Sir,
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Κυριακή 11 Φεβρουαρίου 2018
Stable Metal–Organic Frameworks: Design, Synthesis, and Applications
Abstract
Metal–organic frameworks (MOFs) are an emerging class of porous materials with potential applications in gas storage, separations, catalysis, and chemical sensing. Despite numerous advantages, applications of many MOFs are ultimately limited by their stability under harsh conditions. Herein, the recent advances in the field of stable MOFs, covering the fundamental mechanisms of MOF stability, design, and synthesis of stable MOF architectures, and their latest applications are reviewed. First, key factors that affect MOF stability under certain chemical environments are introduced to guide the design of robust structures. This is followed by a short review of synthetic strategies of stable MOFs including modulated synthesis and postsynthetic modifications. Based on the fundamentals of MOF stability, stable MOFs are classified into two categories: high-valency metal–carboxylate frameworks and low-valency metal–azolate frameworks. Along this line, some representative stable MOFs are introduced, their structures are described, and their properties are briefly discussed. The expanded applications of stable MOFs in Lewis/Brønsted acid catalysis, redox catalysis, photocatalysis, electrocatalysis, gas storage, and sensing are highlighted. Overall, this review is expected to guide the design of stable MOFs by providing insights into existing structures, which could lead to the discovery and development of more advanced functional materials.
Stable metal–organic frameworks (MOFs) with high resistance to harsh chemical environments are reviewed with regard to recent progress in their research and development. Fundamental mechanisms of MOF stability, design and synthesis of stable MOF architectures, and their latest applications are summarized, providing a fundamental outline for the discovery of new stable MOFs.
http://ift.tt/2CeA62P
Uncovering the Circular Polarization Potential of Chiral Photonic Cellulose Films for Photonic Applications
Abstract
Circularly polarized light (CPL) is central to photonic technologies. A key challenge lies in developing a general route for generation of CPL with tailored chiroptical activity using low-cost raw materials suitable for scale-up. This study presents that cellulose films with photonic bandgaps (PBG) and left-handed helical sense have an intrinsic ability for circular polarization leading to PBG-based CPL with extraordinary |g | values, well-defiend handedness, and tailorable wavelength by the PBG change. Using such cellulose films, incident light ranging from near-UV to near-IR can be transformed to passive L-CPL and R-CPL with viewing-side-dependent handedness and |g | values up to 0.87, and spontaneous emission transformed to R-CPL emission with |g | values up to 0.68. Unprecedented evidence is presented with theoretical underpinning that the PBG effect can stimulate the R-CPL emission. The potential of cellulose-based CPL films for polarization-based encryption is illustrated. The evaporation-induced self-assembly coupled with nanoscale mesogens of cellulose nanocrystals opens new venues for technological advances and enables a versatile strategy for rational design and scalable manufacturing of organic and inorganic CPL films for photonic applications.
Chiral photonic cellulose films have intrinsic ability to generate and manipulate circularly polarized light (CPL) with extraordinary |g | values in a broad spectral regime. The CPL handedness is well defined, and the wavelength control is simple to realize. Photonic bandgap effects cause stimulated CPL. It presents a versatile and scalable strategy for customized CPL materials using renewable cellulose for photonic applications.
http://ift.tt/2Ek0myt
Structural Engineering of 2D Nanomaterials for Energy Storage and Catalysis
Abstract
Research on 2D nanomaterials is rising to an unprecedented height and will continue to remain a very important topic in materials science. In parallel with the discovery of new candidate materials and exploration of their unique characteristics, there are intensive interests to rationally control and tune the properties of 2D nanomaterials in a predictable manner. Considerable attention is focused on modifying these materials structurally or engineering them into designed architectures to meet requirements for specific applications. Recent advances in such structural engineering strategies have demonstrated their ability to overcome current material limitations, showing great promise for promoting device performance to a new level in many energy-related applications. Existing in many forms, these strategies can be categorized based on how they intrinsically or extrinsically alter the pristine structure. Achieved through various synthetic routes and practiced in a range of different material systems, they usually share common descriptors that predestine them to be effective in certain circumstances. Therefore, understanding the underlying mechanism of these strategies to provide fundamental insights into structural design and property tailoring is of critical importance. Here, the most recent development of structural engineering of 2D nanomaterials and their significant effects in energy storage and catalysis technologies are addressed.
Structural engineering serves as an important material design concept and offers new inroads into the field of 2D nanomaterials, including both conventional material engineering methods and novel nanotechnology approaches. Recent progress of structural engineering strategies for 2D nanomaterials and their implications for advanced energy storage and catalysis technologies have been presented in this progress report.
http://ift.tt/2ChgHOM
Engineered Living Materials: Prospects and Challenges for Using Biological Systems to Direct the Assembly of Smart Materials
Abstract
Vast potential exists for the development of novel, engineered platforms that manipulate biology for the production of programmed advanced materials. Such systems would possess the autonomous, adaptive, and self-healing characteristics of living organisms, but would be engineered with the goal of assembling bulk materials with designer physicochemical or mechanical properties, across multiple length scales. Early efforts toward such engineered living materials (ELMs) are reviewed here, with an emphasis on engineered bacterial systems, living composite materials which integrate inorganic components, successful examples of large-scale implementation, and production methods. In addition, a conceptual exploration of the fundamental criteria of ELM technology and its future challenges is presented. Cradled within the rich intersection of synthetic biology and self-assembling materials, the development of ELM technologies allows the power of biology to be leveraged to grow complex structures and objects using a palette of bio-nanomaterials.
Engineered living materials (ELMs) harness cellular processes to assimilate energy, carbon, and other nutrients from their environment into the molecular building blocks of materials and assemble those building blocks into multiscale biomaterials. Relevant fundamental advances in genetic engineering, biosensing, and biomanufacturing are reviewed, in addition to examples of ELMs with autonomous, adaptive, and self-renewing characteristics.
http://ift.tt/2Emacjw
Structuring of Hydrogels across Multiple Length Scales for Biomedical Applications
Abstract
The development of new materials for clinical use is limited by an onerous regulatory framework, which means that taking a completely new material into the clinic can make translation economically unfeasible. One way to get around this issue is to structure materials that are already approved by the regulator, such that they exhibit very distinct physical properties and can be used in a broader range of clinical applications. Here, the focus is on the structuring of soft materials at multiple length scales by modifying processing conditions. By applying shear to newly forming materials, it is possible to trigger molecular reorganization of polymer chains, such that they aggregate to form particles and ribbon-like structures. These structures then weakly interact at zero shear forming a solid-like material. The resulting self-healing network is of particular use for a range of different biomedical applications. How these materials are used to allow the delivery of therapeutic entities (cells and proteins) and as a support for additive layer manufacturing of larger-scale tissue constructs is discussed. This technology enables the development of a range of novel materials and structures for tissue augmentation and regeneration.
