Acetylshikonin from Zicao attenuates cognitive impairment and hippocampus senescence in D-galactose-induced aging mouse model via upregulating the expression of SIRT1

Publication date: Available online 9 January 2018
Source:Brain Research Bulletin
Author(s): Qisen Li, Jiacheng Zeng, Meiling Su, Yu He, Banghao Zhu
Zicao acts as a pleiotropic medicine in various diseases due to its particular pharmacological properties, including anti-inflammatory, anti-tumor, anti-oxidative, and wound healing effects. However, few studies have focused on the function in neurodegenerative diseases of Zicao. In this study, we investigated the neuroprotective effect of Acetylshikonin (AS) from Zicao on the hippocampus of the D-galactose (D-gal)-induced sub-acute aging mouse model of Alzheimer's disease (AD). The aging model was established in male Kunming mice by subcutaneous injection of D-gal (150 mg/kg/d) for 60 days, and the mice were given AS (270, 540 and 1080 mg/kg/d) or distilled water intragastrically for 30 days after 30 days of D-gal injection. The behavioral results test by Morris Water Maze (MWM) revealed that chronic AS treatment alleviated D-gal-induced learning and memory deficits compared with the D-gal-treated mice. In addition, AS also ameliorated the oxidative stress and neuroinflammation induced by D-gal through decreasing the level of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), malondialdehyde (MDA) and enhancing the activity of the antioxidant enzymes superoxide dismutase (SOD). Moreover, western blot results showed that AS can up-regulate the expression of Sirtuin 1 (SIRT1) and inhibit D-gal-induced activation of p53/p21 signaling pathway in the hippocampus of mice. These results suggest that AS can execute the prevention and treatment of D-gal-induced brain aging by SIRT1/P53/P21 pathway.



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Serum Haptoglobin in Chinese Patients with Alzheimer’s Disease and Mild Cognitive Impairment: A Case-Control Study

Publication date: Available online 9 January 2018
Source:Brain Research Bulletin
Author(s): Cen-Jing Zhu, Guo-Xin Jiang, Jin-Mei Chen, Zhi-Ming Zhou, Qi Cheng
BackgroundSerum level of Haptoglobin (Hp) maybe associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI).ObjectiveTo investigate associations between serum Hp and AD, as well as between Hp and MCI.MethodsSerum levels of Hp were measured and analyzed for 51 patients with AD, 139 patients with MCI and their healthy controls matched with sex and age. All study subjects were from a survey among residents aged 60 years and over in a community located in the southwest suburb of Shanghai.ResultsSerum levels of Hp were observed significantly higher in AD and MCI cases than controls (both p < 0.0001). A significant positive correlation was found between Hp and Activities of Daily Living (ADL) score (rs = 0.430, p = 0.007), as well as between Hp and Clinical Dementia Rating (CDR) score (rs = 0.359, p = 0.027) in all AD patients. According to the receiver operating characteristic (ROC) curve analysis, the optimal cut-off point for Hp was found to be 67.50 μg/ml (sensitivity, 0.902; specificity, 0.745) in AD patients, and 44.76 μg/ml (sensitivity, 0.986; specificity, 0.403) in MCI patients.ConclusionElevated serum levels of Hp were observed in AD and MCI patients than controls. In addition, Hp may correlate with the severity of AD.



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Harmine enhances GABAergic transmission onto basoamygdala projection neurons in mice

Publication date: Available online 9 January 2018
Source:Brain Research Bulletin
Author(s): Wei-Zhu Liu, Bo-Wei Huang, Wen-Jie You, Ping Hu, Xue-Hui Wang, Jun-Yu Zhang, Xiao-Bin Xu, Zong-Yong Zhang, Bing-Xing Pan, Wen-Hua Zhang
Emerging evidence indicates that loss of inhibitory tone in amygdala with its subsequent overactivation contributes to the development of multiple mental disorders such as anxiety disorders and post-traumatic stress disorder (PTSD). Harmine is a member of natural β-carboline alkaloids which can readily cross the blood brain barrier and displays significant antidepressant and anxiolytic effects in rodents. However, the underlying neurobiological mechanisms are largely unknown. Here, by using whole-cell patch clamp recordings in in vitro amygdala slices, we examined the effect of harmine on glutamatergic and GABAergic transmission onto basal amygdala (BA) projection neurons (PNs). Our results showed that harmine affected neither the amplitude nor the frequency of spontaneous and miniature excitatory postsynaptic currents (sEPSCs/mEPSCs) of PNs. By contrast, it markedly increased both the amplitude and frequency of the spontaneous inhibitory postsynaptic currents (sIPSCs). For mIPSCs, only an increase of their frequency but not amplitude was observed following harmine perfusion, suggesting that harmine might act through presynaptic mechanism. In parallel, a reduction of paired-pulse ratio of evoked IPSCs emerged in the presence of harmine. Furthermore, the intrinsic excitability of PNs was dramatically decreased upon harmine treatment. Together, our study suggests that harmine selectively potentiates the inhibitory but not excitatory transmission onto BA PNs, which may contribute to its antidepressant and anxiolytic influence.



http://ift.tt/2ErCVis

Morphological and Functional Characterization of Non-fast-Spiking GABAergic Interneurons in Layer 4 Microcircuitry of Rat Barrel Cortex

Abstract

GABAergic interneurons are notorious for their heterogeneity, despite constituting a small fraction of the neuronal population in the neocortex. Classification of interneurons is crucial for understanding their widespread cortical functions as they provide a complex and dynamic network, balancing excitation and inhibition. Here, we investigated different types of non-fast-spiking (nFS) interneurons in Layer 4 (L4) of rat barrel cortex using whole-cell patch-clamp recordings with biocytin-filling. Based on a quantitative analysis on a combination of morphological and electrophysiological parameters, we identified 5 distinct types of L4 nFS interneurons: 1) trans-columnar projecting interneurons,2) locally projecting non-Martinotti-like interneurons, 3) supra-granular projecting Martinotti-like interneurons,4) intra-columnar projecting VIP-like interneurons,and5) locally projecting neurogliaform-like interneurons. Trans-columnar projecting interneurons are one of the most striking interneuron types, which have not been described so far in Layer 4. They feature extensive axonal collateralization not only in their home barrel but also in adjacent barrels. Furthermore, we identified that most of the L4 nFS interneurons express somatostatin, while few are positive for the transcription factor Prox1. The morphological and electrophysiological characterization of different L4 nFS interneuron types presented here provides insights into their synaptic connectivity and functional role in cortical information processing.

http://ift.tt/2Es6TTz

Reassessing the Evidence for Capacity Limits in Neural Signals Related to Working Memory

Abstract

In 2004, two landmark studies described the discovery of brain imaging (functional magnetic resonance imaging and electroencephalography) signals that increase with the number of items held in visual working memory (WM). These studies claimed that the signals leveled off (plateaued) once the number of memoranda reached the capacity of WM, as estimated by the prevailing model of the time. However, alternative models were not considered, and changing concepts of WM in the more than a decade since these studies were published necessitate a re-evaluation of their findings; newer models that provide the most accurate account of behavioral data do not incorporate a fixed limit on the number of items stored. Furthermore, an important claim made about the original studies, that signals plateau at each individual's estimated capacity, has never been tested. Here, we pit the plateau model of signal strength against an alternative, saturation model, a biophysically plausible account in which signals increase continuously without plateau. We show that the saturation model provides a better description of the original data, challenging the assumption that imaging results provide evidence for a fixed item limit in WM.

http://ift.tt/2FjqeHL

Heterogeneous Redistribution of Facial Subcategory Information Within and Outside the Face-Selective Domain in Primate Inferior Temporal Cortex

Abstract

The inferior temporal cortex (ITC) contains neurons selective to multiple levels of visual categories. However, the mechanisms by which these neurons collectively construct hierarchical category percepts remain unclear. By comparing decoding accuracy with simultaneously acquired electrocorticogram (ECoG), local field potentials (LFPs), and multi-unit activity in the macaque ITC, we show that low-frequency LFPs/ECoG in the early evoked visual response phase contain sufficient coarse category (e.g., face) information, which is homogeneous and enhanced by spatial summation of up to several millimeters. Late-induced high-frequency LFPs additionally carry spike-coupled finer category (e.g., species, view, and identity of the face) information, which is heterogeneous and reduced by spatial summation. Face-encoding neural activity forms a cluster in similar cortical locations regardless of whether it is defined by early evoked low-frequency signals or late-induced high-gamma signals. By contrast, facial subcategory-encoding activity is distributed, not confined to the face cluster, and dynamically increases its heterogeneity from the early evoked to late-induced phases. These findings support a view that, in contrast to the homogeneous and static coarse category-encoding neural cluster, finer category-encoding clusters are heterogeneously distributed even outside their parent category cluster and dynamically increase heterogeneity along with the local cortical processing in the ITC.

http://ift.tt/2EtQXA1

An Orientation Map for Disparity-Defined Edges in Area V4

Abstract

Binocular disparity information is an important source of 3D perception. Neurons sensitive to binocular disparity are found in almost all major visual areas in nonhuman primates. In area V4, disparity processes are suggested for the purposes of 3D-shape representation and fine disparity perception. However, whether neurons in V4 are sensitive to disparity-defined edges used in shape representation is not clear. Additionally, a functional organization for disparity edges has not been demonstrated so far. With intrinsic signal optical imaging, we studied functional organization for disparity edges in the monkey visual areas V1, V2, and V4. We found that there is an orientation map in V4 activated by edges purely defined by binocular disparity. This map is consistent with the orientation map obtained with regular luminance-defined edges, indicating a cue-invariant edge representation in this area. In contrast, such a map is much weaker in V2 and totally absent in V1. These findings reveal a hierarchical processing of 3D shape along the ventral pathway and the important role that V4 plays in shape-from-disparity detection.

http://ift.tt/2FjqeYh

Effects of Anodal Transcranial Direct Current Stimulation Over the Ventrolateral Prefrontal Cortex on Episodic Memory Formation and Retrieval

Abstract

In the past decade, several studies have investigated the effects of transcranial direct current stimulation (tDCS) on episodic memory abilities. However, the specific conditions under which tDCS affects memory remain largely unclear. Here, we report data from 4 experiments aimed at investigating the effects of anodal tDCS over the left ventrolateral prefrontal cortex (VLPFC) on verbal episodic memory. We evaluated tDCS-induced effects as a function of time of administration, nature of the memory encoding task, and age of the participants. A robust enhancement of memory performance was only found when anodal tDCS was delivered during intentional memorization. This enhancement was evident in young and older adults. tDCS applied during incidental memorization or during retrieval did not induce any modulation of memory performance, and memory was unaffected by offline administration before encoding or retrieval. These results show that the modulation of episodic memory functions by anodal tDCS over the left VLPFC is dependent upon the time of administration and the nature of the memory task. The findings may help profile the optimal stimulation protocols for neurorehabilitation interventions on individuals with memory decline.

