Extraordinarily Stretchable All-Carbon Collaborative Nanoarchitectures for Epidermal Sensors

Multifunctional microelectronic components featuring large stretchability, high sensitivity, high signal-to-noise ratio (SNR), and broad sensing range have attracted a huge surge of interest with the fast developing epidermal electronic systems. Here, the epidermal sensors based on all-carbon collaborative percolation network are demonstrated, which consist 3D graphene foam and carbon nanotubes (CNTs) obtained by two-step chemical vapor deposition processes. The nanoscaled CNT networks largely enhance the stretchability and SNR of the 3D microarchitectural graphene foams, endowing the strain sensor with a gauge factor as high as 35, a wide reliable sensing range up to 85%, and excellent cyclic stability (>5000 cycles). The flexible and reversible strain sensor can be easily mounted on human skin as a wearable electronic device for real-time and high accuracy detecting of electrophysiological stimuli and even for acoustic vibration recognition. The rationally designed all-carbon nanoarchitectures are scalable, low cost, and promising in practical applications requiring extraordinary stretchability and ultrahigh SNRs.

A rational all-carbon collaborative network for constructing epidermal sensors with significantly improved strain distribution and conductive nanochannels is designed based on collaborative networks of carbon nanotubes and graphene hollow backbones. With the structural and compositional advantages, extraordinary stretchability and sensitivity for real-time and high accuracy detecting of electrophysiological stimuli of humans and even for acoustic vibration recognition are achieved.

http://ift.tt/2sza2io

Structure–Property Relationships of Organic Electrolytes and Their Effects on Li/S Battery Performance

Electrolytes, which are a key component in electrochemical devices, transport ions between the sulfur/carbon composite cathode and the lithium anode in lithium–sulfur batteries (LSBs). The performance of a LSB mostly depends on the electrolyte due to the dissolution of polysulfides into the electrolyte, along with the formation of a solid–electrolyte interphase. The selection of the electrolyte and its functionality during charging and discharging is intricate and involves multiple reactions and processes. The selection of the proper electrolyte, including solvents and salts, for LSBs strongly depends on its physical and chemical properties, which is heavily controlled by its molecular structure. In this review, the fundamental properties of organic electrolytes for LSBs are presented, and an attempt is made to determine the relationship between the molecular structure and the properties of common organic electrolytes, along with their effects on the LSB performance.

Selection of the proper electrolyte, including solvents, salts, and additives, for lithium–sulfur batteries strongly depends on its physical and chemical properties, which is heavily controlled by its molecular structure. Structure–property relationships of organic electrolytes and their effects on Li/S battery performance are discussed in this review.

http://ift.tt/2t8SVRl

Three-Dimensional Binder-Free Nanoarchitectures for Advanced Pseudocapacitors

The ever-increasing energy demands for electrification of transportation and powering of portable electronics are driving the pursuit of energy-storage technologies beyond the current horizon. Pseudocapacitors have emerged as one of the favored contenders to fill in this technology gap, owing to their potential to deliver both high power and energy densities. The high specific capacitance of pseudocapacitive materials is rooted in the various available oxidation states for fast surface or near-surface redox charge transfer. However, the practical implementation of pseudocapacitors is plagued by the insulating nature of most pseudocapacitive materials. The wealth of the research dedicated to addressing these critical issues has grown exponentially in the past decade. Here, we briefly survey the current progress in the development of pseudocapacitive electrodes with a focus on the discussion of the recent most exciting advances in the design of three-dimensional binder-free nanoarchitectures, including porous metal/graphene-based electrodes, as well as metal-atom/ion-doping-enhanced systems, for advanced supercapacitors with comparable energy density to batteries, and high power density.

The recent progress in developing pseudocapacitive electrodes is summarized, focusing on the three-dimensional (3D) binder-free nanoarchitecture design, including 3D-porous-metal- and graphene-based electrodes, as well as metal-atom/ion-doping-enhanced electrodes, for advanced pseudocapacitors with comparable energy density to batteries, high power density and excellent cycling stability.

http://ift.tt/2sz5Bny

A Coating-Free Nonfouling Polymeric Elastomer

Medical devices face nonspecific biofouling from proteins, cells, and microorganisms, which significantly contributes to complications and device failure. Imparting these devices with nonfouling capabilities remains a major challenge, particularly for those made from elastomeric polymers. Current strategies, including surface coating and copolymerization/physical blending, necessitate compromise among nonfouling properties, durability, and mechanical strength. Here, a new strategy is reported to achieve both high bulk mechanical strength and excellent surface nonfouling properties, which are typically contradictory, in one material. This is realized through a nonfouling polymeric elastomer based on zwitterionic polycarboxybetaine derivatives. By hiding both charged moieties of the zwitterionic compounds with hydrocarbon ester and tertiary amine groups, the bulk polymer itself is elastomeric and hydrophobic while its superhydrophilic surface properties are restored upon hydrolysis. This coating-free nonfouling elastomer is a highly promising biomaterial for biomedical and engineering applications.

A stable nonfouling polymeric elastomer is demonstrated. This elastomer, based on zwitterionic polycarboxybetaine derivatives, requires no hydrophilic surface coating to achieve excellent nonfouling surface properties. By hiding both charged moieties of the zwitterionic compounds, a hydrophobic elastomer is fabricated; hydrolysis of its outermost surface then restores superhydrophilic and nonfouling surface properties, while maintaining excellent bulk mechanical characteristics.

http://ift.tt/2t8Pday

Electrothermal Control of Graphene Plasmon–Phonon Polaritons

Graphene plasmons are known to offer an unprecedented level of confinement and enhancement of electromagnetic field. They are hence amenable to interacting strongly with various other excitations (for example, phonons) in their surroundings and are an ideal platform to study the properties of hybrid optical modes. Conversely, the thermally induced motion of particles and quasiparticles can in turn interact with electronic degrees of freedom in graphene, including the collective plasmon modes via the Coulomb interaction, which opens up new pathways to manipulate and control the behavior of these modes. This study demonstrates tunable electrothermal control of coupling between graphene mid-infrared (mid-IR) plasmons and IR active optical phonons in silicon nitride. This study utilizes graphene nanoribbons functioning as both localized plasmonic resonators and local Joule heaters upon application of an external bias. In the latter role, they achieve up to ≈100 K of temperature variation within the device area. This study observes increased modal splitting of two plasmon–phonon polariton hybrid modes with temperature, which is a manifestation of increased plasmon–phonon coupling strength. Additionally, this study also reports on the existence of a thermally excited hybrid plasmon–phonon mode. This work can open the door for future optoelectronic devices such as electrically switchable graphene mid-infrared plasmon sources.

Thermally induced phonons can interact with the collective plasmon modes in graphene via the Coulomb interactions, opening up new pathways to manipulate the behavior of the phonon–plasmon hybrid modes. Utilizing graphene nanoribbons as both plasmonic resonators and Joule heaters, graphene plasmons are electrothermally excited, which may have implications for devices such as electrically switchable graphene plasmon sources.

http://ift.tt/2sz47d8

Engineering Novel Targeted Boron-10-Enriched Theranostic Nanomedicine to Combat against Murine Brain Tumors via MR Imaging-Guided Boron Neutron Capture Therapy

Glioblastoma multiforme (GBM) is a very common type of "incurable" malignant brain tumor. Although many treatment options are currently available, most of them eventually fail due to its recurrence. Boron neutron capture therapy (BNCT) emerges as an alternative noninvasive therapeutic treatment modality. The major challenge in treating GBMs using BNCT is to achieve selective imaging, targeting, and sufficient accumulation of boron-containing drug at the tumor site so that effective destruction of tumor cells can be achieved without harming the normal brain cells. To tackle this challenge, this study demonstrates for the first time that an unprecedented ¹⁰B-enriched (96% ¹⁰B enrichment) boron nanoparticle nanomedicine (¹⁰BSGRF NPs) surface-modified with a Fluorescein isothiocyanate (FITC)-labeled RGD-K peptide can pass through the brain blood barrier, selectively target at GBM brain tumor sites, and deliver high therapeutic dosage (50.5 µg ¹⁰B g⁻¹ cells) of boron atoms to tumor cells with a good tumor-to-blood boron ratio of 2.8. The ¹⁰BSGRF NPs not only can enhance the contrast of magnetic resonance (MR) imaging to help diagnose the location/size/progress of brain tumor, but also effectively suppress murine brain tumors via MR imaging-guided BNCT, prolonging the half-life of mice from 22 d (untreated group) to 39 d.

For the first time, an unprecedented ¹⁰B-enriched boron nanoparticle-based theranostic nanomedicine (¹⁰BSGRF NPs) is used to surpass the brain blood barrier and selectively target and effectively destroy murine brain tumors via magnetic resonance imaging-guided boron neutron capture therapy.

http://ift.tt/2t93AvJ

Gingival morphology-controlled design of the complete denture baseplate

Abstract

A removable complete denture is still the main selection for edentulous patients. Over the last five years, digital technologies for producing complete dentures have rapidly developed. Nevertheless, the design method for the baseplate has become the bottleneck of digital complete denture technology development. In this study, we report a novel method for the generation of aesthetic gingiva and polished surfaces of complete dentures that are driven by the feature curve, which can be conveniently modified using the gingival shape factor. A solid modeling method based on Poisson's surface reconstruction is used to generate a high-quality baseplate solid. This method can aid dentists to realize the rapid design process of personalized aesthetic baseplace. Finally, the experimental results verify that the method of digital design for the baseplate proposed is efficient and accurate (standard deviation < 0.01 mm).

http://ift.tt/2t8IbCN

Carers and breathlessness.

Purpose of review: Informal carers play a key role in supporting patients living with breathlessness in advanced disease, but with considerable impacts on their own well being. The purpose was to review recent advances in our understanding of the caring role in refractory breathlessness, its impacts on carers, and interventions to support them. Recent findings: A systematic literature search resulted in 28 included articles that could be mapped to four broad areas of carer enquiry: the carer role (n = 6), role impact (n = 7), carer support (n = 11) and carer views (n = 4). Search terms focused on breathlessness, but few of the included articles were exclusively on breathlessness: most were disease-related, predominantly chronic obstructive pulmonary disease (COPD). There were a range of methodologies, including four systematic reviews; UK studies were most common. Summary: Carers of patients with breathlessness take on a role characterized by uncertainty, largely unsupported by healthcare professionals (HCPs). HCP acknowledgement of these carers, their contribution and the impact of the caring role, is lacking. The patient-carer dyad should be considered the unit of care. Carer intervention should be individualized, supporting carers as clients and coworkers. There was a dearth of studies recruiting via primary care, focusing on conditions other than COPD and longitudinal work. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2s7KmYF

Metaplastic breast carcinoma with chondroid differentiation: a rare variant of infiltrative carcinoma in a 38-year-old woman

Metaplastic breast carcinoma (MBC) is a rare type of invasive breast carcinoma, and chondroid differentiation is even rarer. Here we report a case of MBC with extensive chondroid differentiation in a 38-year-old woman who presented with a lump in her left breast. Ultrasound findings were most compatible with those of giant fibroadenoma. A histopathological examination revealed a malignant lesion comprising neoplastic epithelial cells arranged in solid nests, with large areas of chondroid differentiation. Neoplastic chondroid cells exhibited a positive reaction for S-100, patchy positive reaction for pan-cytokeratin (AE1/AE3) and negative reaction for epithelial membrane antigen. Both carcinomatous and chondroid cells exhibited p53 overexpression. Sentinel lymph node biopsy revealed no tumorous involvement.

http://ift.tt/2shgNSV

It's a cod! Finding Nemo (impacted fishbone) in the emergency department

A 23-year-old woman presented to the emergency department (ED) with a sensation of a 'fish bone' stuck in her throat after eating cod. On physical examination, while she reported an uncomfortable sensation in her throat, no airway compromise was evident. Clinical examination, including ear, nose and throat (ENT) and oropharyngeal assessment, was unremarkable. A linear opacity consistent with a fishbone was visualised on a soft tissue lateral neck X-ray anterior to the vertebral body of C4–6. One attempt to visualise the fishbone on direct laryngoscopy failed in the ED. The fishbone was later removed the next day via direct visualisation with a flexible endoscope in the operating theatre by the ENT surgical team. The patient's recovery was uneventful.

http://ift.tt/2rx8Vja

Late-onset jaw and teeth pain mimicking trigeminal neuralgia associated with chronic vagal nerve stimulation: case series and review of the literature

Vagal nerve stimulation (VNS) for refractory epilepsy is well established. Trigeminal neuralgia itself is a common disease in adults, and thus, late-onset pain in the trigeminal region under VNS, which is extr...

http://ift.tt/2syXSpC

To be active through indoor-climbing: an exploratory feasibility study in a group of children with cerebral palsy and typically developing children

Cerebral Palsy (CP) is the most common cause of motor disabilities in children and young adults and it is also often associated with cognitive and physiological challenges. Climbing requires a multifaceted rep...

http://ift.tt/2t8A892

Are surface markers of cancer stem cells reliable factors for cancer treatment follow-up?

