. The observed polluted data at SDZ and LAN are all strongly affected by regional and local anthropogenic emissions, which lead to the higher GHGs concentrations compared to the background data. However, because the air mass transportation from the north is weak in winter and no winter heating is required and vegetation photosynthesis is still stronger in the south of China, the CO2 concentration at LAN is lower than that at SDZ in autumn and winter. The polluted CO value at SDZ is found considerably higher than that at LAN, especially in spring and winter. By analyzing the correlations of observed regional enhanced values of CO2, CH4 and CO at the two stations, we find the significant correlation between them, which means they may share the common-source of anthropogenic emissions from the regional fossil fuel and biomass burning in cold season. Moreover, the high coal-consumption proportion with the low CO2 emissions factors, and much biomass burning with low combustion efficiency in JJJ region lead to the higher slope values of △CO2 and △CO in spring and winter at SDZ and considerably higher than that at LAN. The results can provide a further understanding of regional/local features of atmospheric GHGs under the influence of human activities in the urban clusters in China.

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Public willingness to pay for urban smog mitigation and its determinants: A case study of Beijing, China

Publication date: January 2018
Source:Atmospheric Environment, Volume 173
Author(s): Kangyin Dong, Xiangang Zeng
With the deteriorating air pollution in the urban areas of China, particularly the unprecedentedly high levels of smog, public demand for clean air is increasing. This study examines the values of public willingness to pay (WTP) for three smog mitigation scenarios in the urban areas of Beijing and investigates their determinants by employing the contingent valuation method (CVM) and interval regression model. The empirical results suggest that more than 80% of the respondents is willing to pay for smog mitigation. Respondents' WTP rises with an increasing smog mitigation percentage, and the amount of WTP for 30%, 45%, and 60% smog mitigation, respectively, is 615.13 CNY, 716.34 CNY, and 914.49 CNY, accounting for 0.55%, 0.64%, and 0.82% of their annual income. In contrast with other cities, the ratio of WTP to income in Beijing seems to situate inside a relatively moderate range. Moreover, respondents' knowledge, risk perception, and attitude toward government are positively and significantly correlated with their WTP, and other determinants such as age, health condition, and annual income also significantly affect the value of WTP. We further recommend several important policy implications, which offer new evidence for developing specific policies to tackle smog pollution.

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Comparative immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine and 4vHPV vaccine administered according to two- or three-dose schedules in girls aged 9–14 years: Results to month 36 from a randomized trial

Publication date: Available online 23 November 2017
Source:Vaccine
Author(s): Ting Fan Leung, Anthony Pak-Yin Liu, Fong Seng Lim, Franck Thollot, Helen May Lin Oh, Bee Wah Lee, Lars Rombo, Ngiap Chuan Tan, Roman Rouzier, Stéphanie De Simoni, Pemmaraju Suryakiran, Marjan Hezareh, Florence Thomas, Nicolas Folschweiller, Frank Struyf
This observer-blind study (clinicaltrials.gov NCT01462357) compared the immunogenicity and safety of two doses (2D) of the HPV-16/18 AS04-adjuvanted vaccine (2D of AS04-HPV-16/18) vs. two or three doses of the 4vHPV vaccine [2D or 3D of 4vHPV] in 1075 healthy girls aged 9–14 years. Girls were randomized (1:1:1) to receive 2D of AS04-HPV-16/18 at months (M) 0, 6 (N = 359), 2D of 4vHPV at M0, 6 (N = 358) or 3D of 4vHPV at M0, 2, 6 (N = 358). 351, 339 and 346 girls, respectively, returned for the concluding visit at M36. Superiority was demonstrated at M7 and M12; comparison of the immune response to both vaccine antigens was made between 2D of AS04-HPV-16/18 and 2D or 3D of 4vHPV at subsequent time points in the according-to-protocol immunogenicity cohort (ATP-I; N = 958 at M36) and the total vaccinated cohort (TVC: N = 1036 at M36). HPV-16/18-specific T-cell- and B-cell-mediated immune responses and safety were also investigated. At M36, anti-HPV-16/18 ELISA responses in the 2D AS04-HPV-16/18 group remained superior to those of the 2D and 3D 4vHPV groups. In the M36 TVC, geometric mean titers were 2.78-fold (HPV-16) and 6.84-fold (HPV-18) higher for 2D of AS04-HPV-16/18 vs. 2D of 4vHPV and 2.3-fold (HPV-16) and 4.14-fold (HPV-18) higher vs. 3D of 4vHPV. Results were confirmed by vaccine pseudovirion-based neutralisation assay. Numbers of circulating CD4⁺ T cells and B cells appeared similar across groups. Safety was in line with the known safety profiles of both vaccines. In conclusion, superior HPV-16/18 antibody responses were elicited by 2D of the AS04-HPV-16/18 compared with 2D or 3D of the 4vHPV vaccine in girls aged 9–14 years.Clinical Trial Registration: NCT0146235.

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Evaluation of three experimental in vitro models for the assessment of the mechanical cleansing efficacy of wound irrigation solutions

Abstract

The aim of this study was to compare different wound-rinsing solutions to determine differences in the efficiency and to evaluate three different in vitro models for wound cleansing. Different wound-rinsing solutions (physiological saline solution, ringer lactate solution for wound irrigation, water and a solution containing polihexanide and the surfactant undecylenamidopropyl-betain) were applied on standardised test models (one- and three-chamber model, flow-cell method and a biofilm model), each challenged with three different standardised wound test soils. In the one-chamber model saline showed a better effect on decontaminating proteins than the ringer lactate solution. In the flow-cell method, water performed better than physiological saline solution, whereas ringer lactate solution demonstrated the lowest cleansing effect. No obvious superiority between the two electrolyte-containing solutions was detectable in the biofilm model. Unfortunately, it was not possible to assess the protein decontamination qualities of the surfactant-containing solution because of the interference with the protein measurement. The flow-cell method was able to detect differences between different rinse solutions because it works at constant flow mechanics, imitating a wound-rinsing procedure. The three-chamber and the less-pronounced modified one-chamber method as well as the biofilm model had generated inhomogeneous results.

