Characterization of thrombosis in patients with Proteus syndrome

Patients with overgrowth and complex vascular malformation syndromes, including Proteus syndrome have an increased risk of thromboembolism. Proteus syndrome is a mosaic, progressive overgrowth disorder involving vasculature, skin, and skeleton, and caused by a somatic activating mutation in AKT1. We conducted a comprehensive review of the medical histories and hematologic evaluations of 57 patients with Proteus syndrome to identify potential risk factors for thrombosis. We found that six of ten patients, who were deceased, died secondary to deep venous thrombosis and/or pulmonary embolism. Of the remaining 47 living patients, six had thromboembolic events that all occurred postoperatively and in an affected limb. Eleven of 21 patients had an abnormal hypercoagulable panel including Factor V Leiden heterozygotes, antithrombin III deficiency, positive lupus anticoagulant, or Protein C or S deficiencies. We observed that eight of 17 patients had an abnormal D-dimer level >0.5 mcg/dl, but deep venous thromboses occurred in only four of those with D-dimer >1.0 mcg/dl. We conclude that the predisposition to thrombosis is likely to be multifaceted with risk factors including vascular malformations, immobility, surgery, additional prothrombotic factors, and possible pathophysiologic effects of the somatic AKT1 mutation on platelet function or the vascular endothelium. The D-dimer test is useful as a screen for thromboembolism, although the screening threshold may need to be adjusted for patients with this disorder. We propose developing a registry to collect D-dimer and outcome data to facilitate adjustment of the D-dimer threshold for Proteus syndrome and related disorders, including PIK3CA-Related Overgrowth Spectrum.

http://ift.tt/2sqQ867

Ultrastable Near-Infrared Conjugated-Polymer Nanoparticles for Dually Photoactive Tumor Inhibition

It is highly desired that satisfactory photoactive agents with ideal photophysical characteristics are explored for potent cancer phototherapeutics. Herein, bifunctional nanoparticles of low-bandgap donor–acceptor (D–A)-type conjugated-polymer nanoparticles (CP-NPs) are developed to afford a highly efficient singlet-to-triplet transition and photothermal conversion for near-infrared (NIR) light-induced photodynamic (PDT)/photothermal (PTT) treatment. CP-NPs display remarkable NIR absorption with the peak at 782 nm, and perfect resistance to photobleaching. Photoexcited CP-NPs undergo singlet-to-triplet intersystem crossing through charge transfer in the excited D–A system and simultaneous nonradiative decay from the electron-deficient electron acceptor isoindigo derivative under single-wavelength NIR light irradiation, leading to distinct singlet oxygen quantum yield and high photothermal conversion efficiency. Moreover, the CP-NPs display effective cellular uptake and cytoplasmic translocation from lysosomes, as well as effective tumor accumulation, thus promoting severe light-triggered damage caused by favorable reactive oxygen species (ROS) generation and potent hyperthermia. Thus, CP-NPs achieve photoactive cell damage through their photoconversion ability for synergistic PDT/PTT treatment with tumor ablation. The proof-of-concept design of D–A-type conjugated-polymer nanoparticles with ideal photophysical characteristics provides a general approach to afford potent photoactive cancer therapy.

Ultrastable donor–acceptor low-bandgap conjugated-polymer nanoparticles are developed to afford a highly efficient singlet-to-triplet transition and nonradiative decay to simultaneously generate singlet oxygen and photohyperthermia for near-infrared photoactive tumor ablation.

http://ift.tt/2sgWDdx

Optical Microresonators for Sensing and Transduction: A Materials Perspective

Optical microresonators confine light to a particular microscale trajectory, are exquisitely sensitive to their microenvironment, and offer convenient readout of their optical properties. Taken together, this is an immensely attractive combination that makes optical microresonators highly effective as sensors and transducers. Meanwhile, advances in material science, fabrication techniques, and photonic sensing strategies endow optical microresonators with new functionalities, unique transduction mechanisms, and in some cases, unparalleled sensitivities. In this progress report, the operating principles of these sensors are reviewed, and different methods of signal transduction are evaluated. Examples are shown of how choice of materials must be suited to the analyte, and how innovations in fabrication and sensing are coupled together in a mutually reinforcing cycle. A tremendously broad range of capabilities of microresonator sensors is described, from electric and magnetic field sensing to mechanical sensing, from single-molecule detection to imaging and spectroscopy, from operation at high vacuum to in live cells. Emerging sensing capabilities are highlighted and put into context in the field. Future directions are imagined, where the diverse capabilities laid out are combined and advances in scalability and integration are implemented, leading to the creation of a sensor unparalleled in sensitivity and information content.

Optical microresonators possess photonic and materials properties that make them sensors of unparalleled sensitivity. These structures confine light to microscale trajectories where their microenvironment can be repeatedly probed. In this manner, optical microresonators offer a diversity of sensing strategies, including chemical sensing down to single molecules, imaging, spectroscopy, electric and magnetic field sensing, and force and mass sensing.

http://ift.tt/2rLWuv7

In Situ Electrochemistry of Rechargeable Battery Materials: Status Report and Perspectives

The development of rechargeable batteries with high performance is considered to be a feasible way to satisfy the increasing needs of electric vehicles and portable devices. It is of vital importance to design electrodes with high electrochemical performance and to understand the nature of the electrode/electrolyte interfaces during battery operation, which allows a direct observation of the complicated chemical and physical processes within the electrodes and electrolyte, and thus provides real-time information for further design and optimization of the battery performance. Here, the recent progress in in situ techniques employed for the investigations of material structural evolutions is described, including characterization using neutrons, X-ray diffraction, and nuclear magnetic resonance. In situ techniques utilized for in-depth uncovering the electrode/electrolyte phase/interface change mechanisms are then highlighted, including transmission electron microscopy, atomic force microscopy, X-ray spectroscopy, and Raman spectroscopy. The real-time monitoring of lithium dendrite growth and in situ detection of gas evolution during charge/discharge processes are also discussed. Finally, the major challenges and opportunities of in situ characterization techniques are outlined toward new developments of rechargeable batteries, including innovation in the design of compatible in situ cells, applications of dynamic analysis, and in situ electrochemistry under multi-stimuli. A clear and in-depth understanding of in situ technique applications and the mechanisms of structural evolutions, surface/interface changes, and gas generations within rechargeable batteries is given here.