Structured soft materials have the potential to revolutionize regenerative medicine. By imparting shear during processing, it is possible to take the small number of materials approved by medical regulators and create self-healing polymeric structures. How so-called fluid gels can facilitate the delivery of cells and proteins and enable additive layer manufacturing of complex biological structures is discussed.
http://ift.tt/2CeGzuk
Reassembly of 89Zr-Labeled Cancer Cell Membranes into Multicompartment Membrane-Derived Liposomes for PET-Trackable Tumor-Targeted Theranostics
Abstract
Nanoengineering of cell membranes holds great potential to revolutionize tumor-targeted theranostics, owing to their innate biocompatibility and ability to escape from the immune and reticuloendothelial systems. However, tailoring and integrating cell membranes with drug and imaging agents into one versatile nanoparticle are still challenging. Here, multicompartment membrane-derived liposomes (MCLs) are developed by reassembling cancer cell membranes with Tween-80, and are used to conjugate 89Zr via deferoxamine chelator and load tetrakis(4-carboxyphenyl) porphyrin for in vivo noninvasive quantitative tracing by positron emission tomography imaging and photodynamic therapy (PDT), respectively. Radiolabeled constructs, 89Zr-Df-MCLs, demonstrate excellent radiochemical stability in vivo, target 4T1 tumors by the enhanced permeability and retention effect, and are retained long-term for efficient and effective PDT while clearing gradually from the reticuloendothelial system via hepatobiliary excretion. Toxicity evaluation confirms that the MCLs do not impose acute or chronic toxicity in intravenously injected mice. Additionally, 89Zr-labeled MCLs can execute rapid and highly sensitive lymph node mapping, even for deep-seated sentinel lymph nodes. The as-developed cell membrane reassembling route to MCLs could be extended to other cell types, providing a versatile platform for disease theranostics by facilely and efficiently integrating various multifunctional agents.
Systematic noninvasive tracking and quantitative investigation of 89Zr-labeled multicompartment membrane-derived liposomes (89Zr-Df-MCLs) is performed to demonstrate rapid clearance of 89Zr-Df-MCLs, which is estimated to be over 63% injected dose (ID) at 72 h post-injection through the hepatobiliary route. 89Zr-Df-MCLs are developed as contrast agents for positron emission tomography for in vivo imaging of tumors and mapping of lymph nodes, as well as for fluorescence imaging and photodynamic therapy after loading with a porphyrin cargo.
http://ift.tt/2EkW3mA
Liquid-Crystalline Dynamic Networks Doped with Gold Nanorods Showing Enhanced Photocontrol of Actuation
Abstract
A near-infrared-light (NIR)- and UV-light-responsive polymer nanocomposite is synthesized by doping polymer-grafted gold nanorods into azobenzene liquid-crystalline dynamic networks (AuNR-ALCNs). The effects of the two different photoresponsive mechanisms, i.e., the photochemical reaction of azobenzene and the photothermal effect from the surface plasmon resonance of the AuNRs, are investigated by monitoring both the NIR- and UV-light-induced contraction forces of the oriented AuNR-ALCNs. By taking advantage of the material's easy processability, bilayer-structured actuators can be fabricated to display photocontrollable bending/unbending directions, as well as localized actuations through programmed alignment of azobenzene mesogens in selected regions. Versatile and complex motions enabled by the enhanced photocontrol of actuation are demonstrated, including plastic "athletes" that can execute light-controlled push-ups or sit-ups, and a light-driven caterpillar-inspired walker that can crawl forward on a ratcheted substrate at a speed of about 13 mm min-1. Moreover, the photomechanical effects arising from the two types of light-triggered molecular motion, i.e., the trans–cis photoisomerization and a liquid-crystalline–isotropic phase transition of the azobenzene mesogens, are added up to design a polymer "crane" that is capable of performing light-controlled, robot-like, concerted macroscopic motions including grasping, lifting up, lowering down, and releasing an object.
The photomechanical effects of two types of light-triggered molecular motions in a liquid-crystalline (LC) dynamic network, i.e., the LC–isotropic phase transition and the trans–cis photoisomerization of azobenzene mesogens, are added up to make a polymer "crane" that is capable of performing light-controlled, robot-like motions to produce physical work.
http://ift.tt/2BoejIX
Reversible and Precisely Controllable p/n-Type Doping of MoTe2 Transistors through Electrothermal Doping
Abstract
Precisely controllable and reversible p/n-type electronic doping of molybdenum ditelluride (MoTe2) transistors is achieved by electrothermal doping (E-doping) processes. E-doping includes electrothermal annealing induced by an electric field in a vacuum chamber, which results in electron (n-type) doping and exposure to air, which induces hole (p-type) doping. The doping arises from the interaction between oxygen molecules or water vapor and defects of tellurium at the MoTe2 surface, and allows the accurate manipulation of p/n-type electrical doping of MoTe2 transistors. Because no dopant or special gas is used in the E-doping processes of MoTe2, E-doping is a simple and efficient method. Moreover, through exact manipulation of p/n-type doping of MoTe2 transistors, quasi-complementary metal oxide semiconductor adaptive logic circuits, such as an inverter, not or gate, and not and gate, are successfully fabricated. The simple method, E-doping, adopted in obtaining p/n-type doping of MoTe2 transistors undoubtedly has provided an approach to create the electronic devices with desired performance.
Precisely controllable and reversible doping of molybdenum ditelluride (MoTe2) transistors is achieved by electrothermal doping (E-doping) processes. E-doping includes electrothermal annealing induced by an electric field in vacuum, which results in electron (n-type) doping, and exposure to air, which induces hole (p-type) doping. No dopant or gas is used in the E-doping processes, E-doping is a simple and efficient method.
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Paediatric Pelvic Fractures: A Review of 2 Cohorts Over 22 Years Revision 1
Publication date: Available online 11 February 2018
Source:Injury
Author(s): Neil Chotai, Sulaiman Alazzawi, Syeda Saman Zehra, Matthew Barry
AimsThe aim of this retrospective review was to identify all children that presented to our institution with a pelvic or acetabular fracture and to compare these children to a previous cohort of paediatric pelvic fractures that we have reported.Patients53 children under the age of 16 were identified over a ten year period.MethodsWe reviewed our trauma database, hospital records and radiological imaging to determine the age, gender, fracture pattern, associated injuries and management of the pelvic fracture.ResultsThere were 32 boys and 21 girls. Mean age of the boys was 8.8 years and the girls 10.7 years. In seven children the pelvic fracture was an isolated injury and in the remaining 46 children, there were 113 additional injuries. 56% of the additional injuries was either a fracture/dislocation (37%) or a head injury (19%). Compared to our first cohort, we had a larger number of children in the second cohort. Age, sex distribution, mechanism of injury was similar in the two groups. In this current cohort, use of CT scan imaging was more frequent, there were more unstable pelvic fracture patterns identified, ISS scores were higher and mortality was lower.ConclusionWe have seen more children with more severe injuries, higher ISS scores but a lower mortality rate.
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Calcar Screw Position in Proximal Humerus Fracture Fixation: Don’t Miss High!
