Porokeratosis derives from a process of abnormal keratinization, resulting in clinical and histologic variants. Follicular involvement is infrequently described, with previous suggestions that it may represent a distinct condition. We describe a case of typical disseminated superficial actinic porokeratosis with additional clinically prominent folliculocentric keratosis. Histologically, this represented follicular cornoid lamellae. These findings support follicular porokeratosis as an anatomic site variant of porokeratosis, as opposed to a distinct condition. We also want to raise awareness of this variant which clinically should be considered when presented with a discrete papular keratotic eruption. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
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Τρίτη 7 Μαρτίου 2017
The local twitch response during trigger point dry needling: Is it necessary for successful outcomes?
Publication date: Available online 7 March 2017
Source:Journal of Bodywork and Movement Therapies
Author(s): Thomas Perreault, James Dunning, Raymond Butts
BackgroundMyofascial trigger point (MTrP) injection and trigger point dry needling (TrPDN) are widely accepted therapies for myofascial pain syndrome (MPS). Empirical evidence suggests eliciting a local twitch response (LTR) during needling is essential.ObjectiveThis is the first review exploring the available literature, regardless of study design, on the neurophysiological effects and clinical significance of the LTR as it relates to reductions in pain and disability secondary to MTrP needling.MethodsPubMed, MEDLINE, Science Direct and Google Scholar were searched up until October 2016 using terms related to trigger point needling and the LTR.Resultsand Discussion: Several studies show that eliciting a LTR does not correlate with changes in pain and disability, and multiple systematic reviews have failed to conclude whether the LTR is relevant to the outcome of TrPDN. Post needling soreness is consistently reported in studies using repeated in and out needling to elicit LTRs and increases in proportion to the number of needle insertions. In contrast, needle winding without LTRs to MTrPs and connective tissue is well supported in the literature, as it is linked to anti-nociception and factors related to tissue repair and remodeling. Additionally, the positive biochemical changes in the MTrP after needling may simply be a wash out effect related to local vasodilation. While the LTR during TrPDN appears unnecessary for managing myofascial pain and unrelated to many of the positive effects of TrPDN, further investigation is required.
http://ift.tt/2lCJpGk
Unenhanced computed tomography for normal appendix detection: comparison of low-dose with statistical iterative reconstruction and regular-dose with filtered back projection
Publication date: May–June 2017
Source:Clinical Imaging, Volume 43
Author(s): Hwi Ryong Park, Sung Bin Park, Eun Sun Lee, Hyun Jeong Park, Jong Beum Lee, Yang Soo Kim
PurposeTo evaluate the differences in visualization of a normal appendix between regular-dose (RD) and low-dose (LD) unenhanced CT.Material and methods179 patients underwent both RDCT and LDCT for urolithiasis. Two reviewers evaluated the appendiceal visualization on a three-point scale. Sensitivities and interobserver agreement were measured.ResultsThere were no significant differences between RDCT and LDCT in sensitivity, regardless of the reviewer. Interobserver agreement was excellent in both RDCT and LDCT.ConclusionUnenhanced LDCT is a good tool for detecting a normal appendix and is also useful for less experienced interpreters who are unfamiliar with using LDCT images.
http://ift.tt/2mWtkLV
An evaluation of our experience in position verification of catheters used for interstitial high-dose-rate brachytherapy of solitary bladder tumors
Source:Brachytherapy
Author(s): S.J.E.A. Bus, N.G. Leus, B.J. Oosterveld, M.P.R. Van Gellekom, G.J.M. van de Loop, E.M. van der Steen-Banasik
PurposeThe goal of this study was to verify the position of catheters used over 4 days for brachytherapy of solitary bladder tumors.Methods and MaterialsThe study covered three phases. Shifting of catheters was studied using daily position verification CT scans of 20 patients. The possibility to omit the CT scan on Day 2 by adding a loading margin of 4 mm on each side was studied using data of 5 patients. Whether the Day 4 verification CT scan could be omitted if this margin was used, was studied for another group of 10 patients, comparing the Day 3 treatment plan to the Day 4 CT scan.ResultsAn average catheter shift on Days 2, 3, and 4 of, respectively, −0.3 mm (−8 to 10 mm), −0.5 mm (−14 to 10 mm), and −0.1 mm (−16 to 28 mm) was found over the measurements at both sites of the catheter. Including only shifts causing underdosing of the clinical target volume (CTV), the average shift on Days 2, 3, and 4 was, respectively, −3.6 mm (−1 to −8 mm), −5.4 mm (−1 to −14 mm), and −5.3 mm (−1 to −16 mm). After adding a loading margin, the CTV was covered on Day 2; however, the margin was not sufficient for Days 3 and 4. On Day 4, in 2/10 patients, the CTV was not completely covered. In 5/10 patients, an increased 200% isodose volume was found.ConclusionsPosition verification is necessary in bladder brachytherapy. If a 4-mm margin on each side of the loading pattern was added, position verification on Day 2 could be omitted. The verification CT scan of Days 3 and 4 is still necessary.
http://ift.tt/2m12r58
Infection control III: Infection prevention and control as mediators
Source:American Journal of Infection Control
Author(s): Harold W. Horowitz
http://ift.tt/2ncTO7V
Could legal requirements in nursing practice trigger actions that would change the rates of urinary tract infections? A case study in Brazil
Source:American Journal of Infection Control
Author(s): Clesnan Mendes-Rodrigues, Eliana Borges Silva Pereira, Renata Lemos de Sousa Neto, Jaqueline Resende, Astrídia Marília de Souza Fontes
We evaluated the influence of a Brazilian resolution, published in 2013, that restricts the performing of urinary catheterization to nurses, as opposed to others from different nursing professional categories, on indicators of catheter-associated urinary tract infection in an intensive care unit. The resolution triggered actions such as the implementation of protocols and nursing staff training that led to behavior changes related to the reduction of catheter-associated urinary tract infection rates.
http://ift.tt/2mWnytu
Nursing students' knowledge about ventilator-associated pneumonia prevention guidelines: Effectiveness of a teaching program
Source:American Journal of Infection Control
Author(s): Sami M. Aloush
This study evaluated the effectiveness of an educational course that aimed to expand student nurses' knowledge about the guidelines for ventilator-associated pneumonia (VAP) prevention. In the pretest, the students revealed poor knowledge (mean score ± SD, 6.3 ± 2.8 out of 20). After completion of the educational program, participants in the experimental group showed a significant improvement (t105 = 14.9, P < .001). The control group showed no significant improvement. More focus on VAP prevention guidelines is essential in nursing curricula.
http://ift.tt/2ncHXXu
An Epstein-Barr Virus-Positive Classical Hodgkin Lymphoma with Exclusive Sinusoidal Growth Pattern: An Unusual Morphologic Variant
Publication date: Available online 7 March 2017
Source:Pathology - Research and Practice
Author(s): Pu Su, Rachel Jug, Xin Liu, Endi Wang
Classical Hodgkin lymphoma (cHL) typically involves lymph node parenchyma, and a case with Hodgkin cells confined within nodal sinusoids is extremely rare. Herein we report a case of cHL with sinusoidal growth pattern. This 15-year old patient presented with B symptoms and was found to have bilateral cervical lymphadenopathy and an anterior mediastinal mass. Biopsy of a cervical lymph node demonstrated cohesive clusters of Reed-Sternberg (RS)-like cells suggestive of sinusoidal growth with an extrasinusoidal mixed inflammatory cell infiltrate characteristic of the microenvironment seen in cHL. The RS cells/variants were positive for CD30 and CD15, and showed down-regulation of B-cell program and CD45, an immunophenotypic profile consistent with cHL. The sinusoidal growth pattern was also highlighted by EBV study. To the best of our knowledge, this is the first case of EBV-positive cHL that displays a sinusoidal growth pattern. The patient was treated with children's high risk cHL chemotherapy protocol and responded well.
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The reproducibility and clinical utility of the 3D camera for measuring scar height, with a protocol for administration
Background
This study aimed to determine the reproducibility and clinical utility of a 3D camera for measuring burn scar height in adults.
Methods
Participants from a larger prospective longitudinal study were included. Reproducibility data were collected using an immediate test-retest interval and a 1-2 week test-retest interval and included reliability and agreement. The LifeViz™ 3D camera was used to measure scar height. Reproducibility was tested using the Intraclass Correlation Coefficient (ICC), percentage agreement within 1 mm between test and retest, standard error of measurement, smallest detectable change (SDC) and Bland Altman limits of agreement.
Results
Burn scar images from 55 adult participants were included. Intra-rater reliability was acceptable using an immediate retest interval (maximum and minimum height ICC=0.85, 0.86 respectively). Agreement using an immediate retest interval was borderline acceptable (maximum and minimum height SDC=1.11, 0.69 respectively) to detect changes of close to 1 mm. Reproducibility was largely not acceptable using a 1-2 week test-retest interval (eg, maximum and minimum height ICC=0.34, 0.68 respectively; maximum and minimum height SDC=2.66, 1.16). The clinical utility of the camera was supported for scars over relatively flat areas and well-defined border margins. A protocol for administration of the camera was developed.
Conclusion
The 3D camera appears capable of detecting gross changes or differences in scar height above the normal skin surface, in adults with scars over relatively flat areas and well-defined border margins. However, further testing of reproducibility using a shorter test-retest interval than 1-2 week retest is recommended to confirm the suitability of the device for measuring changes or differences in scar height.
http://ift.tt/2lCDRM1
Examination of wound healing after curettage by multiphoton tomography of human skin in vivo
Background
The multiphoton tomography (MPT) has evolved into a useful tool for the non-invasive investigation of morphological and biophysical characteristics of human skin in vivo. Until now, changes of the skin have been evaluated mainly by using clinical and histological techniques. In this study, the progress of wound healing was investigated by MPT over 3 weeks with a final examination after 24 months. Especially, the collagen degradation, reepithelization and tissue formation were examined. As specific parameter for wound healing and its course the second-harmonic generation-to-autofluorescence aging index of dermis (SAAID) was used.
Methods
About 10 volunteers aged between 25 and 58 years were examined. Acute wounds were scanned with three Z-stacks taken per visit. The stacks were taken up to a depth of 225 μm at increments of 5 μm and a scan time for 3 seconds per scan. Subsequently, the SAAID was evaluated as an indicator for wound healing. Furthermore, single scans were taken for morphological investigations.
Results
The evaluation revealed a distinct difference in the SAAID behavior between the Z-stacks taken at each visit. Furthermore, the degradation of collagen and cells and their reappearance could be shown in the course of the visits.
