Decrease of Plasma Soluble (Pro)renin Receptor by Bariatric Surgery in Patients with Obstructive Sleep Apnea and Morbid Obesity

Metabolic Syndrome and Related Disorders, Ahead of Print.


http://ift.tt/2FZCaOV

The transition from HLA-I positive to HLA-I negative primary tumors: the road to escape from T-cell responses

Natalia Aptsiauri | Francisco Ruiz-Cabello | Federico Garrido

http://ift.tt/2u648qv

Otolaryngology in Low-Resource Settings

Providing otolaryngology care in low-resource settings requires careful preparation to ensure good outcomes. The level of care that can be provided is dictated by available resources and the supplementary equipment, supplies, and personnel brought in. Other challenges include personal health and safety risks as well as cultural and language differences. Studying outcomes will inform future missions. Educating and developing ongoing partnerships with local physicians can lead to sustained improvements in the local health care system.

http://ift.tt/2FN6y2R

Otolaryngology Around the World

Humankind initially believed that the Earth was flat, and then, several centuries ago, mathematicians and astronomers proved that the Earth was round. As we complete the second decade of this century, we realize that, although the planet is spherical, the changing attitudes, free movement of people across borders, and access to ideas in all areas from cosmopolitan to rural sites, mean that the world is actually "flat." In his book, The World Is Flat: A Brief History of the 21st Century, Thomas Friedman alludes to the perceptual shift required for countries, companies, and individuals to remain competitive in a global market in which historical and geographic divisions have become increasingly irrelevant.

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Is Your Teen Getting Enough Sleep?

How much sleep does a teenager need?

While there are individual differences, it is recommended that on average, adolescents need 8.5-9.5 hours of sleep a night. One study found that 2/3 of high school students get less than seven hours of sleep and another found that 33 percent of teens reported falling asleep in school (Calamaro et al., 2009; Eaton et al., 2010). Overall, the data suggests most adolescents are not receiving the amount of sleep they need.

Why is getting sufficient sleep a challenge in adolescence?

A number of elements make getting sufficient sleep challenging in adolescence. There are physiological changes that occur during this period of development that impact sleep, including a two hour delay in sleep onset after puberty and slower accumulation of their sleep drive. These physiological factors makes it difficult for teens to fall asleep before 11:00 p.m. Paired with the fact many middle and high schools have an early start time can make it difficult to obtain sufficient sleep. On top of all of this, teens often have other commitments that may lead require them to stay up later or get up earlier, such as homework, extracurricular commitments, and part-time jobs.

Additionally, parents are less likely to monitor and be aware of sleep problems in school-age children and teenagers than in younger children. In fact, approximately 70% of parents polled by The National Sleep Foundation reported they believe their teen is obtaining sufficient sleep, although as we've discussed, the data suggests otherwise.

You might be thinking, "My child sleeps in on the weekends, so they make up the difference, right?"

Over time, nights of missed sleep can build into a "sleep debt." While many youth try to make up their "sleep debt" by oversleeping on the weekends, data suggest this oversleep falls short of hitting the normal daily sleep recommendation. The result is many adolescents experience chronic sleep loss and circadian misalignment have very real consequences on their physical and mental health, academic performance, mood, behavior, and safety (think drowsy driving).

Below are some signs your teen may be experiencing insufficient sleep:

• Trouble waking up most mornings
• Acts irritable in the early afternoon
• Falls asleep easily during the day
• Has a sudden drop in grades
• Sleeps for very long periods on the weekends or long naps after school
• More than two hours difference between sleep schedule on weekdays vs. weekends
• Sleep onset lasts more than 30 minutes

If you believe your teenager is not obtaining the recommended amount of sleep, you can start by establishing a regular sleep schedule, including the weekends. Other helpful interventions include avoiding caffeine, increasing light exposure in the morning, not allowing your child to do any activities in bed (no homework, TV, reading, and so on), and limiting their use of electronics prior to bedtime.

The post Is Your Teen Getting Enough Sleep? appeared first on ChildrensMD.

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Optical imaging with a high-resolution microendoscope to identify sinonasal pathology

High-resolution microendoscopy (HRME) is an optical imaging modality that allows real time imaging of epithelial tissue and structural changes within. We hypothesize that HRME, using proflavine, a contrast agent that preferentially stains cell nuclei and allows detection of cellular morphologic changes, can distinguish sinonasal pathology from uninvolved mucosa, potentially enabling real-time surgical margin differentiation.

http://ift.tt/2G707aa

Analysis of chemosensory function in patients with chronic Eustachian tube dysfunction prior to and after balloon dilatation

Eustachian tube dysfunction (ETD) affects approximately 1% of adults in the general population. Non treated Eustachian tube dysfunction can result in chronic middle ear diseases, which have been shown to significantly affect taste sensitivity. A promising treatment is balloon dilatation of the Eustachian tube. The primary aim of the present study was to investigate whether individuals with ETD had impairment in chemosensory functions, and the changes of the chemosensory function after balloon dilatation of the Eustachian tube.

http://ift.tt/2FVl8RH

Female Involvement in School Rampage Plots

Violence and Gender, Ahead of Print.


http://ift.tt/2ppzXWy

Poor Sleep Quality is Associated with Insulin Resistance in Postmenopausal Women With and Without Metabolic Syndrome

Metabolic Syndrome and Related Disorders, Ahead of Print.


http://ift.tt/2HP3YFT

Retraction for Maisonneuve et al., Bacterial persistence by RNA endonucleases [Retraction]

GENETICS Retraction for "Bacterial persistence by RNA endonucleases," by Etienne Maisonneuve, Lana J. Shakespeare, Mikkel Girke Jørgensen, and Kenn Gerdes, which was first published July 25, 2011; 10.1073/pnas.1100186108 (Proc Natl Acad Sci USA 108:13206–13211). The authors wish to note the following: "In this article, we reported that successive deletion of...

http://ift.tt/2GMdOsW

Retraction for Skau et al., Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly [Retraction]

CELL BIOLOGY Retraction for "Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly," by Colleen T. Skau, Sergey V. Plotnikov, Andrew D. Doyle, and Clare M. Waterman, which was first published April 27, 2015; 10.1073/pnas.1505035112 (Proc Natl Acad Sci USA...

http://ift.tt/2u5Yrsv

Correction for Kudalkar et al., From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection [Correction]

PHARMACOLOGY Correction for "From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection," by Shalley N. Kudalkar, Jagadish Beloor, Elias Quijano, Krasimir A. Spasov, Won-Gil Lee, José A. Cisneros, W. Mark Saltzman, Priti Kumar, William L. Jorgensen, and Karen S. Anderson, which was first published December 26,...

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Correction for Lange et al., A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins [Correction]

BIOCHEMISTRY Correction for "A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins," by Heike Lange, Anita Kaut, Gyula Kispal, and Roland Lill, which was first published February 1, 2000; 10.1073/pnas.97.3.1050 (Proc Natl Acad Sci USA 97:1050–1055). The authors wish to note the following: "Recently when we reanalyzed Fig....

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Defaunation shadow on mutualistic interactions [Biological Sciences]

Tregidgo et al. (1) show that size-selective overfishing has drastically depleted and downsized populations of tambaqui (Colossoma macropomum) along the Purus River, Amazonia. Because fishers have historically targeted the largest individuals, tambaqui ∼1,000 km upriver are twofold larger than those near the Manaus rainforest metropolis (1). Here, we demonstrate that...

http://ift.tt/2u2ETp7

Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation [Systems Biology]

Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, as in the development of competence by the bacterium Bacillus subtilis, or on deterministic cell fate decisions that...

http://ift.tt/2FRZWju

Integration of speed and time for estimating time to contact [Psychological and Cognitive Sciences]

To coordinate movements with events in a dynamic environment the brain has to anticipate when those events occur. A classic example is the estimation of time to contact (TTC), that is, when an object reaches a target. It is thought that TTC is estimated from kinematic variables. For example, a...

http://ift.tt/2u9XGi6

Simultaneous imaging and functional studies reveal a tight correlation between calcium and actin networks [Plant Biology]

Tip-growing cells elongate in a highly polarized manner via focused secretion of flexible cell-wall material. Calcium has been implicated as a vital factor in regulating the deposition of cell-wall material. However, deciphering the molecular and mechanistic calcium targets in vivo has remained challenging. Here, we investigated intracellular calcium dynamics in...

http://ift.tt/2GQmDSI

hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons [Neuroscience]

Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein...

http://ift.tt/2u6umJu

Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition [Medical Sciences]

Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable targets to reduce TAM activities remain very few and far between because the signaling mechanisms underpinning protumor macrophage phenotypes are...

http://ift.tt/2FS02rm

Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL [Cell Biology]

The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and triggers the unfolded protein response (UPR). Failure to resolve ER stress leads to apoptotic cell death via a yet unclear mechanism. Here, we show that RNF183, a membrane-spanning RING finger protein, localizes to the ER and...

http://ift.tt/2u2ELWF

Noninvasive detection of macrophage activation with single-cell resolution through machine learning [Biophysics and Computational Biology]

We present a method enabling the noninvasive study of minute cellular changes in response to stimuli, based on the acquisition of multiple parameters through label-free microscopy. The retrieved parameters are related to different attributes of the cell. Morphological variables are extracted from quantitative phase microscopy and autofluorescence images, while molecular...

http://ift.tt/2FS096g

BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure [Neuroscience]

Mutations in the BEST1 gene cause detachment of the retina and degeneration of photoreceptor (PR) cells due to a primary channelopathy in the neighboring retinal pigment epithelium (RPE) cells. The pathophysiology of the interaction between RPE and PR cells preceding the formation of retinal detachment remains not well-understood. Our studies...

http://ift.tt/2u6uoRC

Matching material and cellular timescales maximizes cell spreading on viscoelastic substrates [Biophysics and Computational Biology]

Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains unclear. In this study, we systematically examined the dynamics of motor clutches (i.e., focal adhesions) formed...

http://ift.tt/2u2ESl3

Modeling environmentally mediated rotavirus transmission: The role of temperature and hydrologic factors [Environmental Sciences]

Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic...

http://ift.tt/2u2EKSB

Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference [Engineering]

Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we...

http://ift.tt/2FS06Y8

Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection [Microbiology]

Treatment of bacterial infections is becoming a serious clinical challenge due to the global dissemination of multidrug antibiotic resistance, necessitating the search for alternative treatments to disarm the virulence mechanisms underlying these infections. Uropathogenic Escherichia coli (UPEC) employs multiple chaperone–usher pathway pili tipped with adhesins with diverse receptor specificities to...

http://ift.tt/2FX8xxD

Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe-host interactions [Biochemistry]

Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as...

http://ift.tt/2u40Gg5

BRICHOS domain of Bri2 inhibits islet amyloid polypeptide (IAPP) fibril formation and toxicity in human beta cells [Cell Biology]

Aggregation of islet amyloid polypeptide (IAPP) into amyloid fibrils in islets of Langerhans is associated with type 2 diabetes, and formation of toxic IAPP species is believed to contribute to the loss of insulin-producing beta cells. The BRICHOS domain of integral membrane protein 2B (Bri2), a transmembrane protein expressed in...

http://ift.tt/2GMebDQ

N-terminal arginylation generates a bimodal degron that modulates autophagic proteolysis [Biochemistry]

The conjugation of amino acids to the protein N termini is universally observed in eukaryotes and prokaryotes, yet its functions remain poorly understood. In eukaryotes, the amino acid l-arginine (l-Arg) is conjugated to N-terminal Asp (Nt-Asp), Glu, Gln, Asn, and Cys, directly or associated with posttranslational modifications. Following Nt-arginylation, the...

http://ift.tt/2GOB0XK

Optical imaging with a high-resolution microendoscope to identify sinonasal pathology

Publication date: Available online 20 March 2018
Source:American Journal of Otolaryngology
Author(s): Sarah M. Kidwai, Arjun K. Parasher, Victor J. Schorn, Elizabeth G. Demicco, Rebecca Richards-Kortum, Alfred Marc Iloreta, Satish Govindaraj, Brett A. Miles
ObjectivesHigh-resolution microendoscopy (HRME) is an optical imaging modality that allows real time imaging of epithelial tissue and structural changes within. We hypothesize that HRME, using proflavine, a contrast agent that preferentially stains cell nuclei and allows detection of cellular morphologic changes, can distinguish sinonasal pathology from uninvolved mucosa, potentially enabling real-time surgical margin differentiation.Study designEx vivo imaging of histopathologically confirmed samples of sinonasal pathology and uninvolved, normal sinus epithelium.SettingSingle tertiary-level institution.Subjects and methodsFive inverted papillomas, one oncocytic papilloma, two uninvolved sinus epithelia specimens, and three inflammatory polyps were imaged ex vivo with HRME after surface staining with proflavine. Following imaging, the specimens were submitted for hematoxylin and eosin staining to allow histopathological correlation.ResultsResults show that sinonasal pathology and normal sinus epithelia have distinct HRME imaging characteristics. Schneiderian papilloma specimens show increased nuclear-to-cytoplasmic ratio, nuclear crowding, and small internuclear separation, whereas normal sinus epithelia specimens show small, bright nuclei with dark cytoplasm and relatively large internuclear separation. Inflammatory polyps, however, have varying imaging characteristics, that resemble both Schneiderian papilloma and normal sinus epithelia.ConclusionsThis study demonstrates the feasibility of HRME imaging to discriminate sinonasal pathology from normal sinus epithelia. While the system performed well in the absence of inflammation, discrimination of inflamed tissue was inconsistent, creating a significant limitation for this application. Novel imaging systems such as HRME with alternative contrast agents may assist with real-time surgical margin differentiation, enabling complete surgical resection of inverted papilloma and reducing recurrence rates.