In situ characterization techniques of rechargeable battery materials, applied for the investigation of structural evolution, surface/interface changes, and monitoring of gas generation during battery operation, pave the way for unveiling the battery storage mechanism and its performance fading routes, and provide a fruitful strategy to design electrode materials with superb electrochemical performance. The current challenges and potential development perspectives are summarized with the aim of expanding battery applications.

http://ift.tt/2sJgrYr

Metal–Organic-Framework-Derived Hybrid Carbon Nanocages as a Bifunctional Electrocatalyst for Oxygen Reduction and Evolution

The oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) are cornerstone reactions for many renewable energy technologies. Developing cheap yet durable substitutes of precious-metal catalysts, especially the bifunctional electrocatalysts with high activity for both ORR and OER reactions and their streamlined coupling process, are highly desirable to reduce the processing cost and complexity of renewable energy systems. Here, a facile strategy is reported for synthesizing double-shelled hybrid nanocages with outer shells of Co-N-doped graphitic carbon (Co-NGC) and inner shells of N-doped microporous carbon (NC) by templating against core–shell metal–organic frameworks. The double-shelled NC@Co-NGC nanocages well integrate the high activity of Co-NGC shells into the robust NC hollow framework with enhanced diffusion kinetics, exhibiting superior electrocatalytic properties to Pt and RuO₂ as a bifunctional electrocatalyst for ORR and OER, and hold a promise as efficient air electrode catalysts in Zn–air batteries. First-principles calculations reveal that the high catalytic activities of Co-NGC shells are due to the synergistic electron transfer and redistribution between the Co nanoparticles, the graphitic carbon, and the doped N species. Strong yet favorable adsorption of an OOH* intermediate on the high density of uncoordinated hollow-site C atoms with respect to the Co lattice in the Co-NGC structure is a vital rate-determining step to achieve excellent bifunctional electrocatalytic activity.

A new strategy is developed for constructing a hollow nanostructured bifunctional oxygen reduction reaction/oxygen evolution reaction electrocatalyst with integrated high activity and fast kinetics by surface-stabilized heterogeneous contraction of core–shell metal–organic frameworks. The resultant double-shelled hybrid nanocages with an outer shell of mesoporous Co-N-doped graphitic carbon and an inner shell of microporous N-doped carbon exhibit superior electrocatalytic performance to noble metals for oxygen reduction and evolution reactions.

http://ift.tt/2sqJ5dS

Carbon Nanotube–Multilayered Graphene Edge Plane Core–Shell Hybrid Foams for Ultrahigh-Performance Electromagnetic-Interference Shielding

Materials with an ultralow density and ultrahigh electromagnetic-interference (EMI)-shielding performance are highly desirable in fields of aerospace, portable electronics, and so on. Theoretical work predicts that 3D carbon nanotube (CNT)/graphene hybrids are one of the most promising lightweight EMI shielding materials, owing to their unique nanostructures and extraordinary electronic properties. Herein, for the first time, a lightweight, flexible, and conductive CNT–multilayered graphene edge plane (MLGEP) core–shell hybrid foam is fabricated using chemical vapor deposition. MLGEPs are seamlessly grown on the CNTs, and the hybrid foam exhibits excellent EMI shielding effectiveness which exceeds 38.4 or 47.5 dB in X-band at 1.6 mm, while the density is merely 0.0058 or 0.0089 g cm⁻³, respectively, which far surpasses the best values of reported carbon-based composite materials. The grafted MLGEPs on CNTs can obviously enhance the penetration losses of microwaves in foams, leading to a greatly improved EMI shielding performance. In addition, the CNT–MLGEP hybrids also exhibit a great potential as nano-reinforcements for fabricating high-strength polymer-based composites. The results provide an alternative approach to fully explore the potentials of CNT and graphene, for developing advanced multifunctional materials.

Carbon nanotube–multilayered graphene edge plane core–shell hybrid foams are fabricated by chemical vapor deposition methods for the first time. The seamless junctions of multilayered graphene edge planes on the carbon nanotubes endow the hybrids with potential applications as high-performance nanocomposites and ultrahigh-performance lightweight electromagnetic-interference shielding materials.

http://ift.tt/2rGZspt

3D Printing All-Aromatic Polyimides using Mask-Projection Stereolithography: Processing the Nonprocessable

High-performance, all-aromatic, insoluble, engineering thermoplastic polyimides, such as pyromellitic dianhydride and 4,4′-oxydianiline (PMDA–ODA) (Kapton), exhibit exceptional thermal stability (up to ≈600 °C) and mechanical properties (Young's modulus exceeding 2 GPa). However, their thermal resistance, which is a consequence of the all-aromatic molecular structure, prohibits processing using conventional techniques. Previous reports describe an energy-intensive sintering technique as an alternative technique for processing polyimides with limited resolution and part fidelity. This study demonstrates the unprecedented 3D printing of PMDA–ODA using mask-projection stereolithography, and the preparation of high-resolution 3D structures without sacrificing bulk material properties. Synthesis of a soluble precursor polymer containing photo-crosslinkable acrylate groups enables light-induced, chemical crosslinking for spatial control in the gel state. Postprinting thermal treatment transforms the crosslinked precursor polymer to PMDA–ODA. The dimensional shrinkage is isotropic, and postprocessing preserves geometric integrity. Furthermore, large-area mask-projection scanning stereolithography demonstrates the scalability of 3D structures. These unique high-performance 3D structures offer potential in fields ranging from water filtration and gas separation to automotive and aerospace technologies.

High-performance, thermoplastic, fully aromatic polyimide structures are 3D printed for the first time using mask-projection stereolithography (MPSL). Synthesis of soluble, photo-crosslinkable polyamic diacrylate ester enables MPSL upon dissolution in a solvent. The 3D organogels with micrometer-scale resolution undergo conversion to a 3D polyimide on thermal imidization without loss in part fidelity. Mechanically robust, high-performance, fully aromatic 3D polyimide is obtained.

http://ift.tt/2sqJXiA

Anode Improvement in Rechargeable Lithium–Sulfur Batteries

Owing to their theoretical energy density of 2600 Wh kg⁻¹, lithium–sulfur batteries represent a promising future energy storage device to power electric vehicles. However, the practical applications of lithium–sulfur batteries suffer from poor cycle life and low Coulombic efficiency, which is attributed, in part, to the polysulfide shuttle and Li dendrite formation. Suppressing Li dendrite growth, blocking the unfavorable reaction between soluble polysulfides and Li, and improving the safety of Li–S batteries have become very important for the development of high-performance lithium sulfur batteries. A comprehensive review of various strategies is presented for enhancing the stability of the anode of lithium sulfur batteries, including inserting an interlayer, modifying the separator and electrolytes, employing artificial protection layers, and alternative anodes to replace the Li metal anode.

Anodes play an important role in resolving the issues of conventional lithium sulfur batteries. This review introduces the most recent progress in anodes for lithium–sulfur batteries. To suppress the corrosion reaction occurred and the formation of Li dendrites on the surface of lithium metal, various strategies are summarized. Employing alternative anodes for sulfur-based rechargeable batteries is also discussed.

http://ift.tt/2rGQqsD

Challenges and Perspectives for NASICON-Type Electrode Materials for Advanced Sodium-Ion Batteries

Sodium-ion batteries (SIBs) have attracted increasing attention in the past decades, because of high overall abundance of precursors, their even geographical distribution, and low cost. Apart from inherent thermodynamic disadvantages, SIBs have to overcome multiple kinetic problems, such as fast capacity decay, low rate capacities and low Coulombic efficiencies. A special case is sodium super ion conductor (NASICON)-based electrode materials as they exhibit – besides pronounced structural stability – exceptionally high ion conductivity, rendering them most promising for sodium storage. Owing to the limiting, comparatively low electronic conductivity, nano-structuring is a prerequisite for achieving satisfactory rate-capability. In this review, we analyze advantages and disadvantages of NASICON-type electrode materials and highlight electrode structure design principles for obtaining the desired electrochemical performance. Moreover, we give an overview of recent approaches to enhance electrical conductivity and structural stability of cathode and anode materials based on NASICON structure. We believe that this review provides a pertinent insight into relevant design principles and inspires further research in this respect.