Abstract

Recent studies have explained that cancer stem cells (CSCs) can both instigate and maintain tumours. As a result, they are a good choice for targeted therapy in the treatment of aggressive cancers, and their long-term assessment is essential for the follow-up of therapeutic agent efficacy. However, several studies have revealed that their detection on the basis of surface markers is challenging. In this area, there are two main questions. First, why are surface markers of the CSCs so difficult to detect in in vitro studies? Second, are CSCs' surface markers reliable factors when assessing cancer treatment efficacy? In order to consider these questions, we made three assumptions: (1) CSCs can grow in environmental conditions and in vitro studies, (2) stress exists within in vitro conditions, and (3) isotope diversity in surface markers might lead to problems in reliable identification.

http://ift.tt/2s7LHyT

Phosphatidylethanolamine targeting for cell death imaging in early treatment response evaluation and disease diagnosis

Abstract

Phosphatidylethanolamine (PE) is one of the most abundant phospholipids in mammalian plasma membranes. In healthy cells, PE resides predominantly in the inner leaflet of the cell membrane. In dead or dying cells on the other hand, PE is externalized to the outer leaflet of the plasma membrane. The exposure of PE on the cell surface has therefore become an attractive target for the molecular imaging of cell death using single-photon emission computed tomography (SPECT) and positron emission tomography (PET). This has motivated the development of PE-specific probes to measure cell death in vitro and non-invasively in vivo. In this review, we highlight the biological roles of PE on cell membranes, and PE exposure as a biomarker of cell death in disease processes, along with the use of PE-binding molecular probes to target PE for the characterization of cell death on a cellular and tissue level. We specifically emphasize the preclinical applications of radiolabeled duramycin for the non-invasive imaging of cell death in animal models of disease and in tumors after therapy. In addition, we discuss the clinical relevance, limitations and future perspectives of this imaging approach of cell death.

http://ift.tt/2sFx0nu

Hyperkeratosis and Discoloration of the Toenails in an 8-Year-Old

An 8-year-old boy with no pertinent past medical history presented to the dermatology clinic with a complaint of an abnormal appearance and occasional pain in both great toenails. His mother reported that the nail changes had been present since the patient was born. The child had undergone surgical removal of both toenails 2 years prior, however, the nails grew back with a similar appearance. The patient denied any recent trauma to his toenails. No other family members were known to have a similar condition.

http://ift.tt/2rwWVOE

A Computable Phenotype Improves Cohort Ascertainment in a Pediatric Pulmonary Hypertension Registry

To compare registry and electronic health record (EHR) data mining approaches for cohort ascertainment in patients with pediatric pulmonary hypertension (PH) in an effort to overcome some of the limitations of registry enrollment alone in identifying patients with particular disease phenotypes.

http://ift.tt/2sgTQzc

Editorial: which iron preparation for patients with IBD?

http://ift.tt/2s7FWAU

The Impact of Routine Evaluation of Gastric Residual Volumes on the Time to Achieve Full Enteral Feeding in Preterm Infants

To evaluate the time to full enteral feedings in preterm infants after a practice change from routine evaluation of gastric residual volume before each feeding to selective evaluation of gastric residual volume , and to evaluate the impact of this change on the incidence of necrotizing enterocolitis (NEC).

http://ift.tt/2shmosA

Short-, medium-, and long-term assessment of pulmonary dysfunction in extremely low birth weight neonates

Keller et al1 demonstrated in their randomized controlled trial, the Trial of Late Surfactant (TOLSURF) that treatment of extremely low gestational age neonates with late surfactant in combination with inhaled nitric oxide decreased the use of home oxygen while no difference in the rate of bronchopulmonary dysplasia (BPD) or death at 36 weeks of gestational age was seen. The results presented indicate that measures other than BPD may be more valuable in assessing pulmonary function in this cohort (eg, home oxygen use).

http://ift.tt/2sh4JkB

Reply

We appreciate the opportunity to respond to Meyer et al regarding our recent publication from the Trial of Late Surfactant (TOLSURF), describing the effects of late surfactant with inhaled nitric oxide on the respiratory status of high-risk extremely preterm infants, as determined at 1 year corrected age. We agree with the points raised by the writers, and described by Hines et al,1 regarding variability in the literature related to the diagnosis of bronchopulmonary dysplasia (BPD).1 The clinical definitions of BPD are muddied by clinical practices, while the physiological definitions depend on the cut-off used for adequate oxygen saturation, and require only a relatively brief time period to maintain that saturation level.

http://ift.tt/2rxDOUz

Thyroid Hormone Status in Sitosterolemia Is Modified by Ezetimibe

To assess the association between biomarkers of thyroid status and 5α-stanols in patients with sitosterolemia treated with ezetimibe (EZE).

http://ift.tt/2rxBs85

Prevalence and patterns of use of mantra, mindfulness and spiritual meditation among adults in the United States

Despite a growing body of scientific literature exploring the nature of meditation there is limited information on the characteristics of individuals who use it. This is particularly true of comparative studie...

http://ift.tt/2sFGWxt

Anti-inflammatory effect of Chang-An-Shuan on TNBS-induced experimental colitis in rats

Inflammatory bowel disease (IBD), denominated by Crohn's disease and ulcerative colitis, is often associated with abdominal pain, diarrhea and bloody stool. The standard protocols for treating colitis conditio...

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Editorial: refractory GERD—good drug, wrong patients?

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Editorial: yoga for QoL in ulcerative colitis—any better than other supportive activities? Authors’ reply

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Editorial: yoga for QoL in ulcerative colitis—any better than other supportive activities?

http://ift.tt/2s7Hg6V

Editorial: does disease extension lead to disease progression in proctitis?

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Editorial: when to be suspicious of malignancy-associated pseudoachalasia

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Editorial: is ribavirin needed in the treatment of post-transplant hepatitis C recurrence?

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Letter: the efficacy of oltipraz in patients with non-alcoholic fatty liver disease has not been confirmed—authors’ reply

http://ift.tt/2s7xz8B

Editorial: which iron preparation for patients with IBD? Authors’ reply

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Editorial: tackling hepatorenal syndrome—terlipressin for all, or time for a stratified approach?

http://ift.tt/2rCmWai

Editorial: lower gastrointestinal bleeding and low-dose aspirin—authors’ reply

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Editorial: lower gastrointestinal bleeding and low-dose aspirin

http://ift.tt/2rCgBfh

Ibrutinib Unmasks Critical Role of Bruton Tyrosine Kinase in Primary CNS Lymphoma [Research Articles]

Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with Nuclear factor kappa B (NF-B). The role of BTK in primary CNS lymphoma (PCNSL) is unknown. We performed a Phase 1 clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS Lymphoma. Clinical responses to ibrutinib occurred in 10/13 (77%) PCNSL patients, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of Caspase Recruitment Domain Family Member 11, a known ibrutinib resistance mechanism. Incomplete tumor responses were associated with mutations in the B-Cell Antigen Receptor-associated protein CD79B. CD79B-mutant PCNSLs showed enrichment of mammalian target of rapamycin (mTOR)-related gene sets and increased staining with Phosphatidylinositol 3-kinase (PI3K)/mTOR activation markers. Inhibition of the PI3K-isoforms p110α/p110 or mTOR synergized with ibrutinib to induce cell death in CD79B-mutant PCNSL cells.

http://ift.tt/2rm6Dz7

We could predict good responders to vagus nerve stimulation: a surrogate marker by slow cortical potential shift

Vagus nerve stimulation (VNS) is a palliative treatment option for patients with intractable epilepsy who are not good candidates for surgical resection (Connor et al., 2012). VNS uses an electrical stimulator, like those in cardiac pacemakers, which is implanted in the subclavicular area and delivers trains of electrical pulses to the left vagus nerve via bipolar stimulating electrodes (Terry et al., 1990). The stimulation of the vagus nerve is intermittent, and the usual stimulation condition is set to a signal on-time (VNS ON) of 30 s followed by an off-time (VNS OFF) of 3–5 min (Heck et al., 2002) repeatedly.

http://ift.tt/2rwZU9U

Issue Information - Editorial Board

http://ift.tt/2rxlpaE

Modeling Cancer Mutations in 3-D [News in Brief]

Scientists hope new tool—COSMIC-3D—will aid the design of novel drugs.

http://ift.tt/2sF196y

Pan-Cancer Analysis Pinpoints Targets in PI3K Pathway [News in Brief]

Proteogenomic study reveals genes' unexpected impact on PI3K/AKT/mTOR pathway.

http://ift.tt/2rmCmA6

A Prospective Multicenter Study Evaluating Learning Curves and Competence in Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography Among Advanced Endoscopy Trainees: The Rapid Assessment of Trainee Endoscopy Skills (RATES) Study

Based on the Next Accreditation System, trainee assessment should occur on a continuous basis with individualized feedback. We aimed to validate endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) learning curves among advanced endoscopy trainees (AETs) using a large national sample of training programs and to develop a centralized database that allows assessment of performance in relation to peers.

http://ift.tt/2tte2NC

MR-OPERA – A Multi-center/multi-vendor validation of MRI-only prostate treatment planning using synthetic CT images

This study aimed to validate a commercially available software for MR to synthetic CT conversion for the use in an MRI-only prostate external radiotherapy workflow. A multi-center study design was used to compare CT-based treatment plans to recalculated synthetic CT plans for 170 prostate cancer patients. The software was found to be robust for a variety of field strengths, vendors and treatment techniques.

http://ift.tt/2ttkCE5

Risk of pneumonia caused by Pneumocystis jirovecii in inflammatory bowel disease: the role of concomitant pulmonary comorbidities

http://ift.tt/2ttlGYm

Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review

A comprehensive knowledge of the natural history of UC helps understand disease evolution, identify poor prognostic markers and impact of treatment strategies and facilitates shared decision-making. We systematically reviewed the natural history of UC in adult population-based cohort studies with long-term follow-up.