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Early Experience With CliniMACS Prodigy CCS (IFN-gamma) System in Selection of Virus-specific T Cells From Third-party Donors for Pediatric Patients With Severe Viral Infections After Hematopoietic Stem Cell Transplantation

Viral reactivation is a frequent complication of allogeneic hematopoietic stem cell transplantation especially in children. For refractory cases, rapid virus-specific T-cell therapy would be ideally implemented within a few days. Over the course of a year in our pediatric cohort of 43 allogeneic transplantation, 9 patients fulfilled criteria for virus-specific T-cell therapy. Viral infections were due to cytomegalovirus (CMV) in 3, Epstein-Barr virus (EBV) in 2, and adenovirus (AdV) in 1 case, whereas >1 virus was detected in 3 cases. Viral diseases necessitating a T-cell therapy were CMV pneumonitis and colitis, AdV enteritis and cystitis, and EBV-induced posttransplantation lymphoproliferative disease. Cells were produced by the CliniMACS Prodigy CCS (IFN-gamma) System within 24 hours after mononuclear leukapheresis. Eight patients became completely asymptomatic, whereas 7 also cleared the virus. Six patients are alive without viral illness or sequelae demonstrating viral DNA clearance in peripheral blood with a median follow-up of 535 (350–786) days. One patient with CMV pneumonitis died of respiratory insufficiency. In 2 cases the viral illness improved or cleared, however, the patients died of invasive aspergillosis. No cases of graft-versus-host disease, rejection, organ toxicity, or recurrent infection were noticed. Virus-specific T-cell therapy implemented by the CliniMACS Prodigy CCS (IFN-gamma) System is an automated, fast, safe, and probably effective way to control resistant viral diseases after pediatric hematopoietic stem cell transplantation.

http://ift.tt/2FXYUPd

NKG2D Immunoligand rG7S-MICA Enhances NK Cell-mediated Immunosurveillance in Colorectal Carcinoma

Colorectal carcinoma (CRC) is one of the most common malignant cancers worldwide. The poor response of CRC to chemotherapy has whipped up the interest in targeted therapy with monoclonal antibodies for its potential efficiency. However, cetuximab, as one of the first-line targeted drugs in the treatment of CRC, has drug resistance and poor prognosis in clinic. To address this, a novel bispecific protein with CRC targeting and natural killer (NK) cell triggering was used for treatment. NK cell-mediated immunosurveillance is normally activated by the activating receptor natural killer cell receptor NK group 2, member D (NKG2D), which binds its key ligand major histocompatibility complex (MHC) class I-related chain A (MICA) expressed on the tumor cells. To trigger NK cell-mediated cytotoxicity, we fused MICA portion to a single-chain antibody fragment rG7S targeting the tumor-associated antigen CD24. In vitro, flow cytometry, cytotoxicity assay, degranulation, and cytokines release assay revealed that the fusion protein rG7S-MICA could both binds to CD24 and NKG2D which enhances NK cell sensitivity and NKG2D-mediated immunosurveillance against CD24+ CRC cells. Furthermore, in a CD24+ CRC-bearing nude mice model, rG7S-MICA effectively recruits NK cell to the tumor site and increase the release of cytokines such as interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α), and shows potential antitumor effects. In conclusion, rG7S-MICA provides a novel immunotherapeutic strategy for CRC, which could be further developed against other CD24+ malignancies.

http://ift.tt/2Gc2NDw

Whole Recombinant Saccharomyces cerevisiae Yeast Expressing Ras Mutations as Treatment for Patients With Solid Tumors Bearing Ras Mutations: Results From a Phase 1 Trial

We are developing whole, heat-killed, recombinant Saccharomyces cerevisiae yeast, engineered to encode target proteins, which stimulate immune responses against malignant cells expressing those targets. This phase 1 trial, enrolling patients with advanced colorectal or pancreas cancer, was designed to evaluate safety, immunogenicity, response, and overall survival of ascending doses of the GI-4000 series of products, which express 3 different forms of mutated Ras proteins. The study enrolled 33 heavily pretreated subjects (14 with pancreas and 19 with colorectal cancer), whose tumors were genotyped before enrollment to identify the specific ras mutation and thereby to identify which GI-4000 product to administer. No dose limiting toxicities were observed and no subject discontinued treatment due to a GI-4000 related adverse event (AE). The majority of AEs and all fatal events were due to underlying disease progression and AE frequencies were not significantly different among dose groups. GI-4000 was immunogenic, as Ras mutation-specific immune responses were detected on treatment in ∼60% of subjects. No objective tumor responses were observed but based on imaging, clinical status and/or biochemical markers, stable disease was observed in 6 subjects (18%) on day 29, while 1 subject had stable disease at days 57 and 85 follow-up visits. The median overall survival was 3.3 months (95% confidence interval, 2.3–5.3 mo), and 5 subjects survived past the 48-week follow-up period. No significant dose-dependent trends for survival were observed. This first clinical trial in humans with GI-4000 demonstrated a favorable safety profile and immunogenicity in the majority of subjects.

http://ift.tt/2HRFdsV

HMGN2: An Antitumor Effector Molecule of γδT Cells

γδT cells function in the regulation of T-cell activation in cancer and have been identified as a novel target for cancer immunotherapy. Activated γδT cells release a series of cytotoxic molecules-including granulysin, perforin, Fas/Fas ligand (Fas-L), and granzymes A and B-to kill target cells. Our previous research has shown that high mobility group nucleosomal-binding domain 2 (HMGN2), which is expressed at a high level in activated CD8+T cells, is an antitumor effector molecule of CD8+T cells. In the present study, we examined the expression and antitumor effects of HMGN2 in γδT cells. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors with a PBMC separation column. PMBCs were stimulated with isopentenyl pyrophosphate (IPP) and interleukin-2 (IL-2) for 10 days for activation and expansion. Activated γδT cells were isolated from IPP-pretreated PBMCs with a Moflo XDP flow cytometry sorter. The expression of HMGN2 in γδT cells was detected by flow cytometry and enzyme-linked immunosorbent assay. The cytotoxic effects of γδT cells and HMGN2 were analyzed by carboxyfluorescein succinimidyl ester labeling. IPP combined with IL-2 induced significant activation and expansion of γδT cells in vitro. HMGN2 was constitutively expressed in γδT cells. IPP-activated γδT cells expressed a high level of HMGN2 that could be detected intracellularly and in the supernatant. Moreover, supernatants of purified γδT cells were sufficient to kill tumor cells and could be blocked with anti-human HMGN2 antibody. This study suggests that HMGN2 is an antitumor effector molecule of γδT cells.

http://ift.tt/2G5VblQ

The Risk of Diarrhea and Colitis in Patients With Advanced Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Systematic Review and Meta-Analysis

Checkpoint inhibitors are a first-line therapy for advanced melanoma, though their use is limited by diarrhea and colitis. The aim of our study was to determine the risk of these toxicities associated with immunotherapy in advanced melanoma. Electronic databases were searched through June 2017 for prospective studies reporting the risk of diarrhea and colitis in advanced melanoma treated with anti–programmed death-1 (PD-1) or anti–cytotoxic T-lymphocyte antigen-4 (CTLA-4) inhibitors. Standardized definitions assessed the grade of diarrhea and colitis. Pooled incidence and weighted relative risk estimates with 95% confidence intervals (CI) were estimated using random effects model. Eighteen studies were included: 6 studies (1537 patients) with PD-1 inhibitors and 15 studies (3116 patients) with CTLA-4 inhibitors. The incidence of all-grade diarrhea was 13.7% (95% CI, 10.1%–17.2%) for anti-PD-1 and 35.4% (95% CI, 30.4%–40.5%) for anti-CTLA-4. The incidence of all-grade colitis was 1.6% (95% CI, 0.7%–2.4%) for anti-PD-1, and 8.8% (95% CI, 6.1%–11.5%) for anti-CTLA-4. When PD-1 inhibitors were compared directly with CTLA-4 inhibitors, the relative risk of all-grade diarrhea was 0.58 (95% CI, 0.43–0.77), and the relative risk of all-grade colitis was 0.16 (95% CI, 0.05–0.51). The rate of therapy discontinuation was numerically higher for anti-CTLA-4 therapy compared with anti-PD-1 therapy. Finally, 2 studies compared combination immunotherapy with anti-CTLA-4 therapy alone. The relative risk of developing all-grade diarrhea and colitis with combination therapy was 1.31 (95% CI, 1.09–1.57) and 1.21 (95% CI, 0.73–1.99), respectively. Diarrhea and colitis are frequent toxicities associated with checkpoint inhibitors, and seem to be most common with CTLA-4 inhibitors.

http://ift.tt/2HO9rNg

Brief Communication; A Heterologous Oncolytic Bacteria-Virus Prime-Boost Approach for Anticancer Vaccination in Mice

Anticancer vaccination is becoming a popular therapeutic approach for patients with cancers expressing common tumor antigens. One variation on this strategy is a heterologous virus vaccine where 2 viruses encoding the same tumor antigen are administered sequentially to prime and boost antitumor immunity. This approach is currently undergoing clinical investigation using an adenovirus (Ad) and the oncolytic virus Maraba (MRB). In this study, we show that Listeria monocytogenes can be used in place of the Ad to obtain comparable immune priming efficiency before MRB boosting. Importantly, the therapeutic benefits provided by our heterologous L. monocytogenes-MRB prime-boost strategy are superior to those conferred by the Ad-MRB combination. Our study provides proof of concept for the heterologous oncolytic bacteria-virus prime-boost approach for anticancer vaccination and merits its consideration for clinical testing.

http://ift.tt/2GO4g0L

A Dose-escalation Study of Recombinant Human Interleukin-18 in Combination With Ofatumumab After Autologous Peripheral Blood Stem Cell Transplantation for Lymphoma

Interleukin-18 (IL-18) is an immunostimulatory cytokine that augments antibody-dependent cellular cytotoxicity mediated by human natural killer cells against antibody-coated lymphoma cells in vitro and that has antitumor activity in animal models. Ofatumumab is a CD20 monoclonal antibody with activity against human B-cell lymphomas. A phase I study of recombinant human (rh) IL-18 given with ofatumumab was undertaken in patients with CD20+ lymphoma who had undergone high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Cohorts of 3 patients were given intravenous infusions of ofatumumab 1000 mg weekly for 4 weeks with escalating doses of rhIL-18 as a intravenous infusion weekly for 8 consecutive weeks. Nine male patients with CD20+ lymphomas were given ofatumumab in combination with rhIL-18 at doses of 3, 10, and 30 μg/kg. No unexpected or dose-limiting toxicities were observed. The mean reduction from predose levels in the number of peripheral blood natural killer cells after the first rhIL-18 infusion was 91%, 96%, and 97% for the 3, 10, and 30 μg/kg cohorts, respectively. Serum concentrations of interferon-γ and chemokines transiently increased following IL-18 dosing. rhIL-18 can be given in biologically active doses by weekly infusions in combination with ofatumumab after peripheral blood stem cell transplantation to patients with lymphoma. A maximum tolerated dose of rhIL-18 plus ofatumumab was not determined. Further studies of rhIL-18 and CD20 monoclonal antibodies in B-cell malignancies are warranted.

http://ift.tt/2FZ9AwO

Preclinical Assessment of CAR T-Cell Therapy Targeting the Tumor Antigen 5T4 in Ovarian Cancer

Chimeric antigen receptor (CAR) T cells represent a novel targeted approach to overcome both quantitative and qualitative shortfalls of the host immune system relating to the detection and subsequent destruction of tumors. The identification of antigens expressed specifically on the surface of tumor cells is a critical first step in the ability to utilize CAR T cells for the treatment of cancer. The 5T4 is a tumor-associated antigen which is expressed on the cell surface of most solid tumors including ovarian cancer. Matched blood and tumor samples were collected from 12 patients with ovarian cancer; all tumors were positive for 5T4 expression by immunohistochemistry. Patient T cells were effectively transduced with 2 different anti-5T4 CAR constructs which differed in their affinity for the target antigen. Co-culture of CAR T cells with matched autologous tumor disaggregates resulted in antigen-specific secretion of IFN-gamma. Furthermore, assessment of the efficacy of anti-5T4 CAR T cells in a mouse model resulted in therapeutic benefit against established ovarian tumors. These results demonstrate proof of principle that 5T4 is an attractive target for immune intervention in ovarian cancer and that patient T cells engineered to express a 5T4-specific CAR can recognize and respond physiologically to autologous tumor cells.