Sodium super ion conductor (NASICON)-based electrode materials, exhibiting pronounced structural stability and exceptionally high ion conductivity are promising materials for sodium storage. Here, challenges and perspectives of NASICON-type electrode materials are discussed, electrode structure design principles for obtaining the desired electrochemical performance are highlighted. Recent progress in enhancing electrical conductivity and structural stability of NASICON materials is summarized.

http://ift.tt/2sqSoKJ

Fabrication of Millimeter-Long Carbon Tubular Nanostructures Using the Self-Rolling Process Inherent in Elastic Protein Layers

Millimeter-long conducting fibers can be fabricated from carbon nanomaterials via a simple method involving the release of a prestrained protein layer. This study shows how a self-rolling process initiated by polymerization of a micropatterned layer of fibronectin (FN) results in the production of carbon nanomaterial-based microtubular fibers. The process begins with deposition of carbon nanotube (CNT) or graphene oxide (GO) particles on the FN layer. Before polymerization, particles are discrete and nonconducting, but after polymerization the carbon materials become entangled to form an interconnected conducting network clad by FN. Selective removal of FN using high-temperature combustion yields freestanding CNT or reduced GO microtubular fibers. The properties of these fibers are characterized using atomic force microscopy and Raman spectroscopy. The data suggest that this method may provide a ready route to rapid design and fabrication of aligned biohybrid nanomaterials potentially useful for future electronic applications.

Millimeter-long conducting fiberscan be fabricated from carbon nanomaterials via a simple method involving the release of a prestrained protein layer. Before the self-rolling process, nanoparticles are discrete, but after self-rolling process the nanoparticles become entangled to form an interconnected network clad. Selective removal of the protein layer yields a long freestanding, conducted carbon nanotube or graphene oxide microtubular fiber.

http://ift.tt/2tiftPN

Conductive Carbon Nitride for Excellent Energy Storage

Conductive carbon nitride, as a hypothetical carbon material demonstrating high nitrogen doping, high electrical conductivity, and high surface area, has not been fabricated. A major challenge towards its fabrication is that high conductivity requires high temperature synthesis, but the high temperature eliminates nitrogen from carbon. Different from conventional methods, a facile preparation of conductive carbon nitride from novel thermal decomposition of nickel hydrogencyanamide in a confined space is reported. New developed nickel hydrogencyanamide is a unique precursor which provides self-grown fragments of ⋅NCN⋅ or NCCN and conductive carbon (C-sp²) catalyst of Ni metal during the decomposition. The final product is a tubular structure of rich mesoporous and microporous few-layer carbon with extraordinarily high N doping level (≈15 at%) and high extent of sp² carbon (≈65%) favoring a high conductivity (>2 S cm⁻¹); the ultrahigh contents of nongraphitic nitrogen, redox active pyridinic N (9 at%), and pyrrolic N (5 at%), are stabilized by forming NiN bonds. The conductive carbon nitride harvests a large capacitance of 372 F g⁻¹ with >90% initial capacitance after 10 000 cycles as a supercapacitor electrode, far exceeding the activated carbon electrodes that have <250 F g⁻¹.

Conductive carbon nitride, simultaneously gaining high nitrogen doping and high electrical conductivity, is obtained from novel space-confined reaction. Nickel hydrogencyanamide provides self-grown fragments of ⋅NCN⋅ or NC−CN and conductive carbon (C-sp²) catalyst of Ni metal during the decomposition. The final product is a tubular structure of extraordinarily high N doping level (≈15 at%) and high conductivity (>2 S cm⁻¹).

http://ift.tt/2sJ5Hcy

Polysaccharide production by lactic acid bacteria: from genes to industrial applications

Abstract

The ability to produce polysaccharides with diverse biological functions is widespread in bacteria. In lactic acid bacteria (LAB), production of polysaccharides has long been associated with the technological, functional and health-promoting benefits of these microorganisms. In particular, the capsular polysaccharides and exopolysaccharides have been implicated in modulation of the rheological properties of fermented products. For this reason, screening and selection of exocellular polysaccharide-producing LAB has been extensively carried out by academia and industry. To further exploit the ability of LAB to produce polysaccharides, an in-depth understanding of their biochemistry, genetics, biosynthetic pathways, regulation and structure–function relationships is mandatory. Here, we provide a critical overview of the latest advances in the field of glycosciences in LAB. Surprisingly, the understanding of the molecular processes involved in polysaccharide synthesis is lagging behind, and has not accompanied the increasing commercial value and application potential of these polymers. Seizing the natural diversity of polysaccharides for exciting new applications will require a concerted effort encompassing in-depth physiological characterization of LAB at the systems level. Combining high-throughput experimentation with computational approaches, biochemical and structural characterization of the polysaccharides and understanding of the structure–function–application relationships is essential to achieve this ambitious goal.

http://ift.tt/2rGEwyL

Experimental evolution and the adjustment of metabolic strategies in lactic acid bacteria

Abstract

Experimental evolution of microbes has gained lots of interest in recent years, mainly due to the ease of strain characterisation through next-generation sequencing. While evolutionary and systems biologists use experimental evolution to address fundamental questions in their respective fields, studies with lactic acid bacteria are often more directed by applied questions. Insight into population and genome dynamics are valuable for experimental design and data interpretation, and it is becoming increasingly apparent how different constraints limit and govern the outcome of microbial adaptation to a selective environment. Examples for such constraints are the finite membrane and cellular space which can lead to trade-offs between cellular strategies. A powerful perspective is that of resource allocation, which allows cells to maximise fitness. This impacts on metabolic strategies that have different protein/resource demands. This review focuses on parameters and forces that shape cellular optimisation processes and that are determining for the outcome of laboratory evolution experiments. Phenotypic changes of experimentally evolved lactic acid bacteria will be discussed in the light of the selection conditions and the prevailing constraints.

http://ift.tt/2sralJi

A comprehensive approach needed to address regional variation [Letters]

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Health Canada wants more funds from pharma [News]

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Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial [Research]

BACKGROUND:

The 2013–2016 Ebola virus outbreak in West Africa was the most widespread in history. In response, alive attenuated recombinant vesicular stomatitis virus (rVSV) vaccine expressing Zaire Ebolavirus glycoprotein (rVSVG-ZEBOV-GP) was evaluated in humans.

METHODS:

In a phase 1, randomized, dose-ranging, observer-blind, placebo-controlled trial, healthy adults aged 18–65 years were randomized into 4 groups of 10 to receive one of 3 vaccine doses or placebo. Follow-up visits spanned 180 days postvaccination for safety monitoring, immunogenicity testing and any rVSV virus shedding.