http://ift.tt/2ErvQOJ

Overexpression of CTNNB1: Clinical implication in Chinese de novo acute myeloid leukemia

Publication date: Available online 9 January 2018
Source:Pathology - Research and Practice
Author(s): Xi-xi Li, Hong Guo, Jing-dong Zhou, De-hong Wu, Ji-chun Ma, Xiang-mei Wen, Wei Zhang, Zi-jun Xu, Jiang Lin, Jun Qian
CTNNB1 expression has been identified in numerous solid tumors. The present study was designed to determine CTNNB1 expression and its clinical significance in Chinese de novo acute myeloid leukemia (AML) patients. Real-time quantitative PCR was carried out to detect the pattern of CTNNB1 expression in 140 AML patients and 46 controls. The level of CTNNB1 transcript in AML patients was significantly up-regulated compared with controls (P < 0.001). CTNNB1^high patients showed significantly older age than CTNNB1^low patients (P < 0.05). The frequency of high CTNNB1 expression was significantly observed in patients with intermediate/poor karyotypes. CTNNB1^high patients had a significantly lower complete remission (CR) rate than CTNNB1^low patients (P = 0.004). Among cytogenetically normal AML (CN-AML), CTNNB1^high patients presented significantly shorter overall survival (OS, P = 0.004) and leukemia-free survival (LFS, P = 0.038) than CTNNB1^low patients. Multivariate analysis confirmed that CTNNB1 expression was an independent prognostic factor in affecting OS among CN-AML. Moreover, our study revealed that CTNNB1 level significantly decreased after CR in 59 AML patients (P = 0.032) and increased in 28 relapsed AML patients (P = 0.015). Our findings suggest that Wnt/β-catenin is overexpressed and confers a poor prognosis in AML, and could be used in the monitoring of CN-AML.



http://ift.tt/2CX9xEq

MiR-21-5p, miR-34a, and human telomerase RNA component as surrogate markers for cervical cancer progression

Publication date: Available online 9 January 2018
Source:Pathology - Research and Practice
Author(s): Yue Zhu, Ying Han, Tian Tian, Peihong Su, Guan Jin, Juan Chen, Yungui Cao
ObjectiveThis study aimed to demonstrate the predictive value of miR-21-5p, miR-34a, and human telomerase RNA component (hTERC) in cervical cancer (CC) development and evaluated their potential possibility for future clinical applications.MethodsSpecimens were collected from the normal cervix, cervical intraepithelial neoplasia (CIN) I, CIN II/III, cervical squamous cell carcinoma. Cytological evaluations and histopathologic examinations were conducted in all subjects, along with the assessment of human papillomavirus (HPV) DNA. The expression levels of the miR-21-5p and miR-34a were detected by RT-PCR. hTERC amplification was detected by dual-color interphase fluorescence in situ hybridization (FISH). Then miRNA, hTERC expressions were compared with the cytological and histologic examination.ResultsCompared to that in the benign samples, the expression of miR-21-5p and miR-34a in abnormal samples was significantly upregulated and downregulated, gradually corresponding to the severity of cervical lesions (P < 0.05). There was a trend toward an increasing amplification of hTERC with the increasing severity of cervical lesions. miR-21-5p and miR-34a expression, and hTERC amplification were more specific than HPV positivity in differentiating low-grade cervical disorders from high-grade ones (P < 0.05).ConclusionsMiR-21-5p upregulation, miR-34a downregulation, and hTERC amplification were associated with the aggressive progression of CC, which suggests that miR-21-5p, miR-34a and hTERC might serve as surrogate markers for CC progression and potential molecular targets for blockage of the development of CC.



http://ift.tt/2ALXqE3

Modification of the Fitzpatrick system of skin phototype classification for the Indian population, and its correlation with narrowband diffuse reflectance spectrophotometry

Summary

Background

The Fitzpatrick classification for skin phototyping is widely used, but its usefulness in dark-skinned populations has been questioned by some researchers. Recently, skin colour measurement has been proposed for phototyping skin colour objectively.

Aims

To modify the Fitzpatrick system of skin phototyping for the Indian population and to study its correlation with skin colour using narrowband diffuse reflectance spectrophotometry

Methods

Answer choices for three items (eye colour, hair colour, colour of unexposed skin) out of 10 in the original Fitzpatrick questionnaire were modified, followed by self-administration of the original and the modified Fitzpatrick questionnaire by 70 healthy Indian volunteers. Skin colour (melanin and erythema indices) was measured from two photoexposed and two photoprotected sites using a narrowband reflectance spectrophotometer.

Results

The mean ± SD scores for the original and modified Fitzpatrick questionnaires were 25.40 ± 4.49 and 23.89 ± 4.82, respectively (r = 0.97, P < 0.001). The two items related to tanning habits were deemed irrelevant based on the subjects' response and were removed from the modified questionnaire. The Melanin Index (MI) of all sites correlated moderately well with both the modified (r = 0.61–0.64, P < 0.001) and original Fitzpatrick questionnaire scores (r = 0.64–0.67, P < 0.001), while the Erythema Index showed poor correlation with both. An MI value of ≧42 was found to be the cut-off between skin phototypes I–III and IV, and ≥ 47 between IV and V–VI.

Conclusions

Our modification of the Fitzpatrick questionnaire makes it more relevant to the Indian population. Spectrophotometry can be a useful objective tool for skin phototyping.

http://ift.tt/2CWxX0J

Giant panda foraging and movement patterns in response to bamboo shoot growth

Abstract

Diet plays a pivotal role in dictating behavioral patterns of herbivorous animals, particularly specialist species. The giant panda (Ailuropoda melanoleuca) is well-known as a bamboo specialist. In the present study, the response of giant pandas to spatiotemporal variation of bamboo shoots was explored using field surveys and GPS collar tracking. Results show the dynamics in panda-bamboo space-time relationships that have not been previously articulated. For instance, we found a higher bamboo stump height of foraged bamboo with increasing elevation, places where pandas foraged later in spring when bamboo shoots become more fibrous and woody. The time required for shoots to reach optimum height for foraging was significantly delayed as elevation increased, a pattern which corresponded with panda elevational migration patterns beginning from the lower elevational end of Fargesia robusta distribution and gradually shifting upward until the end of the shooting season. These results indicate that giant pandas can respond to spatiotemporal variation of bamboo resources, such as available shoots. Anthropogenic interference of low-elevation F. robusta habitat should be mitigated, and conservation attention and increased monitoring should be given to F. robusta areas at the low- and mid-elevation ranges, particularly in the spring shooting season.

http://ift.tt/2mktCdz

Analysis of the evolution of gross alpha and gross beta activities in airborne samples in Valencia (Spain)

Publication date: March 2018
Source:Journal of Environmental Radioactivity, Volume 183
Author(s): Marina Sáez-Muñoz, María del Carmen Bas, Josefina Ortiz, Sebastián Martorell
Gross alpha (Aα) and gross beta activities (Aβ) were measured weekly in the airborne of the Universitat Politècnica de Valencia campus (in the east of Spain) during the period 2009–2015 (7 years). The geometric mean values of weekly Aα and Aβ were 0.53·10⁻⁴ Bq m⁻³ and 5.77·10⁻⁴ Bq m⁻³, respectively; with an average ratio Aα/Aβ of 0.097. This study highlights the heterogeneity of gross alpha and gross beta activities depending on the different periods of the year. Data show seasonal variations with the highest activity in summer months and the lowest one in winter months. Several atmospheric factors were considered in order to explain this intra-annual variation (wind speed, temperature, relative humidity, precipitations, dust content and prevailing wind directions). Multiple Linear Regression Analysis were performed in order to obtain information on significant atmospheric factors that affect gross α and gross β variability, which could be useful in identifying meteorological or atmospheric changes that could cause deviations in gross α and gross β activity depending on the seasons considered. Models obtained explain more than 60% of variability for global data, and also for winter and spring-autumn months. However, more research is needed to explain gross α and gross β variability in summer months, because the atmospheric factors considered in the MLR explain less than 35% of variability.



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Linking dynamic patterns of neural activity in orbitofrontal cortex with decision making

Publication date: April 2018
Source:Current Opinion in Neurobiology, Volume 49
Author(s): Erin L Rich, Frederic M Stoll, Peter H Rudebeck
Humans and animals demonstrate extraordinary flexibility in choice behavior, particularly when deciding based on subjective preferences. We evaluate options on different scales, deliberate, and often change our minds. Little is known about the neural mechanisms that underlie these dynamic aspects of decision-making, although neural activity in orbitofrontal cortex (OFC) likely plays a central role. Recent evidence from studies in macaques shows that attention modulates value responses in OFC, and that ensembles of OFC neurons dynamically signal different options during choices. When contexts change, these ensembles flexibly remap to encode the new task. Determining how these dynamic patterns emerge and relate to choices will inform models of decision-making and OFC function.



http://ift.tt/2D0s7vh

Boron-chelating membranes based in hybrid mesoporous silica nanoparticles for water purification

Publication date: 5 March 2018
Source:Materials & Design, Volume 141
Author(s): Federica Albertini, Tânia Ribeiro, Sérgio Alves, Carlos Baleizão, José Paulo S. Farinha
Boron is a key element for some biological processes,but it becomes toxic for humans and plants in concentrations above a few ppm. We have design a new approach for boron scavenging, based in hybrid membranes of functional mesoporous silica nanoparticles immobilized in cellulose acetate. The mesoporous silica nanoparticles, with diameters around 150nm, were functionalized with vicinal diol groups that complex boron very efficiently. The functional nanoparticles were covalently immobilized in a cellulose acetate membrane using a di-terminated alkoxisilane that react with the remaining silanol groups at the nanoparticles surfaces and with the hydroxyl groups of the cellulose. The functional nanoparticles and the hybrid membranes show boron removal efficiencies of phenyl boronic acid of up to 93%. The membranes can be used in multistage filtering systems, with sequential membranes modules in continuous operation, in a cheap, simple and efficient process for boron scavenging.

