18 F-FDG PET and high-resolution MRI co-registration for pre-surgical evaluation of patients with conventional MRI-negative refractory extra-temporal lobe epilepsy

Abstract

Purpose

Epilepsy that originates outside of the temporal lobe can present some of the most challenging problems for surgical therapy, especially for patients with conventional magnetic resonance imaging (MRI)-negative refractory extra-temporal lobe epilepsy (ETLE). This study aimed to evaluate the clinical value of pre-surgical ¹⁸F-fluoro-deoxy-glucose positron emission tomography (¹⁸F-FDG PET) and high-resolution MRI (HR-MRI) co-registration in patients with conventional MRI-negative refractory ETLE, and compare their surgical outcomes.

Methods

Sixty-seven patients with conventional MRI-negative refractory ETLE were prospectively included for pre-surgical ¹⁸F-FDG PET and HR-MRI examinations. Under the guidance of ¹⁸F-FDG PET and HR-MRI co-registration, HR-MRI images were re-read. Based on the image result changes from first reading to re-reading, patients were divided into three groups: Change-1 (lesions of subtle abnormality could be identified in re-read), Change-2 (non-specific abnormalities reported in the first reading were considered as lesions on HR-MRI re-read) and No-change. Post-surgical follow-ups were conducted for up to 59 months.

Results

Visual analysis of ¹⁸F-FDG PET showed focal or regional abnormality in 46 patients (68.6%), while the abnormal rate increased to 94.0% (P < 0.05) by co-registration. Of the 67 patients, 46.3% of them were identified as Change-1, and 11.9% as Change-2 after co-registration and HR-MRI re-read. Patients with Change-1 and -2 were more likely to be recommended to receive surgical resection (P < 0.001). In the 17 post-surgical patients, 88% had good outcomes, whereas 11.7% had poor outcomes during our study period.

Conclusion

Pre-surgical evaluation by co-registration of ¹⁸F-FDG PET and HR-MRI could improve the identification of the epileptogenic onset zone (EOZ), and may further guide the surgical decision-making and improve the outcome of the refractory ETLE with normal conventional MRI; therefore, it should be recommended as a standard procedure for pre-surgical evaluation of these patients.

https://ift.tt/2u5bvwb

Noradrenaline transporter availability on [ 11 C]MRB PET predicts weight loss success in highly obese adults

Abstract

Purpose

Although the mechanisms by which the central noradrenaline (NA) system influences appetite and controls energy balance are quite well understood, its relationship to changes in body weight remains largely unknown. The main goal of this study was to further clarify whether the brain NA system is a stable trait or whether it can be altered by dietary intervention.

Methods

We aimed to compare central NA transporter (NAT) availability in ten obese, otherwise healthy individuals with a body mass index (BMI) of 42.4 ± 3.7 kg/m² (age 34 ± 9 years, four women) and ten matched non-obese, healthy controls (BMI 23.9 ± 2.5 kg/m², age 33 ± 10 years, four women) who underwent PET with the NAT-selective radiotracer (S,S)-[¹¹C]O-methylreboxetine (MRB) before and 6 months after dietary intervention.

Results

MRI-based individual volume-of-interest analyses revealed an increase in binding potential (BP_ND) in the insula and the hippocampus of obese individuals, which correlated well with changes in BMI (−3.3 ± 5.3%; p = 0.03) following completion of the dietary intervention. Furthermore, voxel-wise regression analyses showed that lower BP_ND in these regions, but also in the midbrain and the prefrontal cortex, at baseline was associated with higher achieved weight loss (e.g., hippocampal area R² = 0.80; p < 0.0001). No changes were observed in non-obese controls.

Conclusion

These first longitudinal interventional data on NAT availability in highly obese individuals indicate that the central NA system is modifiable. Our findings suggest that NAT availability before intervention could help predict the amount and success of weight loss in obese individuals and help adjust treatment options individually by allowing prediction of the benefit of a dietary intervention.

https://ift.tt/2IVp1GZ

Laser treatment contributes to maintain membrane integrity in stem cells from human exfoliated deciduous teeth (shed) under nutritional deficit

Abstract

This study aimed to analyze the effects of laser irradiation on the membrane integrity and viability of stem cells from human exfoliated deciduous teeth (SHED) that were kept in serum starvation. Nutritional deficit was used to mimic the cellular stress conditions of SHED isolation for regenerative dental approaches, where laser therapy could be beneficial. SHED were cultured under serum starvation (MEMα + 1%FBS) for 1 or 24 h pre-irradiation (protocols A and B, respectively). Then, cells received low-level laser therapy (LLLT; 660 nm) at 2.5 J/cm² (0.10 W; groups I and V), 5.0 J/cm² (0.20 W; groups II and VI), 7.5 J/cm² (0.30 W; groups III and VII), or remained non-irradiated (groups IV and VIII). During irradiation, cells were maintained in 1% FBS (groups I–IV) or 10% FBS (normal culture conditions; groups V–VIII). Membrane integrity was evaluated by quantifying lactate dehydrogenase (LDH) release (immediately after irradiation), and cell viability was assessed by the MTT assay (24, 48, and 72 h post-irradiation). Serum starvation did not alter LDH release by non-irradiated SHED, while LDH release decreased significantly in groups irradiated in 1% FBS (I and III), but not in groups irradiated in 10% FBS (V–VII), regardless the pre-irradiation conditions (protocols A/B). Cell viability was significantly higher 24 h after irradiation, in most protocol A groups. In contrast, cell viability remained mostly unaltered in protocol B groups. LLLT contributed to maintain membrane integrity in SHED subjected to nutritional deficit before and during irradiation with 0.10 or 0.30 W. Short serum starvation before irradiation improved SHED viability at 24 h post-irradiation.

https://ift.tt/2lYu54E

Evaluating the effect of photobiomodulation with a 940-nm diode laser on post-operative pain in periodontal flap surgery

Abstract

The aim of this study was to evaluate the efficacy of low-power of 940-nm diode laser on post-operative pain after undisplaced flap surgery. This randomized clinical trial study was conducted using a split-mouth design. The study participants comprised 30 patients who needed periodontal flap surgery for periodontal pockets on the same tooth on both sides of the mandible. One side of the mandible was subjected to undisplaced flap surgery plus treatment with a 940-nm diode laser, and on the contralateral side, the surgery was conducted without applying the laser. Patients received anti-inflammatory medication and analgesics after surgery. The patients were asked to report the number of analgesics they took and the pain they experienced each night for 1 week using a visual analogue scale. An independent-sample t test was used to compare the results between the two groups. Patients reported less pain on days 2, 3, 4, 5, 6, and 7 after surgery in the laser-treated group (p < 0.05). Furthermore, fewer analgesics were used in this group on days 3, 4, 5, 6, and 7 following the surgery (p < 0.05). The 940-nm diode laser with the settings used in this study could significantly reduce pain and the number of analgesics taken by patients after undisplaced flap surgery.

https://ift.tt/2u6yKFh

Amyloid involvement in subcortical regions predicts cognitive decline

Abstract

Purpose

We estimated whether amyloid involvement in subcortical regions may predict cognitive impairment, and established an amyloid staging scheme based on degree of subcortical amyloid involvement.

Methods

Data from 240 cognitively normal older individuals, 393 participants with mild cognitive impairment, and 126 participants with Alzheimer disease were acquired at Alzheimer's Disease Neuroimaging Initiative sites. To assess subcortical involvement, we analyzed amyloid deposition in amygdala, putamen, and caudate nucleus. We staged participants into a 3-stage model based on cortical and subcortical amyloid involvement: 382 with no cortical or subcortical involvement as stage 0, 165 with cortical but no subcortical involvement as stage 1, and 203 with both cortical and subcortical involvement as stage 2.

Results

Amyloid accumulation was first observed in cortical regions and spread down to the putamen, caudate nucleus, and amygdala. In longitudinal analysis, changes in MMSE, ADAS-cog 13, FDG PET SUVR, and hippocampal volumes were steepest in stage 2 followed by stage 1 then stage 0 (p value <0.001). Stage 2 showed steeper changes in MMSE score (β [SE] = −0.02 [0.004], p < 0.001), ADAS-cog 13 (0.05 [0.01], p < 0.001), FDG PET SUVR (−0.0008 [0.0003], p = 0.004), and hippocampal volumes (−4.46 [0.65], p < 0.001) compared to stage 1.

Conclusions

We demonstrated a downward spreading pattern of amyloid, suggesting that amyloid accumulates first in neocortex followed by subcortical structures. Furthermore, our new finding suggested that an amyloid staging scheme based on subcortical involvement might reveal how differential regional accumulation of amyloid affects cognitive decline through functional and structural changes of the brain.

https://ift.tt/2u8sUTH

Reclassification as NIFTP: a Retrospective Review in a Single Institution with an Emphasis on Workload

Abstract

The aim of this study was to determine the number of cases of papillary thyroid carcinoma (PTC) which could be reclassified as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) in our institute over a 10-year period, document their clinical status and assess the number of slides that had to be reviewed per case to exclude NIFTP. The histopathology reports for thyroid resections for all papillary carcinoma over a 10-year period (2007–2016) were reviewed. Five hundred forty-five histopathology reports were reviewed, and 71 cases were identified as potential cases of NIFTP. Forty-nine (69%) cases had been referred from external departments and the slides were not available for review. Of the remaining 22 (31% of 71) cases, 5 were reclassified as NIFTP. The 17 cases that were not reclassified as NIFTP required review of 114 of 356 slides (median 5.5 slides per case) was required to exclude NIFTP. For the 5 NIFTP cases, 58 slides were reviewed (median 12 slides per case). We found that review of the histology reports alone was adequate for exclusion in most cases, e.g. classic PTC or EVPTC cases with documented lymphovascular invasion or capsular invasion. As a single exclusion criterion is required for exclusion from reclassification as NIFTP, this can be achieved efficiently. Two of the five patients received radioactive iodine [RAI] as per standard treatment at time of diagnosis, on the basis of tumour size. None have recurrent or metastatic disease with mean follow-up of 5.8 years.

https://ift.tt/2KQMZYY

New software and breast boundary landmarks to calculate breast volumes from 3D surface images

Abstract

Background

A method to accurately calculate breast volumes helps achieving a better breast surgery outcome. 3D surface imaging potentially allows these calculations in a harmless, quick, and practicable way. The calculated volume from a 3D surface image is dependent on the determined breast boundary and the method of chest wall simulation by software. Currently, there is no consensus on a robust set of breast boundary landmarks and validation studies on breast volume calculation software are scarce. The purposes of this study were to determine the robustness of newly introduced breast boundary landmarks and introduce and validate a new method to simulate a chest wall.

Methods

Sixteen subjects who underwent a unilateral simple mastectomy were included. In addition to the natural skin fold of the breast, the sternomanubrial joint, the transition of the pectoral muscle curve into the breast curvature, and the midaxillary line were used as landmarks to indicate the breast boundary. The intra- and interrater variability of these landmarks was tested. Furthermore, new chest wall simulation software was validated on the breastless chest side of the subjects.