Conclusions
Clear differences in the curve behavior of the SAAID at every visit were shown in this study. The SAAID curves and morphological images could be correlated with findings of the clinical examination of different wound healing phases. Therefore, SAAID curves and morphological MPT imaging could provide a non-invasive tool for the determination of wound healing phases in patients in vivo.
http://ift.tt/2m0Mr3d
Tri-stimuli-responsive biodegradable theranostics for mild hyperthermia enhanced chemotherapy
Source:Biomaterials, Volume 126
Author(s): Nan Lu, Peng Huang, Wenpei Fan, Zhantong Wang, Yijing Liu, Sheng Wang, Guofeng Zhang, Junkai Hu, Wenfei Liu, Gang Niu, Richard D. Leapman, Guangming Lu, Xiaoyuan Chen
The combination of hyperthermia and chemotherapy is able to greatly enhance the treatment efficacy mainly due to the synergistic interactions between these two treatments. In this study, we propose a new concept of mild hyperthermia enhanced chemotherapy to explore and validate the synergistic mechanism in vitro and in vivo. To do this, a novel kind of biodegradable nanotheranostics based on copper sulfide doped periodic mesoporous organosilica nanoparticles (CuS@PMOs) was constructed via an in situ growth method for light-triggered mild hyperthermia and drug delivery. The as-prepared CuS@PMOs exhibit a high doxorubicin (DOX) loading capacity of 470 mg/g. The DOX release from CuS@PMOs can be precisely controlled by three stimuli, including intracellular glutathione (GSH), acidic environment in tumor cells, and external laser irradiation. Most intriguingly, mild hyperthermia induced by laser-irradiated CuS nanoparticles can dramatically improve the cell uptake of nanotheranostics both in vitro and in vivo, thus significantly enhancing the chemotherapeutic efficacy for complete tumor growth suppression without recurrence. Meanwhile, the fluorescence recovery following the DOX release can be used as an indicator to monitor the chemotherapeutic progress.
http://ift.tt/2ncuP4G
Germ cell apoptosis and expression of Bcl-2 and Bax in porcine testis under normal and heat stress conditions
Source:Acta Histochemica
Author(s): Xiaorui Fan, Huaming Xi, Zhen Zhang, Yajun Liang, Qinghong Li, Junping He
The aim of this study was to examine whether an elevated ambient temperature (37–40°C) had an effect on the apoptosis of germ cells and the expression of Bcl-2 and Bax in porcine testis. Six boars were used. Three boars were subjected to an elevated ambient temperature (37–40°C, 7days, 3h per day) as a heat stress (HS) group. The other 3 boars were kept in a room temperature house (20–27°C) as a control group. All boars were castrated and the testes were harvested. TUNEL assay was used for the detection of apoptotic cells. Immunohistochemistry, Western blotting and quantitative real-time PCR were used to analyze protein and mRNA levels of Bcl-2 and Bax in response to heat treatment. The results showed that apoptotic signals increased under heat stress conditions compared with the control (P<0.01), and the cell types most affected by heat treatment were spermatocytes and spermatids. In both the control and experimental groups, Bcl-2 was expressed in the cytoplasm and nucleus of spermatogonia, spermatocytes and differentiating spermatids and Bcl-2 preferentially localized close to the seminiferous tubule's luminal surface in late spermatocytes and spermatids. Compared with the control group, the expression levels of Bcl-2 protein and mRNA significantly increased in heat treatment group, while the expression levels of Bax protein and mRNA did not show significant changes between the control and experimental group. Low to moderate Bax immunoreactivity staining was observed in all kinds of germ cells in the control group. Strong staining was observed in spermatogonia, and low to moderate Bax staining was observed in spermatocytes and spermatids. A redistribution of Bax from a cytoplasmic to perinuclear or nuclear localization could be observed in the spermatogonia, spermatocytes and spermatids obtained in the heat treated group. These results showed that elevated ambient temperatures induced germ cell apoptosis. In response to heat stress, the expression of Bcl-2 increased and a redistribution of Bax from a cytoplasmic to a perinuclear or nuclear localization. This indicates that Bcl-2 and Bax may be involved in regulation of germ cell apoptosis induced by heat stress in boars.
http://ift.tt/2mW0xqy
Klotho, APOEε4, cognitive ability, brain size, atrophy and survival: A study in the Aberdeen Birth Cohort of 1936
Publication date: Available online 7 March 2017
Source:Neurobiology of Aging
Author(s): Clarisse F. de Vries, Roger T. Staff, Sarah E. Harris, Dorota Chapko, Daniel S. Williams, Polina Reichert, Trevor Ahearn, Christopher J. McNeil, Lawrence J. Whalley, Alison D. Murray
A single copy of klotho allele KL-VS is associated with longevity, better health, increased cognition and bigger regional brain volume. However, its longitudinal effects on cognition and brain volumes, both global and regional, in late life are unclear. In this study we show [1] KL-VS heterozygotes had shorter survival and [2] smaller white matter volumes than non-carriers; [3] had slower cognitive decline; and [4] had greater right frontal lobe volumes. The KL-VS heterozygote survival and white matter volume disadvantages were unexpected. A possible explanation for these results in the context of the literature is a potential interaction between the environment and/or age of the participants, leading to a heterozygote disadvantage. The longitudinal cognitive trajectories indicate that heterozygotes would have an advantage in very late life. Collectively these results suggest that the genotype-survival advantage of the KL-VS allele is age-dependent and possibly mediated through differential cognition and brain volume.
http://ift.tt/2mDQlCD
Effect of groups at α-position and side-chain structure of comonomers on surface free energy and surface reorganization of fluorinated methacrylate copolymer
Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Zixu Gu, Jun Cheng, Mingzu Zhang, Jinlin He, Peihong Ni
Surface free energy and surface reorganization, two essential properties for low surface free energy materials, have been researched by studying the effects of the groups (H or CH3) at α-position and the side-chain structures (flexible or rigid) of alkyl (meth)acrylate on a series of fluorinated copolymers poly (perfluorohexylethyl methacrylate)-co-poly [alkyl (meth)acrylate]. The static contact angle, X-ray photoelectron spectroscopy (XPS), and surface tension studies indicate that both the groups at α-position and the side-chain structures of alkyl (meth)acrylate can significantly influence the arrangement of perfluoroalkyl chains at the interface, resulting in different fluorine-enriched concentrations on the interface, which will finally affect the surface free energy of the copolymer. The dynamic contact angle measurement shows that the surface reorganization of the fluorinated chains are directly associated with the Tg of these copolymers, and decrease with the increasing Tg. All these results show that the copolymers containing H at the α-position and flexible side-chain in comonomer have lower surface free energy and higher surface reorganization, while the steric hindrance effects of α-methyl groups and/or rigid side-chain in comonomer allow the copolymers having higher surface free energy and lower surface reorganization.
Graphical abstract
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Development of structure–property relationships that allow independent control of glass transition temperature, melting temperature, and rheology in a library of bio-based succinate polyester polyols
Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Alan K. Schrock, Heather S.C. Hamilton, Baylen D. Thompson, Kenneth Ulrich, Cathlene del Rosario, Carl Jacky Saint-Louis, William D. Coggio
A library of 20 bio-based succinate (SA) diol, co-diol, and co-diacid polyester polyols (PESPs) was generated and characterized, giving detailed understanding for tuning of their thermal transitions and rheological parameters. SA and 1,3-propanediol, 1,4-butanediol (BDO), 1,6-hexanediol, 2,2-dimethyl-1,3-propanediol, 3-methyl-1,5-pentanediol, diethylene glycol (DEG), adipic acid, or sebacic acid, and the blended diols were oligomerized to 1000 and 2000 Da Mn. The SA PESP melting point and its ability to crystallize can be set by controlling the structures and ratios of co-diols or co-diacids. We also show that the PESPs follow the expected Arrhenius temperature–viscosity relationship, but with a clear break in activation energy between PESPs with and without pendent methyl substituents and with DEG. PESP glass transition temperature, melting points, and rheology can be controlled independently by use of co-monomers with and without pendent methyl groups and with DEG.
Graphical abstract
http://ift.tt/2mVN1TU
Carbon nanotube induced double percolation in polymer blends: Morphology, rheology and broadband dielectric properties
Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Ivonne Otero-Navas, Mohammad Arjmand, Uttandaraman Sundararaj
In this study, we investigate the effect of multi-walled carbon nanotube (MWCNT) on the rheology, morphology and broadband dielectric properties of polypropylene:polystyrene (PP:PS) blends (PP:PS—10:90, 50:50 and 90:10). Transmission electron microscopy showed that MWCNTs were localized at the interface and inside the PS phase, regardless of the polymer blend ratio. Employing scanning electron microscopy, we observed that addition of MWCNT led to a transition from dispersed to interconnected morphology for the blends with PS as minor phase (PP:PS/50:50 and PP:PS/90:10). We propose that the selective localization of MWCNT in PS and at the interface slowed down the breakup mechanisms, increasing the lifetime of PS/MWCNT elongated domains, thus decreasing the amount of PS/MWCNT needed to percolate in PP phase. In addition, it is proposed that MWCNT located at the interface act as bridges between PS/MWCNT domains, favouring the coarsening of PS/MWCNT domains. The dielectric properties of the polymer blends PP:PS/50:50 and PP:PS/90:10 confirmed that double percolation was achieved with increase in MWCNT content. This transition provided the possibility to tune dielectric properties of the PP:PS/MWCNT blends. The double percolated structure offered high imaginary permittivity, while the dispersed morphology presented low imaginary permittivity. In other words, this study reveals that manipulating blend morphology can lead to blends with capacitive or dissipative characteristics.
Graphical abstract
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Poly(2,6-dimethyl-1,4-phenylene oxide) blends with a poly(arylene ether ketone) for gas separation membranes
Publication date: 7 April 2017
Source:Polymer, Volume 114
Author(s): Andrew Shaver, Joshua D. Moon, Donald Savacool, Wenrui Zhang, Gurtej Narang, Gregory Miller, Britannia Vondrasek, J.J. Lesko, Benny D. Freeman, J.S. Riffle, James E. McGrath
Poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) is utilized for gas separation membranes. It has a relatively high free volume with high gas permeabilities but suffers from low selectivities. PPO polymers with Mn's from 2000 to 22,000 g/mole were synthesized and blended with a poly(arylene ether ketone) derived from bisphenol A and difluorobenzophenone (BPA-PAEK). DSC showed that the blends with all but the lowest molecular weight PPO had two Tg's, thus suggesting that two phases were present. The ketone carbon and benzylic methyl groups on the BPA-PAEK and the PPO polymers crosslinked upon exposure to UV light. The gel fractions after UV exposure were high and the tensile properties were similar to the PPO control polymer that is currently used as a gas separation membrane. The crosslinked blends had improved gas selectivities over their linear counterparts. The 90/10 wt/wt 22k PPO/BPA PAEK crosslinked blends gained the most O2/N2 selectivity and maintained a high permeability.