Graphical abstract

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Extension induced phase separation and crystallization in semidilute solutions of ultra high molecular weight polyethylene

Publication date: 31 January 2018
Source:Polymer, Volume 136
Author(s): Sara Lindeblad Wingstrand, Luna Imperiali, Roman Stepanyan, Ole Hassager
We investigate the influence of controlled uniaxial extension on various flow induced phenomena in semidilute solutions of ultra high molecular weight polyethylene. Concentrations range from 9w% to 29w% and the choice of solvent is paraffin oil. The start-up extensional behavior is measured at various Hencky strain rates ε˙ and at two different temperatures (150∘C and 170∘C) well above the melting point. For Hencky strains ε>0.9 the qualitative behavior of the samples differ significantly depending on the imposed conditions and the concentration of the samples. Overall we propose two flow scenarios: Scenario 1 - flow induced phase separation resulting in an unstable bulky filament and Scenario 2 - flow induced phase separation and crystallization resulting in a stable deformation and a smooth strongly strain hardening filament. Scenario 2 is observed only at 150∘C at high ε˙ and high concentrations. Scenario 1, observed at both temperatures, is most pronounced at low rates and/or high concentrations.

Graphical abstract

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Comparative evaluation of skin moisture after topical application of 10% and 30% lactobionic acid

Summary

Background

Dry skin is characterized by symptoms such as itching, redness, excessive exfoliation. These symptoms cause discomfort and contribute to secondary bacterial infections. Dry skin treatments are based on topical applications of various formulations. Among many of them are polyhydroxy acids, which recently gained more attention.

Aims

The aim of this study was a comparative assessment of hydration level (corneometric) after application of lactobionic acid (LA) in the form of peel at concentrations of 10% and 30%.

Material and Methods

The study involved 10 Caucasian individuals aged 26-73 years. Eight treatments were performed at weekly intervals. The peels were applied using the "Split face" method—on the left side of the face 10% LA, and the right side 30% LA which consisted of specified concentration of LA, deionized water, xanthan gum, ethoxydiglycol. The test subjects received a 5% LA cream for overnight use. The cream consisted of deionized water, LA, isopropyl palmitate, ascorbyl palmitate, methylparaben. The products for this study were provided by Grehen Ltd. Celestynów, Poland. Prior to each procedure, the skin hydration level was measured using Corneometer CM 825 from Courage + Khazaka electronic GmbH.

Results

There was a statistically significant improvement in hydration level after 8 treatments for all measuring points and both concentrations. The difference of the skin hydration level between 10% LA and 30% LA could not be determined.

Conclusions

Lactobionic acid is a highly moisturizing agent. There was no significant difference in moisturizing effect between 10% LA concentration and 30% LA concentration.

http://ift.tt/2mffUHV

Metabolic Reprogramming via Targeting CD38 NADase Augments Adoptive T Cell Therapy

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Mario R. Fernandez, John L. Cleveland
One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4⁺ T cell functions and memory can be improved by targeting a CD38-NAD⁺-Sirt1-Foxo1 metabolic circuit.

Teaser

One strategy to improve the potency of adoptive T cell therapy is to augment the function and persistence of anti-tumor T cells. In this issue of Cell Metabolism, Chatterjee et al. (2018) demonstrate that intratumoral CD4⁺ T cell functions and memory can be improved by targeting a CD38-NAD⁺-Sirt1-Foxo1 metabolic circuit.


http://ift.tt/2ALMy9e

Apoptotic Regulatory T Cells Retain Suppressive Function through Adenosine

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Ulf H. Beier
Regulatory T cells maintain tolerance and prevent autoimmunity, but their suppressive effects can hinder immune responses against cancer. In Nature Immunology, Maj et al., 2017 report that regulatory T cells can execute these actions through the nucleoside adenosine even after cell death.

Teaser

Regulatory T cells maintain tolerance and prevent autoimmunity, but their suppressive effects can hinder immune responses against cancer. In Nature Immunology, Maj et al., 2017 report that regulatory T cells can execute these actions through the nucleoside adenosine even after cell death.


http://ift.tt/2CWDZP1

SERCA2b Cycles Its Way to UCP1-Independent Thermogenesis in Beige Fat

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Emilio P. Mottillo, Vanesa D. Ramseyer, James G. Granneman
A new study in Nature Medicine, by Ikeda et al. (2017), reports that calcium cycling in beige adipocytes elevates energy expenditure and glucose oxidation in the absence of uncoupling protein 1. Thermogenic calcium cycling in beige fat is mediated by SERCA2b and improves cold tolerance and metabolic status.

Teaser

A new study in Nature Medicine, by Ikeda et al. (2017), reports that calcium cycling in beige adipocytes elevates energy expenditure and glucose oxidation in the absence of uncoupling protein 1. Thermogenic calcium cycling in beige fat is mediated by SERCA2b and improves cold tolerance and metabolic status.


http://ift.tt/2ALEUf1

Aminoacylation of Proteins: New Targets for the Old ARSenal

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Seyed Mehdi Jafarnejad, Sung-Hoon Kim, Nahum Sonenberg
Besides charging tRNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARSs) are involved in a plethora of non-canonical functions, including development, immune response, and angiogenesis. In this issue of Cell Metabolism, He et al. (2018) report a novel biochemical function of ARSs: posttranslational addition of amino acids to lysine residues in proteins.

Teaser

Besides charging tRNAs with their cognate amino acids, aminoacyl-tRNA synthetases (ARSs) are involved in a plethora of non-canonical functions, including development, immune response, and angiogenesis. In this issue of Cell Metabolism, He et al. (2018) report a novel biochemical function of ARSs: posttranslational addition of amino acids to lysine residues in proteins.


http://ift.tt/2CW931a

Anatomical, Physiological, and Functional Diversity of Adipose Tissue

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Rachel K. Zwick, Christian F. Guerrero-Juarez, Valerie Horsley, Maksim V. Plikus
Adipose tissue depots can exist in close association with other organs, where they assume diverse, often non-traditional functions. In stem cell-rich skin, bone marrow, and mammary glands, adipocytes signal to and modulate organ regeneration and remodeling. Skin adipocytes and their progenitors signal to hair follicles, promoting epithelial stem cell quiescence and activation, respectively. Hair follicles signal back to adipocyte progenitors, inducing their expansion and regeneration, as in skin scars. In mammary glands and heart, adipocytes supply lipids to neighboring cells for nutritional and metabolic functions, respectively. Adipose depots adjacent to skeletal structures function to absorb mechanical shock. Adipose tissue near the surface of skin and intestine senses and responds to bacterial invasion, contributing to the body's innate immune barrier. As the recognition of diverse adipose depot functions increases, novel therapeutic approaches centered on tissue-specific adipocytes are likely to emerge for a range of cancers and regenerative, infectious, and autoimmune disorders.

Teaser

Collections of lipid-filled adipocytes, called adipose depots, are often closely associated with other tissues throughout the body. In this review, Zwick, Guerrero-Juarez et al. discuss adipose tissue functions in body sites, including skin, mammary gland, bone marrow, intestine, and skeletal structures, and highlight adipose depot diversity in the natural world.


http://ift.tt/2ALEMfx

Repression of Adipose Tissue Fibrosis through a PRDM16-GTF2IRD1 Complex Improves Systemic Glucose Homeostasis

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Yutaka Hasegawa, Kenji Ikeda, Yong Chen, Diana L. Alba, Daniel Stifler, Kosaku Shinoda, Takashi Hosono, Pema Maretich, Yangyu Yang, Yasushi Ishigaki, Jingyi Chi, Paul Cohen, Suneil K. Koliwad, Shingo Kajimura
Adipose tissue fibrosis is a hallmark of malfunction that is linked to insulin resistance and type 2 diabetes; however, what regulates this process remains unclear. Here we show that the PRDM16 transcriptional complex, a dominant activator of brown/beige adipocyte development, potently represses adipose tissue fibrosis in an uncoupling protein 1 (UCP1)-independent manner. By purifying the PRDM16 complex, we identified GTF2IRD1, a member of the TFII-I family of DNA-binding proteins, as a cold-inducible transcription factor that mediates the repressive action of the PRDM16 complex on fibrosis. Adipocyte-selective expression of GTF2IRD1 represses adipose tissue fibrosis and improves systemic glucose homeostasis independent of body-weight loss, while deleting GTF2IRD1 promotes fibrosis in a cell-autonomous manner. GTF2IRD1 represses the transcription of transforming growth factor β-dependent pro-fibrosis genes by recruiting PRDM16 and EHMT1 onto their promoter/enhancer regions. These results suggest a mechanism by which repression of obesity-associated adipose tissue fibrosis through the PRDM16 complex leads to an improvement in systemic glucose homeostasis.

Graphical abstract

Teaser

Hasegawa et al. identify GTF2IRD1 as a cold-inducible transcription factor that represses adipose tissue fibrosis through a PRDM16-EHMT1 complex. Repression of adipose tissue fibrosis by the complex improves systemic glucose homeostasis independent of UCP1-mediated thermogenesis and body weight. In humans, GTF2IRD1 expression inversely correlates with subcutaneous WAT fibrosis and visceral adiposity.


http://ift.tt/2CYrUsL

Three-Dimensional Adipose Tissue Imaging Reveals Regional Variation in Beige Fat Biogenesis and PRDM16-Dependent Sympathetic Neurite Density

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Jingyi Chi, Zhuhao Wu, Chan Hee J. Choi, Lily Nguyen, Saba Tegegne, Sarah E. Ackerman, Audrey Crane, François Marchildon, Marc Tessier-Lavigne, Paul Cohen
While the cell-intrinsic pathways governing beige adipocyte development and phenotype have been increasingly delineated, comparatively little is known about how beige adipocytes interact with other cell types in fat. Here, we introduce a whole-tissue clearing method for adipose that permits immunolabeling and three-dimensional profiling of structures including thermogenic adipocytes and sympathetic innervation. We found that tissue architecture and sympathetic innervation differ significantly between subcutaneous and visceral depots. Subcutaneous fat demonstrates prominent regional variation in beige fat biogenesis with localization of UCP1⁺ beige adipocytes to areas with dense sympathetic neurites. We present evidence that the density of sympathetic projections is dependent on PRDM16 in adipocytes, providing another potential mechanism underlying the metabolic benefits mediated by PRDM16. This powerful imaging tool highlights the interaction of tissue components during beige fat biogenesis and reveals a previously undescribed mode of regulation of the sympathetic nervous system by adipocytes.