RESULTS:

Forty participants were injected with rVSVG-ZEBOV-GP vaccine (n = 30) or saline placebo (n = 10). No serious adverse events related to the vaccine or participant withdrawals were reported. Solicited adverse events during the 14-day follow-up period were mild to moderate and self-limited, with the exception of injection-site pain and headache. Viremia following vaccination was transient and no longer detectable after study day 3, with no virus shedding in saliva or urine. All vaccinated participants developed serum immunoglobulin G (IgG), as measured by Ebola virus envelope glycoprotein-based enzyme-linked immunosorbent assay (ELISA). Immunogenicity was comparable across all dose groups, and sustained IgG titers were detectable through to the last visit, at study day 180.

INTERPRETATION:

In this phase 1 study, there were no safety concerns after a single dose of rVSVG-ZEBOV-GP vaccine. IgG ELISA showed persistent high titers at 180 days postimmunization. There was a period of reactogenicity, but in general, the vaccine was well tolerated. This study provides evidence of the safety and immunogenicity of rVSVG-ZEBOV-GP vaccine and importance of its further investigation. Trial registration: Clinical-Trials.gov no., NCT02374385

http://ift.tt/2timUX4

Hot bodies; Cold War: the forgotten history of breast thermography [Correction]

http://ift.tt/2sJ0kKs

Diagnosis and management of bronchiectasis [Review]

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Importation of drugs into the United States from Canada [Commentary]

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Superficial dyspareunia [Practice]

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Response to: "A comprehensive approach needed to address regional variation" [Letters]

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Traumatic pseudoaneurysm of the superficial temporal artery [Practice]

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A game-changer for hereditary cancer patients [News]

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The spaces in between [Humanities]

http://ift.tt/2ti4Vjz

Researchers unite in demand for funding [News]

http://ift.tt/2ti1vgP

Bilateral ischaemic optic neuropathy and retinopathy along with cortical infarct in a case of Takayasu disease

Description

A 27-Year-old female presented with complaints of sudden onset visual loss along with right sided deviation of the angle of mouth since past 30 days. Vision loss had worsened in the last week. There was history of severe headache which was not associated with vomiting. There was no history of any other neurological deficit or prior systemic illness. Examination for cranial nerve function revealed a left sided upper motor neuron facial nerve palsy and rest of the neurological examination was within normal limits. On ocular examination, the patient had best-corrected visual acuity of light perception (PL) in right eye (RE) and 6/36 in left eye (LE). A grade four relative afferent pupillary defect was noted in RE, while slit lamp examination and tonometry were normal. On fundus examination, RE optic disc had yellowish-white pallor while LE optic disc had temporal pallor (figure 1A,B). Multiple retinal...

http://ift.tt/2rLFoNZ

Saksenaea vasiformis infection in an immunocompetent patient in rural Australia

An 81-year-old man from rural Australia presented with right pretibial cellulitis 7 days after minor trauma against furniture. He failed to improve despite antibiotics and surgical debridement. Subsequent cultures grew the rare fungus Saksenaea vasiformis, which was treated with further surgical debridement, amphotericin B and posaconazole. This was successful and the patient made a full recovery. We present the case and discuss lessons learnt.

http://ift.tt/2sgGMM4

QUAD fever: beware of non-infectious fever in high spinal cord injuries

A case of cervical spinal cord injury and quadriparesis with prolonged fever is being described. Initially, the patient received treatment for well-documented catheter-related bloodstream infection. High spiking fever returned and persisted with no obvious evidence of infection. The usual non-infectious causes too were carefully excluded. QUAD fever or fever due to spinal cord injury itself was considered. The pathogenetic basis of QUAD fever is unclear but could be attributed to autonomic dysfunction and temperature dysregulation. Awareness of this little known condition could help in avoiding unnecessary antimicrobial therapy and in more accurate prognostication. Unlike several previous reported cases that ended fatally, the present case ran a relatively benign course. The spectrum of presentations may therefore be broader than hitherto appreciated.

http://ift.tt/2rLMpOz

Tumour necrosis factor (TNF) inhibitor-induced isolated pleural granulomas: a rare adverse effect

A 53-year-old man with a history of Crohn's disease on infliximab, presented with several weeks of cough and dyspnoea. He had a right-sided pleural effusion, found to be exudative with lymphocytic predominance. He underwent right-sided video-assisted thoracic surgery (VATS) with biopsies and pleurodesis. Histopathology showed pleural-based non-caseating granulomas with unremarkable lung parenchyma. Cultures were only positive for Propionibacterium acnes. 8 months later, he was found to have a left-sided exudative, lymphocytic predominant pleural effusion. Left-sided VATS and biopsies again showed pleural-based non-caseating granulomas with normal lung parenchyma. Having ruled out an active infection and malignant lesions, we diagnosed infliximab-induced pleural granulomas. Infliximab was stopped. The patient continues to do well at 6 years of follow-up. We believe this is the first report of tumour necrosis factor (TNF) inhibitor-induced isolated pleural granulomas. P. acnes and cytokine imbalance might be responsible for the pathogenesis of TNF inhibitor-induced granulomas.

http://ift.tt/2sgMDkq

A case of recurrent, multifocal anastomosing haemangiomas

Anastomosing haemangiomas are relatively rare lesions, with a renal predilection, and which, given their imaging and pathologic appearance, mimic aggressive malignancies such as angiosarcoma. The imaging characteristics of this case are informative when evaluating a vascular lesion of the adrenal gland.

http://ift.tt/2rLxUKW

Internal carotid artery occlusion and stroke as a complication of cisplatin-based chemotherapy for metastatic testicular germ cell tumour

Testicular tumours are the most common tumours in young men. Germ cell tumours (GCTs) account for 95% of all testicular cancers, and the non-seminomatous type (NSGCT) accounts for 50% of all GCTs. Cisplatin-based chemotherapy is curative in up to 90% of patients, but it is not without its inherent risks. Ischaemic stroke is a very uncommon, but severe complication of cisplatin-based chemotherapy. Strokes in young patients cause a disproportionately large economic impact by leaving victims disabled during their most productive years and strains the healthcare system with expensive hospital stays. We present a case of a young male patient with past medical history of metastatic NSGCT with the sudden onset of dysarthria, left hemiplegia and ipsilateral hemisensory loss 3 days after receiving cisplatin-based chemotherapy. Subsequent studies revealed a stroke involving the right middle cerebral artery territory secondary to an acute right internal carotid occlusion.

http://ift.tt/2sh3m7m

Ominous triad triggered by high-dose glucocorticosteroid therapy

Glucocorticosteroids (CS) play a key role in the treatment of numerous diseases. Nonetheless, they can be accompanied by several adverse effects. We present the case of a 51-year-old woman who was treated with high-dose CS for a relapse of her multiple sclerosis. After 5 days of treatment, the patient developed severe diabetic ketoacidosis, hypertriglyceridemia and acute pancreatitis—a potentially life-threatening triad which has previously been described, in our case, however, for the first time as a complication of CS therapy. Our patient's condition was further aggravated by a circulatory shock, haemodynamic relevant bleeding from a duodenal ulcer and psychotic symptoms. In the intensive care unit, intravenous insulin infusion, fluid resuscitation, catecholamine support, electrolyte supplementation, endoscopic haemoclipping and antibiotic and antipsychotic treatment were administered, leading to a continuous improvement of the patient's health state.