Results

The intra- and interrater variability of the three breast boundary markers was small (mean 3.5–6.7 mm), and no significant difference was found between the intra- and interrater variability (p = 0.08, p = 0.06, and p = 0.10). The mean volume error of the most accurately simulated chest wall was 4.6 ± 37 ml.

Conclusion

The newly introduced landmarks showed to be robust and our new chest wall simulation algorithm showed accurate results.

Level of Evidence: Level IV, diagnostic study.

https://ift.tt/2IXdib0

18 F-NaF and 18 F-FDG as molecular probes in the evaluation of atherosclerosis

Abstract

The early detection of atherosclerotic disease is vital to the effective prevention and management of life-threatening cardiovascular events such as myocardial infarctions and cerebrovascular accidents. Given the potential for positron emission tomography (PET) to visualize atherosclerosis earlier in the disease process than anatomic imaging modalities such as computed tomography (CT), this application of PET imaging has been the focus of intense scientific inquiry. Although ¹⁸F-FDG has historically been the most widely studied PET radiotracer in this domain, there is a growing body of evidence that ¹⁸F-NaF holds significant diagnostic and prognostic value as well. In this article, we review the existing literature on the application of ¹⁸F-FDG and ¹⁸F-NaF as PET probes in atherosclerosis and present the findings of original animal and human studies that have examined how well ¹⁸F-NaF uptake correlates with vascular calcification and cardiovascular risk.

https://ift.tt/2KxyQR8

Transcriptomics and metabonomics analyses of maternal DEHP exposure on male offspring

Abstract

The objectives of this study were to evaluate the effect of maternal Di-2-ethylhexyl phthalate (DEHP) exposure on male offspring and to explore the mechanism of changes with the metabolic alterations and differential genes. Pregnant female Sprague-Dawley (SD) rats were intragastrically administered with 600 mg/kg body weight of DEHP or corn oil (CON) throughout pregnancy and lactation. The growth of male offspring was investigated until 14 weeks old, the indices of blood were detected, and mechanism was studied using metabonomics and transcriptomics. Compared with the CON group, body weight, body length, food intake, body fat weight, Lee's index, organ coefficient, blood lipids, and oral glucose tolerance test (OGTT) of male offspring were not significantly changed in maternal DEHP group. However, serum biochemical indexes such as alanine transaminase (ALT), total protein (TP), albumin (ALB), blood urea nitrogen (BUN), and creatinine (CREA) were markedly reduced in maternal DEHP group (p < 0.05). In addition, insulin level was elevated and catalase (CAT) level was decreased notably in maternal DEHP group compared with the CON group (p < 0.05). Furthermore, thyroxine (T₄) level was lower and thyroid stimulating hormone (TSH) level was higher in maternal DEHP group (p < 0.05). Metabonomics revealed seven principal metabolites were identified, including increased L-allothreonine, creatine, uric acid, retinyl ester, L-palmitoylcarnitine, and decreased glycocholic acid and LysoPC (18:3). Transcriptomics displayed 35 differential genes were involved in the mechanism of maternal DEHP exposure. Therefore, this research confirms the effect of a certain dose of maternal DEHP exposure on male offspring and understands exactly the mechanism of these changes with metabonomics and transcriptomics.

https://ift.tt/2lZ5D34

Definition, Classification and Diagnosis of Diabetes Mellitus

Exp Clin Endocrinol Diabetes 2018; 126: 406-410
DOI: 10.1055/a-0584-6223

Aim of recommendations like this one issued by the German Diabetes Association is to provide the GP and diabetologist and his team with information he needs for his daily practice. These recommendations are updated annually. They are written by a group of experts, but they are not evidence based guidelines. This specific recommendation for diabetes diagnosis briefly describes the diabetes types and the different options for diagnosis. Also the caveats and the practical procedure are presented.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

https://ift.tt/2uazt8a

Practical Recommendations for Glucose Measurement, Glucose Monitoring and Glucose Control in Patients with Type 1 or Type 2 Diabetes in Germany

Exp Clin Endocrinol Diabetes 2018; 126: 411-428
DOI: 10.1055/a-0586-5302

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Full text

https://ift.tt/2lY6D7B

The Eye’s Mind – visual imagination, neuroscience and the humanities

Publication date: Available online 5 July 2018

Source: Cortex

Author(s): Adam Zeman, Matthew MacKisack, John Onians

https://ift.tt/2KSBv4b

Alternative scenarios for ecological urbanizations using ENVI-met model

Abstract

Natural areas are quickly degraded by opening new settlement and industrial areas in order to meet the increasing demand of the growing population. Concreting, modification of land surfaces, complex urban structures, and depressed urban environments contribute to the formation of an Urban Heat Island (UHI). In this study, the outdoor measurements, meteorological parameters related to the thermal indices such as humidity, temperature, wind velocity, and direction for 24 h measurements, were evaluated. The ENVI-met micro-scale model was performed for evaluating alternative scenarios for winter and summer on thermal comfort for better urban environments. Meteorological parameters together with vegetation characteristics were analyzed for making possible scenarios in botanical garden_, auto industrial area_, city center, and rural open area. The average of the vegetated simulations of the botanical garden was about 2.2 °C cooler than this of the mean of current situation in the city center. Based upon the average of all stations, it was determined that the temperature increased 1.4 °C with the simulation of both wooded areas in winter. However, the mean temperature of all stations with coniferous plants was 1.2 °C cooler, in summer. It was concluded that deciduous plants in city center produced more positive results than coniferous plants in winter. In general, it can be said that afforestation in cold climatic regions provides great advantages for both summer and winter and positively affects outdoor thermal comfort. However, it needs further measurement and further research in this regard.

https://ift.tt/2m0c19X

Sleep Disturbances and Their Impact in Pediatric Cystic Fibrosis

Cystic fibrosis is a chronic, life-shortening illness that affects multiple systems and results in frequent respiratory infections, chronic cough, fat malabsorption and malnutrition. Poor sleep is often reported by patients with cystic fibrosis. Although objective data to explain these complaints have been limited, they do show poor sleep efficiency and frequent arousals. Abnormalities in gas-exchange are also observed during sleep in patients with cystic fibrosis. The potential impact of these abnormalities in sleep on health and quality of life remains largely unstudied.

https://ift.tt/2NxEaSC

Internal dose of particles in the elderly—modeling based on aerosol measurements

Abstract

The paper presents an integrated methodology that combines experimental and modeling techniques and links exposure to airborne particulate matter (PM) with internal dose in the respiratory system and burden in adjacent tissues over a period of time. The methodology is used to estimate doses in the respiratory systems of elders that reside in 10 elderly care centers (ECCs) in the metropolitan area of Lisbon. Measurements of PM were performed in the ECCs and combined with a time-budget survey for the occupants. This information served as input to the first model that estimated particle doses in the different regions of the respiratory tract of the elderly, and then a second model was used to calculate particle build-up in the alveolar region, the interstitium and the hilar lymph nodes of the elders over a 5-year exposure period. It was found that in 5 years of continuous exposure to the average particle concentration measured over all ECCs, 258 mg of all particles are deposited on the surface of the alveoli of which 79.6% are cleared, 18.8% are retained in the alveolar region, 1.5% translocate to the hilar lymph nodes, and 0.1% are transferred to the interstitium.

https://ift.tt/2NvhEcY

Human Acellular Dermis Increases Surgical Site Infection and Overall Complication Profile When Compared with Submuscular Breast Reconstruction: An Updated Meta-Analysis Incorporating New Products

Human acellular dermal matrix (HADM) is an increasingly used adjunct to breast reconstruction. Previous meta-analysis demonstrate increased risks of complications, but these studies represent largely represent one product. The purpose of this study is to stratify outcomes based on a meta-analysis of complications incorporating all new studies after 2012 and their associated new human-based products.

https://ift.tt/2zeKR90

Contribution of Eisenia andrei earthworms in pathogen reduction during vermicomposting

Abstract

Vermicomposting is a process of degradation of biowaste which involves complex interactions between earthworms and microorganisms. This process lacks a thermophilic stage and thus, the possible presence of pathogens poses a potential health hazard. To assess the contribution of earthworms during the selective reduction of various pathogens, apple pomace substrate was artificially inoculated with Escherichia coli, Salmonella spp., thermotolerant coliform bacteria, and Enterococci. The artificial bacterial load did not influence the weight, reproduction, or intestinal enzymatic activity of the earthworms, but it caused reversible histological changes to the epithelial layer and chloragogen tissue of their intestines. The reduction of pathogenic Enterococci and E. coli from the substrate was accelerated by earthworms (63-fold, 77-fold, and 840-fold for Enterococci and 6-fold, 36-fold, and 7-fold for E. coli inoculated substrates after 2, 4, and 6 weeks, respectively). Moreover, the rapid elimination of Salmonella spp. was supported by the upregulated expression of two pattern recognition receptors which bind lipopolysaccharide, coelomic cytolytic factor, and lipopolysaccharide-binding protein. Further, the microbiomes of the intestine and the composting substrate differed significantly.

Graphical abstract

https://ift.tt/2MSKXoO

Stable carbon and nitrogen isotopic composition of PM 10 over Indo-Gangetic Plains (IGP), adjoining regions and Indo-Himalayan Range (IHR) during a winter 2014 campaign

Abstract

For source identification, a field campaign involving simultaneous sampling of particulate matter (PM₁₀) was conducted at eight sampling sites in the Indian mainland during winter 2014. The sampling sites include Delhi (upper IGP), Lucknow (middle IGP), and Kolkata (lower IGP) in the Indo-Gangetic Plains (IGP); Mohal-Kullu and Darjeeling in the Indo-Himalayan Range (IHR). In addition, Ajmer, located upwind of the IGP in NW-India and Giridih and Bhubaneswar, in the downwind to the IGP has also been chosen. To characterize the sources of the ambient PM₁₀, stable isotope ratios of carbon (δ¹³C_TC) and nitrogen (δ¹⁵N_TN) for the total carbon (TC) and total nitrogen (TN) fractions have been considered. Ancillary chemical parameters, such as organic carbon (OC), elemental carbon (EC), and water-soluble ionic components (WSIC) mass concentrations are also presented in this paper. There was very small variation in the daily average δ¹³C_TC ratios (− 24.8 to − 25.9‰) among the sites. Comparison with end-member stable C isotopic signatures of major typical sources suggests that the PM₁₀ at the sites was mainly from fossil fuel and biofuel and biomass combustion. Daily average δ¹⁵N_TN ratios were not observed to vary much between sites either (8.3 to 11.0‰), and the low δ¹⁵N_TN levels also indicate substantial contributions from biofuel and biomass burning of primarily C3 andC4 plant matter.