http://ift.tt/2svE9qg

Thyroid cancer in adolescents and young adults

Future Oncology Ahead of Print.


http://ift.tt/2rmsjeE

Decision-making in Swiss home-like childbirth: A grounded theory study

Publication date: Available online 16 June 2017
Source:Women and Birth
Author(s): Yvonne Meyer, Franziska Frank, Franziska Schläppy Muntwyler, Valerie Fleming, Jessica Pehlke-Milde
BackgroundDecision-making in midwifery, including a claim for shared decision-making between midwives and women, is of major significance for the health of mother and child. Midwives have little information about how to share decision-making responsibilities with women, especially when complications arise during birth.AimTo increase understanding of decision-making in complex home-like birth settings by exploring midwives' and women's perspectives and to develop a dynamic model integrating participatory processes for making shared decisions.MethodsThe study, based on grounded theory methodology, analysed 20 interviews of midwives and 20 women who had experienced complications in home-like births.FindingsThe central phenomenon that arose from the data was "defining/redefining decision as a joint commitment to healthy childbirth". The sub-indicators that make up this phenomenon were safety, responsibility, mutual and personal commitments. These sub-indicators were also identified to influence temporal conditions of decision-making and to apply different strategies for shared decision-making. Women adopted strategies such as delegating a decision, making the midwife's decision her own, challenging a decision or taking a decision driven by the dynamics of childbirth. Midwives employed strategies such as remaining indecisive, approving a woman's decision, making an informed decision or taking the necessary decision.Discussion and conclusionTo respond to recommendations for shared responsibility for care, midwives need to strengthen their shared decision-making skills. The visual model of decision-making in childbirth derived from the data provides a framework for transferring clinical reasoning into practice.



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In Response.

No abstract available

http://ift.tt/2rC7POa

Daily Activity of the Housefly, Musca domestica, Is Influenced by Temperature Independent of 3' UTR period Gene Splicing

Circadian clocks orchestrate daily activity patterns and free running periods of locomotor activity under constant conditions. While the first often depends on temperature, the latter is temperature-compensated over a physiologically relevant range. Here, we explored the locomotor activity of the temperate housefly, Musca domestica. Under low temperatures, activity was centered round a major and broad afternoon peak, while high temperatures resulted in activity throughout the photophase with a mild mid-day depression, which was especially pronounced in males exposed to long photoperiods. While period (per) mRNA peaked earlier under low temperatures, no temperature-dependent splicing of the last per 3' end intron was identified. The expression of timeless, vrille, and Par domain protein 1 was also influenced by temperature, each in a different manner. Our data indicated that comparable behavioral trends in daily activity distribution have evolved in Drosophila melanogaster and Musca domestica, yet the behaviors of these two species are orchestrated by different molecular mechanisms.

http://ift.tt/2rBZNFd

Wind of Change or Siren Song?.

No abstract available

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In Response.

No abstract available

http://ift.tt/2rCcwHF

In Response.

No abstract available

http://ift.tt/2s7sgpy

Intraperitoneal Instillation of Local Anesthetics: Is This a Suitable Alternative for Postcesarean Pain Relief Without Toxicity Profiling?.

No abstract available

http://ift.tt/2rCeh7R

Evaluation of the Temple Touch Pro, a Novel Noninvasive Core-Temperature Monitoring System.

BACKGROUND: The Temple Touch Pro (TTP) is a novel system that estimates core temperature from skin over the temporal artery. We tested the hypothesis that this noninvasive system estimates core temperature to an accuracy within 0.5[masculine ordinal indicator]C. METHODS: Core temperature was continuously monitored in 50 adult and pediatric surgical patients by positioning the sensor patch of a TTP over one temporal artery. The sensor consists of a thermistor array near the skin surface, another set of thermistors above an insulator, and a second insulator between the upper unit and the environment. The sensor measures skin temperature and heat flux, from which the monitor unit estimates core temperature from a proprietary algorithm. Reference core temperature was measured from the esophagus or nasopharynx. We conducted agreement analysis between the TTP and the reference core temperature measurements using the 95% Bland-Altman limits of agreement for repeated measurement data. The proportion of all differences that were within 0.5[masculine ordinal indicator]C and repeat measures concordance correlation coefficient (CCC) were estimated as well. RESULTS: TTP and the reference core temperature measurements agreed well in both adults and pediatric patients. Bland-Altman plots showed no evidence of systematic bias or variability over the temperature from 35.2[masculine ordinal indicator]C to 37.8[masculine ordinal indicator]C. The estimated 95% lower and upper limits of agreement were -0.57[masculine ordinal indicator]C (95% confidence interval [CI], -0.76 to -0.41) and 0.57[masculine ordinal indicator]C (95% CI, 0.44 to 0.71), indicating good agreement between the 2 methods. Ninety-four percentage (95% CI, 87% to 99%) of the TTP temperatures were within 0.5[masculine ordinal indicator]C of the reference temperature. Good agreement was also supported by an estimated repeated measures CCC of 0.82 (95% CI, 0.66 to 0.91). The TTP core temperature measurements also agreed well with nasopharyngeal reference temperatures. CONCLUSIONS: The noninvasive TTP system is sufficiently accurate and reliable for routine intraoperative core temperature monitoring. (C) 2017 International Anesthesia Research Society

http://ift.tt/2s7dOOl

The R148.3 Gene Modulates Caenorhabditis elegans Lifespan and Fat Metabolism

Despite many advances, the molecular links between energy metabolism and longevity are not well understood. Here, we have used the nematode model Caenorhabditis elegans to study the role of the yet uncharacterized gene R148.3 in fat accumulation and lifespan. In wild-type worms, a R148.3p::GFP reporter showed enhanced expression throughout life in the pharynx, in neurons, and in muscles. Functionally, a protein fusing a predicted 22 aa N-terminal signal sequence (SS) of R148.3 to mCherry displayed robust accumulation in coelomyocytes, indicating that R148.3 is a secreted protein. Systematic depletion of R148.3 by RNA interference (RNAi) at L1 but not at young adult stage enhanced triglyceride accumulation, which was associated with increased food uptake and lower expression of genes involved in lipid oxidation. However, RNAi of R148.3 at both L1 and young adult stages robustly diminished mean and maximal lifespan of wild-type worms, and also abolished the long-lived phenotypes of eat-2 and daf-2/InsR mutants. Based on these data, we propose that R148.3 is a secreted signal that modulates fat mass and longevity in an independent manner.

http://ift.tt/2s79aQr

A Genetic Screen Reveals an Unexpected Role for Yorkie Signaling in JAK/STAT-dependent Hematopoietic Malignancies in Drosophila melanogaster

A gain-of-function mutation in the tyrosine kinase JAK2 (JAK2^V617F) causes human myeloproliferative neoplasms (MPNs). These patients present with high numbers of myeloid lineage cells and have numerous complications. Since current MPN therapies are not curative, there is a need to find new regulators and targets of JAK/STAT signaling that may represent additional clinical interventions. Drosophila melanogaster offers a low complexity model to study MPNs as JAK/STAT signaling is simplified with only one JAK (Hopscotch (Hop)) and one STAT (Stat92E). hop^{Tumorous-lethal (Tum-l)} is a gain-of-function mutation that causes dramatic expansion of myeloid cells, which then form lethal melanotic tumors. Through an F1 deficiency (Df) screen, we identified 11 suppressors and 35 enhancers of melanotic tumors in hop^Tum-l animals. Dfs that uncover the Hippo (Hpo) pathway genes expanded (ex) and warts (wts) strongly enhanced the hop^Tum-l tumor burden, as did mutations in ex, wts and other Hpo pathway genes. Target genes of the Hpo pathway effector Yorkie (Yki) were significantly upregulated in hop^Tum-l blood cells, indicating that Yki signaling was increased. Ectopic hematopoietic activation of Yki in otherwise wild-type animals increased hemocyte proliferation but did not induce melanotic tumors. However, hematopoietic depletion of Yki significantly reduced the hop^Tum-l tumor burden, demonstrating that Yki is required for melanotic tumors in this background. These results support a model in which elevated Yki signaling increases the number of hemocytes, which become melanotic tumors as a result of elevated JAK/STAT signaling.

http://ift.tt/2s74gD4

A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affected by Spongy Degeneration with Cerebellar Ataxia (SDCA2)

Spongy degeneration with cerebellar ataxia (SDCA) is a genetically heterogeneous neurodegenerative disorder with autosomal recessive inheritance in Malinois dogs, one of the four varieties of the Belgian Shepherd breed. Using a combined linkage and homozygosity mapping approach we identified a ~10.6 Mb critical interval on chromosome 5 in a Malinois family with four puppies affected by cerebellar dysfunction. Visual inspection of the 10.6 Mb interval in whole genome sequencing data from one affected puppy revealed a 227 bp SINE insertion into the ATP1B2 gene encoding the β₂ subunit of the Na⁺/K⁺-ATPase holoenzyme (ATP1B2:c.130_131insLT796559.1:g.50_276). The SINE insertion caused aberrant RNA splicing. Immunohistochemistry indicated a reduction of ATP1B2 protein expression in the central nervous system of affected puppies. Atp1b2 knock-out mice had previously been reported to show clinical and neurohistopathological findings similar to the affected Malinois puppies. Therefore, we consider ATP1B2:c.130_131ins227 the most likely candidate causative variant for a second subtype of SDCA in Malinois dogs, which we propose to term spongy degeneration with cerebellar ataxia subtype 2 (SDCA2). Our study further elucidates the genetic and phenotypic complexity underlying cerebellar dysfunction in Malinois dogs and provides the basis for a genetic test to eradicate one specific neurodegenerative disease from the breeding population in Malinois and the other varieties of the Belgian Shepherd breed. ATP1B2 thus represents another candidate gene for human inherited cerebellar ataxias, and SDCA2 affected Malinois puppies may serve as naturally occurring animal model for this disorder.

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Multidimensional Genetic Analysis of Repeated Seizures in the Hybrid Mouse Diversity Panel Reveals a Novel Epileptogenesis Susceptibility Locus

Epilepsy has many causes and comorbidities affecting as many as 4% of people in their lifetime. Both idiopathic and symptomatic epilepsies are highly heritable, but genetic factors are difficult to characterize among humans due to complex disease etiologies. Rodent genetic studies have been critical to the discovery of seizure susceptibility loci, including Kcnj10 mutations identified in both mouse and human cohorts. However, genetic analyses of epilepsy phenotypes in mice to date have been carried out as acute studies in seizure-naive animals or in Mendelian models of epilepsy, while humans with epilepsy have a history of recurrent seizures that also modify brain physiology. We have applied a repeated seizure model to a genetic reference population, following seizure susceptibility over a 36-day period. Initial differences in generalized seizure threshold among the Hybrid Mouse Diversity Panel were associated with a well-characterized seizure susceptibility locus found in mice; Seizure susceptibility 1. Remarkably, Szs1 influence diminished as subsequent induced seizures had diminishing latencies in certain HMDP strains. Administration of eight seizures, followed by an incubation period and an induced retest seizure, revealed novel associations within the calmodulin-activated transcription factor 1, Camta1. Using systems genetics, we have identified 4 candidate genes that are differentially expressed between seizure-sensitive and -resistant strains close to Esf1 that may act individually or as a coordinated response to the neuronal stress of seizures.