http://ift.tt/2GdIdT0

Bullous Pemphigoid–like Skin Lesions and Overt Eosinophilia in a Patient With Melanoma Treated With Nivolumab: Case Report and Review of the Literature

The widespread use of immune checkpoint inhibitors has shed light to several unusual immune-related adverse effects of the drugs. Severe cutaneous adverse reactions are generally rare with anti-PD1 agents. We present in this paper the case of a 48-year-old patient with melanoma who developed bullous pemphigoid–like skin lesions along with fever, arthralgia and overt eosinophilia following adjuvant treatment with nivolumab. The condition was successfully treated with corticosteroids and a rechallenge with another anti-PD1 agent did not lead to recurrence of the skin lesions. We also reviewed the literature on the epidemiologic, clinical, and histopathologic characteristics of bullous pemphigoid as well as on the treatment and prognosis of this dermatologic condition in patients with melanoma or other malignancies under treatment with immune checkpoint inhibitors.

http://ift.tt/2HPfwZU

The Potential of Behavioral Counseling to Prevent Skin Cancer

Skin cancers, ie, melanoma and keratinocyte skin cancer, are the most common cancers. The number of melanomas is expected to nearly double by 2030, tripling annual treatment costs in the United States. Because skin cancer is strongly associated with UV radiation (UVR) exposure, the Centers for Disease Control and Prevention recommend reducing unprotected exposure to UVR. The US Surgeon General issued a Call to Action to Prevent Skin Cancer, appealing for efforts to identify effective skin cancer prevention interventions.

http://ift.tt/2GNG7r9

Extra-axial chordoma: a clinicopathologic analysis of six cases

Abstract

Extra-axial chordoma is an exceedingly rare tumor, with only 28 cases reported in the literature to date. Axial and extra-axial chordoma exhibits complete morphologic and immunophenotypic (expression of brachyury) overlap. However, in consideration of the non-canonical presentation, extra-axial chordoma is under-recognized and often misdiagnosed, most often as extraskeletal myxoid chondrosarcoma or myoepithelioma. To increase our understanding of the clinicopathologic features of extra-axial chordoma, six cases have been retrieved from the files of the Istituto Ortopedico Rizzoli and of the General Hospital of Treviso. The clinicoradiologic, morphologic, and molecular features have been analyzed, and the follow-up was updated. Our series included four female and two male patients; their ages ranged from 20 to 67 years (mean 45.8 years). All patients presented with a single mass localized in four cases in the soft tissue (posterior arm, left leg, dorsal aspect of the foot, and popliteal fossa), and in two cases in the bone (radius and second metacarpal bone). Grossly, the neoplasm was lobulated, with a fleshy cut surface and a diameter ranging between 0.8 and 8 cm (mean 3.4 cm). Morphologically, all six cases showed an epithelioid cell proliferation organized in nests and cords demarcated by fibrous septa and set in an abundant extracellular myxoid matrix. Neoplastic cells featured hyperchromatic nuclei and abundant vacuolated cytoplasm. Immunohistochemically, all six cases were strongly positive for EMA, cytokeratin AE1/AE3, S100, and brachyury. INI1 nuclear expression was retained. Smooth muscle actin, calponin, p63, and GFAP were all negative. Fluorescent in situ hybridization (FISH) analysis did not reveal rearrangements involving NR4A3, FUS, and EWSR1 genes. At follow-up (mean 55 months), all patients were alive without disease after local surgical treatment. One patient underwent thigh amputation following multiple local recurrences and inguinal node metastases treated with marginal resection. In conclusion, primary extra-axial chordoma is an extremely rare neoplasm with distinct morphological and immunohistochemical features. Immunomorphology and molecular analysis allow distinction from both extraskeletal myxoid chondrosarcoma and myoepithelioma. Complete surgical resection appears to be curative.

http://ift.tt/2G687rY

Monopolar Radiofrequency Ablation of Thyroid Nodules: A Prospective Austrian Single-Center Study

Thyroid, Ahead of Print.


http://ift.tt/2HRj39V

Limiting Work Shifts for Medical Trainees Affects Satisfaction, But Not Educational Outcomes

Limiting first-year medical residents to 16-hour work shifts, compared to "flexing" them to allow for some longer shifts, generally makes residents more satisfied with their training and work-life balance, but their training directors more dissatisfied with curtailed educational opportunities. That's one conclusion of a new study published online March 20 in the New England Journal of Medicine.

http://ift.tt/2HPCoZo

Complications of HIV Infection

Viral Immunology, Ahead of Print.


http://ift.tt/2DH1S8H

ANNz2: Photometric Redshift and Probability Distribution Function Estimation using Machine Learning

Sadeh, I; Abdalla, FB; Lahav, O; (2016) ANNz2: Photometric Redshift and Probability Distribution Function Estimation using Machine Learning. Publications of the Astronomical Society of the Pacific , 128 (968) 10.1088/1538-3873/128/968/104502 . Green open access

http://ift.tt/2pqBCdC

Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings

Panebianco, C; Oben, JA; Vinciguerra, M; Pazienza, V; (2016) Senescence in hepatic stellate cells as a mechanism of liver fibrosis reversal: a putative synergy between retinoic acid and PPAR-gamma signalings. Clinical and Experimental Medicine , 17 (3) pp. 269-280. 10.1007/s10238-016-0438-x . Green open access

http://ift.tt/2psUitl

Understanding the neuropsychology of aesthetic paradox: The dual phase oscillation hypothesis

Mukhopadhyay, D; (2014) Understanding the neuropsychology of aesthetic paradox: The dual phase oscillation hypothesis. Review of General Psychology , 18 (3) pp. 237-248. 10.1037/gpr0000009 . Green open access

http://ift.tt/2IAJORk

Markov Chain Monte Carlo for Exact Inference for Diffusions

Sermaidis, G; Papaspiliopoulos, O; Roberts, GO; Beskos, A; Fearnhead, P; (2013) Markov Chain Monte Carlo for Exact Inference for Diffusions. Scandinavian Journal of Statistics , 40 (2) pp. 294-321. 10.1111/j.1467-9469.2012.00812.x . Green open access

http://ift.tt/2pq4jHN

Recognising and intervening in non-alcoholic fatty liver disease

Cremonesini, L; Oben, J; Li, J; Temple, J; Nguyen, V; (2017) Recognising and intervening in non-alcoholic fatty liver disease. Independent Nurse , 2017 (2) pp. 21-25. 10.12968/indn.2017.2.21 . Green open access

http://ift.tt/2IGgrxa

Value encoding in the globus pallidus: fMRI reveals an interaction effect between reward and dopamine drive.

Fiore, VG; Nolte, T; Rigoli, F; Smittenaar, P; Gu, X; Dolan, RJ; (2018) Value encoding in the globus pallidus: fMRI reveals an interaction effect between reward and dopamine drive. Neuroimage , 173 pp. 249-257. 10.1016/j.neuroimage.2018.02.048 . Green open access

http://ift.tt/2pqCa3a

Advanced MCMC methods for sampling on diffusion pathspace

Beskos, A; Kalogeropoulos, K; Pazos, E; (2013) Advanced MCMC methods for sampling on diffusion pathspace. Stochastic Processes and their Applications , 123 (4) pp. 1415-1453. 10.1016/j.spa.2012.12.001 . Green open access

http://ift.tt/2IFgZmI

Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk?

MacLaughlin, HL; Macdougall, LC; Hall, WL; Dew, T; Mantzoukis, K; Oben, JA; (2016) Does Intragastric Balloon Treatment for Obesity in Chronic Kidney Disease Heighten Acute Kidney Injury Risk? American Journal of Nephrology , 44 (6) pp. 411-418. 10.1159/000450765 . Green open access