http://ift.tt/2rM5osi

Chest X-ray of a patient with history of pleural effusion

The presented chest X-ray depicts the thoracic duct anatomy of a 50-year-old man who underwent heart transplantation. His postoperative course was complicated by Candida mediastinitis, treated with débridements and closure of the anterior chest wound with myocutaneous flaps. Postoperatively, he had persistent output from a right-sided chest tube. The fluid appeared milky and its triglycerides level was elevated at 254 mg/dL. The drainage persisted despite a low fat diet. The interventional radiologist identified a leak in the upper thoracic duct. It was embolised with coil and onyx. After the procedure, the chylous pleural effusions resolved. The thoracic duct has been visualised on subsequent chest X-rays (figures 1 and 2).

http://ift.tt/2sgWl6v

Port site endometrioma: a rare cause of abdominal wall pain following laparoscopic surgery

Endometriomas are a rare cause of abdominal wall pain. We report a case of a port site endometrioma presenting with an umbilical swelling. The patient underwent a laparoscopy for pelvic endometriosis 6 months previously and presented with a swelling around her umbilical port site scar associated with cyclical pain during menses. Ultrasound scan reported a well-defined lesion in the umbilicus and MRI scanning excluded other pathology. As she was symptomatic, she underwent an exploration of the scar and excision of the endometrioma with resolution of her symptoms. Precautions should be taken to reduce the risk of endometrial seeding during laparoscopic surgery. All tissues should be removed in an appropriate retrieval bag and the pneumoperitoneum should be deflated completely before removing ports to reduce the chimney effect of tissue being forced through the port site. The diagnosis should be considered in all women of reproductive age presenting with a painful port site scar.

http://ift.tt/2rLEPUr

Multipathogenic necrotising supraglottitis in an immunocompetent patient

Supraglottitis is a potentially life-threatening condition. It is now uncommon due to the Haemophilus influenzae type B vaccination and is more recently caused by Streptococcus pneumoniae, S. pyogenes, H. influenzae non-type B, H. parainfluenzae, Staphylococcus aureus and Pasteurella multocida. Very rarely, it can cause necrotising supraglottitis/epiglottitis, and this has been reported in immunocompromised individuals. We present a unique case of multipathogenic supraglottitis causing laryngeal fibrinoid necrosis in an immunocompetent patient. During his admission, the patient was critically unwell and required surgical intervention and tracheostomy. However, he made a full recovery with no persisting morbidity. We believe that this was owed to the aggressive antimicrobial therapy, timely surgical management of the disease process and the patientâ™s immunocompetency.

http://ift.tt/2rLCAjX

An unusual case of Escherichia coli O157:H7 infection with pseudomembranous colitis-like lesions associated with haemolytic-uraemic syndrome and neurological sequelae

A 75-year-old man was admitted with abdominal pain and fresh rectal bleeding. Significantly, he had no risk factors for Clostridium difficile infection. An abdominal CT demonstrated colonic thickening, and flexible sigmoidoscopy identified pseudomembranous colitis-like lesions. After initial treatment as C. difficile colitis, a stool sample revealed Escherichia coli O157:H7 infection. Antibiotic therapy was stopped due to the risk of lysis-mediated toxin release, but unfortunately, the patient continued to deteriorate. He developed several of the severe sequelae of E. coli O157:H7 infection, including haemolytic-uraemic syndrome with an acute kidney injury necessitating haemofiltration, plus progressively severe seizures requiring escalating antiepileptic treatment and intubation for airway protection. After a prolonged intensive care admission and subsequent recovery on the ward, our patient was discharged alive.

http://ift.tt/2sh3ljO

Electro-clinical criteria and surgical outcome: Is there a difference between mesial and lesional temporal lobe epilepsy?

Objectives

Mesial temporal lobe epilepsy syndrome (MTLE) with specific electrophysiological and clinical characteristics and hippocampal sclerosis (HS) on MRI is considered the prototype of a syndrome with good surgical prognosis. Ictal onset zones in MTLE have been found to extend outside the hippocampus and neocortical seizures often involve mesial structures. It can, thus, be questioned whether MTLE with HS is different from lesional temporal epilepsies with respect to electro-clinical characteristics and surgical prognosis. We assessed whether MTLE with HS is distinguishable from lesional TLE and which criteria determine surgical outcome.

Methods

People in a retrospective cohort of 389 individuals with MRI abnormalities who underwent temporal lobectomy, were divided into "HS only" or "lesional" TLEs. Twenty-six presented with dual pathology and were excluded from further analysis. We compared surgical outcome and electro-clinical characteristics.

Results

Over half (61%) had "HS only." Four electro-clinical characteristics (age at epilepsy onset, febrile seizures, memory dysfunction and contralateral dystonic posturing) distinguished "HS only" from "lesional" TLE, but there was considerable overlap. Seizure freedom 2 years after surgery (Engel class 1) was similar: 67% ("HS only") vs 69% ("lesional" TLE). Neither presence of HS nor electro-clinical criteria was associated with surgical outcome.

Conclusions

Despite small differences in electrophysiological and clinical characteristics between MTLE with HS and lesional TLE, surgical outcomes are similar, indicating that aetiology seems irrelevant in the referral for temporal surgery.

http://ift.tt/2squjUi

Controlled population-based comparative study of USA and international adult [55-74] neurological deaths 1989-2014

Objectives

A population-based controlled study to determine whether adult (55-74 years) neurological disease deaths are continuing to rise and are there significant differences between America and the twenty developed countries 1989-91 and 2012-14.

Method

Total Neurological Deaths (TND) rates contrasted against control Cancer and Circulatory Disease Deaths (CDD) extrapolated from WHO data. Confidence intervals compare USA and the other countries over the period. The Over-75's TND and population increases are examined as a context for the 55-74 outcomes.

Results

Male neurological deaths rose >10% in eleven countries, the other countries average rose 20% the USA 43% over the period. Female neurological deaths rose >10% in ten counties, averaging 14%, the USA up 68%. USA male and female neurological deaths increased significantly more than twelve and seventeen countries, respectively. USA over-75s population increased by 49%, other countries 56%. Other countries TND up 187% the USA rose fourfold. Male and female cancer and CDD fell in every country averaging 26% and 21%, respectively, and 64% and 67% for CDD. Male neurological rates rose significantly more than Cancer and CCD in every country; Female neurological deaths rose significantly more than cancer in 17 countries and every country for CDD. There was no significant correlation between increases in neurological deaths and decreases in control mortalities.

Conclusions

There are substantial increases in neurological deaths in most countries, significantly so in America. Rises in the 55-74 and over-75's rates are not primarily due to demographic changes and are a matter of concern warranting further investigation.

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Equal Treatment and Outcomes for Everyone with Multiple Myeloma: Are We There Yet?

Abstract

Multiple myeloma treatment has changed tremendously over recent years leading to overall improvement in patient outcomes. With therapeutic advancements, patient care has become increasingly complex and variability is seen in healthcare delivery as well as outcomes when various patient subgroups are analyzed based on sociodemographic factors. It is imperative to understand this variability so that while overall the outcomes get better, specific focus is placed on subgroups that may remain disadvantaged and may not be able to fully access the advancements in therapeutics. Research in multiple myeloma has specifically looked at several such patient subgroups based on socioeconomic status, age, race/ethnicity, insurance carrier, and geographic location that may affect healthcare utilization and patient outcomes. Exploring and understanding these would certainly help address disparities and lead to further equity in healthcare access and, hopefully, patient outcomes.