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Unilateral pectoralis major muscle flap for the treatment of sternal wounds due to Ludwig's angina

Abstract

Necrotising descending mediastinitis may rarely originate from Ludwig's angina, which is an infection of the submandibular space. The use of the bilateral pectoralis major muscle flap for the treatment of sternal wound dehiscence is common, but reports of the unilateral application of this flap are scarce. This study aims to report the use of the unilateral pectoralis major muscle flap for the treatment of sternotomy dehiscence in a patient with mediastinitis due to Ludwig's angina. A 21-year-old male patient underwent an exploratory cervicotomy and median sternotomy for drainage of a submandibular infection that extended to the anterior, retropharyngeal and mediastinal cervical spaces. The patient had dehiscence of the sternal wound, and the unilateral pectoralis major muscle flap was used for reconstruction of the defect. This flap was able to completely cover the area of dehiscence of the sternotomy, and the patient presented a good postoperative evolution, without complications. The reconstruction technique using the unilateral pectoralis major muscle flap was considered a good option for the treatment of sternotomy dehiscence. It is an adjuvant method in the treatment of infections such as mediastinitis and osteomyelitis of the sternum secondary to Ludwig's angina, allowing a stable coverage of the sternum.

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Mechanical effects of negative pressure wound therapy on abdominal wounds – effects of different pressures and wound fillers

Abstract

The mechanical deformation of the wound edge resulting from negative pressure wound therapy (NPWT) at the standard setting of around −120 mmHg has positive effects in promoting wound healing. However, it may cause pain to the patient during treatment. It is therefore important to study the mechanical effects of the wound edges using lower pressure and different wound fillers. Abdominal wounds were created on eight pigs. The wounds were sealed for NPWT using foam or gauze. Negative pressures between −20 and −160 mmHg were applied, and the decrease in wound diameter and the force with which the edges of the wound were drawn together (wound edge force) were measured. Increasing levels of negative pressure resulted in a gradual decrease in wound diameter and increase in wound edge force and reached a maximum at −120 mmHg, which is the pressure commonly used in clinical practice. Both the decrease in wound diameter and the increase in wound edge force was greater with foam than with gauze. A pressure of −80 mmHg has only 15% less effect than −120 mmHg, while a lower pressure (−40 mmHg) diminished the effects on diameter and force markedly. The NPWT-induced decrease in wound diameter and increase in wound edge force are greater at higher levels of negative pressure and when using foam than when using gauze as a wound filler. It may be possible to tailor the type of wound filler and level of negative pressure to obtain the best balance between wound healing and patient comfort.

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Negative pressure wound therapy in complex cranio-maxillofacial and cervical wounds

Abstract

The care and the management of the healing of difficult wounds at the level of the skull-facial face many problems related to patient compliance and the need to perform multiple dressings, with long periods of healing and, occasionally, a very long hospitalisation period. The introduction and evolution of negative pressure wound therapy (NPWT) in the treatment of difficult wounds has resulted in better healing, with a drastic reduction in terms of time and biological costs to the patient and cost to the health care system. The main aim of this study is to describe and discuss, using out our experience, the usefulness of NPWT in the cranial-facial-cervical region. We studied 16 patients with complex wounds of the cranial-facial-cervical region treated with NPWT. We divided clinical cases in four groups: cervicofacial infectious disease, healing complications in oncological-reconstructive surgery, healing complications of injury with exposure of bone and/or internal fixations and healing complications in traumatic injury with loss of substance. We evaluated complete or incomplete wound healing; application time, related also to hospitalisation time; days of intensive care unit (ICU) stay; management of the upper airways; timing of medication renewal; and patient comfort and compliance (on a scale of 1–5). Depression values were always between −75 and −125 mmHg in a continuous aspiration pattern. For every patient, we used the ActiVAC Therapy Unit, derived from the vacuum-assisted closure system (Kinetic Concepts Inc., San Antonio, TX). Medication renewals were performed every 48–72 hours. The NPWT application time ranged from 4 to 22 days (mean of 11·57 day). Therapy was effective to gain a complete restitutio ad integrum in every patient included in the group of cervicofacial infectious disease. Therapy has, however, been well tolerated in our series; this is probably due to the decreased number of applications, the ease of use and the comfort of the system relative to traditional dressing. Results were satisfactory for most of cases treated; faster and more effective wound healing was achieved. The lower number of NPWT applications, relating to standard dressings, led to an increase in patient comfort and compliance and a decrease in the use of medical, and in some cases economic, resources according to international literature.

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Cause-specific mortality in HPV+ and HPV− oropharyngeal cancer patients: insights from a population-based cohort

Abstract

Identifying the causes of death in head and neck cancer patients can optimize follow-up and therapeutic strategies, but studies in oropharyngeal squamous cell carcinoma (OPSCC) patients stratified by HPV status are lacking. We report cause-specific mortality in a population-based cohort of patients with OPSCC. Patients who had been diagnosed with OPSCC (n = 1541) between 2000 and 2014 in eastern Denmark were included in the study. Causes of death were collected through medical files and the Danish National Cause of Death registry. Deaths were grouped as (1) primary oropharyngeal cancer, (2) secondary malignancies, (3) cardiovascular and pulmonary disease, or (4) other/unspecified. The cumulative incidence of death and specific causes of death were determined using risk analysis. At follow-up, 723 (47.5%) patients had died. The median time to and cause of death were determined: oropharyngeal cancer (n = 432; 1.00 year), secondary malignancies (n = 131; 2.37 years), cardiovascular and pulmonary causes (n = 58; 3.48 years), and unspecified causes (n = 102; 3.42 years). HPV/p16 status was the strongest predictor of improved survival across all causes of death. The only cause of death to decrease in incidence over the 2 years after treatment was death from OPSCC. HPV/p16 positivity was an independent factor for improved survival across all causes of death in patients with OPSCC. In addition, both HPV-positive and HPV-negative OPSCC patients faced high 5- and 10-year mortality rates. Implementing secondary screening and prevention strategies for late toxicity and mortality are major goals in managing the treatment of these patients.

Identifying cause of death in oropharyngeal cancer patients may aid in optimizing follow-up and therapeutic strategies, but studies stratified on HPV status is lacking. We report cause-specific mortality in a population-based cohort of oropharyngeal cancer patients from 2000 to 2014.