Graphical abstract
http://ift.tt/2m0pv4d
Graphical Contents list & Author index
Publication date: 10 March 2017
Source:Polymer, Volume 112
http://ift.tt/2m0Gvae
The first fossil Platyrrhini (Primates: Anthropoidea) from Venezuela: A capuchin monkey from the Plio-Pleistocene of El Breal de Orocual
Source:Journal of Human Evolution
Author(s): Damián Ruiz-Ramoni, Ascanio D. Rincón, Andrés Solórzano, Salvador Moyà-Solà
http://ift.tt/2m0v3vr
Antidiabetic medication adherence and associated factors among patients in Botswana; implications for the future
Publication date: Available online 6 March 2017
Source:Alexandria Journal of Medicine
Author(s): Godfrey Mutashambara Rwegerera, Thato Moshomo, Marea Gaenamong, Taibat Aderonke Oyewo, Sivasomnath Gollakota, Francis Apolinary Mhimbira, Joseph Fadare, Brian Godman, Johanna C. Meyer, Yordanka Piña Rivera
BackgroundDiabetes mellitus (DM) is a major global public health problem. Lack of adherence to medication causes suboptimal glycemic control increasing complication rates, costs and mortality. The objective of the study was to determine current antidiabetic medication adherence in Botswana and assess associated factors so as to direct potential future interventions.Materials and methodsA cross-sectional study among 376 randomly selected diabetic patients attending a leading clinic in Gaborone, Botswana. Eight item Morisky Medication adherence questionnaire was used to assess antidiabetic medication adherence. A structured questionnaire was also used to collect information on factors influencing adherence including age, gender, education, type and duration of diabetes, treatment, complications and HIV status. Data were entered and analyzed using STATA Version 14, and logistic regression performed.ResultsOver forty percent (41.8%) of patients were non-adherent to antidiabetic medications. Studied sociodemographic characteristics and clinical variables did not affect adherence. HIV positive status was associated with a statistically significant better adherence at multivariate analysis.ConclusionAdherence to antidiabetic medication was found to be suboptimal in a setting where medicines are provided free of charge. Only HIV positivity was found to be significantly associated with better adherence, probably due to effect of greater psychosocial support and counselling as part of HIV treatment. There is a need to carry out studies to further improve understanding of factors associated with medication adherence that are pertinent to Botswana and similar settings given the growing prevalence of diabetes.
http://ift.tt/2mzjrmj
IGF-I and IGFBP-3 levels and their correlations with carcinoembryonic antigen in colorectal cancer patients
Publication date: Available online 7 March 2017
Source:Alexandria Journal of Medicine
Author(s): Çiğdem Yağcıoğlu Yücel, Gönül Erden, Fatma Meriç Yılmaz, Sevilay Sezer, Esin Çalcı
BackgroundColorectal cancer is one of the most frequently seen cancers worldwide. Currently, CEA is the most commonly used tumor marker in colorectal cancer. The changes in IGF/IGFBP equilibrium is also known to cause carcinogenesis. In this study, we aimed to monitor IGF-I/IGFBP-3 levels, the changes in IGF-I/IGFBP-3 ratio and correlations of these peptides with the common tumor marker CEA.Materials and methods55 colorectal cancer patients and 35 control group patients were included in this study. Serum CEA, IGF-I and IGFBP-3 levels of all specimens were measured with chemiluminescence method.ResultsIn colorectal cancer patients, IGF-I levels was found to be increased, IGFBP-3 levels decreased and IGF-I/IGFBP-3 ratio was increased; when compared to control group (p<0.05). A moderately significant correlation was found between the conventional tumor marker CEA and IGF-I and IGF-BP3 (p=0.001, r=0.533 and p=0.001, r=−0.573 respectively).ConclusionsIGF-I/IGFBP-3 ratio seems to be increased in the colorectal cancer patients. When considered with the moderate correlation levels of these peptides with CEA, this increase in IGF-I/IGF-BP3 ratio may be useful in monitoring carcinogenesis in colorectal cancer patients among with CEA but more detailed and extensive studies in larger study groups needed to be carried out.
http://ift.tt/2ncBueS
Comparing pre-therapeutic 124 I and 131 I uptake tests with intra-therapeutic 131 I uptake in benign thyroid disorders
Abstract
Purpose
124I-PET/CT can be used for pre-therapeutic assessment of radioactive iodine uptake in benign thyroid disorders, however systematic comparisons with intra-therapeutic uptake are still lacking for these disorders. The goals of this study were to compare 124I RAIU and conventional 131I RAIU tests with each other; to compare both tests with intra-therapeutic uptake (reference); and to verify the time course of radioactive iodine uptake at three time points (30, 102, and 336 h [14 days] post administration; p.a.).
Methods
Thirteen patients with benign thyroid diseases underwent 131I RAIU test and 124I RAIU test one after another before the intra-therapeutic 131I uptake (reference) was measured via short-range and long-range measurements. After correction for decay, relative uptake differences were calculated and subjected to the Bland-Altman method for the evaluation of levels of agreement.
Results
Radioactive iodine uptake tests with 124I-PET/CT and 131I probe did not show systematic deviations at any time point. Likewise, at 30 and 102 h p.a. there was no systematic discrepancy between pre-therapeutic and intra-therapeutic uptake levels. At 14 days p.a., however, both pre-therapeutic tests tended to overestimate the uptake compared to reference. Findings showed, for the first time with 124I, that radioiodine therapy has some early radiobiological effects possibly limiting the accuracy of pre-therapeutic dosimetry.
Conclusions
124I RAIU tests represent a feasible alternative to standard 131I RAIU tests. The additional benefits of 124I-PET/CT (e.g., functional topography, inclusion of retrosternal areas, possibility to enable fusion imaging) may thus increase the scope of this technology in benign thyroid disorders.
http://ift.tt/2lYWwOb
Migraine – a look down the nose
Studies have suggested that contact between opposing mucosal surfaces in the nasal wall and cavity can be a target of the surgical treatment of migraines. Unfortunately, not enough is known about the role of nasal pathology in the pathogenesis of this condition. The co-existence of further rhinological disorders can be an impediment in defining the cause and effect of anatomical variants. The authors compared MRI scans of migraine- and non-migraine patients to determine the prevalence of such mucosal contact points in an effort to extrapolate whether there is a significant association with migraines.
http://ift.tt/2mDqKK8
Management of metastatic castration-resistant prostate cancer: a focus on radium-223
Source:Critical Reviews in Oncology/Hematology
Author(s): Sergio Baldari, Giuseppe Boni, Roberto Bortolus, Orazio Caffo, Giario Conti, Giuseppe De Vincentis, Fabio Monari, Giuseppe Procopio, Daniele Santini, Ettore Seregni, Riccardo Valdagni
Radium-223, a calcium mimetic bone-seeking radionuclide that selectively targets bone metastases with alpha particles, is approved for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) and symptomatic bone metastases. In patients with mCRPC, treatment with radium-223 has been associated with survival benefit, regardless of prior docetaxel use, and also has a positive impact on symptomatic skeletal events and quality of life. Radium-223 is best suited for patients with symptomatic mCRPC and bone-predominant disease and no visceral metastases, and may lead to better outcomes when given early in the course of the disease. An expert multidisciplinary panel convened in Milan, Italy to review the current best-evidence literature on radium-223 and to convey their personal expertise with the use of radium-223 and identify possible strategies for best practice. This article summarizes the best available evidence for the use of radium-223, discusses the essential role of the multidisciplinary team in delivering effective treatment for mCRPC, clarifies pre- and post-treatment evaluation and monitoring, and outlines future scenarios for radium-223 in the treatment of men with MCRPC.
http://ift.tt/2mz8Ibg
Autonomic Imbalance as a Predictor of Metabolic Risks, Cardiovascular Disease, Diabetes, and Mortality Autonomic Imbalance Predicts CVD, DM, Mortality
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2nc5ZBF
WITHDRAWN: Eligibility for Statin Therapy According to New Cholesterol Guidelines on Primary Aldosteronism
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2mz4tNe
WITHDRAWN: High Prevalence of Nonalcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels (article published in final form as 10.1210/jc.2015-1966)
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2ncdaKl
WITHDRAWN: Low-density lipoprotein cholesterol is associated with fracture risk in diabetes patients – a nested case-control study
The Journal of Clinical Endocrinology &Metabolism, Early Release.
http://ift.tt/2mzclhE
MRI of the Digital Nerves of the Hand: Anatomy and Spectrum of Pathology
Source:Current Problems in Diagnostic Radiology
Author(s): Charles H. Mitchell, Laura M. Fayad, Shivani Ahlawat
Digital nerves are intrinsic to the sensory and motor function of the hand. These nerves represent the terminal ramifications of the ulnar, median and radial nerves and are located distal to the carpal tunnel and Guyon′s canal. With magnetic resonance imaging (MRI), traumatic and non-traumatic abnormalities of the digital nerves can be shown with high contrast as well as high spatial resolution. Digital nerve abnormalities are most commonly post-traumatic in nature; however, infection, inflammatory, vascular malformations and neoplasms can rarely occur. MRI is playing an increasing role in the assessment of peripheral nerve injury throughout the body, and in the hand, can accurately identify the extent and character of digital nerve abnormalities prior to operative intervention.
http://ift.tt/2mVg75O
Protochlamydia phocaeensis sp. nov., a new Chlamydiales species with host dependent replication cycle
Source:Microbes and Infection
Author(s): Jacques Y. Bou Khalil, Samia Benamar, Fabrizio Di Pinto, Caroline Blanc-Tailleur, Didier Raoult, Bernard La Scola
Chlamydiae are pathogenic and symbiotic bacteria, which form an important part of amoeba-associated microorganisms. In this paper, we report the isolation, developmental cycle and genome analysis of Protochlamydia phocaeensis sp. nov., an obligate intracellular parasite with a large host spectrum, able to infect Acanthamoeba castellanii, Acanthamoeba polyphaga, and Vermamoeba vermiformis. The genome size is 3,424,182 bp with a GC content of 42 %. This bacterium displayed a particular developmental cycle depending on the infected host. The P. phocaeensis showed typical inclusion vacuoles in A. castellanii, while these were absent in Vermamoeba. vermiformis. Since "Chlamydiae – amoebae" interactions are supposed to depend on the chlamydial species, our findings speculate that variations in the developmental cycle of certain Chlamydiae is also host dependent.
http://ift.tt/2myX9RD
Transcription Factor T-bet Orchestrates Lineage Development and Function in the Immune System
Publication date: Available online 7 March 2017
Source:Trends in Immunology
Author(s): Axel Kallies, Kim L. Good-Jacobson
T-bet was originally described as the key transcription factor defining type 1 T helper (Th) cells. However, it is now clear that it drives the orchestrated generation of effector and memory cells in multiple different lymphocyte lineages. In addition to Th1 cells, CD8 T cells, B cells and some innate lymphocyte populations require T-bet for their development or differentiation in response to antigen. Furthermore, other Th cell populations, including T follicular helper and Th17, as well as regulatory T cells can co-opt T-bet expression to promote functional diversification and colocalization. Thus, T-bet broadly regulates transcriptional programs in response to type 1 inflammatory signals and mediates the coordinated differentiation, function, migration and survival of effector and memory lymphocyte subsets in the affected tissue. Therefore, T-bet expression is essential for effective clearance of pathogens and maintenance of immunity.
http://ift.tt/2mgEEz2
The S(c)ensory Immune System Theory
Publication date: Available online 7 March 2017
Source:Trends in Immunology
Author(s): Henrique Veiga-Fernandes, António A. Freitas
Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms. This context determined the emergence of the 'sensory immune system', which operates in a s(c)ensor mode to ensure systems physiology, organismic homeostasis, and perpetuation of its replicating molecules.
http://ift.tt/2mV8Seq
Dynamin-Related Protein 1-Dependent Mitochondrial Fission Changes in the Dorsal Vagal Complex Regulate Insulin Action
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Beatrice M. Filippi, Mona A. Abraham, Pamuditha N. Silva, Mozhgan Rasti, Mary P. LaPierre, Paige V. Bauer, Jonathan V. Rocheleau, Tony K.T. Lam
Mitochondria undergo dynamic changes to maintain function in eukaryotic cells. Insulin action in parallel regulates glucose homeostasis, but whether specific changes in mitochondrial dynamics alter insulin action and glucose homeostasis remains elusive. Here, we report that high-fat feeding in rodents incurred adaptive dynamic changes in mitochondria through an increase in mitochondrial fission in parallel to an activation of dynamin-related protein 1 (Drp1) in the dorsal vagal complex (DVC) of the brain. Direct inhibition of Drp1 negated high-fat-feeding-induced mitochondrial fission, endoplasmic reticulum (ER) stress, and insulin resistance in the DVC and subsequently restored hepatic glucose production regulation. Conversely, molecular activation of DVC Drp1 in healthy rodents was sufficient to induce DVC mitochondrial fission, ER stress, and insulin resistance. Together, these data illustrate that Drp1-dependent mitochondrial fission changes in the DVC regulate insulin action and suggest that targeting the Drp1-mitochondrial-dependent pathway in the brain may have therapeutic potential in insulin resistance.