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Positional changes of maxillary central incisors following orthodontic treatment using single-crown implants as fixed reference markers

Abstract

Objectives

This follow-up study (1) compares tooth displacement of central incisors in patients with and without pre-implant orthodontic treatment and (2) investigates whether sex, age, or orthodontic retention have an effect on tooth displacement after the insertion of single-crown implants.

Materials and Methods

Fifty-seven patients – thirty-seven with (test group) and twenty without pre-implant orthodontic treatment (control group) – were rehabilitated with 89 single-crown implants in the upper maxilla. Clinical and radiographic data, clinical photographs, and dental casts were collected during baseline examinations after prosthetic rehabilitation and at the final follow-up examination at least 5 years later. A total of 114 dental casts were digitalized and aligned using a software program to measure changes in the positions of the central incisors.

Results

After a follow-up period of at least five years, 87% of the central incisors measured in the test group were displaced >0.25 mm vertically compared with 70% in the control group. Seventy-eight percent of the test group teeth had moved >0.25 mm horizontally compared with 55% in the control group. These differences were not significant, and there were no significant correlations with patient age or sex.

Conclusion

The majority of patients had minor vertical (60%) or horizontal (67%) tooth displacement of the central incisors (0.25–0.75 mm) after a minimum follow-up period of 5 years. This study found no significant differences in tooth displacement comparing patients with and without pre-implant orthodontic treatment. No significant effect of sex, age, orthodontic retention, or implant location was observed on tooth displacement.

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Surgical treatment of peri-implantitis intrabony lesions by means of deproteinized bovine bone mineral with 10% collagen: 7-year-results

Abstract

Objectives

The aim of this study was to evaluate the long-term results of the surgical treatment of single peri-implantitis intrabony defects, by means of deproteinized bovine bone mineral with 10% collagen (DBBMC).

Material and Methods

The original population consisted of 26 patients with one crater-like defect, around either sandblasted and acid-etched (SLA) or titanium plasma-sprayed (TPS) dental implants, with a probing depth (PD) ≥6 mm and no implant mobility (Roccuzzo et al. J Clin Periodontol. 2011; 38: 738). Implants were mechanically debrided and treated using EDTA gel and chlorhexidine gel. The bone defects were filled with DBBMC, and the flap was sutured around the non-submerged implant. Patients were placed on an individually tailored supportive periodontal therapy (SPT).

Results

Two patients were lost to follow-up. During SPT, additional antibiotic and/or surgical therapy was necessary in eight implants, and four of these were removed for biologic complications. At 7-year, the survival rate was 83.3% for SLA implants and 71.4% for TPS. PD was significantly reduced from 6.6 ± 1.3 to 3.2 ± 0.7 mm in SLA and 7.2 ± 1.5 to 3.4 ± 0.6 mm in TPS. Bleeding on probing decreased from 75.0 ± 31.2% to 7.5 ± 12.1% (SLA) and from 90.0 ± 12.9% to 30.0 ± 19.7% (TPS). When successful therapy was defined as PD ≤5 mm, absence of bleeding/suppuration on probing, and no further bone loss, treatment success was obtained in 2 of 14 (14.3%) of the TPS and in 7 of 12 (58.3%) of the SLA implants.

Conclusions

Seven years after surgical treatment with DBBMC, patients, in an adequate SPT, maintained sufficient peri-implant conditions in many cases, particularly around SLA implants. Nevertheless, some patients required further treatment and some lost implants. The clinical decision on whether implants should be treated or removed should be based on several factors, including implant surface characteristics.

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Clinical and radiographic evaluation of early loaded narrow-diameter implants: 5-year follow-up of a multicenter prospective clinical study

Abstract

Objective

This study was initiated to evaluate the 5-year implant survival rate and marginal bone levels around a 3.0-mm implant when replacing a single tooth in the anterior region.

Materials and methods

The study was designed as a prospective, single-arm, multicenter clinical study. Patients missing 12, 22, 32, 31, 41 or 42 teeth were included, and implants of 3.0 mm diameter and different lengths were placed by a one-stage surgery protocol. Definitive cemented crowns were placed 6–10 weeks later. Clinical and radiographic measurements were taken at implant installation, at loading and at the 6-, 12-, 24-, 36-, 48- and 60-month follow-up visits.

Results

Sixty-nine patients with 97 implants were included in this study. Four implants were lost before loading (4.12% failure rate). Implant marginal bone levels did not differ statistically after the 1-year follow-up visit. After 5 years, no bone loss was observed for 50.60% of the implants and only 8.43% of them lost more than 1 mm. Similarly, probing pocket depths and gingival zenith scores did not change significantly.

Conclusions

The use of the two-piece narrow 3.0-mm titanium dental implant for the restoration of upper lateral or lower incisors is safe and results in stable marginal bone levels and probing pocket depths after 5 years of function.

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Schisandrin B Prevents Hind Limb from Ischemia-Reperfusion-Induced Oxidative Stress and Inflammation via MAPK/NF-κB Pathways in Rats

Schisandrin B (ScB), isolated from Schisandra chinensis (S. chinensis), is a traditional Chinese medicine with proven cardioprotective and neuroprotective effects. However, it is unclear whether ScB also has beneficial effects on rat hind limb ischemia/reperfusion (I/R) injury model. In this study, ScB (20 mg/kg, 40 mg/kg, and 80 mg/kg) was administered via oral gavage once daily for 5 days before the surgery. After 6 h ischemia and 24 h reperfusion of left hind limb, ScB reduced I/R induced histological changes and edema. ScB also suppressed the oxidative stress through decreasing MDA level and increasing SOD activity. Moreover, above changes were associated with downregulated TNF-α mRNA expression and reduced level of IL-1 in plasma. Meanwhile, ScB treatment downregulated activation of p38MAPK, ERK1/2, and NF-κB in ischemic skeletal muscle. These results demonstrate that ScB treatment could prevent hind limb I/R skeletal muscle injury possibly by attenuating oxidative stress and inflammation via p38MAPK, ERK1/2, and NF-κB pathways.

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Genetic Variant of Kalirin Gene Is Associated with Ischemic Stroke in a Chinese Han Population

Introduction. Ischemic stroke is a complex disorder resulting from the interplay of genetic and environmental factors. Previous studies showed that kalirin gene variations were associated with cardiovascular disease. However, the association between this gene and ischemic stroke was unknown. We performed this study to confirm if kalirin gene variation was associated with ischemic stroke. Methods. We enrolled 385 ischemic stroke patients and 362 controls from China. Three SNPs of kalirin gene were genotyped by means of ligase detection reaction-PCR method. Data was processed with SPSS and SHEsis platform. Results. SNP rs7620580 (dominant model: OR = 1.590, p = 0.002 and adjusted OR = 1.662, p = 0.014; additive model: OR = 1.490, p = 0.002 and adjusted OR = 1.636, p = 0.005; recessive model: OR = 2.686, p = 0.039) and SNP rs1708303 (dominant model: OR = 1.523, p = 0.007 and adjusted OR = 1.604, p = 0.028; additive model: OR = 1.438, p = 0.01 and adjusted OR = 1.476, p = 0.039) were associated with ischemic stroke. The GG genotype and G allele of SNP rs7620580 were associated with a risk for ischemic stroke with an adjusted OR of 3.195 and an OR of 1.446, respectively. Haplotype analysis revealed that A–T–G,G-T-A, and A-T-A haplotypes were associated with ischemic stroke. Conclusions. Our results provide evidence that kalirin gene variations were associated with ischemic stroke in the Chinese Han population.