Publication date: Available online 11 February 2018
Source:Injury
Author(s): Samir Mehta, Matthew Chin, Jennifer Sanville, Surena Namdari, Michael W. Hast
IntroductionIn locked plate fixation of proximal humerus fractures, the calcar is an important anchor point for screws providing much-needed medial column support. Most locking plate implants utilize a fixed-trajectory locking screw to achieve this goal. Consequently, adjustments of plate location to account for patient-specific anatomy may result in a screw position outside of the calcar. To date, little is known about the consequences of "missing" the calcar during plate positioning. This study sought to characterize the biomechanics associated with proximal and distal placement of locking plates in a two-part fracture model.Materials and methodsThis experiment was performed twice, first with elderly cadaveric specimens and again with osteoporotic sawbones. Two-part fractures were simulated and specimens were divided to represent proximal, neutral, and distal plate placements. Non-destructive torsional and axial compression tests were performed prior to an axial fatigue test and a ramp to failure. Torsional stiffness, axial stiffness, humeral head displacement and stiffness during fatigue testing, and ultimate load were compared between groups.ResultsCadavers: Proximal implant placement led to trends of decreased mechanical properties, but there were no significant differences found between groups. Sawbones: Distal placement increased torsional stiffness in both directions (p = 0.003, p = 0.034) and axial stiffness (p = 0.018) when compared to proximal placement. Distal placement also increased torsional stiffness in external rotation (p = 0.020), increased axial stiffness (p = 0.024), decreased humeral head displacement during fatigue testing, and increased stiffness during fatigue testing when compared to neutral placement.DiscussionThe distal and neutral groups had similar mechanical properties in many cadaveric comparisons while the proximal group trended towards decreased construct stiffness.Resultsfrom the Sawbones model were more definitive and provided further evidence that proximal calcar screw placements are undesirable and distal implant placement may provide improved construct stability.ConclusionSuccessful proximal humerus fracture reconstruction is inherent upon anatomic fracture reduction coupled with medial column support. Results from this experiment suggest that missing the calcar proximally is deleterious to fixation strength, while it is safe, and perhaps even desirable, to aim slightly distal to the intended target.
http://ift.tt/2H6rVJz
Dynamic changes and molecular analysis of cell death in the spinal cord of SJL mice infected with the BeAn strain of Theiler’s murine encephalomyelitis virus
Abstract
Theiler's murine encephalomyelitis (TME) is caused by the TME virus (TMEV) and represents an important animal model for multiple sclerosis (MS). Oligodendroglial apoptosis and reduced apoptotic elimination of encephalitogenic leukocytes seem to participate in autoimmune demyelination in MS. The present study quantified apoptotic cells in BeAn–TMEV-induced spinal cord white matter lesions at 14, 42, 98, and 196 days post infection (dpi) using immunostaining. Apoptotic cells were identified by transmission electron microscopy and double-immunofluorescence. The mRNA expression of apoptosis-related genes was investigated using microarray analysis. Oligodendroglial apoptosis was already detected in the predemyelinating phase at 14 dpi. Apoptotic cell numbers peaked at 42 dpi and decreased until 196 dpi partly due to reduced T cell apoptosis. In addition to genes involved in the classical pathways of apoptosis induction, microarray analysis detected the expression of genes related to alternative mechanisms of cell death such as pyroptosis, necroptosis, and endoplasmic reticulum stress. Consequently, oligodendroglial apoptosis is involved in the initiation of the TME demyelination process, whereas the development of apoptosis resistance of T cells potentially favors the maintenance of inflammation and myelin loss.
http://ift.tt/2G3AYt6
Plagioneurin B, a potent isolated compound induces apoptotic signalling pathways and cell cycle arrest in ovarian cancer cells
Abstract
Plagioneurin B belongs to acetogenin group has well-established class of compounds. Acetogenin group has attracted worldwide attention in the past few years due their biological abilities as inhibitors for several types of tumour cells. Plagioneurin B was isolated via conventional chromatography and tested for thorough mechanistic apoptosis activity on human ovarian cancer cells (CAOV-3). Its structure was also docked at several possible targets using Autodock tools software. Our findings showed that plagioneurin B successfully inhibits the growth of CAOV-3 cells at IC50 of 0.62 µM. The existence of apoptotic bodies, cell membrane blebbing and chromatin condensation indicated the hallmark of apoptosis. Increase of Annexin V-FITC bound to phosphatidylserine confirmed the apoptosis induction in the cells. The apoptosis event was triggered through the extrinsic and intrinsic pathways via activation of caspases 8 and 9, respectively. Stimulation of caspase 3 and the presence of DNA ladder suggested downstream apoptotic signalling were initiated. Further confirmation of apoptosis was conducted at the molecular levels where up-regulation in Bax, as well as down-regulation of Bcl-2, Hsp-70 and survivin were observed. Plagioneurin B was also seen to arrest CAOV-3 cells cycle at the G2/M phase. Docking simulation of plagioneurin B with CD95 demonstrated that the high binding affinity and hydrogen bonds formation may explain the capability of plagioneurin B to trigger apoptosis. This study is therefore importance in finding the effective compound that may offer an alternative drug for ovarian cancer treatment.
http://ift.tt/2H5ybku
High-Performance n-Channel Organic Transistors Using High-Molecular-Weight Electron-Deficient Copolymers and Amine-Tailed Self-Assembled Monolayers
Abstract
While high-performance p-type semiconducting polymers are widely reported, their n-type counterparts are still rare in terms of quantity and quality. Here, an improved Stille polymerization protocol using chlorobenzene as the solvent and palladium(0)/copper(I) as the catalyst is developed to synthesize high-quality n-type polymers with number-average molecular weight up to 105 g mol−1. Furthermore, by sp2-nitrogen atoms (sp2-N) substitution, three new n-type polymers, namely, pBTTz, pPPT, and pSNT, are synthesized, and the effect of different sp2-N substitution positions on the device performances is studied for the first time. It is found that the incorporation of sp2-N into the acceptor units rather than the donor units results in superior crystalline microstructures and higher electron mobilities. Furthermore, an amine-tailed self-assembled monolayer (SAM) is smoothly formed on a Si/SiO2 substrate by a simple spin-coating technique, which can facilitate the accumulation of electrons and lead to more perfect unipolar n-type transistor performances. Therefore, a remarkably high unipolar electron mobility up to 5.35 cm2 V−1 s−1 with a low threshold voltage (≈1 V) and high on/off current ratio of ≈107 is demonstrated for the pSNT-based devices, which are among the highest values for unipolar n-type semiconducting polymers.
High-molecular-weight (Mn) n-type semiconducting copolymers are synthesized via an improved Stille polymerization with Pd(0)/Cu(I) cocatalysts and chlorobenzene as the solvent. Due to the synergistic effects of the high Mn, rational molecular design of sp2-nitrogen substitution, and an amine-tailed self-assembled monolayer, unipolar n-channel organic transistors with remarkably high electron mobilities up to 5.35 cm2 V−1 s−1 are achieved.
http://ift.tt/2nSSl9r
Phase IIa study of the CD19 antibody MOR208 in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
Abstract
Background
This two-stage, phase IIa study (ClinicalTrials.gov: NCT01685008) investigated the antitumor activity and safety of MOR208, an Fc-engineered, humanized, CD19 antibody, in patients with relapsed or refractory (R-R) B-cell non-Hodgkin's lymphoma (NHL). CD19 is broadly expressed across the B-lymphocyte lineage, including in B-cell malignancies, but not by hematological stem cells. Patients and methods
Patients aged ≥18 years, with R-R NHL progressing after ≥1 prior rituximab containing regimen were enrolled into subtype-specific cohorts: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), other indolent (i)NHL and mantle cell lymphoma (MCL). Treatment was MOR208, 12 mg/kg intravenously, weekly, for 8 weeks. Patients with at least stable disease could continue treatment for an additional 4 weeks. Those with a partial or complete response after 12 weeks could receive extended MOR208 treatment (12 mg/kg, either monthly or every second week) until progression. The primary endpoint was overall response rate. Results
Ninety-two patients were enrolled: DLBCL (n=35), FL (n=34), other iNHL (n=11) and MCL (n=12). Responses were observed in DLBCL, FL and other iNHL cohorts (26%, 29% and 27%, respectively). They lasted ≥12 months in 5/9 responding patients with DLBCL, 4/9 with FL and 2/3 with other iNHL. Responses in nine patients are ongoing (>26 months in five instances). Patients with rituximab refractory disease showed a similar response rate and progression-free survival time to patients with non-refractory disease. The most common adverse events (any grade) were infusion-related reactions (IRRs; 12%) and neutropenia (12%). One patient experienced a grade 4 IRR and eight patients (9%) grade 3/4 neutropenia. No treatment-related deaths were reported. Conclusions
MOR208 monotherapy demonstrated promising clinical activity in patients with R-R DLBCL and R-R FL, including in patients with rituximab refractory tumors. These efficacy data and the favorable safety profile support further investigation of MOR208 in phase II/III combination therapy trials in R-R DLBCL. ClinicalTrials.gov number
NCT01685008http://ift.tt/2H47vk9
Prehospital stroke scales and large vessel occlusion: A systematic review
Background and purpose
Time sensitivity for pharmacological and mechanical arterial recanalization in acute ischemic stroke influences the choice of the reference hospital. The accurate selection and identification of patients with high probability of a large vessel occlusion (LVO) in the prehospital setting improve the rationalization of the transport in the more suitable centers. Aim of this analysis was to determine the diagnostic accuracy of prehospital stroke scales detecting LVO.