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Microbiology of Acute Rhinosinusitis in Immunosuppressed Patients.

Objective: The aim of this study was to identify causative organisms of acute rhinosinusitis in immunosuppressed patients by a retrospective chart review. Methods: Records were reviewed using International Classification of Disease, Ninth Edition codes for inpatient treatment of acute sinusitis. Patients were included only if they had formal sinus cultures obtained and were immunosuppressed, either carrying a diagnosis of a hematologic malignancy or receiving chemotherapy. Demographics, underlying malignancy, and culture results were recorded. Results: Records of 74 patients with 104 cultures were obtained. There were 43 males and 31 females. The mean age was 51. The most common primary diagnoses were leukemia (65%) and lymphoma (23%). Sixty cultures resulted in either no growth or growth of usual respiratory flora. Of the 44 positive cultures, 5 were polymicrobial, resulting in 61 organisms isolated in total. Bacteria cultured were 73% Gram positive, whereas 27% were Gram negative. The most common Gram-positive organisms cultured were Staphylococcus species. Pseudomonas species were the predominant Gram-negative bacteria. Thirteen samples grew fungal organisms. Conclusions: Medical management of sinusitis in an immunosuppressed patient seems to be adequate in most cases. Patients who fail to improve should undergo evaluation by an otolaryngologist to obtain cultures for directed antibiotic therapy. Infections by Staphylococcus species as well as quinolone- and cephalosporin-resistant Gram-negative organisms may be encountered, and clinicians should suspect their presence in patients with persistent disease and expand their antibiotic coverage appropriately. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Pseudomonas Aeruginosa Bacteremia in Patients With Hematologic Malignancies.

Introduction: Pseudomonas aeruginosa is a gram-negative rod that is a major cause of bacteremia in patients with a hematologic malignancy. Neutropenia from induction chemotherapy is the main risk factor for P. aeruginosa bacteremia and sepsis in this population. We analyzed risk factors, antibiotic susceptibility patterns, and outcomes due to P. aeruginosa bacteremia in these patients from our institution and compared these with those of similar studies. Methods: This is a retrospective chart review analyzing P. aeruginosa bacteremia in patients with hematologic malignancies. Results: Between January 2012 and February 2016, a total of 71 patients met the requirements for inclusion in our study. The average age of study participants was 57.9 years. Of the 71 patients included, 43 (60.6%) were neutropenic at the time of positive blood culture, 28 (39.4%) were not neutropenic at the time of positive of blood culture, 23 (32.4%) developed either sepsis or severe sepsis during the course of their hospital stay, 8 (11.3%) developed septic shock, 10 (14.1%) required vasopressor administration, 8 (11.3%) required mechanical ventilation, and 6 (8.5%) required both vasopressor administration and mechanical ventilation. Discussion: Our research reaffirms the general severity of P. aeruginosa infections. Ultimately, 9 of 71 patients died as a result of their infection, with a mortality rate of 12.7%. Individuals whose bacteremia progressed to septic shock were much more likely to die. The case fatality rate of septic shock was 62.5%. Our data are congruent with other research that finds advanced age to be a significant risk factor for mortality. Our study also found that individuals who received a bone marrow transplant before developing bacteremia were more likely to survive than individuals who did not receive a bone marrow transplant. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Concomitant Primary Labial and Genital Herpes Simplex I Infections.

There has been a decrease in the prevalence of herpes simplex type I (HSV I) infection in adolescents in the United States while the relative number of genital infections caused by HSV I has increased. Although transmission is more likely to occur during active skin lesions, asymptomatic shedding of herpes simplex virus from oral or genital sources can lead to infection in susceptible hosts. I wish to report the acquisition of concomitant primary labial and genital HSV I infection in a man and woman from an asymptomatic woman with a history of labial HSV I infection. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Liver Abscess in Patients With Leukemia and Prolonged Neutropenia.

Patients with leukemia are at a high risk of developing disseminated invasive fungal and/or bacterial infections due to prolonged neutropenia, which is usually caused by myelosuppressive chemotherapy. Disseminated fungal infections in the setting of prolonged neutropenia result in high mortality. The most effective means to improve patient outcome is early diagnosis and treatment when preventive measures have failed. The most common fungal pathogens are Candida spp and Aspergillus spp. Rare causes of such infection are by Mucor and Entomopthorales spp, Fusarium spp, and Scedosporium spp, each having unique epidemiology, pathophysiology, and treatment options. We present a case of disseminated hepatic, pulmonary, bowel, and appendix mucormycosis successfully treated with antifungal therapy and without surgical intervention. We also review the literature regarding hepatic abscesses and disseminated invasive fungal infections along with current treatment strategies for Mucor infections. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Oral Serum-Derived Bovine Immunoglobulin for Management of Infectious Diarrhea due to Norovirus and Cryptosporidiosis in Solid Organ Transplant Patients.

Diarrhea and its sequelae are commonly seen in renal transplant recipients. Current effective options to treat many causes of infectious diarrhea in this population are limited. Oral serum-derived bovine immunoglobulin was recently successfully used to manage 2 renal transplant patients with diarrhea due to cryptosporidiosis and norovirus infection, respectively. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Treatment of Klebsiella pneumoniae Carbapenemase-Producing Klebsiella pneumoniae Bacteremia With Meropenem, Colistin, and Ceftazidime-Avibactam: A Case Report.

Ceftazidime-avibactam is a novel combination antimicrobial agent consisting of a broad-spectrum cephalosporin, ceftazidime, and a non-[beta]-lactam [beta]-lactamase inhibitor, avibactam. This agent has demonstrated activity against resistant gram-negative bacteria, including Klebsiella pneumoniae carbapenemase-producing organisms; however, it is US Food and Drug Administration approved for use in urinary tract and intra-abdominal infections only. We present a case of successful treatment of K. pneumoniae carbapenemase-producing K. pneumoniae bacteremia with a combination of meropenem and colistin followed by ceftazidime-avibactam and colistin. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Central Nervous System Varicella Zoster Virus Vasculopathy in Human Immunodeficiency Virus Patients.

Central nervous system varicella zoster virus (CNS-VZV)-related vasculopathy can be severe and fatal. Delayed diagnosis impedes recovery. We reviewed case reports and case series in the literature. Fifty-five patients were identified. Forty patients (85%) had CD4 counts of less than 200 cells/[mu]L. Eight patients (15%) had VZV vasculopathy secondary to CNS immune reconstitution inflammatory syndrome (IRIS). A quarter of the patients never had a history of VZV rash. Eighty-five percent of the reported angiographic studies were abnormal. Cerebrospinal fluid (CSF) pleocytosis was found in 58% (21/36). Eighty-six percent (24/28) of patients had VZV DNA in their CSF, and 71% of patients (12/17) had anti-VZV immunoglobulin G antibodies. Eighty-nine percent of the patients without CNS-IRIS who received acyclovir with corticosteroids had a good recovery. Only 30% of patients who received acyclovir alone had good outcomes. All CNS-IRIS patients except 1 had a good outcome whether they received corticosteroids. The mortality in patients without CNS-IRIS was 55%; it was 12% in CNS-IRIS patients. A history of VZV rash, abnormal vascular imaging, and CSF studies usually make the diagnosis of VZV vasculopathy in human immunodeficiency virus patients, but negative studies do not rule it out in some cases. A combination of acyclovir and corticosteroids seems to improve the outcome in patients without CNS-IRIS. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Human Immunodeficiency Virus as Progressive Primary Myopathy: A Possibility in Children? A Rare Case Report.

Human immunodeficiency virus infection in children has a different way of presentation. The involvement of muscular system is most commonly described as pyomyositis because of opportunistic infections or myopathy secondary to highly active antiretroviral therapy in both children and adults. Primary myopathy presenting as a progressive weakness is usually seen in adults and rarely observed in children with only a few cases described in the literature. In this case, we report a 7-year-old Indian girl with perinatal HIV infection presenting with progressive weakness and otherwise asymptomatic. An improvement was observed after antiretroviral and rehabilitative therapy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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No to Pip-Tazo: Identifying Inappropriate Use of Piperacillin-Tazobactam for Treatment of Skin and Soft Tissue Infections.

Background: Overuse of broad-spectrum antibiotics for the treatment of skin and soft tissue infections (SSTIs) is common. The objective of this study is to identify inappropriate use of piperacillin-tazobactam in the setting of SSTIs to help enhance future stewardship efforts to promote guideline concordant treatments of SSTIs at our institution. Methods: Pharmacy records of all piperacillin-tazobactam orders from October 2013 to June 2015 were retrospectively reviewed at a tertiary Veterans Affairs (VA) medical center. Empiric piperacillin-tazobactam use for patients admitted with SSTIs was identified and evaluated for inappropriateness according to infection type (diabetic foot infection, nonpurulent, purulent, surgical site infection) and severity (mild, moderate, severe) based on institutional and national guidelines. Results: Piperacillin-tazobactam was ordered empirically in 212 SSTI episodes, 166 of which were started in the emergency department. One hundred fifty-two patients had piperacillin-tazobactam orders continued or started on admission; of these, only 40 uses (26.3%) were appropriate, with use in severe infection associated with the highest rate of appropriateness compared with moderate or mild infection (severe, 50.0%; moderate, 12.5%; mild, 15.3%; P

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Pasteurella Multocida Cardiovascular Implantable Electronic Device Infection With Recurrent Bacteremia: A Case Report.

The annual rate of placement of cardiovascular implantable electronic devices (CIEDs), which includes pacemakers and implantable cardiac defibrillators, has steadily increased over the last several decades. With an increasing number of implantations has been an increasing incidence of CIED infections. It is generally recommended that patients with infections of CIEDs complete a course of antibiotics and have the device removed if possible. However, gram-negative organisms are uncommon in CIED infection, and it has been suggested that cases of suspected gram-negative CIED infection may not necessitate the same management approach. Here, we report a case of presumed Pasteurella multocida CIED infection and share our experience with its several management challenges. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Myroides Soft Tissue Infections: Falling Outside of Practice Guidelines A Propos an Instructive Case.

Previously classified as Flavobacterium odoratum, Myroides species, although not regular constituents of the normal endogenous human flora may occasionally cause clinical disease. Most infections follow either exposure to environmental sources or acquired nosocomially often linked to contaminated water. The bulk of nonhealthcare-associated infections involve skin and soft tissues resulting from a traumatic event frequently accompanied by bacteremia. Once considered to be "opportunistic pathogens," infections with Myroides also occur in immunocompetent individuals. Their unanticipated involvement and inherent multidrug resistance often lead to treatment failures when empiric and practice guideline recommended antimicrobial regimens be administered. However, other than in specific circumstances, it remains in the best interest of "good practice," antibiotic stewardship efforts, and patient care to adhere to evidence-based guidelines and avoid influences such as the case we present and anecdotal experiences suggesting that broad-spectrum empiric antibiotic prescribing is a prudent practice in the initial treatment of undefined skin and soft tissues. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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A Complete Guide on Crushing Tablets and/or Opening Capsules of Human Immunodeficiency Virus Medications.

There are limited data regarding the ability to crush tablets or open capsules for antiretroviral agents. This lack of data is problematic when encountering patients who cannot swallow these tablets or capsules, especially for patients who are mechanically ventilated. Furthermore, many antiretroviral agents do not have an oral or intravenous solution available. The authors address this issue by reviewing all commercially available antiretroviral agents to determine whether they could crush tablets or open capsules. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Fecal Microbiota Transplant in Severe/Complicated Clostridium difficile Infection: A Retrospective Case Series.