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Filippi et al. find that induction of Drp1-dependent mitochondrial fission in the dorsal vagal complex of rodents under high-fat feeding can induce ER stress and insulin resistance.http://ift.tt/2lVeyQu
Mutations that Allow SIR2 Orthologs to Function in a NAD+-Depleted Environment
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Caitlin R. Ondracek, Vincent Frappier, Alison E. Ringel, Cynthia Wolberger, Leonard Guarente
Sirtuin enzymes depend on NAD+ to catalyze protein deacetylation. Therefore, the lowering of NAD+ during aging leads to decreased sirtuin activity and may speed up aging processes in laboratory animals and humans. In this study, we used a genetic screen to identify two mutations in the catalytic domain of yeast Sir2 that allow the enzyme to function in an NAD+-depleted environment. These mutant enzymes give rise to a significant increase of yeast replicative lifespan and increase deacetylation by the Sir2 ortholog, SIRT1, in mammalian cells. Our data suggest that these mutations increase the stability of the conserved catalytic sirtuin domain, thereby increasing the catalytic efficiency of the mutant enzymes. Our approach to identifying sirtuin mutants that permit function in NAD+-limited environments may inform the design of small molecules that can maintain sirtuin activity in aging organisms.
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Ondracek et al. report the identification of two adaptive mutations in yeast Sir2 that allow the enzyme to function in an NAD+-depleted environment by enhancing protein stability and increasing enzyme catalysis, which increases yeast replicative lifespan and deacetylation of in vivo substrates by the Sir2 ortholog, SIRT1, in mammalian cells.http://ift.tt/2lV3rHj
R-spondin1 Controls Muscle Cell Fusion through Dual Regulation of Antagonistic Wnt Signaling Pathways
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Floriane Lacour, Elsa Vezin, C. Florian Bentzinger, Marie-Claude Sincennes, Lorenzo Giordani, Arnaud Ferry, Robert Mitchell, Ketan Patel, Michael A. Rudnicki, Marie-Christine Chaboissier, Anne-Amandine Chassot, Fabien Le Grand
Wnt-mediated signals are involved in many important steps in mammalian regeneration. In multiple cell types, the R-spondin (Rspo) family of secreted proteins potently activates the canonical Wnt/β-catenin pathway. Here, we identify Rspo1 as a mediator of skeletal muscle tissue repair. First, we show that deletion of Rspo1 results in global alteration of muscle regeneration kinetics following acute injury. We find that muscle progenitor cells lacking Rspo1 show delayed differentiation due to reduced activation of Wnt/β-catenin target genes. Furthermore, muscle cells lacking Rspo1 have a fusion phenotype leading to larger myotubes containing supernumerary nuclei both in vitro and in vivo. The increase in muscle fusion was dependent on downregulation of Wnt/β-catenin and upregulation of non-canonical Wnt7a/Fzd7/Rac1 signaling. We conclude that reciprocal control of antagonistic Wnt signaling pathways by Rspo1 in muscle stem cell progeny is a key step ensuring normal tissue architecture restoration following acute damage.
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Using mice lacking the Wnt enhancer Rspo1, Lacour et al. demonstrate that Rspo1 controls muscle cell fusion during skeletal muscle regeneration. Rspo1-null muscle progenitor cells differentiate less efficiently but fuse extensively compared to wild-type cells. Rspo1 is shown to regulate the antagonism between canonical and non-canonical Wnt signaling pathways.http://ift.tt/2lVpwoZ
ATR Mutations Promote the Growth of Melanoma Tumors by Modulating the Immune Microenvironment
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Chi-Fen Chen, Rolando Ruiz-Vega, Priya Vasudeva, Francisco Espitia, Tatiana B. Krasieva, Sebastien de Feraudy, Bruce J. Tromberg, Sharon Huang, Chad P. Garner, Jie Wu, Dave S. Hoon, Anand K. Ganesan
Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet somehow suppress the immune response to facilitate continued growth. In this study, we identify a subset of human melanomas that have loss-of-function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a mechanism by which melanoma cells modulate the immune microenvironment to promote continued growth.
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Tumors grow not only because they acquire mutations that promote their growth but also because they prevent the immune system from recognizing them. Chen et al. identify ATR mutations in human melanoma tumors and determine that ATR mutant melanomas harness the immune system to accelerate tumor growth.http://ift.tt/2lVe3pC
Interrogation of Functional Cell-Surface Markers Identifies CD151 Dependency in High-Grade Serous Ovarian Cancer
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Mauricio Medrano, Laudine Communal, Kevin R. Brown, Marcin Iwanicki, Josee Normand, Joshua Paterson, Fabrice Sircoulomb, Paul Krzyzanowski, Marian Novak, Sasha A. Doodnauth, Fernando Suarez Saiz, Jane Cullis, Rima Al-awar, Benjamin G. Neel, John McPherson, Ronny Drapkin, Laurie Ailles, Anne-Marie Mes-Massons, Robert Rottapel
The degree of genetic aberrations characteristic of high-grade serous ovarian cancer (HGSC) makes identification of the molecular features that drive tumor progression difficult. Here, we perform genome-wide RNAi screens and comprehensive expression analysis of cell-surface markers in a panel of HGSC cell lines to identify genes that are critical to their survival. We report that the tetraspanin CD151 contributes to survival of a subset of HGSC cell lines associated with a ZEB transcriptional program and supports the growth of HGSC tumors. Moreover, we show that high CD151 expression is prognostic of poor clinical outcome. This study reveals cell-surface vulnerabilities associated with HGSC, provides a framework for identifying therapeutic targets, and reports a role for CD151 in HGSC.
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Medrano et al. conduct whole-genome short hairpin RNA screens in 27 high-grade serous ovarian carcinoma (HGSC) cell lines to identify vulnerabilities in HGSC. Analysis of the cell surface reveals that CD151 is essential for cell survival through a ZEB-dependent mechanism.http://ift.tt/2lV4uqQ
Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Melanie Paillard, György Csordás, Gergö Szanda, Tünde Golenár, Valentina Debattisti, Adam Bartok, Nadan Wang, Cynthia Moffat, Erin L. Seifert, András Spät, György Hajnóczky
Mitochondrial Ca2+ uptake through the Ca2+ uniporter supports cell functions, including oxidative metabolism, while meeting tissue-specific calcium signaling patterns and energy needs. The molecular mechanisms underlying tissue-specific control of the uniporter are unknown. Here, we investigated a possible role for tissue-specific stoichiometry between the Ca2+-sensing regulators (MICUs) and pore unit (MCU) of the uniporter. Low MICU1:MCU protein ratio lowered the [Ca2+] threshold for Ca2+ uptake and activation of oxidative metabolism but decreased the cooperativity of uniporter activation in heart and skeletal muscle compared to liver. In MICU1-overexpressing cells, MICU1 was pulled down by MCU proportionally to MICU1 overexpression, suggesting that MICU1:MCU protein ratio directly reflected their association. Overexpressing MICU1 in the heart increased MICU1:MCU ratio, leading to liver-like mitochondrial Ca2+ uptake phenotype and cardiac contractile dysfunction. Thus, the proportion of MICU1-free and MICU1-associated MCU controls these tissue-specific uniporter phenotypes and downstream Ca2+ tuning of oxidative metabolism.
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Paillard et al. report that the relative abundance of the pore-forming protein of the mitochondrial Ca2+ uniporter (MCU) and its Ca2+-sensing regulator (MICU1) define the proportion of MCU complexes with or without MICU1. This ratio is central to programming tissue-specific mitochondrial Ca2+ uptake phenotypes in the heart and liver.http://ift.tt/2lV82cq
Enhancer-Mediated Oncogenic Function of the Menin Tumor Suppressor in Breast Cancer
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Koen M.A. Dreijerink, Anna C. Groner, Erica S.M. Vos, Alba Font-Tello, Lei Gu, David Chi, Jaime Reyes, Jennifer Cook, Elgene Lim, Charles Y. Lin, Wouter de Laat, Prakash K. Rao, Henry W. Long, Myles Brown
While the multiple endocrine neoplasia type 1 (MEN1) gene functions as a tumor suppressor in a variety of cancer types, we explored its oncogenic role in breast tumorigenesis. The MEN1 gene product menin is involved in H3K4 trimethylation and co-activates transcription. We integrated ChIP-seq and RNA-seq data to identify menin target genes. Our analysis revealed that menin-dependent target gene promoters display looping to distal enhancers that are bound by menin, FOXA1 and GATA3. In this fashion, MEN1 co-regulates a proliferative breast cancer-specific gene expression program in ER+ cells. In primary mammary cells, MEN1 exerts an anti-proliferative function by regulating a distinct expression signature. Our findings clarify the cell-type-specific functions of MEN1 and inform the development of menin-directed treatments for breast cancer.