Graphical abstract

Scatter plot of the average (± 1 standard deviation (SD)) δ¹³C_TC (‰) compared to δ¹⁵N_TN (‰) at the sampling sites.

https://ift.tt/2KMPoDX

Novel magnetic ion-imprinted polymer: an efficient polymeric nanocomposite for selective separation and determination of Pb ions in aqueous media

Abstract

A novel ion-imprinted polymer (IIP) toward Pb(II) recognition was synthesized on the surface of magnetic multi-walled carbon nanotubes (magnetic MWCNTs). In order to prepare magnetic functionalized-MWCNT/IIP (magnetic f-MWCNT/IIP), copolymerization of methylenebisacrylamide (MBAm) and acrylamide (AM) in the presence of dithizone-Pb(II) complex was carried out on the surface of the magnetic f-MWCNTs. Selectivity of the new synthesized sorbent toward Pb(II) and the influence of a variety of foreign ions on the recognition, preconcentration, and removal of Pb(II) were evaluated using adsorption experiments in aqueous solution. The synthesized sorbent exhibited a good affinity with high adsorption capacity (Q = 80.81 mg/g) and an excellent selectivity toward Pb(II) in comparison with other common cations including alkaline, alkaline earth, and transition metals such as Na⁺, K⁺, Mg²⁺, Ca²⁺, Cd²⁺, and Ni²⁺. The parameters such as adsorption and desorption time, adsorption capacity, effect of the sorbent mass, eluent type, concentration and volume, and also pH of the solutions were investigated. The result demonstrated that the proposed sorbent provided a fast removal and higher maximum binding capacity compared to other reported synthesized sorbents. The characteristics of the magnetic f-MWCNT/IIP were analyzed using Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), energy-dispersive spectroscopy (EDS), vibrating sample magnetometer (VSM), and elemental analysis (EA).

Graphical abstract

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https://ift.tt/2MPtvBq

Discretized Modeling of Motionless Printing Based on Retarded Bending Motion and Deposition Control of Electrically Driven Jet

3D Printing and Additive Manufacturing, Ahead of Print.


https://ift.tt/2MQiHD3

Comparing the Establishment of Operation Space Between High Position and Low Position in Endoscopic Thyroid Surgery

Conditions:   Thyroid Cancer;   Endoscopy
Interventions:   Procedure: high position space group;   Procedure: low position space group
Sponsor:   Fujian Medical University
Recruiting

https://ift.tt/2u5xdPN

Comparative study of the physicochemical and photocatalytic properties of water-soluble polymer-capped TiO 2 nanoparticles

Abstract

TiO₂ shows great potential as ideal and powerful photocatalyst to degrade and eliminate harmful organic pollutants from waste water. It is desirable to prepare anatase TiO₂ with good aqueous solubility and photocatalytic activity for water decontamination. In this paper, water-soluble TiO₂ nanoparticles were successfully prepared using polytetramethylene ether glycol (PTMG), poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) as stabilizers. The anatase phase of TiO₂ was well controlled by introduction of HCl in the reaction system. The results showed that all the polymer-capped TiO₂ were well dissolved in water and their aqueous solutions could maintain stable for more than 2 months. The photocatalytic activities of polymer-capped TiO₂ were evaluated by monitoring the degradation of Rhodamine B (RhB) with Degussa P25 as a control. The results showed that all the polymer-capped TiO₂ presented better photocatalytic activity than that of Degussa P25. PTMG capped TiO₂ exhibited the longest average lifetime of charge carriers, indicating the lowest charge recombination rate. Thus, PTMG capped TiO₂ presented the best photocatalytic activity. In summary, PTMG, PEG, and PPG can be used as stabilizers to prepare water-soluble TiO₂. PTMG is an ideal stabilizer for the synthesis of water-soluble TiO₂ with good photocatalytic activity.

https://ift.tt/2MQnQLj

Radiation-induced acute toxicities after image-guided intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for patients with spinal metastases (IRON-1 trial)

Abstract

Purpose

Radiation therapy (RT) provides an important treatment approach in the palliative care of vertebral metastases, but radiation-induced toxicities in patients with advanced disease and low performance status can have substantial implications for quality of life. Herein, we prospectively compared toxicity profiles of intensity-modulated radiotherapy (IMRT) vs. conventional three-dimensional conformal radiotherapy (3DCRT).

Methods

This was a prospective randomized monocentric explorative pilot trial to compare radiation-induced toxicity between IMRT and 3DCRT for patients with spinal metastases. A total of 60 patients were randomized between November 2016 and May 2017. In both cohorts, RT was delivered in 10 fractions of 3 Gy each. The primary endpoint was radiation-induced toxicity at 3 months.

Results

Median follow-up was 4.3 months. Two patients suffered from grade 3 acute toxicities in the IMRT arm, along with 1 patient in the 3DCRT group. At 12 weeks after treatment (t2), 1 patient reported grade 3 toxicity in the IMRT arm vs. 4 patients in the 3DCRT group. No grade 4 or 5 adverse events occurred in either group. In the IMRT arm, the most common side effects by the end of irradiation (t1) were grade 1–2 xerostomia and nausea in 8 patients each (29.6%), and dyspnea in 7 patients (25.9%). In the 3DCRT group, the most frequent adverse events (t1) were similar: grade 1–2 xerostomia (n = 10, 35.7%), esophagitis (n = 10, 35.8%), nausea (n = 10, 35.8%), and dyspnea (n = 5, 17.9%).

Conclusion

This is the first randomized trial to evaluate radiation-induced toxicities after IMRT versus 3DCRT in patients with vertebral metastases. This trial demonstrated an additional improvement for IMRT in terms of acute side effects, although longer follow-up is required to further ascertain other endpoints.

https://ift.tt/2KzFA14

An autophagy-targeting peptide to treat chronic inflammatory demyelinating polyneuropathies

Publication date: Available online 5 June 2018

Source: Journal of Autoimmunity

Author(s): Susana Brun, Nicolas Schall, Srinivasa Reddy Bonam, Kévin Bigaut, Ayikoe-Guy Mensah-Nyagan, Jérôme de Sèze, Sylviane Muller

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or misfolded proteins, it has not been addressed whether autophagy, a central "clearance" system delivering damaged intracellular components to lysosomes, is affected in CIDP. The focus of the present investigation was therefore to determine if some defects exist in autophagy processes in this setting and if they can be corrected or minimized using an appropriate treatment targeting this survival pathway. Experiments were performed using a rat model mimicking human CIDP, also known as chronic experimental autoimmune neuritis (c-EAN), the disease establishment and development of which was followed at both the clinical and biological levels (indices of disease severity, histopathological alteration, cytokines and antibodies rates). Based on immunofluorescence and western immunoblotting experiments on sciatic nerves and spleen cells from c-EAN rats, we demonstrate that both, macroautophagy and chaperone-mediated autophagy (CMA), are significantly altered in non-neuronal cells of the peripheral nervous system. We show further that a 21-mer synthetic phosphopeptide called P140, known to target CMA and successfully used in pathological settings where CMA markers are overexpressed, considerably ameliorates the clinical and biological course of the disease in c-EAN rats. P140 displayed prophylactic and therapeutic effects, both in terms of disease intensity and chronicity, and preserved sciatic nerves from disease-related damages. Our findings uncover new disrupted molecular pathways in a c-EAN model and provide a proof-of-concept that targeting CMA might represent a promising therapeutic strategy for treating inflammatory neuropathies for which no disease-specific treatment is currently available.

https://ift.tt/2KPVgJC

TGF-β signalling defect is linked to low CD39 expression on regulatory T cells and methotrexate resistance in rheumatoid arthritis

Publication date: June 2018

Source: Journal of Autoimmunity, Volume 90

Author(s): Raphael S. Peres, Paula B. Donate, Jhimmy Talbot, Nerry T. Cecilio, Patricia R. Lobo, Caio C. Machado, Kalil W.A. Lima, Rene D. Oliveira, Vanessa Carregaro, Helder I. Nakaya, Thiago M. Cunha, José Carlos Alves-Filho, Foo Y. Liew, Paulo Louzada-Junior, Fernando Q. Cunha

Abstract

Rheumatoid arthritis (RA) is an autoimmune arthropathy characterized by chronic articular inflammation. Methotrexate (MTX) remains the first-line therapy for RA and its anti-inflammatory effect is associated with the maintenance of high levels of extracellular adenosine (ADO). Nonetheless, up to 40% of RA patients are resistant to MTX treatment and this is linked to a reduction of CD39 expression, an ectoenzyme involved in the generation of extracellular ADO by ATP metabolism, on circulating regulatory T cells (Tregs). However, the mechanism mediating the reduction of CD39 expression on Tregs is unknown. Here we demonstrated that the impairment in TGF-β signalling lead to the reduction of CD39 expression on Tregs that accounts for MTX resistance. TGF-β increases CD39 expression on Tregs via the activation of TGFBRII/TGFBRI, SMAD2 and the transcription factor CREB, which is activated in a p38-dependent manner and induces CD39 expression by promoting ENTPD1 gene transcription. Importantly, unresponsive patients to MTX (UR-MTX) show reduced expression of TGFBR2 and CREB1 and decreased levels of p-SMAD2 and p-CREB in Tregs compared to MTX-responsive patients (R-MTX). Furthermore, RA patients carrying at least one mutant allele for rs1431131 (AT or AA) of the TGFBR2 gene are significantly (p = 0.0006) associated with UR-MTX. Therefore, we have uncovered a molecular mechanism for the reduced CD39 expression on Tregs, and revealed potential targets for therapeutic intervention for MTX resistance.

Graphical abstract

https://ift.tt/2KRGAgs

Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging of macrophages in large vessel vasculitis: Current status and future prospects

Publication date: July 2018

Source: Autoimmunity Reviews, Volume 17, Issue 7

Author(s): William Febry Jiemy, Peter Heeringa, Jan A.A.M. Kamps, Conny J. van der Laken, Riemer H.J.A. Slart, Elisabeth Brouwer

Abstract

Macrophages are key players in the pathogenesis of large-vessel vasculitis (LVV) and may serve as a target for diagnostic imaging of LVV. The radiotracer, ¹⁸F-FDG has proven to be useful in the diagnosis of giant cell arteritis (GCA), a form of LVV. Although uptake of ¹⁸F-FDG is high in activated macrophages, it is not a specific radiotracer as its uptake is high in any proliferating cell and other activated immune cells resulting in high non-specific background radioactivity especially in aging and atherosclerotic vessels which dramatically lowers the diagnostic accuracy. Evidence also exists that the sensitivity of ¹⁸F-FDG PET drops in patients upon glucocorticoid treatment. Therefore, there is a clinical need for more specific radiotracers in imaging GCA to improve diagnostic accuracy. Numerous clinically established and newly developed macrophage targeted radiotracers for oncological and inflammatory diseases can potentially be utilized for LVV imaging. These tracers are more target specific and therefore may provide lower background radioactivity, higher diagnostic accuracy and the ability to assess treatment effectiveness. However, current knowledge regarding macrophage subsets in LVV lesions is limited. Further understanding regarding macrophage subsets in vasculitis lesion is needed for better selection of tracers and new targets for tracer development. This review summarizes the development of macrophage targeted tracers in the last decade and the potential application of macrophage targeted tracers currently used in other inflammatory diseases in imaging LVV.