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Prevalencia de alteraciones en el complejo estilohioideo y tonsilolitos en la tomografía computarizada de haz cónico realizada en individuos con fisura labiopalatina

Publication date: Available online 23 November 2017
Source:Acta Otorrinolaringológica Española
Author(s): Eymi Valery Cazas-Duran, Izabel Regina Fischer Rubira-Bullen, Otávio Pagin, Bruna Stuchi Centurion-Pagin
Introducción y objetivosLos tonsilolitos y alteraciones en el complejo estilohioideo pueden presentar similar sintomatología a otras de diferente etiología. Los individuos con fisura labiopalatina describen similares síntomas en razón de las repercusiones anatómicas propias de esta anomalía. El objetivo de este estudio fue determinar la prevalencia de alteraciones del complejo estilohioideo y tonsilolitos en exámenes de tomografía computarizada de haz cónico en individuos con fisura labiopalatina.MétodosSegún criterios de inclusión y exclusión fueron analizadas 66 tomografías de 2.794 tomografías, en el software i- Cat visión ® con índice Kappa 0,8 intraexaminador.ResultadosLa prevalencia total de osificación del complejo estilohioideo incompleto en individuos con fisura labiopalatina fue de 66,6%, la prevalencia de estos hallazgos en el género femenino fue de 75% y 61,9% en el género masculino. La prevalencia total de tonsilolitos fue de 7,5%.ConclusiónEs de relevancia constatar en el informe radiológico la presencia de la calcificación del complejo estilo-hioideo y tonsilolitos. Debido a la proximidad anatómica y similar sintomatología clínica con otras alteraciones orofaciales presentes en los individuos con fisura labiopalatina, haciendo énfasis en individuos con fisura labiopalatina del género femenino, pacientes con fisura tipo transformen incisivo y posforamen incisivo por presentar mayor prevalencia. Conocer más sobre la morfometría anatómica de individuos con fisura labiopalatina coadyuva relevantemente en la elección de conductas clínicas y calidad de vida de estos pacientes, teniendo presente que la fisura labiopalatina es una de las anomalías más comunes.Introduction and objectivesTonsilloliths and abnormal stylohyoid complex may have similar symptoms to others of different aetiology. Individuals with cleft lip and palate describe similar symptoms because of the anatomical implications that are peculiar to this anomaly. The aim of this study was to determine the prevalence of abnormal stylohyoid complex and tonsilloliths on cone beam computed tomography in individuals with cleft lip and palate.MethodsAccording to the inclusion and exclusion criteria, 66 CT scans out of of 2,794 were analysed, on i- Cat ® vision software with 0.8 index Kappa intra-examiner.ResultsThe total prevalence of ossification of the incomplete stylohyoid complex in individuals with cleft lip and palate was 66.6%; the prevalence of these findings in females was 75% and 61.9% in males. The total prevalence of tonsilloliths was 7.5%.ConclusionIt is important to ascertain calcification of the stylohyoid complex and tonsilloliths in the radiological report, due to the anatomical proximity and similarsymptomatology to other orofacial impairments inindividuals with cleft lip and palate, focusing on females with oral cleft formation, patients with incisive trans foramen cleft and incisive post foramen cleft because they are more prevalent. Greater knowledge of the anatomical morphometry of individuals with cleft lip and palate greatly contributes towards the selection of clinical behaviours and the quality of life of these patients, since cleft lip and palateis one of the most common anomalies.

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Prevalencia de alteraciones en el complejo estilohioideo y tonsilolitos en la tomografía computarizada de haz cónico realizada en individuos con fisura labiopalatina

Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Adam Ferro, Hee Joon Bae, Gayane Yenokyan, Yi Le, Todd McNutt, Omar Mian, Carol Gergis, Chloe Haviland, Theodore L. DeWeese, Daniel Y. Song
PurposeInterest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction.Methods and MaterialsPatients treated with Pd-103 to either 125 Gy or 90–100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90–100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model.ResultsOne hundred ninety-one and 41 patients were treated with 125 Gy versus 90–100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS.ConclusionLower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy.

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The impact of adjuvant vaginal brachytherapy in women with Stage II uterine endometrioid carcinoma: Results of a National Cancer Database analysis

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Joon K. Lee, Ahmed I. Ghanem, Ankit Modh, Charlotte Burmeister, Omar Mahmoud, G. Larry Maxwell, Mohamed A. Elshaikh
PurposeTo report survival outcomes in women with Stage II uterine endometrioid carcinoma who received adjuvant radiation therapy (RT) without chemotherapy using the National Cancer Database.Methods and MaterialsThe National Cancer Database was queried for women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma who underwent hysterectomy followed by adjuvant RT without chemotherapy. The χ² tests were performed to compare differences in outcome by type of adjuvant RT (external beam radiation therapy [EBRT] alone, vaginal brachytherapy [VBT] alone, or combination of EBRT and VBT). Overall survival (OS) was assessed by Kaplan–Meier and log-rank tests. Univariate and multivariate analyses were performed to identify predictors of OS.ResultsWe identified 2681 women. Simple hysterectomy was performed on 2261 women (84%). Adjuvant EBRT, VBT, and combination RT were administered to 27%, 36%, and 37%, respectively. There was a statistically significant difference in OS by modality of adjuvant RT (p = 0.01) favoring women who received VBT alone or in combination with EBRT. The 5-year OS was 80%, 87%, and 83% for women who received EBRT, VBT, and combination RT, respectively (p = 0.001). On multivariate analysis, old age, African-American race, no or fewer number of examined lymph nodes, and higher tumor grade were independent predictors of worse OS. RT modality did not sustain its independent prognostic significance as a predictor of OS.ConclusionsIn this nationwide hospital-based study of women with International Federation of Gynecology and Obstetrics Stage II uterine endometrioid carcinoma, adjuvant VBT alone provided excellent survival outcomes and may be a reasonable adjuvant RT modality for properly selected women with adequate lymph node dissection and low-grade tumors.