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Dreijerink et al. describe the oncogenic actions of the tumor suppressor menin in breast cancer cells. In mammary progenitor cells, menin regulates anti-proliferative genes. Menin is present at FOXA1 and GATA3-bound enhancers that associate with promoters through chromatin looping. Insight into menin's context-dependent function suggests therapeutic strategies.http://ift.tt/2lV3piF
Circulating NOD1 Activators and Hematopoietic NOD1 Contribute to Metabolic Inflammation and Insulin Resistance
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Kenny L. Chan, Theresa H. Tam, Parastoo Boroumand, David Prescott, Sheila R. Costford, Nichole K. Escalante, Noah Fine, YuShan Tu, Susan J. Robertson, Dilshaayee Prabaharan, Zhi Liu, Philip J. Bilan, Michael W. Salter, Michael Glogauer, Stephen E. Girardin, Dana J. Philpott, Amira Klip
Insulin resistance is a chronic inflammatory condition accompanying obesity or high fat diets that leads to type 2 diabetes. It is hypothesized that lipids and gut bacterial compounds in particular contribute to metabolic inflammation by activating the immune system; however, the receptors detecting these "instigators" of inflammation remain largely undefined. Here, we show that circulating activators of NOD1, a receptor for bacterial peptidoglycan, increase with high fat feeding in mice, suggesting that NOD1 could be a critical sensor leading to metabolic inflammation. Hematopoietic depletion of NOD1 did not prevent weight gain but protected chimeric mice against diet-induced glucose and insulin intolerance. Mechanistically, while macrophage infiltration of adipose tissue persisted, notably these cells were less pro-inflammatory, had lower CXCL1 production, and consequently, lower neutrophil chemoattraction into the tissue. These findings reveal macrophage NOD1 as a cell-specific target to combat diet-induced inflammation past the step of macrophage infiltration, leading to insulin resistance.
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Chan et al. identify that activators of NOD1, a receptor for bacterial cell wall peptidoglycan, increase in the bloodstream during high fat feeding. Moreover, depleting NOD1 from the immune system prevents pro-inflammatory macrophage activation and neutrophil infiltration in adipose tissue during a high fat diet, to improve whole-body insulin sensitivity.http://ift.tt/2lV3p29
CD95/Fas Increases Stemness in Cancer Cells by Inducing a STAT1-Dependent Type I Interferon Response
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Abdul S. Qadir, Paolo Ceppi, Sonia Brockway, Calvin Law, Liang Mu, Nikolai N. Khodarev, Jung Kim, Jonathan C. Zhao, William Putzbach, Andrea E. Murmann, Zhuo Chen, Wenjing Chen, Xia Liu, Arthur R. Salomon, Huiping Liu, Ralph R. Weichselbaum, Jindan Yu, Marcus E. Peter
Stimulation of CD95/Fas drives and maintains cancer stem cells (CSCs). We now report that this involves activation of signal transducer and activator of transcription 1 (STAT1) and induction of STAT1-regulated genes and that this process is inhibited by active caspases. STAT1 is enriched in CSCs in cancer cell lines, patient-derived human breast cancer, and CD95high-expressing glioblastoma neurospheres. CD95 stimulation of cancer cells induced secretion of type I interferons (IFNs) that bind to type I IFN receptors, resulting in activation of Janus-activated kinases, activation of STAT1, and induction of a number of STAT1-regulated genes that are part of a gene signature recently linked to therapy resistance in five primary human cancers. Consequently, we identified type I IFNs as drivers of cancer stemness. Knockdown or knockout of STAT1 resulted in a strongly reduced ability of CD95L or type I IFN to increase cancer stemness. This identifies STAT1 as a key regulator of the CSC-inducing activity of CD95.
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Chronic stimulation of the death receptor CD95/Fas by CD95 ligand induces cancer stemness. Qadir et al. report that this activity involves induction of type I interferons followed by activation of STAT1 and Janus kinases downstream of the type I interferon receptors.http://ift.tt/2lVbKCX
MAP3K4 Controls the Chromatin Modifier HDAC6 during Trophoblast Stem Cell Epithelial-to-Mesenchymal Transition
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Robert J. Mobley, Deepthi Raghu, Lauren D. Duke, Kayley Abell-Hart, Jon S. Zawistowski, Kyla Lutz, Shawn M. Gomez, Sujoy Roy, Ramin Homayouni, Gary L. Johnson, Amy N. Abell
The first epithelial-to-mesenchymal transition (EMT) occurs in trophoblast stem (TS) cells during implantation. Inactivation of the serine/threonine kinase MAP3K4 in TS cells (TSKI4 cells) induces an intermediate state of EMT, where cells retain stemness, lose epithelial markers, and gain mesenchymal characteristics. Investigation of relationships among MAP3K4 activity, stemness, and EMT in TS cells may reveal key regulators of EMT. Here, we show that MAP3K4 activity controls EMT through the ubiquitination and degradation of HDAC6. Loss of MAP3K4 activity in TSKI4 cells results in elevated HDAC6 expression and the deacetylation of cytoplasmic and nuclear targets. In the nucleus, HDAC6 deacetylates the promoters of tight junction genes, promoting the dissolution of tight junctions. Importantly, HDAC6 knockdown in TSKI4 cells restores epithelial features, including cell-cell adhesion and barrier formation. These data define a role for HDAC6 in regulating gene expression during transitions between epithelial and mesenchymal phenotypes.
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Mobley et al. find that HDAC6 is regulated by MAP3K4 during trophoblast stem cell differentiation and EMT. MAP3K4 promotes HDAC6 ubiquitination and degradation, maintaining the epithelial state. During EMT, HDAC6 directly deacetylates histones on epithelial gene promoters such as claudin6 and occludin, promoting the dissolution of tight junctions.http://ift.tt/2lVewrQ
A Bach2-Cebp Gene Regulatory Network for the Commitment of Multipotent Hematopoietic Progenitors
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Ari Itoh-Nakadai, Mitsuyo Matsumoto, Hiroki Kato, Junichi Sasaki, Yukihiro Uehara, Yuki Sato, Risa Ebina-Shibuya, Mizuho Morooka, Ryo Funayama, Keiko Nakayama, Kyoko Ochiai, Akihiko Muto, Kazuhiko Igarashi
Hematopoietic stem cell and multipotent progenitor (MPP) commitment can be tuned in response to an infection so that their differentiation is biased toward myeloid cells. Here, we find that Bach2, which inhibits myeloid differentiation in common lymphoid progenitors, represses a cohort of myeloid genes and activates those linked to lymphoid function. Bach2 repressed both Cebpb and its target Csf1r, encoding C/EBPβ and macrophage colony-stimulating factor receptor (M-CSFr), respectively, whereas C/EBPβ repressed Bach2 and activated Csf1r. Bach2 and C/EBPβ further bound to overlapping regulatory regions at their myeloid target genes, suggesting the presence of a gene regulatory network (GRN) with mutual repression between these factors and a feedforward loop leading to myeloid gene regulation. Lipopolysaccharide reduced the expression of Bach2, resulting in enhanced myeloid differentiation. The Bach2-C/EBPβ GRN pathway thus tunes MPP commitment to myeloid and lymphoid lineages both under normal conditions and after infection.
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Microbes skew the balance of innate and acquired immune cells. Itoh-Nakadai et al. report that Bach2 and C/EBP form a gene regulatory network with mutual repression and antagonistic, feedforward regulation of myeloid genes. Bach2 tunes the commitment of multipotent progenitors to myeloid and lymphoid lineages under both normal and infectious conditions.http://ift.tt/2lVpuxp
Macrophage Death following Influenza Vaccination Initiates the Inflammatory Response that Promotes Dendritic Cell Function in the Draining Lymph Node
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Nikolaos Chatziandreou, Yagmur Farsakoglu, Miguel Palomino-Segura, Rocco D'Antuono, Diego Ulisse Pizzagalli, Federica Sallusto, Veronika Lukacs-Kornek, Mariagrazia Uguccioni, Davide Corti, Shannon J. Turley, Antonio Lanzavecchia, Michael C. Carroll, Santiago F. Gonzalez
The mechanism by which inflammation influences the adaptive response to vaccines is not fully understood. Here, we examine the role of lymph node macrophages (LNMs) in the induction of the cytokine storm triggered by inactivated influenza virus vaccine. Following vaccination, LNMs undergo inflammasome-independent necrosis-like death that is reliant on MyD88 and Toll-like receptor 7 (TLR7) expression and releases pre-stored interleukin-1α (IL-1α). Furthermore, activated medullary macrophages produce interferon-β (IFN-β) that induces the autocrine secretion of IL-1α. We also found that macrophage depletion promotes lymph node-resident dendritic cell (LNDC) relocation and affects the capacity of CD11b+ LNDCs to capture virus and express co-stimulatory molecules. Inhibition of the IL-1α-induced inflammatory cascade reduced B cell responses, while co-administration of recombinant IL-1α increased the humoral response. Stimulation of the IL-1α inflammatory pathway might therefore represent a strategy to enhance antigen presentation by LNDCs and improve the humoral response against influenza vaccines.
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The mechanism by which inflammation influences the antibody response to vaccines is unclear. Chatziandreou et al. found that lymph node macrophages are key players in the initiation of the IL-1α-mediated inflammatory response that follows influenza vaccination.http://ift.tt/2lVewbk
Distinct Kinase-Independent Role of RIPK3 in CD11c+ Mononuclear Phagocytes in Cytokine-Induced Tissue Repair
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Kenta Moriwaki, Sakthi Balaji, John Bertin, Peter J. Gough, Francis Ka-Ming Chan
Receptor interacting protein kinase 3 (RIPK3) induces necroptosis, a type of regulated necrosis, through its kinase domain and receptor interacting protein (RIP) homotypic interaction motif (RHIM). In addition, RIPK3 has been shown to regulate NLRP3 inflammasome and nuclear factor κB (NF-κB) activation. However, the relative contribution of these signaling pathways to RIPK3-dependent inflammation in distinct immune effectors is unknown. To investigate these questions, we generated RIPK3-GFP reporter mice. We found that colonic CD11c+CD11b+CD14+ mononuclear phagocytes (MNPs) expressed the highest level of RIPK3 in the lamina propria. Consequently, deletion of the RIPK3 RHIM in CD11c+ cells alone was sufficient to impair dextran sodium sulfate (DSS)-induced interleukin (IL)-23 and IL-1β expression, leading to severe intestinal inflammation. In contrast, mice expressing kinase inactive RIPK3 were not hypersensitive to DSS. Thus, a key physiological function of RIPK3 is to promote reparative cytokine expression through intestinal CD11c+ MNPs in a kinase- and necroptosis-independent manner.
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Moriwaki et al. demonstrate that RIPK3 promotes cytokine production in CD11c+ mononuclear phagocytes in an RHIM-dependent, but kinase-independent manner. This necroptosis-independent function of RIPK3 is crucial for tissue repair in response to intestinal injury.http://ift.tt/2lVkuZT
Anterograde Transport of Rab4-Associated Vesicles Regulates Synapse Organization in Drosophila
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Swagata Dey, Gary Banker, Krishanu Ray
Local endosomal recycling at synapses is essential to maintain neurotransmission. Rab4GTPase, found on sorting endosomes, is proposed to balance the flow of vesicles among endocytic, recycling, and degradative pathways in the presynaptic compartment. Here, we report that Rab4-associated vesicles move bidirectionally in Drosophila axons but with an anterograde bias, resulting in their moderate enrichment at the synaptic region of the larval ventral ganglion. Results from FK506 binding protein (FKBP) and FKBP-Rapamycin binding domain (FRB) conjugation assays in rat embryonic fibroblasts together with genetic analyses in Drosophila indicate that an association with Kinesin-2 (mediated by the tail domain of Kinesin-2α/KIF3A/KLP64D subunit) moves Rab4-associated vesicles toward the synapse. Reduction in the anterograde traffic of Rab4 causes an expansion of the volume of the synapse-bearing region in the ventral ganglion and increases the motility of Drosophila larvae. These results suggest that Rab4-dependent vesicular traffic toward the synapse plays a vital role in maintaining synaptic balance in this neuronal network.