https://ift.tt/2lWXBHI

Endoplasmic reticulum stress in autoimmune diseases: Can altered protein quality control and/or unfolded protein response contribute to autoimmunity? A critical review on Sjögren's syndrome

Publication date: Available online 8 June 2018

Source: Autoimmunity Reviews

Author(s): María-José Barrera, Sergio Aguilera, Isabel Castro, Sergio González, Patricia Carvajal, Claudio Molina, Marcela A. Hermoso, María-Julieta González

Abstract

For many years, researchers in the field of autoimmunity have focused on the role of the immune components in the etiopathogenesis of autoimmune diseases. However, some studies have demonstrated the importance of target tissues in their pathogenesis and the breach of immune tolerance. The immune system as well as target tissue cells (plasmatic, β-pancreatic, fibroblast-like synoviocytes, thyroid follicular and epithelial cells of the lachrymal glands, salivary glands, intestine, bronchioles and renal tubules) share the characteristic of secretory cells with an extended endoplasmic reticulum (ER). The function of these cells depends considerably on a normal ER function and calcium homeostasis, so they can produce and secrete their main components, which include glycoproteins involved in antigenic presentation such as major histocompatibility complex (MHC) class I and II. All these proteins are synthesized and modified in the ER, and for this reason disturbances in the normal functions of this organelle such as protein folding, protein quality control, calcium homeostasis and redox balance, promote accumulation of unfolded or misfolded proteins, a condition known as ER stress. Autoimmune diseases are characterized by inflammation, which has been associated with an ER stress condition. Interestingly, patients with these diseases contain circulating auto-antibodies against chaperone proteins (such as Calnexin and GRP94), thus affecting the folding and assembly of MHC class I and II glycoproteins and their loading with peptide.

The main purpose of this article is to review the involvement of the protein quality control and unfolded protein response (UPR) in the ER protein homeostasis (proteostasis) and their alterations in autoimmune diseases. In addition, we describe the interaction between ER stress and inflammation and evidences are shown of how autoimmune diseases are associated with an ER stress condition, with a special emphasis on the second most prevalent autoimmune rheumatic disease, Sjögren's syndrome.

https://ift.tt/2u6Hyeg

Polyautoimmunity: Risk factors for a unique clinical entity

Publication date: Available online 6 June 2018

Source: Autoimmunity Reviews

Author(s): Oded Shamriz

https://ift.tt/2u6H4os

Teaching Radiologists Who Perform Image Guided Interventions Effective Communication Skills Through Simulation

Publication date: Available online 5 July 2018

Source: Current Problems in Diagnostic Radiology

Author(s): Carolynn M. DeBenedectis, Max P. Rosen

https://ift.tt/2IX23PT

Radiology Trainee vs Faculty Radiologist Fluoroscopy Time for Imaging-Guided Procedures: A Retrospective Study of 17,966 Reports Over a 5.5-Year Period

Publication date: July–August 2018

Source: Current Problems in Diagnostic Radiology, Volume 47, Issue 4

Author(s): Ariadne K. DeSimone, Andrew Post, Richard Duszak, Phuong-Anh T. Duong

To evaluate differences in fluoroscopy time (FT) for common vascular access and gastrointestinal procedures performed by radiology trainees vs faculty radiologists. Report information was extracted for all 17,966 index fluoroscopy services performed by trainees or faculty, or both from 2 university hospitals over 66 months. Various vascular access procedures (eg, peripherally inserted central catheters [PICCs] and ports) and gastrointestinal fluoroscopy procedures (eg, upper gastrointestinal and contrast enema studies) were specifically targeted. Statistical analysis was performed. FT was recorded in 17,549 of 17,966 reports (98%) The 1393 procedures performed by nonphysician providers or transitional year interns were excluded. Residents, fellows, and faculty were primary operators in 5066, 6489, and 4601 procedures, respectively. Average FT (in seconds) for resident and fellow services, respectively, was less than that of faculty only for PICCs (75 and 101 vs 148, P < 0.01). For all other procedures, average FT of trainee services was greater than that for faculty. This was statistically significant (P < 0.05) for fellows vs faculty port placement (121 vs 87), resident vs faculty small bowel series (130 vs 96), and both resident and fellow vs faculty esophagram procedures (143 and 183 vs 126 ). FT for residents was significantly less than that for fellows only for PICCs (75 vs 101, P < 0.01). For most, but not all, fluoroscopy procedures commonly performed by radiology trainees, FT is greater than that for procedures performed by faculty radiologists. Better awareness and understanding of such differences may aid training programs in developing benchmarks, protocols, and focused teaching in the safe use of fluoroscopy for patients and operators.

https://ift.tt/2KT1WXg

Experience of the Implementation of Rapid On-Site Evaluation in Ultrasound-Guided Fine-Needle Aspiration Biopsy of Thyroid Nodules

Publication date: July–August 2018

Source: Current Problems in Diagnostic Radiology, Volume 47, Issue 4

Author(s): Flor Marina Medina Chamorro, José Abella Calle, Juliana Escobar Stein, Lina Merchancano, Andrés Mauricio Mendoza Briñez, Andrés Arturo Pulido Wilches

Objective

To evaluate the effect of the implementation of the rapid on-site evaluation (ROSE) technique in ultrasound-guided fine-needle aspiration biopsy of thyroid nodules.

Materials and Methods

We conducted an observational and retrospective study approved by the Institutional Ethics Committee as an investigation without risk. Between January 2012 and December 2015, 892 ultrasound-guided fine-needle aspiration biopsy procedures were performed under ultrasound guidance. In our study, we included 522 procedures from 473 patients that were taken as part of an investigation of the thyroid nodule (average age: 56 ± 14; 84% were women). We compared the percentage of unsatisfactory samples in the procedures performed with and without the use of the ROSE technique, the cytology adequacy agreement with the cytopathology, and we also assessed the relationship with the number of years of experience of the radiologist.

Results

The ROSE technique led to a decrease of 30.5% of unsatisfactory samples. By 2014, more than half of the procedures were performed with the ROSE technique, and the percentage of unsatisfactory samples decreased progressively each year. The technical implementation of ROSE improved the results of all radiologists; however, those radiologists with the least number of years of experience showed the greatest benefits from the implementation of the ROSE technique. The concordance between the ROSE technique and the cytopathology report was good (Cohen κ = 0.75).

Conclusion

In our experience, the implementation of the ROSE technique has helped to reduce the percentage of unsatisfactory samples, which improves the quality and safety of patient care.

https://ift.tt/2KO8GFL

Diffusion Tensor Imaging of the Spinal Cord: Clinical Value, Investigational Applications, and Technical Limitations

Publication date: July–August 2018

Source: Current Problems in Diagnostic Radiology, Volume 47, Issue 4

Author(s): Aaron M. Rutman, Daniel J. Peterson, Wendy A. Cohen, Mahmud Mossa-Basha

Although diffusion-weighted imaging (DWI) has become a mainstay in modern brain imaging, it remains less utilized in the evaluation of the spinal cord. Many studies have shown promise in using DWI and diffusion-tensor imaging (DTI) for evaluation of the spinal cord; however, application has been stalled by technical obstacles and artifacts, and questions remain regarding its clinical utility on an individual examination level. This review discusses the background, concepts, and technical aspects of DWI and DTI, specifically for imaging of the spinal cord. The clinical and investigational applications of spinal cord DTI, as well as the practical difficulties and limitations of DWI and DTI for the evaluation of the spinal cord are examined.

https://ift.tt/2KSbMc3

A Chief Resident-Driven Curriculum Designed to Improve Core Exam Performance at a Small Community Radiology Residency Program

Publication date: Available online 27 June 2018

Source: Current Problems in Diagnostic Radiology

Author(s): Cory M Pfeifer

https://ift.tt/2NsFaaz

Molecular Imaging in Diagnosis of Tumor Induced Osteomalacia,

Publication date: Available online 27 June 2018

Source: Current Problems in Diagnostic Radiology

Author(s): Ming Yang, Krupa B. Doshi, Michael C. Roarke, Ba D. Nguyen

https://ift.tt/2tUPwYI

The Financial Burden of Missed Appointments: Uncaptured Revenue Due to Outpatient No-Shows in Radiology

Publication date: Available online 12 June 2018

Source: Current Problems in Diagnostic Radiology

Author(s): Rebecca J. Mieloszyk, Joshua I. Rosenbaum, Christopher S. Hall, Usha Nandini Raghavan, Puneet Bhargava

https://ift.tt/2ITRtJu

How Well Do We Represent Ourselves? A Student-Centric Analysis of Radiology Residency Website Content

Publication date: Available online 1 June 2018

Source: Current Problems in Diagnostic Radiology

Author(s): Sherwin A. Novin, Paul H Yi, Taylor Vanderplas, Donna Magid

https://ift.tt/2NpKRG2

Factors associated with participation in life situations for adults with stroke: a systematic review

Publication date: Available online 5 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Leisle Ezekiel, Johnny Collett, Helen Dawes, Nancy E. Mayo, Lori Pang, Leanne Field

Abstract

Objectives

To identify biopsychosocial factors associated with participation outcomes for adults with stroke and to investigate factors associated with participation at different time points post stroke.

Data sources

Medline, CINAHL, AMED, PyschINFO and Web of Science were systematically searched using key words "stroke", "participation" and "outcomes" and their synonyms on 15th May 2017.

Study selection

Observational studies reporting on biopsychosocial factors and participation outcomes for community dwelling adults with stroke were selected. Studies were eligible for inclusion if participation outcomes were measured using indices that mapped to the participation domain of the ICF. Intervention studies were excluded. A second reviewer checked all studies against eligibility criteria at each stage.

Data extraction

Data were extracted on any statistically determined association between biopsychosocial factors and participation outcomes.

Data synthesis

The proportion of studies reporting significant associations with variables were classified according to the ICF. The exact binomial test was used to determine the probability that the proportion of studies reporting significant associations was due to chance alone. Qualitative descriptive summaries of each study allowed consideration of interactions between variables and changes in participation over time points.

Conclusions

Whilst depressive symptoms, cognitive functioning and mobility were found to have the strongest associations with participation, we found that other frequently occurring factors (such as fatigue and environmental factors) were less extensively considered. The diversity of outcome measures encountered within the review highlight the need for a consensus on a core set of outcome measures to evaluate long term participation in life situations after stroke.

https://ift.tt/2NttuV5

Determining peak cough flow cut-off values to predict aspiration pneumonia among patients with dysphagia using the citric acid reflexive cough test

Publication date: Available online 5 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Donggyun Sohn, Geun-Young Park, HyungJung Koo, YongJun Jang, Yeonjae Han, Sun Im

Abstract

Objective

To investigate the clinical usefulness of the peak cough flow generated during the citric acid reflexive cough test (0.28 mol/L) by determining the appropriate cut-off values that could accurately predict aspiration pneumonia within the first 6 months after onset.

Design

Retrospective analysis of a prospectively maintained database.