Clostridium difficile infection (CDI) is the most common hospital-acquired infection in the United States. Fecal microbiota transplant (FMT) has become a highly efficacious therapy for recurrent mild/moderate disease; however, the efficacy and optimal delivery method in severe/complicated disease is unknown. A retrospective chart review was performed for all FMT recipients at the University of Alabama at Birmingham. Those with severe/complicated disease were isolated and their clinical course documented via chart review and phone calls. Eight patients with severe/complicated CDI who received FMT via both lower and/or upper routes were documented. Six experienced eventual cure, 2 died, with 1 death attributed to CDI, the other to another nosocomial infection. Fecal microbiota transplant is a reasonable option and should be considered in patients who are not surgical candidates. If lower endoscopy is not possible, delivery of FMT via nasogastric tube should also be considered. More studies comparing the efficacy of these routes are needed. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Vancomycin-Resistant Enterococcal Meningitis, Disseminated Strongyloidiasis, and Hypogammaglobulinemia.

The role of immunoglobulins in control of strongyloidiasis has not been well appreciated. This case of disseminated strongyloidiasis with vancomycin-resistant Enterococcus faecium meningitis illustrates the critical role of immunoglobulins in preventing the Strongyloides hyperinfection syndrome. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Loss of FAM46C promotes cell survival in myeloma

FAM46C is one of the most recurrently mutated genes in multiple myeloma (MM), however its role in disease pathogenesis has not been determined. Here we demonstrate that wild type (WT) FAM46C overexpression induces substantial cytotoxicity in MM cells. In contrast, FAM46C mutations found in MM patients abrogate this cytotoxicity, indicating a survival advantage conferred by the FAM46C mutant phenotype. WT FAM46C overexpression downregulated IRF4, CEBPB, and MYC and upregulated immunoglobulin (Ig) light chain and HSPA5/BIP. Furthermore, pathway analysis suggests that enforced FAM46C expression activated the unfolded protein response (UPR) pathway and induced mitochondrial dysfunction. CRISPR-mediated depletion of endogenous FAM46C enhanced MM cell growth, decreased Ig light chain and BIP expression, activated ERK and anti-apoptotic signaling, and conferred relative resistance to dexamethasone and lenalidomide treatments. Genes altered in FAM46C-depleted cells were enriched for signaling pathways regulating estrogen, glucocorticoid, B cell receptor signaling, and ATM signaling. Together these results implicate FAM46C in myeloma cell growth and survival and identify FAM46C mutation as a contributor to myeloma pathogenesis and disease progression via perturbation in plasma cell differentiation and endoplasmic reticulum homeostasis.

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IGFBP7 Deletion Promotes Hepatocellular Carcinoma

Activation of IGF signaling is a major oncogenic event in diverse cancers, including hepatocellular carcinoma (HCC). In this setting, the insulin-like growth factor binding protein IGFBP7 inhibits IGF signaling by binding the IGF-1 receptor (IGF-1R), functioning as a candidate tumor suppressor. IGFBP7 abrogates tumors by inhibiting angiogenesis and inducing cancer-specific senescence and apoptosis. Here we report that Igfbp7-deficient mice exhibit constitutively active IGF signaling, presenting with pro-inflammatory and immunosuppressive microenvironments and spontaneous liver and lung tumors occurring with increased incidence in carcinogen-treated subjects. Igfbp7 deletion increased proliferation and decreased senescence of hepatocytes and mouse embryonic fibroblasts, effects that were blocked by treatment with IGF-1 receptor inhibitor. Significant inhibition of genes regulating immune surveillance was observed in Igfbp7-/- murine livers, which was associated with a marked inhibition in antigen cross-presentation by Igfbp7-/- dendritic cells. Conversely, IGFBP7 overexpression inhibited growth of HCC cells in syngeneic immunocompetent mice. Depletion of CD4+ or CD8+ T lymphocytes abolished this growth inhibition, identifying it as an immune-mediated response. Our findings define an immune component of the pleiotropic mechanisms through which IGFBP7 suppresses HCC. Furthermore, they offer a genetically based preclinical proof of concept for IGFBP7 as a therapeutic target for immune management of HCC.

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Heme-oxygenase-1 production by intestinal CX3CR1+ macrophages helps to resolve inflammation and prevents carcinogenesis

CX3CR1+ macrophages in the intestinal lamina propria contribute to gut homeostasis through the immunomodulatory interleukin IL-10, but there is little knowledge on how these cells or the CX3CR1 receptor may affect colorectal carcinogenesis. In this study, we show that CX3CR1-deficient mice fail to resolve gut inflammation despite high production of IL-10 and have increased colitis and adenomatous polyps in chemical and genetic models of colon carcinogenesis. Mechanistically, CX3CL1-mediated engagement of the CX3CR1 receptor induced upregulation of hemoxygenase-1 (HMOX-1), an antioxidant and anti-inflammatory enzyme. CX3CR1-deficient mice exhibited significantly lower expression of HMOX-1 in their adenomatous colon tissues. Combining LPS and CX3CL1 displayed a strong synergistic effect in vitro, but HMOX-1 levels were significantly lower in KO macrophages. Co-housing of wild-type and CX3CR1-/- mice during the AOM/DSS treatment attenuated disease severity in CX3CR1-/- mice, indicating the importance of the microbiome, but did not fully reinstate HMOX-1 levels and did not abolish polyp formation. In contrast, pharmacological induction of HMOX-1 in vivo by cobalt protoporphyrin-IX treatment eradicated intestinal inflammation and fully protected KO mice from carcinogenesis. Taken together, our results establish an essential role for the receptor CX3CR1 in gut macrophages in resolving inflammation in the intestine, where it helps protects against colitis-associated cancer by regulating HMOX-1 expression.

http://ift.tt/2syot68

ARHGAP18 downregulation by miR-200b suppresses metastasis of triple negative breast cancer by enhancing activation of RhoA

Rho GTPases activated in cancer cells drive proliferation, migration and metastasis. Thus, RhoGAP proteins which negatively regulate Rho GTPases are generally thought to function as tumor suppressors. Here this expectation was challenged by characterization of ARHGAP18, a RhoGAP family member that is selectively overexpressed in highly migratory triple negative breast cancer (TNBC) cells. In human breast tumors, higher ARHGAP18 levels associated with worse overall survival, recurrence-free survival and metastasis-free survival. In TNBC cells, ARHGAP18 deletion increased RhoA activation but reduced growth, migration and metastatic capacity. Mechanistic investigations revealed that ARHGAP18 levels were controlled by miR-200b, the enforced expression of which was sufficient to activate RhoA, enhance formation of focal adhesions and actin stress fibers, and reduced migration and metastasis. Enforced elevation of ARHGAP18 where miR-200b was stably expressed reduced RhoA activity but increased cell migration. Pharmacological inhibition of the Rho effector kinase ROCK blocked RhoA signaling and reversed the inhibitory effect of miR-200b on cell migration. Lastly, ARHGAP18 overexpression or ROCK inhibition was sufficient to overcome metastatic blockade by miR-200b. Taken together, these results define opposing roles for oncogenic ARHGAP18 and tumor suppressive miR-200b in determining TNBC cell migration and metastatic prowess.

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Langerhans und Merkel: a nervous epidermal dispute

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Unexpired Nitroglycerin Injection in 5 Percent Dextrose USP by Advanced Pharma in Houston: Recall - Sub Potency

[Posted 06/15/2017] AUDIENCE: Pharmacy, Cardiology, Nursing ISSUE: Advanced Pharma, Inc. d/b/a Avella of Houston ("Advanced Pharma") is voluntarily recalling all unexpired lots of Nitroglycerin products that were produced at Advanced...

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Clinical tools to assess nutritional risk and malnutrition in hospitalizaed children and adolescents

Malnutrition in children and adolescents may be underestimated during hospital stay. In western countries, children were often hospitalized for acute or chronic diseases that are not necessarily related to malnutrition. However, acute or chronic injuries may hamper nutritional status, prolonging recovery after admission and consequently length of hospital stay.

Several methods and techniques are known to investigate malnutrition in children, even if their use is not widespread in clinical practice. Many of these are simple and easy to perform and could be useful to a better management of every kind of illness.

In this review, we will focus on clinical tools necessary to reveal a nutritional risk at admission and to assess nutritional status in hospitalized children and adolescents.

L'articolo Clinical tools to assess nutritional risk and malnutrition in hospitalizaed children and adolescents sembra essere il primo su European Review.

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Biomarkers for the Management of Castration-Resistant Prostate Cancer: We Are Not There Yet

Abstract

In recent years, there has been a marked increase in the number of approved therapies that increase survival of patients with castration-resistant prostate cancer. Current treatment guidelines provide therapeutic management recommendations, but these are primarily based on clinical factors such as performance status or site of metastasis (bone vs. visceral), and not on underlying molecular or cellular features of disease that may predict response. The ability to tailor treatment based on molecular or cellular features of disease could potentially reduce the occurrence of unnecessary side effects and ineffective treatments, and thereby reduce both direct and indirect medical costs. As such, it is important to identify and validate new prognostic and predictive molecular biomarkers that can be used to direct cancer treatment. This review will focus on existing and potential biomarkers in the context of castration-resistant prostate cancer management and discuss the need for continued discovery and validation of new biomarkers and biomarker panels for prostate cancer.

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Acquired Resistance to Erlotinib in EGFR Mutation-Positive Lung Adenocarcinoma among Hispanics (CLICaP)

Abstract

Background

Lung cancer harboring epidermal growth factor receptor (EGFR) mutations and treated with EGFR tyrosine kinase inhibitors (TKIs) all eventually develop acquired resistance to the treatment, with half of the patients developing EGFR T790M resistance mutations.

Objective

The purpose of this study was to assess histological and clinical characteristics and survival outcomes in Hispanic EGFR mutated lung cancer patients after disease progression.

Patients and Methods

EGFR mutation-positive lung cancer patients (n = 34) with acquired resistance to the EGFR-TKI erlotinib were identified from 2011 to 2015. Post-progression tumor specimens were collected for molecular analysis. Post-progression interventions, response to treatment, and survival were assessed and compared among all patients and those with and without T790M mutations.

Results

Mean age was 59.4 ± 13.9 years, 65% were never-smokers, and 53% had a performance status 0–1. All patients received erlotinib as first-line treatment. Identified mutations included: 60% DelE19 (Del746–750) and 40% L858R. First-line erlotinib overall response rate (ORR) was 61.8% and progression free survival (PFS) was 16.8 months (95% CI: 13.7–19.9). Acquired resistance mutations identified were T790M mutation (47.1%); PI3K mutations (14.7%); EGFR amplification (14.7%); KRAS mutation (5.9%); MET amplification (8.8%); HER2 alterations (5.9%, deletions/insertions in e20); and SCLC transformation (2.9%). Of patients, 79.4% received treatment after progression. ORR for post-erlotinib treatment was 47.1% (CR 2/PR 14) and median PFS was 8.3 months (95% CI: 2.2–36.6). Median overall survival (OS) from treatment initiation was 32.9 months (95% CI: 30.4–35.3), and only the use of post-progression therapy affected OS in a multivariate analysis (p = 0.05).