Graphical abstract

Teaser

Chi et al. use Adipo-Clear, a whole-tissue clearing method that permits immunolabeling and three-dimensional profiling, to identify differences in tissue architecture and sympathetic innervation between subcutaneous and visceral adipose depots. Localized beigeing of subcutaneous fat correlates with areas of dense sympathetic neurites, highlighting adipocyte regulation of the sympathetic nervous system.


http://ift.tt/2CXQs57

Extracellular Vesicles Provide a Means for Tissue Crosstalk during Exercise

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Martin Whitham, Benjamin L. Parker, Martin Friedrichsen, Janne R. Hingst, Marit Hjorth, William E. Hughes, Casey L. Egan, Lena Cron, Kevin I. Watt, Rhiannon P. Kuchel, Navind Jayasooriah, Emma Estevez, Tim Petzold, Catherine M. Suter, Paul Gregorevic, Bente Kiens, Erik A. Richter, David E. James, Jørgen F.P. Wojtaszewski, Mark A. Febbraio
Exercise stimulates the release of molecules into the circulation, supporting the concept that inter-tissue signaling proteins are important mediators of adaptations to exercise. Recognizing that many circulating proteins are packaged in extracellular vesicles (EVs), we employed quantitative proteomic techniques to characterize the exercise-induced secretion of EV-contained proteins. Following a 1-hr bout of cycling exercise in healthy humans, we observed an increase in the circulation of over 300 proteins, with a notable enrichment of several classes of proteins that compose exosomes and small vesicles. Pulse-chase and intravital imaging experiments suggested EVs liberated by exercise have a propensity to localize in the liver and can transfer their protein cargo. Moreover, by employing arteriovenous balance studies across the contracting human limb, we identified several novel candidate myokines, released into circulation independently of classical secretion. These data identify a new paradigm by which tissue crosstalk during exercise can exert systemic biological effects.

Graphical abstract

Teaser

Using quantitative proteomic techniques and intravital imaging experiments, Whitham et al. characterize the exercise-induced secretion of proteins contained in extracellular vesicles (EVs) and identify several novel candidate myokines that are released into the circulation independently of classical secretion.


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An Adipose Tissue Atlas: An Image-Guided Identification of Human-like BAT and Beige Depots in Rodents

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Fang Zhang, Guiyang Hao, Mengle Shao, Kien Nham, Yu An, Qiong Wang, Yi Zhu, Christine M. Kusminski, Gedaa Hassan, Rana K. Gupta, Qiwei Zhai, Xiankai Sun, Philipp E. Scherer, Orhan K. Oz
[¹⁸F]Fluorodeoxyglucose-PET/CT (¹⁸F-FDG-PET/CT) imaging has been invaluable for visualizing metabolically active adipose tissues in humans with potential anti-diabetic and anti-obesity effects. To explore whether mice display human-like fat depots in anatomically comparable regions, we mapped fat depots using glucose or fatty acid imaging tracers, such as ¹⁸F-FDG through PET/CT or [^123/125I]-β-methyl-p-iodophenyl-pentadecanoic acid with SPECT/CT imaging, to analogous depots in mice. Using this type of image analysis with both probes, we define a large number of additional areas of high metabolic activity corresponding to novel fat pads. Histological and gene expression analyses validate these regions as bona fide fat pads. Our findings indicate that fat depots of rodents show a high degree of topological similarity to those of humans. Studies involving both glucose and lipid tracers indicate differential preferences for these substrates in different depots and also suggest that fatty acid-based visualized approaches may reveal additional brown adipose tissue and beige depots in humans.

Graphical abstract

Teaser

¹⁸F-FDG-PET/CT imaging in humans has been invaluable for visualizing metabolically active adipose tissues. Using PET/CT and SPECT/CT for imaging glucose and lipid metabolism, respectively, in mice, Zhang et al. define an atlas of fat depots, topologically analogous to those observed in humans.


http://ift.tt/2ALMAy1

Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur Proteins

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Oliver Stehling, Judita Mascarenhas, Ajay A. Vashisht, Alex D. Sheftel, Brigitte Niggemeyer, Ralf Rösser, Antonio J. Pierik, James A. Wohlschlegel, Roland Lill




http://ift.tt/2AJalqC

SnapShot: Niche Determines Adipocyte Character I

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Devika P. Bagchi, Isabel Forss, Susanne Mandrup, Ormond A. MacDougald
Adipose tissues are complex organs, with central roles in energy homeostasis as well as local functions. Adipocytes develop in diverse, discrete locations throughout the body. Important regional differences in adipocytes exist, and diseases that affect adipose tissues often demonstrate depot-specific effects. Herein, we depict the widespread locations of major and minor rodent adipose depots. Depot-specific molecular and functional characteristics will be described in Part II.

Teaser

Adipose tissues are complex organs, with central roles in energy homeostasis as well as local functions. Adipocytes develop in diverse, discrete locations throughout the body. Important regional differences in adipocytes exist, and diseases that affect adipose tissues often demonstrate depot-specific effects. Herein, we depict the widespread locations of major and minor rodent adipose depots. Depot-specific molecular and functional characteristics will be described in Part II.


http://ift.tt/2CX0gMK

SnapShot: Niche Determines Adipocyte Character II

Publication date: 9 January 2018
Source:Cell Metabolism, Volume 27, Issue 1
Author(s): Devika P. Bagchi, Isabel Forss, Susanne Mandrup, Ormond A. MacDougald
The intrinsic cellular and metabolic properties of an adipocyte are shaped by the specific niche in which it resides. The diverse and discrete locations of major and minor rodent adipose depots are depicted in Part I. In Part II, the molecular and functional characteristics of four major types of adipocytes are described. Identified functions of relatively understudied but undoubtedly important depots are also highlighted.

Teaser

The intrinsic cellular and metabolic properties of an adipocyte are shaped by the specific niche in which it resides. The diverse and discrete locations of major and minor rodent adipose depots are depicted in Part I. In Part II, the molecular and functional characteristics of four major types of adipocytes are described. Identified functions of relatively understudied but undoubtedly important depots are also highlighted.


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A Qualitative Assessment of Academic Radiation Oncology Department Chairs’ Insights on Diversity, Equity, and Inclusion: Progress, Challenges, and Future Aspirations

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rochelle D. Jones, Christina H. Chapman, Emma B. Holliday, Nafisha Lalani, Emily Wilson, James A. Bonner, Benjamin Movsas, Shalom Kalnicki, Silvia C. Formenti, Charles R. Thomas, Steve M. Hahn, Fei-Fei Liu, Reshma Jagsi
PurposeA lack of diversity has been observed in radiation oncology (RO), with women and certain racial/ethnic groups underrepresented as trainees, faculty, and practicing physicians. The authors sought to gain a nuanced understanding of how to best promote diversity, equity, and inclusion (DEI) based on the insights of RO department chairs, with particular attention given to the experiences of the few women and underrepresented minorities (URM) in these influential positions.MethodsIn March-June 2016, the authors conducted telephone interviews with 24 RO department chairs (of 27 invited). Purposive sampling was employed to invite all chairs who were women (n=13) or URM (n=3), along with 11 male chairs who were not URM. Multiple analysts coded verbatim transcripts.ResultsFive themes were identified: (1) commitment to DEI promotes quality healthcare and innovation, (2) gaps remain despite some progress with promoting diversity in RO, (3) women and URM faculty continue to experience challenges in various career domains, (4) solutions to DEI issues would be facilitated by acknowledging realities of gender and race, and (5) expansion of the career pipeline is needed.ConclusionsChairs' insights had policy-relevant implications. Bias training should broach tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage students before their application to medical school.

Teaser

This qualitative study sought to understand how to promote diversity, equity, and inclusion in radiation oncology. The authors conducted telephone interviews with department chairs, with attention to the experiences of the few women and underrepresented minorities in these positions. Chairs' insights had policy-relevant implications. Bias training should attempt to tap into the sensitive contextual areas of tokenism, blindness, and intersectionality. Efforts to recruit and support diverse talent should be deliberate and proactive. Bridge programs could engage diverse learners across the education spectrum.


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Endoscopic Surgery for Delayed Sinonasal Complications of Radiotherapy for Nasopharyngeal Carcinoma: a Subjective Outcome

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Rachel Shemesh, Eran E. Alon, Iris Gluck, Arkadi Yakirevitch
BackgroundDelayed sino-nasal complications of radiotherapy include choanal stenosis, osteoradionecrosis, chronic sinusitis and intranasal synechiae. There are only sporadic reports on their surgical treatment with equivocal results.MethodsThis is a prospective case series of all patients surgically treated for delayed sino-nasal complications of radiotherapy in our institution during the last 10 years. The inclusion criteria required at least a 6-month follow up after the surgery. Included patients were asked to fill a SNOT-16 questionnaire preoperatively and 6 months after the surgery.Resultsnine patients with history of radiotherapy for nasopharyngeal carcinoma were included in our series. In all cases partial or complete subjective improvement was seen.ConclusionIn select cases, endoscopic sinus surgery may be of benefit in the treatment of delayed sino-nasal complications of radiotherapy.

Teaser

Delayed sino-nasal complications of radiotherapy include choanal stenosis, osteoradionecrosis, chronic sinusitis and intranasal synechiae. Their incidence and burden on their quality of life are underestimated. Results of our prospective study show good subjective outcome of surgical treatment of these delayed sino-nasal complications. It should encourage clinicians to be cognizant of symptoms suspicious for this pathology and to be diligent in referring the patients for further evaluation and treatment.


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Radiation Therapy to Sites of Metastatic Disease as Part of Consolidation in High-risk Neuroblastoma: Can Long-term Control be Achieved?

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Dana L. Casey, Ken L. Pitter, Brian H. Kushner, Nai-Kong V. Cheung, Shakeel Modak, Michael P. LaQuaglia, Suzanne L. Wolden
BackgroundAs part of consolidative therapy in high-risk neuroblastoma, modern protocols recommend radiation therapy (RT) both to the primary site and to sites of metastatic disease that persist after induction chemotherapy. Although there is abundant data showing excellent local control with 21 Gy directed at the primary site, there is little data describing the feasibility and efficacy of RT directed at metastatic sites of disease as part of consolidation.MethodsAll patients with neuroblastoma who received RT to metastatic sites of disease as a part of consolidative therapy at a single institution between 2000 and 2015 were reviewed. Among 159 patients, 244 metastases were irradiated.ResultsMedian follow up among surviving patients was 7.4 years. Over 85% of the irradiated metastases were treated with 21 Gy (range 10.5 Gy - 36 Gy). Tumor recurrence occurred in 43 of 244 (18%) irradiated metastases. The 5-year local control (LC) of treated metastatic sites was 81%. Metastatic sites that cleared with induction chemotherapy had improved LC compared to sites with persistent uptake on MIBG (LC 92% vs 67%, p<0.0001). LC at irradiated metastatic sites did not differ based on total number of sites irradiated or site of disease irradiated (bone vs soft tissue). Patients with bulky, resistant disease who were treated with 30-36 Gy had worse LC (p=0.02). However, on multivariate analysis, only persistence after induction chemotherapy remained a significant prognostic factor for LC (hazard ratio = 3.7, p<0.0001). Patients with LC at irradiated metastatic sites had improved overall survival (OS) compared to those who did not (OS 71% vs 50%, p<0.0001).ConclusionsResponse to chemotherapy is an important prognostic factor for LC at irradiated metastatic sites in neuroblastoma. Overall, consolidative RT appears to be an effective modality of LC. Long-term disease control can be achieved with such an approach.