Material and methods
Studies were searched into MEDLINE, EMBASE, and CINHAL databases between January 1990 and September 2017. Principal measurements of the meta-analysis were the overall accuracy level, sensitivity, and specificity of prehospital stroke scales.
Results
Nineteen scoring systems were included in the analysis coming from 13 studies. A total of 9824 patients were considered. Although a higher heterogeneity was observed in the analysis, three scores showed better results in predicting a LVO (the stroke Vision, Aphasia, Neglect assessment, the National Institute of Health Stroke scale and the Los Angeles Motor Scale). We observed significant differences of overall accuracy only for scores including hemineglect as cortical neurological sign (P < .05).
Conclusions
This meta-analysis suggests that some prehospital scoring systems including cortical signs showed better accuracy to predict stroke due to LVO. However, the assessment of these signs could be difficult to investigate by paramedics and personnel of Emergency Medical Services, and for this reason, further prospective evaluations are needed.
http://ift.tt/2BSwVly
Trajectories of income and social benefits for mothers and fathers of children with cancer: A national cohort study in Sweden
BACKGROUND
The contribution of different income sources from work and social benefits to trajectories of income for the parents of children with cancer has not been empirically investigated.
METHODS
Using Swedish registers, parents of children with an incidence cancer diagnosis between 2004 and 2009 were identified and matched with parents of children without cancer (reference parents). A total of 20,091 families were followed from the year before the diagnosis to a maximum of 8 years. Generalized linear models estimated the ratios of mean incomes from work and social benefits and of its total.
RESULTS
Around the time of the child's cancer diagnosis, the total income was on average up to 6% higher among the mothers of children with cancer compared with reference mothers, but no differences were noted among fathers. Income from work dropped to the lowest level around the time of a cancer diagnosis, with swift recovery noted for fathers but not for mothers. Sickness and childcare-related benefits were up to 6 times larger for the parents of children with cancer than reference parents. As social benefits diminished after approximately 3 years, the total income of mothers of children with cancer became lower than that of reference mothers, and the gap widened over time.
CONCLUSIONS
Social benefits appeared to ease the financial burden during the years around a cancer diagnosis. However, mothers experienced persistently lower income after benefits diminished. Experiences differed by single-parent versus dual-parent households, the survival of the child with cancer, and other relevant characteristics. Further investigation is needed for potential long-term consequences for mothers, including their career and future pension in retirement. Cancer 2018. © 2018 American Cancer Society.
http://ift.tt/2BpQKjf
Morbidity and mortality meetings: gold, silver or bronze?
Abstract
Background
Morbidity and mortality (M&M) meetings contribute to surgical education and improvements in patient care through the review of surgical outcomes; however, they often lack defined structure, objectives and resource support. The aim of this study was to investigate the factors that impact the effective conduct of M&M meetings.
Methods
We conducted a rapid systematic literature review. Three biomedical databases (PubMed, the Cochrane Library and the University of York Centre for Reviews and Dissemination), clinical practice guideline clearinghouses and grey literature sources were searched from May 2009 to September 2016. Studies that evaluated the function of a hospital-based M&M process were included. Two independent reviewers conducted study selection and data extraction. Study details and key findings were reported narratively.
Results
Nineteen studies identified enablers, and seven identified barriers, to the effective conduct of M&M meetings. Enabling factors for effective M&M meetings included a structured meeting format, a structured case identification and presentation, and a systems focus. Absence of key personnel from meetings, lack of education regarding the meeting process, poor perceptions of the process, logistical issues and heterogeneity in case evaluation were identified as barriers to effective M&M meetings.
Conclusion
Taking steps to standardize and incorporate the enabling factors into M&M meetings will ensure that the valuable time spent reviewing M&M is used effectively to improve patient care.
http://ift.tt/2BU1cAA
Acute pain management in children: challenges and recent improvements
Purpose of review The evidence regarding the efficacy of analgesics available to guide postoperative pain treatment in pediatric patients is limited. Opioid medications are very often an important component of pediatric postoperative pain treatment but have been associated with perioperative complications. We will focus on initiatives aiming to provide effective treatment minimizing the use of opioids and preventing the long-term consequences of pain. Recent findings Interpatient variability in postoperative pain is currently managed by applying protocols or by trial and error, thus often leading to patients being either undertreated or overtreated. Few evidence-based reports are available to guide the use of opioid medications in children, including the prescription of opioids after hospital discharge. Using combinations of nonopioid analgesics in a multimodal approach may limit the need for opioids, thus decreasing the risk of toxicity and dose-related side effects. There is a lack of adequate research in this field, and more specifically on identifying which patient is at higher risk of poor postoperative pain management. Summary Treatment options have evolved in recent years, including the combinations of multimodal regimens and regional anesthetic techniques. Using combinations of nonopioid analgesics in a multimodal approach may limit the need for opioids. Correspondence to Pablo M. Ingelmo, MD, Department of Anesthesia, Montreal Children's Hospital, B.04.2427, 1001 Boulevard Decarie, Montreal, QC, Canada H4A3J1. Tel: +1 514 412 4448; e-mail: pablo.ingelmo@mcgill.ca Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2sru278
http://ift.tt/2sru278
Is spinal anaesthesia in young infants really safer and better than general anaesthesia?