Conclusions

Hispanic patients with acquired resistance to erlotinib continued to be sensitive to other treatments after progression. The proportion of T790M+ patients appears to be similar to that previously reported in Caucasians.

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Extreme assay sensitivity in molecular diagnostics further unveils intratumour heterogeneity in metastatic colorectal cancer as well as artifactual low-frequency mutations in the KRAS gene

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Tumour heterogeneity poses a significant challenge to cancer biomarker research

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Caveats in the Established Understanding of CMT1A

Abstract

Charcot-Marie-Tooth disease type-1A (CMT1A) is one of the most common types of inherited peripheral nerve diseases. It is caused by the trisomy of chromosome 17p12 (c17p12), a large DNA segment of 1.4 Mb containing PMP22 plus eight other genes. The size of c17p12 is formidable for any cloning technique to manipulate, and thus precludes production of models in vitro and in vivo that can precisely recapitulate the genetic alterations in humans with CMT1A. This limitation and other factors have led to several assumptions, which have yet been carefully scrutinized, serving as key principles in our understanding of the disease. For instance, one extra copy of c17p12 in patients with CMT1A results in a higher gene dosage of PMP22, thereby expected to produce a higher level of PMP22 mRNA/proteins that cause the disease. However, there has been increasing evidence that PMP22 levels are highly variable among patients with CMT1A and may fall into the normal range at a given time point. This raises an alternative mechanism causing the disease by dysregulation of PMP22 expression or excessive fluctuation of PMP22 levels, not the absolute increase of PMP22. This has become a pressing issue since recent clinical trials using ascorbic acid failed to alter the clinical outcome of CMT1A patients, leaving no effective therapy for the disease. In this article, we will discuss how this fundamental issue might be investigated. In addition, several other key issues in CMT1A will be discussed, including potential mechanisms responsible for the uniform slowing of conduction velocities. A clear understanding of these issues could radically change how therapies should be developed against CMT1A.

http://ift.tt/2s6pBwE

Nontuberculosis mycobacterial infections at a specialized tuberculosis treatment centre in the Republic of Korea

The incidence of nontuberculous mycobacteria (NTM) infections is increasing worldwide, however formal evaluations of the epidemiology of NTM infections are limited. Understanding the trends and true prevalence...

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Patterns of antimicrobial resistance in intensive care unit patients: a study in Vietnam

Antimicrobial resistance has emerged as a major concern in developing countries. The present study sought to define the pattern of antimicrobial resistance in ICU patients with ventilator-associated pneumonia.

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Measuring influenza laboratory capacity: use of a tool to measure improvements

To collect information, identify training needs, and assist with influenza capacity building voluntary laboratory capacity assessments were conducted using a standardized tool in CDC cooperative agreement coun...

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High expression of heat shock proteins and heat shock factor-1 distinguishes an aggressive subset of clear cell renal cell carcinoma

Abstract

Aims

Heat shock proteins (HSPs) are a group of molecules induced by a variety of environmental and pathophysiologic stresses, including cancer. HSPs are implicated in the regulation of apoptosis and immunity in neoplasm. Transcription factor heat shock factor1 (HSF1) acts as the master regulator to control HSP expression, and therefore is involved in tumorigenesis. The purpose of this study was to evaluate the expression and clinicopathologic relevance of HSPs and HSF1 in clear cell renal cell carcinoma (ccRCC).

Methods and results

The expression of HSP27, HSP60, HSP70, HSP90 and HSF1 was assessed in 428 cases of ccRCC using immunohistochemistry. High expression of HSP60 and HSP70 was positively correlated with grade and stage. High expression of HSF1 was positively correlated with stage. Univariate and multivariate analyses demonstrated that 216 patients (52%) with tumour expressing 3 or 4 markers in a panel of HSP60, HSP70, HSP90, and HSF1 had a significantly heightened risk for cancer-specific mortality than tumours expressing <3 markers (P<0.0001; concordance index, 0.81).

Conclusions

Immunohistochemical examination of HSPs and HSF1 provides useful prognostic information that may contribute to the design of therapeutic strategies for patients with ccRCC.

This article is protected by copyright. All rights reserved.

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Genetic analysis of varicella-zoster virus in the aqueous humor in uveitis with severe hyphema

Genetic variations have been identified in the genome of varicella-zoster virus (VZV) strains using vesicle fluid, varicella scabs and throat swab samples. We report a rare case of VZV-associated uveitis with ...

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Assessing changes in knowledge, attitude and practices on dengue diagnosis and management among primary care physicians after the largest dengue epidemic in Singapore

Dengue results in high morbidity and mortality globally. The knowledge, attitude and practices (KAP) of dengue management, including diagnosis, among primary care physicians (PCPs) are important to reduce deng...

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A delicate balance: Understanding acid-base issues in EMS patients

A basic understanding of how acid-base imbalances can affect the patient's presentation can help make sense of conflicting symptoms

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Focal b-catenin mutation identified on formalin-fixed and paraffin-embedded inflammatory hepatocellular adenomas

Abstract

The identification of hepatocellular adenoma (HCA) with mutation in exon 3 of the CTNNB1 gene encoding for b-catenin is clinically relevant due to higher risk of malignant transformation. Inflammatory HCA (IHCA) can exhibit b-catenin activation (b-IHCA). We report 2 cases with multiple IHCA in which focal b-catenin activation has been found in one of the IHCA. In both cases, the diagnosis of IHCA was confirmed on the resected nodules by routine stains, immunohistochemical detection of C-reactive protein (CRP), and molecular biology on frozen material. An additional molecular analysis was performed on formalin fixed paraffin embedded (FFPE) material that showed focal glutamine synthetase (GS) staining, the surrogate marker of b-catenin activation. In case one, it was a 1.8 cm area within the 7.5 cm IHCA, and in case two, a small 0.3 cm area within a 1.8 cm resected IHCA located close to a larger IHCA, negative for GS. In both cases, nuclear beta-catenin expression and decreased reticulin network were observed in the GS expressing foci, together with cholestasis and diffuse CD34 expression in case one. Molecular analysis by pyrosequencing on FFPE material using the GS stained slides as reference to select areas with/without positive staining revealed a CTNNB1 exon 3 mutation restricted to the areas exhibiting both positive GS and CRP expression, whereas wild-type CTNNB1 was found in areas showing only CRP staining. These 2 cases illustrate focal b-catenin activation that can occur within IHCAs. Additional data are needed to tell if b-catenin mutation is a secondary event in IHCA.

This article is protected by copyright. All rights reserved.

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EMT-Regulome: a database for EMT-related regulatory interactions, motifs and network

EMT-Regulome: a database for EMT-related regulatory interactions, motifs and network

Cell Death and Disease 8, e2872 (June 2017). doi:10.1038/cddis.2017.267

Authors: Zhangxiang Zhao, Wenbin Zhou, Yue Han, Fuduan Peng, Ruiping Wang, Ruihan Yu, Chengyu Wang, Haihai Liang, Zheng Guo & Yunyan Gu

http://ift.tt/2t7q404

Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop

Isodeoxyelephantopin induces protective autophagy in lung cancer cells via Nrf2-p62-keap1 feedback loop

Cell Death and Disease 8, e2876 (June 2017). doi:10.1038/cddis.2017.265

Authors: Yang Wang, Jing Zhang, Zhi-Hao Huang, Xiao-Hui Huang, Wei-Bin Zheng, Xing-Feng Yin, Yao-Lan Li, Bin Li & Qing-Yu He

http://ift.tt/2sxwQ1U

Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

Connective tissue growth factor promotes temozolomide resistance in glioblastoma through TGF-β1-dependent activation of Smad/ERK signaling

Cell Death and Disease 8, e2885 (June 2017). doi:10.1038/cddis.2017.248

Authors: Huijun Zeng, Zhao Yang, Ningbo Xu, Boyang Liu, Zhao Fu, Changlin Lian & Hongbo Guo

http://ift.tt/2t7bANw

Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway

Titanium particle-induced osteogenic inhibition and bone destruction are mediated by the GSK-3β/β-catenin signal pathway

Cell Death and Disease 8, e2878 (June 2017). doi:10.1038/cddis.2017.275

Authors: Ye Gu, Zhirong Wang, Jiawei Shi, Liangliang Wang, Zhenyang Hou, Xiaobin Guo, Yunxia Tao, Xiexing Wu, Wei Zhou, Yu Liu, Wen Zhang, Yaozeng Xu, Huilin Yang, Feng Xue & Dechun Geng

http://ift.tt/2sxIlX3

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1–42 toxicity in astrocytes

Heme oxygenase-1 derived carbon monoxide suppresses Aβ1–42 toxicity in astrocytes

Cell Death and Disease 8, e2884 (June 2017). doi:10.1038/cddis.2017.276

Authors: Nishani T Hettiarachchi, John P Boyle, Mark L Dallas, Moza M Al-Owais, Jason L Scragg & Chris Peers

http://ift.tt/2t7fA0q

Interaction between autophagy and senescence is required for dihydroartemisinin to alleviate liver fibrosis

Interaction between autophagy and senescence is required for dihydroartemisinin to alleviate liver fibrosis

Cell Death and Disease 8, e2886 (June 2017). doi:10.1038/cddis.2017.255

Authors: Zili Zhang, Zhen Yao, Shifeng Zhao, Jiangjuan Shao, Anping Chen, Feng Zhang & Shizhong Zheng

http://ift.tt/2sxiuyB

The NF-κB1 is a key regulator of acute but not chronic renal injury

The NF-κB1 is a key regulator of acute but not chronic renal injury

Cell Death and Disease 8, e2883 (June 2017). doi:10.1038/cddis.2017.233

Authors: Amy Fearn, Gerhard R Situmorang, Christopher Fox, Fiona Oakley, Rachel Howarth, Caroline L Wilson, Agklinta Kiosia, Michael G Robson, Derek A Mann, Anna Moles & Neil S Sheerin

http://ift.tt/2t7lIpA

Concomitant epigenetic targeting of LSD1 and HDAC synergistically induces mitochondrial apoptosis in rhabdomyosarcoma cells

Concomitant epigenetic targeting of LSD1 and HDAC synergistically induces mitochondrial apoptosis in rhabdomyosarcoma cells

Cell Death and Disease 8, e2879 (June 2017). doi:10.1038/cddis.2017.239

Authors: Tinka Haydn, Eric Metzger, Roland Schuele & Simone Fulda

http://ift.tt/2sy7HEe

Cdc20 directs proteasome-mediated degradation of the tumor suppressor SMAR1 in higher grades of cancer through the anaphase promoting complex

Cdc20 directs proteasome-mediated degradation of the tumor suppressor SMAR1 in higher grades of cancer through the anaphase promoting complex

Cell Death and Disease 8, e2882 (June 2017). doi:10.1038/cddis.2017.270

Authors: Debasish Paul, Suvankar Ghorai, U S Dinesh, Praveenkumar Shetty, Samit Chattopadhyay & Manas Kumar Santra

http://ift.tt/2t7fzJU

Bilirubin neurotoxicity is associated with proteasome inhibition

Bilirubin neurotoxicity is associated with proteasome inhibition

Cell Death and Disease 8, e2877 (June 2017). doi:10.1038/cddis.2017.274

Authors: Hongbiao Huang, Mingxing Guo, Ningning Liu, Chong Zhao, Haoyu Chen, Xiaoli Wang, Siyan Liao, Ping Zhou, Yuning Liao, Xin Chen, Xiaoying Lan, Jinghong Chen, Dacai Xu, Xiaofen Li, Xianping Shi, Li Yu, Yuqiang Nie, Xuejun Wang, Chang-E Zhang & Jinbao Liu

http://ift.tt/2sxVHTp

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

Nicotine protects rat hypoglossal motoneurons from excitotoxic death via downregulation of connexin 36