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Plesiobrachytherapy for chest wall recurrences of breast cancer after mastectomy and radiotherapy for breast cancer

Publication date: Available online 23 November 2017
Source:Brachytherapy
Author(s): Nadia Besson, Christophe Hennequin, Sophie Guillerm, Ingrid Fumagalli, Valentine Martin, Sophie Michaud, Luis Texeira, Laurent Quero
PurposeThe purpose of the study was to evaluate the results of high-dose-rate plesiobrachytherapy for local relapse after mastectomy and radiotherapy in terms of both local control and survival.MethodsWe reviewed retrospectively 43 patients who experienced a chest wall relapse of breast cancer after local excision (22 patients) or not (21 patients). Patients were treated with an individually designed mold with four to six fractions of 3–6 Gy high-dose-rate brachytherapy, two fractions per week. Mean total dose was 24 Gy.ResultsAfter surgical resection, the 3- and 5-year local control rates were 80% and 73%, respectively. For nonresectable patients, the overall response rate was 86%, and the 3-year infield local control and chest wall local control were 51% and 26%, respectively. The 5-year survival rate was 50.5% for the whole population, 62% after surgery, and 45.4% for irresectable patients. Acute Grade 2 or 3 toxicity occurred in 43% of the patients, resolving in a few days. Two patients had a local necrosis lasting 3 to 7 months. Late toxicity was observed in 5 patients.ConclusionsHigh-dose-rate plesiobrachytherapy is a simple outpatient technique to treat chest wall local relapse of breast cancer. As a reirradiation technique, its tolerance is acceptable. This technique may obtain long-term local control after incomplete surgery; in case of nonresectable disease, a high response rate was observed, which might improve the quality of life of these patients.

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Comparison of the gut microbiota composition between wild and captive sika deer (Cervus nippon hortulorum) from feces by high-throughput sequencing

The gut microbiota is characterized as a complex ecosystem that has effects on health and diseases of host with the interactions of many other factors together. Sika deer is the national level for the protecti...

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Stroke-like migraine attacks after radiation therapy: A misnomer?

Summary

Objective

To understand the frequency of electrographic and clinical seizures in patients with stroke-like migraine attacks after radiation therapy (SMART), and determine whether SMART warrants comprehensive electroencephalographic (EEG) monitoring and aggressive seizure management.

Methods

We searched our magnetic resonance brain imaging report database for all patients between January 2013 and December 2015 for suspected SMART syndrome. Clinical inclusion criteria were further applied as follows: inpatient adults (>18 years of age) with history of cranial radiation presenting with acute neurologic deficits as primary admission reason who lacked evidence of recurrent or new brain malignancy, stroke, or infectious agents in cerebrospinal fluid. Six patients were identified. All 6 patients underwent prolonged video EEG monitoring as part of our standard protocol.

Results

All patients but 1 were found to have multiple or prolonged electrographic seizures consistent with status epilepticus during video EEG monitoring. Their neurological deficit and/or mental status change improved in parallel with resolution of the seizure activity.

Significance

SMART is likely a misnomer that underestimates the significance of seizures and status epilepticus in the pathophysiology and clinical presentation of the syndrome. Systematic continuous EEG monitoring and appropriate seizure management is warranted to reduce symptom duration and optimize clinical outcome.

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BAD knockout provides metabolic seizure resistance in a genetic model of epilepsy with sudden unexplained death in epilepsy

Summary

Metabolic alteration, either through the ketogenic diet (KD) or by genetic alteration of the BAD protein, can produce seizure protection in acute chemoconvulsant models of epilepsy. To assess the seizure-protective role of knocking out (KO) the Bad gene in a chronic epilepsy model, we used the Kcna1^−/− model of epilepsy, which displays progressively increased seizure severity and recapitulates the early death seen in sudden unexplained death in epilepsy (SUDEP). Beginning on postnatal day 24 (P24), we continuously video monitored Kcna1^−/− and Kcna1^−/−Bad^−/− double knockout mice to assess survival and seizure severity. We found that Kcna1^−/−Bad^−/− mice outlived Kcna1^−/− mice by approximately 2 weeks. Kcna1^−/−Bad^−/− mice also spent significantly less time in seizure than Kcna1^−/− mice on P24 and the day of death, showing that BadKO provides seizure resistance in a genetic model of chronic epilepsy.

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Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects

Abstract

Background

Currently available tests are unable to distinguish between asymptomatic sensitization and clinically relevant Hymenoptera venom allergy. A reliable serological marker to monitor venom immunotherapy (VIT) does also not exist. Our aim was to find reliable serological markers to predict tolerance to bee and vespid stings.

Methods

We included 77 asymptomatically-sensitized subjects, 85 allergic-patients with acute systemic sting reactions, and 61 allergic-patients currently treated with VIT. Levels of sIgE and sIgG₄ to bee and vespid venom, rApi-m-1 and rVes-v-5 were measured immediately after allergic sting-reactions or before sting-challenges and four weeks later. All sting challenges were tolerated. The inhibitory activity was determined using BAT-inhibition and ELIFAB-assay.

Results

Median sIgG₄ levels were 96-fold higher in VIT patients (p<0.001) while sIgE/sIgG₄ ratios were consistently lower (p<0.001). The ELIFAB-assay was paralleled by low sIgE/sIgG₄ ratios in VIT-patients, showing markedly higher allergen-blocking capacity (p<0.001). An almost complete inhibition of the basophil response was seen in all patients treated with vespid venom, but not in those treated with bee venom. Four weeks after the sting, sIgE and sIgG₄ levels were increased in allergic and asymptomatically-sensitized patients, but not in VIT-patients.

Conclusion

Immunological responses after stings varied in bee and vespid venom allergic patients. In patients under VIT, sIgE and sIgG₄ remained completely stable after sting-challenges. Monitoring VIT efficacy was only possible in vespid venom allergy and the sIgG₄ threshold for rVes-v-5 had the highest sensitivity to confirm tolerance. The BAT-inhibition test was the most reliable tool to confirm tolerance on an individual basis.