Purpose of review Concerns regarding the potential neurotoxic effects of general anaesthesia have seen resurgence in awake spinal anaesthesia in neonates and infants. This review includes recently published data from a large prospective randomized controlled trial with view to determining if spinal anaesthesia is safer and better than general anaesthesia in this population. Recent findings Compared with general anaesthesia, spinal anaesthesia results in less haemodynamic instability and fewer early (
http://ift.tt/2Ewhe4v
http://ift.tt/2Ewhe4v
Long-term neurocognitive outcomes following surgery and anaesthesia in early life
Purpose of review Repeated controversial and alarming statements of the potential dangers of anaesthetic agents on neurological outcomes in children continue to be issued based primarily on preclinical studies. This review assesses the current evidence of laboratory and clinical data and identifies areas of concerns. Recent findings Published animal and laboratory data consistently indicate that prolonged and excessive use of anaesthetic agents can lead to morphological changes and neurocognitive impairment in animals without a clear cut-off age or a superiority of one technique over another. Retrospective human studies and prospective clinical trials indicate that short exposures to anaesthesia and surgery are safe and have no effect on long-term neurological outcomes. Small and consistent continuing improvements in the perioperative period (aggregation of marginal gains) will impact on long-term neurological morbidity in humans. Summary It is biologically plausible that anaesthetic agents may induce structural changes during mammalian brain development and beyond. However, in the absence of alternatives the impact of the choice of anaesthetic drugs on long-term neurocognitive outcomes is almost certainly to be of limited relevance in humans. The underlying disease processes, surgical intervention, and trauma as well as other known perioperative factors more significantly affect these outcomes. Correspondence to Tom G. Hansen, MD, PhD, Department of Anaesthesia & Intensive Care – Paediatric Section, Odense University Hospital, 5000 Odense C, Denmark. Tel: +45 6541 3812; fax: +45 6611 3415; e-mail: tomghansen@dadlnet.dk Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.
http://ift.tt/2Ew76J5
http://ift.tt/2Ew76J5
Cancer gene-panel testing identifies two loss-of-function alleles in PALB2 and PTEN
Synchronous loss-of-function mutations in the cancer predisposing genes, PTEN and PALB2 identified by multigene panel.
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Irradiated Human Umbilical Vein Endothelial Cells Undergo Endothelial-Mesenchymal Transition via the Snail/miR-199a-5p Axis to Promote the Differentiation of Fibroblasts into Myofibroblasts
Radiation induced pulmonary fibrosis (RIPF) is one of the major side effects of radiotherapy for lung cancer. Previous studies have shown that endothelial cells and activated myofibroblasts play a key role in RIPF. However, the interaction between irradiated endothelial cells and activation of myofibroblasts has not been reported. The aim of the present study was to examine whether irradiated endothelial cells would affect the differentiation of fibroblasts into myofibroblasts in the process of RIPF. In the current study, we used a coculture system that allowed direct contact between human fetal lung fibroblasts (MRC-5) and irradiated human umbilical vein endothelial cells (HUVECs). After 24 or 48 h, cells were sorted by flow cytometry. Radiation induced endothelial-mesenchymal transition (EndMT) by significantly increasing the expression of Snail and vimentin and reducing the expression of CD31 in HUVECs. In addition, irradiation of HUVECs induced the expression of collagen type I and α-smooth muscle actin (α-SMA) in MRC-5 cells. Further investigation indicated that irradiation of HUVECs induced the differentiation of fibroblasts into myofibroblasts through the Snail/miR-199a-5p axis. We conclude that irradiated endothelial cells undergo EndMT to promote differentiation of fibroblasts into myofibroblasts via the Snail/miR-199a-5p axis.
http://ift.tt/2smyXGB
Nonsurgical Clinical Management of Periapical Lesions Using Calcium Hydroxide-Iodoform-Silicon-Oil Paste
Background. The study aim is to avoid tooth extraction by nonsurgical treatment of periapical lesion. It assesses healing progress in response to calcium hydroxide-iodoform-silicon oil paste (CHISP). Numeric Pain Rating Scale was used to validate the approach. Furthermore, CHISP was used to treat cystic lesions secondary to posttraumatic avulsion of permanent teeth. Materials and Methods. Over 200 patients with radicular cysts were treated with CHISP through the root canal. Radiographs were used to verify lesion size and position, ensure correct delivery to the site, and monitor the progress of bone healing in the lesion area. Ten males and 10 females were randomly selected for statistical assessment. Results. No severe pain, complications, or failure in cyst healing was reported. Complete healing was achieved in an average of 75 days. Furthermore, healing of radicular cyst secondary to posttraumatic tooth avulsion was successful. Conclusion. CHISP indicated an antiseptic effect, which enhanced and shortened healing time of periapical lesions. The less invasive procedure avoids tooth extraction and reduces bone resorption. Cyst management with CHISP can remedy failed root canal treatments. The results show a bone regenerative capacity of CHISP suggested in first rapid phase and a second slow phase.
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Less or more? Maternal requests that go against medical advice
Publication date: Available online 11 February 2018
Source:Women and Birth
Author(s): Martine Hollander, Lianne Holten, Annemieke Leusink, Jeroen van Dillen, Esteriek de Miranda
Problem and backgroundThis study explores the experiences of Dutch midwives and gynaecologists with pregnant women who request more, less or no care during pregnancy and/or childbirth.MethodsAll Dutch midwives and (trainee) gynaecologists were invited to fill out a questionnaire specifically designed for the purposes of this study. Holistic midwives were analysed separately from regular community midwives.FindingsMost maternity care providers in the Netherlands receive requests for less care than recommended at least once a year. The most frequently maternal requests were declining testing for gestational diabetes (66.3%), opting for a home birth in case of a high risk pregnancy (65.3%), and declining foetal monitoring during labour (39.6%). Holistic midwives are more convinced of an increasing demand for less care than community midwives (73.1% vs. 35.2%, p=<0.001). More community midwives than hospital staff reported to have declined one or more request for less care than recommended (48.6% vs. 27.9%, p=<0.001). The majority of hospital staff also receive at least one request for an elective caesarean section every year.Discussion and conclusionRequests for more and less care than indicated during pregnancy and childbirth are equally prevalent in this study. However, a request for less care is more likely to be declined than a request for more care. Counselling women who disagree with their care provider demands time. In case of requests for less care, second best care should be considered.
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10-10 Electrode Placement System
In a good overview of electrode nomenclature, Seeck et al. (2017) describe the methods for naming recording regions between the major 10-20 electrode nomenclature locations. This excellent presentation describes and illustrates current ideas about high density sampling sites.
http://ift.tt/2EhXsWU
To warn or not to warn: A reappraisal of brainstem auditory evoked potential warning criteria during surgery
Neurophysiologic intraoperative monitoring (NIOM) is widely used to reduce neurologic morbidity in many types of surgeries where nervous tissue is at risk. Somatosensory and motor evoked potentials (SEP, MEP) have been shown to reduce the risk of paraplegia in spinal surgeries (Nuwer et al., 2012). Brainstem auditory evoked potentials (BAEP), similarly, have been shown to reduce the risk of hearing loss in surgeries involving the manipulation of the vestibulocochlear nerve, brainstem or cerebellum (Radtke et al., 1989).
http://ift.tt/2EVL2Fk
On the origin of epileptic High Frequency Oscillations observed on clinical electrodes
In drug-resistant partial epilepsies, resective surgery is the treatment of choice to suppress seizures, provided that the epileptogenic zone (EZ) is clearly identified and that it can be safely removed. In this context, the capacity to rely on objective biomarkers of the EZ is fundamental to define the optimal surgical approach in the specific context of each patient. Prior to surgery, patients may benefit from pre-surgical investigations, among which depth-EEG recordings which play a key role as the use of intracranial electrodes offer the unique opportunity to directly and locally record field potentials from brain areas with an excellent temporal resolution (sub-millisecond).
http://ift.tt/2ElxiTq
Fabrication of Spherical and Worm-shaped Micellar Nanocrystals by Combining Electrospray, Self-assembly, and Solvent-based Structure Control
The present work describes a method to fabricate micellar nanocrystals, an emerging major class of nanobiomaterials. This method combines top-down electrospray, bottom-up self-assembly, and solvent-based structure control. The fabrication method is largely continuous, can produce high quality products, and possesses an inexpensive means of structure control.
http://ift.tt/2EAyK7w
Application of MRI for the Diagnosis of Neoplasms
Aim. The aim of the study was to determine the most commonly diagnosed neoplasms in the MRI scanned patient population and indicate correlations based on the descriptive variables. Methods. The SPSS software was used to determine the incidence of neoplasms within the specific diagnoses based on the descriptive variables of the studied population. Over a five year period, 791 patients and 839 MRI scans were identified in neoplasm category (C00-D48 according to the International Statistical Classification of Diseases and Related Health Problems ICD-10). Results. More women (56%) than men (44%) represented C00-D48. Three categories of neoplasms were recorded. Furthermore, benign neoplasms were the most numerous, diagnosed mainly in patients in the fifth decade of life, and included benign neoplasms of the brain and other parts of the central nervous system. Conclusions. Males ≤ 30 years of age with neoplasms had three times higher MRI scans rate than females of the same age group; even though females had much higher scans rate in every other category. The young males are more often selected for these scans if a neoplasm is suspected. Finally, the number of MRI-diagnosed neoplasms showed a linear annual increase.
http://ift.tt/2BT8fcP
What is a bifid uvula?