http://ift.tt/2psWh0B

A gravitational-wave standard siren measurement of the Hubble constant

Abbott, BP; Abbott, R; Abbott, TD; Acernese, F; Ackley, K; Adams, C; Adams, T; ... Serra-Ricart, M; + view all Abbott, BP; Abbott, R; Abbott, TD; Acernese, F; Ackley, K; Adams, C; Adams, T; Addesso, P; Adhikari, RX; Adya, VB; Affeldt, C; Afrough, M; Agarwal, B; Agathos, M; Agatsuma, K; Aggarwal, N; Aguiar, OD; Aiello, L; Ain, A; Ajith, P; Allen, B; Allen, G; Allocca, A; Altin, PA; Amato, A; Ananyeva, A; Anderson, SB; Anderson, WG; Angelova, SV; Antier, S; Appert, S; Arai, K; Araya, MC; Areeda, JS; Arnaud, N; Arun, KG; Ascenzi, S; Ashton, G; Ast, M; Aston, SM; Astone, P; Atallah, DV; Aufmuth, P; Aulbert, C; AultO'Neal, K; Austin, C; Avila-Alvarez, A; Babak, S; Bacon, P; Bader, MKM; Bae, S; Baker, PT; Baldaccini, F; Ballardin, G; Ballmer, SW; Banagiri, S; Barayoga, JC; Barclay, SE; Barish, BC; Barker, D; Barkett, K; Barone, F; Barr, B; Barsotti, L; Barsuglia, M; Barta, D; Bartlett, J; Bartos, I; Bassiri, R; Basti, N; Batch, JC; Bawaj, M; Bayley, JC; Bazzan, M; Becsy, B; Beer, C; Bejger, M; Belahcene, I; Bell, AS; Berger, BK; Bergmann, G; Bero, JJ; Berry, CPL; Bersanetti, D; Bertolini, A; Betzwieser, J; Bhagwat, S; Bhandare, R; Bilenko, IA; Billingsley, G; Billman, CR; Birch, J; Birney, R; Birnholtz, O; Biscans, S; Biscoveanu, S; Bisht, A; Bitossi, M; Biwer, C; Bizouard, A; Blackburn, JK; Blackman, J; Blair, CD; Blair, DG; Blair, RM; Bloemen, S; Bock, O; Bode, N; Boer, M; Bogaert, G; Bohe, A; Bondu, F; Bonilla, E; Bonnand, R; Boom, BA; Bork, R; Boschi, V; Bose, S; Bossie, K; Bouffanais, Y; Bozzi, A; Bradaschia, C; Brady, PR; Branchesi, M; Brau, JE; Briant, T; Brillet, A; Brinkmann, M; Brisson, V; Brockill, R; Broida, JE; Brooks, NF; Brown, DA; Brown, DD; Brunett, S; Buchanan, CC; Buikema, A; Bulik, H; Bulten, HJ; Buonanno, A; Buskulic, D; Buy, C; Byer, RL; Cabero, M; Cadonati, L; Cagnoli, G; Cahillane, C; Bustillo, JC; Callister, TA; Calloni, E; Camp, JB; Canepa, M; Canizares, P; Cannon, KC; Cao, H; Cao, J; Capano, CD; Capocasa, E; Carbognani, F; Caride, S; Carney, MF; Diaz, JC; Casentini, C; Caudill, S; Cavaglia, M; Cavalier, F; Cavalieri, R; Cella, G; Cepeda, CB; Cerda-Duran, P; Cerretani, G; Cesarini, E; Chamberlin, SJ; Chan, M; Chao, S; Charlton, P; Chase, E; Chassande-Mottin, E; Chatterjee, D; Chatziioannou, K; Cheeseboro, BD; Chen, HY; Chen, X; Chen, Y; Cheng, H-P; Chia, H; Chincarini, N; Chiummo, A; Chmiel, T; Cho, HS; Cho, M; Chow, JH; Christensen, N; Chu, Q; Chua, AJK; Chua, S; Chung, AKW; Chung, S; Ciani, G; Ciolfi, R; Cirelli, CE; Cirone, N; Clara, F; Clark, JA; Clearwater, P; Cleva, F; Cocchieri, C; Coccia, E; Cohadon, P-F; Cohen, D; Colla, A; Collette, CG; Cominsky, LR; Constancio, M; Conti, L; Cooper, SJ; Corban, P; Corbitt, TR; Cordero-Carrion, I; Corley, KR; Cornish, N; Corsi, A; Cortese, S; Costa, CA; Coughlin, MW; Coughlin, SB; Coulon, J-P; Countryman, ST; Couvares, P; Covas, PB; Cowan, EE; Coward, DM; Cowart, MJ; Coyne, DC; Coyne, R; Creighton, JDE; Creighton, TD; Cripe, J; Crowder, SG; Cullen, TJ; Cumming, A; Cunningham, L; Cuoco, E; Dal Canton, T; Dalya, G; Danilishin, SL; D'Antonio, S; Danzmann, K; Dasgupta, A; Costa, CFDS; Datrier, LEH; Dattilo, V; Dave, I; Davier, M; Davis, EJ; Daw, EJ; Day, B; De, S; DeBra, D; Degallaix, J; De laurentis, M; Deleglise, S; Del Pozzo, W; Demos, N; Denker, T; Dent, T; De Pietri, R; Dergachev, V; De Rosa, R; DeRosa, RT; De Rossi, C; DeSalvo, R; de Verona, O; Devenson, J; Dhurancihar, S; Diaz, MC; Di Fiore, L; Di Giovanni, M; Di Girolamo, T; Di Lieto, A; Di Pace, S; Di Palma, I; Di Renzo, F; Doctor, Z; Dolique, V; Donovan, F; Dooley, KL; Doravari, S; Dorrington, I; Douglas, R; Alvarez, MD; Downes, TP; Drago, M; Dreissigacker, C; Driggers, JC; Du, Z; Ducrot, M; Dupej, P; Dwyer, SE; Edo, TB; Edwards, MC; Effler, N; Eggenstein, H-B; Ehrens, P; Eichholz, J; Eikenberry, SS; Eisenstein, RA; Essick, RC; Estevez, D; Etienne, ZB; Etzel, T; Evans, M; Evans, TM; Factourovich, M; Fafone, V; Fair, H; Fairhurst, S; Fan, X; Farinon, S; Farr, B; Farr, WM; Fauchon-Jones, EJ; Favata, M; Fays, M; Fee, C; Fehrmann, H; Feicht, J; Fejer, MM; Fernandez-Galiana, A; Ferrante, I; Ferreira, EC; Ferrini, F; Fidecaro, F; Finstad, D; Fiori, I; Fiorucci, D; Fishbach, M; Fisher, RP; Fitz-Axen, M; Flaminio, R; Fletcher, M; Fong, H; Font, JA; Forsyth, PWF; Forsyth, SS; Fournier, J-D; Frasca, S; Frasconi, E; Frei, Z; Freise, A; Frey, R; Frey, V; Fries, EM; Fritschel, P; Frolov, VV; Fulda, P; Fyffe, M; Gabbard, H; Gadre, BU; Gaebel, SM; Gair, JR; Gammaitoni, L; Ganija, MR; Gaonkar, SG; Garcia-Quiros, C; Garufi, F; Gateley, B; Gaudio, S; Gaur, G; Gayathril, V; Gehrels, N; Gemme, G; Genin, E; Gennai, A; George, D; George, J; Gergely, L; Germain, V; Ghonge, S; Ghosh, A; Ghosh, A; Ghosh, S; Giaime, JA; Giardina, KD; Giazotto, A; Gill, K; Glover, L; Goetz, E; Goetz, R; Gomes, S; Goncharov, B; Gonzalez, G; Castro, JMG; Gopakumar, A; Gorodetsky, ML; Gossan, SE; Gosselin, M; Gouaty, R; Grado, A; Graef, C; Granata, M; Grant, A; Gras, S; Gray, C; Greco, G; Green, AC; Gretarsson, EM; Groot, P; Grote, H; Grunewald, S; Gruning, P; Guidi, GM; Guo, X; Gupta, A; Gupta, MK; Gushwa, KE; Gustafson, EK; Gustafson, R; Halim, O; Hall, BR; Hall, ED; Hamilton, EZ; Hammond, G; Haney, M; Hanke, MM; Hanks, J; Hanna, C; Hannam, MD; Hannuksela, OA; Hanson, J; Hardwick, I; Harms, J; Harry, GM; Harry, IW; Hart, MJ; Hester, C-J; Haughian, K; Healy, J; Heidmann, N; Heintze, MC; Heitmann, H; Hello, P; Hemming, G; Hendry, M; Heng, IS; Hennig, J; Heptonstall, AW; Heurs, M; Hild, S; Hinderer, T; Hoak, D; Hofman, D; Holt, K; Holz, DE; Hopkins, P; Horst, C; Hough, J; Houston, EA; Howell, EJ; Hreibi, A; Hu, YM; Huerta, EA; Huet, D; Hughey, B; Husa, S; Huttner, SH; Huynh-Dinh, T; Indik, N; Inta, R; Intini, G; Isa, HN; Isac, J-M; Isi, M; Iyer, BR; Izumi, K; Jacqmin, T; Jani, K; Jaranowski, P; Jawahar, S; Jimenez-Forteza, F; Johnson, WW; Jones, DI; Jones, R; Jonker, RJG; Ju, L; Junker, J; Kalaghatgi, CV; Kalogera, V; Kamai, B; Kandhasamy, S; Kang, G; Kanner, JB; Kapadia, SJ; Karki, S; Karvinen, KS; Kasprzack, M; Katolik, M; Katsavounidis, E; Katzman, W; Kaufer, S; Kawabe, K; Kefelian, E; Keitel, D; Kemball, AJ; Kennedy, R; Kent, C; Key, JS; Khalili, FY; Khan, I; Khan, S; Khan, Z; Khazanov, EA; Kijbunchoo, N; Kim, C; Kim, JC; Kim, K; Kim, W; Kim, WS; Kim, Y-M; Kimbrell, SJ; King, EJ; King, PJ; Kinley-Hanlon, M; Kirchhoff, R; Kissel, JS; Kleybolte, L; Klimenko, S; Knowles, TD; Koch, P; Koehlenbeck, SM; Koley, S; Kondrashov, V; Kontos, A; Korobko, M; Korth, WZ; Kowalska, I; Kozak, DB; Kraemer, C; Kringel, V; Krishnan, B; Krolak, A; Kuehn, G; Kumar, P; Kumar, R; Kumar, S; Kuo, L; Kutynia, A; Kwang, S; Lackey, BD; Lai, KH; Landry, M; Lang, RN; Lange, J; Lantz, B; Lanza, RK; Lartaux-Vollard, N; Lasky, PD; Laxen, M; Lazzarini, A; Lazzaro, C; Leaci, P; Leavey, S; Lee, CH; Lee, HK; Lee, HM; Lee, HW; Lee, K; Lehmann, J; Lenon, A; Leonardi, M; Leroy, N; Letendre, N; Levin, Y; Li, TGF; Linker, SD; Littenberg, TB; Liu, J; Liu, X; Lo, RKL; Lockerbie, NN; London, LT; Lord, JE; Lorenzini, M; Loriette, V; Lormand, M; Losurdo, G; Lough, JD; Lousto, CO; Lovelace, G; Lueock, H; Lumaca, D; Lundgren, AP; Lynch, R; Ma, Y; Macas, R; Macfoy, S; Machenschalk, B; Maclnnis, M; Macleod, DM; Hernandez, IM; Magana-Sandoval, F; Zertuche, LM; Magee, RM; Majorana, E; Maksimovic, I; Man, N; Mandic, V; Mangano, V; Mansell, GL; Manske, M; Mantovani, M; Marchesoni, F; Marion, F; Marka, S; Marka, Z; Markakis, C; Markosyan, AS; Markowitz, A; Maros, E; Marquina, A; Martelli, F; Martellini, L; Martin, IW; Martin, RM; Martynov, DV; Mason, K; Massera, E; Masserot, A; Massinger, TJ; Masso-Reid, M; Mastrogiovanni, S; Matas, A; Matichard, F; Matone, L; Mavalvala, N; Mazumder, N; McCarthy, R; McClelland, DE; McCormick, S; McCuller, L; McGuire, SC; McIntyre, G; McIver, J; McManus, DJ; McNeill, L; McRae, T; McWilliams, ST; Meacher, D; Meadors, GD; Mehmet, M; Meidam, J; Mejuto-Villa, E; Melatos, A; Mendell, G; Mercer, RA; Merilh, EL; Merzougui, M; Meshkov, S; Messenger, C; Messick, C; Metzdorff, R; Meyers, PM; Miao, H; Michel, C; Middleton, H; Mikhailov, EE; Milano, L; Miller, AL; Miller, BB; Miller, J; Millhouse, M; Milovich-Goff, MC; Minazzoli, O; Minenkov, Y; Ming, J; Mishra, C; Mitra, S; Mitrofanov, VR; Mitselmakher, G; Mittleman, R; Moffa, D; Moggi, N; Mogushi, K; Mohan, M; Mohapatra, SRP; Montani, M; Moore, CJ; Moraru, D; Moreno, G; Morriss, SR; Mours, B; Mow-Lowry, CM; Mueller, G; Muir, AW; Mukherjee, A; Mukherjee, D; Mukherjee, S; Mukund, N; Mullavey, A; Munch, J; Muniz, EA; Muratore, M; Murray, PG; Napier, K; Nardecchia, I; Naticchioni, L; Nayak, RK; Neilson, J; Nelemans, G; Nelson, TJN; Nery, M; Neunzert, A; Nevin, L; Newport, JM; Newton, G; Ng, KKY; Nguyen, TT; Nichols, D; Nielsen, AB; Nissanke, S; Nitz, A; Noack, A; Nocera, F; Nolting, D; North, C; Nuttall, LK; Oberling, J; O'Dea, GD; Ogin, GH; Oh, JJ; Oh, SH; Ohme, F; Okada, MA; Oliver, M; Oppermann, P; Oram, RJ; O'Reilly, B; Ormiston, R; Ortega, LF; O'Shaughnessy, R; Ossokine, S; Ottaway, DJ; Overmier, H; Owen, BJ; Pace, AE; Page, J; Page, MA; Pai, A; Pai, SA; Palamos, JR; Palashov, O; Palomba, C; Pal-Singh, A; Pan, H; Pan, H-W; Pang, B; Pang, PTH; Pankow, C; Pannarale, F; Pant, BC; Paoletti, F; Paoli, A; Papa, MA; Parida, A; Parker, W; Pascucci, D; Pasqualetti, A; Passaquieti, R; Passuello, D; Patil, M; Patricelli, B; Pearlstone, BL; Pedraza, M; Pedurand, R; Pekowsky, L; Pele, A; Penn, S; Perez, CJ; Perreca, A; Perri, LM; Pfeiffer, HP; Phelps, M; Piccinni, OJ; Pichot, M; Piergiovanni, F; Pierro, V; Pillant, G; Pinard, L; Pinto, IM; Pirello, M; Pitkin, M; Poe, M; Poggiani, R; Popolizio, P; Porter, EK; Post, A; Powell, J; Prasad, J; Pratt, JWW; Pratten, G; Predoi, V; Prestegard, T; Prijatelj, M; Principe, M; Privitera, S; Prodi, GA; Prokhorov, LG; Puncken, O; Punturo, M; Puppo, P; Puerrer, M; Qi, H; Quetschke, V; Quintero, EA; Quitzow-James, R; Raab, FJ; Rabeling, DS; Radkins, H; Raffai, P; Raja, S; Rajan, C; Rajbhandari, B; Rakhmanov, M; Ramirez, KE; Ramos-Buades, A; Rapagnani, P; Raymond, V; Razzano, M; Read, J; Regimbau, T; Rei, L; Reid, S; Reitze, DH; Ren, W; Reyes, SD; Ricci, F; Ricker, PM; Rieger, S; Riles, K; Rizzo, M; Robertson, NA; Robie, R; Robinet, F; Rocchi, A; Rolland, L; Rollins, JG; Roma, VJ; Romano, JD; Romano, R; Romel, CL; Romie, JH; Rosinska, D; Ross, MP; Rowan, S; Ruediger, A; Ruggi, P; Rutins, G; Ryan, K; Sachdev, S; Sadecki, I; Sadeghian, L; Sakellariadou, M; Salconi, L; Saleem, M; Salemi, F; Samajdar, A; Sammut, L; Sampson, LM; Sanchez, EJ; Sanchez, LE; Sanchis-Gual, N; Sandberg, V; Sanders, JR; Sassolas, B; Sathyaprakash, BS; Saulson, PR; Sauter, O; Savage, RL; Sawadsky, A; Schale, P; Scheel, M; Schauer, J; Schmidt, J; Schmidt, P; Schnabel, R; Schofield, RMS; Schoenbeck, A; Schreiber, E; Schuette, D; Schulte, BW; Schutz, BF; Schwalbe, SG; Scott, J; Scott, SM; Seidel, E; Sellers, D; Sengupta, AS; Sentenac, D; Sequino, V; Sergeev, A; Shaddock, DA; Shaffer, TJ; Shah, AA; Shahriar, MS; Shaner, MB; Shao, L; Shapiro, B; Shawhan, P; Shepard, A; Shoemaker, DH; Shoemaker, DM; Siellez, K; Siemens, X; Sieniawska, M; Sigg, D; Silva, AD; Singer, LP; Singh, A; Singhal, A; Sintes, AM; Slagmolen, BJJ; Smith, B; Smith, JR; Smith, RJE; Somala, S; Son, EJ; Sonnenberg, JN; Sorazu, B; Sorrentino, F; Souradeep, T; Spencer, AP; Srivastava, AK; Staats, K; Staley, A; Steer, D; Steinke, M; Steinlechner, J; Steinlechner, S; Steinmeyer, D; Stevenson, SP; Stone, R; Stops, DJ; Strain, KA; Stratta, G; Strigin, SE; Strunk, A; Sturani, R; Stuver, AL; Summerscales, TZ; Sun, L; Sunil, S; Suresh, J; Sutton, PJ; Swinkels, BL; Szczepanczyk, MJ; Tacca, M; Tait, SC; Talbot, C; Talukder, D; Tanner, DB; Tapai, M; Taracchini, A; Tasson, JD; Taylor, JA; Taylor, R; Tewari, SV; Theeg, T; Thies, F; Thomas, EG; Thomas, M; Thomas, P; Thorne, KA; Thrane, E; Tiwari, S; Tiwari, V; Tokmakov, KV; Toland, K; Tonelli, M; Tornasi, Z; Torres-Forne, N; Torrie, CI; Toyra, D; Travasso, F; Traylor, G; Trinastic, J; Tringali, MC; Trozzon, L; Tsang, KW; Tse, M; Tso, R; Tsukada, L; Tsuna, D; Tuyenbayev, D; Ueno, K; Ugolini, D; Unnikrishnan, CS; Urban, AL; Usman, SA; Vahlbruch, H; Vajente, G; Valdese, G; van Bakel, N; van Beuzekom, M; van den Brand, JFJ; Van den Broeck, C; Vander-Hyde, DC; van der Schaaf, L; van Heijningen, JV; van Veggel, AA; Vardaro, M; Varma, V; Vass, S; Vasuth, M; Vecchio, A; Vedovato, G; Veitch, J; Veitch, PJ; Venkateswara, K; Venugopalan, G; Verkindt, D; Vetrano, F; Vicere, A; Viets, AD; Vinciguerra, S; Vine, DJ; Vinet, J-Y; Vitale, S; Vo, T; Vocca, H; Vorvick, C; Vyatchanin, SP; Wade, AR; Wade, LE; Wade, M; Walet, R; Walker, M; Wallace, L; Walsh, S; Wang, G; Wang, H; Wang, JZ; Wang, WH; Wang, YF; Ward, RL; Warner, J; Was, M; Watchi, J; Weaver, B; Wei, L-W; Weinert, M; Weinstein, AJ; Weiss, R; Wen, L; Wessel, EK; Wessels, P; Westerweck, J; Westphal, T; Wette, K; Whelan, JT; Whitcomb, SE; Whiting, BF; Whittle, C; Wilken, D; Williams, D; Williams, RD; Williamson, AR; Willis, JL; Willke, B; Wimmer, MH; Winkler, W; Wipfl, CC; Wittel, H; Woan, G; Woehler, J; Wofford, J; Wong, KWK; Worden, J; Wright, JL; Wu, DS; Wysocki, DM; Xiao, S; Yamamoto, H; Yancey, CC; Yang, L; Yap, MJ; Yazback, M; Yu, H; Yu, H; Yvert, M; Zadrozny, A; Zanolin, M; Zelenova, T; Zendri, J-P; Zevin, M; Zhang, L; Zhang, M; Zhang, T; Zhang, Y-H; Zhao, C; Zhou, M; Zhou, Z; Zhu, SJ; Zhu, XJ; Zimmerman, AB; Zucker, ME; Zweizig, J; Foley, RJ; Coulter, DA; Drout, MR; Kasen, D; Kilpatrick, CD; Madore, BF; Murguia-Berthier, A; Pan, Y-C; Piro, AL; Prochaska, JX; Ramirez-Ruiz, E; Rest, A; Rojas-Bravo, C; Shappee, BJ; Siebert, MR; Simon, JD; Ulloas, N; Annis, J; Soares-Santos, M; Brout, D; Scolnic, D; Diehl, HT; Frieman, J; Berger, E; Alexander, KD; Allam, S; Balbinot, E; Blanchard, P; Butler, RE; Chornock, R; Cook, ER; Cowpertwaite, P; Drlica-Wagner, A; Drout, MR; Durret, F; Eftekhari, T; Finley, DA; Fong, W; Fryer, CL; Garcia-Bellido, J; Gill, MSS; Gruendl, RA; Hanna, C; Hartley, W; Herner, K; Huterer, D; Kasen, D; Kessler, R; Li, TS; Lin, H; Lopes, PAA; Lourenco, ACC; Margutti, R; Marriner, J; Marshall, JL; Matheson, T; Medina, GE; Metzger, BD; Munoz, RR; Muir, J; Nicholl, M; Nugent, P; Palmese, A; Paz-Chinchon, F; Quataert, E; Sako, M; Sauseda, M; Schlegel, DJ; Secco, LF; Smith, N; Sobreira, F; Stebbins, A; Villar, VA; Vivas, AK; Wester, W; Williams, PKG; Yanny, B; Zenteno, A; Abbott, TMC; Abdalla, FB; Bechtol, K; Benoit-Levy, A; Bertin, E; Bridle, SL; Brooks, D; Buckley-Geer, E; Burke, DL; Rosell, AC; Kind, MC; Carretero, J; Castander, FJ; Cunha, CE; D'Andrea, CB; da Costa, LN; Davis, C; DePoy, DL; Desai, S; Dietrich, JP; Estrada, J; Fernandez, E; Flaugher, B; Fosalba, P; Gaztanaga, E; Gerdes, DW; Giannantonio, T; Goldstein, DA; Gruen, D; Gutierrez, G; Hartley, WG; Honscheid, K; Jain, B; James, DJ; Jeltema, T; Johnson, MWG; Kent, S; Krause, E; Kron, R; Kuehn, K; Kuhlmann, S; Kuropatkin, N; Lahav, O; Lima, M; Maia, MAG; March, M; Miller, CJ; Miquel, R; Neilsen, E; Nord, B; Ogando, RLC; Plazas, AN; Romer, AK; Roodman, A; Rykoff, ES; Sanchez, E; Scarpine, V; Schubnell, M; Sevilla-Noarbe, I; Smith, M; Smith', RC; Suchyta, E; Tarle, G; Thomas, D; Thomas, RC; Troxel, MA; Tucker, DL; Vikram, V; Walker, AR; Weller, J; Zhang, Y; Haislip, JB; Kouprinov, VV; Reichart, DE; Tartaglia, L; Sand, DJ; Valenti, S; Yang, S; Arcavi, I; Hosseinzadeh, G; Howell, DA; McCully, C; Poznanski, D; Vasylyev, S; Tanvir, NR; Levan, NJ; Hjorth, J; Cano, Z; Copperwheat, C; de Ugarte-Postigo, A; Evans, PA; Fynbo, JPU; Gonzalez-Fernandez, C; Greiner, J; Irwin, M; Lyman, J; Mandel, I; McMahon, R; Milvang-Jensen, B; O'Brien, P; Osborne, JP; Perley, DA; Pian, E; Palazzi, E; Rol, E; Rosetti, S; Rosswog, S; Rowlinson, A; Schulze, S; Steeghs, DTH; Thone, CC; Ulaczyk, K; Watson, D; Wiersema, K; Lipunov, VM; Gorbovskoy, E; Kornilov, VG; Tyurina, N; Balanutsa, P; Vlasenko, D; Gorbunov, I; Podesta, R; Levato, H; Saffe, C; Buckley, DAH; Budnev, NM; Gress, O; Yurkov, V; Rebolo, R; Serra-Ricart, M; - view fewer (2017) A gravitational-wave standard siren measurement of the Hubble constant. Nature , 551 (7678) pp. 85-88. 10.1038/nature24471 .