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TNFα induces tolerant production of CXC chemokines in colorectal cancer HCT116 cells via A20 inhibition of ERK signaling

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Xin Zhou, Dongjian An, Xueting Liu, Manli Jiang, Chuang Yuan, Jinyue Hu
Ubiquitin editing enzyme A20 functions as a tumor suppressor in various cancer. However, the mechanism for A20 regulation of cancer progress is not fully understood. In this study, we found that in human colorectal cancer HCT116 cells, TNFα induced a tolerant production of CXC chemokines, including CXCL1, 2, and 8 in a dose and time dependent manner. TNFα pre-treatment of HCT116 cells down-regulated the chemokine production induced by TNFα re-treatment. TNFα induced the phosphorylation of MAPKs ERK, JNK, P38 and NF-κB P65, but only ERK inhibition decreased TNFα-induced chemokine production. Both RT-PCR and FACS results showed that TNFα treatment did not regulate the expression of TNF receptors. However, TNFα up-regulated the expression of A20 at both mRNA and protein levels significantly. TNFα pre-treatment inhibited the signal transduction of MAPKs induced by TNFα re-stimulation, and A20 over-expression decreased the signal transduction of ERK and P38. Meanwhile, A20 inhibition by RNA interference reversed chemokine down-regulation induced by TNFα re-stimulation after TNFα pre-treatment. Taken together, these results suggested that in human colorectal cancer cells, A20 may function to inhibit cancer progression via down-regulation of TNFα-induced chemokine production by suppression of ERK signaling.

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CD26 expression is down-regulated on CD8+ T cells in patients with Hashimoto's thyroiditis

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Yalei Liu, Yuan Li, Yan Gong, Nan Yu, Yang Zhang, Ran You, Chenxue Qu, Guizhi Lu, Youyuan Huang, Ying Gao, Yanming Gao, Xiaohui Guo
The immune mechanism underlying Hashimoto's thyroiditis (HT) remains unclear. CD26, also known as dipeptidyl peptidase 4 (DPP-4), is a multifunctional molecule involved in the pathophysiology of autoimmune diseases. This study aimed to investigate the role of CD26 in the pathogenesis of HT. Peripheral blood was drawn from 20 healthy controls and 31 HT patients (19 mild HT patients and 12 severe HT patients). Plasma sCD26 concentrations were measured by ELISA, and sCD26 enzymatic activity was assessed using a luciferase-based assay. The expression levels of membrane-bound CD26 were analyzed by flow cytometry. Plasma sCD26 concentrations were lower in HT patients than in healthy controls, although the difference in sCD26 concentrations between the two groups did not reach statistical significance (P=0.07). The percentages of CD8⁺ T cells and Tc1 cells with CD26 expression were decreased in HT patients compared with those in healthy controls, and the mean fluorescence intensity (MFI) values of CD26 on CD8⁺ T cells and Tc17 cells in HT patients were significantly lower than in healthy controls (P<0.05). In HT patients, the expression of CD26 on CD8⁺ T cells and Tc subsets was decreased in the hypothyroidism group compared with that in the euthyroid group (P<0.05). These results suggest that the sCD26 concentrations and membrane-bound CD26 levels on CD8⁺ T cells are aberrant in HT and that the reduced CD26 expression may be involved in the progression of HT.

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The mast cell stabilizing activity of Chaga mushroom critical for its therapeutic effect on food allergy is derived from inotodiol

Publication date: January 2018
Source:International Immunopharmacology, Volume 54
Author(s): Thi Minh Nguyen Nguyet, Maria Lomunova, Ba Vinh Le, Ji Sun Lee, Seol Kyu Park, Jong Seong Kang, Young Ho Kim, Inkyu Hwang
While an anti-allergic effect of Chaga mushroom (Inonotus obliquus) has been indicated, its therapeutic effect on allergy and immunoregulatory mechanisms and chemical constituents directly responsible for that are hardly known. We examined the effect of 70% ethanol extract of Chaga mushroom (EE) and its dichloromethane (DF) and aqueous (AF) fractions using a mouse model of chicken ovalbumin (cOVA)-induced food allergy, and found that only EE and DF ameliorated allergy symptoms to a significant extent. The in vivo mast cell-stabilizing activity was also found only in EE and DF whereas the activities to suppress Th2 and Th17 immune responses and cOVA-specific IgE production in the small intestine were observed in all three treatment regimens, implying that inhibition of the mast cell function by lipophilic compounds was vital for the therapeutic effect. Results also indicated that inotodiol, a triterpenoid predominantly present in DF, played an active role as a mast cell stabilizer.

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Management of Acute Hip Fracture

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Foreword. This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the authors' clinical recommendations. Stage. A 65-year-old…

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Immunological differences between insect venom-allergic patients with and without immunotherapy and asymptomatically sensitized subjects

Abstract

Background

Methods

Results

Conclusion

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Prenatal diagnosis of posterior fossa anomalies: additional value of chromosomal microarray analysis in fetuses with cerebellar hypoplasia

Abstract

Objective

To elucidate the relationship between copy number variations (CNVs) detected by high-resolution chromosomal microarray analysis (CMA) and the type of prenatal posterior fossa anomalies (PFAs), especially cerebellar hypoplasia (CH).

Methods

This study involved 77 pregnancies with PFAs who underwent CMA.

Results

Chromosomal aberrations including pathogenic CNVs and variants of unknown significance (VOUS) were detected in 31.2% (24/77) of all cases by CMA and in 18.5 % (12/65) in fetuses with normal karyotypes. The high detection rate of clinically significant CNVs was evident in fetuses with cerebellar hypoplasia (54.55%, 6/11), vermis hypoplasia (33.33%, 1/3) and Dandy-Walker malformation (25.00%, 3/12). Compare with fetuses without other anomalies, cases with CH and additional malformations had the higher CMA detection rate (50.0% vs 77.8%). Three cases of isolated unilateral CH with intact vermis and normal CMA result had normal outcomes. The deletion of 5p15, 6q terminal deletion and X chromosome aberrations were the most frequent genetic defects associated with cerebellar hypoplasia.

Conclusion

Among fetuses with PFA, those with cerebellar hypoplasia, vermis hypoplasia or Dandy-Walker malformation are at the highest risk of clinically significant CNVs. CMA revealed the most frequent chromosomal aberrations associated with CH.

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The 2D axial transverse views of the fetal face: A new technique to visualize the fetal hard palate; methodology description and feasibility.

Abstract

Objectives

To describe the methodology and to assess the feasibility of a simple 2D ultrasound technique to visualize the fetal hard palate (FHP) using a strict axial transverse view (ATV).

Methods

Prospective cohort of 100 singleton pregnancies, screened routinely during second trimester scans. Three operators imaged the FHP through a strict 2D ATV according to a simple methodology. An expert sonographer reviewed all images and palate normality was confirmed at birth. Univariate and multivariate analysis of factors modifying the ability to assess the palate were performed.