Setting

University affiliated hospital.

Participants

Patients with first-ever diagnosed dysphagia attributable to cerebrovascular disease, who had undergone the citric acid reflexive cough test on the same day they underwent the instrumental assessment of swallowing, such as videofluoroscopy or the functional endoscopic swallowing test.

Interventions

Not applicable.

Main outcome measures

Peak cough flow (L/min) from the citric acid reflexive cough test.

Results

A final 163 patients had full medical records with 6-month follow-up. Receiver operating curve analysis showed that peak cough flow cut-off values set at 59 L/min were significantly associated with aspiration pneumonia [area under the curve (AUC) 95% confidence interval (CI) = 0.88 (0.83–0.93)]. This cut-off value significantly (P < 0.001) predicted the risk of aspiration pneumonia with an odds ratio of 21.56 (9.62–48.28). A multivariate regression logistic regression analysis model including initial dysphagia severity, low body mass index, and decreased level of cognition showed that inclusion of the peak cough flow from the citric acid reflexive cough test significantly improved the predictive model of aspiration pneumonia within the first 6 months after onset (AUC = 0.91 vs. 0.79).

Conclusions

Those with reflexive cough strength less than 59 L/min may be at high risk of respiratory infections within the first 6 months after dysphagia onset. Objective measurement of reflexive cough strength may help to predict those at risk of aspiration pneumonia.

https://ift.tt/2KO6MoB

Relationship of fitness and wheelchair mobility with encounters, avoidances, and perception of environmental barriers among manual wheelchair users with Spinal Cord Injury

Publication date: Available online 5 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Morgan K. Callahan, Rachel E. Cowan

Abstract

Objective

To assess a) if fitness and mobility are related to behavior and perception of physical barriers and b) if behavior and physical barrier perception are related.

Design

Cross-sectional case series

Setting

Academic Medical Laboratory

Participants

50 manual wheelchair users with chronic spinal cord injury (62% Paraplegia)

Intervention

None.

Main Outcome Measures

Participants completed the following assessments; 1) Fitness: Graded exercise test (Aerobic) & Wingate (Anaerobic); 2) Mobility: 6 minute push test and 30 second sprint test; 3) Physical barrier behavior: Encounters of Environmental Features in the Environmental Aspects of Mobility Questionnaire (EAMQ); and 4) Physical Barrier Perception: Craig Hospital Inventory of Environmental Factor Environmental Barriers domain.

Results

Individuals with paraplegia had higher fitness, mobility, and environmental barrier encounter rates and lower avoidance per encounter rates versus tetraplegia (all p≤05). For individuals with tetraplegia only, as mobility and fitness increased, frequencies of a) encounters increased, and b) avoidances per encounter decreased, in multiple EAMQ domains (all p≤.05). Perception of barriers did not differ between lesion levels (p=0.79). Mobility and fitness were not related to environmental barriers perception in both groups (all p >.17).

Conclusions

Fitness and mobility are associated with barrier behaviors (i.e. encounters and avoidances) among individuals with tetraplegia, but not paraplegia. Despite a greater barrier avoidance rate, persons with tetraplegia do not perceive more physical barriers than persons with paraplegia. Surprisingly, fitness and mobility were not related to perception of barriers in either group. More research is required on if barrier perception, behavior, or both influence participation, to enable rehabilitation programs to tailor interventions to enhance participation.

https://ift.tt/2Nu0Lzx

Does home-based progressive resistance or high intensity circuit training improve strength, function, activity or participation in children with cerebral palsy?

Publication date: Available online 4 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Christian Schranz, Annika Kruse, Teresa Belohlavek, Gerhardt Steinwender, Markus Tilp, Thomas Pieber, Martin Svehlik

Objective

Does home-based progressive resistance or high intensity circuit training improve strength, function, activity or participation in children with cerebral palsy?

Design

This was the first study on high intensity circuit training for children with cerebral palsy. This study was conducted as a randomized prospective controlled pilot-study.

Setting

Evaluation took place at the gait laboratory of the university hospital, training sessions were performed at home.

Participants

22 children with CP (average age:12 years, 10 months, 19 GMFCS I, 3 GMFCS II) were randomly assigned either to PRT or HICT.

Interventions

The PRT-group trained with progressive overload while the HICT-group performed as many repetitions as possible within 30s-intervals (8-weeks, 3 times weekly in both groups).

Outcome measures

Outcome measures stretched over all domains of the International Classification of Functioning, Disability and Health and included muscle strength, Muscle power sprint test, Timed-stairs-test, 6-minute walking test, Gait Profile Score, Timed-up-and-go test and participation questionnaires.

Results

Only the HICT-group was able to improve strength. Furthermore, HICT-group scored better in the Muscle power sprint test while PRT-participants improved in the timed-stairs-test and Timed-up-and-go test. There was no change of any other measures of mobility or participation for both groups.

Conclusion

Both programs improved function specific to intervention. However, only HICT-group showed significant strength improvements. Compliance was decent in both groups, but the average training unit was shorter in the HICT-group. Both exercise programs showed functional benefits but HICT might be the preferable option for strengthening in highly functional children with CP.

https://ift.tt/2IVc0NT

Inadequate Postoperative Energy Intake Relative to Total Energy Requirements Diminishes Acute Phase Functional Recovery from Hip Fracture

Publication date: Available online 4 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Tatsuro Inoue, Shogo Misu, Toshiaki Tanaka, Hiroki Sakamoto, Kentaro Iwata, Yuki Chuman, Rei Ono

Abstract

Objective

To investigate whether postoperative voluntary energy intake (EI) affects functional recovery with hip fracture during the acute phase.

Design

Prospective cohort study.

Setting

Three acute care hospitals.

Participants

Hip fracture patients (N = 200) who were consecutively admitted to 3 acute hospitals because of falling.

Interventions

Not applicable.

Main Outcome Measure

Patients were stratified into three groups based on the ratio of measured EI to estimated total energy expenditure (TEE) as inadequate (EI/TEE < 0.7), intermediate (0.7 ≤ EI/TEE < 1), and adequate (EI/TEE ≥ 1) groups. The functional status was evaluated using the motor domain of a functional independence measure (FIM). We calculated efficiency based on the motor FIM scores (change in postoperative motor FIM scores/length of the rehabilitation period) to assess the beneficial effect of rehabilitation.

Results

The median hospital stay was 24 days. The inadequate group comprised 73 (36.5%) patients (median EI/TEE: 0.54; interquartile range: 0.42–0.64); intermediate group comprised 92 (46.0%) patients (median EI/TEE: 0.87; interquartile range: 0.78–0.94), and adequate group comprised 35 (17.5%) patients (median EI/TEE: 1.10; interquartile range: 1.04–1.15). Absolute functional gain (AFG) and efficiency of motor FIM gain (EFG) scores were higher in the adequate group than in the others (P < 0.01). After adjustment for potential confounders, a significant association between postoperative EI/TEE group and logarithm of EFG scores was observed to persist (inadequate group, standardized β = −0.14; reference: adequate group; P = 0.03; R² for the entire model = 0.25).

Conclusions

Postoperative EI less than 70% of TEE diminishes functional recovery with hip fracture.

https://ift.tt/2KREOs8

Energetic Cost of Walking and its Physiological Correlates in Persons with Multiple Sclerosis who have Moderate Mobility Disability

Publication date: Available online 4 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Brenda Jeng, Brian M. Sandroff, Robert W. Motl

Abstract

Objective

This study examined aerobic capacity, upper leg muscular strength, and static postural control as correlates of the energetic cost of walking (C_w) in moderate MS mobility disability.

Design

Cross-sectional study

Setting

University-based laboratory

Participants

44 persons with MS (aged 48.43±8.64 years) who have reached a benchmark of moderate mobility disability (i.e., Expanded Disability Status Scale scores between 4.0-6.0) participated in the study.

Main Outcome Measures

C_w was based on (a) net oxygen consumption collected using a portable metabolic unit and (b) walking speed during the 6-Minute Walk (6MW). Participants underwent standard assessments of peak aerobic capacity, upper leg muscular strength, and static postural control.

Results

The data were analyzed using bivariate correlation and linear regression analyses. C_w was inversely correlated with peak oxygen consumption (r=‒.308, p<0.05), peak power output (r=‒.548, p<0.00), and peak torque at 75° knee flexion (r=‒.340, p<0.05), whereas C_w was positively correlated COP area sway (r=0.319, p<0.05), and mediolateral sway velocity (r=.411, p<0.05). 40.3% of variance in C_w was explained by peak power output (β=‒.526, p<0.01) and mediolateral sway velocity (β=.339, p<0.05).

Conclusion

Our findings demonstrate that aerobic power and postural sway may be important correlates of C_w in moderate MS mobility disability. Peak power output reflects a person's physiological functional reserve that is directly relevant for understanding the penalty of walking impairment on the energetic demands of walking. The association between mediolateral postural sway and C_w suggests that mechanical inefficiency controlling the trajectory of the body's center of pressure during ambulation may contribute to the elevated C_w.

https://ift.tt/2KPO9AN

A Systematic Review and Meta-Analysis of Rehabilitative Interventions for Unilateral Spatial Neglect and Hemianopia from 2006 through 2016

Publication date: Available online 4 July 2018

Source: Archives of Physical Medicine and Rehabilitation

Author(s): Karen P.Y. Liu, Jessica Hanly, Paul Fahey, Shirley S.M. Fong, Rosalind Bye

Abstract

Objective

To evaluate the effectiveness of activity-based, non-activity-based, and combined activity- and non-activity-based, rehabilitative interventions for individuals presenting with unilateral spatial neglect (USN) and hemianopia.

Data Sources

We searched CINAHL, Cochrane Library, EMBASE, MEDLINE and PubMed from 2006 to 2016.

Study Selection

Randomized controlled trials (RCTs), with a score of 6 or above in the PEDro Scale, that examined the effects of activity-based and non-activity-based rehabilitation interventions for people with USN or hemianopia. Two reviewers selected studies independently.

Data Extraction

Extracted data from the published RCTs. Mean differences (MD) or Standardized mean differences (SMD), and 95% confidence intervals (CIs), were calculated. Heterogeneity was assessed using the I² statistic.

aData Synthesis

Twenty RCTs for USN and five for hemianopia, involving 594 and 206 stroke participants respectively, were identified. Encouraging results were found in relation to activity-based interventions for visual scanning training and compensatory training for hemianopia (MD=5.11; CI=0.83 to 9.4; P=0.019; I²=25.16% on visual outcomes), and optokinetic stimulation and smooth pursuit training for USN (SMD=0.49, CI=0.01 to 0.97, P=0.045, I²=49.35% on functional performance in activities of daily living; SMD=0.96; CI=0.09 to 1.82; P=0.031; I²=89.57% on neglect).