http://ift.tt/2IAJHoS

Joyce and the Rhythms of the Alphabet

Baron, S; (2016) Joyce and the Rhythms of the Alphabet. In: Crowley, R and Van Hulle, D, (eds.) New Quotatoes: Joycean Exogenesis in the Digital Age. (pp. 18-44). Brill | Rodopi: Leiden/Boston.

http://ift.tt/2IDBuQF

Artist’s Essay: Post-digital Neo-Baroque: Reinterpreting Baroque Reality and Beauty in Contemporary Architectural Design

Colletti, M; (2016) Artist's Essay: Post-digital Neo-Baroque: Reinterpreting Baroque Reality and Beauty in Contemporary Architectural Design. In: Moser, W and Ndalianis, A and Krieger, P, (eds.) Neo-Baroques: From Latin America to the Hollywood Blockbuster. Edited by Walter Moser, Angela Ndalianis and Peter Krieger, Brill/Rodopi: Leiden, 2016. (pp. 307-320). Brill | Rodopi: Leiden/Boston.

http://ift.tt/2pu9179

Rates and Risk Factors for Arterial Ischemic Stroke Recurrence in Children

Stacey, A; Toolis, C; Ganesan, V; (2018) Rates and Risk Factors for Arterial Ischemic Stroke Recurrence in Children. Stroke 10.1161/STROKEAHA.117.020159 . (In press).

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MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load.

Ng, YS; Lax, NZ; Maddison, P; Alston, CL; Blakely, EL; Hepplewhite, PD; Riordan, G; ... Gorman, GS; + view all Ng, YS; Lax, NZ; Maddison, P; Alston, CL; Blakely, EL; Hepplewhite, PD; Riordan, G; Meldau, S; Chinnery, PF; Pierre, G; Chronopoulou, E; Du, A; Hughes, I; Morris, AA; Kamakari, S; Chrousos, G; Rodenburg, RJ; Saris, CGJ; Feeney, C; Hardy, SA; Sakakibara, T; Sudo, A; Okazaki, Y; Murayama, K; Mundy, H; Hanna, MG; Ohtake, A; Schaefer, AM; Champion, MP; Turnbull, DM; Taylor, RW; Pitceathly, RDS; McFarland, R; Gorman, GS; - view fewer (2018) MT-ND5 Mutation Exhibits Highly Variable Neurological Manifestations at Low Mutant Load. EBioMedicine 10.1016/j.ebiom.2018.02.010 . (In press). Green open access

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Anaemia in patients with chronic liver disease and its association with morbidity and mortality following liver transplantation.

Collas, O; Robertson, FP; Fuller, BJ; Davidson, BR; (2018) Anaemia in patients with chronic liver disease and its association with morbidity and mortality following liver transplantation. Int J Surg 10.1016/j.ijsu.2018.02.053 . (In press).

http://ift.tt/2IDB90l

Plasma DNA and Metastatic Castration-Resistant Prostate Cancer – the odyssey to a clinical biomarker test

Jayaram, A; Wetterskog, K; Attard, G; (2018) Plasma DNA and Metastatic Castration-Resistant Prostate Cancer – the odyssey to a clinical biomarker test. Cancer Discovery (In press).

http://ift.tt/2puqRa2

Inequity in out-of-pocket payments for hospitalisation in India: Evidence from the National Sample Surveys, 1995-2014

Pandey, A; Clarke, L; Dandona, L; Ploubidis, GB; (2018) Inequity in out-of-pocket payments for hospitalisation in India: Evidence from the National Sample Surveys, 1995-2014. Social Science & Medicine , 201 pp. 136-147. 10.1016/j.socscimed.2018.01.031 . Green open access

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Kinship underlies costly cooperation in Mosuo villages

Thomas, MG; Ji, T; Wu, J; He, Q; Tao, Y; Mace, R; (2018) Kinship underlies costly cooperation in Mosuo villages. Royal Society Open Science , 5 (2) p. 171535. 10.1098/rsos.171535 . Green open access

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The Aghlabids and their Neighbors: An Introduction

Anderson, G; Fenwick, C; Rosser-Owen, M; (2017) The Aghlabids and their Neighbors: An Introduction. In: Anderson, G and Fenwick, C and Rosser-Owen, M, (eds.) The Aghlabids and their Neighbors: Art and Material Culture in Ninth-Century North Africa. (pp. 1-30). Brill: Leiden/Boston.

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Contributory factors in surgical incidents as delineated by a confidential reporting system

Mushtaq, F; O'Driscoll, C; Smith, F; Wilkins, D; Kapur, N; Lawton, R; (2018) Contributory factors in surgical incidents as delineated by a confidential reporting system. Annals of The Royal College of Surgeons of England 10.1308/rcsann.2018.0025 . (In press).

