A case of facial burn due to the misuse of garlic face mask for acne

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A case of facial burn due to the misuse of garlic face mask for acne

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Clinical translation and regulatory aspects of CAR/TCR-based adoptive cell therapies—the German Cancer Consortium approach

Abstract

Adoptive transfer of T cells genetically modified by TCRs or CARs represents a highly attractive novel therapeutic strategy to treat malignant diseases. Various approaches for the development of such gene therapy medicinal products (GTMPs) have been initiated by scientists in recent years. To date, however, the number of clinical trials commenced in Germany and Europe is still low. Several hurdles may contribute to the delay in clinical translation of these therapeutic innovations including the significant complexity of manufacture and non-clinical testing of these novel medicinal products, the limited knowledge about the intricate regulatory requirements of the academic developers as well as limitations of funds for clinical testing. A suitable good manufacturing practice (GMP) environment is a key prerequisite and platform for the development, validation, and manufacture of such cell-based therapies, but may also represent a bottleneck for clinical translation. The German Cancer Consortium (DKTK) and the Paul-Ehrlich-Institut (PEI) have initiated joint efforts of researchers and regulators to facilitate and advance early phase, academia-driven clinical trials. Starting with a workshop held in 2016, stakeholders from academia and regulatory authorities in Germany have entered into continuing discussions on a diversity of scientific, manufacturing, and regulatory aspects, as well as the benefits and risks of clinical application of CAR/TCR-based cell therapies. This review summarizes the current state of discussions of this cooperative approach providing a basis for further policy-making and suitable modification of processes.

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A systematic review of pyoderma gangrenosum with pulmonmary involvement: clinical presentation, diagnosis, and management

Abstract

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis that often has extracutaneous manifestations, with lung involvement being the most common (1, 2). In this systematic review we have summarized the clinical presentation, predisposing factors, and treatment of PG patients with pulmonary involvement and compared them to classic neutrophilic disorders. Using the search terms "pulmonary, lung, respiratory, bronchi, or bronchopulmonary" AND "pyoderma gangrenosum" a systematic review was conducted using PubMed and Web of Science.

This article is protected by copyright. All rights reserved.

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Basal cell carcinoma of the scrotum: an important but easily overlooked entity

Abstract

Basal cell carcinoma (BCC) is the most common skin cancer worldwide [1]. In Germany, 82/100.000 inhabitants are yearly diagnosed with BCC [2]. Since chronic exposure to UV-light is the major risk factor for the development of BCC, the tumor is rarely seen in non-sun-exposed anatomical sites such as the genital area [1]. So far, only a few case reports or small case series have been published about BCC in this location, the pathogenic mechanisms underlying the development of scrotal BCCs are unknown.

This article is protected by copyright. All rights reserved.

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Progeria: case report and new drugs perspectives

Abstract

Hutchinson-Gilford progeria syndrome (HGPS) is one of the rarest human diseases, an autosomal dominant premature aging disorder ¹. Its incidence is 1-4 per 8 million newborns ². There are aging-associated symptoms, including lack of subcutaneous fat, hair loss, joint contractures, progressive cardiovascular disease resembling atherosclerosis, and death due to heart attacks and strokes in childhood.

This article is protected by copyright. All rights reserved.

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A fifth subtype of Kaposi's sarcoma, classic Kaposi's sarcoma in men who have sex with men: a cohort study in Paris

Abstract

Background

Classic Kaposi's sarcoma (CKS) occurs predominantly among elderly men and is associated with KSHV (Kaposi's Sarcoma-Associated Herpesvirus). In low endemic countries, KSHV infects predominantly men having sex with men (MSM).

Objectives

To describe a cohort of classic Kaposi sarcoma in a low endemic area for KSHV, to highlight the features of CKS in MSM and identify prognostic factors.

Methods

Retrospective single-center study of CKS cases. We compared MSM to heterosexual patients. Then, we divided the patients into two subgroups, those requiring a systemic treatment and the others, and we performed univariate and multivariate analysis to determine aggressiveness of CKS.

Results

Between 2006 and 2015, seventy-four patients were included. Mean age at diagnosis was 68.9 years, sex ratio (M/F) was 6.4 and 28% were MSM; MSM patients were younger (p=0.02), less often originated from endemic areas (p<0.0001). KS was less severe (p=0.04), required more often a local treatment than a systemic one (p=0.03). On multivariate analysis, CD4 T cell count> 500/mm³ at baseline was associated with a reduced risk of severe evolution.

Conclusion

First CKS cohort in low endemic zone. We describe a fifth subtype of KS: KS in MSM. The CD4 T-cell count was found to correlate with prognosis.

This article is protected by copyright. All rights reserved.

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Hypertrichosis of the pinnae in a patient using panitumumab

Abstract

Various subgroups of epidermal growth factor receptor inhibitors (EGFRIs) are increasingly being used in the treatment of several cancers. However, as a generalized class effect, they are frequently associated with a wide spectrum of dermatological adverse reactions affecting skin, hair and nail of varying severity.A 53-year-old male with metastatic rectal cancer receiving every two weeks infusions of panitumumab, a human monoclonal antibody targeting EGFR, presented with a generalized acneiform papulopustular eruption (Grade 3 according to the Common Terminology Criteria for Adverse Events version 4.03).

This article is protected by copyright. All rights reserved.

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Reversed actinic damage in two children with xeroderma pigmentosum treated with topical imiquimod

Abstract

Xeroderma pigmentosum (XP) is a group of genetic diseases with high incidence of ultraviolet-related skin cancers that usually appear in childhood. Treatment options for skin cancer in XP include surgery, electrocoagulation, topical 5-fluorouracil or imiquimod 5% cream¹. Oral retinoids have been used for skin cancer prevention, alone or in combination with topical imiquimod, with good response².

This article is protected by copyright. All rights reserved.

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Diagnostic approach to subcutaneous nodules in patients with neuroendocrine tumors treated with depot somatostatin analogs: a cross-sectional study

Abstract

Background

The presence of cutaneous nodules in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) receiving depot somatostatin analogs (SSAs) is a diagnostic challenge as differential diagnosis between injection site reactions and metastases is essential.

Objective

To characterize the clinical, radiological, cytological and histopathological features of subcutaneous nodules in patients with GEP-NETs treated with SSAs.

Materials and Methods

Retrospective, cross-sectional study of patients with GEP-NETs treated with SSAs in whom subcutaneous nodules were detected on routine abdominal CT scans. High resolution and color Doppler ultrasonography was performed. Those patients with inconclusive radiological studies went through fine-needle aspiration cytology (FNAC) and/or biopsy.

Results

Twelve patients (5 males, 7 females) were included (6 midgut carcinoid NETs, 6 pancreatic NETs). Three patients received intramuscular depot octreotide, 7 subcutaneous lanreotide, and 2 both treatments. CT scan findings were nonspecific. Sonography revealed a hyperechoic pattern in recent injections, and a hypoechoic pattern with a characteristic hyperechoic peripheral rim in long-term injections (more than 3 months after injection). On color Doppler sonography, nodules showed no signs of intralesional vascularity. Fine-needle aspiration cytology (FNAC) was performed in 5 patients, revealing a characteristic acellular proteinaceous material. Biopsy in 4 patients showed different reactional infiltrates around the acellular material.

Conclusions

High resolution and color Doppler ultrasonography may be very useful for the differential diagnosis of subcutaneous nodules in patients with GEP-NETs treated with SSAs. FNAC and a biopsy are useful tests for confirmation of the diagnosis in patients with inconclusive findings. We propose a management algorithm.

This article is protected by copyright. All rights reserved.

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Atopic Dermatitis and Alcohol Use: A Meta-Analysis and Systematic Review

Abstract

While several maternal exposures have been associated with an increased risk of atopic dermatitis (AD) in offspring, the effect of alcohol use during pregnancy on the risk of AD in offspring is unclear. Furthermore, it is unclear whether adults with AD have an increased alcohol use, though other poor health behaviors have been associated with AD including smoking and physical inactivity as well as psychiatric disease. In this systematic review and meta-analysis, the association between alcohol use and AD were investigated in two ways: 1) whether alcohol use (drinkers versus abstainers) during pregnancy is associated with AD in offspring, and 2) whether AD is associated with increased alcohol use. The medical databases Pubmed, Embase and Web of Science were searched and data extraction was done by two independent reviewers. Eighteen studies were included in the qualitative analysis (comparing alcohol drinkers to abstainers) and 12 studies were included in the quantitative analysis. There was a positive association between alcohol use during pregnancy and development of AD in offspring (pooled odds ratio [OR] 1.16; 95% confidence interval [CI] 1.09-1.24). However, there was no consistent association between AD in adults and adolescents and alcohol use (pooled OR 1.06; 95% CI 0.92-1.23). There is a need for future well-designed prospective studies to firmly establish the association between alcohol use and AD.

This article is protected by copyright. All rights reserved.

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Optical clearing agent reduces scattering of light by the stratum corneum and modulates the physical properties of coenocytes via hydration

Abstract

Background

The interaction between light and the skin determine how the skin looks to the human eye. Light can be absorbed, scattered, and reflected by different components of the skin in a variety of different ways. Here, we focus on the scattering properties of the outmost layer, the stratum corneum (SC). However, we currently have limited methods with which to distinguish the scattering of light by SC from the changes due to other components of the skin.

Materials and methods

Dark-field images of tape-striped corneocytes were used in vitro to study the differences in light scattered by the SC and other skin components. Several optical clearing agents (OCAs) were tested for their ability to reduce light scattering. Physical properties of the SC (water content, keratin configuration, and volume) after OCA treatment were investigated using FT-IR, confocal Raman microscopy, and 3D laser microscopy.