Results

Feasibility of imaging the FHP was obtained in 95% of cases with no difference between the operators (p=0.7). The palate was visualized directly without fetal mobilization in 46%. An earlier gestational age at scanning, a prolonged duration of the scan, fetal back positioned anteriorly, fetal head flexed, a smaller amniotic pocket and an unmoving fetal limb significantly reduced the feasibility. All failed attempts were in fetuses with their back located in anterior and in those with a deflexed head. Multivariate analysis did not converge due to the collinearity of most parameters.

Conclusions

The ATV is an easy, simple and accessible 2D method to visualize the FHP with no additional time.

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The Treatment In Morning versus Evening (TIME) study: analysis of recruitment, follow-up and retention rates post-recruitment

The use of information technology (IT) is now the preferred method of capturing and storing clinical research data. The Treatment In Morning versus Evening (TIME) study predominantly uses electronic data captu...

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Standardised Outcomes in Nephrology—Polycystic Kidney Disease (SONG-PKD): study protocol for establishing a core outcome set in polycystic kidney disease

Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially life threatening inherited kidney disease and is responsible for 5–10% of cases of end-stage kidney disease (ESKD). Cystic ki...

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Network methods to support user involvement in qualitative data analyses: an introduction to Participatory Theme Elicitation

While Patient and Public Involvement (PPI) is encouraged throughout the research process, engagement is typically limited to intervention design and post-analysis stages. There are few approaches to participat...

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The effects of using the PReDicT Test to guide the antidepressant treatment of depressed patients: study protocol for a randomised controlled trial

Antidepressant medication is commonly used to treat depression. However, many patients do not respond to the first medication prescribed and improvements in symptoms are generally only detectable by clinicians...

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6 Steps to Treating Tinnitus

Tinnitus Causes Strange Sounds Inside the Inner Ear.

If you have tinnitus, then the constant sounds inside your ear canals can disrupt your life. Tinnitus affects numerous individuals worldwide, but researchers are still trying to understand this condition. In many cases, the cause of the strange sounds inside the ears isn't known, making treating tinnitus more difficult. Occasionally, a physician will identify the cause of ringing in the ears because a patient has had an infection in the ear canal, or she has experienced a severe injury to the inner ear.

Six Treatments For Overcoming Tinnitus

This medical condition affects one in five individuals at some point in their lifetime, so finding ways for treating tinnitus is imperative. Here are some of the ways that experts care for the patients who have tinnitus.

Treatment 1: Making Repairs To the Inner Ear

First, a physician will perform an examination to determine if there is a problem inside the inner ear from an accident, injury or growth. Surgeons can make repairs to the tiny bones, eardrum or other structures inside the skull. If a patient has a growth or tumor, then removing it can reduce the occurrence of tinnitus.

Treatment 2: Medications For Infection or Depression

A physician can prescribe medications for tinnitus to eliminate an infection that is inside the ear's components. When a patient feels distraught from the constant sounds in the ear, she can take antidepressants to overcome her anxious feelings.

Treatment 3: Ear Irrigation To Cleanse the Ear Canal

Professional cleaning of the ear canal can remove debris such as wax, skin or foreign bodies so that the eardrum can work normally. To have ear irrigation, a patient should visit a specialist who has the proper medical equipment.

Treatment 4: Treating an Underlying Condition

It is possible to have ringing in the ears from an underlying condition such as high blood pressure or a circulatory problem. When a physician can identify the underlying condition, you can take medications, or you can have treatments to reduce your blood pressure and to repair your blood circulation.

Treatment 5: Wearing a Hearing Aid

Wearing hearing aids is another method for treating tinnitus. In some cases, a hearing loss will lead to the perception of unusual sounds in the ear, and with the correct types of hearing aids, your tinnitus is reduced or will go away. Visit an audiologist to learn more about customized hearing aids.

Treatment 6: Living a Healthier Lifestyle

When you have tinnitus, living a healthier lifestyle is vital. If you smoke cigarettes, then your physician will recommend stopping this bad habit. Additional ways for treating tinnitus include eating a nutritious diet and exercising to lose weight.

Please note: the following information does not constitute professional medical advice, and is provided for general informational purposes only. Please speak to your doctor if you have tinnitus.

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Concerns about a New Preterm MR Imaging Scoring System [LETTERS]

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Reply: [LETTERS]

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The Role of Hemodynamics in Intracranial Bifurcation Arteries after Aneurysm Treatment with Flow-Diverter Stents [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Treatment of intracranial bifurcation aneurysms with flow-diverter stents can lead to caliber changes of the distal vessels in a subacute phase. This study aims to evaluate whether local anatomy and flow disruption induced by flow-diverter stents are associated with vessel caliber changes in intracranial bifurcations.

MATERIALS AND METHODS:

Radiologic images and demographic data were acquired for 25 patients with bifurcation aneurysms treated with flow-diverter stents. Whisker plots and Mann-Whitney rank sum tests were used to evaluate if anatomic data and caliber changes could be linked. Symmetry/asymmetry were defined as diameter ratio 1 = symmetric and diameter ratio <1 = asymmetric. Computational fluid dynamics was performed on idealized and patient-specific anatomies to evaluate flow changes induced by flow-diverter stents in the jailed vessel.

RESULTS:

Statistical analysis identified a marked correspondence between asymmetric bifurcation and caliber change. Symmetry ratios were lower for cases showing narrowing or subacute occlusion (medium daughter vessel diameter ratio = 0.59) compared with cases with posttreatment caliber conservation (medium daughter vessel diameter ratio = 0.95). Computational fluid dynamics analysis in idealized and patient-specific anatomies showed that wall shear stress in the jailed vessel was more affected when flow-diverter stents were deployed in asymmetric bifurcations (diameter ratio <0.65) and less affected when deployed in symmetric anatomies (diameter ratio ~1.00).

CONCLUSIONS:

Anatomic data analysis showed statistically significant correspondence between caliber changes and bifurcation asymmetry characterized by diameter ratio <0.7 (P < .001). Similarly, computational fluid dynamics results showed the highest impact on hemodynamics when flow-diverter stents are deployed in asymmetric bifurcations (diameter ratio <0.65) with noticeable changes on wall sheer stress fields. Further research and clinical validation are necessary to identify all elements involved in vessel caliber changes after flow-diverter stent procedures.