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Dey et al. show that in Drosophila larvae, binding to the Kinesin-2α tail propels Rab4-associated vesicles toward the synapse. Reduced Rab4 transport expands the synapse-bearing region of the ventral ganglion and enhances larval motility. Hence, Kinesin-2-mediated Rab4 trafficking appears to regulate synapse homeostasis in a neuronal network.http://ift.tt/2lVe2SA
Agrin as a Mechanotransduction Signal Regulating YAP through the Hippo Pathway
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Sayan Chakraborty, Kizito Njah, Ajaybabu V. Pobbati, Ying Bena Lim, Anandhkumar Raju, Manikandan Lakshmanan, Vinay Tergaonkar, Chwee Teck Lim, Wanjin Hong
The Hippo pathway effectors YAP and TAZ act as nuclear sensors of mechanical signals in response to extracellular matrix (ECM) cues. However, the identity and nature of regulators in the ECM and the precise pathways relaying mechanoresponsive signals into intracellular sensors remain unclear. Here, we uncover a functional link between the ECM proteoglycan Agrin and the transcriptional co-activator YAP. Importantly, Agrin transduces matrix and cellular rigidity signals that enhance stability and mechanoactivity of YAP through the integrin-focal adhesion- and Lrp4/MuSK receptor-mediated signaling pathways. Agrin antagonizes focal adhesion assembly of the core Hippo components by facilitating ILK-PAK1 signaling and negating the functions of Merlin and LATS1/2. We further show that Agrin promotes oncogenesis through YAP-dependent transcription and is clinically relevant in human liver cancer. We propose that Agrin acts as a mechanotransduction signal in the ECM.
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Chakraborty et al. report that the extracellular matrix protein Agrin is a mechanotransducing signal activating YAP through the integrin-focal adhesion-Lrp4/MuSK receptor pathway. Agrin signals matrix and cellular rigidity by activating FAK-ILK-PAK1 signaling that negates the Hippo tumor-suppressor pathway. Importantly, Agrin relies on YAP for oncogenic activities underlying liver cancer.http://ift.tt/2lVidxQ
Integrin Beta 3 Regulates Cellular Senescence by Activating the TGF-β Pathway
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Valentina Rapisarda, Michela Borghesan, Veronica Miguela, Vesela Encheva, Ambrosius P. Snijders, Amaia Lujambio, Ana O'Loghlen
Cellular senescence is an important in vivo mechanism that prevents the propagation of damaged cells. However, the precise mechanisms regulating senescence are not well characterized. Here, we find that ITGB3 (integrin beta 3 or β3) is regulated by the Polycomb protein CBX7. β3 expression accelerates the onset of senescence in human primary fibroblasts by activating the transforming growth factor β (TGF-β) pathway in a cell-autonomous and non-cell-autonomous manner. β3 levels are dynamically increased during oncogene-induced senescence (OIS) through CBX7 Polycomb regulation, and downregulation of β3 levels overrides OIS and therapy-induced senescence (TIS), independently of its ligand-binding activity. Moreover, cilengitide, an αvβ3 antagonist, has the ability to block the senescence-associated secretory phenotype (SASP) without affecting proliferation. Finally, we show an increase in β3 levels in a subset of tissues during aging. Altogether, our data show that integrin β3 subunit is a marker and regulator of senescence.
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Rapisarda et al. show that integrin β3 subunit expression induces senescence by activating TGF-β, while β3 knockdown overcomes senescence. β3 is dynamically upregulated in OIS and has ligand-independent activity. They also find a positive correlation between β3 levels and aging in a subset of tissues.http://ift.tt/2lVpvkV
Negative Regulators of an RNAi-Heterochromatin Positive Feedback Loop Safeguard Somatic Genome Integrity in Tetrahymena
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Jan H. Suhren, Tomoko Noto, Kensuke Kataoka, Shan Gao, Yifan Liu, Kazufumi Mochizuki
RNAi-mediated positive feedback loops are pivotal for the maintenance of heterochromatin, but how they are downregulated at heterochromatin-euchromatin borders is not well understood. In the ciliated protozoan Tetrahymena, heterochromatin is formed exclusively on the sequences that are removed from the somatic genome by programmed DNA elimination, and an RNAi-mediated feedback loop is important for assembling heterochromatin on the eliminated sequences. In this study, we show that the heterochromatin protein 1 (HP1)-like protein Coi6p, its interaction partners Coi7p and Lia5p, and the histone demethylase Jmj1p are crucial for confining the production of small RNAs and the formation of heterochromatin to the eliminated sequences. The loss of Coi6p, Coi7p, or Jmj1p causes ectopic DNA elimination. The results provide direct evidence for the existence of a dedicated mechanism that counteracts a positive feedback loop between RNAi and heterochromatin at heterochromatin-euchromatin borders to maintain the integrity of the somatic genome.
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Regulation of a small RNA-mediated positive feedback loop is pivotal for confining heterochromatin to proper locations. Suhren et al. show the existence of a dedicated mechanism that counteracts a small RNA-heterochromatin positive feedback loop at heterochromatin-euchromatin borders to maintain the integrity of the somatic genome in Tetrahymena.http://ift.tt/2lVgoRe
Reversal of DDK-Mediated MCM Phosphorylation by Rif1-PP1 Regulates Replication Initiation and Replisome Stability Independently of ATR/Chk1
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Robert C. Alver, Gaganmeet Singh Chadha, Peter J. Gillespie, J. Julian Blow
Dbf4-dependent kinases (DDKs) are required for the initiation of DNA replication, their essential targets being the MCM2-7 proteins. We show that, in Xenopus laevis egg extracts and human cells, hyper-phosphorylation of DNA-bound Mcm4, but not phosphorylation of Mcm2, correlates with DNA replication. These phosphorylations are differentially affected by the DDK inhibitors PHA-767491 and XL413. We show that DDK-dependent MCM phosphorylation is reversed by protein phosphatase 1 (PP1) targeted to chromatin by Rif1. Loss of Rif1 increased MCM phosphorylation and the rate of replication initiation and also compromised the ability of cells to block initiation when challenged with replication inhibitors. We also provide evidence that Rif1 can mediate MCM dephosphorylation at replication forks and that the stability of dephosphorylated replisomes strongly depends on Chk1 activity. We propose that both replication initiation and replisome stability depend on MCM phosphorylation, which is maintained by a balance of DDK-dependent phosphorylation and Rif1-mediated dephosphorylation.
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Teaser
Alver et al. find that DDK-dependent MCM2-7 phosphorylation is opposed by Rif1-targeted PP1. Lack of Rif1 increases MCM phosphorylation and abolishes the ability to block origin firing, even when undergoing replication stress. In the absence of CHK1, the stability of stalled replisomes is severely compromised upon Rif-PP1-mediated dephosphorylation.http://ift.tt/2lVcLek
Unsupervised Spike Sorting for Large-Scale, High-Density Multielectrode Arrays
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Gerrit Hilgen, Martino Sorbaro, Sahar Pirmoradian, Jens-Oliver Muthmann, Ibolya Edit Kepiro, Simona Ullo, Cesar Juarez Ramirez, Albert Puente Encinas, Alessandro Maccione, Luca Berdondini, Vittorio Murino, Diego Sona, Francesca Cella Zanacchi, Evelyne Sernagor, Matthias Helge Hennig
We present a method for automated spike sorting for recordings with high-density, large-scale multielectrode arrays. Exploiting the dense sampling of single neurons by multiple electrodes, an efficient, low-dimensional representation of detected spikes consisting of estimated spatial spike locations and dominant spike shape features is exploited for fast and reliable clustering into single units. Millions of events can be sorted in minutes, and the method is parallelized and scales better than quadratically with the number of detected spikes. Performance is demonstrated using recordings with a 4,096-channel array and validated using anatomical imaging, optogenetic stimulation, and model-based quality control. A comparison with semi-automated, shape-based spike sorting exposes significant limitations of conventional methods. Our approach demonstrates that it is feasible to reliably isolate the activity of up to thousands of neurons and that dense, multi-channel probes substantially aid reliable spike sorting.
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Data volume and complexity make spike sorting for large-scale extracellular recordings computationally extremely challenging. Hilgen et al. introduce a method enabling analysis of recordings with thousands of channels and provide tools for automated quality control and unit selection.http://ift.tt/2lVfR1O
A Knockin Reporter Allows Purification and Characterization of mDA Neurons from Heterogeneous Populations
Publication date: 7 March 2017
Source:Cell Reports, Volume 18, Issue 10
Author(s): Ninuo Xia, Fang Fang, Pengbo Zhang, Jun Cui, Chhavy Tep-Cullison, Tim Hamerley, Hyun Joo Lee, Theo Palmer, Brian Bothner, Jin Hyung Lee, Renee Reijo Pera
Generation of midbrain dopaminergic (mDA) neurons from human pluripotent stem cells provides a platform for inquiry into basic and translational studies of Parkinson's disease (PD). However, heterogeneity in differentiation in vitro makes it difficult to identify mDA neurons in culture or in vivo following transplantation. Here, we report the generation of a human embryonic stem cell (hESC) line with a tyrosine hydroxylase (TH)-RFP (red fluorescent protein) reporter. We validated that RFP faithfully mimicked TH expression during differentiation. Use of this TH-RFP reporter cell line enabled purification of mDA-like neurons from heterogeneous cultures with subsequent characterization of neuron transcriptional and epigenetic programs (global binding profiles of H3K27ac, H3K4me1, and 5-hydroxymethylcytosine [5hmC]) at four different stages of development. We anticipate that the tools and data described here will contribute to the development of mDA neurons for applications in disease modeling and/or drug screening and cell replacement therapies for PD.