Conclusions

Activity-based interventions are effective and commonly used in the treatment of USN and hemianopia. Non-activity-based and combined approaches, for both impairments, have not been refuted, as more studies are required for substantiated conclusions to be drawn.

https://ift.tt/2tX5h1j

Differences in Physical Performance Measures Among Patients With Unilateral Lower-Limb Amputations Classified as Functional Level K3 Versus K4

Publication date: July 2018

Source: Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 7

Author(s): Jaclyn Megan Sions, Emma Haldane Beisheim, Tara Jo Manal, Sarah Carolyn Smith, John Robert Horne, Frank Bernard Sarlo

Abstract

Objective

To determine whether differences in physical function, assessed via self-report questionnaires and physical performance tests, exist between individuals with lower-limb loss using a prosthetic device classified as a K3 versus a K4 functional level.

Design

Cross-sectional study.

Setting

A university physical therapy amputee clinic.

Participants

Participants (N=55) were included if they (1) were aged ≥18 years with a unilateral transfemoral or transtibial amputation; (2) were classified as K3 or K4 functional level; (3) completed all relevant outcome measures; and (4) were currently using a prosthesis.

Interventions

Not applicable.

Main Outcome Measures

Locomotor Capabilities Index (LCI), Prosthetic Evaluation Questionnaire–Mobility Section (PEQ-MS), Timed Up and Go (TUG), 10-Meter Walk Test (10MWT), Amputee Mobility Predictor (AMPPRO), and 6-Minute Walk Test (6MWT). K level was determined by group consensus based on a standardized clinical evaluation.

Results

After controlling for covariates, patients classified as K3 had slower TUG times (P=.002) and self-selected and fast gait speeds (P<.001), lower AMPPRO scores (P<.001), and walked shorter distances during the 6MWT (P=.003) when compared with patients classified as K4. No significant between-group differences for the LCI or PEQ-MS were found.

Conclusions

Clinicians involved in prosthetic prescription may consider including the TUG, 10MWT, AMPPRO, and 6MWT during their clinical evaluations to help differentiate between individuals of higher functional mobility. The LCI and PEQ-MS may be less useful in classifying individuals as K3 versus K4 because of a ceiling effect.

https://ift.tt/2KO6Gxf

Detection of Acute and Long-Term Effects of Concussion: Dual-Task Gait Balance Control Versus Computerized Neurocognitive Test

Publication date: July 2018

Source: Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 7

Author(s): David R. Howell, Louis R. Osternig, Li-Shan Chou

Abstract

Objective

To examine the acute (within 72h of injury) and long-term (2mo postinjury) independent associations between objective dual-task gait balance and neurocognitive measurements among adolescents and young adults with a concussion and matched controls.

Design

Longitudinal case-control.

Setting

Motion analysis laboratory.

Participants

A total of 95 participants completed the study: 51 who sustained a concussion (mean age, 17.5±3.3y; 71% men) and 44 controls (mean age, 17.7±2.9y; 72% men). Participants who sustained a concussion underwent a dual-task gait analysis and computerized neurocognitive testing within 72 hours of injury and again 2 months later. Uninjured controls also completed the same test protocol in similar time increments.

Interventions

Not applicable.

Main Outcome Measures

We compared dual-task gait balance control and computerized neurocognitive test performance between groups using independent samples t tests. Multivariable binary logistic regression models were then constructed for each testing time to determine the association between group membership (concussion vs control), dual-task gait balance control, and neurocognitive function.

Results

Medial-lateral center-of-mass displacement during dual-task gait was independently associated with group membership at the initial test (adjusted odds ratio [aOR], 2.432; 95% confidence interval [CI], 1.269–4.661) and 2-month follow-up test (aOR, 1.817; 95% CI, 1.014–3.256) tests. Visual memory composite scores were significantly associated with group membership at the initial hour postinjury time point (aOR, .953; 95% CI, .833–.998). However, the combination of computerized neurocognitive test variables did not predict dual-task gait balance control for participants with concussion, and no single neurocognitive variable was associated with dual-task gait balance control at either testing time.

Conclusions

Dual-task assessments concurrently evaluating gait and cognitive performance may allow for the detection of persistent deficits beyond those detected by computerized neurocognitive deficits alone.

https://ift.tt/2IV9Cqm

Reasons for Distress Among Burn Survivors at 6, 12, and 24 Months Postdischarge: A Burn Injury Model System Investigation

Publication date: July 2018

Source: Archives of Physical Medicine and Rehabilitation, Volume 99, Issue 7

Author(s): Shelley A. Wiechman, Kara McMullen, Gretchen J. Carrougher, Jame A. Fauerbach, Colleen M. Ryan, David N. Herndon, Radha Holavanahalli, Nicole S. Gibran, Kimberly Roaten

Abstract

Objective

To identify important sources of distress among burn survivors at discharge and 6, 12, and 24 months postinjury, and to examine if the distress related to these sources changed over time.

Design

Exploratory.

Setting

Outpatient burn clinics in 4 sites across the country.

Participants

Participants who met preestablished criteria for having a major burn injury (N=1009) were enrolled in this multisite study.

Interventions

Participants were given a previously developed list of 12 sources of distress among burn survivors and asked to rate on a 10-point Likert-type scale (0=no distress to 10=high distress) how much distress each of the 12 issues was causing them at the time of each follow-up.

Main Outcomes Measures

The Medical Outcomes Study 12-Item Short-Form Health Survey was administered at each time point as a measure of health-related quality of life. The Satisfaction With Appearance Scale was used to understand the relation between sources of distress and body image. Finally, whether a person returned to work was used to determine the effect of sources of distress on returning to employment.

Results

It was encouraging that no symptoms were worsening at 2 years. However, financial concerns and long recovery time are 2 of the highest means at all time points. Pain and sleep disturbance had the biggest effect on ability to return to work.

Conclusions

These findings can be used to inform burn-specific interventions and to give survivors an understanding of the temporal trajectory for various causes of distress. In particular, it appears that interventions targeted at sleep disturbance and high pain levels can potentially effect distress over financial concerns by allowing a person to return to work more quickly.

https://ift.tt/2tSS75l

Effect of Vitamin D supplementation on body composition and cardiorespiratory fitness in overweight men—a randomized controlled trial

Abstract

Purpose

Several observational studies have shown an association between vitamin D deficiency and non-skeletal major health issues including impaired cardiorespiratory fitness and adiposity. Only a few studies have examined the impact of vitamin D supplementation on these conditions and the results are ambiguous. The aim of this study was to examine the effect of vitamin D supplementation on body composition and cardiorespiratory fitness in overweight/obese men with vitamin D deficiency.

Methods

This study was a prospective, placebo controlled, double blinded, randomized trial with a study period of 6 months. Forty overweight/obese men (BMI > 25 kg/m²) with vitamin D deficiency (25(OH)D ≤ 55 nmol/L) were randomized to receive either 2000 IU Cholecalciferol drops or the equivalent amount of drops of placebo. At baseline and follow up body composition and cardiorespiratory fitness were measured and blood samples were obtained. Body composition was measured using bioelectrical impedance analysis (BIA) and cardiorespiratory fitness using cardiopulmonary exercise test (CPET). The primary outcomes were changes in percentage body fat and in maximum oxygen uptake (VO_2max).

Results

No statistically significant difference between the placebo and the intervention group regarding changes in percentage body fat (p = 0.54) and VO_2max (p = 0.90) was observed. Moreover, there was no statistically significant difference between the groups concerning changes in BMI (p = 0.26), maximum load (p = 0.89) and oxygen uptake at anaerobic threshold (AT) (p = 0.14).

Conclusions

We conclude that treatment with 2000 IU/d vitamin D for 6 months does not impact body composition or maximum oxygen uptake in overweight/obese men with vitamin D deficiency.

https://ift.tt/2KPJ77u

The Editor's Choice

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s):

https://ift.tt/2KTwPLv

Stabilization of microtubules restores barrier function after cytokine-induced defects in reconstructed human epidermis

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Chiung-Yueh Hsu, Nicolas Lecland, Valérie Pendaries, Cécile Viodé, Daniel Redoulès, Carle Paul, Andreas Merdes, Michel Simon, Christiane Bierkamp

Abstract

Background

A variety of human skin disorders is characterized by defects in the epidermal barrier, leading to dehydration, itchiness, and rashes. Previously published literature suggests that microtubule stabilization at the cortex of differentiating keratinocytes is necessary for the formation of the epidermal barrier.

Objectives

We tested whether stabilization of microtubules with paclitaxel or epothilone B can repair barrier defects that were experimentally induced in three-dimensional culture models of epidermis.

Methods

We established two models of defective epidermis in vitro, using three-dimensional cultures of primary human keratinocytes on filter supports: immature reconstructed human epidermis (RHE), and RHE that was compromised by treatment with inflammatory cytokines, the latter mimicking defects seen in atopic dermatitis.

Results

Both paclitaxel and epothilone B promoted keratinocyte differentiation, accumulation of junctional proteins at the cell cortex, and the early appearance of lamellar bodies in immature RHE, whereas destabilization of microtubules by nocodazole had the reverse effect. Moreover, stabilization of microtubules rescued the barrier after cytokine treatment. The rescued barrier function correlated with the restoration of filaggrin and loricrin protein levels, the cortical accumulation of junctional proteins (E-cadherin, β-catenin, and claudin-1), and with the secretion of lamellar bodies.

Conclusions

Our data suggest that the microtubule network is important for the formation of the epidermis, and that stabilization of microtubules promotes barrier formation. Microtubule stabilization may support regeneration of damaged skin, by restoring or improving the barrier.

https://ift.tt/2NrMEul

RIPK1 downregulation in keratinocyte enhances TRAIL signaling in psoriasis

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Nao Saito, Masaru Honma, Takashi Shibuya, Shin Iinuma, Satomi Igawa, Mari Kishibe, Akemi Ishida-Yamamoto

Abstract

Background

Psoriasis, a common inflammatory skin disorder characterized by scaly erythema and plaques, is induced by dysregulation of dendritic cell- and T cell-mediated immune reaction. Receptor-interacting protein kinase 1 (RIPK1) regulates inflammatory signaling in response to stimuli such as TNF-α, TRAIL, and TLRs, resulting in apoptosis, necroptosis and NF-κB activation. However, the physiological relevance in human epidermis remains elusive.

Objective

In this study, we examined whether RIPK1 is involved in the pathogenesis of psoriasis vulgaris.

Methods

Skin samples of eight patients with psoriasis vulgaris were investigated by western blotting and immunohistochemistry. The functions of RIPK1 in keratinocytes were examined by RT-PCR and ELISA in vitro. TRAIL-neutralization-experiment was employed in an imiquimod-induced murine psoriasis model.

Results

In lesional psoriatic epidermis, RIPK1-expression was decreased compared with that in normal epidermis. Cytokines involved in the pathomechanism of psoriasis, such as IL-1β, IL-17A, IL-22 and TRAIL, reduced RIPK1-expression in normal human epidermal keratinocytes (HEK) in vitro. In addition, RIPK1-knockdown enhanced TRAIL-mediated expression of psoriasis-relating cytokines, such as IL-1β, IL-6, IL-8, TNF-α, in HEK. Numerous TRAIL-positive cells were detected in the dermis of lesional psoriatic skin, and TRAIL receptors were expressed in psoriatic epidermis and HEK in conventional cultures. Moreover, TRAIL-neutralization in an imiquimod-induced murine psoriasis model remarkably improved skin phenotypes, such as ear thickness, and TNF-α expression in lesional skin.