Results

Urea derivatives, several reducing sugars, and sugar alcohols, which were used as OCA in optics and also used as humectants in cosmetic area, could reduce scattering. However, unlike dehydration in optics, penetration of water into the keratin was increased at low OCA concentrations. In such conditions, the volume of corneocytes was increased but their stiffness was reduced.

Conclusion

By analyzing the tape-striped SC, we were able to measure the changes in the optical and physical properties of corneocytes in response to OCAs. Hydration of the SC layer by OCAs reduces light scattering from the corneocytes and would be helpful in moisturizing the skin and helping the skin look healthy.

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Handheld 3-dimensional wound measuring system

Abstract

Background

Measuring wound dimensions is important for monitoring and predicting the healing process. In our paper we propose and validate a handheld measuring system with dedicated software for measuring wound dimensions.

Methods

The measuring system comprises a commercial DSLR camera and a light pattern projection system. It is based on triangulation and structured illumination principles which enable handheld measuring. An edge of the wound is detected from the colour information of the measurement. Across the area of the wound, virtual healthy skin is approximated which enables the calculation of the wound volume and area, in addition to the wound circumference, which is calculated from the detected edge.

Results

In vitro verification using virtual standards showed that the accuracy of the analysis software is over 95% and 93% for measuring the area and volume respectively. A significant part of the error can be attributed to the inability of approximation to replicate entirely missing features. The accuracy of measuring the volume reduced to about 89% when a 3D measuring step was included in the analysis. When measuring in vivo wounds, the unrepeatability of the system was under 8% for measuring the area, which is a bit lower than comparable systems, and 5% for measuring the volume, which is about 4 times lower.

Conclusion

Based on these results and the ease of use, we conclude that the system is suitable to be used in daily clinical practice for measuring wound dimensions.

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Association of detoxification enzymes with butene-fipronil in larvae and adults of Drosophila melanogaster

Abstract

Insecticide resistance is a major challenge in successful insect pest control as the insects have the ability to develop resistance to various widely used insecticides. Butene-fipronil is a novel compound with high toxicity to insects and less toxicity to the non-target organisms. In the present study, the effect of butene-fipronil alone and in combination with three enzyme inhibitors, piperonyl butoxide (PBO), diethyl maleate (DEM), and triphenyl phosphate (TPP), was carried out on larvae and adults of Drosophilia melanogaster. Our results indicated that the co-toxicity indices of butene-fipronil + PBO, butene-fipronil + TPP, and butene-fipronil + DEM mixtures were 437.3, 335.0, and 210.3, respectively, in the second-instar larvae, while 186.6, 256.2, and 238.5, respectively, in the adults, indicating synergistic effects. Interestingly, butene-fipronil increased the expression of CYP28A5 in the larvae; CYP9F2, CYP304A1, CYP28A5, and CYP318A1 in the female adults; and CYP303A1 and CYP28A5 in the male adults. Furthermore, high-level expression of Est-7 was observed in the female adults compared to larvae and male adults. Our results suggest that there is no difference in butene-fipronil metabolism in larvae and male and female adults of D. melanogaster.

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Functional connectivity under six anesthesia protocols and the awake condition in rat brain

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Jaakko Paasonen, Petteri Stenroos, Raimo A. Salo, Vesa Kiviniemi, Olli Gröhn
Resting-state functional magnetic resonance imaging (rsfMRI) is a translational imaging method with great potential in several neurobiologic applications. Most preclinical rsfMRI studies are performed in anesthetized animals, but the confounding effects of anesthesia on the measured functional connectivity (FC) are poorly understood. Therefore, we measured FC under six commonly used anesthesia protocols and compared the findings with data obtained from awake rats. The results demonstrated that each anesthesia protocol uniquely modulated FC. Connectivity patterns obtained under propofol and urethane anesthesia were most similar to that observed in awake rats. FC patterns in the α-chloralose and isoflurane-medetomidine combination groups had moderate to good correspondence with that in the awake group. The FC patterns in the isoflurane and medetomidine groups differed most from that in the awake rats. These results can be directly exploited in rsfMRI study designs to improve the data quality, comparability, and interpretation.



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General, crystallized and fluid intelligence are not associated with functional global network efficiency: A replication study with the human connectome project 1200 data set

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): J.D. Kruschwitz, L. Waller, L.S. Daedelow, H. Walter, I.M. Veer
One hallmark example of a link between global topological network properties of complex functional brain connectivity and cognitive performance is the finding that general intelligence may depend on the efficiency of the brain's intrinsic functional network architecture. However, although this association has been featured prominently over the course of the last decade, the empirical basis for this broad association of general intelligence and global functional network efficiency is quite limited. In the current study, we set out to replicate the previously reported association between general intelligence and global functional network efficiency using the large sample size and high quality data of the Human Connectome Project, and extended the original study by testing for separate association of crystallized and fluid intelligence with global efficiency, characteristic path length, and global clustering coefficient. We were unable to provide evidence for the proposed association between general intelligence and functional brain network efficiency, as was demonstrated by van den Heuvel et al. (2009), or for any other association with the global network measures employed. More specifically, across multiple network definition schemes, ranging from voxel-level networks to networks of only 100 nodes, no robust associations and only very weak non-significant effects with a maximal R² of 0.01 could be observed. Notably, the strongest (non-significant) effects were observed in voxel-level networks. We discuss the possibility that the low power of previous studies and publication bias may have led to false positive results fostering the widely accepted notion of general intelligence being associated to functional global network efficiency.



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Fluid intelligence and gross structural properties of the cerebral cortex in middle-aged and older adults: A multi-occasion longitudinal study

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Peng Yuan, Manuel C. Voelkle, Naftali Raz
According to Parieto-Frontal Integration Theory (P-FIT, Jung and Haier, 2007), individual differences in a circumscribed set of brain regions account for variations in general intelligence (g). The components of g, fluid (Gf) and crystallized (Gc) reasoning, exhibit distinct trajectories of age-related change. Because the brain also ages differentially, we hypothesized that age-related cognitive and neural changes would be coupled. In a sample of healthy middle-aged and older adults, we examined changes in Gf (operationalized by Cattell Culture Fair Test) and Gc (indexed by two vocabulary tests) as well as in structural properties of 19 brain regions. We fitted linear mixed models to the data collected on 73 healthy adults who participated in baseline assessment, with 43 returning for at least one follow-up, and 16 of them contributing four repeated assessments over seven years. We observed age differences as well as longitudinal decline in Gf, contrasted to a lack of age differences and stability in Gc. Cortical thickness and cortical volume exhibited significant age differences and longitudinal declines, which were accelerated in P-FIT regions. Gf (but not Gc) was associated with cortical thickness, but no such relationship was found for cortical volume. Uniformity of cognitive change (lack of reliable individual differences) precluded examination of the coupling between cognitive and brain changes. Cortical shrinkage was greater in high-Gc individuals, whereas in participants with higher Gf cortical volume slower volume shrinkage was observed.



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Changes in dynamic functional connections with aging

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Lixia Tian, Qizhuo Li, Chaomurilige Wang, Jian Yu
Despite numerous studies on age-related changes in static functional connections (FCs), the available literature on the changes in dynamic FCs with aging is lacking. This study investigated the changes in dynamic FCs with aging based on resting state fMRI data of 61 healthy adults aged 30–85 years. The time-resolved FCs among 160 pre-defined regions of interest (ROIs) were first estimated using sliding-window correlation. Based on the dynamic FC matrices, we then analyzed the dynamic switches between different FC states using k-means clustering, and correlated age with the dwell time of each FC state across subjects. The elderly were observed to spend more time in an FC state characterized by weak interactions throughout the brain and less time in an FC state characterized by strong interactions within the sensory-motor network and the cognitive control network. These results may reflect an overall weakening of connections in the elderly, which support less efficient information transfer in them. Based on the dynamic FC matrices, we also evaluated the variability and amplitude of FC time-series, which measure the relative (to mean) and absolute strength of FC fluctuations, respectively, and correlated age with the two measures across subjects. Relatively weak age-vs-variability correlations were observed, but we did observe significant negative age-vs-amplitude correlations at both the global and regional level. These results indicate that amplitude may be another effective metric for assessing FC fluctuations, in addition to the widely-used variability metric. Moreover, the observed declines in the amplitude of FC fluctuations in the elderly may support the assumption that it should be the weakening of absolute interactions between brain regions, rather than toggling between positive and negative correlations, that causes the repeatedly reported widespread (static) FC decreases with aging. Overall, the present results not only reflect an overall weakening of connections in the elderly, but indicate the potential of dynamic FC analyses in studies of age-related psychiatric and neurological disorders.



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Insulin sensitivity predicts brain network connectivity following a meal

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): John P. Ryan, Helmet T. Karim, Howard J. Aizenstein, Nicole L. Helbling, Frederico G.S. Toledo
There is converging evidence that insulin plays a role in food-reward signaling in the brain and has effects on enhancing cognition. Little is known about how these effects are altered in individuals with insulin resistance. The present study was designed to identify the relationships between insulin resistance and functional brain connectivity following a meal. Eighteen healthy adults (7 male, 11 female, age: 41-57 years-old) completed a frequently-sampled intravenous glucose tolerance test to quantify insulin resistance. On separate days at least one week apart, a resting state functional magnetic resonance imaging scan was performed: once after a mixed-meal and once after a 12-h fast. Seed-based resting state connectivity of the caudate nucleus and eigenvector centrality were used to identify relationships between insulin resistance and functional brain connectivity. Individuals with greater insulin resistance displayed stronger connectivity within reward networks following a meal suggesting insulin was less able to suppress reward. Insulin resistance was negatively associated with eigenvector centrality in the dorsal anterior cingulate cortex following a meal. These data suggest that individuals with less sensitivity to insulin may fail to shift brain networks away from reward and toward cognitive control following a meal. This altered feedback loop could promote overeating and obesity.