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Xia et al. create a knockin human tyrosine hydroxylase (TH) reporter line to isolate TH-positive dopaminergic neurons from heterogeneous population and examine their transcriptional landscape.http://ift.tt/2lVpv4p
The role of thoracodorsal artery perforator flap in oncoplastic breast surgery
Publication date: Available online 6 March 2017
Source:Journal of the Egyptian National Cancer Institute
Author(s): Ayman A. Amin, Mohamed Rifaat, Ahmed Farahat, Tarek Hashem
Background and aimThoracodorsal artery perforator flap (TDAP) is one of the relatively new techniques in breast reconstruction. In this study, we try to evaluate the outcome of this flap in oncoplastic procedures.MethodsThis study included 40 patients of stage II breast cancer who underwent partial mastectomy with skin excision at the National Cancer Institute of Cairo University between 2011 and 2014. The resultant defects were immediately reconstructed using the thoracodorsal artery perforator flap. Operative time and complication rates were recorded. The cosmetic outcome was assessed through a questionnaire.ResultsThe mean operative time was 227min. The total complication rate was 20% with flap congestion being the most common complication. The cosmetic outcome was acceptable with 80% of patients rating their outcome as either good or excellent. The subjectively assessed functional outcome showed a mean time of 10days postoperative for patients to regain their full range of shoulder movements.ConclusionThoracodorsal artery perforator flap can play a significant role in oncoplastic surgery and breast reconstruction with acceptable cosmetic and functional outcome.
http://ift.tt/2mUUaDX
Influence of humidity on the removal of volatile organic compounds using solid surfaces
Publication date: Available online 6 March 2017
Source:Catalysis Today
Author(s): Eun Ji Park, Hyun Ook Seo, Young Dok Kim
In recent years, much attention has been devoted to understand how the humidity affects the volatile organic compound (VOC) removal efficiencies using absorbents, photocatalysts or dark-catalysts and both positive and negative effects of humidity on VOC removal have been reported. We show that sorption capability of VOCs of absorbents with high surface areas can be significantly reduced by the competitive adsorption with water in the air and, by hydrophobically modifying the absorbent surfaces, selective sorption of VOCs to water molecules is achieved. For the TiO2 photocatalysts, humidity was found to have both positive and negative effects on catalytic activity; humidity facilitates the total oxidation of toluene to CO2 allowing the long-term stability of the catalytic activity, on the other hand, reduces the adsorption of VOCs on the catalyst surface. By depositing TiO2 islands on hydrophilic nanodiamond nanoparticles, positive effect of humidity becomes more pronounced. Positive and negative effects of humidity analogous to those on photocatalyst were also observed for the dark-catalysts, NiO nanoparticle decorated mesoporous silica. TiO2 interlayer with a high affinity toward toluene was applied between SiO2 and NiO and, as a result, negative effect of humidity, reduction of toluene adsorption in the presence on water, is suppressed.
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http://ift.tt/2lZUOMg
Carbon nanodots: mechanisms of photoluminescence and principles of application
Publication date: Available online 6 March 2017
Source:TrAC Trends in Analytical Chemistry
Author(s): Irina Yu. Goryacheva, Andrei V. Sapelkin, Gleb B. Sukhorukov
Carbon nanoparticles are relatively new and promising area of research receiving increasingly growing attention. They are small, cheap to produce, and do not contain potentially toxic components while showing bright and tunable light emission. They can thus potentially replace inorganic quantum dots in applications such as bioimaging, solar cells, photocatalysis and sensor applications. Units of nanometer size carbon dots (CDs) stable in aqueous solutions with photoluminescence in visible range can be obtained in one-step synthesis from variety of available materials. Currently, application of CDs is restricted by the lack of understanding of fundamental relationship between synthesis routes (and ingredients including raw materials), CDs' structure and CDs' properties. This review is focused on evaluating recent trends in CDs research and application, including CDs synthesis, understanding of their photoluminescent properties. We also discuss the principles, perspectives and current limitations in CDs applications.
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http://ift.tt/2m01euM
Preface
Publication date: March 2017
Source:Journal of Photochemistry and Photobiology C: Photochemistry Reviews, Volume 30
Author(s): Takashi Hirano, Takehiko Wada
http://ift.tt/2m03KkQ
Electroacupuncture improves gait locomotion, H-reflex and ventral root potentials of spinal compression injured rats
Source:Brain Research Bulletin
Author(s): Carlos Escobar-Corona, Sergio Torres-Castillo, Erika Elizabeth Rodríguez-Torres, Bertha Segura-Alegría, Ismael Jiménez-Estrada, Salvador Quiroz-González
This study explored the effect of electroacupuncture stimulation (EA) on alterations in the Hoffman reflex (H-reflex) response and gait locomotion provoked by spinal cord injury (SCI) in the rat. A compression lesion of the spinal cord was evoked by insufflating a Fogarty balloon located in the epidural space at the T8–9 spinal level of adult Wistar male rats (200-250 gr; n=60). In different groups of SCI rats, EA (frequencies: 2, 50 and 100Hz) was applied simultaneously to Huantiao (GB30), Yinmen (BL37), Jizhong (GV6) and Zhiyang (GV9) acupoints from the third post-injury day until the experimental session. At 1, 2, 3 and 4 post-injury weeks, the BBB scores of the SCI group of rats treated with EA at 50Hz showed a gradual but greater enhancement of locomotor activity than the other groups of rats. Unrestrained gait kinematic analysis of SCI rats treated with EA–50Hz stimulation showed a significant improvement in stride duration, length and speed (p<0.05), whereas a discrete recovery of gait locomotion was observed in the other groups of animals. After four post-injury weeks, the H-reflex amplitude and H-reflex/M wave amplitude ratio obtained in SCI rats had a noticeable enhancement (217%) compared to sham rats (n=10). Meanwhile, SCI rats treated with EA at 50Hz manifested a decreased facilitation of the H-reflex amplitude and H/M amplitude ratio (154%) and a reduced frequency-dependent amplitude depression of the H-reflex (66%). In addition, 50 Hz-EA treatment induced a recovery of the presynaptic depression of the Gs-VRP evoked by PBSt conditioning stimulation in the SCI rat (63.2±8.1%; n=9). In concordance with the latter, it could be suggested that 50 Hz-EA stimulation reduced the hyper-excitability of motoneurons and provokes a partial improvement of the locomotive performance and H reflex responses by a possible recovery of presynaptic mechanisms in the spinal cord of experimentally injured rats.
http://ift.tt/2mUypEb
Altered functional efficacy of hippocampal interneuron during epileptogenesis following febrile seizures
Source:Brain Research Bulletin
Author(s): Yeon Hee Yu, Kahyun Lee, Dal Sik Sin, Kyung-Ho Park, Dae-Kyoon Park, Duk-Soo Kim
Febrile seizure (FS) is the most common seizure type in infants and young children. FS may induce functional changes in the hippocampal circuitries. Abnormality of excitatory and inhibitory neurotransmissions was previously related to wide-spread seizure attack in the hippocampus following recurrent seizure onset. To clarify the involvement of expressional changes and functional alterations of hippocampal interneurons with epileptogenesis following FS, we investigated long-term effects following recurrent seizure in a hyperthermia-induced seizure animal model. At 12 weeks following FS, the recurrent seizure time period, local field potentials (LFP) revealed high amplitude potential and a sharp wave characteristic of epilepsy. Mossy fiber reorganization in the hippocampus was also detected as abnormal synaptic connection at 8 weeks. Calretinin (CR) −positive interneurons were transiently enhanced during epileptogenic period at 7-9 weeks after FS in the CA1 and DG region and it is double labeled with VGLUT-1. However, although GABAA-α1 immunoreactivities were un-changed as similar to control hippocampus at 7-9 weeks after seizure onset, its expression was significantly enhanced at 4 weeks and 12 weeks and it is colocalized with GABA. Furthermore, the field excitatory postsynaptic potential (fEPSP) and the paired-pulse responses including population spike (PS) latency, excitability ratio and PS2/PS1 ratio were markedly altered in the CA1 and DG region at 12 weeks after FS. Therefore, our findings in present study indicate that these time-dependent changes may be based on the persistent alterations of hippocampal neuronal circuits in balance between excitatory and inhibitory responses, and may lead to the epileptogenesis and spread of seizure activity following FS.
http://ift.tt/2lUQoWq
Possible role of endothelin receptor against hyperhomocysteinemia and β-amyloid induced AD type of vascular dementia in rats
Source:Brain Research Bulletin
Author(s): Major Singh, Atish Prakash
Vascular dementia (VaD) is considered as the second commonest form of dementia after Alzheimer's disease (AD). The study was designed to investigate the effect of endothelin receptor against β-amyloid induced AD type of vascular dementia. This disease was induced by combine administration of single ICV (intracerebroventricle) infusion of β-amyloid (Aβ) once and chronic oral administration of L-Methionine for 21 days. Bosentan (dual endothelin receptor antagonist) was administered for 21 days. Behavioral alterations were observed during different time interval of the study. Animals were killed immediately following the last behavior session. Oxidative parameters, acetylcholinesterase activity, neuro-inflammatory markers, amyloid beta levels were determined in hippocampus and cortex while serum homocysteine, serum nitrite carotid artery superoxide anion level were also determined. Endothelial function was measured on isolated carotid artery using myograph instrument. Aβ+L-Methionine showed more significant development of cognitive and vascular endothelial deficits, manifested in terms of increase in serum homocysteine level, endothelial dysfunction, impairment of learning and memory, enhanced brain acetylcholinesterase activity, marked mito-oxidative damage in rats. We have observed that L-Methionine and combination of Aβ+L-Methionine significantly enhanced Aβ level both in cortex as well as hippocampus. Treatment of bosentan attenuated Aβ+L-Methionine induced impairment of learning and memory, enhanced Aβ level, mitochondrial and endothelial dysfunction. The results of present study concluded that bosentan offers protection against β-amyloid-induced vascular dementia in rats. Endothelin receptor may be considered as a potential pharmacological target for the management of AD type of vascular dementia.
http://ift.tt/2mUzqwh
The role of aquaporin-4 in synaptic plasticity, memory and disease
Source:Brain Research Bulletin
Author(s): Jacqueline A. Hubbard, Jenny I. Szu, Devin K. Binder
Since the discovery of aquaporins, it has become clear that the various mammalian aquaporins play critical physiological roles in water and ion balance in multiple tissues. Aquaporin-4 (AQP4), the principal aquaporin expressed in the central nervous system (CNS, brain and spinal cord), has been shown to mediate CNS water homeostasis. In this review, we summarize new and exciting studies indicating that AQP4 also plays critical and unanticipated roles in synaptic plasticity and memory formation. Next, we consider the role of AQP4 in Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), multiple sclerosis (MS), neuromyelitis optica (NMO), epilepsy, traumatic brain injury (TBI), and stroke. Each of these conditions involves changes in AQP4 expression and/or distribution that may be functionally relevant to disease physiology. Insofar as AQP4 is exclusively expressed on astrocytes, these data provide new evidence of "astrocytopathy" in the etiology of diverse neurological diseases.