Teaser

Although radiation therapy to persistent sites of metastatic disease is recommended as part of consolidative therapy for high-risk neuroblastoma, there is little data evaluating the value of this approach in achieving long-term control. Our results show that irradiation of metastatic sites of disease is effective in achieving local control, and that response to induction chemotherapy is a significant prognostic factor for control at irradiated sites.


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Current and Future Initiatives for Radiation Oncology at the National Cancer Institute in the Era of Precision Medicine

Publication date: Available online 8 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Charles A. Kunos, C. Norman Coleman




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Patient Experiences and Clinician Views on the Role of Radiotherapy for Ductal Carcinoma In-Situ

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Dean A. Shumway, Chandler M. McLeod, Monica Morrow, Yun Li, Allison W. Kurian, Aaron Sabolch, Ann S. Hamilton, Kevin C. Ward, Steven J. Katz, Sarah T. Hawley, Reshma Jagsi
PurposeTo evaluate patient experiences with decisions regarding radiotherapy for ductal carcinoma in situ (DCIS), and to assess clinician views on the role of radiotherapy for DCIS with favorable features in the present era.MethodsA sample of women with newly diagnosed breast cancer from the population-based Georgia and Los Angeles County (LA) SEER registries were sent surveys approximately 2 months after undergoing breast conserving surgery (70% response rate). The analytic sample was limited to 538 respondents with unilateral DCIS. We also surveyed 761 surgeons and radiation oncologists treating breast cancer in those regions, of whom 539 responded (71%).ResultsAfter breast conserving surgery (BCS), 23% of patients omitted radiotherapy, with twice the rate of omission in LA relative to Georgia (31% vs 16%, p<0.001). The most common reasons for omitting radiotherapy were advice from a clinician that it wasn't needed (62%) and concern about side effects (24%). Cost and transportation were not reported as influential considerations. After covariate adjustment, low and intermediate grade disease (OR 5.5, 95% CI 2.5-12; OR 3.2, 95% CI 1.7-6.1) and LA SEER site (OR 4.3, 95% CI 2.3-8.2) were significantly associated with greater radiotherapy omission. Among responding clinicians, 62% would discuss radiotherapy omission for a patient with DCIS with favorable features. Clinicians in LA were more likely to discuss radiotherapy omission than those in Georgia (67% vs 56%, p = 0.01). Approximately one-third of clinicians would obtain the Oncotype DX DCIS Score.ConclusionsThere continues to be substantial heterogeneity in radiotherapy omission after breast conserving surgery for DCIS, with systematic differences in provider opinions across the two regions we studied. Enhanced precision of recurrence estimates, guidance from professional organizations, and better communication are needed to improve the consistency of treatment in this controversial area.

Teaser

In a population-based survey of patients with DCIS, we observed that a quarter of patients omit radiotherapy after breast conserving surgery, with a two-fold difference in the rate of radiotherapy omission between the 2 SEER regions studied. In a corresponding survey of clinicians, we observed systematic differences in opinions between the two SEER regions regarding the role of radiation.


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The radiation resistance of human multipotent mesenchymal stromal cells is independent of their tissue of origin

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Alexander Rühle, Oliver Xia, Ramon Lopez Perez, Thuy Trinh, Wiltrud Richter, Anna Sarnowska, Patrick Wuchter, Jürgen Debus, Rainer Saffrich, Peter E. Huber, Nils H. Nicolay
PurposeHuman mesenchymal stromal cells (MSCs) may aid the regeneration of ionizing radiation-induced tissue damage. They can be harvested from different tissues for clinical purposes; however, the role of the tissue source on the radiation response of human MSCs remains unknown.Methods and MaterialsHuman MSCs were isolated from adipose tissue, bone marrow and umbilical cord, and cellular survival, proliferation and apoptosis were measured after irradiation. The influence of ionizing radiation (IR) on the defining functions of MSCs was assessed, and cell morphology, surface marker expression and the differentiation potential were examined. Western blot analyses were performed to assess the activation of DNA damage signaling and repair pathways.ResultsMSCs from adipose tissue, bone marrow and umbilical cord exhibited a relative radioresistance independent of their tissue of origin. Defining properties including cellular adhesion and surface marker expression were preserved, and irradiated MSCs maintained their potential for multi-lineage differentiation irrespective of their tissue source. Analysis of activated DNA damage recognition and repair pathways demonstrated an efficient repair of IR-induced DNA double-strand breaks in MSCs from different tissues, thereby influencing the induction of apoptosis.ConclusionsThese data show for the first time that MSCs are resistant to IR and largely preserve their defining functions after irradiation irrespective of their tissue of origin. Efficient repair of IR-induced DNA double-strand breaks and consecutive reduction of apoptosis induction may contribute to the tissue-independent radiation resistance of MSCs.

Teaser

Mesenchymal stromal cells (MSCs) from different tissues may aid the regeneration of radiation-induced organ lesions; however, the influence of ionizing radiation on tissue-specific human MSCs is unknown. Here we show that the radiation resistance of MSCs is independent of their tissue of origin, and irradiated MSCs from adipose tissue, bone marrow and umbilical cord preserved their defining characteristics. Efficient repair of radiation-induced DNA damage may contribute to this radiation resistance.


http://ift.tt/2CW5l7Q

The efficacy and safety of conventional and hypofractionated high-dose radiotherapy for prostate cancer in an elderly population: a subgroup analysis of the CHHiP trial

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): James M. Wilson, David Dearnaley, Isabel Syndikus, Vincent Khoo, Alison Birtle, David Bloomfield, Ananya Choudhury, John Graham, Catherine Ferguson, Zafar Malik, Julian Money-Kyrle, Joe M. O'Sullivan, Miguel Panades, Chris Parker, Yvonne Rimmer, Christopher Scrase, John Staffurth, Andrew Stockdale, Clare Cruickshank, Clare Griffin, Emma Hall
IntroductionOutcome data on radiotherapy for prostate cancer in an elderly population are sparse. The CHHiP trial provides a large, prospectively collected, contemporary dataset in which to explore outcomes by age.Methods and MaterialsCHHiP participants received 3-6 months of androgen deprivation therapy and were randomly assigned (1:1:1) to receive 74Gy in 37 fractions (conventional fractionation), 60Gy in 20 fractions or 57Gy in 19 fractions. Toxicity was assessed using clinician-reported and patient-reported outcome (CRO/PRO) questionnaires. Participants were categorised as aged less than 75 (<75) or 75 years and older (75+).Outcomes were compared by age-group.Results491/3216 (15%) were 75+. There was no difference in biochemical or clinical failure (BCF) rates between the <75 and the 75+ group for any of the fractionation schedules. In the 75+ group BCF-free rates favoured hypofractionation and at 5 years were 74Gy: 84.7%, 60Gy: 91%, 57Gy: 87.7%. The incidence of CRO (G3) acute bowel toxicity was 2% in both age-groups. Grade 3 acute bladder toxicity was 8% and 7%. Five year cumulative incidence of CRO grade 2+ late bowel side effects was similar in both age groups. However, in the 75+ group, there was a suggestion of a higher cumulative incidence of bowel bother (≥small) with 60Gy compared to 74Gy and 57Gy. Patient-reported bladder bother was slightly higher in the 75+ group than the <75 group and there was a suggestion of a lower cumulative incidence of bladder bother with 57Gy compared to 74Gy and 60Gy in the 75+ group which was not evident in those <75.ConclusionHypofractionated radiotherapy appears to be well tolerated and effective in men over 75. The 57 Gy schedule has potential advantages in that it may moderate long term side effects without compromising treatment efficacy in this group.

Teaser

The efficacy and toxicity of radiotherapy for localised prostate cancer in CHHiP trial participants aged 75 and over was compared with patients younger than 75. There was no evidence of a difference in biochemical or clinical recurrence free survival or clinically significant toxicity between the older and younger patient groups. Hypofractionated radiotherapy is an effective and well tolerated treatment for localised prostate cancer in an elderly population with good performance status.


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The Role of Radiation Therapy in Patients with Relapsed/Refractory Hodgkin Lymphoma: Guidelines from the International Lymphoma Radiation Oncology Group

Publication date: Available online 9 January 2018
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Louis S. Constine, Joachim Yahalom, Andrea K. Ng, David C. Hodgson, Andrew Wirth, Sarah A. Milgrom, N. George Mikhaeel, Hans Theodor Eich, Tim Illidge, Umberto Ricardi, Karin Dieckmann, Craig H. Moskowitz, Ranjana Advani, Peter M. Mauch, Lena Specht, Richard T. Hoppe
Relapsed and refractory Hodgkin lymphoma (HL) challenges clinicians to devise treatment strategies that are effective and safe. This problem is particularly prominent in an era when de-escalation trials are designed to minimize therapeutic toxicities in both early and advanced stage disease. Radiation therapy is the single most effective treatment modality for HL, and its integration into salvage regimens, or its independent use in select patients, must be understood in order to maximize our success in treating these patients. The complexity of treating relapsed/refractory HL derives from the spectrum of primary treatment approaches currently in use that creates heterogeneity in both treatment exposure and the potential toxicities of salvage therapy. Patients can have relapsed or refractory disease after limited or aggressive primary therapy (with or without radiation therapy), at early or delayed time points, with limited or extensive disease volumes, and with varying degrees of residual morbidity from primary therapy. Their response to salvage systemic therapy can be partial or complete, and the use of consolidative stem cell transplant is variably applied. New biologics and immunotherapeutic approaches have broadened but also complicated salvage treatment approaches. Through all of this, radiation therapy remains an integral component of treatment for many patients but it must be used effectively and judiciously. The purpose of this review is to describe the different treatment scenarios and provide guidance for radiation dose, volume, and timing in patients with relapsed or refractory HL.



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The effect of white matter hyperintensities on cognition is mediated by cortical atrophy

Publication date: April 2018
Source:Neurobiology of Aging, Volume 64
Author(s): Batool Rizvi, Atul Narkhede, Briana S. Last, Mariana Budge, Giuseppe Tosto, Jennifer J. Manly, Nicole Schupf, Richard Mayeux, Adam M. Brickman
White matter hyperintensities (WMH) have been linked to cognitive dysfunction and dementia, although the reasons are unclear. One possibility is that WMH promote neurodegeneration, which, in turn, affects cognition. We examined whether cortical thickness, a marker of neurodegeneration, mediates the relationship between WMH and cognition among 519 older adults. Using conditional process analysis modeling techniques, we examined the association between WMH volume and global cognition and tested whether cortical thickness mediates this relationship statistically. We also tested specific regional hypotheses to determine whether cortical thickness or volume in the medial temporal lobe mediates the relationship between WMH volume and memory. Increased total WMH volume was associated with poorer global cognition and memory. Global cortical thickness and medial temporal lobe thickness/volume mediated the relationship of WMH volume on global cognition and memory functioning. The mediating relationship was similar across racial and ethnic groups and across diagnostic groups (i.e., mild cognitive impairment/Alzheimer's disease). The findings suggest that WMH promote atrophy, which, in turn, drives cognitive decline and highlight a potential pathway in which small vessel cerebrovascular disease affects cognition by promoting neurodegenerative changes directly.