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Evaluation of standardized and study-specific diffusion tensor imaging templates of the adult human brain: Template characteristics, spatial normalization accuracy, and detection of small inter-group FA differences

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Shengwei Zhang, Konstantinos Arfanakis
Digital diffusion tensor imaging (DTI) templates of the adult human brain are commonly used in neuroimaging research, and their characteristics influence the accuracy of the application. However, a systematic evaluation of the characteristics and performance of standardized and study-specific DTI templates has not been conducted. The purpose of this work was to compare eight available standardized DTI templates to each other (ICBM81, ENIGMA, FMRIB58, SRI24, IIT2, NTU-DSI-122-DTI, IIT v.3.0, Eve), as well as to study-specific templates, in terms of template characteristics (image sharpness, ability to identify small brain structures, artifacts, mean values, noise properties) and performance in spatial normalization and detection of small inter-group FA differences. The IIT v.3.0 template was shown to combine a number of desirable characteristics: includes full-tensor information, is population-based, has high image sharpness, shows no visible artifacts, has low noise levels, has diffusion tensor properties and spatial features representative of data from the average individual adult brain. Furthermore, the IIT v.3.0 template was shown to allow higher inter-subject DTI spatial normalization accuracy, and detection of smaller inter-group FA differences, compared to all other templates, including study-specific templates. These findings were consistent when evaluating the templates in younger as well as older adult cohorts.

Graphical abstract

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The human body odor compound androstadienone increases neural conflict coupled to higher behavioral costs during an emotional Stroop task

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Jonas Hornung, Lydia Kogler, Michael Erb, Jessica Freiherr, Birgit Derntl
The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing.For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI.Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related brain activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy.To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words.



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Reference ability neural networks and behavioral performance across the adult life span

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Christian Habeck, Teal Eich, Ray Razlighi, Yunglin Gazes, Yaakov Stern
To better understand the impact of aging, along with other demographic and brain health variables, on the neural networks that support different aspects of cognitive performance, we applied a brute-force search technique based on Principal Components Analysis to derive 4 corresponding spatial covariance patterns (termed Reference Ability Neural Networks –RANNs) from a large sample of participants across the age range. 255 clinically healthy, community-dwelling adults, aged 20–77, underwent fMRI while performing 12 tasks, 3 tasks for each of the following cognitive reference abilities: Episodic Memory, Reasoning, Perceptual Speed, and Vocabulary. The derived RANNs (1) showed selective activation to their specific cognitive domain and (2) correlated with behavioral performance. Quasi out-of-sample replication with Monte-Carlo 5-fold cross validation was built into our approach, and all patterns indicated their corresponding reference ability and predicted performance in held-out data to a degree significantly greater than chance level. RANN-pattern expression for Episodic Memory, Reasoning and Vocabulary were associated selectively with age, while the pattern for Perceptual Speed showed no such age-related influences. For each participant we also looked at residual activity unaccounted for by the RANN-pattern derived for the cognitive reference ability. Higher residual activity was associated with poorer brain-structural health and older age, but –apart from Vocabulary-not with cognitive performance, indicating that older participants with worse brain-structural health might recruit alternative neural resources to maintain performance levels.



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Surface-based characteristics of the cerebellar cortex visualized with ultra-high field MRI

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Yohan Boillat, Pierre-Louis Bazin, Kieran O'Brien, Mário João Fartaria, Guillaume Bonnier, Gunnar Krueger, Wietske van der Zwaag, Cristina Granziera
Although having a relatively homogeneous cytoarchitectonic organization, the cerebellar cortex is a heterogeneous region characterized by different amounts of myelin, iron and protein expression profiles. In this study, we used quantitative T1 and T2* mapping at ultra-high field (7T) MRI to investigate the tissue characteristics of the cerebellar gray matter surface and its layers. Detailed subject-specific surfaces were generated at three different cortical depths and averaged across subjects to create averaged T1- and T2*-maps on the cerebellar surface. T1 surfaces showed an alternation of lower and higher T1 values when going from the median to the lateral part of the cerebellar hemispheres. In addition, longer T1 values were observed in the more superficial gray matter layers. T2*-maps showed a similar longitudinal pattern, but no change related to the cortical depths. These patterns are possibly due to variations in the level of myelination, iron and zebrin protein expression.



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Incorporating spatial constraint in co-activation pattern analysis to explore the dynamics of resting-state networks: An application to Parkinson's disease

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Xiaowei Zhuang, Ryan R. Walsh, Karthik Sreenivasan, Zhengshi Yang, Virendra Mishra, Dietmar Cordes
The dynamics of the brain's intrinsic networks have been recently studied using co-activation pattern (CAP) analysis. The CAP method relies on few model assumptions and CAP-based measurements provide quantitative information of network temporal dynamics. One limitation of existing CAP-related methods is that the computed CAPs share considerable spatial overlap that may or may not be functionally distinct relative to specific network dynamics. To more accurately describe network dynamics with spatially distinct CAPs, and to compare network dynamics between different populations, a novel data-driven CAP group analysis method is proposed in this study. In the proposed method, a dominant-CAP (d-CAP) set is synthesized across CAPs from multiple clustering runs for each group with the constraint of low spatial similarities among d-CAPs. Alternating d-CAPs with less overlapping spatial patterns can better capture overall network dynamics. The number of d-CAPs, the temporal fraction and spatial consistency of each d-CAP, and the subject-specific switching probability among all d-CAPs are then calculated for each group and used to compare network dynamics between groups.The spatial dissimilarities among d-CAPs computed with the proposed method were first demonstrated using simulated data. High consistency between simulated ground-truth and computed d-CAPs was achieved, and detailed comparisons between the proposed method and existing CAP-based methods were conducted using simulated data. In an effort to physiologically validate the proposed technique and investigate network dynamics in a relevant brain network disorder, the proposed method was then applied to data from the Parkinson's Progression Markers Initiative (PPMI) database to compare the network dynamics in Parkinson's disease (PD) and normal control (NC) groups. Fewer d-CAPs, skewed distribution of temporal fractions of d-CAPs, and reduced switching probabilities among final d-CAPs were found in most networks in the PD group, as compared to the NC group. Furthermore, an overall negative association between switching probability among d-CAPs and disease severity was observed in most networks in the PD group as well. These results expand upon previous findings from in vivo electrophysiological recording studies in PD. Importantly, this novel analysis also demonstrates that changes in network dynamics can be measured using resting-state fMRI data from subjects with early stage PD.



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A high-resolution computational localization method for transcranial magnetic stimulation mapping

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Shinta Aonuma, Jose Gomez-Tames, Ilkka Laakso, Akimasa Hirata, Tomokazu Takakura, Manabu Tamura, Yoshihiro Muragaki
BackgroundTranscranial magnetic stimulation (TMS) is used for the mapping of brain motor functions. The complexity of the brain deters determining the exact localization of the stimulation site using simplified methods (e.g., the region below the center of the TMS coil) or conventional computational approaches.ObjectiveThis study aimed to present a high-precision localization method for a specific motor area by synthesizing computed non-uniform current distributions in the brain for multiple sessions of TMS.MethodsPeritumoral mapping by TMS was conducted on patients who had intra-axial brain neoplasms located within or close to the motor speech area. The electric field induced by TMS was computed using realistic head models constructed from magnetic resonance images of patients. A post-processing method was implemented to determine a TMS hotspot by combining the computed electric fields for the coil orientations and positions that delivered high motor-evoked potentials during peritumoral mapping. The method was compared to the stimulation site localized via intraoperative direct brain stimulation and navigated TMS.ResultsFour main results were obtained: 1) the dependence of the computed hotspot area on the number of peritumoral measurements was evaluated; 2) the estimated localization of the hand motor area in eight non-affected hemispheres was in good agreement with the position of a so-called "hand-knob"; 3) the estimated hotspot areas were not sensitive to variations in tissue conductivity; and 4) the hand motor areas estimated by this proposal and direct electric stimulation (DES) were in good agreement in the ipsilateral hemisphere of four glioma patients.Conclusion(s)The TMS localization method was validated by well-known positions of the "hand-knob" in brains for the non-affected hemisphere, and by a hotspot localized via DES during awake craniotomy for the tumor-containing hemisphere.



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Effects of hunger state on the brain responses to food cues across the life span

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): L. Charbonnier, F. van Meer, A.M. Johnstone, D. Crabtree, W. Buosi, Y. Manios, O. Androutsos, A. Giannopoulou, M.A. Viergever, P.A.M. Smeets
The abundant exposure to food cues in our environment is one of the main drivers of overconsumption. Food evaluation is important for the regulation of food intake by the brain and it's interaction with hunger state. Children are especially susceptible to food cues. Understanding the mechanisms behind this regulation in healthy individuals across the life span can help to elucidate the mechanisms underlying overconsumption and aid the development of future obesity prevention strategies. Few functional neuroimaging studies have been done in children and elderly. Furthermore, it is unknown how hunger state affects neural food cue reactivity in these groups, since this has not been examined consistently.We examined the effects of hunger state and age on the brain responses to low- and high calorie foods. On two mornings, 122 participants (17 children; 38 teens; 36 adults; 31 elderly) performed a food image viewing task while being scanned using fMRI, either fasted or sated.Hunger induced greater activation during high versus low calorie food image viewing than satiety in the bilateral dorsomedial (dmPFC) and in the right dorsolateral prefrontal cortex (dlPFC) across all age groups. There was no significant main effect of age group on high versus low calorie food image viewing and no interaction between age group and hunger state.The greater activation of the dlPFC across all age groups during high calorie food image viewing in a fasted state might reflect increased inhibitory control in response to these foods. This may underlie the ability to resist overconsumption of high calorie foods. Furthermore, increased medial prefrontal cortex activation during hunger might reflect increased reward value of high calorie foods, which declines with satiation. Further studies are needed to better understand these results. Notably, overweight and obese individuals should be included to examine whether these responses are altered by weight status across the life span.