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Temporal Lobe Malformations in Achondroplasia: Expanding the Brain Imaging Phenotype Associated with FGFR3-Related Skeletal Dysplasias [PEDIATRICS]

SUMMARY:

Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the fibroblast growth factor receptor 3 (FGFR3) group of genetic skeletal disorders. Temporal lobe abnormalities have been documented in thanatophoric dysplasia and hypochondroplasia, and in 1 case of achondroplasia. We retrospectively identified 13 children with achondroplasia who underwent MR imaging of the brain between 2002 and 2015. All children demonstrated a deep transverse temporal sulcus on MR imaging. Further common neuroimaging findings were incomplete hippocampal rotation (12 children), oversulcation of the mesial temporal lobe (11 children), loss of gray-white matter differentiation of the mesial temporal lobe (5 children), and a triangular shape of the temporal horn (6 children). These appearances are very similar to those described in hypochondroplasia, strengthening the association of temporal lobe malformations in FGFR3-associated skeletal dysplasias.

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Feasibility of Brain Atrophy Measurement in Clinical Routine without Prior Standardization of the MRI Protocol: Results from MS-MRIUS, a Longitudinal Observational, Multicenter Real-World Outcome Study in Patients with Relapsing-Remitting MS [ADULT BRAIN]

BACKGROUND AND PURPOSE:

Feasibility of brain atrophy measurement in patients with MS in clinical routine, without prior standardization of the MRI protocol, is unknown. Our aim was to investigate the feasibility of brain atrophy measurement in patients with MS in clinical routine.

MATERIALS AND METHODS:

Multiple Sclerosis and Clinical Outcome and MR Imaging in the United States (MS-MRIUS) is a multicenter (33 sites), retrospective study that included patients with relapsing-remitting MS who began treatment with fingolimod. Brain MR imaging examinations previously acquired at the baseline and follow-up periods on 1.5T or 3T scanners with no prior standardization were used, to resemble a real-world situation. Brain atrophy outcomes included the percentage brain volume change measured by structural image evaluation with normalization of atrophy on 2D-T1-weighted imaging and 3D-T1WI and the percentage lateral ventricle volume change, measured by VIENA on 2D-T1WI and 3D-T1WI and NeuroSTREAM on T2-fluid-attenuated inversion recovery examinations.

RESULTS:

A total of 590 patients, followed for 16 months, were included. There were 585 (99.2%) T2-FLAIR, 425 (72%) 2D-T1WI, and 166 (28.2%) 3D-T1WI longitudinal pairs of examinations available. Excluding MR imaging examinations with scanner changes, the analyses were available on 388 (65.8%) patients on T2-FLAIR for the percentage lateral ventricle volume change, 259 and 257 (43.9% and 43.6%, respectively) on 2D-T1WI for the percentage brain volume change and the percentage lateral ventricle volume change, and 110 (18.6%) on 3D-T1WI for the percentage brain volume change and percentage lateral ventricle volume change. The median annualized percentage brain volume change was –0.31% on 2D-T1WI and –0.38% on 3D-T1WI. The median annualized percentage lateral ventricle volume change was 0.95% on 2D-T1WI, 1.47% on 3D-T1WI, and 0.90% on T2-FLAIR.

CONCLUSIONS:

Brain atrophy was more readily assessed by estimating the percentage lateral ventricle volume change on T2-FLAIR compared with the percentage brain volume change or percentage lateral ventricle volume change using 2D- or 3D-T1WI in this observational retrospective study. Although measurement of the percentage brain volume change on 3D-T1WI remains the criterion standard and should be encouraged in future prospective studies, T2-FLAIR–derived percentage lateral ventricle volume change may be a more feasible surrogate when historical or other practical constraints limit the availability of percentage brain volume change on 3D-T1WI.

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Vertebroplasty and Kyphoplasty for Osteoporotic Vertebral Fractures: What Are the Latest Data? [REVIEW ARTICLE]

SUMMARY:

Osteoporotic vertebral compression fractures frequently result in significant morbidity and health care resource use. For patients with severe and disabling pain, vertebral augmentation (vertebroplasty and kyphoplasty) is often considered. Although vertebroplasty was introduced >30 years ago, there are conflicting opinions regarding the role of these procedures in the treatment of osteoporotic vertebral compression fractures. This review article updates clinicians on the published prospective randomized controlled data, including the most recent positive trials that followed initial negative trials in 2009. Analysis of multiple national claim datasets has also provided further insight into the utility of these procedures. Finally, we considered the recent recommendations of national organizations and medical societies that advise on the use of vertebral augmentation procedures for osteoporotic vertebral compression fractures.

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Optimization of Quantitative Dynamic Postgadolinium MRI Technique Using Normalized Ratios for the Evaluation of Temporomandibular Joint Synovitis in Patients with Juvenile Idiopathic Arthritis [HEAD & NECK]

BACKGROUND AND PURPOSE:

MR imaging has been shown to be useful in the diagnosis of juvenile idiopathic arthritis of the temporomandibular joint. Prior MR imaging approaches have relied mainly on the subjective interpretation of synovial enhancement as a marker for synovial inflammation. Although, more recently, several attempts have been made to quantify synovial enhancement, these methods have not taken into account the dynamic enhancement characteristics of the temporomandibular joint and the effect of sampling time. Our aim was to develop a clinically feasible, reproducible, dynamic, contrast-enhanced MR imaging technique for the quantitative assessment of temporomandibular joint synovitis in patients with juvenile idiopathic arthritis and to study the effect of sampling time on the evaluation of synovitis.

MATERIALS AND METHODS:

This was a retrospective study of all patients who had dynamic, contrast-enhanced coronal T1 3T MR imaging through the temporomandibular joint at our institution between January 1, 2015, and July 8, 2016. Patients in this cohort included those with a history of juvenile idiopathic arthritis and control patients who underwent MR imaging for other routine, clinical purposes. Synovial enhancement was calculated for each temporomandibular joint using 3 different types of equations termed normalization ratios. The enhancement profiles generated by each equation were studied to determine which provided the best discrimination between affected and unaffected joints, was the least susceptible to sampling errors, and was the most clinically feasible.