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MyD88 and TLR4 Expression in Epithelial Ovarian Cancer

Block, MS; Vierkant, RA; Rambau, PF; Winham, SJ; Wagner, P; Traficante, N; Tołoczko, A; ... Goode, EL; + view all Block, MS; Vierkant, RA; Rambau, PF; Winham, SJ; Wagner, P; Traficante, N; Tołoczko, A; Tiezzi, DG; Taran, FA; Sinn, P; Sieh, W; Sharma, R; Rothstein, JH; Ramón Y Cajal, T; Paz-Ares, L; Oszurek, O; Orsulic, S; Ness, RB; Nelson, G; Modugno, F; Menkiszak, J; McGuire, V; McCauley, BM; Mack, M; Lubiński, J; Longacre, TA; Li, Z; Lester, J; Kennedy, CJ; Kalli, KR; Jung, AY; Johnatty, SE; Jimenez-Linan, M; Jensen, A; Intermaggio, MP; Hung, J; Herpel, E; Hernandez, BY; Hartkopf, AD; Harnett, PR; Ghatage, P; García-Bueno, JM; Gao, B; Fereday, S; Eilber, U; Edwards, RP; de Sousa, CB; de Andrade, JM; Chudecka-Głaz, A; Chenevix-Trench, G; Cazorla, A; Brucker, SY; Australian Ovarian Cancer Study Group, .; Alsop, J; Whittemore, AS; Steed, H; Staebler, A; Moysich, KB; Menon, U; Koziak, JM; Kommoss, S; Kjaer, SK; Kelemen, LE; Karlan, BY; Huntsman, DG; Høgdall, E; Gronwald, J; Goodman, MT; Gilks, B; García, MJ; Fasching, PA; de Fazio, A; Deen, S; Chang-Claude, J; Candido Dos Reis, FJ; Campbell, IG; Brenton, JD; Bowtell, DD; Benítez, J; Pharoah, PDP; Köbel, M; Ramus, SJ; Goode, EL; - view fewer (2018) MyD88 and TLR4 Expression in Epithelial Ovarian Cancer. Mayo Clinic Proceedings , 93 (3) pp. 307-320. 10.1016/j.mayocp.2017.10.023 . Green open access

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Relationship between severity of periodontitis and masseter muscle activity during waking and sleeping hours

Publication date: June 2018
Source:Archives of Oral Biology, Volume 90
Author(s): Seiya Kato, Daisuke Ekuni, Shigehisa Kawakami, Acing Habibie Mude, Manabu Morita, Shogo Minagi
ObjectiveThis study was conducted to investigate whether the masseter muscle activity shows any specific pattern in relation to the severity of periodontitis.DesignSixteen subjects with no or mild periodontitis (NMP group) and 15 subjects with moderate or severe periodontitis (MSP group) were enrolled. Plasma IgG antibody titer was examined using Porphyromonas gingivalis as a bacterial antigen. Surface electromyography (EMG) of the masseter muscles was continuously recorded using an ambulatory surface EMG recording device while patients were awake and asleep. Masseter muscle activity was analyzed using intensities of 5%–10% maximal voluntary clenching (MVC), 10%–20% MVC, and >20% MVC. Furthermore, EMG levels of 20% MVC were adopted as the threshold for analysis of phasic, tonic, and mixed EMG activities. The cumulative duration of masseter muscle activity and bruxism episodes was calculated as duration per hour.ResultsThere was no significant difference in plasma IgG antibody titers against P. gingivalis between the NMP and MSP groups (p = 0.423). During waking hours, the duration of masseter muscle activity with an intensity of >20% MVC was significantly longer in the MSP group than in the NMP group (p = 0.037). During sleeping hours, the duration of masseter muscle activity at all MVC intensities was significantly longer in the MSP group than in the NMP group (all p < 0.05). Additionally, the duration of phasic and mixed episodes was significantly longer in the MSP group than those in the NMP group while both awake and asleep (all p < 0.05).ConclusionsThe results of this study suggested that masseter muscle activity might be related to the severity of periodontitis.



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The role of bone morphogenetic proteins 2 and 4 in mouse dentinogenesis

Publication date: June 2018
Source:Archives of Oral Biology, Volume 90
Author(s): Priyam Jani, Chao Liu, Hua Zhang, Khaled Younes, M. Douglas Benson, Chunlin Qin
ObjectiveThe bone morphogenetic proteins (BMPs) play crucial roles in tooth development. However, several BMPs retain expression in the dentin of the fully patterned and differentiated tooth. We hypothesized that BMP signaling therefore plays a role in the function of the differentiated odontoblast, the job of which is to lay down and mineralize the dentin matrix.DesignWe generated mice deficient in Bmp2 and 4 using a dentin matrix protein 1 (Dmp1) promoter-driven cre recombinase that was expressed in differentiated odontoblasts.ResultsThe first and second molars of these Bmp2 and Bmp4 double conditional knockout (DcKO) mice displayed reduced dentin and enlarged pulp chambers compared to cre-negative littermate controls. DcKO mouse dentin in first molars was characterized by small, disorganized dentinal fibers, a wider predentin layer, and reduced expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), and bone sialoprotein (BSP). DcKO mouse odontoblasts demonstrated increased type I collagen mRNA production, indicating that the loss of BMP signaling altered the rate of collagen gene expression in these cells. Bmp2 and Bmp4 single Dmp1-cre knockout mice displayed no discernable dentin phenotype.ConclusionsThese data demonstrate that BMP signaling in differentiated odontoblasts is necessary for proper dentin production in mature teeth.



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Intramural duodenal haematoma caused by pancreatic fistula due to exacerbation of chronic pancreatitis

Description

Intramural duodenal haematoma (IDH) is a rare condition forming haematoma within the wall of the duodenum, which was first reported in 1838 by MacLauchlan.1 IDH derived from acute or chronic pancreatitis is rarely described, the mechanism remaining unknown. A 65-year-old man with history of heavy drinking and chronic hepatitis was admitted to our hospital with sudden vomiting and right-lateral abdominal pain. Abdominal pain and vomiting continued after admission, so a nasogastric tube was inserted. Contrast-enhanced CT scans of the abdomen found a 60x80 mm heterogeneous mass with intraluminal leakage of contrast agent-like bleeding along the second portion of the duodenum, diffuse expansion of the pancreatic duct with pancreatic stone and ascites on the surface of the liver (figure 1). We first considered whether the mass might be duodenal gastrointestinal stromal tumour with internal bleeding according to symptoms and enhanced CT image. However, gastrointestinal endoscopy...

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Giant coronary artery aneurysm at autopsy

This case presents a woman in her early 20s who died after the sudden onset of chest pain. Five years earlier, she was investigated for a cardiac murmur during pregnancy and an echocardiogram revealed a 6.0x3.0 cm blood-filled sac compressing the left atrium and anterolateral aspect of the left ventricle with communication to the aortic root. She later had a CT scan of the chest with contrast, which showed aneurysmal dilatation of the left main coronary artery. She was placed on aspirin but defaulted from clinic 11 months post partum. At autopsy, a left coronary aneurysmal sac measuring 10.0x9.0 cm. was identified with a rupture measuring 7.0 cm in length and the pericardial sac contained 900 mL of blood with clots. The cause of death was cardiac tamponade secondary to rupture of the coronary artery aneurysm.

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Spontaneous periorbital ecchymosis: a rare presentation of acute lymphoblastic leukaemia

Description

A 45-year-old woman presented with spontaneous discolouration around the left eye for 1 week. She also gave a history of easy fatigability for 1 month. There was no history of any preceding injury in the head and neck area. She denied any headache, vomiting or visual disturbances. Examination showed hepatosplenomegaly and ecchymosis around the left eye (raccoon eye), along with subconjunctival haemorrhage (figure 1A). Her fundus examination was unremarkable. Her haemoglobin was 138 g/L, white blood cell count was 51x10⁹/L and platelet was 19x10⁹/L. Her peripheral blood smear had 24% blast with CD34, CD10 and CD19 positivity on flow cytometry, confirming a diagnosis of acute lymphoblastic leukaemia. A biopsy from the periorbital area could not be done due to denial of consent from the patient. She was managed with chemotherapy and transfusion support. She showed gradual improvement in periorbital ecchymosis and took 2 weeks to resolve (figure 1B).

Figure 1

Clinical...

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Giant bezoar: young Rapunzel

Description

Surgeons and radiologists encounter a challenge regarding the type of diagnostic imaging techniques to use when faced with a possible small bowel obstruction (SBO). However, with a sensitivity of 82%–100% for high-grade and complete SBOs, multidetector CT is the preferred imaging method.1 2

A high-grade obstruction can be identified by the degree of distal collapse, proximal bowel dilation and small bowel faeces sign.2 3

The transition point is defined by a calibre change between the dilated proximal and collapsed distal small bowel loops.1 2

Bezoars are an unusual cause of acute abdomen due to SBO (1–2), causing a mostly complete mechanical obstruction. Bezoars are commonly located in the jejunum or in the proximal ileum.1–3

Our images demonstrate the importance of CT for bezoar identification (figures 1 and...

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Intertrigo of streptococcal aetiology: a different kind of diaper dermatitis

Description

A 3-month-old infant presented with a 3-day history of an intertriginous eruption. His previous history was irrelevant and his last vaccination was at 2 months old according to the Portuguese immunisation schedule.

No other family members were affected and the child was otherwise well. Physical examination revealed an exuberant area of erythema and maceration of the inguinal folds and genitals (figures 1 and 2). This rash was bright red in colour and had well-defined borders. No satellite lesions were present.

Figure 1

Intertriginous eruption on the third day after initial appearance.

Figure 2

Intertriginous eruption on the third day after initial appearance.

Bacterial culture of the affected region was obtained by a skin swab, and empirical treatment with oral flucloxacillin was started, admitting probable bacterial aetiology. The culture yielded a growth...

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Extracorporeal membrane oxygenation (ECMO) for near-fatal asthma refractory to conventional ventilation

We describe a case of near-fatal asthma, treated successfully by initiation of extracorporeal membrane oxygenation (ECMO). A 29-year-old woman, known asthmatic on steroid inhalers, inhaled/nebulised bronchodilators, long-term oral prednisolone, theophylline and montelukast, presented with acute shortness of breath. She deteriorated following initial treatment with nebulised bronchodilators and magnesium sulfate requiring intubation and mechanical ventilation. Severe bronchospasm ensued following mechanical ventilation and peak airway pressures remained at 55 cm H₂O with intrinsic positive end expiratory pressure(PEEP) of 14 cm H₂O. Despite treatment with sedation, paralysis, intravenous salbutamol and inhaled sevoflurane, her condition deteriorated. She was commenced on mobile ECMO by the retrieval team. While on ECMO, her CO₂ normalised within 48 hours. She was extubated within 72 hours of initiating ECMO and was discharged to the ward next day. We reiterate that ECMO should be considered sooner for status asthmatics not responding to maximal pharmacological therapy and ventilatory support to prevent ongoing lung injury and mortality.

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Combined ACL reconstruction and Segond fracture fixation fails to abolish anterolateral rotatory instability

The Segond fracture (SF) is considered pathognomonic of an anterior cruciate ligament (ACL) tear. However, the anatomy of the soft-tissue attachments responsible for the avulsion of SFs has been a cause of controversy. A 31-year-old male patient presented with an injury to his right knee that resulted in ACL tear and a SF. Open SF fixation and arthroscopic ACL reconstruction were performed. The anatomical dissection demonstrated that the avulsion of SFs had occurred because of the tibial attachment of the anterolateral ligament (ALL) with an intact Iliotibial band. At 1-year postoperative follow-up, the ACL graft had restored anterior tibial translation to within normal limits. However, residual rotational knee laxity was observed. This finding highlights that patients with SF may be at increased risk of persistent instability after ACL reconstruction. Consideration should be given to recession of the fixation or augmentation of the ALL when dealing with this injury pattern.

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Pyeloduodenal fistula diagnosed with technetium-99m scintigraphy and managed with a conservative strategy

We present a case of pyeloduodenal fistula in an 89-year-old woman with history of nephrolithiasis and recurrent urinary tract infection (UTI) who presented to the emergency department with back pain. CT revealed a malrotated right kidney with a large renal stone and possible fistulous connection between the second portion of the duodenum and the right renal collecting system. Technetium-99m scintigraphy confirmed presence of the fistula. The patient declined intervention and was discharged from the hospital with oral antibiotic suppressive therapy. The patient remained clinically stable at time of follow-up 3 months later. Spontaneous pyeloduodenal fistula is an aetiology of recurrent upper or lower UTIs or persistent bacteriuria though uncommonly recognised. Diagnosis may be achieved using several modalities, including technetium-99m scintigraphy. Nephrectomy and primary fistula closure has traditionally been the treatment of choice for this condition; however, conservative management is an option for patients with intact renal function.

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Prostate cancer with an unusual metastatic affinity for the appendix, inducing acute appendicitis

Acute appendicitis induced by metastatic disease is uncommon. We present the case of an 82-year-old man with known bony metastases secondary to prostatic cancer who presents with a short history of acute abdominal pain. A CT scan was indicative of acute appendicitis and the patient underwent a laparoscopic appendicectomy; a phlegmonous mass seen intraoperatively was suspicious for malignancy, and histopathology confirmed acute appendicitis as well as metastases of prostate cancer. Metastatic disease should be considered as an important differential in all patients with a known history of malignancy, as this may in turn complicate their presenting surgical complaint.

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Sinus pericranii: long-term outcome in a 10-year-old boy with a review of literature

Sinus pericranii is a rare cranial venous anomaly in which there is an abnormal communication between intracranial dural sinuses and extracranial venous structures, usually via an emissary transosseous vein. We report the case of a 10-year-old boy who was successfully managed conservatively. The clinical findings, investigations and management are discussed. We focus on the long-term management of these patients, with a review of the relevant literature.