A look at bifid uvula, a condition affecting the palate of the mouth. Included is detail on complications of the condition and outlook for a bifid uvula.
http://ift.tt/2G6FO8X
Evaluation and Management of Dehydration in Children
The article discusses the evaluation of dehydration in children and reviews the literature on physical findings of dehydration. Pediatric dehydration is a common problem in emergency departments and wide practice variation in treatment exists. Dehydration can be treated with oral, nasogastric, subcutaneous, or intravenous fluids. Although oral rehydration is underutilized in the United States, most children with dehydration can be successfully rehydrated via the oral route. Selection of oral rehydration solution and techniques for successful oral rehydration are presented. Appropriate selection and rate of administration of intravenous fluids are also discussed for isonatremic, hyponatremic, and hypernatremic dehydration.
http://ift.tt/2BoGNTc
Pediatric Major Head Injury
Traumatic brain injury is a highly prevalent and devastating cause of morbidity and mortality in children. A rapid, stepwise approach to the traumatized child should proceed, addressing life-threatening problems first. Management focuses on preventing secondary injury from physiologic extremes such as hypoxemia, hypotension, prolonged hyperventilation, temperature extremes, and rapid changes in cerebral blood flow. Initial Glasgow Coma Score, hyperglycemia, and imaging are often prognostic of outcome. Surgically amenable lesions should be evacuated promptly. Reduction of intracranial pressure through hyperosmolar therapy, decompressive craniotomy, and seizure prophylaxis may be considered after stabilization. Nonaccidental trauma should be considered when evaluating pediatric trauma patients.
http://ift.tt/2BQYlrQ
Bronchiolitis
The American Academy of Pediatrics' clinical practice guideline in bronchiolitis was last updated in 2014 with recommendations to improve care for pediatric patients with bronchiolitis. As most treatments of bronchiolitis are supportive, the guideline minimizes the breadth of treatments previously used and cautions the use of tests and therapies that have a limited evidence base. Emergency physicians must be familiar with the guidelines in order to apply best practices appropriately.
http://ift.tt/2BoGI1Q
Emergency Department Management of Pediatric Shock
Shock, a state of inadequate oxygen delivery to tissues resulting in anaerobic metabolism, lactate accumulation, and end-organ dysfunction, is common in children in emergency department. Shock can be divided into 4 categories: hypovolemic, distributive, cardiogenic, and obstructive. Early recognition of shock can be made with close attention to historical clues, physical examination and vital sign abnormalities. Early and aggressive treatment can prevent or reverse organ dysfunction and improve morbidity and mortality.
http://ift.tt/2BSHncL
Pediatric Emergency Noninvasive Ventilation
Noninvasive ventilation (NIV) has emerged as a powerful tool for the pediatric emergency management of acute respiratory failure (ARF). This therapy is safe and well tolerated and seems to frequently prevent both the need for invasive mechanical ventilation and the associated risks/complications. Although NIV can be the primary treatment of ARF resulting from multiple respiratory disease states, it must be meticulously monitored and, when unsuccessful, may aid in preoxygenation for prompt endotracheal intubation and invasive mechanical ventilation. The following article reviews the physiologic effects of NIV and its role in common respiratory diseases encountered in pediatric emergency medicine.
http://ift.tt/2BmarZ4
Postoperative Tonsillectomy Hemorrhage
Post-tonsillectomy hemorrhage represents a potentially life-threatening condition that occurs in up to 5% of pediatric patients. Minor bleeding often precedes severe hemorrhage. Patients with minor or self-resolving bleeding should be observed in the emergency department or admitted for monitoring. Patients with severe bleeding should be immediately assessed for airway and hemodynamic stability. Management of severe bleeding includes immediate surgical consultation or initiation of the transfer process to a center with surgical capabilities, direct pressure to the site of hemorrhage with or without the additional of a hemostatic agent, possible rapid sequence intubation, and management of hemodynamic instability with volume resuscitation.
http://ift.tt/2BQMNVM
Pediatric Syncope
Syncope is a common presentation to the emergency room. Unlike in the adult population, most pediatric syncope has non-life-threatening causes, and minimal evaluation in the emergency department is appropriate with parental reassurance. Despite this benign prognosis, care must be made to find uncommon and potentially fatal causes. The primary purpose of evaluation of the patient with syncope is to determine whether the patient is at increased risk for death and needs either admission to the hospital or an expedited outpatient evaluation. This article reviews some of the most dangerous causes of syncope in the pediatric patient.
http://ift.tt/2BnPnBh
What to Do when Babies Turn Blue
The term "brief resolved unexplained event" was created to replace "apparent life-threatening event," narrowing the definition and providing evidence-based guidelines for management. The emphasis is placed on using clinical clues to classify patients as low risk or exclude them from the categorization altogether. Infants who meet low-risk classification can be briefly observed in the emergency department and be discharged home. Infants who demonstrate elements suggestive of a specific etiology should be evaluated and treated accordingly. Patients who demonstrate no specific findings yet who are high risk should be evaluated for the most common etiologies of apneic events and be admitted.
http://ift.tt/2BQaDRx
Pediatric Thoracic Trauma
Thoracic injuries account for less than one-tenth of all pediatric trauma-related injuries but comprise 14% of pediatric trauma-related deaths. Thoracic trauma includes injuries to the lungs, heart, aorta and great vessels, esophagus, tracheobronchial tree, and structures of the chest wall. Children have unique anatomic features that change the patterns of observed injury compared with adults. This review article outlines the clinical presentation, diagnostic testing, and management principles required to successfully manage injured children with thoracic trauma.
http://ift.tt/2BoGpEe
Availability of Dental Prosthesis Procedures in Brazilian Primary Health Care
Objectives. To describe dental prosthesis provision in the Brazilian public health service and report the performance of dental prosthesis procedures according to the Brazilian macroregions. Methods. A structured interview was conducted with senior-level health professionals from each of the 18,114 oral health teams (OHT). The dependent variables were performance of removable prostheses and prosthesis procedures, including provision of fixed prostheses by OHT. Descriptive statistics were produced together with performing a cluster analysis using SPSS version 19.0. Results. The manufacture of any type of prosthesis was done by a minority of OHT (43%). The most commonly provided types of dental prosthesis were removable full and partial dentures. Cluster 1 (teams that performed prosthesis procedures the most) was composed of a smaller number of teams ( = 5,531), and Cluster 2 (composed of teams that do not perform prosthetics or that perform them in small amounts) consisted of 12,583 teams. The geographic distribution of clusters reveals that the largest proportion of Cluster 1 teams is located in the Northeast (33.9%) and Southeast (33.6%). Conclusions. A minority of OHT produce dental prostheses. There is an unequal geographical distribution of clusters.