http://ift.tt/2EjtYc8

Investigating the effects of a penetrating vessel occlusion with a multi-scale microvasculature model of the human cerebral cortex

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Wahbi K. El-Bouri, Stephen J. Payne
The effect of the microvasculature on observed clinical parameters, such as cerebral blood flow, is poorly understood. This is partly due to the gap between the vessels that can be individually imaged in humans and the microvasculature, meaning that mathematical models are required to understand the role of the microvasculature. As a result, a multi-scale model based on morphological data was developed here that is able to model large regions of the human microvasculature. From this model, a clear layering of flow (and 1-dimensional depth profiles) was observed within a voxel, with the flow in the microvasculature being driven predominantly by the geometry of the penetrating vessels. It also appears that the pressure and flow are decoupled, both in healthy vasculatures and in those where occlusions have occurred, again due to the topology of the penetrating vessels shunting flow between them. Occlusion of a penetrating arteriole resulted in a very high degree of overlap of blood pressure drop with experimentally observed cell death. However, drops in blood flow were far more widespread, providing additional support for the theory that pericyte controlled regulation on the capillary scale likely plays a large part in the perfusion of tissue post-occlusion.



http://ift.tt/2DIILMa

Human aging reduces the neurobehavioral influence of motivation on episodic memory

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Maiya R. Geddes, Aaron T. Mattfeld, Carlo de los Angeles, Anisha Keshavan, John D.E. Gabrieli
The neural circuitry mediating the influence of motivation on long-term declarative or episodic memory formation is delineated in young adults, but its status is unknown in healthy aging. We examined the effect of reward and punishment anticipation on intentional declarative memory formation for words using an event-related functional magnetic resonance imaging (fMRI) monetary incentive encoding task in twenty-one younger and nineteen older adults. At 24-hour memory retrieval testing, younger adults were significantly more likely to remember words associated with motivational cues than neutral cues. Motivational enhancement of memory in younger adults occurred only for recollection ("remember" responses) and not for familiarity ("familiar" responses). Older adults had overall diminished memory and did not show memory gains in association with motivational cues. Memory encoding associated with monetary rewards or punishments activated motivational (substantia nigra/ventral tegmental area) and memory-related (hippocampus) brain regions in younger, but not older, adults during the target word periods. In contrast, older and younger adults showed similar activation of these brain regions during the anticipatory motivational cue interval. In a separate monetary incentive delay task that did not require learning, we found evidence for relatively preserved striatal reward anticipation in older adults. This supports a potential dissociation between incidental and intentional motivational processes in healthy aging. The finding that motivation to obtain rewards and avoid punishments had reduced behavioral and neural influence on intentional episodic memory formation in older compared to younger adults is relevant to life-span theories of cognitive aging including the dopaminergic vulnerability hypothesis.



http://ift.tt/2Ekn3PR

Predicting future learning from baseline network architecture

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Marcelo G. Mattar, Nicholas F. Wymbs, Andrew S. Bock, Geoffrey K. Aguirre, Scott T. Grafton, Danielle S. Bassett
Human behavior and cognition result from a complex pattern of interactions between brain regions. The flexible reconfiguration of these patterns enables behavioral adaptation, such as the acquisition of a new motor skill. Yet, the degree to which these reconfigurations depend on the brain's baseline sensorimotor integration is far from understood. Here, we asked whether spontaneous fluctuations in sensorimotor networks at baseline were predictive of individual differences in future learning. We analyzed functional MRI data from 19 participants prior to six weeks of training on a new motor skill. We found that visual-motor connectivity was inversely related to learning rate: sensorimotor autonomy at baseline corresponded to faster learning in the future. Using three additional scans, we found that visual-motor connectivity at baseline is a relatively stable individual trait. These results suggest that individual differences in motor skill learning can be predicted from sensorimotor autonomy at baseline prior to task execution.



http://ift.tt/2DLg1CJ

Suprathreshold fiber cluster statistics: Leveraging white matter geometry to enhance tractography statistical analysis

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Fan Zhang, Weining Wu, Lipeng Ning, Gloria McAnulty, Deborah Waber, Borjan Gagoski, Kiera Sarill, Hesham M. Hamoda, Yang Song, Weidong Cai, Yogesh Rathi, Lauren J. O'Donnell
This work presents a suprathreshold fiber cluster (STFC) method that leverages the whole brain fiber geometry to enhance statistical group difference analyses. The proposed method consists of 1) a well-established study-specific data-driven tractography parcellation to obtain white matter tract parcels and 2) a newly proposed nonparametric, permutation-test-based STFC method to identify significant differences between study populations. The basic idea of our method is that a white matter parcel's neighborhood (nearby parcels with similar white matter anatomy) can support the parcel's statistical significance when correcting for multiple comparisons. We propose an adaptive parcel neighborhood strategy to allow suprathreshold fiber cluster formation that is robust to anatomically varying inter-parcel distances. The method is demonstrated by application to a multi-shell diffusion MRI dataset from 59 individuals, including 30 attention deficit hyperactivity disorder patients and 29 healthy controls. Evaluations are conducted using both synthetic and in-vivo data. The results indicate that the STFC method gives greater sensitivity in finding group differences in white matter tract parcels compared to several traditional multiple comparison correction methods.



http://ift.tt/2Ei4DPI

Systemic inflammation as a predictor of brain aging: Contributions of physical activity, metabolic risk, and genetic risk

Publication date: 15 May 2018
Source:NeuroImage, Volume 172
Author(s): Fabian Corlier, George Hafzalla, Joshua Faskowitz, Lewis H. Kuller, James T. Becker, Oscar L. Lopez, Paul M. Thompson, Meredith N. Braskie
Inflammatory processes may contribute to risk for Alzheimer's disease (AD) and age-related brain degeneration. Metabolic and genetic risk factors, and physical activity may, in turn, influence these inflammatory processes. Some of these risk factors are modifiable, and interact with each other. Understanding how these processes together relate to brain aging will help to inform future interventions to treat or prevent cognitive decline.We used brain magnetic resonance imaging (MRI) to scan 335 older adult humans (mean age 77.3 ± 3.4 years) who remained non-demented for the duration of the 9-year longitudinal study. We used structural equation modeling (SEM) in a subset of 226 adults to evaluate whether measures of baseline peripheral inflammation (serum C-reactive protein levels; CRP), mediated the baseline contributions of genetic and metabolic risk, and physical activity, to regional cortical thickness in AD-relevant brain regions at study year 9.We found that both baseline metabolic risk and AD risk variant apolipoprotein E ε4 (APOE4), modulated baseline serum CRP. Higher baseline CRP levels, in turn, predicted thinner regional cortex at year 9, and mediated an effect between higher metabolic risk and thinner cortex in those regions. A higher polygenic risk score composed of variants in immune-associated AD risk genes (other than APOE) was associated with thinner regional cortex. However, CRP levels did not mediate this effect, suggesting that other mechanisms may be responsible for the elevated AD risk.We found interactions between genetic and environmental factors and structural brain health. Our findings support the role of metabolic risk and peripheral inflammation in age-related brain decline.

Graphical abstract

http://ift.tt/2DGGph6

Distant from input: Evidence of regions within the default mode network supporting perceptually-decoupled and conceptually-guided cognition

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Charlotte Murphy, Elizabeth Jefferies, Shirley-Ann Rueschemeyer, Mladen Sormaz, Hao-ting Wang, Daniel S. Margulies, Jonathan Smallwood
The default mode network supports a variety of mental operations such as semantic processing, episodic memory retrieval, mental time travel and mind-wandering, yet the commonalities between these functions remains unclear. One possibility is that this system supports cognition that is independent of the immediate environment; alternatively or additionally, it might support higher-order conceptual representations that draw together multiple features. We tested these accounts using a novel paradigm that separately manipulated the availability of perceptual information to guide decision-making and the representational complexity of this information. Using task based imaging we established regions that respond when cognition combines both stimulus independence with multi-modal information. These included left and right angular gyri and the left middle temporal gyrus. Although these sites were within the default mode network, they showed a stronger response to demanding memory judgements than to an easier perceptual task, contrary to the view that they support automatic aspects of cognition. In a subsequent analysis, we showed that these regions were located at the extreme end of a macroscale gradient, which describes gradual transitions from sensorimotor to transmodal cortex. This shift in the focus of neural activity towards transmodal, default mode, regions might reflect a process of where the functional distance from specific sensory enables conceptually rich and detailed cognitive states to be generated in the absence of input.



http://ift.tt/2Ei69Bt

TMS uncovers details about sub-regional language-specific processing networks in early bilinguals

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Sini Hämäläinen, Niko Mäkelä, Viljami Sairanen, Minna Lehtonen, Teija Kujala, Alina Leminen
Despite numerous functional neuroimaging and intraoperative electrical cortical mapping studies aimed at investigating the cortical organisation of native (L1) and second (L2) language processing, the neural underpinnings of bilingualism remain elusive. We investigated whether the neural network engaged in speech production over the bilateral posterior inferior frontal gyrus (pIFG) is the same (i.e., shared) or different (i.e., language-specific) for the two languages of bilingual speakers. Navigated transcranial magnetic stimulation (TMS) was applied over the left and right posterior inferior gyrus (pIFG), while early simultaneous bilinguals performed a picture naming task with their native languages. An ex-Gaussian distribution was fitted to the naming latencies and the resulting parameters were compared between languages and across stimulation conditions. The results showed that although the naming performance in general was highly comparable between the languages, TMS produced a language-specific effect when the pulses were delivered to the left pIFG at 200 ms poststimulus. We argue that this result causally demonstrates, for the first time, that even within common language-processing areas, there are distinct language-specific neural populations for the different languages in early simultaneous bilinguals.