Conclusions

These results lead us to conclude that RIPK1-downregulation in keratinocytes increases their susceptibility to TRAIL stimulation, and plays a role in the pathogenesis of psoriasis vulgaris.

https://ift.tt/2IVWYat

Reversal of the hair loss phenotype by modulating the estradiol-ANGPT2 axis in the mouse model of female pattern hair loss

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Yujiro Endo, Yuko Obayashi, Tomoji Ono, Tetsushi Serizawa, Michiaki Murakoshi, Manabu Ohyama

Abstract

Background

Despite high demand for a remedy, the treatment options for female pattern hair loss (FPHL) are limited. FPHL is frequent in postmenopausal women. In ovariectomized (OVX) mice, which lack β-estradiol (E2) and manifest hair loss mimicking FPHL, E2 supplementation has been shown to increase hair density. However, the mechanism by which E2 exhibits its biological activity remains elusive.

Objective

To identify the downstream targets of E2 in the context of FPHL pathophysiology and discover a potential therapeutic agent for the E2-dependent subtype of FPHL.

Methods

Human dermal papilla cells (hDPCs) were cultured with E2, and a microarray analysis was performed to identify the genes regulated by E2. Using OVX mice, the identified gene product was intradermally administered and then quantitative image analysis of hair density was conducted. In silico analysis to link E2 and the identified gene was performed.

Results

Global gene expression and bioinformatics analyses revealed that the genes associated with the angiopoietin-2 (ANGPT2) pathway were upregulated by E2 in hDPCs. ANGPT2 was significantly downregulated in OVX mice than in sham-operated mice (P < 0.01). Importantly, hair density was higher in OVX mice treated with ANGPT2 than in control mice (P < 0.05). In silico analysis showed DNA sequences with high possibility of estrogen receptor binding in the promoter region of ANGPT2.

Conclusion

The E2-ANGPT2 axis is present in hair follicles. ANGPT2 provides a strategy for the management of E2-dependent and postmenopausal subsets of FPHL.

https://ift.tt/2IUfsby

UV-induced DNA methyltransferase 1 promotes hypermethylation of tissue inhibitor of metalloproteinase 2 in the human skin

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Ha-Young Kim, Dong Hun Lee, Mi Hee Shin, Hye Sun Shin, Min-Kyoung Kim, Jin Ho Chung

Abstract

Background

Ultraviolet (UV) radiation has been reported to influence epigenetic regulation by affecting the expression of genome regulators such as DNA methyltransferase 1 (DNMT1). DNMT1 is a "gene silencer," that is responsible for the maintenance of DNA methylation and contribution to de novo methylation. Implications of DNMT1′s involvement in the expression of UV-induced proteins have been previously reported.

Objective

To investigate for changes in DNA methylation-associated gene expressions by UV and to analyze the role of DNA methylation in the suppression of TIMP2 in UV-irradiated human skin.

Methods

The expression of DNA methylation-associated proteins and TIMP2 were analyzed in UV-irradiated human skin in vivo and in human dermal fibroblasts in vitro. To investigate the relationship between DNMT1 and TIMP2, we assessed the effect of DNMT1 knockdown, inhibition and overexpression on TIMP2 levels in human dermal fibroblasts. Lastly, methylation-specific PCR was used to confirm increased DNA methylation in TIMP2 promoter in response to UV.

Results

DNMT1 expression significantly increased whereas TIMP2 expression decreased in UV-irradiated human skin in vivo and in vitro. Downregulation of DNMT1 by knockdown or inhibition resulted in increased TIMP2 expression, whereas the overexpression of DNMT1 resulted in decreased TIMP2 expression. Lastly, methylation-specific PCR confirmed increased methylation on the CpG island residing in TIMP2 promoter in UV-irradiated human dermal fibroblasts.

Conclusion

These findings suggest that UV-induced expression of DNMT1 may be responsible for mediating DNA hypermethylation in TIMP2, and thus, silencing its expression, in UV-exposed human skin.

https://ift.tt/2tUfjAi

Characterization of centriole duplication in human epidermis, Bowen’s disease, and squamous cell carcinoma

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Saori Watanuki, Harumi Fujita, Keisuke Kouyama, Masayuki Amagai, Akiharu Kubo

Abstract

Background

Centrosomes contain two centrioles: a pre-existing mature centriole and a newly formed immature centriole. Each centriole is duplicated once within a cell cycle, which is crucial for proper centrosome duplication and cell division.

Objective

To describe the centrosome duplication cycle in human epidermis, Bowen's disease (BD), and squamous cell carcinoma (SCC).

Methods

Immunofluorescent staining of centriolar proteins and Ki-67 was used to evaluate cell cycles and the number of centrioles. Centrobin and Outer dense fiber of sperm tails 2 (ODF2) were used as markers for immature and mature centrioles, respectively.

Results

Normal human primary epidermal keratinocytes in a monolayered culture have one centrobin⁺ centriole (CTRB¹⁺ cells) supposed in G0/G1 phases or have two centrobin⁺ centrioles (CTRB²⁺ cells) supposed in S−G2 phase. In a three-dimensional culture and in vivo human epidermis, the majority of suprabasal cells were CTRB²⁺ cells, in spite of their non-proliferative Ki-67⁻ nature. The tumor mass of BD and SCC contained CTRB¹⁺ cells and Ki-67⁺ proliferating and Ki-67⁻ non-proliferative CTRB²⁺ cells. Clumping cells in BD had increased numbers of centrioles, with an approximate 1:1 to 2:1 ratio of centrobin⁺ to ODF2⁺ centrioles.

Conclusions

The cell cycle arrest of suprabasal cells is distinct from the G0 arrest of monolayered epithelial cells. Tumor mass of BD and SCC contained non-proliferative cells with the characteristics of the suprabasal cells of normal epidermis. A constant ratio of the number of centrobin⁺ to ODF2⁺ centrioles indicates that multiple centrioles were induced by cell division failure rather than centriole overduplication in clumping cells.

https://ift.tt/2KShOJQ

Recent advancement in the mechanism of basophil activation

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Chisa Nakashima, Atsushi Otsuka, Kenji Kabashima

Abstract

Basophils have been recognized as crucial players in allergic inflammation. Basophils have the potential to initiate and expand inflammation through the production of specific cytokines and proteases, and are associated with T helper 2 (Th2) immune responses. In addition, recent studies revealed the heterogeneity in basophil populations. Basophils have been clarified important roles in not only IgE-mediated allergic inflammation but also TSLP-mediated and IgE-independent inflammation. Moreover, basophils infiltrate in many human cutaneous diseases. Basophils are responsible for recruiting other inflammatory cells such as macrophages, eosinophils, and fibroblasts. In this review, we discuss recent advances in our understanding of basophil activation and migration in allergic inflammation.

https://ift.tt/2Nv1rEr

Agerarin inhibits α-MSH–induced TYR gene transcription via STAT3 suppression independent of CREB-MITF pathway

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Soon Young Shin, Ha-Na Gil, Ji Hye Choi, Yoongho Lim, Young Han Lee

https://ift.tt/2KPVqkh

Editorial board

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s):

https://ift.tt/2Nnnopb

Influence of epidermal basement membrane integrity on cutaneous permeability barrier function

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s): Shunsuke Iriyama, Yuko Matsuura-Hachiya, Makoto Tsunenaga

https://ift.tt/2IXCI8r

JSID’s Fellowship Shiseido Research Grant

Publication date: July 2018

Source: Journal of Dermatological Science, Volume 91, Issue 1

Author(s):

https://ift.tt/2u3pXor

Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in hepatocellular carcinoma

Publication date: August 2018

Source: Neoplasia, Volume 20, Issue 8

Author(s): Iftikhar Ali Khawar, Jong Kook Park, Eun Sun Jung, Myung Ah Lee, Suhwan Chang, Hyo-Jeong Kuh

Abstract

Interactions between cancer cells and cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) play an important role in promoting the profibrotic microenvironment and epithelial-mesenchymal transition (EMT), resulting in tumor progression and drug resistance in hepatocellular carcinoma (HCC). In the present study, we developed a mixed-cell spheroid model using Huh-7 HCC cells and LX-2 stellate cells to simulate the in vivo tumor environment with respect to tumor-CAF interactions. Spheroids were cultured from cancer cells alone (monospheroids) or as a mixture (mixed-cell spheroids) in ultra-low-attachment plates. Compact, well-mixed, and stroma-rich mixed-cell spheroids were successfully established with heterotypic cell-cell contacts shown by the presence of gap junctions and desmosomes. Mixed-cell spheroids showed enhanced expression of collagen type-I (Col‐I) and pro‐fibrotic factors such as, transforming growth factor beta1 (TGF-β1), and connective tissue growth factor (CTGF) compared to the levels expressed in mono-spheroids. The EMT phenotype was evident in mixed-cell spheroids as shown by the altered expression of E-cadherin and vimentin. Differential drug sensitivity was observed in mixed-cell spheroids, and only sorafenib and oxaliplatin showed dose-dependent antiproliferative effects. Simultaneous treatment with TGF-β inhibitors further improved sorafenib efficacy in the mixed-cell spheroids, indicating the involvement of TGF-β in the mechanism of sorafenib resistance. In 3D matrix invasion assay, mixed-cell spheroids exhibited fibroblast-led collective cell movement. Overall, our results provide evidence that mixed-cell spheroids formed with Huh-7 and LX-2 cells well represent HCC tumors and their TME in vivo and hence are useful in studying tumor-stroma interactions as mechanisms associated with drug resistance and increased cell motility.

https://ift.tt/2KHtBhh

A Novel Flavonoid Composition Targets Androgen Receptor Signaling and Inhibits Prostate Cancer Growth in Preclinical Models

Publication date: August 2018

Source: Neoplasia, Volume 20, Issue 8

Author(s): Kenza Mamouni, Shumin Zhang, Xin Li, Yanhua Chen, Yang Yang, Jaeah Kim, Michael G. Bartlett, Ilsa M. Coleman, Peter S. Nelson, Omer Kucuk, Daqing Wu

Abstract

The high prevalence and long latency period of prostate cancer (PCa) provide a unique opportunity to control disease progression with dietary and nutraceutical approaches. We developed ProFine, a standardized composition of luteolin, quercetin, and kaempferol, and investigated its potential as a nutraceutical for PCa in preclinical models. The three ingredients of ProFine demonstrated synergistic in vitro cytotoxicity and effectively induced apoptosis in PCa cells. ProFine markedly affected the transcriptome of PCa cells, suppressed the expression of androgen receptor, and inhibited androgen-regulated genes. Oral administration of ProFine did not exhibit obvious toxicities in mice, and the three ingredients retained their individual pharmacokinetic and bioavailability profiles. Importantly, ProFine significantly retarded the growth of PCa xenografts in athymic nude mice and extended the survival of animals. This study provides preclinical evidence supporting the promise of ProFine as a safe, efficacious, and affordable intervention to control PCa progression and improve clinical outcomes.