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Age-related differences in the neural correlates of empathy for pleasant and unpleasant touch in a female sample

Publication date: Available online 9 January 2018
Source:Neurobiology of Aging
Author(s): Federica Riva, Melanie Tschernegg, Patrizia Andrea Chiesa, Isabella C. Wagner, Martin Kronbichler, Claus Lamm, Giorgia Silani
Empathy is essential for successful social interactions and relationships. The neural underpinnings of empathy have predominantly been studied in the young adult population, while little is known about how they evolve across the life-span. In the present study, we used functional magnetic resonance imaging (fMRI) to investigate age-related differences of brain activity associated to empathy for positive and negative emotions. Female participants of three age groups – adolescents, young, and older adults- underwent an experimental paradigm inducing both first-hand and empathic experience of pleasant and unpleasant touch. Group comparisons and regression analyses revealed that older adults showed lower activation within the anterior insula with respect to young adults, during both empathy conditions. Further analyses provided evidence that years of education, Theory of Mind ability, grey matter volume, as well as first-hand affect processing did not account for these effects. These findings indicate that the neural bases of empathy change across different age groups, which selectively cover large parts of the human life span, from adolescence to old age, suggesting that the way in which we represent other's positive and negative emotions may go through important modifications throughout different ages.



http://ift.tt/2ALziRZ

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients

Abstract

Purpose

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden.

Methods

This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels.

Results

Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p < 0.001), and Haller's layer (p < 0.001) thicknesses, with no differences in Sattler's/choriocapillaris layer thickness. Multiple point measurements in the posterior pole area showed equally increased nasal and temporal parts of the choroid. The retinal thickness maps of the two groups did not significantly differ. Correlation analysis indicated that choroidal thickness was significantly correlated with disease duration (p = 0.01), serum IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor.

Conclusion

The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

http://ift.tt/2mcBkW6

Elevated serum IGF-1 level enhances retinal and choroidal thickness in untreated acromegaly patients

Abstract

Purpose

1) To compare the retinal, choroidal, Haller's layer, and Sattler's/choriocapillaris thicknesses of untreated acromegaly patients without chiasm compression or diabetes mellitus and healthy controls. 2) To evaluate the correlations of retinal and choroidal thicknesses with serum growth hormone (GH) and insulin-like growth factor 1 (IGF) burden.

Methods

This prospective, case-control study included 27 untreated acromegaly patients and 27 sex-matched and age-matched controls. Subfoveal choroidal, Haller's layer and Sattler's/choriocapillaris thicknesses were determined by enhanced-depth imaging optical coherence tomography (EDI-OCT). Foveal and macular retinal thicknesses were determined with SD-OCT. GH and IGF-1 burdens were defined as the product of disease duration and treatment-naïve serum GH and IGF-1 levels.

Results

Compared with healthy controls, patients with acromegaly exhibited significantly increased foveal retinal (p = 0.003), subfoveal choroidal (p < 0.001), and Haller's layer (p < 0.001) thicknesses, with no differences in Sattler's/choriocapillaris layer thickness. Multiple point measurements in the posterior pole area showed equally increased nasal and temporal parts of the choroid. The retinal thickness maps of the two groups did not significantly differ. Correlation analysis indicated that choroidal thickness was significantly correlated with disease duration (p = 0.01), serum IGF-1 level (p = 0.03) and IGF-1 burden (p = 0.009). No significant correlations were detected between choroidal thickness and GH burden (p = 0.44). Retinal thickness was not significantly correlated with any factor.

Conclusion

The choroidal thickness of acromegaly patients was greater than that of healthy controls and was significantly correlated with disease duration, IGF-1 level and IGF-1 burden, indicating that excessive serum IGF-1 and its exposure time have a combined effect on choroidal thickness.

http://ift.tt/2mcBkW6

Learning how to use IAM chromatography for predicting permeability

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Giuseppe Ermondi, Maura Vallaro, Giulia Caron
The interest for IAM (Immobilized Artificial Membranes) chromatography in the prediction of drug permeability is increasing. Here we firstly set-up a dataset of 253 molecules including neutral and ionized drugs and few organic compounds for which we either measured or retrieved from the literature IAM.PC.DD2 log Kw^IAM data. Then we applied block relevance (BR) analysis to extract from PLS models the relative contribution of intermolecular forces governing log Kw^IAM and Δlog Kw^IAM (a combined descriptor calculated from log Kw^IAM). Finally, the relationship between log Kw^IAM, Δlog Kw^IAM and passive permeability determined in both PAMPA and MDCK-LE systems was looked for. Models provided the basis for a rational application of IAM chromatography in permeability prediction.

Graphical abstract

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A trade-off between solubility enhancement and physical stability upon simultaneous amorphization and nanonization of curcumin in comparison to amorphization alone

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Jerome Jie Long Wong, Hong Yu, Li Ming Lim, Kunn Hadinoto
The numerous health benefits of curcumin (CUR) have not been fully realized due to its low aqueous solubility, resulting in poor bioavailability. While amorphization of CUR via amorphous solid dispersion (ASD) represents a well-established CUR solubility enhancement strategy, simultaneous amorphization and nanonization of CUR via amorphous CUR nanoparticles (or nano-CUR in short) have emerged only recently as the plausibly superior alternative to ASD. Herein we examined for the first time the amorphous nano-CUR versus the ASD of CUR in terms of their (1) in vitro solubility enhancement capability and (2) long-term physical stability. The ASD of CUR was prepared by spray drying with hydroxypropylmethylcellulose (HPMC) acting as crystallization inhibitor. The amorphous nano-CUR was investigated in both its (i) aqueous suspension and (ii) dry-powder forms in which the latter was prepared by spray drying with adjuvants (i.e. HPMC, trehalose, and soy lecithin). The results showed that the amorphous nano-CUR (in both its aqueous suspension and dry-powder forms) exhibited superior solubility enhancement to the ASD of CUR attributed to its faster dissolution rates. This was despite the ASD formulation contained a larger amount of HPMC. The superior solubility enhancement, however, came at the expense of low physical stability, where the amorphous nano-CUR showed signs of transformation to crystalline after three-month accelerated storage, which was not observed with the ASD. Thus, despite its inferior solubility enhancement, the conventional ASD of CUR was found to represent the more feasible CUR solubility enhancement strategy.

Graphical abstract

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Imitation of phase I metabolism reactions of MAO-A inhibitors by titanium dioxide photocatalysis

Publication date: 1 March 2018
Source:European Journal of Pharmaceutical Sciences, Volume 114
Author(s): Maciej Gawlik, Jakub Trawiński, Robert Skibiński
The imitation of phase I metabolism of moclobemide and toloxatone, two monoamine oxidase type A (MAO-A) inhibitors, was performed with the use of titanium dioxide photocatalytic process. Ultra high pressure liquid chromatography system coupled with an accurate hybrid ESI-Q-TOF mass spectrometer was used for the evaluation of metabolic profiles, structural elucidation of the identified transformation products and quantitative analysis of the process. Based on high resolution MS and MS/MS data, eleven transformation products were characterized in photocatalytic experiments for moclobemide and seven products for toloxatone. A significant number of these products were found as hepatic metabolites under the incubation of the selected MAO-A inhibitors with human liver microsomes (HLM). What is important, some of these HLM metabolites are not yet described in the literature. It was also found that the multivariate chemometric analysis allowed an effortless characterization of the registered metabolic profiles which can be a useful method for a fast preliminary drug metabolism study. Additionally, principal component analysis (PCA) of the registered TOF (MS) photocatalytic and HLM profiles of moclobemide and toloxatone shows that shorter irradiation time is preferred for photocatalytic metabolism experiments. A heterogeneous photocatalysis with the use of titanium dioxide was found to be a powerful tool for mimicking phase I metabolic reactions, as a fast, sensitive and inexpensive method.

Graphical abstract

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siRNA-mediated c-Rel knockdown ameliorates collagen-induced arthritis in mice

Publication date: March 2018
Source:International Immunopharmacology, Volume 56
Author(s): Tingting Fan, Fuhua Zhong, Ruiling Liu, Youhai H. Chen, Ting Wang, Qingguo Ruan
Previous studies have shown that inflammatory mediators involved in the development of rheumatoid arthritis (RA) are regulated by the Rel/nuclear factor-κB (Rel/NF-κB) transcription factor family. c-Rel, a member of the Rel/NF-κB family that is preferentially expressed by immune cells, is a risk factor for several inflammatory diseases including RA. In the current study, we investigated whether targeting c-Rel can be used to treat collagen-induced arthritis, an animal model for RA. c-Rel specific siRNA (siRel) delivered by nanoparticles was used to knockdown the expression of c-Rel. Our results showed that siRel treatment significantly ameliorated collagen-induced arthritis. Further study revealed that c-Rel expression in the dendritic cells and macrophages from mice treated with siRel was significantly down-regulated. Consistent with the phenotypical result, the expression of inflammatory cytokines TNF-α, IL-1β, IL-6, IL-12 and IL-23 by peritoneal macrophages and splenocytes were significantly decreased. In addition, attenuated systemic and collagen-specific Th1 and Th17 immune responses were observed. Furthermore, we found that the expression of inflammatory cytokines was significantly down-regulated and the infiltration of CD3⁺ T cells and F4/80⁺ macrophages was markedly reduced in hind paws of mice treated with siRel. Collectively, our study provides strong evidence that siRNA-mediated c-Rel knockdown can suppress the development of collagen-induced arthritis in mice. Therefore, blocking c-Rel may represent an attracting strategy for the treatment of human rheumatoid arthritis.