http://ift.tt/2DGGjWM

Behavioral interventions for reducing head motion during MRI scans in children

Publication date: 1 May 2018
Source:NeuroImage, Volume 171
Author(s): Deanna J. Greene, Jonathan M. Koller, Jacqueline M. Hampton, Victoria Wesevich, Andrew N. Van, Annie L. Nguyen, Catherine R. Hoyt, Lindsey McIntyre, Eric A. Earl, Rachel L. Klein, Joshua S. Shimony, Steven E. Petersen, Bradley L. Schlaggar, Damien A. Fair, Nico U.F. Dosenbach
A major limitation to structural and functional MRI (fMRI) scans is their susceptibility to head motion artifacts. Even submillimeter movements can systematically distort functional connectivity, morphometric, and diffusion imaging results. In patient care, sedation is often used to minimize head motion, but it incurs increased costs and risks. In research settings, sedation is typically not an ethical option. Therefore, safe methods that reduce head motion are critical for improving MRI quality, especially in high movement individuals such as children and neuropsychiatric patients. We investigated the effects of (1) viewing movies and (2) receiving real-time visual feedback about head movement in 24 children (5–15 years old). Children completed fMRI scans during which they viewed a fixation cross (i.e., rest) or a cartoon movie clip, and during some of the scans they also received real-time visual feedback about head motion. Head motion was significantly reduced during movie watching compared to rest and when receiving feedback compared to receiving no feedback. However, these results depended on age, such that the effects were largely driven by the younger children. Children older than 10 years showed no significant benefit. We also found that viewing movies significantly altered the functional connectivity of fMRI data, suggesting that fMRI scans during movies cannot be equated to standard resting-state fMRI scans. The implications of these results are twofold: (1) given the reduction in head motion with behavioral interventions, these methods should be tried first for all clinical and structural MRIs in lieu of sedation; and (2) for fMRI research scans, these methods can reduce head motion in certain groups, but investigators must keep in mind the effects on functional MRI data.



http://ift.tt/2Ej5EH7

Effects of malathion and nitrate exposure on the zooplankton community in experimental mesocosms

Abstract

Surface waters are likely to be contaminated by both pesticides and fertilizers. Such contamination can result in changes in community composition if there is differential toxicity to individual taxa. We conducted a fully factorial mesocosm experiment that examined the single and interactive effects of environmentally realistic concentrations of nitrate and malathion on zooplankton communities and phytoplankton productivity. Malathion significantly decreased the abundance of total zooplankton, cyclopoid copepods, copepod nauplii, and Ceriodaphnia, and increased the abundance of rotifers. Nitrate addition generally had no effect on zooplankton; however, Ceriodaphnia abundance was higher in control mesocosms than in nitrate-treated mesocosms. There was only one significant interaction between malathion and nitrate treatments: For Ceriodaphnia, the no malathion, no nitrate mesocosms had much higher abundances than all other combinations of treatments. Without nitrate addition, chl a levels were uniformly low across all malathion treatments, whereas in the presence of nitrate, there were differences among the malathion treatments. In conclusion, our results demonstrate that malathion contamination of aquatic ecosystems can result in changes in the abundance and composition of zooplankton communities. In contrast, nitrate contamination appeared to have much less potential impact on zooplankton communities, either on its own or in interaction with malathion. Our results reinforce the notion that the effects of contaminants on aquatic ecosystems can be complex and further research examining the single and interactive effects of chemical stressors is needed to more fully understand their effects.

http://ift.tt/2GsGgzt

Ecologically friendly ways to clean up oil spills in harbor water areas: crude oil and diesel sorption behavior of natural sorbents

Abstract

This work aimed to evaluate the sorption capacity of natural sorbents (wool, moss, straw, peat) and their composites during the sorption of crude oil and of diesel overspread on the water surface. The work presents the research results of the maximum sorption capacity of the sorbents/their composites using crude oil/diesel; the sorption capacity of the sorbents/their composites when crude oil/diesel is spilled on the water surface; and the research results of the unrealized part of the crude oil/diesel in the sorbents. The results of the analysis showed that all the sorbents and their composites have their selectivity to crude oil less than 50%. Also the results showed that the distribution of diesel and water in the sorbents and their composites is very different compared with the distribution of crude oil during the sorption analyses. In total, the diesel in the liquid mass absorbed by the straw and the peat amounted to 17 and 20%, respectively. This shows that these sorbents are much more selective for water but not for diesel. A larger part of the diesel was in the liquid amount absorbed by the composites—up to 33%. Accordingly, the use of these composites in watery environments is much more effective than the use of individual sorbents. The composition of sorbents in the composite enhanced both the hydrophobic and the oleophilic properties; as a result, a more effective removal of the diesel and oil from the water surface was achieved.

http://ift.tt/2rOFIk2

Pollution characteristics of surface runoff under different restoration types in manganese tailing wasteland

Abstract

A great deal of manganese and associated heavy metals (such as Ni, Cu, Zn, Cd, Pb, etc.) was produced in manganese mining, smelting, and other processes and weathering and leaching of waste slag, which entered rainwater runoff by different means under the action of rainfall runoff. It caused heavy metal pollution in water environment to surrounding areas, and then environmental and human health risks were becoming increasingly serious. In the Xiangtan manganese mine, we studied the characteristics of nutritional pollutants and heavy metals by using the method of bounded runoff plots on the manganese tailing wasteland after carrying out some site treatments using three different approaches, such as (1) exposed tailings, the control treatment (ET), (2) external-soil amelioration and colonization of Cynodon dactylon (Linn.) Pers. turf (EC), and (3) external-soil amelioration and seedling seeding propagation of Cynodon dactylon (Linn.) Pers. (ES). The research showed that the maximum runoff occurred in 20,140,712 rainfall events, and the basic law of runoff was EC area > ET area > ES area in the same rainfall event. The concentration of total suspended solids (TSS) and chemical oxygen demand (COD) of three ecological restoration areas adopted the following rule: ET area > EC area > ES area. Nitrogen (N) existed mainly in the form of water soluble while phosphorus (P) was particulate. The highest concentrations of total nitrogen (TN) and total phosphorus (TP) were 11.57 ± 2.99 mg/L in the EC area and 1.42 ± 0.56 mg/L in the ET area, respectively. Cr, Ni, Pb, Zn, Mn, and Cu in surface runoff from three restoration types all exceeded the class V level of the environmental quality standard for surface water except Cu in EC and ES areas. Pollution levels of heavy metals in surface runoff from three restoration areas are shown as follows: ET area > EC area > ES area. There was a significant positive correlation between TSS and runoff, COD, and TP. And this correlation was significant between total dissolved nitrogen (TDN), TN, total dissolved phosphorus (TDP), and TP. The six heavy metals (Cu, Ni, Pb, Zn, Mn, and Cr) in surface runoff of different ecological restoration areas were strongly related to each other, and were significantly related to the TSS.

http://ift.tt/2GslAI2

The cardiovascular robustness hypothesis: Unmasking young adults' hidden risk for premature cardiovascular death

Publication date: Available online 17 January 2018
Source:Medical Hypotheses
Author(s): Lutz E. Kraushaar, Alexander Dressel
An undetected high risk for premature death of cardiovascular disease (CVD) among individuals with low-to-moderate risk factor levels is an acknowledged obstacle to CVD prevention.In this paper, we present the hypothesis that the vasculature's robustness against risk factor load will complement conventional risk factor models as a novel stratifier of risk. Figuratively speaking, mortality risk prediction without robustness scoring is akin to predicting the breaking risk of a lake's ice sheet considering load only while disregarding the sheet's bearing strength.Taking the cue from systems biology, which defines robustness as the ability to maintain function against internal and external challenges, we develop a robustness score from the physical parameters that comprehensively quantitate cardiovascular function. We derive the functional parameters using a recently introduced novel system, VascAssist 2 (iSYMED GmbH, Butzbach, Germany). VascAssist 2 (VA) applies the electronic-hydraulic analogy to a digital model of the arterial tree, replicating non-invasively acquired pule pressure waves by modulating the electronic equivalents of the physical parameters that describe in-vivo arterial hemodynamics.As the latter is also subject to aging-associated degeneration which (a) progresses at inter-individually different rates, and which (b) affects the biomarker-mortality association, we express the robustness score as a correction factor to calendar age (CA), the dominant risk factor in all CVD risk factor models. We then propose a method for the validation of the score against known time-to-event data in reference populations.Our conceptualization of robustness implies that risk factor-challenged individuals with low robustness scores will face preferential elimination from the population resulting in a significant robustness-CA correlation in this strata absent in the unchallenged stratum. Hence, we also present an outline of a cross-sectional study design suitable to test this hypothesis. We finally discuss the objections that may validly be raised against our robustness hypothesis, and how available evidence encourages us to refute these objections.



http://ift.tt/2DGzOmM

Impulsive Mechanisms Influencing Relapse in Alcohol Drinking

Publication date: Available online 17 January 2018
Source:Medical Hypotheses
Author(s): Hugo E. Reyes-Huerta, Cristiano dos Santos, Kalina Martínez
Impulsivity has been related to different features of addictive behaviors. Growing data, generated in separated lines of research, suggest that different processes underlying impulsivity are associated to relapse in alcohol drinking. Considering the evidence, relapse can be understood as an impulsive choice or as an impulsive action. In the first case, the return to drinking behavior is a consequence of insensitive to delayed consequence, that is, to the discounting of delayed rewards. In the second case, relapse is a consequence of failures to inhibit prepotent responses. Nevertheless, conditions that control the action of each mechanism or their interaction to influence relapse still unknown. We hypothesize that both mechanisms interact to produce relapse depending on framing effects, the moments of a drinking episode or context. The implication of the hypothesis is that relapse prevention strategies need to reduce discounting of delayed rewards, but also to increase behavioral inhibition in the presence of cues related to alcohol.



http://ift.tt/2Eh2Zhl

Determining the venous oxygen reservoir: a novel, hypothetical approach to titration of supplemental oxygen in preterm newborns.