http://ift.tt/2BS8iW5
Cancers, Vol. 10, Pages 49: Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies
Cancers, Vol. 10, Pages 49: Beyond Brooding on Oncometabolic Havoc in IDH-Mutant Gliomas and AML: Current and Future Therapeutic Strategies
Cancers doi: 10.3390/cancers10020049
Authors: Hanumantha Madala Surendra Punganuru Viswanath Arutla Subhasis Misra T. Thomas Kalkunte Srivenugopal
Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. The oncometabolite D-2HG, which accumulates >35 mM, is widely accepted to drive a progressive oncogenesis besides exacerbating the already increased oxidative stress in these cancers. More importantly, D-2HG competes with α-KG and inhibits a large number of α-KG-dependent dioxygenases such as TET (Ten-eleven translocation), JmjC domain-containing KDMs (histone lysine demethylases), and the ALKBH DNA repair proteins that ultimately lead to hypermethylation of the CpG islands in the genome. The resulting CpG Island Methylator Phenotype (CIMP) accounts for major gene expression changes including the silencing of the MGMT (O6-methylguanine DNA methyltransferase) repair protein in gliomas. Glioma patients with IDH1 mutations also show better therapeutic responses and longer survival, the reasons for which are yet unclear. There has been a great surge in drug discovery for curtailing the mutant IDH activities, and arresting tumor proliferation; however, given the unique and chronic metabolic effects of D-2HG, the promise of these compounds for glioma treatment is uncertain. This comprehensive review discusses the biology, current drug design and opportunities for improved therapies through exploitable synthetic lethality pathways, and an intriguing oncometabolite-inspired strategy for primary glioblastoma.
http://ift.tt/2CcCLtR
Spindle cell predominant epithelioid fibrous histiocytoma
Abstract
No affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.
This article is protected by copyright. All rights reserved.
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Malignant mesothelioma with squamous differentiation
Abstract
We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity. The patient had a history of asbestos exposure, and the chest computed tomography on initial admission demonstrated an extrapleural sign suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, the patient died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumor lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumor was composed of a mixture of mesothelioma and tumor cells with squamous differentiation mimicking squamous cell carcinoma. To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in English literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma.
This article is protected by copyright. All rights reserved.
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A Monoclonal Antibody to SV40 Large T Antigen (PAb416) Does Not Label Merkel Cell Carcinoma
Abstract
Aims
Merkel cell carcinoma represents poorly differentiated neuroendocrine carcinoma of cutaneous origin. In most studies the vast majority of Merkel cell carcinomas are Merkel cell polyomavirus (MCPyV)-associated. SV40 polyomavirus immunohistochemistry is typically used in the diagnosis other polyomavirus-associated diseases including tubulointerstitial nephritis and progressive multifocal leukoencephalopathy, given cross-reactivity with BK and JC polyomaviruses. MCPyV-specific immunohistochemistry is commercially available, but if SV40 immunohistochemistry also cross-reacted with MCPyV that would be advantageous from a resource-utilization perspective.
Methods and results
Tissue microarrays were constructed from 39 Merkel cell carcinomas, 24 small cell lung carcinomas, and 18 extrapulmonary visceral small cell carcinomas. SV40 large T antigen immunohistochemistry (clone PAb416) was performed; MCPyV large T antigen immunohistochemistry (clone CM2B4) had been previously performed. UniProt was used to compare the amino acid sequences of the SV40, BK, JC, and Merkel cell polyomavirus large T antigens, focusing on areas recognized by the PAb416 and CM2B4 clones. SV40 immunohistochemistry was negative in all tumors; MCPyV immunohistochemistry was positive in 38% of Merkel cell carcinomas and 0% of non-cutaneous poorly differentiated neuroendocrine carcinomas. UniProt analysis revealed a high degree of similarity between SV40, BK, and JC viruses in the region recognized by PAb416. There was less homology between SV40 and MCPyV in this region, which was also interrupted by 2 long stretches of amino acids unique to MCPyV. The CM2B4 clone recognizes a unique epitope in one of these stretches.
Conclusions
SV40 large T antigen immunohistochemistry does not cross react with MCPyV large T antigen and, thus, does not label Merkel cell carcinoma.
This article is protected by copyright. All rights reserved.
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Reduced low-frequency power and phase locking reflect restoration in the auditory continuity illusion
Abstract
Interruptions in auditory input can be perceptually restored if they coincide with a masking sound, resulting in a continuity illusion. Previous studies have shown that this continuity illusion is associated with reduced low-frequency neural oscillations in the auditory cortex. However, the precise contribution of oscillatory amplitude changes and phase alignment to auditory restoration remains unclear. Using electroencephalography, we investigated induced power changes and phase locking in response to 3 Hz amplitude-modulated tones during the interval of an interrupting noise. We experimentally manipulated both the physical continuity of the tone (continuous vs. interrupted) and the masking potential of the noise (notched vs. full). We observed an attenuation of 3 Hz power during continuity illusions in comparison to both continuous tones and veridically perceived interrupted tones. This illusion-related suppression of low-frequency oscillations likely reflects a blurring of auditory object boundaries that supports continuity perception. We further observed increased 3 Hz phase locking during fully masked continuous tones compared with the other conditions. This low-frequency phase alignment may reflect the neural registration of the interrupting noise as a newly appearing object, whereas during continuity illusions, a spectral portion of this noise is delegated to filling the interruption. Taken together, our findings suggest that the suppression of slow cortical oscillations in both the power and phase domains supports perceptual restoration of interruptions in auditory input.
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GABA- and serotonin-expressing neurons take part in inhibitory as well as excitatory input pathways to the circadian clock of the Madeira cockroach Rhyparobia maderae
Abstract
In the Madeira cockroach pigment-dispersing factor-immunoreactive (PDF-ir) neurons innervating the circadian clock, the accessory medulla (AME) in the brain′s optic lobes, control circadian behavior. Circadian activity rhythms are entrained to daily light-dark cycles only by compound eye photoreceptors terminating in the lamina and medulla. Still, it is unknown which neurons connect the photoreceptors to the clock to allow for light-entrainment. Here, we characterized by multiple-label immunocytochemistry the serotonin (5-HT)-ir anterior fiber fan and GABA-ir pathways connecting the AME- and optic lobe neuropils. Colocalization of 5-HT with PDF was confirmed in PDF-ir lamina neurons (PDFLAs). Double-labeled fibers were traced to the AME originating from colabeled PDFLAs branching in accessory laminae and proximal lamina. The newly discovered GABA-ir medial layer fiber tract connected the AME to the medulla′s medial layer fiber system and the distal tract fibers connected the AME to the medulla. With Ca2+-imaging on primary cell cultures of the AME and with loose patch clamp recordings in vivo we showed that both neurotransmitters either excite or inhibit AME clock neurons. Because we found no colocalization of GABA and 5-HT in any optic lobe neuron, GABA- and 5-HT-neurons form separate clock input circuits. Among others, both pathways converged also on AME neurons that coexpressed mostly inhibitory GABA- and excitatory 5-HT-receptors. Our physiological and immunocytochemical studies demonstrate that GABA- and 5-HT-immunoreactive neurons constitute parallel excitatory or inhibitory pathways connecting the circadian clock either to the lamina and/or medulla where photic information from the compound eye is processed.