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Astaxanthin ameliorates cerulein-induced acute pancreatitis in mice

Publication date: March 2018
Source:International Immunopharmacology, Volume 56
Author(s): Hui Zhang, Wenjuan Yang, Yueyue Li, Liangkai Hu, Ying Dai, Jianqing Chen, Shuqi Xu, Xuanfu Xu, Haiqiong Jiang
BackgroundA various of pharmacological effects of astaxanthin has been confirmed. However, the mechanism underlying protective effect of astaxanthin on acute pancreatitis (AP) induced by cerulein still unclear. The present study is to investigate the mechanism underlying the effect of astaxanthin on autophagy and apoptosis via the JAK/STAT3 pathway.MethodsIntraperitoneal injection of cerulein at hourly intervals followed by lipopolysaccharide injection were used in Balb/C mice. Vehicle or astaxanthin, which intraperitoneal injected in two doses (20 mg/kg and 40 mg/kg), were injected in mice 1 h before the first cerulein injection. At 3 h after the last injection, when the pathological changes were most severe, pancreatic tissue was analyzed by pathologically scored and hematoxylin and eosin (H&E) staining. The severity of AP was assessed by histological grading, proinflammatory cytokine levels, biochemistry, myeloperoxidase (MPO) activity, and analysis of JAK/STAT3 activity.ResultsAstaxanthin administration markedly reduced serum digestive enzyme activities, pancreatic histological scores, proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6)), MPO and JAK/STAT3 activity.ConclusionCollectively, these results indicate that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated apoptosis and autophagy.



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Kaempferol alleviates LPS-induced neuroinflammation and BBB dysfunction in mice via inhibiting HMGB1 release and down-regulating TLR4/MyD88 pathway

Publication date: March 2018
Source:International Immunopharmacology, Volume 56
Author(s): Xiao Cheng, Ying-Lin Yang, Huan Yang, Yue-Hua Wang, Guan-Hua Du
Kaempferol is a natural flavonoid with many biological activities including anti-oxidation and anti-inflammation. Nevertheless, its anti-neuroinflammation role and the relevant mechanism remain unclear. The present study was to investigate effects of kaempferol against LPS-induced neuroinflammation and blood-brain barrier dysfunction as well as the mechanism in mice. BALB/c mice were treated with LPS 5mg/kg to induce inflammation after pre-treatment with kaempferol 25, 50, or 100mg/kg for 7days. The results showed that kaempferol reduced the production of various pro-inflammatory factors and inflammatory proteins including IL-1β, IL-6, TNF-α, MCP-1, COX-2 and iNOS in brain tissues. In addition, kaempferol also protected BBB integrity and increased BBB related proteins including occludin-1, claudin-1 and CX43 in brain of LPS-induced mice. Furthermore, kaempferol significantly reduced HMGB1 level and suppressed TLR4/MyD88 inflammatory pathway in both transcription level and translation level. These results collectively suggested that kaempferol might be a promising neuroprotective agent for alleviating inflammatory responses and BBB dysfunction by inhibiting HMGB1 release and down-regulating TLR4/MyD88 inflammatory pathway.



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NFAT-1 hyper-activation by methionine enkephalin (MENK) significantly induces cell apoptosis of rats C6 glioma in vivo and in vitro

Publication date: March 2018
Source:International Immunopharmacology, Volume 56
Author(s): Wei-cheng Lu, Hui Xie, Xin-xin Tie, Ruizhe Wang, An-hua Wu, Feng-ping Shan
The aim of the work was to investigate the effect and possible mechanism of MENK on the growth of rat C6 glioma in vivo or in vitro. Our findings showed that MENK could inhibit the growth of rat C6 glioma, prolong median survival times in tumor-bearing rats, and induce glioma cell apoptosis. Moreover, MENK could increase the activities of caspase-3, caspase-8 and caspase-9. It also increased the expression of Fas, FasL, Bax, while decreased the expression of Bcl-2. We further confirmed that MENK could increase opioid receptors MOR and DOR expressions, Ca²⁺ influx into the cytoplasm, and a substantial increase of NFAT1accumulation in the nuclei in C6 glioma cell. When we specifically knocked down NFAT1, there was no effect of MENK on the cell viability and FasL up-regulation in NFAT1 knocked-down cell. These results demonstrate that MENK could bind to opioid receptors MOR and DOR on C6 glioma cells and trigger a Ca²⁺ influx into the cytoplasm, resulting in translocation of NFAT1 into the nucleus. The hyper-activation of NFAT1 may regulate transcription of downstream gene, such as FasL, and induce apoptosis of rat C6 glioma cells.



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Vaginal delivery-related changes in the pelvic organ position and vaginal cross-sectional area in the general population

Publication date: July–August 2018
Source:Clinical Imaging, Volume 50
Author(s): Shotaro Naganawa, Eriko Maeda, Akifumi Hagiwara, Shiori Amemiya, Wataru Gonoi, Shouhei Hanaoka, Takeharu Yoshikawa, Kuni Ohtomo
PurposeEvaluate the effect of vaginal delivery on pelvic organ positions and vaginal cross-sectional areas.MethodsMRI of 119 premenopausal women were grouped according to the number of deliveries. The distances from the three 3-reference points (bladder, uterus, and rectum) to two 2-lines (pubococcygeal-line (PCL) and midpubic-line (MPL)), length of H- and M-lines and vaginal cross-sectional area were compared between the groups.ResultsWith increasing parity, distance from the rectum to PCL tended to increase (nullipara vs. bipara; p<0.01). Vaginal cross-sectional area was larger in bipara and tripara than in nullipara (p<0.01).ConclusionsRectal position is more caudally located and vaginal cross-sectional area is larger in bipara than in nullipara.



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The unusual suspects: A review of unusual benign and malignant male breast imaging cases

Publication date: July–August 2018
Source:Clinical Imaging, Volume 50
Author(s): Victoria L. Mango, Sarah Goodman, Kim Clarkin, Ralph T. Wynn, Lauren Friedlander, Hanina Hibshoosh, Richard Ha
Male breast disease is uncommon. Men presenting with breast symptoms may represent unique diagnostic challenges for the radiologist, particularly if imaging findings are not classic for gynecomastia or carcinoma. In this paper we review 10 unusual male breast cases, 5 benign and 5 malignant, including the radiologic findings, differential diagnosis, pathology and management.



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Cystic mediastinal masses and the role of MRI

Publication date: July–August 2018
Source:Clinical Imaging, Volume 50
Author(s): Rachna Madan, Lisa Ratanaprasatporn, Linda Ratanaprasatporn, Brett W. Carter, Jeanne B. Ackman
While some cystic masses can be definitively diagnosed on CT, others remain indeterminate. Because of its intrinsic superior soft tissue resolution, MR is an important tool in the evaluation of select mediastinal masses that are incompletely characterized on CT. This review describes how non-vascular MR provides greater diagnostic precision in the evaluation of indeterminate cystic mediastinal masses on CT. It also emphasizes key MR pulse sequences for optimal evaluation of problematic mediastinal masses.



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A Wrapped Multi-label Classifier for the Automatic Diagnosis and Prognosis of Alzheimer’s Disease

Publication date: Available online 9 January 2018
Source:Journal of Neuroscience Methods
Author(s): C. Salvatore, I. Castiglioni
BackgroundAD is the most frequent neurodegenerative disease, severely impacting our society. Early diagnosis and prognosis are challenging tasks in the management of AD patients.New MethodWe implemented a machine-learning classifier for the automatic early diagnosis and prognosis of AD by means of features extracted, selected and optimized from structural MRI brain images. The classifier was designed to perform multi-label automatic classification into the following four classes: HC, ncMCI, cMCI, and AD.ResultsFrom our analyses, it emerged that MMSE and hippocampus-related measures must be included as primary measures in automatic-classification systems for both the early diagnosis and the prognosis of AD. The voting scheme mainly based on the binary-classification performances on the different four groups is the best choice to model the multi-label decision function for AD, when compared with a simple majority-vote scheme or with a scheme aimed at discriminating patients with high vs low risk of conversion to AD and therapy addressing.Comparison with Existing Method(s)The accuracies of our binary classifications were higher than or comparable to previously published methods. An improvement is needed on the approach we used to combine binary-classification outputs to obtain the final multi-label classification.ConclusionsThe performance of multi-label automatic-classification systems strongly depends on the choice of the voting scheme used for combining binary-classification labels.



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Antimicrobial activity of Psidium cattleianum associated with calcium hydroxide against Enterococcus faecalis and Candida albicans : an in vitro study

Abstract

Objective

Evaluate, in vitro, the antimicrobial activity of Psidium cattleianum leaf extracts combined with calcium hydroxide against Enterococcus faecalis and Candida albicans biofilm.

Materials and methods

Dentin specimens obtained from extracted bovine incisors were infected during 14 days with E. faecalis ATCC 29212 and C. albicans ATCC 10231. The specimens were filled with calcium hydroxide pastes prepared with the following vehicles: Psidium cattleianum ethanolic, Psidium cattleianum propylene glycolic, distilled water, and saline as control. After 24 h, 3, 7, and 14 days, the canals were irrigated with sterile saline and dried. Dentin samples were collected from the canals with burs of increasing diameters. To determine the number of colony-forming units (CFU), samples were inoculated onto BHI agar supplemented with yeast extract (0.5%), at 37 °C, for 48 h, in CO₂ enriched atmosphere. Comparisons among the groups for the variation factors were performed by ANOVA and Tukey's test.

Results

Ethanolic and propylene glycolic extracts showed significantly higher antimicrobial activity against E. faecalis (p < 0.01) when compared with distilled water. The ethanolic extract exhibited in 24 h the same antibacterial activity that propylene glycolic extract and distilled water after 7 and 14 days. For C. albicans, all were effective in reducing the number of CFU at all periods.

Conclusion

The P. cattleianum ethanolic extract presented the fastest and highest antimicrobial activity against E. faecalis, significantly reducing the microbial load in 24 h. All medications were effective against C. albicans.

Clinical relevance

The antibacterial potential of P. cattleianum and its biological compatibility associated with calcium hydroxide indicate promising applications in the field of dentistry.