Publication date: Available online 17 January 2018
Source:Medical Hypotheses
Author(s): Chad C. Andersen, Nicolette A. Hodyl, Nina M. Ziegler, Michael J. Stark
While normal oxygen saturation is commonly thought to be a marker of normal oxygenation, cutaneous saturation does not account for the sufficiency of oxygen within each cell or that of the system overall. Rather, cutaneous oximetry simply defines the saturation of haemoglobin (Hb) with oxygen in a pulsatile vessel. Assessment of sufficiency is best determined by measurement of the amount of oxygen left over following aerobic respiration. This left over oxygen is 'stored' on Hb in the venous compartment and can be calculated as the venous oxygen content. We hypothesize that the development of a venous oxygen content or saturation reference range in a group of well, uninjured very preterm newborns and subsequent application, in a randomised trial, with a structural, functional and molecular outcome will resolve the method for assessment of oxygen sufficiency in preterms by demonstrating both clinical safety and effectiveness. This method could be subsequently used for titration of supplemental oxygen.



http://ift.tt/2DDub8L

Linked help from bacterial proteins drives autoantibody production in small vessel vasculitis

Publication date: Available online 17 January 2018
Source:Medical Hypotheses
Author(s): David B.G. Oliveira
The small vessel vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis are associated with autoantibodies to neutrophil cytoplasm antigens (ANCA), principally proteinase-3 (PR3) and myeloperoxidase (MPO). There is an association between GPA and nasal carriage of Staphylococcus aureus. The recent finding that S. aureus produces proteins that bind tightly to and block the function of both PR3 and MPO suggests a mechanism for ANCA formation. The bacterial protein-autoantigen conjugate is recognised by B cells with ANCA specificity, internalised, and the bacterial protein processed and presented to T cells with specificity for bacterial peptides. The T cell can then provide help to the B cell, allowing class switching, affinity maturation and the production of pathogenic ANCA. This mechanism predicts that T cells with this specificity will be found in patients, and that the bacterial protein-autoantigen conjugate will be particularly efficient at eliciting ANCA production.



http://ift.tt/2Eh7uZa

The use of polysulfated polysaccharides heparin like compounds, glycosaminoglycans and Vitamin B17 as a possible treatment for prostate Cancer

Publication date: Available online 12 January 2018
Source:Medical Hypotheses
Author(s): Jamil Hantash
Prostate cancer is impacting many men globally. It is a disease that has no effective treatment is available in the market. The understanding of the biophysical and biochemical aspects of the disease and the mechanism that allow it to metastasize is key to finding an effect treatment. Maintenance or pretreatment drug as well as a post treatment drug can be effective to avoid or delay the disease from appearing. The polysaccharides and monosaccharides polymers combined with vitamins can be the ingredient to developing the treatment. There are many evidences that investigators examined the individual components of the therapy proposed but never a combination of all these therapies. The one item that is not discussed is how to formulate the ingredient into an effective form which is a proprietary work being conducted currently. Nevertheless, the hypothesis seems reasonable to us and worth sharing with the scientific community.



http://ift.tt/2DHd1r0

Ultrasonographic assessment of pubertal breast development in obese children: compliance with the clinic

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2EkyneY

Late presentation of glycogen storage disease types Ia and III in children with short stature and hepatomegaly

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print


http://ift.tt/2DH3ujI

"Asian Pac J Cancer Prev"[jour]; +43 new citations

43 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Asian Pac J Cancer Prev"[jour]

These pubmed results were generated on 2018/01/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2rNOajw

Recurrent Syncope, a Clue in Amyloid Cardiomyopathy

Infiltrative cardiomyopathies include a variety of disorders that lead to myocardial thickening resulting in a constellation of clinical manifestations and eventually heart failure that could be the first clue to reach the diagnosis. Among the more described infiltrative diseases of the heart is amyloid cardiomyopathy. The disease usually presents with subtle, nonspecific symptoms. Herein, we illustrate a case of recurrent syncope as the initial presenting symptom for systemic amyloid with polyneuropathy and cardiomyopathy as a cause of syncope. The article illustrates the role of advanced cardiac imaging in the diagnosis of the disease with a focused literature review. We also highlight the role of early, shared decision-making between patient, family, and medical team in the management of cardiac amyloidosis.

http://ift.tt/2rJUsRz

"Otolaryngol Head Neck Surg"[jour]; +24 new citations

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Otolaryngol Head Neck Surg"[jour]

These pubmed results were generated on 2018/01/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2Fp6bGR

Using gold nanoparticles in diagnosis and treatment of melanoma cancer.

Related Articles

Using gold nanoparticles in diagnosis and treatment of melanoma cancer.

Artif Cells Nanomed Biotechnol. 2018 Jan 26;:1-10

Authors: Bagheri S, Yasemi M, Safaie-Qamsari E, Rashidiani J, Abkar M, Hassani M, Mirhosseini SA, Kooshki H

Abstract
Several studies have been devoted to clear functionalization of gold nanoparticles (AuNPs) in different fields such as cellular and molecular biology, microbiology, immunology and physiology. In line with the high diagnostic value of AuNPs, its therapeutic application has been intensively developed in tumour therapy, in recent years. One of the best clinical applications of AuNPs is its use in targeted delivery of anti-cancer drugs. Recent studies have focused on the application of AuNPs to treat melanoma - a malignant neoplasm sourced from melanocytes skin cells - with poor prognosis in advanced stages. Furthermore, early diagnosis can be successfully achieved through utilizing this technique even at early stages with localized distribution. Herein, this study details the previous researches focusing on the use of AuNPs as a novel diagnostic and therapeutic option in management of melanoma.

PMID: 29373944 [PubMed - as supplied by publisher]

http://ift.tt/2rOg3Z3

Zein nanoparticle as a novel BMP6 derived peptide carrier for enhanced osteogenic differentiation of C2C12 cells.

Related Articles

Zein nanoparticle as a novel BMP6 derived peptide carrier for enhanced osteogenic differentiation of C2C12 cells.

Artif Cells Nanomed Biotechnol. 2018 Jan 26;:1-9

Authors: Hadavi M, Hasannia S, Faghihi S, Mashayekhi F, Homazadeh H, Mostofi SB

Abstract
Zein nanoparticles as a carrier system for BMP6-derived peptide were prepared by liquid-liquid phase separation procedure and characterized with SEM, DLS, FTIR and thermogravimetric methods. After peptide encapsulation, nanoparticle size increased from 236.3 ± 92.2 nm to 379.4 ± 116.8 nm. The encapsulation efficiency of peptide was 72.6% and the release of peptide from Zein nanoparticles was partly sustained in trypsin containing phosphate buffered saline (pH 7.4) for up to 14 days. Peptide-loaded nanoparticles showed similar cell viability compared with blank ones. ALP activity of C2C12 cells treated with peptide-loaded nanoparticles (500 µg/mL) was evaluated 7, 14, 21 and 28 days after culture. In peptide-loaded nanoparticles, ALP activity was significantly higher (p < .05) compared with other groups at day 14. Alizarin Red S staining showed, C2C12 cells behind peptide-loaded nanoparticles had significantly (p < .05) higher calcium deposition at day 21. The results of RT-qPCR show that the BMP-6 peptide activated expression of RUNX2 as a transcription factor. In turn, RUNX2 regulates SPP1 and BGLAP gene expression, as osteogenic marker genes. The results confirm that the peptide-loaded Zein nanoparticles, as osteoinductive material, may be used to repair small area of bone defects, with low load bearing.

PMID: 29373940 [PubMed - as supplied by publisher]

http://ift.tt/2GnE9Nn

Comparative study of oral lipid nanoparticle formulations (LNFs) for chemical stabilization of antitubercular drugs: physicochemical and cellular evaluation.

Related Articles

Comparative study of oral lipid nanoparticle formulations (LNFs) for chemical stabilization of antitubercular drugs: physicochemical and cellular evaluation.

Artif Cells Nanomed Biotechnol. 2018 Jan 26;:1-19

Authors: Banerjee S, Roy S, Nath Bhaumik K, Kshetrapal P, Pillai J

Abstract
Rifampicin (RIF) and Isoniazid (INH) are two major first-line antitubercular drugs (ATDs) that are typically administered orally, in combination. However, INH-catalysed degradation of RIF under acidic pH environment of the stomach is a major concern related to its oral delivery, and is dramatically accelerated upon further exposure to and interaction with INH. This interaction, in turn, triggers a direct decline in the available RIF dose below the sub-therapeutic level, thereby diminishing its therapeutic efficacy. We hypothesized that encapsulation of both these important ATDs into lipid nanoparticle formulations (LNFs) may help mitigate the acid hydrolysis of RIF, its subsequent interaction with INH and its eventual INH-mediated accelerated chemical degradation in the gastric environment. We further hypothesized that these LNFs would be capable of enhanced uptake and localization into intra-cellular compartments of lung macrophages, thereby potentially targeting the Tb pathogen in its in vivo niche. For this purpose, we evaluated two promising LNFs, viz., solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for encapsulating these ATDs. Here, we report on the design, development and comparative evaluation of SLN and NLC-based lipid formulations of both INH and RIF. Our strategy of nanoencapsulation substantially prolonged encapsulated RIF release and improved its chemical stability in presence of INH in a simulated gastric acidic environment. In vitro cell culture studies showed a well-quantifiable uptake of LNFs in a human alveolar macrophage cell line. Overall, these evaluations provided promising results for establishing the potential of both formulations for TB therapy.