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Issue Cover (June 2017)

Cover image by Naoki Ihara, Ai Nakashima, Naosuke Hoshina, Yuji Ikegaya and Haruki Takeuchi

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A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

We introduce a tissue displacement-based contusive spinal cord injury model that can produce a consistent contusive spinal cord injury in adult mice.

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Glomangioma of the Kidney: A Rare Case of Glomus Tumor and Review of the Literature

Background. Glomus tumors are rare mesenchymal tumors originating from glomus bodies in the skin. Glomus tumors of the kidney are rare tumors and only a few cases have been reported in the medical literature. An extensive search revealed a very limited number of primary renal glomus tumors. Although most of these cases were benign in nature, including a case with uncertain diagnosis of malignant potential, two were malignant. Case Report. We present a unique case of a 57-year-old male patient with an incidentally discovered 2 cm left renal mass. Histopathology examination and immunohistochemical studies confirm the diagnosis of glomangioma (a form of glomus tumor). The patient was followed for one year after partial nephrectomy and showed a benign course without any evidence of local recurrence or metastasis. Conclusion. To the best of our knowledge, this is the 16th case of primary benign renal glomus tumors. Primary renal glomus tumors are rare and may mimic other mesenchymal renal neoplasms radiologically. Proper investigation (including histopathological analysis and immunohistochemical staining) of kidney tumors is essential to make the diagnosis of glomus tumors, which usually show a benign clinical course following resection.

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The Effect of Osteopontin on Microglia

Osteopontin (OPN) is a proinflammatory cytokine that can be secreted from many cells, including activated macrophages and T-lymphocytes, and is widely distributed in many tissues and cells. OPN, a key factor in tissue repairing and extracellular matrix remodeling after injury, is a constituent of the extracellular matrix of the central nervous system (CNS). Recently, the role of OPN in neurodegenerative diseases has gradually caused widespread concern. Microglia are resident macrophage-like immune cells in CNS and play a vital role in both physiological and pathological conditions, including restoring the integrity of the CNS and promoting the progression of neurodegenerative disorders. Microglia's major function is to maintain homeostasis and the normal function of the CNS, both during development and in response to CNS injury. Although the functional mechanism of OPN in CNS neurodegenerative diseases has yet to be fully elucidated, most studies suggest that OPN play a role in pathogenesis of neurodegenerative diseases or in neuroprotection by regulating the activation and function of microglia. Here, we summarize the functions of OPN on microglia in response to various stimulations in vitro and in vivo.

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ExCNVSS: A Noise-Robust Method for Copy Number Variation Detection in Whole Exome Sequencing Data

Copy number variations (CNVs) are structural variants associated with human diseases. Recent studies verified that disease-related genes are based on the extraction of rare de novo and transmitted CNVs from exome sequencing data. The need for more efficient and accurate methods has increased, which still remains a challenging problem due to coverage biases, as well as the sparse, small-sized, and noncontinuous nature of exome sequencing. In this study, we developed a new CNV detection method, ExCNVSS, based on read coverage depth evaluation and scale-space filtering to resolve these problems. We also developed the method ExCNVSSnoRatio, which is a version of ExCNVSS, for applying to cases with an input of test data only without the need to consider the availability of a matched control. To evaluate the performance of our method, we tested it with 11 different simulated data sets and 10 real HapMap samples' data. The results demonstrated that ExCNVSS outperformed three other state-of-the-art methods and that our method corrected for coverage biases and detected all-sized CNVs even without matched control data.

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Proliferation of Interstitial Cells in the Cyclophosphamide-Induced Cystitis and the Preventive Effect of Imatinib

Cyclophosphamide- (CYP-) induced cystitis in the rat is a well-known model of bladder inflammation that leads to an overactive bladder, a process that appears to involve enhanced nitric oxide (NO) production. We investigated the changes in the number and distribution of interstitial cells (ICs) and in the expression of endothelial NO synthase (eNOS) in the bladder and urethra of rats subjected to either intermediate or chronic CYP treatment. Pronounced hyperplasia and hypertrophy of ICs were evident within the lamina propria and in the muscle layer. IC immunolabeling with CD34, PDGFRα, and vimentin was enhanced, as reflected by higher colocalization indexes of the distinct pairs of markers. Moreover, de novo expression of eNOS was evident in vimentin and CD34 positive ICs. Pretreatment with the receptor tyrosine kinase inhibitor Imatinib prevented eNOS expression and ICs proliferation, as well as the increased voiding frequency and urinary tract weight provoked by CYP. As similar results were obtained in the urethra, urethritis may contribute to the uropathology of CYP-induced cystitis.

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The Effect of Personality on Online Game Flow Experience and the Eye Blink Rate as an Objective Indicator

This study aimed to explore the effects of dominant and compliant personalities, on both flow experience and the external characteristics of flow experience. A total of 48 participants were recruited to play an online game and subsequently asked to recall the songs they had heard while they were playing the game. Eye blink rate was recorded. The results demonstrated that (1) the participant was immersed in the game more if he/she was relatively dominant or noncompliant; (2) the perceptions about the external environment declined remarkably while being in a flow state; and (3) eye blink rates decreased only when the flow happened at the beginning of the game, rather than throughout the whole process. The results suggested that gamers who tend to be dominant or noncompliant were more likely to experience flow. Eye blink rate and perceptions of the external environment could be objective indicators of flow experience.

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Cancers, Vol. 9, Pages 68: Promotion of Tumor Invasion by Tumor-Associated Macrophages: The Role of CSF-1-Activated Phosphatidylinositol 3 Kinase and Src Family Kinase Motility Signaling

Macrophages interact with cells in every organ to facilitate tissue development, function and repair. However, the close interaction between macrophages and parenchymal cells can be subverted in disease, particularly cancer. Motility is an essential capacity for macrophages to be able to carry out their various roles. In cancers, the macrophage's interstitial migratory ability is frequently co-opted by tumor cells to enable escape from the primary tumor and metastatic spread. Macrophage accumulation within and movement through a tumor is often stimulated by tumor cell production of the mononuclear phagocytic growth factor, colony-stimulating factor-1 (CSF-1). CSF-1 also regulates macrophage survival, proliferation and differentiation, and its many effects are transduced by its receptor, the CSF-1R, via phosphotyrosine motif-activated signals. Mutational analysis of CSF-1R signaling indicates that the major mediators of CSF-1-induced motility are phosphatidyl-inositol-3 kinase (PI3K) and one or more Src family kinase (SFK), which activate signals to adhesion, actin polymerization, polarization and, ultimately, migration and invasion in macrophages. The macrophage transcriptome, including that of the motility machinery, is very complex and highly responsive to the environment, with selective expression of proteins and splice variants rarely found in other cell types. Thus, their unique motility machinery can be specifically targeted to block macrophage migration, and thereby, inhibit tumor invasion and metastasis.