https://ift.tt/2MRhJXg

Snail-overexpressing Cancer Cells Promote M2-Like Polarization of Tumor-Associated Macrophages by Delivering MiR-21-Abundant Exosomes

Publication date: August 2018

Source: Neoplasia, Volume 20, Issue 8

Author(s): Chia-Hsin Hsieh, Shyh-Kuan Tai, Muh-Hwa Yang

Abstract

Epithelial-mesenchymal transition (EMT) is a major event during cancer progression and metastasis; however, the definitive role of EMT in remodeling tumor microenvironments (TMEs) is unclear. Tumor-associated macrophages (TAMs) are a major type of host immune cells in TMEs, and they perform a wide range of functions to regulate tumor colonization and progression by regulating tumor invasiveness, local tumor immunity, and angiogenesis. TAMs are considered to have an M2-like, i.e., alternatively activated, phenotype; however, how these EMT-undergoing cancer cells promote M2 polarization of TAMs as a crucial tumor-host interplay during cancer progression is unclear. In this study, we investigated the mechanism of EMT-mediated TAM activation. Here, we demonstrate that the EMT transcriptional factor Snail directly activates the transcription of MIR21 to produce miR-21-abundant tumor-derived exosomes (TEXs). The miR-21-containing exosomes were engulfed by CD14⁺ human monocytes, suppressing the expression of M1 markers and increasing that of M2 markers. Knockdown of miR-21 in Snail-expressing human head and neck cancer cells attenuated the Snail-induced M2 polarization, angiogenesis, and tumor growth. In head and neck cancer samples, a high expression of miR-21 was correlated with a higher level of SNAI1 and the M2 marker MRC1. This study elucidates the mechanism of EMT-mediated M2 polarization through delivery of the miR-21-abundant exosomes, which may serve as a candidate biomarker of tumor progression and provide a potential target for intercepting EMT-mediated TME remodeling.

https://ift.tt/2zee9V3

Current Treatment of Bilateral Retinoblastoma: The Impact of Intraarterial and Intravitreous Chemotherapy

Publication date: August 2018

Source: Neoplasia, Volume 20, Issue 8

Author(s): Jasmine H. Francis, Nelli Roosipu, Ariana M. Levin, Scott E. Brodie, Ira J. Dunkel, Y. Pierre Gobin, David H. Abramson

Abstract

PURPOSE: To evaluate the management and outcomes of naïve bilateral retinoblastoma treated at a single-center over a 5-year period during the era of ophthalmic artery chemosurgery (OAC) and intravitreous chemotherapy. METHODS: Retrospective cohort study of 46 patients (92 eyes) with naïve bilateral retinoblastoma treated at Memorial Sloan Kettering Cancer Center between January 2012 and February 2017. Indirect ophthalmoscopy, fundus photography, ultrasonography, and ultrasonic biomicroscopy were used to evaluate clinical response. Patient, ocular, ocular progression-free, ocular recurrent event–free, and second ocular survivals were assessed by Kaplan-Meier estimates. Retinal toxicity was evaluated by electroretinography. Snellen visual acuity and complete blood count metrics were recorded. RESULTS: Sixty-four eyes (70%) in 41 patients (89%) received ophthalmic artery chemosurgery as part of their treatment. Twenty-six patients (56%) received tandem OAC (bilateral simultaneous infusions). Seven eyes were primarily enucleated. No eye receiving initial OAC was enucleated. There was a single secondary enucleation in an eye initially treated with focal therapy with anterior chamber recurrence. The 3-year Kaplan-Meier estimates for overall ocular, secondary ocular (survival after treatment for recurrence), progression-free, and recurrent event–free survival were 91.3% [95% confidence interval (CI) 83.4-95.5], 98.7% (95% CI 91.3-99.8), 91.5% (95% CI 83.0-95.8), and 78.9% (95% CI 68.2-86.3), respectively. Overall and secondary ocular survivals were 100% for International Classification of Retinoblastoma (ICRB) groups A-C. Overall ocular survival was 91.5% (95% CI 70-97.8) for ICRB group D and 71.4% (95% CI 47.1-79.4) for group E. Secondary ocular survival was 95.4% (95% CI 71.8-99.3) for ICRB group D and 100% for group E. There were no treatment-related deaths, three patients developed trilateral retinoblastoma (one died), and one patient (who did not receive OAC) developed metastatic disease and is in remission at 32-month follow-up. CONCLUSION: The majority (89%) of bilateral retinoblastoma patients in the current era and at this center were treated with OAC. This has resulted in saving a historic number of eyes. A quarter of eyes developed recurrent disease (defined as recurrent disease requiring any treatment including focal), the majority of which occurred in the first year after treatment, and all but one was saved. There has been no compromise in patient survival.

https://ift.tt/2MRhcoe

SIRT2 Promotes the Migration and Invasion of Gastric Cancer through RAS/ERK/JNK/MMP-9 Pathway by Increasing PEPCK1-Related Metabolism

Publication date: July 2018

Source: Neoplasia, Volume 20, Issue 7

Author(s): Yang Li, Mingming Zhang, Robert G. Dorfman, Yida Pan, Dehua Tang, Lei Xu, Zhenguo Zhao, Qian Zhou, Lixing Zhou, Yuming Wang, Yuyao Yin, Shanshan Shen, Bo Kong, Helmut Friess, Shimin Zhao, Lei Wang, Xiaoping Zou

Abstract

Metastasis is the most important feature of gastric cancer (GC) and the most widely recognized reason for GC-related deaths. Unfortunately, the underlying mechanism behind this metastasis remains unknown. Mounting evidence suggests the dynamic regulatory role of sirtuin2 (SIRT2), a histone deacetylase (HDAC), in cell migration and invasion. The present study aims to evaluate the biological function of SIRT2 in GC and identify the target of SIRT2 as well as evaluate its therapeutic efficacy. We found that SIRT2 was upregulated in GC tissues compared to adjacent normal tissues, and this was correlated with reduced patient survival. Although CCK8 and colony-formation assays showed that SIRT2 overexpression marginally promoted proliferation in GC cell lines, SIRT2 knockdown or treatment with SirReal2 decreased the migration and invasion of GC cells. We demonstrated both in vitro and in vivo that SirReal2 could inhibit the deacetylation activity of SIRT2 and its downstream target PEPCK1, which is related to mitochondrial metabolism and RAS/ERK/JNK/MMP-9 pathway. Taken together, these results demonstrate for the first time that SirReal2 selectively targets SIRT2 and decreases migration as well as invasion in human GC cells. SirReal2 therefore shows promise as a new drug candidate for GC therapy.

https://ift.tt/2KBKZ7O

Improved Brain Penetration and Antitumor Efficacy of Temozolomide by Inhibition of ABCB1 and ABCG2

Publication date: July 2018

Source: Neoplasia, Volume 20, Issue 7

Author(s): Mark C. de Gooijer, Nienke A. de Vries, Tessa Buckle, Levi C.M. Buil, Jos H. Beijnen, Willem Boogerd, Olaf van Tellingen

Abstract

The anticancer drug temozolomide is the only drug with proven activity against high-grade gliomas and has therefore become a part of the standard treatment of these tumors. P-glycoprotein (P-gp; ABCB1) and breast cancer resistance protein (BCRP; ABCG2) are transport proteins, which are present at the blood-brain barrier and limit the brain uptake of substrate drugs. We have studied the effect of P-gp and BCRP on the pharmacokinetics and pharmacodynamics of temozolomide, making use of a comprehensive set of in vitro transport experiments and in vivo pharmacokinetic and antitumor efficacy experiments using wild-type, Abcg2^−/−, Abcb1a/b^−/−, and Abcb1a/b;Abcg2^−/− mice. We here show that the combined deletion of Abcb1a/b and Abcg2 increases the brain penetration of temozolomide by 1.5-fold compared to wild-type controls (P < .001) without changing the systemic drug exposure. Moreover, the same increase was achieved when temozolomide was given to wild-type mice in combination with the dual P-gp/BCRP inhibitor elacridar (GF120918). The antitumor efficacy of temozolomide against three different intracranial tumor models was significantly enhanced when Abcb1a/b and Abcg2 were genetically deficient or pharmacologically inhibited in recipient mice. These findings call for further clinical testing of temozolomide in combination with elacridar for the treatment of gliomas, as this offers the perspective of further improving the antitumor efficacy of this already active agent.

https://ift.tt/2KyBCFH

Coexpression of p-IGF-1R and MMP-7 Modulates Panitumumab and Cetuximab Efficacy in RAS Wild-Type Metastatic Colorectal Cancer Patients

Publication date: July 2018

Source: Neoplasia, Volume 20, Issue 7

Author(s): Vicente Alonso, Pilar Escudero, Carlos Fernández-Martos, Antonia Salud, Miguel Méndez, Javier Gallego, Jose-R. Rodriguez, Marta Martín-Richard, Julen Fernández-Plana, Hermini Manzano, José-Carlos Méndez, Monserrat Zanui, Esther Falcó, Mireia Gil-Raga, Federico Rojo, Miriam Cuatrecasas, Jaime Feliu, Xabier García-Albéniz, Joan Maurel

Abstract

INTRODUCTION: The coexpression of pIGF-1R and MMP-7 (double-positive phenotype, DP) correlates with poor overall survival (OS) in KRAS wild-type (WT) (exon 2) metastatic colorectal cancer (mCRC) patients treated with irinotecan-cetuximab in second/third line. METHODS: We analyzed two prospective biomarker design trials of newly diagnosed RAS-WT mCRC patients treated with panitumumab-FOLFOX6 (PULSE trial; NCT01288339) or cetuximab plus either FOLFOX6/FOLFIRI (POSIBA trial; NCT01276379). The main exposure was DP phenotype (DP/non-DP), as assessed by two independent pathologists. DP cases were defined by immunohistochemistry as >70% expression of moderate or strong intensity for both MMP-7 and pIGF-1R. Primary endpoint: progression-free survival (PFS); secondary endpoints: OS and response rate. PFS and OS were adjusted by baseline characteristics using multivariate Cox models. RESULTS: We analyzed 67 patients (30 non-DP, 37 DP) in the PULSE trial and 181 patients in the POSIBA trial (158 non-DP, 23 DP). Response rates and PFS were similar between groups in both studies. DP was associated with prolonged OS in PULSE (adjusted HR: 0.23; 95%CI: 0.11-0.52; P=.0004) and with shorter OS in POSIBA (adjusted HR: 1.67; 95%CI: 0.96-2.90; P=.07). CONCLUSION: A differential effect of anti-EGFRs on survival by DP phenotype was observed. Panitumumab might be more beneficial for RAS-WT mCRC patients with DP phenotype, whereas cetuximab might improve OS in non-DP.

https://ift.tt/2lUWCb6