PMID: 29373927 [PubMed - as supplied by publisher]

http://ift.tt/2nenrYX

Development and biological evaluation of vesicles containing bile salt of telmisartan for the treatment of diabetic nephropathy.

Related Articles

Development and biological evaluation of vesicles containing bile salt of telmisartan for the treatment of diabetic nephropathy.

Artif Cells Nanomed Biotechnol. 2018 Jan 26;:1-8

Authors: Ahad A, Raish M, Ahmad A, Al-Jenoobi FI, Al-Mohizea AM

Abstract
The aim of present study was to develop and evaluate vesicles containing bile salt formulation of telmisartan for the treatment of diabetic nephropathy. Different vesicles containing bile salt formulations were developed by varying ratios of soybean phosphatidylcholine and sodium deoxycholate. Prepared formulations were characterized for their size, polydispersity index, zeta potential, morphology and entrapment efficiency. Further, the renoprotective outcome of optimized formulation was studied in streptozotocin-induced diabetic nephropathy rat model. Results of the present study demonstrated that the average vesicles size, polydispersity index, zeta potential and entrapment efficiency were found to be in the range of 64.98 ± 1.40 to 167.60 ± 6.46 nm, 0.02 ± 0.04 to 0.31 ± 0.01, -24.30 ± 1.39 to -42.60 ± 6.67 mV and 29.68 ± 1.08% to 77.21 ± 0.52%, respectively. Further, the best chosen formulation F4 presented vesicles size, polydispersity index, zeta potential and entrapment efficiency of 64.98 ± 1.40 nm, 0.24 ± 0.02, -35.40 ± 1.48 mV and 77.21 ± 0.52%, respectively. In addition, formulation F4 improved the biological indices in streptozotocin-induced diabetic nephropathy in rats. It was concluded that prepared formulation exerts a valuable results on diabetic nephropathy and it may be a potential pharmaceutical dosage form for the treatment of diabetic nephropathy.

PMID: 29373922 [PubMed - as supplied by publisher]

http://ift.tt/2rOfTRr

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation.

Related Articles

Physico-Chemical Properties, Aerosolization and Dissolution of Co-Spray Dried Azithromycin Particles with L-Leucine for Inhalation.

Pharm Res. 2018 Jan 08;35(2):28

Authors: Mangal S, Nie H, Xu R, Guo R, Cavallaro A, Zemlyanov D, Zhou QT

Abstract
PURPOSE: Inhalation therapy is popular to treat lower respiratory tract infections. Azithromycin is effective against some bacteria that cause respiratory tract infections; but it has poor water solubility that may limit its efficacy when administrated as inhalation therapy. In this study, dry powder inhaler formulations were developed by co-spray drying azithromycin with L-leucine with a purpose to improve dissolution.
METHODS: The produced powder formulations were characterized regarding particle size, morphology, surface composition and in-vitro aerosolization performance. Effects of L-leucine on the solubility and in-vitro dissolution of azithromycin were also evaluated.
RESULTS: The spray dried azithromycin alone formulation exhibited a satisfactory aerosol performance with a fine particle fraction (FPF) of 62.5 ± 4.1%. Addition of L-leucine in the formulation resulted in no significant change in particle morphology and FPF, which can be attributed to enrichment of azithromycin on the surfaces of composite particles. Importantly, compared with the spray-dried amorphous azithromycin alone powder, the co-spray dried powder formulations of azithromycin and L-leucine demonstrated a substantially enhanced in-vitro dissolution rate. Such enhanced dissolution of azithromycin could be attributed to the formation of composite system and the acidic microenvironment around azithromycin molecules created by the dissolution of acidic L-leucine in the co-spray dried powder. Fourier transform infrared spectroscopic data showed intermolecular interactions between azithromycin and L-leucine in the co-spray dried formulations.
CONCLUSIONS: We developed the dry powder formulations with satisfactory aerosol performance and enhanced dissolution for a poorly water soluble weak base, azithromycin, by co-spray drying with an amino acid, L-leucine.

PMID: 29374368 [PubMed - in process]

http://ift.tt/2rG5iaU

Do we need new trials of procalcitonin-guided antibiotic therapy?

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Do we need new trials of procalcitonin-guided antibiotic therapy?

Crit Care. 2018 Jan 27;22(1):17

Authors: Lisboa T, Salluh J, Povoa P

Abstract
Using biomarkers as a guide to tailor the duration of antibiotic treatment in respiratory infections is an attractive hypothesis assessed in several studies. Recent work aiming to summarize the evidence assessed the effect of a procalcitonin (PCT)-guided antibiotic treatment on outcomes in acute lower respiratory tract infections (LRTI), suggesting that significant reductions in antibiotic duration occur when using a PCT-guided algorithm. However, controversial evidence also suggested PCT-guided algorithms were associated with increased antibiotic duration and increased incidence of Clostridium difficile, without any impact on mortality, in real-world settings. So, although using PCT-guided antibiotic stewardship is promising, after more than a decade of randomized controlled trials on this topic the evidence in its favor is still less than compelling due to limitations in trial design, not taking into consideration fundamental aspects of PCT biology, and the absence of evidence-based antimicrobial duration in intervention and control groups. In this commentary we highlight some questions and limitations of primary PCT study data that might impact interpretation and clinical use of PCT at the bedside.

PMID: 29373980 [PubMed - in process]

http://ift.tt/2GoNPY1

Birth weight and body mass index z-score in childhood brain tumors: A cross-sectional study.

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Birth weight and body mass index z-score in childhood brain tumors: A cross-sectional study.

Sci Rep. 2018 Jan 26;8(1):1642

Authors: Wang KW, de Souza RJ, Fleming A, Johnston DL, Zelcer SM, Rassekh SR, Burrow S, Thabane L, Samaan MC

Abstract
Children with brain tumors (CBT) are at higher risk of cardiovascular disease and type 2 diabetes compared to the general population, in which birth weight is a risk factor for these diseases. However, this is not known in CBT. The primary aim of this study was to explore the association between birth weight and body mass measures in CBT, compared to non-cancer controls. This is a secondary data analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n = 133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported, and confirmed through examination of the medical records. Body mass index (BMI) was calculated from height and weight measures and reported as kg/m2. BMI z-scores were obtained for subjects under the age of 20 years. Multivariable linear regression was used to evaluate the relationship between birth weight and BMI and BMI z-score, adjusted for age, sex, puberty, and fat mass percentage. Higher birth weight was associated with higher BMI and BMI z-score among CBT and controls. In conclusion, birth weight is a risk factor for higher body mass during childhood in CBT, and this may help the identification of children at risk of future obesity and cardiometabolic risk.

PMID: 29374278 [PubMed - in process]

http://ift.tt/2nfRLl4

"Otolaryngol Head Neck Surg"[jour]; +24 new citations

24 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Otolaryngol Head Neck Surg"[jour]

These pubmed results were generated on 2018/01/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2DIhiOW

"Asian Pac J Cancer Prev"[jour]; +43 new citations

43 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

"Asian Pac J Cancer Prev"[jour]

These pubmed results were generated on 2018/01/28

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

http://ift.tt/2Ei5pfx

TLR signaling inhibitor, phenylmethimazole, in combination with tamoxifen inhibits human breast cancer cell viability and migration.

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TLR signaling inhibitor, phenylmethimazole, in combination with tamoxifen inhibits human breast cancer cell viability and migration.

Oncotarget. 2017 Dec 26;8(69):113295-113302

Authors: Schwartz AL, Dickerson E, Dagia N, Malgor R, McCall KD

Abstract
Heightened co-expression and dysregulated signaling associated with Toll-like receptor 3 (TLR3) and Wnt5a is an integral component of solid tumors and hematological malignancies. Our previous findings in pancreatic cancer and melanoma suggest that inhibition of these pathways by a TLR3 signaling inhibitor, phenylmethimazole (C10), results in significantly decreased IL-6 levels, STAT3 phosphorylation, minimal cancer cell migration and reduced cancer cell growth in vitro and in vivo. In this study, we extended our earlier observations by performing studies in human breast cancer cells. We found that human MCF-7 breast cancer cells express high basal levels of TLR3 and Wnt5a RNA. C10 treatment resulted in significantly decreased TLR3 and Wnt5a expression levels. This functionally translated into significantly reduced IL-6 levels and STAT3 phosphorylation in vitro. In addition, the inhibition of this signaling cascade by C10 further resulted in decreased cell viability and migration of MCF-7 cells. Strikingly, the combination of C10 and tamoxifen, the standard of care therapy for breast cancer, further decrease cancer cell growth better than either agent alone. These data support the novel finding that inhibition of TLR3 signaling in combination with tamoxifen, may increase the effectiveness of current treatments of breast cancer.

PMID: 29371911 [PubMed]

http://ift.tt/2DGbuBw

Head and neck cancer patient experience of a new dietitian-delivered health behaviour intervention: 'you know you have to eat to survive'.

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Head and neck cancer patient experience of a new dietitian-delivered health behaviour intervention: 'you know you have to eat to survive'.