http://ift.tt/2lUXo5p
Nutritional Status of Rural Older Adults Is Linked to Physical and Emotional Health
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Seung Eun Jung, Alex J. Bishop, Minjung Kim, Janice Hermann, Giyeon Kim, Jeannine Lawrence
BackgroundAlthough nutritional status is influenced by multidimensional aspects encompassing physical and emotional well-being, there is limited research on this complex relationship.ObjectiveThe purpose of this study was to examine the interplay between indicators of physical health (perceived health status and self-care capacity) and emotional well-being (depressive affect and loneliness) on rural older adults' nutritional status.DesignThe cross-sectional study was conducted from June 1, 2007, to June 1, 2008.Participants/settingA total of 171 community-dwelling older adults, aged 65 years and older, residing within nonmetro rural communities in the United States participated in this study.Main outcome measuresParticipants completed validated instruments measuring self-care capacity, perceived health status, loneliness, depressive affect, and nutritional status.Statistical analyses performedStructural equation modeling was employed to investigate the complex interplay of physical and emotional health status with nutritional status among rural older adults. The χ2 test, comparative fit index, root mean square error of approximation, and standardized root mean square residual were used to assess model fit.ResultsThe χ2 test and the other model fit indexes showed the hypothesized structural equation model provided a good fit to the data (χ2 (2)=2.15; P=0.34; comparative fit index=1.00; root mean square error of approximation=0.02; and standardized root mean square residual=0.03). Self-care capacity was significantly related with depressive affect (γ=–0.11; P=0.03), whereas self-care capacity was not significantly related with loneliness. Perceived health status had a significant negative relationship with both loneliness (γ=–0.16; P=0.03) and depressive affect (γ=–0.22; P=0.03). Although loneliness showed no significant direct relationship with nutritional status, it showed a significant direct relationship with depressive affect (β=.4; P<0.01). Finally, the results demonstrated that depressive affect had a significant negative relationship with nutritional status (β=–.30; P<0.01). The results indicated physical health and emotional indicators have significant multidimensional associations with nutritional status among rural older adults.ConclusionsThe present study provides insights into the importance of addressing both physical and emotional well-being together to reduce potential effects of poor emotional well-being on nutritional status, particularly among rural older adults with impaired physical health and self-care capacity.
http://ift.tt/2lUAo6B
Exploring the Role of Sugar-Sweetened Beverage Consumption in Obesity among New Yorkers Using Propensity Score Matching
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Marissa Burgermaster, Hiershenee Bhana, M. Dot Fullwood, Diego A. Luna Bazaldua, Elizabeth Tipton
BackgroundResults from clinical trials have shown that sugar-sweetened beverages (SSBs) lead to increased body mass index (BMI) and obesity. This relationship has yet to be explored in observational data for nonclinical populations of adults.ObjectiveTo compare adults who drank 4+ SSBs daily to those who drank 0 in the population of adults in New York City, and to better understand adult risk factors associated with higher daily SSB consumption and BMI.DesignSecondary analysis of cross-sectional data using propensity score matching.Participants/settingThe 2009 New York City Community Health Survey (N=9,934) was used.Main outcome measureBMI.Statistical analysesFor each participant who consumed 4+ SSBs daily, propensity score matching identified matched comparisons who did not drink any SSBs. BMI in unadjusted and matched pairs was tested using t tests. A post hoc analysis compared features of those likely to drink SSBs and those not likely to drink SSBs.ResultsIn unmatched analyses, participants who consumed 4+ SSBs daily (n=475) had higher BMI than those who consumed 0 SSBs (n=3,818; BMI difference=1.4±0.29; t value=4.81; P<0.001); however, when compared with similar participants using nearest neighbor with replacement matching (n=1,062), the difference between those who consumed 4+ SSBs daily and those who consumed none decreased (BMI difference=0.37±0.36; t value=1.01; P=0.32). Analyses also indicated that those likely to drink SSBs and those unlikely to drink SSBs differed in several important characteristics, including sex, age, race, ethnicity, socioeconomic status, education, diet, and exercise.ConclusionsThe data preclude strong causal conclusions about the role of SSB in obesity. However, our results suggest that there is a subset of participants demographically and behaviorally similar with higher BMI regardless of their self-reported SSB intake. In addition to targeting SSBs, public health policies and programs should identify and address other modifiable aspects of this profile and tailor approaches to the groups identified to be most affected by high BMI.
http://ift.tt/2lBzJvw
Gender Disparities in the Food Insecurity–Overweight and Food Insecurity–Obesity Paradox among Low-Income Older Adults
Publication date: Available online 6 March 2017
Source:Journal of the Academy of Nutrition and Dietetics
Author(s): Daphne C. Hernandez, Layton Reesor, Rosenda Murillo
BackgroundObesity and obesity-related comorbidities are increasing among older adults. Food insecurity is a nutrition-related factor that coexists with obesity among low-income individuals. The majority of the research on the food insecurity–obesity paradox has been conducted on low-income mothers and children, with research lacking on large diverse samples of older adults.ObjectiveThe purpose of this study was to assess gender disparities in the association between food insecurity and overweight and obesity among low-income older adults.Study designCross-sectional 2011 and 2012 National Health Interview Survey data were used. Food insecurity status was determined by ≥3 affirmative responses on the 10-item US Department of Agriculture Food Security Scale (FSS). Body mass index (BMI) was calculated as outlined by the Centers for Disease Control and Prevention based on self-reported height and weight.Participants/settingsAdults included were low-income (≤1.99 federal poverty level [FPL]), older (aged ≥60 years), with a normal BMI (18.5) or greater who had complete data on FSS, BMI, and the following covariates: age, race or ethnicity, marital status, income, nativity status, physical activity, poor health status, health insurance coverage, problems paying medical bills or for medicine, and region of residency (N=5,506).Statistical analyses performedMultivariate logistic regression models were stratified by gender to estimate the association between food insecurity and higher weight status. All models included covariates.ResultsIn covariate-adjusted models, compared with low-income, food secure men, low-income, food-insecure men had 42% and 41% lower odds of being overweight and overweight or obese, respectively. Despite the high prevalence rate of obesity among low-income, food-insecure women, food insecurity was not significantly related to overweight, obesity, or overweight or obesity for older adult women in adjusted models.ConclusionsFood insecurity–overweight and –obesity paradox appears not to be present in older men. However, food insecurity and obesity coexist among low-income, older women.
http://ift.tt/2lUFsYK
The addition of silica nanoparticles on the mechanical properties of dental stone
Publication date: Available online 6 March 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Leonardo De Cesero, Elisa Magno Nunes de Oliveira, Luiz Henrique Burnett Junior, Ricardo Meurer Papaléo, Eduardo Gonçalves Mota
Statement of problemThe current application of nanotechnology in dentistry is limited to nanoparticles incorporated into adhesive systems and composite resins. Dental stone is a widely used material, and the incorporation of silica nanoparticles is still unexplored.PurposeThe purpose of this in vitro study was to evaluate the mechanical properties of dental stone after the addition of silica nanoparticles in different concentrations.Material and methodsA total of 180 specimens were prepared, 90 for each dental stone (Durone and Fuji Rock). For the control group (CG), no silica particles were added, while test group TGnI had silica nanoparticles added to 1 wt%, and test group TGnV had silica nanoparticles added to 5 wt%. The roughness, diametral tensile strength (DTS), and compressive strength were measured 24 hours after the start of spatulation.ResultsThe mean roughness values for Durone were 0.55, 0.36, and 0.28 μm for CG, TGnI, and TGnV; for Fuji Rock, the mean roughness values were 0.47 for CG, 0.31 for TGnI, and 0.35 μm for TGnV. The mean DTS values for Durone were 6.0, 5.1, and 5.0 MPa for CG, TGnI, and TGnV, respectively, and for Fuji Rock, the mean DTS values were 6.4, 5.2, and 4.5 MPa for CG, TGnI, and TGnV, respectively. The mean compressive strength values for Durone were 35.4, 32.7, and 32.4 MPa for CG, TGnI, and TGnV, respectively, and for Fuji Rock, the mean compressive strength values were 42.9, 31.2, and 29.8 MPa for CG, TGnI, and TGnV respectively.ConclusionsSurface roughness was statistically lower for the Durone and Fuji Rock stones (P<.001) when silica nanoparticles were added. The addition of silica nanoparticles did not significantly affect the DTS and compressive strength of Durone compared with CG (P>.05) but did affect the DTS of Fuji Rock when 5 wt% was added and the compressive strength in both concentrations (P<.05).
http://ift.tt/2n30VAo
Combination antitumor therapy with targeted dual-nanomedicines
Publication date: Available online 7 March 2017
Source:Advanced Drug Delivery Reviews
Author(s): Wenbing Dai, Xiaoyou Wang, Ge Song, Tongzhou Liu, Bing He, Hua Zhang, Xueqing Wang, Qiang Zhang
Combination therapy is one of important treatment strategies for cancer at present. However, the outcome of current combination therapy based on the co- administration of conventional dosage forms is suboptimal, due to the short half-lives of chemodrugs, their deficient tumor selectivity and so forth. Nanotechnology-based targeted delivery systems show great promise in addressing the associated problems and providing superior therapeutic benefits. In this review, we focus on the combination therapeutic strategies between different nanomedicines or drug-loaded nanocarriers, rather than the co-delivery of different drugs via a single nanocarrier. We introduce the general concept of various targeting strategies of nanomedicines, present the principles of combination antitumor therapy with dual-nanomedicines, analyze their advantages and limitations compared with co-delivery strategies, and overview the recent advances of combination therapy based on targeted nanomedicines. Finally, we reviewed the challenges and future perspectives regarding the selection of therapeutic agents, targeting efficiency and the gap between the preclinical and clinical outcome.
Graphical abstract
http://ift.tt/2nbBoEp
Inhalation of progesterone inhibits chronic airway inflammation of mice exposed to ozone
Source:Molecular Immunology, Volume 85
Author(s): Xia Fei, Wuping Bao, Pengyu Zhang, Xue Zhang, Guoqing Zhang, Yingying Zhang, Xin Zhou, Min Zhang
Chronic ozone exposure leads to a model of mice with lung inflammation, emphysema and oxidative stress. Progesterone plays an important role in attenuating the neuroinflammation. We assume that progesterone will reduce the chronic airway inflammation exposed to ozone and evaluate whether combination of progesterone with glucocorticoids results in synergistic effects. C57/BL6 mice were exposed to ozone (2.5ppm, 3h) 12 times over 6 weeks, and were administered with progesterone (0.03 or 0.3mg/L; inhaled) alone or combined with budesonide (BUD) (0.2g/L) after each exposure until the tenth week. Mice were studied 24h after final exposure, cells and inflammatory mediators were assessed in bronchoalveolar lavage fluid (BALF) and lungs used for evaluation of glucocorticoids receptors (GR), p38 mitogen-activated protein kinase (MAPK) phosphorylation and nuclear transcription factor κB (NF-κB) activation. Exposure to ozone resulted in a marked lung neutrophilia. Moreover, in ozone-exposed group, the levels of oxidative stress-related interleukin (IL)-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, airway inflammatory cells infiltration density, mean linear intercept (Lm) were greatly increased, FEV25 and glucocorticoids receptors (GR) were markedly decreased. Comparable to BUD, progesterone treatment dose-dependently led to a significant reduction of IL-1β, IL-6, IL-8, IL-17A, activated NF-κB and p38MAPK, and an increase of FEV25 and GR. Progesterone combined with BUD resulted in dramatic changes, compared to monotherapy of BUD or progesterone. Therefore, these results demonstrate that chronic ozone exposure has profound airway inflammatory effects counteracted by progesterone and progesterone acts synergistically with glucocorticoids in attenuating the airway inflammation dose-dependently.
http://ift.tt/2nbiLQW
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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