Cell Death and Disease 8, e2881 (June 2017). doi:10.1038/cddis.2017.232

Authors: Silvia Corsini, Maria Tortora, Rossana Rauti & Andrea Nistri

http://ift.tt/2t7mMcZ

Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development

This protocol describes an optogenetic strategy to modulate mitogen-activated protein kinase (MAPK) activity during cell differentiation and Xenopus embryonic development. This method allows for the reversible activation of the MAPK signaling pathway in mammalian cell culture and in multicellular live organisms, like Xenopus embryos, with high spatial and temporal resolution.

http://ift.tt/2sxL3vL

Frameless Stereotaxic Navigation Systems: FDA Safety Communication - Navigational Accuracy Errors

[Posted 06/15/2017] AUDIENCE: Otolaryngology, Orthopedics, Surgery ISSUE: The FDA is aware that some health care providers have experienced navigational accuracy errors during surgical procedures when using frameless stereotaxic navigation systems....

http://ift.tt/2rB0qyz

Paliperidone Extended-Release Tablets 3mg by Teva Pharmaceuticals: Recall - Dissolution Test Failure

[Posted 06/15/2017] AUDIENCE: Pharmacy, Psychiatry, Patient ISSUE: Teva Pharmaceuticals USA, Inc. (Teva) initiated a voluntary recall to retail-level on 05/31/2017 for one lot of Paliperidone Extended-Release Tablets, 3mg, 90 count bottles, lot...

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The enteric nervous system is a potential autoimmune target in multiple sclerosis

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) in young adults that has serious negative socioeconomic effects. In addition to symptoms caused by CNS pathology, the majority of MS patients frequently exhibit gastrointestinal dysfunction, which was previously either explained by the presence of spinal cord lesions or not directly linked to the autoimmune etiology of the disease. Here, we studied the enteric nervous system (ENS) in a B cell- and antibody-dependent mouse model of MS by immunohistochemistry and electron microscopy at different stages of the disease. ENS degeneration was evident prior to the development of CNS lesions and the onset of neurological deficits in mice. The pathology was antibody mediated and caused a significant decrease in gastrointestinal motility, which was associated with ENS gliosis and neuronal loss. We identified autoantibodies against four potential target antigens derived from enteric glia and/or neurons by immunoprecipitation and mass spectrometry. Antibodies against three of the target antigens were also present in the plasma of MS patients as confirmed by ELISA. The analysis of human colon resectates provided evidence of gliosis and ENS degeneration in MS patients compared to non-MS controls. For the first time, this study establishes a pathomechanistic link between the well-established autoimmune attack on the CNS and ENS pathology in MS, which might provide a paradigm shift in our current understanding of the immunopathogenesis of the disease with broad diagnostic and therapeutic implications.

http://ift.tt/2rAJ6dh

High burden of antimicrobial resistance among gram negative bacteria causing healthcare associated infections in a critical care unit of Nepal

Healthcare associated infections (HCAI) and antimicrobial resistance are principal threats to the patients of intensive care units and are the major determining factors for patient outcome. They are associated...

http://ift.tt/2stPTJL

Use of 90% ethanol to decontaminate stethoscopes in resource limited settings

In developing countries like Nepal, 90% ethanol is cheap and is available in most hospitals. The unavailability of isopropyl alcohol (IPA) in these settings led us to compare the efficacy between 90% ethanol a...

http://ift.tt/2trRxJ3

Protocols for C-Brick DNA Standard Assembly Using Cpf1

CRISPR-associated protein Cpf1 can be guided by a specially designed CRISPR RNA (crRNA) to cleave double-stranded DNA at desired sites, generating sticky ends. Based on this characteristic, a DNA assembly standard (C-Brick) was established, and a protocol detailing its use is described here.

http://ift.tt/2stD4PA

Remember REHAB for prolonged incidents

This article first appeared on FireRehab.com, sponsored by Masimo. It's a sunny summer day, and the tones sound for a residential fire, smoke and flames showing from an apartment complex. You and your partner respond in the ambulance. En route, the first arriving engine company gives their first-in report: "Engine 1 is on scene of a three-story, multi-unit apartment structure, with smoke ...

http://ift.tt/2sfCaUA

piR-823 contributes to colorectal tumorigenesis by enhancing the transcriptional activity of HSF1

Abstract

Piwi-interacting RNAs (piRNAs), a novel class of small non-coding RNA, were first discovered in germline cells and are thought to silence transposons in spermatogenesis. Recently, piRNAs have also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. However, the function of piR-823 in colorectal cancer (CRC) remains unclear. Here, we first found that piR-823 was significantly up-regulated in CRC tissues compared with its expression in the adjacent tissues. Inhibition of piR-823 suppressed cell proliferation, arrested the cell cycle in the G1 phase and induced cell apoptosis in CRC cell lines HCT116 and DLD-1, whereas over-expression of piR-823 promoted cell proliferation in normal colonic epithelial cell line FHC. Interestingly, Inhibition of piR-823 repressed the expression of heat shock protein (HSP) 27, 60, 70. Furthermore, elevated HSPs expression partially abolished the effect of piR-823 on cell proliferation and apoptosis. In addition, we further demonstrated that piR-823 increased the transcriptional activity of HSF1, the common transcription factor of HSPs, by binding to HSF1 and promoting its phosphorylation at Ser326. Our study reveals that piR-823 plays a tumor-promoting role by up-regulating phosphorylation and transcriptional activity of HSF1 and suggests piR-823 as a potential therapeutic target for CRC.

This article is protected by copyright. All rights reserved.

http://ift.tt/2sfv1DZ

Assessment of short and long-term outcomes of diabetes patient education using the health education impact questionnaire (HeiQ)

Type 2 diabetes is a progressive chronic illness that will affect more than 500 million people worldwide by 2030. It is a significant cause of morbidity and mortality. Finding the right care management for dia...

http://ift.tt/2rvykd7

Generation of Genetically Modified Mice through the Microinjection of Oocytes

The microinjection of mouse oocytes is commonly used for both classic transgenesis (i.e., the random integration of transgenes) and CRISPR-mediated gene targeting. This protocol reviews the latest developments in microinjection, with a particular emphasis on quality control and genotyping strategies.

http://ift.tt/2sfnd5d

Using a Whole-mount Immunohistochemical Method to Study the Innervation of the Biliary Tract in Suncus murinus

A whole-mount immunohistochemical approach, to visualize neurofilament protein expression in the extrahepatic biliary tract in Suncus murinus. is presented here. This protocol can be used to analyze the innervation of all visceral organs in S. murinus or other species.

http://ift.tt/2sfCov0

LifeFlow® Rapid Infuser named a JEMS Hot Product at EMS Today 2017

LifeFlow was one of only 30 innovative products to receive recognition by JEMS at the 36th Annual JEMS EMS Today Conference & Exposition DURHAM, N.C., June 05, 2017 — 410 Medical, Inc., a medical device company focused on developing innovative technologies for the resuscitation of critically ill patients, today announced the selection of the LifeFlow® Rapid Infuser by JEMS (Journal of ...

http://ift.tt/2sfanE4

Remember REHAB for prolonged incidents

Use the acronym to plan for five key elements needed to handle rehab operations for dozens of firefighters over several hours

http://ift.tt/2rvDKVx

What is the impact of local control in Ewing sarcoma: analysis of the first Brazilian collaborative study group – EWING1

Abstract

Background

Relapse in localized Ewing sarcoma patients has been a matter of concern regarding poor prognosis. Therefore, we investigated the impact of local control modality (surgery, surgery plus radiotherapy, and radiotherapy) on clinical outcomes such as survival and recurrence in patients with non-metastatic Ewing sarcoma treated on the first Brazilian Collaborative Group Trial of the Ewing Family of Tumors (EWING1).

Methods

Seventy-three patients with localized Ewing sarcoma of bone aged < 30 years were included. The treating physicians defined the modality of local control based on the recommendations of the coordinating center and the patient and tumor characteristics. Possible associations of local control modality with local failure (LF), disease-free survival (DFS), event-free survival (EFS), overall survival (OS), and clinical characteristics were analyzed.

Results

Mean patient age was 12.8 years (range, 2 to 25 years) and median follow-up time was 4.5 years (range, 2.3 to 6.7 years). Forty-seven patients underwent surgery, 13 received radiotherapy, and 13 received both. The 5-year EFS, OS, and DFS for all patients was 62.1%, 63.3%, and 73.1%, respectively. The 5-year cumulative incidence (CI) of LF was 7.6% for surgery, 11.1% for radiotherapy, and 0% for postoperative radiotherapy (PORT) (p = 0.61). The 5-year EFS was 71.7% for surgery, 30.8% for radiotherapy, and 64.1% for PORT (p = 0.009).

Conclusions

There was a significant effect of local control modality on EFS and OS in the study. Surgery and PORT modalities yielded very close results. The group treated with radiotherapy alone had considerably worse outcomes. This may be confounded by greater risk factors in these patients. There was no significant effect of local control modality on the CI of LF and DFS.

http://ift.tt/2sfmPUh

A Proton Pump Inhibitor in the Reformulation Setting: Bioequivalence and Potential Implications for Long-Term Safety

Proton pump inhibitors (PPIs) have become known for both their therapeutic effect and good safety profile. An application was submitted to the US Food and Drug Administration for approval of a reformulated PPI product that failed bioequivalence testing, but was submitted on the basis of the long history of PPI use as a "surrogate" for equivalence. This review evaluates the safety data for PPIs, discuss variability of pharmacokinetic parameters of PPIs in the reformulation setting, and potential implications of those changes for long-term safety.

http://ift.tt/2sfmwIQ

Beneficial effects of phytochemicals in diabetic retinopathy: experimental and clinical evidence

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and a major preventable cause of blindness. Strict control of blood glucose, blood pressure, and lipid profiles are the pivotal criteria to reduce the risk of developing DR. Although timely intervention with laser photocoagulation therapy could mitigate the progression of DR, it may not significantly improve visual acuity. Therefore, invasive surgical interventions such as vitrectomy are sometimes the only option to treat or manage advanced stages of DR. However, the risk of intra-ocular infections outweighs the benefits of the surgery. Newer therapies such as intraocular injection of anti-vascular endothelial growth factor (VEGF) antibody and steroids serve as a viable option for the treatment of DR. However, several clinical studies that assessed the long-term efficacy and safety of this therapy have yielded inconclusive results. Therefore, there is an urgent need to develop potent and safe drugs for the effective management of DR. In this review, we discuss various plant-derived small molecules (phytochemicals) that have been investigated for retinal cytoprotective effects in pre-clinical and clinical studies. Furthermore, we highlight the caveats on using phytochemicals for the management of DR.

L'articolo Beneficial effects of phytochemicals in diabetic retinopathy: experimental and clinical evidence sembra essere il primo su European Review.

http://ift.tt/2sDwyGu

Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study

OBJECTIVE: Sleep apnoea is common after stroke, and has adverse effects on the clinical outcome of affected cases. Its pathophysiological mechanisms are only partially known. Increases in brain connectivity after stroke might influence networks involved in arousal modulation and breathing control. The aim of this study was to investigate the resting state functional MRI thalamic hyper-connectivity of stroke patients affected by sleep apnoea (SA) with respect to cases not affected, and to healthy controls (HC).