Support Care Cancer. 2018 Jan 27;:

Authors: McCarter K, Baker AL, Britton B, Halpin SA, Beck A, Carter G, Wratten C, Bauer J, Wolfenden L, Burchell K, Forbes E

Abstract
PURPOSE: The aim of this study was to explore head and neck cancer (HNC) patient experiences of a novel dietitian delivered health behaviour intervention.
METHODS: This study is a qualitative study which employed semi-structured individual interviews using open and axial coding and then final selective coding to organise the data. Patients with HNC who had participated in a dietitian delivered health behaviour intervention to reduce malnutrition were invited to discuss their experience of this intervention. Individual interviews were conducted, transcribed and analysed using grounded theory.
RESULTS: Nine patients participated in the interviews. Four dimensions were identified in the initial coding process: 'information', which described patients' desire for tailored advice during their treatment; 'challenges of treatment experience', which described the difficulties related to treatment side effects; 'key messages: importance of eating and maintaining weight', which covered perceived integral messages delivered to patients by dietitians; and 'dietitian's approach' describing patient experiences of empathic and compassionate dietitians. Two overarching themes resulted from examining the connections and relationships between these dimensions: 'survival', a connection between eating and living; and 'support', describing the valued working partnership between dietitian and patient.
CONCLUSIONS: Dimensions and themes overlapped with the qualitative literature on HNC patient experience of treatment. However, some themes, such as the empowerment of a message linking eating to survival, appeared unique to this study. Patients found this message to be delivered in a supportive manner that motivated change.

PMID: 29374300 [PubMed - as supplied by publisher]

http://ift.tt/2rLyy01

SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma.

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SOX2 activation predicts prognosis in patients with head and neck squamous cell carcinoma.

Sci Rep. 2018 Jan 26;8(1):1677

Authors: Chung JH, Jung HR, Jung AR, Lee YC, Kong M, Lee JS, Eun YG

Abstract
SOX2 copy number and mRNA expression were analysed to examine the clinical significance of SOX2 activation in HNSCC. Gene expression signatures reflecting SOX2 activation were identified in an HNSCC cohort. Patients with HNSCC were classified into two subgroups according to the gene expression signature: SOX2-high and SOX2-low. The clinical significance of SOX2 activation was further validated in two independent cohorts. Moreover, clinical significance of SOX2 activation in response to radiotherapy was assessed in patients with HNSCC. The relationship between SOX2 activation and radiotherapy was validated in an in vitro experiment. Patients in the SOX2-high subgroup had a better prognosis than patients in the SOX2-low subgroup in all three patient cohorts. Results of multivariate regression analysis showed that SOX2 signature was an independent predictor of the overall survival of patients with HNSCC (hazard ratio, 1.45; 95% confidence interval, 1.09-1.92; P = 0.01). Interestingly, SOX2 activation was a predictor of therapy outcomes in patients receiving radiotherapy. Moreover, SOX2 overexpression enhanced the effect of radiotherapy in HNSCC cell lines. SOX2 activation is associated with improved prognosis of patients with HNSCC and might be used to predict which patients might benefit from radiotherapy.

PMID: 29374236 [PubMed - in process]

http://ift.tt/2GpWF7F

RapidArc vs Conventional IMRT for Head and Neck Cancer Irradiation: Is Faster Necessary Better?

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RapidArc vs Conventional IMRT for Head and Neck Cancer Irradiation: Is Faster Necessary Better?

Asian Pac J Cancer Prev. 2018 01 27;19(1):207-211

Authors: Mashhour K, Kamaleldin M, Hashem W

Abstract
Purpose: The aim of this study was to dosimetrically evaluate and compare double arc RapidArc (RA) with conventional IMRT (7 fields) plans for irradiation of locally advanced head and neck cancers (LAHNC), focusing on target coverage and doses received by organs at risk (OAR). Methods: Computed tomography scans of 20 patients with LAHNC were obtained. Contouring of the target volumes and OAR was done. Two plans were made for each patient, one using IMRT and the other double arc RA, and calculated doses to planning target volume (PTV) and OAR were compared. Monitor units for each technique were also calculated. Results: PTV coverage was similar with both techniques. The homogeneity index (HI) was higher for the IMRT plans with a value of 0.108 ± 0.021 compared to 0.0975 ± 0.017 for double arc RA plans (p-value of 0.540). The double arc RA plans achieved a better conformity with a CI95%= 1.01 ± 0.021 compared to 1.05 ± 0.057 achieved with the IMRT plans (p-value of 0.036). The average monitor units (MU) ±SD were 930.5 ± 142.42 for the IMRT plans as opposed to 484.25 ± 69.47 for the double arc RA plans (P-value of 0.002). Double arc plans provided better OAR sparing with a significant p-value of 0.002 and 0.004 for the right and left parotid glands, respectively. Conclusions: RA is a rapid and accurate technique that uses lower MUs than conventional IMRT. Double arc plans provide better dose conformity, OAR sparing and a more homogeneous target coverage compared to IMRT.

PMID: 29373915 [PubMed - as supplied by publisher]

http://ift.tt/2rO54i4

Epstein–Barr virus strain heterogeneity impairs human T-cell immunity

Abstract

The Epstein–Barr virus (EBV) establishes lifelong infections in > 90% of the human population. Although contained as asymptomatic infection by the immune system in most individuals, EBV is associated with the pathogenesis of approximately 1.5% of all cancers in humans. Some of these EBV-associated tumors have been successfully treated by the infusion of virus-specific T-cell lines. Recent sequence analyses of a large number of viral isolates suggested that distinct EBV strains have evolved in different parts of the world. Here, we assessed the impact of such sequence variations on EBV-specific T-cell immunity. With the exceptions of EBNA2 and the EBNA3 family of proteins, an overall low protein sequence disparity of about 1% was noted between Asian viral isolates, including the newly characterized M81 strain, and the prototypic EBV type 1 and type 2 strains. However, when T-cell epitopes including their flanking regions were compared, a substantial proportion was found to be polymorphic in different EBV strains. Importantly, CD4+ and CD8+ T-cell clones specific for viral epitopes from one strain often showed diminished recognition of the corresponding epitopes in other strains. In addition, T-cell recognition of a conserved epitope was affected by amino acid exchanges within the epitope flanking region. Moreover, the CD8+ T-cell response against polymorphic epitopes varied between donors and often ignored antigen variants. These results demonstrate that viral strain heterogeneity may impair antiviral T-cell immunity and suggest that immunotherapeutic approaches against EBV should preferably target broad sets of conserved epitopes including their flanking regions.

http://ift.tt/2DG2SuG

Skin CanceR Brachytherapy vs External beam radiation therapy (SCRiBE) meta-analysis

Publication date: Available online 19 January 2018
Source:Radiotherapy and Oncology
Author(s): Nicholas G. Zaorsky, Charles T. Lee, Eddie Zhang, Thomas J. Galloway
Background and purposeTo compare cosmesis and local recurrence (LR) of definitive external beam radiation therapy (EBRT) vs brachytherapy (BT) for indolent basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin.Materials and methodsStudies including patients with T1-2 N0 SCCs/BCCs treated with definitive EBRT/BT and ≥10 months follow-up were analyzed. The primary endpoint was post-treatment cosmesis, categorized as "good," "fair," or "poor." The secondary endpoint was LR. Mixed effects regression models were used to estimate weighted linear relationships between biologically equivalent doses with α/β = 3 (BED3) and cosmetic outcomes.ResultsA total of 9965 patients received EBRT and 553 received BT across 24 studies. Mean age was 73 years, median follow-up was 36 months, and median dose was 45 Gy/10 fractions at 4.4 Gy/fraction. At BED3 of 100 Gy, "good" cosmesis was more frequently observed in patients receiving BT, 95% (95% CI: 88–100%) vs 79% (95% CI: 60–82%), p < 0.05. Similar results were found for "good" cosmesis at BED3 >100 Gy. No difference in "poor" cosmesis was noted at any BED3. LR was <7% for both at one year.ConclusionBT has favorable cosmesis over EBRT for skin SCCs/BCCs at common fractionation regimens. Prospective studies comparing EBRT vs BT are warranted.



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Photon vs. proton radiochemotherapy: Effects on brain tissue volume and perfusion

Publication date: Available online 19 January 2018
Source:Radiotherapy and Oncology
Author(s): Jan Petr, Ivan Platzek, Frank Hofheinz, Henri J.M.M. Mutsaerts, Iris Asllani, Matthias J.P. van Osch, Annekatrin Seidlitz, Pawel Krukowski, Andreas Gommlich, Bettina Beuthien-Baumann, Christina Jentsch, Jens Maus, Esther G.C. Troost, Michael Baumann, Mechthild Krause, Jörg van den Hoff
Background and purposeTo compare the structural and hemodynamic changes of healthy brain tissue in the cerebral hemisphere contralateral to the tumor following photon and proton radiochemotherapy.Materials and methodsSixty-seven patients (54.9 ±14.0 years) diagnosed with glioblastoma undergoing adjuvant photon (n = 47) or proton (n = 19) radiochemotherapy with temozolomide after tumor resection underwent T1-weighted and arterial spin labeling MRI. Changes in volume and perfusion before and 3 to 6 months after were compared between therapies.ResultsA decrease in gray matter (GM) (−2.2%, P<0.001) and white matter (WM) (−1.2%, P<0.001) volume was observed in photon-therapy patients compared to the pre-radiotherapy baseline. In contrast, for the proton-therapy group, no significant differences in GM (0.3%, P = 0.64) or WM (−0.4%, P = 0.58) volume were observed. GM volume decreased with 0.9% per 10 Gy dose increase (P<0.001) and differed between the radiation modalities (P<0.001). Perfusion decreased in photon-therapy patients (−10.1%, P = 0.002), whereas the decrease in proton-therapy patients, while comparable in magnitude, did not reach statistical significance (−9.1%, P = 0.12). There was no correlation between perfusion decrease and either dose (P = 0.64) or radiation modality (P = 0.94).ConclusionsOur results show that the tissue volume decrease depends on radiation dose delivered to the healthy hemisphere and differs between treatment modalities. In contrast, the decrease in perfusion was comparable for both irradiation modalities. We conclude that proton therapy may reduce brain-volume loss when compared to photon therapy.



http://ift.tt/2EfCusD