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Aesthetic Refinements after Radial Free Flap Phalloplasty: Optimizing the Donor Site and the Phallus

Background: Phalloplasty with radial forearm flap is the gold standard for female-to-male sex reassignment surgery. However, it leaves a stigmatizing forearm scar, and as the new phallus is created with the forearm's skin and fat, it does not look like that of a biological man. The aesthetic appearance of the donor site and the neophallus can be optimized after phalloplasty. In this study, we review refinement techniques (RTs) performed after radial forearm flap phalloplasty. Methods: We present a historical cohort of patients who underwent the following RTs: forearm fat grafting and localized laser in the forearm's scars, and micropigmentation of the neophallus. Patient's aesthetic satisfaction was evaluated using the Patient and Observer Scar Assessment Scale for the forearm's refinements and the Male Genital Self-Image Scale for the neophallus. Results: Between January 2014 and January 2016, 8 patients underwent forearm fat grafting with localized laser, and 7 patients micropigmentation of the neophallus after radial flap phalloplasties. All Patient and Observer Scar Assessment Scale parameters showed a statistically significant reduction between preoperative and postoperative values. Male Genital Self-Image Scale survey showed that all patients felt positively about their genitals after micropigmentation. Patients who underwent refinement procedures were highly satisfied with the aesthetic outcome and felt more confident. They also claim that they would choose to have the refinement procedure done again. Conclusions: The proposed RTs are minimally invasive interventions to complement and enhance female-to-male sex reassignment surgery with very few complications and excellent aesthetic results of both the forearm scars and the constructed phallus.

http://ift.tt/2CW7aSj

Laterality and Left-sidedness in the Nose, Face, and Body: A New Finding

Background: Asymmetry is a common occurrence in bilaterian animals, particularly human beings. Through examination of patients and their photographs during rhinoplasty, we noted wider left-sided nasal and facial features in most patients. This observation led us to hypothesize that this might be consistent to the whole body. Methods: We conducted a study in 3 parts to test the question above. First, we analyzed operating notes of 50 rhinoplasty patients to determine the wider side of the upper, middle, and lower thirds of the nose. Second, we analyzed the width of the face and chest wall in 31 patients to discern any correlation between facial and bodily asymmetry. Third, computerized tomographic scans of the thorax and body of 48 patients were studied to measure the width of the hemithorax and hemipelvic bone. Results: (1) Upper vault width was wider on left side (78%). Left middle vault width was wider (88%). The lower lateral cartilage, lateral crura convexity was more prominent on left side (48%), and a wider scroll area was found and trimmed in 21 (left) and 0 (right) cases. The alar base was wider on left side (56%). (2) In the body and face analysis, 64.5% had a wider left-sided face and body. (3) In the computed tomographic scan analysis, same-sided thorax and pelvis asymmetry was seen (85.35%), 33 and 7 of which were left- and right-sided, respectively. Conclusion: We observed generalized asymmetry of the face and body with left-sided predominance.

http://ift.tt/2CYWzWU

Late-Onset Inflammatory Response to Hyaluronic Acid Dermal Fillers

Objective: Even though injectable hyaluronic acid (HA)–based fillers are considered safe, rare complications, such as late-onset inflammatory reactions have been reported. Possible causes and effective treatments have not been formally described, so this work aims to discuss these and offer a formal protocol for treatment. Methods: This article presents 5 clinical cases of late-onset inflammatory response occurring at least 3 months after uneventful injection of HA dermal filler. Results: Inflammation appeared spontaneously, usually 4–5 months after the last injection, but in 1 patient, almost 14 months later. One patient was injected at the same time with fillers manufactured by 2 different technologies. In this case, all areas treated with the same filler showed diffuse swelling of inflammatory nature, whereas the lips, treated with the second filler brand, remained unaffected. Four patients reported a flu-like illness or gastrointestinal upset a few days before the onset of dermal filler inflammation. Conclusion: Late-onset inflammatory reactions to HA fillers may be self-limiting but are easily and rapidly treatable with oral steroids, and with hyaluronidase in the case of lumps. It is likely these reactions are due to a Type IV delayed hypersensitivity response. Delayed inflammation associated with HA fillers is nonbrand specific. However, the case where 2 different brands were injected during the same session, but only 1 brand triggered a hypersensitivity reaction, suggests that the technology used in the manufacturing process, and the subsequent differing products of degradation, may have an influence on potential allergic reactions to HA fillers.

http://ift.tt/2CYWr9S

Successfully Closing an Acquired Palatal-fistula Using a Turnover Flap from a Previously Transferred Forearm-free-flap

Summary: Palatal fistula between the oral and nasal cavities occurs in about 20% of palatal repairs after oncologic resection. Although healing by secondary intention may be employed as an initial strategy, persistent nonhealing symptomatic fistula necessitates intervention. Folded free flap used for primary repair of palatectomy defects enables placement of epithelialized tissue on both the oral and nasal cavities. In case of acquired palatal fistula, a turnover flap can be easily created, based on the free margin of the folded forearm free flap to serve as a reconstructive lifeboat.

http://ift.tt/2CYWjHq

Novel Pressure-Sensing Smart Insole System Used for the Prevention of Pressure Ulceration in the Insensate Foot

Summary: Wounds of the foot challenge reconstructive surgeons to manage multiple factors: sensibility, stability, and durability. In this article, we focus on the insensate foot, which poses challenges to wound prevention with its propensity to develop pressure ulceration. The authors present the innovative use of a pressure-sensing smart insole system (SurroSense Rx, Orpyx Medical Technologies Inc., Calgary, Canada) in the management of the insensate foot in a patient following foot reconstruction. The pressure-sensing smart insole system provided unique feedback to both patient and provider in ways that contributed to the prevention of pressure ulcer recurrence, as well as highlight the importance of prescribed footwear in both the affected and unaffected foot. Wearable real-time monitoring and feedback faces the challenge of patient adherence. Future studies are indicated to examine the specific behaviors that are associated with favorable outcomes and long-term behavior changes.

http://ift.tt/2CXAcB4

Consensus Recommendations for Treatment Strategies in Indians Using Botulinum Toxin and Hyaluronic Acid Fillers

Background: Indians constitute one of the largest population groups in the world. Facial anthropometry, morphology, and age-related changes in Indians differ from those of other ethnic groups, necessitating a good understanding of their facial structure and the required aesthetic treatment strategies. However, published recommendations specific to Indians are few, particularly regarding combination treatment. Methods: The Indian Facial Aesthetics Expert Group (19 dermatologists, plastic surgeons, and aesthetic physicians with a mean 15.5 years' aesthetic treatment experience) met to develop consensus recommendations for the cosmetic facial use of botulinum toxin and hyaluronic acid fillers, alone and in combination, in Indians. Treatment strategies and dosage recommendations (agreed by ≥ 75% of the group) were based on results of a premeeting survey, peer-reviewed literature, and the experts' clinical experience. Results: The need for combination treatment increases with age. Tear trough deficiency is the most common midface indication in Indian women aged 20–40 years. In older women, malar volume loss and jowls are the most common aesthetic concerns. Excess medial soft tissue on a relatively smaller midface precedes age-related sagging. Hence, in older Indians, fillers should be used peripherally to achieve lift and conservatively in the medial zones to avoid adding bulk medially. The shorter, wider lower face requires 3-dimensional correction, including chin augmentation, to achieve increased facial height and the oval shape desired by most Indian women. Conclusions: These recommendations give physicians treating Indians worldwide a better understanding of their unique facial characteristics and provide treatment strategies to achieve optimal aesthetic outcomes.

http://ift.tt/2CX3xvl

Orthognathic Relevant Scales of FACE-Q: Translation and Validation for Hong Kong Chinese Patients

Background: A validated questionnaire is needed to study a more holistic outcome assessment including postsurgical aesthetic satisfaction and psychosocial changes in orthognathic patients. The aim of this study was to determine the reliability and validity of 9 orthognathically relevant translated FACE-Q scales among Hong Kong Chinese orthognathic patients. Methods: Two hundred fifty adult Cantonese-speaking patients of 18 years or older who underwent orthognathic treatment were recruited in the Prince Philip Dental Hospital of Hong Kong. Nine of an overall of 40 independent FACE-Q scales were selected and translated into Hong Kong Chinese. The reliability, validity, and test–retest reliability were examined using Cronbach's alpha, paired t test and Pearson's correlation coefficients. Results: The Hong Kong Chinese version of the 9 FACE-Q scales was obtained by forward-backward translation. One hundred eight male (mean age, 25.57 ± 4.49) and 142 female (mean age, 24.61 ± 4.54) patients were recruited for the reliability and validation process. The internal consistency (0.89–0.97) and the test–retest reliability (0.73–0.90) were found to be high. The validity of the translated questionnaires was comparable with that of the original FACE-Q. Conclusion: The results presented here prove that the 9 translated FACE-Q scales are reliable and valid instruments for research and clinical purposes in Hong Kong Chinese orthognathic patients.

http://ift.tt/2CW77G7

Complete Lower Lip Reconstruction with a Large Lip Switch Flap and a Composite Modiolus Advancement Flap

Summary: Total loss of the lower lip is debilitating and poses a reconstructive challenge. Aiming to restore oral continence and function and also cosmetic appearance, a successful reconstruction has a huge impact on the quality of life for the individual patient. Early sources of local tissue rearrangement for lip reconstruction date back 3000 years, with earliest reports of lip switch procedures more than 2 centuries ago in Europe, when noma was still endemic in Europe, indicating that the anatomy was better understood by the barber surgeons of the past than we like to acknowledge. We are still faced with such challenging cases all over the world where resources are limited. Our current understanding of perforator anatomy and blood supply makes more frequent revisits to flaps of the past with modern advances. Innovative solutions are imperative for salvage, and old ideas tend to reappear when they prove to be useful. Herein, we describe in open access a new reconstructive method where we combined a large lip switch flap together with a composite advancement modiolus flap to reconstruct a whole lower lip and the donor defect of the upper lip all at once, a procedure that is simple to perform and works in settings where it is greatly needed.

http://ift.tt/2CVRcYh

Ultrasound Diagnosis and Treatment of Breast Lumps after Breast Augmentation with Autologous Fat Grafting

Background: Breast augmentation with autologous fat has been performed in Japan for over 30 years. However, complications include breast lumps and oil cysts. Such breast lumps greatly reduce patient satisfaction, and are currently difficult to diagnose and treat for many cosmetic surgery clinics. This study aimed to elucidate the effectiveness of ultrasound diagnosis and treatment of patients with breast lumps after breast augmentation with autologous fat grafting. Methods: We used diagnostic and therapeutic ultrasound to examine 256 patients with breast lumps between April 2012 and April 2017. We determined the nature, size, and location of the maximal lump. Breast lumps were classified into five types: cystic, complex, solid, calcification, and unclassifiable. The method of treatment (including fine-needle aspiration, VASER liposuction, lumpectomy, and extended lumpectomy) was selected according to the lump type, and the efficacy of treatment was determined by postoperative palpation and ultrasound. Results: A total of 198 patients (198/256, 77%) requested treatment. Cystic lumps (79/256, 31%) were treated by fine-needle aspiration. VASER liposuction was used to treat complex (64/256, 25%) and solid lumps (50/256, 19%). Calcification (58/256, 23%) and unclassifiable lumps (5/256, 2%) were removed via periareolar incision. There were no serious complications. In all cases, the lumps were no longer palpable after treatment, and ultrasound showed that they had either contracted or disappeared. Conclusions: The appropriate treatment for breast lumps after breast augmentation with autologous fat grafting must be selected according to the nature of the lumps. Ultrasound is essential for diagnosing the breast lump type and determining the best treatment.

http://ift.tt/2CW77pB