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Current Status and Future Perspective of Stenting for Symptomatic Intracranial Atherosclerotic Disease: A Meta-Analysis

The aim of this study was to evaluate the safety and effectiveness of percutaneous transluminal angioplasty and stenting (PTAS) for intracranial atherosclerotic disease (ICAD) by conducting a meta-analysis. Two independent observers searched PubMed, EMBASE, and Cochrane Library for relevant studies up to 31 December 2016. A meta-analysis was conducted using Review Manager 5.3. Three studies involving 581 cases were included. The meta-analysis indicated that any stroke (RR = 3.13; 95% CI: 1.80–5.42), ischemic stroke (RR = 2.15; 95% CI: 1.19–3.89), and intracranial hemorrhage (RR = 14.71; 95% CI: 1.96–110.48) within 30 days in medical therapy alone were lower compared with PTAS plus medical therapy, but there were no significant differences in any stroke and ischemic stroke beyond 30 days between the two groups. There were also no significant differences in any death and myocardial infarction between the two groups. This meta-analysis demonstrated that, compared with medical therapy alone, PTAS for ICAD had a high risk of complication, but most complications in PTAS group occurred within 30 days after the operation, and beyond 30 days the PTAS was not inferior compared with medical therapy alone. Further studies are needed to reduce the periprocedural complications and reappraise the PTAS.

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Natriuretic Peptides as Biomarkers for Congestive States: The Cardiorenal Divergence

Congestion represents the primary reason for hospitalization of patients with heart failure and is associated with adverse outcomes. Fluid overload has been shown to be inadequately addressed in a significant subset of these patients in part due to lack of robust, reliable, and readily available biomarkers for objective assessment and monitoring of therapy. Natriuretic peptides have long been used in this setting, often in conjunction with other assessment tools such as imaging studies. Patients presenting with concomitant cardiac and renal dysfunction represent a unique population with regard to congestion in that the interactions between the heart and the kidney can affect the utility and performance of biomarkers of fluid overload. Herein, we provide an overview of the currently available evidence on the utility of natriuretic peptides in these patients and discuss the clinical conundrum associated with their use in the setting of renal dysfunction. We highlight the potential divergence in the role of natriuretic peptides for assessment of volume status in a subset of patients with renal dysfunction who receive renal replacement therapy and call for future research to elucidate the utility of the biomarkers in this setting.

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Preclinical Studies and Translational Applications of Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) which refers to bleeding in the brain is a very deleterious condition with high mortality and disability rate. Surgery or conservative therapy remains the treatment option. Various studies have divided the disease process of ICH into primary and secondary injury, for which knowledge into these processes has yielded many preclinical and clinical treatment options. The aim of this review is to highlight some of the new experimental drugs as well as other treatment options like stem cell therapy, rehabilitation, and nanomedicine and mention some translational clinical applications that have been done with these treatment options.

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Lower Extremity Abscess Formation in Premature Infants due to Routine Infant Vaccinations

Since the introduction of vaccines, the impact of vaccinations has been immeasurable. Under the current immunization guidelines, infants receive the first of their routine infant vaccinations at 2 months of age. While the benefits of routine infant vaccinations in premature infants have been demonstrated, there is relatively little data on the dosing of these vaccines in premature infants. The medical records of two premature infants who developed intramuscular abscesses after receiving their routine infant vaccinations were reviewed. Both patients developed pain in the area of the injection after receiving their vaccinations. Magnetic resonance imaging findings confirmed the formation of an abscess. No other causes of abscess formation were observed. Both patients required surgical intervention and were treated with a course of antibiotics. To our knowledge, this is the first case report to suggest routine vaccinations as a potential cause of abscess formation in premature infants.

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Complete Chloroplast Genome Sequence of Coptis chinensis Franch. and Its Evolutionary History

The Coptis chinensis Franch. is an important medicinal plant from the Ranunculales. We used next generation sequencing technology to determine the complete chloroplast genome of C. chinensis. This genome is 155,484 bp long with 38.17% GC content. Two 26,758 bp long inverted repeats separated the genome into a typical quadripartite structure. The C. chinensis chloroplast genome consists of 128 gene loci, including eight rRNA gene loci, 28 tRNA gene loci, and 92 protein-coding gene loci. Most of the SSRs in C. chinensis are poly-A/T. The numbers of mononucleotide SSRs in C. chinensis and other Ranunculaceae species are fewer than those in Berberidaceae species, while the number of dinucleotide SSRs is greater than that in the Berberidaceae. C. chinensis diverged from other Ranunculaceae species an estimated 81 million years ago (Mya). The divergence between Ranunculaceae and Berberidaceae was 111 Mya, while the Ranunculales and Magnoliaceae shared a common ancestor during the Jurassic, 153 Mya. Position 104 of the C. chinensis ndhG protein was identified as a positively selected site, indicating possible selection for the photosystem-chlororespiration system in C. chinensis. In summary, the complete sequencing and annotation of the C. chinensis chloroplast genome will facilitate future studies on this important medicinal species.

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Anti-Platelet Factor 4/Heparin Antibody Formation Occurs Endogenously and at Unexpected High Frequency in Polycythemia Vera

Background. Myeloproliferative neoplasms (MPN) encounter thromboses due to multiple known risk factors. Heparin-induced thrombocytopenia (HIT) is a thrombotic syndrome mediated by anti-platelet factor 4 (PF4)/heparin antibodies with undetermined significance for thrombosis in MPN. We hypothesized that anti-PF4/heparin Ab might occur in MPN and promote thrombosis. Methods. Anti-PF4/heparin antibodies were analyzed in 127 MPN patients including 76 PV and 51 ET. Screening, validation testing, and isotype testing of anti-PF4/heparin Ab were correlated with disease characteristics. Results. Anti-PF4/heparin antibodies were detected in 21% of PV and 12% of ET versus 0.3–3% in heparin-exposed patients. Validation testing confirmed anti-PF4/heparin immunoglobulins in 15% of PV and 10% of ET. Isotype testing detected 9.2% IgG and 5.3% IgM in PV and exclusively IgM in ET. IgG-positive PV patients encountered thromboses in 57.1% suggesting anti-PF4/heparin IgG may contribute to higher risk for thrombosis in MPN. Overall, 45% of PV patients experienced thromboses with 11.8% positive for anti-PF4/heparin IgG versus 7.1% in PV without thrombosis. Conclusion. Anti-PF4/heparin antibodies occur endogenously and more frequently in MPN than upon heparin exposure. Thrombotic risk increases in anti-PF4/heparin IgG-positive PV reflecting potential implications and calling for larger, confirmatory cohorts. Anti-PF4/heparin IgG should be assessed upon thrombosis in PV to facilitate avoidance of heparin in anti-PF4/heparin IgG-positive PV.

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