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Probing the limits of alpha power lateralizationas a neural marker of selective attention in middle-aged and older listeners
Abstract
In recent years, hemispheric lateralization of alpha power has emerged as a neural mechanism thought to underpin spatial attention across sensory modalities. Yet, how healthy aging, beginning in middle adulthood, impacts the modulation of lateralized alpha power supporting auditory attention remains poorly understood. In the current electroencephalography (EEG) study, middle-aged and older adults (N = 29; ~40–70 years) performed a dichotic listening task that simulates a challenging, multi-talker scenario. We examined the extent to which the modulation of 8–12 Hz alpha power would serve as neural marker of listening success across age. With respect to the increase in inter-individual variability with age, we examined an extensive battery of behavioral, perceptual, and neural measures. Similar to findings on younger adults, middle-aged and older listeners' auditory spatial attention induced robust lateralization of alpha power, which synchronized with the speech rate. Notably, the observed relationship between this alpha lateralization and task performance did not co-vary with age. Instead, task performance was strongly related to an individual's attentional and working memory capacity. Multivariate analyses revealed a separation of neural and behavioral variables independent of age. Our results suggest that in age-varying samples as the present one, the lateralization of alpha power is neither a sufficient nor necessary neural strategy for an individual's auditory spatial attention, as higher age might come with increased use of alternative, compensatory mechanisms. Our findings emphasize that explaining inter-individual variability will be key to understanding the role of alpha oscillations in auditory attention in the aging listener.
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Neonatal adoptive transfer of lymphocytes rescues social behavior during adolescence in immune deficient mice
Abstract
Accumulating evidence has shown that lymphocytes modulate behavior and cognition by direct interactions with the central nervous system. Studies have shown that reconstitution by adoptive transfer of lymphocytes from wild type into immune deficient mice restores a number of neurobehavioral deficits observed in these models. Moreover, it has been shown that these effects are mostly mediated by T lymphocytes. Studies of adoptive transfer thus far have employed adult mice, but whether lymphocytes may also modulate behavior during development remains unknown. In the present study, neonate lymphocyte deficient Rag2-/- mice were reconstituted within 48 hours after birth with lymphoid cells from transgenic donors expressing green fluorescent protein, allowing for their identification in various tissues in recipient mice while retaining all functional aspects. Adolescent Rag2-/- and reconstituted Rag2-/- along with C57BL/6J WT mice underwent a series of behavioral tests, including open field, social interaction and sucrose preference tests. At 12 weeks they were evaluated in the Morris Water Maze (MWM). Reconstituted mice showed changes in almost all aspects of behavior that were assessed, with a remarkable complete rescue of impaired social behavior displayed by adolescent Rag2-/- mice. Consistent with previous reports in adult mice, neonatal reconstitution in Rag2-/- mice restored spatial memory in the MWM. The presence of donor lymphocytes in the brain of neonatally reconstituted Rag2-/- mice was confirmed at various developmental points. These findings provide evidence that lymphocytes colonize the brain during postnatal development and modulate behavior across the lifespan supporting a role for adaptive immunity during brain maturation.
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Novel 3-substituted N-methylcarbazole–imidazolium salt derivatives: Synthesis and cytotoxic activity
A series of novel 3-substituted N-methylcarbazole–imidazolium salt derivatives has been prepared and evaluated in vitro against a panel of tumor cell lines (Hep G-2, Hela and PC12). The results suggest that the presence of substituted 2-methyl-imidazole or imidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl or 4-bromophenacyl group were important for improving cytotoxic activity. Compounds 17, 18, 27 and 28 with 4-bromophenacyl and naphthylacyl groups displayed good activities with IC50 values of 0.09–7.20 μM against three tumor cell lines investigated and more active than DDP. Compound 35 exhibited cytotoxic activity selectively against Hela cell.
This article is protected by copyright. All rights reserved.
A series of novel 3-substituted N-methylcarbazole–imidazolium salt derivatives were synthesized and their cytotoxic structure-activity relationship studies were reported. Compounds 17, 18 and 28 displayed good activities with IC50 values of 0.09–7.20 μM against three tumor cell lines investigated. Compound 35 exhibited cytotoxic activity selectively against Hela cell.
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Elevated Serum Levels of Mixed Lineage Kinase Domain-Like Protein Predict Survival of Patients during Intensive Care Unit Treatment
Mixed lineage kinase domain-like (MLKL), a crucial regulator of necroptotic cell death, was shown to play a role in inflammatory diseases. However, its role as a biomarker in critical illness and sepsis is currently unknown. We analyzed serum levels of MLKL in 136 critically ill patients at admission to the intensive care unit (ICU) and after three days of ICU treatment. Results were compared with 36 healthy controls and correlated with clinical and laboratory patients' data. MLKL serum levels of critically ill patients at admission to the ICU were similar compared to healthy controls. At ICU admission, MLKL serum concentrations were independent of disease severity, presence of sepsis, and etiology of critical illness. In contrast, median serum levels of MLKL after three days of ICU treatment were significantly lower compared to those at admission to the ICU. While serum levels of MLKL at admission were not predictive for short-term survival during ICU treatment, elevated MLKL concentrations at day three were an independent negative predictor of patients' ICU survival. Thus, elevated MLKL levels after three days of ICU treatment were predictive for patients' mortality, indicating that sustained deregulated cell death is associated with an adverse prognosis in critical illness.
http://ift.tt/2Ez7kz6
Evaluation of Individual and Combined Markers of Urine Dipstick Parameters and Total Lymphocyte Count as a Substitute for CD4 Count in Low-Resource Communities in Ghana
We evaluated the individual and combined levels of urine dipstick and total lymphocyte count (TLC) as surrogate markers for CD4 count in a low-resource community in Ghana. This cross-sectional study recruited 200 HIV-infected patients from the Saint Francis Xavier Hospital, Assin Fosu, Ghana. Complete blood count, CD4 count, and urine dipstick analysis were measured for participants. The threshold values were determined as
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Cancers, Vol. 10, Pages 48: Early Diagnosis to Improve the Poor Prognosis of Pancreatic Cancer
Cancers, Vol. 10, Pages 48: Early Diagnosis to Improve the Poor Prognosis of Pancreatic Cancer
Cancers doi: 10.3390/cancers10020048
Authors: Masataka Kikuyama Terumi Kamisawa Sawako Kuruma Kazuro Chiba Shinya Kawaguchi Shuzo Terada Tatsunori Satoh
Pancreatic cancer (PC) has a poor prognosis due to delayed diagnosis. Early diagnosis is the most important factor for improving prognosis. For early diagnosis of PC, patients with clinical manifestations suggestive of PC and high risk for developing PC need to be selected for examinations for PC. Signs suggestive of PC (e.g., symptoms, diabetes mellitus, acute pancreatitis, or abnormal results of blood examinations) should not be missed, and the details of risks for PC (e.g., familial history of PC, intraductal mucin producing neoplasm, chronic pancreatitis, hereditary pancreatitis, or life habit) should be understood. Multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) can be performed for diagnosing PC, but the diagnostic ability of these examinations for PC is limited. Endoscopic diagnostic procedures, such as endoscopic ultrasonography, including fine-needle aspiration, and endoscopic retrograde pancreatocholangiography, including Serial Pancreatic-juice Aspiration Cytologic Examination (SPACE), could be recommended for a detailed examination to diagnose pancreatic carcinoma earlier.
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
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