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Common variable immunodeficiency presenting in a man with recurrent pneumonia caused by Staphylococcus lugdunensis

Common variable immunodeficiency (CVID) refers to a group of disorders where differentiation and maturation of B cells into plasma cells are affected, leading to decreased or defective immunoglobulin production and subsequent immunodeficiency. Symptoms may present at any age between 5 and 72 years, although more severe forms often manifest earlier in life. Milder forms may not be detected. We present an intriguing case of a 69-year-old man presenting with recurrent pneumonia caused by a rare organism Staphylococcus lugdunensis, eventually determined to be caused by CVID. The patient had a good clinical outcome after receiving immunoglobulin replacement therapy.

http://ift.tt/2GKpOv3

Pyomyositis and osteomyelitis: an unusual cause of abdominal pain

Description

A previously healthy 12-year-old boy was referred with a 2-day history of fever and abdominal pain in the right lower quadrant. He had no traumatic episodes. A physical examination indicated tenderness of the right lower quadrant without rebound tenderness and muscular defence. His gait was normal. His white blood cell count was 4.6x10⁹/L and his C reactive protein (CRP) value was 5.9 mg/dL. The findings of abdominal ultrasound examination and enhanced CT were normal and ruled out appendicitis. Mesenteric lymphadenitis was initially diagnosed and empirical therapy with intravenous cefmetazole 100 mg/kg/day was started. On day 3 after admission, his fever abated. However, his blood culture was positive for methicillin-susceptible Staphylococcus aureus (MSSA), and his abdominal pain persisted. Contrast-enhanced MRI revealed hyperintense signals on T2-weighted images in the right internal abdominal oblique muscles (figure 1A) and in the right proximal femur (figure 1B). Inflammation did not involve the...

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A large pseudoaneurysm of the superficial femoral artery in a patient with SLE with Salmonella group D infection

Pseudoaneurysm in Salmonella infection is a rare complication of lupus. We describe a 51-year-old woman with lupus who suffered from swelling and painful sensation of right lower limbs. The Doppler ultrasound study revealed a large pseudoaneurysm of right superficial femoral artery and the tissue culture was Salmonella group D. Surgical repair with stent grafting was performed successfully. This vascular complication with Salmonella infection has not been previously described in lupus.

http://ift.tt/2FNzWG6

Acute Exudative Polymorphous Vitelliform Maculopathy Syndrome; natural history and evolution of fundal and OCT images over time

A 33-year-old man presented with a 10-day history of bilateral blurred vision on a background of a prodromal influenza-like illness. Ocular Coherence Tomography (OCT) and fundal examination coincided with a diagnosis of atypical central serous retinopathy. The patient's symptoms worsened during follow-up, and he was started on steroids. Subsequent fundal examination revealed yellow deposits in a honeycomb pattern and hard exudates in the perimacular region. Serial OCTs revealed progression of bilateral macular intraretinal and subretinal fluid. He was subsequently admitted to hospital for a full paraneoplastic workup. Liaison with our colleagues in other specialist retinal centres led us to a diagnosis of acute exudative polymorphous vitelliform maculopathy syndrome. We subsequently took fundal images to monitor disease progression and to monitor changes seen with autofluorescence in this rare disease entity.

http://ift.tt/2u7jnzw

Cold Snare Polypectomy for Duodenal Adenomas in Familial Adenomatous Polyposis

Condition:   Familial Adenomatous Polyposis
Intervention:  
Sponsor:   Western Sydney Local Health District
Recruiting

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Short-term LXR activation improves epidermal barrier features in mild-to-moderate atopic dermatitis: a randomized controlled trial

Publication date: Available online 19 March 2018
Source:Annals of Allergy, Asthma & Immunology
Author(s): Tali Czarnowicki, Anders B. Dohlman, Kunal Malik, Diane Antonini, Robert Bissonnette, Tom C. Chan, Lisa Zhou, Huei-Chi Wen, Yeriel Estrada, Hui Xu, Catherine Bryson, Jie Shen, Deepak Lala, Avi Ma'ayan, Gerard McGeehan, Richard Gregg, Emma Guttman-Yassky




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Neuroendocrine Carcinomas of the Larynx and Head and Neck: Challenges in Classification and Grading

Abstract

Primary neuroendocrine carcinomas (NECs) of the larynx and head and neck are an uncommon and heterogeneous group of neoplasms categorized by the 2017 WHO Classification of Head and Neck Tumors as: (a) well-differentiated (WD-NEC), (b) moderately-differentiated (MD-NEC), and (c) poorly-differentiated (PD-NEC) with small cell and large cell types. The classification incorporates elements of differentiation and grading and closely correlates to the 5-year disease specific survival of 100, 52.8, 19.3 and 15.3% for each diagnostic category. These survival rates are based on historical data limited by the previous lack of standard pathologic diagnostic criteria. The classification has de-emphasized the use of the terms "carcinoid" and "atypical carcinoid" as diagnostic categories. The adoption of uniform pathologic criteria for the classification of NECs of the head and neck should enable the design of high quality studies in order to understand the molecular alterations of these neoplasms.

http://ift.tt/2ID6jFt

Intramuscular (Infiltrating) Lipoma of the Floor of the Mouth

Lipoma is a very common soft tissue neoplasm, but only infrequently found in the oral region. Intramuscular lipoma (IML) is a relatively common variant of lipoma. The most common site for IML is the large muscles of the extremities, and it is quite rare in the oral cavity. A case of IML affecting the floor of the mouth/tongue of a 42-year-old female is described. The patient presented with a 4 cm diameter yellow mass in the right side of the sublingual area. Axial and coronal magnetic resonance imaging demonstrated its infiltrating nature that can be distinguished from the ordinary well-encapsulated lesion. The lesion was excised with adequate surgical margins. Histopathologically, the lesion was composed of mature adipose tissue that infiltrated the muscle in a diffuse manner. No lipoblasts, atypical cells, or high mitotic index were found. There was no evidence of recurrence two years postoperatively. Review of the literature yielded that IML occurring in the sublingual region is extremely rare.

http://ift.tt/2u8YB2A

The role of curriculum based measures in assessing writing products

Dockrell, J; Connelly, V; Walter, K; Critten, S; (2017) The role of curriculum based measures in assessing writing products. In: Miller, B and McCardle, P and Connelly, V, (eds.) Writing development in struggling learners: Understanding the needs of writers across the lifecourse. (pp. 182-200). Brill: Leiden/Boston.

http://ift.tt/2FMIzAB

Postoperative Complications Associated with External Skeletal Fixators in Dogs

Beever, LJ; Giles, K; Meeson, RL; (2018) Postoperative Complications Associated with External Skeletal Fixators in Dogs. VCOT - Veterinary and Comparative Orthopaedics and Traumatology , 31 (2) pp. 137-143. 10.1055/s-0038-1627477 .

http://ift.tt/2FWI3w6

Gender-specific changes in well-being in older people with coronary heart disease: evidence from the English Longitudinal Study of Ageing

Zaninotto, P; Sacker, A; Breeze, E; McMunn, A; Steptoe, A; (2016) Gender-specific changes in well-being in older people with coronary heart disease: evidence from the English Longitudinal Study of Ageing. Aging & Mental Health , 20 (4) pp. 432-440. 10.1080/13607863.2015.1020410 . Green open access

http://ift.tt/2FOKdC3

Towards a framework to evaluate the ‘total’ performance of buildings

Taylor, J; Liu, Y; Lin, B; Burman, E; Hong, SM; Yu, J; Wang, Z; ... Davies, M; + view all Taylor, J; Liu, Y; Lin, B; Burman, E; Hong, SM; Yu, J; Wang, Z; Mumovic, D; Shrubsole, C; Vermeer, D; Davies, M; - view fewer (2018) Towards a framework to evaluate the 'total' performance of buildings. Building Services Engineering Research and Technology 10.1177/0143624418762662 . (In press). Green open access

http://ift.tt/2HQD40x

The Subversive Humphry Davy: Aristocracy and Establishing Chemical Research Laboratories in Late Eighteenth- and Early Nineteenth-Century England

James, F; (2017) The Subversive Humphry Davy: Aristocracy and Establishing Chemical Research Laboratories in Late Eighteenth- and Early Nineteenth-Century England. In: Roberts, L and Werrett, S, (eds.) Compound Histories: Materials, Governance and Production, 1760-1840. (pp. 269-288). Brill: Leiden/Boston. Green open access

http://ift.tt/2Gau9d0

Prostitution in Moscow and St. Petersburg, Russia

Hetherington, PL; (2017) Prostitution in Moscow and St. Petersburg, Russia. In: Rodríguez García, M and van Nederveen Meerkerk, E and Heerma van Voss, L, (eds.) Selling Sex in the City: A Global History of Prostitution, 1600s-2000s. (pp. 138-170). Brill: Leiden/Boston.

http://ift.tt/2HQkK7H

Estimation of thermophysical properties from in-situ measurements in all seasons: quantifying and reducing errors using dynamic grey-box methods

Gori, V; Elwell, C; (2018) Estimation of thermophysical properties from in-situ measurements in all seasons: quantifying and reducing errors using dynamic grey-box methods. Energy and Buildings , 167 pp. 290-300. 10.1016/j.enbuild.2018.02.048 . (In press). Green open access

http://ift.tt/2Gb9aqG

Mean-field and quantum-fluctuation dynamics in the driven dispersive Jaynes-Cummings model

Mavrogordatos, T; Szafulski, P; Ginossar, E; Szymanska, MH; (2016) Mean-field and quantum-fluctuation dynamics in the driven dispersive Jaynes-Cummings model. In: Mullerova, J and Senderakova, D and Ladanyi, L and Scholtz, L, (eds.) (Proceedings) 20th Slovak-Czech-Polish Optical Conference on Wave and Quantum Aspects of Contemporary Optics (SCPOC), Jasna, Slovakia. SPIE - The International Society for Optical Engineering Green open access

http://ift.tt/2HL9NV1

Christ’s Suppurating Wounds: Leprosy in the Vita of Alice of Schaerbeek (d. 1250)

Spencer-Hall, A; (2015) Christ's Suppurating Wounds: Leprosy in the Vita of Alice of Schaerbeek (d. 1250). In: DeVries, K, (ed.) Wounds and Wound Repair in Medieval Culture. (pp. 389-416). Brill: Leiden/Boston.

http://ift.tt/2G9lCqQ

Tension pneumoperitoneum after surgery for endometrial cancer and hernia in a morbidly obese female: a case report

Obesity is a risk factor for the development of endometrial cancer and abdominal wall hernias. We report a case of tension pneumoperitoneum that developed after gynecological surgery and mesh repair of a ventr...

http://ift.tt/2IDHNnw

When tyrosine kinase inhibitor sunitinib can be discontinued in metastatic renal cell carcinoma to pancreas: a case report

Long-term survival with durable response remains possible in the area of targeted therapies. Discontinuation of sunitinib could improve quality of life and reduce treatment costs in metastatic renal cell carci...

http://ift.tt/2ppx1II

Neuroendocrine Carcinomas of the Larynx and Head and Neck: Challenges in Classification and Grading

Abstract

Primary neuroendocrine carcinomas (NECs) of the larynx and head and neck are an uncommon and heterogeneous group of neoplasms categorized by the 2017 WHO Classification of Head and Neck Tumors as: (a) well-differentiated (WD-NEC), (b) moderately-differentiated (MD-NEC), and (c) poorly-differentiated (PD-NEC) with small cell and large cell types. The classification incorporates elements of differentiation and grading and closely correlates to the 5-year disease specific survival of 100, 52.8, 19.3 and 15.3% for each diagnostic category. These survival rates are based on historical data limited by the previous lack of standard pathologic diagnostic criteria. The classification has de-emphasized the use of the terms "carcinoid" and "atypical carcinoid" as diagnostic categories. The adoption of uniform pathologic criteria for the classification of NECs of the head and neck should enable the design of high quality studies in order to understand the molecular alterations of these neoplasms.

http://ift.tt/2ID6jFt

Intraoperative red blood cell transfusion, delayed graft function, and infection after kidney transplant: an observational cohort study

Abstract

Background

Kidney transplant patients are frequently anemic and at risk for red blood cell (RBC) transfusion. Previous studies suggest that pre-transplant RBC transfusion may improve kidney transplant outcomes; however, RBC transfusion is also associated with infection. The purpose of our study was to characterize the relationships between intraoperative RBC transfusion, delayed graft function (DGF), postoperative surgical site infection (SSI), and sepsis.

Methods

Analysis was performed on a historical cohort of adult kidney transplant patients from a single medical center during a two-year period. Crude odds ratios for DGF, superficial and deep SSI, and sepsis were calculated for transfused patients and multivariate regression was used to control for potential confounders when significant relationships were identified.

Results

Four hundred forty-one patients had kidney transplant during the study period; 27.0% had RBC transfusion, 38.8% had DGF, 7.0% had superficial SSI, 7.9% had deep SSI, and 1.8% had sepsis. High dose RBC transfusion was associated with improved graft function, but this was negated after adjusting for confounders (OR = 0.86, 95% CI  0.26 to 2.88). There was no association between RBC transfusion and SSI. RBC transfusion was independently associated with sepsis (OR = 8.98, 95% CI  1.52 to 53.22), but the confidence interval was wide.