RESULTS:

A ratio of synovial enhancement (defined as the difference between the postgadolinium and the pregadolinium T1 signal of the synovium) to the postgadolinium signal of the longus capitis provided the best discrimination between affected and unaffected joints, the least susceptibility to sampling error, and was thought to be the most clinically feasible method of quantification of synovial inflammation. Additional synovial enhancement ratios studied did not provide the same level rates of discrimination between the affected and unaffected joints and were thought to be too temporally variable to provide reliable clinical use.

CONCLUSIONS:

We provide a robust, reproducible, dynamic gadolinium-enhanced MR imaging technique for the quantitative assessment of temporomandibular joint synovitis in patients with juvenile idiopathic arthritis.

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Leukoaraiosis Attenuates Diagnostic Accuracy of Large-Vessel Occlusion Scales [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Prehospital stroke scales may help identify patients likely to have large-vessel occlusion to facilitate rapid triage to thrombectomy-capable stroke centers. Scale misclassification may result in inaccurate decisions and possible harm. Pre-existing leukoaraiosis has been shown to attenuate the association between deficit type and stroke severity. We sought to determine whether leukoaraiosis affects the predictive ability of 5 commonly used large-vessel occlusion scales.

MATERIALS AND METHODS:

We retrospectively analyzed 274 consecutive patients with stroke with available brain MR imaging and vessel imaging. We used the following large-vessel occlusion scales: the 3-Item Stroke Scale; Field Assessment Stroke Triage for Emergency Destination; Rapid Arterial Occlusion Evaluation; Vision, Aphasia, Neglect score; and Cincinnati Prehospital Stroke Severity Scale. For diagnostic scale accuracy, we assessed sensitivity, specificity, positive predictive value, negative predictive value, and . Multivariable logistic regression was used to determine the predictive ability of the scales after adjustment for leukoaraiosis and potential confounders.

RESULTS:

In unadjusted analyses, all scales predicted the presence of large-vessel occlusion (n = 46, P < .01 each), though diagnostic accuracy was attenuated among patients with moderate-to-severe leukoaraiosis. After adjustment, the Field Assessment Stroke Triage for Emergency Destination (OR = 3.2; 95% CI, 1.1–9.5; P = .033) and Rapid Arterial Occlusion Evaluation (OR = 3.7; 95% CI, 1.3–10.8; P = .015), but not the 3-Item Stroke Scale (OR = 5.4; 95% CI, 0.86–33.9; P = .073), Vision, Aphasia, Neglect score (OR = 2.5; 95% CI, 0.8–7.2), and Cincinnati Prehospital Stroke Severity Scale (OR = 2.8; 95% CI, 1.0–8.0), predicted large-vessel occlusion.

CONCLUSIONS:

The diagnostic accuracy of the tested large-vessel occlusion scales was attenuated in the presence of moderate-to-severe leukoaraiosis. This information that may aid the design of future studies that require large-vessel occlusion scale screening of patients who are likely to have concomitant leukoaraiosis.

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Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial [INTERVENTIONAL]

BACKGROUND AND PURPOSE:

Endovascular therapy has become the standard of care for patients with disabling anterior circulation ischemic stroke due to proximal intracranial thrombi. Our aim was to determine whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in posttreatment infarct volume in the Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) trial.

MATERIALS AND METHODS:

The REVASCAT trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 206 enrolled subjects (endovascular treatment, n = 103; control, n = 103), posttreatment infarct volume was measured in 204 subjects. Posttreatment infarct volumes were compared with treatment assignment and recanalization status. Appropriate statistical models were used to assess the relationship among baseline clinical and imaging variables, posttreatment infarct volume, the 24-hour NIHSS score, and functional status with the 90-day modified Rankin Scale score.

RESULTS:

The median posttreatment infarct volume in all subjects was 23.7 mL (interquartile range = 68.9 mL) and 16.3 mL (interquartile range = 50.2 mL) in the endovascular treatment arm and 38.6 mL (interquartile range = 74.9 mL) in the control arm (P = .02 for endovascular treatment versus control subjects). Baseline NIHSS (P < .01), site of occlusion (P < .03), baseline NCCT ASPECTS (P < .01), and recanalization status (P = .02) were independently associated with posttreatment infarct volume. Baseline NIHSS (P < .01), time from symptom onset to randomization (P = .02), treatment type (P = .04), and recanalization status (P < .01) were independently associated with the 24-hour NIHSS scores. The 24-hour NIHSS score strongly mediated the relationship between treatment type and 90-day mRS (P < .01 for indirect effect when adjusted for age), while posttreatment infarct volume did not (P = .26).

CONCLUSIONS:

Endovascular treatment saves brain and improves 90-day clinical outcomes primarily through a beneficial effect on the 24-hour stroke severity.

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Perivascular Spaces in Old Age: Assessment, Distribution, and Correlation with White Matter Hyperintensities [ADULT BRAIN]

BACKGROUND AND PURPOSE:

The visual rating scales for perivascular spaces vary considerably. We sought to develop a new scale for visual assessment of perivascular spaces and to further describe their distribution and association with white matter hyperintensities in old age.

MATERIALS AND METHODS:

This population-based study included 530 individuals who did not have dementia and were not institutionalized (age, ≥60 years or older; mean age, 70.7 years; 58.9% women) who were living in central Stockholm, Sweden. A semiquantitative visual rating scale was developed to score the number and size of visible perivascular spaces in 7 brain regions in each hemisphere. A modified Scheltens visual rating scale was used to assess white matter hyperintensities.

RESULTS:

The global scores for perivascular spaces ranged from 4–32 for number, 3–22 for size, and 7–54 for the combination of number and size. The weighted statistics for the intra- and interrater reliability both were 0.77. The global score for the number of perivascular spaces increased with advancing age (P < .001). The scores for the number of perivascular spaces in the basal ganglia and subinsular regions were significantly correlated with the load of white matter hyperintensities, especially in lobar and deep white matter regions (partial correlation coefficients, >0.223; P < .01).

CONCLUSIONS:

The new visual rating scale for perivascular spaces shows excellent intra- and interrater reliability. The number of perivascular spaces globally and, especially, in the basal ganglia, is correlated with the load of lobar and deep white matter hyperintensities, supporting the view that perivascular spaces are a marker for cerebral small-vessel disease.

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Πέμπτη 23 Νοεμβρίου 2017

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