PATIENTS AND METHODS: A series of stabilized strokes were submitted to 3T resting state functional MRI imaging and full polysomnography. The ventral-posterior-lateral thalamic nucleus was used as seed.

RESULTS: At the between groups comparison analysis, in SA cases versus HC, the regions significantly hyper-connected with the seed were those encoding noxious threats (frontal eye field, somatosensory association, secondary visual cortices). Comparisons between SA cases versus those without SA revealed in the former group significantly increased connectivity with regions modulating the response to stimuli independently to their potentiality of threat (prefrontal, primary and somatosensory association, superolateral and medial-inferior temporal, associative and secondary occipital ones). Further significantly functionally hyper-connections were documented with regions involved also in the modulation of breathing during sleep (pons, midbrain, cerebellum, posterior cingulate cortices), and in the modulation of breathing response to chemical variations (anterior, posterior and para-hippocampal cingulate cortices).

CONCLUSIONS: Our preliminary data support the presence of functional hyper connectivity in thalamic circuits modulating sensorial stimuli, in patients with post-stroke sleep apnoea, possibly influencing both their arousal ability and breathing modulation during sleep.

L'articolo Resting state functional thalamic connectivity abnormalities in patients with post-stroke sleep apnoea: a pilot case-control study sembra essere il primo su European Review.

http://ift.tt/2tqS4uK

Comparative Visualization of the RNA Suboptimal Conformational Ensemble In Vivo

When a ribonucleic acid (RNA) molecule folds, it often does not adopt a single, well-defined conformation. The folding energy landscape of an RNA is highly dependent on its nucleotide sequence and molecular environment. Cellular molecules sometimes alter the energy landscape, thereby changing the ensemble of likely low-energy conformations. The effects of these energy landscape changes on the conformational ensemble are particularly challenging to visualize for large RNAs. We have created a robust approach for visualizing the conformational ensemble of RNAs that is well suited for in vitro versus in vivo comparisons.

http://ift.tt/2sf2aQh

Type II CRISPR/Cas9 approach in the oncological therapy

Abstract

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a prokaryotic adaptable immune mechanism used by many bacteria and archaea to protect themselves from foreign nucleic acids. This complex system can recognize and cut non-self DNA in order to provide the prokaryotic organisms a strong defense against foreign viral or plasmid attacks and make the cell immune from further assaults. Today, it has been adapted to be used in vitro and in vivo in eukaryotic cells to perform a complete and highly selective gene knockout or a specific gene editing. The ease of use and the low cost are only two features that have made it very popular among the scientific community and the possibility to be used as a clinical treatment in several genetic derived pathologies has rapidly spread its fame worldwide. However, CRISPR is still not fully understood and many efforts need to be done in order to make it a real power tool for the human clinical treatment especially for oncological patients. Indeed, since cancer originates from non-lethal genetic disorders, CRISPR discovery fuels the hope to strike tumors on their roots. More than 4000 papers regarding CRISPR were published in the last ten years and only few of them take in count the possible applications in oncology. The purpose of this review is to clarify many problematics on the CRISPR usage and highlight its potential in oncological therapy.

http://ift.tt/2swzO74

Anti-Toxoplasma gondii antibodies in patients with beta-hemoglobinopathies: the first report in the Americas

In Brazil, there have been no previous studies of Toxoplasma gondii infection in sickle cell anemia patients and carriers of severe forms of beta-thalassemia. This study evaluated T. gondii infection in patients ...

http://ift.tt/2sf6cYD

Characterisation of Roseomonas mucosa isolated from the root canal of an infected tooth

The genus Roseomonas comprises a group of pink-pigmented, slow-growing, aerobic, non-fermentative Gram-negative bacteria, which have been isolated from environmental sources such as water and soil, but are also a...

http://ift.tt/2rv6Sw7

Comparative Visualization of the RNA Suboptimal Conformational Ensemble In Vivo

When a ribonucleic acid (RNA) molecule folds, it often does not adopt a single, well-defined conformation. The folding energy landscape of an RNA is highly dependent on its nucleotide sequence and molecular environment. Cellular molecules sometimes alter the energy landscape, thereby changing the ensemble of likely low-energy conformations. The effects of these energy landscape changes on the conformational ensemble are particularly challenging to visualize for large RNAs. We have created a robust approach for visualizing the conformational ensemble of RNAs that is well suited for in vitro versus in vivo comparisons.

http://ift.tt/2sf2aQh

Serial immunomonitoring of cancer patients receiving combined antagonistic anti-CD40 and chemotherapy reveals consistent and cyclical modulation of T cell and dendritic cell parameters

Abstract

Background

CD40 signalling can synergise with chemotherapy in preclinical cancer models, and early clinical studies are promising. We set out to define the immunological changes associated with this therapeutic combination to identify biomarkers for a response to the therapy. Here, we present serial immunomonitoring examining dendritic cell and T cell subpopulations over sequential courses of chemoimmunotherapy.

Methods

Fifteen patients with mesothelioma received up to six 21-day cycles of pemetrexed plus cisplatin chemotherapy and anti-CD40 (CP-870,893). Peripheral blood was collected weekly, and analysed by flow cytometry. Longitudinal immunophenotyping data was analysed by linear mixed modelling, allowing for variation between patients. Exploratory analyses testing for any correlation between overall survival and immunophenotyping data were undertaken up to the third cycle of treatment.

Results

Large statistically significant cyclical variations in the proportions of BDCA-1+, BDCA-2+ and BDCA-3+ dendritic cells were observed, although all subsets returned to baseline levels after each cycle and no significant changes were observed between start and end of treatment. Expression levels of CD40 and HLA-DR on dendritic cells were also cyclically modulated, again without significant change between start and end of treatment. CD8 and CD4 T cell populations, along with regulatory T cells, effector T cells, and markers of proliferation and activation, showed similar patterns of statistically significant cyclical modulation in response to therapy without changes between start and end of treatment. Exploratory analysis of endpoints revealed that patients with a higher than average proportion of BDCA-2+ dendritic cells (p = 0.010) or a higher than average proportion of activated (ICOS+) CD8 T cells (0.022) in pretreatment blood samples had better overall survival. A higher than average proportion of BDCA-3+ dendritic cells was associated with poorer overall survival at both the second (p = 0.008) and third (p = 0.014) dose of anti-CD40.

Conclusions

Substantial cyclical variations in DC and T cell populations during sequential cycles of chemoimmunotherapy highlight the critical importance of timing of immunological biomarker assessments in interpretation of results and the value of linear mixed modelling in interpretation of longitudinal change over a full treatment course.

Trial registration

Australia New Zealand Clinical Trials Registry number ACTRN12609000294257 (18th May 2009).

http://ift.tt/2swndR4

Effect of transcutaneous electrical stimulation treatment on lower urinary tract symptoms after class III radical hysterectomy in cervical cancer patients: study protocol for a multicentre, randomized controlled trial

Abstract

Background

Class III radical hysterectomy (RH III)_plus pelvic lymphadenectomy is the standard surgery for early stage cervical cancer (CC) patients, the 5 year survival rate is about 90%, but pelvic floor disorders especially bladder dysfunction are common due to damaged vessels and nerve fibers following surgery. Transcutaneous electrical stimulation (TENS) treatment has been used to treat bladder disorders for many years, but its effect on cervical cancer patients, the best treatment time point and stimulated protocol, had never been assessed. The aim of this study is to investigate the efficacy of TENS treatment on lower urinary tract symptoms (LUTS) after RH III in CC patients.

Methods/Design

The study will be conducted as a clinical, multicentre, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 208 participants (at 1:1 ratio, 104 subjects in each group). At 5–7 days after RH III, patients are screened according to operative and pathological findings. Enrolled participants are randomised into an intervention group (TENS plus conventional clinical care) or control group (conventional clinical care), with stratification by menopausal status (menopause vs. non-menopause) and surgical modality (laparoscopic RH or abdominal RH). Participants in both groups will be followed up at 14 days, 21 days, 28 days, 3 months, 6 months, 12 months, 18 months and 24 months after surgery. The primary endpoint is improvement rate of urination function which is defined as recovery (residual urine ≤50 ml) or improvement (residual urine 50–100 ml). Secondary endpoints include urodynamic parameter, urinary incontinence, anorectal function, pelvic function, quality of life (QOL), disease-free survival and adverse events. Primary endpoint analyses will be carried out by Cochran-Mantel-Haenszel tests taking into center effect.

Discussion

To our knowledge this is the first trial to investigate the effect of TENS treatment on bladder function recovery after RH III among CC patients. This study will provide new information on TENS efficacy for bladder function recovery. Once confirmed, it may help to provide a new, non-invisive treatment for those postoperative CC patients with poor pelvic function, which would help improve their quality of life.

Trial registration

The study is registered to Clinical Trials.gov (NCT02492542) on June 25, 2015.

http://ift.tt/2swSrYh

Prognostic impact of blood and urinary angiogenic factor levels at diagnosis and during treatment in patients with osteosarcoma: a prospective study

Abstract

Background

Angiogenesis is essential for the progression and metastatic spread of solid tumours. Expression of vascular endothelial growth factor (VEGF) has been linked to poor survival among osteosarcoma patients but the clinical relevance of monitoring blood and urine angiogenic factors is uncertain. The aim of this study was to determine the prognostic significance of blood VEGF and blood and urinary basic fibroblast growth factor (bFGF) levels in osteosarcoma patients, both at diagnosis and during treatment.

Methods

Patients with localised or metastatic osteosarcoma enrolled in OS2005 and OS2006 studies between 2005 and 2011 were prospectively included in this study. VEGF and bFGF levels in serum and plasma and bFGF levels in urine were measured by ELISA at diagnosis, before surgery, and at the end of treatment. Endpoints considered for the prognostic analysis were histological response, progression-free and overall survival. Kruskal-Wallis tests were used to compare the distribution of baseline biomarker values across the different subgroups, and paired sample Wilcoxon rank tests were used to analyze changes over time. Association between biomarker levels and outcomes were assessed in multivariable models (logistic regression for histologic response, and Cox models for survival).

Results

Samples were available at diagnosis for 269 patients (54% males; age ≤ 18 years: 73%; localised disease in 68%, doubtful lung lesions in 17%, and metastases in 15%). High serum VEGF and bFGF levels were observed in respectively 61% and 51% of patients. Serum and plasma VEGF values were not strongly correlated with one another (r = 0.53). High serum and plasma VEGF levels were significantly more frequent in patients with large tumours (≥10 cm; p = 0.003 and p = 0.02, respectively). VEGF levels fell significantly during pre-operative chemotherapy (p < 0.0001). No significant correlation was found between this variation and either the histological response, progression-free survival or overall survival (p = 0.26, p = 0.67, and p = 0.87, respectively). No significant association was found between blood or urinary bFGF levels and clinical characteristics, histological response, or survival.

Conclusions

Levels of VEGF and bFGF angiogenic factors are high in most osteosarcoma patients, but have no significant impact on response to chemotherapy or outcome in this large prospective series.

OS 2006 trial registration number

clinicaltrials.gov NCT00470223; date of registration: May 3th 2007.

http://ift.tt/2swqW14