Conclusions

Intraoperative RBC transfusion during kidney transplant is not associated with improved allograft function or incisional SSI, but is associated with postoperative sepsis. RBCs should not be liberally transfused during kidney transplant surgery to improve graft outcomes.

http://ift.tt/2FORRvY

Acute Mastoiditis Complicated with Concomitant Bezold’s Abscess and Lateral Sinus Thrombosis

Bezold's abscess is a very rare extracranial complication of acute mastoiditis. Lateral sinus thrombosis is another intracranial complication of acute mastoiditis that can occur, but there are only few reports of concomitant ispilateral Bezold's abscess and lateral sinus thrombosis with favorable outcome. We diagnosed and treated successfully a 14-year-old girl suffering from Streptococcus pneumoniae acute mastoiditis complicated with Bezold's abscess and lateral sinus thrombosis. Surgical treatment included myringotomy, cortical mastoidectomy, and Bezold's abscess incision and drainage. During the course of treatment, we concluded that lateral sinus thrombosis was not caused from mastoiditis by direct spread but from pressure on internal jugular vein caused from Bezold's abscess.

http://ift.tt/2DGubUA

Neuroendocrine Carcinomas of the Larynx and Head and Neck: Challenges in Classification and Grading

Abstract

Primary neuroendocrine carcinomas (NECs) of the larynx and head and neck are an uncommon and heterogeneous group of neoplasms categorized by the 2017 WHO Classification of Head and Neck Tumors as: (a) well-differentiated (WD-NEC), (b) moderately-differentiated (MD-NEC), and (c) poorly-differentiated (PD-NEC) with small cell and large cell types. The classification incorporates elements of differentiation and grading and closely correlates to the 5-year disease specific survival of 100, 52.8, 19.3 and 15.3% for each diagnostic category. These survival rates are based on historical data limited by the previous lack of standard pathologic diagnostic criteria. The classification has de-emphasized the use of the terms "carcinoid" and "atypical carcinoid" as diagnostic categories. The adoption of uniform pathologic criteria for the classification of NECs of the head and neck should enable the design of high quality studies in order to understand the molecular alterations of these neoplasms.

http://ift.tt/2ID6jFt

Auditory steady-state response in cochlear implant patients

Publication date: Available online 19 March 2018
Source:Acta Otorrinolaringológica Española
Author(s): Alejandro Torres-Fortuny, Isabel Arnaiz-Marquez, Heivet Hernández-Pérez, Eduardo Eimil-Suárez
Introduction and objectiveAuditory steady state responses to continuous amplitude modulated tones at rates between 70 and 110Hz, have been proposed as a feasible alternative to objective frequency specific audiometry in cochlear implant subjects. The aim of the present study is to obtain physiological thresholds by means of auditory steady-state response in cochlear implant patients (Clarion HiRes 90K), with acoustic stimulation, on free field conditions and to verify its biological origin.Methods11 subjects comprised the sample. Four amplitude modulated tones of 500, 1000, 2000 and 4000Hz were used as stimuli, using the multiple frequency technique. The recording of auditory steady-state response was also recorded at 0dB HL of intensity, non-specific stimulus and using a masking technique.ResultsThe study enabled the electrophysiological thresholds to be obtained for each subject of the explored sample. There were no auditory steady-state responses at either 0dB or non-specific stimulus recordings. It was possible to obtain the masking thresholds. A difference was identified between behavioral and electrophysiological thresholds of −6±16, −2±13, 0±22 and −8±18dB at frequencies of 500, 1000, 2000 and 4000Hz respectively.ConclusionsThe auditory steady state response seems to be a suitable technique to evaluate the hearing threshold in cochlear implant subjects.



http://ift.tt/2ppTjei

Do Glutathione S-Transferase Genes Modify the Link between Indoor Air Pollution and Asthma, Allergies, and Lung Function? A Systematic Review

Abstract

Purpose of Review

Glutathione S-transferase (GST) genes are involved in oxidative stress management and may modify the impact of indoor air pollution. We aimed to assess the influence of GST genes on the relationship between indoor air pollution and allergy/lung function.

Recent Findings

Our systematic review identified 22 eligible studies, with 15 supporting a gene-environment interaction. Carriers of GSTM1/T1 null and GSTP1 val genotypes were more susceptible to indoor air pollution exposures, having a higher risk of asthma and lung function deficits. However, findings differed in terms of risk alleles and specific exposures. High-exposure heterogeneity precluded meta-analysis.

Summary

We found evidence that respiratory effects of indoor air pollution depend on the individual's GST profile. This may help explain the inconsistent associations found when gene-environment interactions are not considered. Future studies should aim to improve the accuracy of pollution assessment and investigate this finding in different populations.

http://ift.tt/2DHbuAb

HMGB1 regulates T helper 2 and T helper17 cell differentiation both directly and indirectly in asthmatic mice

Publication date: May 2018
Source:Molecular Immunology, Volume 97
Author(s): Ruiting Li, Jing Wang, Fangfang Zhu, Ruifang Li, Bing Liu, Wenjuan Xu, Guangzhen He, Huan Cao, Yimin Wang, Jiong Yang
The Th (T helper) 2 response is characteristic of allergic asthma, and Th17 cells are involved in more severe asthma. Recent studies demonstrated that HMGB1 (High mobility group box 1 protein) regulates airway inflammation and the Th2, Th17 inflammatory response in asthma. HMGB1 can interact with Toll-like receptors (TLR) 2 and 4, and the receptor for advanced glycation end products (RAGE), activating the NF-κB (nuclear factor kappa B) signaling pathway and inducing the release of downstream inflammatory mediators. Both Th cells and dendritic cells express TLR2, TLR4, and RAGE receptors. Therefore, we speculate that HMGB1 could regulate the differentiation of Th2, Th17 cells in asthma through direct and indirect mechanisms. An ovalbumin (OVA)-induced mouse asthmatic model was established. Anti-HMGB1 antibody or rHMGB1 was administered to OVA-sensitized mice 30 min prior to each challenge. For in vitro studies, magnetically separated CD4⁺ naive T cells were stimulated with or without rHMGB1 and/or anti-HMGB1 antibody. BMDCs (bone marrow-derived dendritic cells)-stimulated with or without rHMGB1 and/or anti-HMGB1 antibody were cocultured with CD4⁺ naive T cells. Our study showed that administration of rHMGB1 aggravated airway inflammation and mucus production, and induced Th2, Th17 polarization in asthmatic mice, and that anti-HMGB1 antibody weakened characteristic features of asthma and blocked the Th2, Th17 inflammatory responses. HMGB1 could directly act on naive T cells to induce differentiation of Th2, Th17 cells in vitro through activating the TLR2, TLR4, RAGE-NF-κB signal pathway in CD4⁺ naive T cells. HMGB1 could also indirectly promote Th2, Th17 differentiation via activating the TLR2, TLR4, RAGE-NF-κB signal pathway in DCs to mediate their maturation and antigen-presenting ability in vitro.



http://ift.tt/2GKmgsO

In silico design of Mycobacterium tuberculosis epitope ensemble vaccines

Publication date: May 2018
Source:Molecular Immunology, Volume 97
Author(s): Preksha Shah, Jaymisha Mistry, Pedro A. Reche, Derek Gatherer, Darren R. Flower
Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa. Our approach selects an optimal set of highly conserved, experimentally validated epitopes, with high projected population coverage (PPC). Through rigorous data analysis, five different potential vaccine combinations were selected each with PPC above 80% for East Africa and above 90% for the World. Two potential vaccines only contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes. Our prime vaccine candidate was a putative seven-epitope ensemble comprising: SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL, QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC.



http://ift.tt/2u3lQuT

Do Glutathione S-Transferase Genes Modify the Link between Indoor Air Pollution and Asthma, Allergies, and Lung Function? A Systematic Review

Abstract

Purpose of Review

Glutathione S-transferase (GST) genes are involved in oxidative stress management and may modify the impact of indoor air pollution. We aimed to assess the influence of GST genes on the relationship between indoor air pollution and allergy/lung function.

Recent Findings

Our systematic review identified 22 eligible studies, with 15 supporting a gene-environment interaction. Carriers of GSTM1/T1 null and GSTP1 val genotypes were more susceptible to indoor air pollution exposures, having a higher risk of asthma and lung function deficits. However, findings differed in terms of risk alleles and specific exposures. High-exposure heterogeneity precluded meta-analysis.

Summary

We found evidence that respiratory effects of indoor air pollution depend on the individual's GST profile. This may help explain the inconsistent associations found when gene-environment interactions are not considered. Future studies should aim to improve the accuracy of pollution assessment and investigate this finding in different populations.

http://ift.tt/2DHbuAb

Some HCI Priorities for GDPR-Compliant Machine Learning

Veale, M; Binns, R; Van Kleek, M; (2018) Some HCI Priorities for GDPR-Compliant Machine Learning. In: (Proceedings) Workshop at the ACM Conference on Human Factors in Computing Systems (CHI'18). ACM: New York, USA. (In press).

http://ift.tt/2FUA0zQ

To what extent can behaviour change techniques be identified within an adaptable implementation package for primary care? A prospective directed content analysis

Glidewell, L; Willis, TA; Petty, D; Lawton, R; McEachan, RRC; Ingleson, E; Heudtlass, P; ... ASPIRE programme team, .; + view all Glidewell, L; Willis, TA; Petty, D; Lawton, R; McEachan, RRC; Ingleson, E; Heudtlass, P; Davies, A; Jamieson, T; Hunter, C; Hartley, S; Gray-Burrows, K; Clamp, S; Carder, P; Alderson, S; Farrin, AJ; Foy, R; Ward, V; West, R; Rathfelder, M; Hulme, C; Richardson, J; Stokes, T; Watt, I; ASPIRE programme team, .; - view fewer (2018) To what extent can behaviour change techniques be identified within an adaptable implementation package for primary care? A prospective directed content analysis. Implementation Science , 13 , Article 32. 10.1186/s13012-017-0704-7 . Green open access

http://ift.tt/2HNQxpI

'More than boy, girl, male, female': exploring young people’s views on gender diversity within and beyond school contexts

Bragg, S; Renold, E; Ringrose, J; Jackson, C; (2018) 'More than boy, girl, male, female': exploring young people's views on gender diversity within and beyond school contexts. Sex Education 10.1080/14681811.2018.1439373 . (In press). Green open access

http://ift.tt/2GM5Sbl

Efficient Batch Zero-Knowledge Arguments for Low Degree Polynomials

Bootle, J; Groth, J; (2018) Efficient Batch Zero-Knowledge Arguments for Low Degree Polynomials. In: PKC 2018: Public-Key Cryptography – PKC 2018. (pp. pp. 561-588). Springer Verlag Green open access

http://ift.tt/2HKvvIw

Performance Analysis of Cache-Enabled Millimeter Wave Small Cell Networks

Zhu, Y; Zheng, G; Wong, KK; Jin, S; Lambotharan, S; (2018) Performance Analysis of Cache-Enabled Millimeter Wave Small Cell Networks. IEEE Transactions on Vehicular Technology 10.1109/TVT.2018.2797047 . (In press). Green open access

http://ift.tt/2FZ6Nne

Prefrontal cortical thickness in motor neuron disease

Machts, J; Cardenas-Blanco, A; Acosta-Cabronero, J; Kaufmann, J; Loewe, K; Kasper, E; Schuster, C; ... Nestor, PJ; + view all Machts, J; Cardenas-Blanco, A; Acosta-Cabronero, J; Kaufmann, J; Loewe, K; Kasper, E; Schuster, C; Prudlo, J; Vielhaber, S; Nestor, PJ; - view fewer (2018) Prefrontal cortical thickness in motor neuron disease. NeuroImage: Clinical , 18 pp. 648-655. 10.1016/j.nicl.2018.03.002 . Green open access

http://ift.tt/2GJUMDu

Spatial differences in dissolved silicon utilization in Lake Baikal, Siberia: Examining the impact of high diatom biomass events and eutrophication

Panizzo, VN; Roberts, S; Swann, GEA; Mcgowan, S; Mackay, AW; Vologina, E; Pashley, V; Panizzo, VN; Roberts, S; Swann, GEA; Mcgowan, S; Mackay, AW; Vologina, E; Pashley, V; Horstwood, MSA; - view fewer (2018) Spatial differences in dissolved silicon utilization in Lake Baikal, Siberia: Examining the impact of high diatom biomass events and eutrophication. Limnology and Oceanography 10.1002/lno.10792 . (In press). Green open access

http://ift.tt/2HKw84Q

Virulent poxviruses inhibit DNA sensing by preventing STING activation

Georgana, I; Sumner, RP; Towers, GJ; Maluquer de Motes, C; (2018) Virulent poxviruses inhibit DNA sensing by preventing STING activation. Journal of Virology 10.1128/JVI.02145-17 . (In press). Green open access

http://ift.tt/2Ga4alY

Patterns of regional variation of opioid prescribing in primary care in England: a retrospective observational study

Mordecai, L; Reynolds, C; Donaldson, LJ; Williams, ACDEC; (2018) Patterns of regional variation of opioid prescribing in primary care in England: a retrospective observational study. British Journal of General Practice , 68 (668) e225-e233. 10.3399/bjgp/18X695057 .

http://ift.tt/2HO4vYZ