Distribution of persistent organic pollutants (POPs) in atmospheric particles during district heating period (DHP) and non-district heating period (N-DHP) in Shandong province, China

Abstract

Persistent organic pollutants (POPs), including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), phthalic acid esters (PAEs), and polychlorinated biphenyls (PCBs), were systemically investigated in total solid particles (TSPs) sampled at seven sites in Shandong province, China. The congener profile and space distribution were compared during district heating period (DHP) in winter and non-district heating period (N-DHP) in spring. The air pollution at in-land sites was worse than that at seashore sites due to the different ventilation conditions and pollutant sources. The concentrations of PAHs associated to the distribution of TSP, severer in DHP, since coal burning was the major source for both pollutants, according to the analysis of these results and diagnostic ratios. FLT, PYR, and BBF were top PAH congeners by specific mass concentrations. On the profile, OCPs, PCBs, and PAEs were more related to the ambient temperature due to the evaporation and revealed higher abundancy in N-DHP than in DHP. Based on the diagnostic ratio analysis, the source of pollution was more likely local than remote.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzUUDq
via IFTTT

Multivariate statistical analyses of air pollutants and meteorology in Chicago during summers 2010-2012

Abstract

Aerosol, trace gas, and meteorological data were collected in Chicago, Illinois during 2010–2012 summer air studies. Ozone, nitrogen oxides, acetate, formate, chloride, nitrate, sulfate, and oxalate concentrations as well as temperature, wind speed, wind direction, and humidity data were explored by both principal component analysis (PCA) and canonical correlation analysis (CCA). Multivariate statistical techniques were applied to uncover existing relationships between meteorology and air pollutant concentrations and also reduce data dimensions. In PCA, principal components (PCs) revealed a relationship of ozone and nitrate concentrations with respect to temperature and humidity, coupled with transport of species from the south in relation to the sampling site (PC1). PC2 was a measure of secondary aerosols but also suggested acetate and formate presence was a result of primary emissions or transport. Both PC3 and PC4 contained residual information with the former representing days of lower pollution and the latter representing northerly wind transport of chloride, nitrate, and ozone to the sampling site. In CCA, three canonical functions were statistically significant. The first indicated high temperature and low wind speed had a strong linear relationship ozone, oxalate, and nitrogen oxide concentrations whereas the second function showed a strong influence of wind direction on acetate, formate, and chloride concentrations. Residuals of temperature, wind speed, trace gases, and oxalate also were in the second function. The only new information in the third function was humidity. Overall, PCA and CCA bring forth multivariable relationships, not represented in descriptive statistics, useful in understanding pollution variability.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wvdmKF
via IFTTT

Examining colorectal cancer survivors’ surveillance patterns and experiences of care: a SEER-CAHPS study

Abstract

Purpose

We examined associations between experiences of care and adherence to surveillance guidelines among Medicare Fee-For-Service beneficiaries with colorectal cancer (CRC).

Methods

Using linked data from the National Cancer Institute's Surveillance, Epidemiology, and End results (SEER) cancer registry program and the Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS^®) patient experience surveys (SEER-CAHPS), we identified local/regional CRC survivors diagnosed in 1999–2009 aged 65+, who underwent surgical resection and completed a CAHPS survey <36 months of diagnosis. Adherence for a 3-year observation period was defined as receiving a colonoscopy; ≥2 carcinoembryonic antigen (CEA) tests; and each year had ≥2 office visits and ≥1 computerized tomography test.

Results

Many of the 314 participants reported ratings of a 9 or 10 out of 10 for overall care (55.4%), personal doctor (58.6%), health plan (59.6%), and specialist doctor (47.0%). Adherence to post-resection surveillance was 76.1% for office visits, 36.9% for CEA testing, 48.1% for colonoscopy, and 10.3% for CT Imaging. Overall, 37.9% of the sample were categorized as non-adherent (adhering to ≤1 surveillance guideline). In multivariable models, ratings of personal doctor and specialist doctor were positively associated with adherence to office visits, and ratings of personal doctor were associated with adherence overall.

Conclusions

Findings point to the potentially important role of patient-provider relationships in adherence to office visits for CRC surveillance. As adherence may increase survival among CRC survivors, further investigation is needed to identify specific components of this relationship that impact office visit adherence, and other potentially modifiable drivers of surveillance guidelines.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vSUKSM
via IFTTT

Rituximab Monotherapy Is Effective in Treating Orbital Necrobiotic Xanthogranuloma.

The authors report a case of a patient with bilateral orbital necrobiotic xanthogranuloma and no associated systemic paraproteinemia. Orbital biopsy showed strong expression of CD20-positive cells. The patient was treated with systemic rituximab monotherapy, with excellent clinical response and marked regression of the orbital lesions on imaging. At the time of writing, the patient has been treated with bimonthly rituximab maintenance therapy for 22 months and has stable clinical and imaging findings with sustained response to treatment and no reported side effects. To the authors' knowledge, this is the first reported case of orbital necrobiotic xanthogranuloma successfully treated with rituximab monotherapy. They hope that this well-documented case will encourage clinicians to consider rituximab monotherapy as a possible treatment option, albeit one entailing an off-label use of this drug, for patients with necrobiotic xanthogranuloma of the orbit. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzwARX
via IFTTT

Peri-Punctal Lymphangioma Treated With Bleomycin.

No abstract available

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wvwoAg
via IFTTT

Effect of Optic Nerve Disinsertion During Evisceration on Nonporous Implant Migration: A Comparative Case Series and a Review of Literature.

Aim: To determine whether evisceration with optic nerve disinsertion and nonporous implant placement increases the risk of implant migration. Methods: This was a single-center, retrospective consecutive comparative interventional case series including patients undergoing evisceration with nonporous implant between January and December 2014. Patients were grouped into 2 groups: group I where the optic nerve was not disinserted (n = 37) and group II with optic nerve disinsertion (n = 50). Implant migration was assessed clinically and on patient photographs. Migration was subclassified as decentration that did not affect the prosthetic outcome and displacement that affected the prosthetic outcome. The secondary outcome measures were the mean implant diameter, volume of the custom ocular prosthesis, and implant-related complications like exposure and extrusion between the 2 groups. Results: At a mean follow up of 12.5 months, none of the sockets in group I and 3 (6%) sockets in group II (p = 0.35) had evidence of implant decentration. There were no cases of implant displacement in both groups. The mean implant diameter in group I was 16.97 mm +/- 0.65 mm and in group II 19.2 mm +/- 0.83 mm (p = 0.0001). Implant extrusion was not different between the 2 groups. The mean custom ocular prosthesis volume in group I was 3.86 ml +/- 0.52 ml and in group II 2.50 ml +/- 0.68 ml (p

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vyYAoO
via IFTTT

Assessing the Accuracy of Eyelid Measurements Utilizing the Volk Eye Check System and Clinical Measurements.

Purpose: The purpose of this study was to validate the accuracy of marginal reflex distance 1 (MRD1) measurements obtained by the Volk Eye Check system, a modified smartphone that measures MRD1 automatically, relative to clinical and digital measurements. Methods: In this prospective observational study of adults with normal eyelids and ptosis, MRD1 was measured clinically, digitally, and automatically with the Volk device. Eyes were divided into successful versus unsuccessful Volk trial groups; successful eyes were then subdivided into control and ptosis subgroups. The primary outcome measures were mean MRD1 obtained by the 3 modalities. Secondary outcome measures included the success rate of the device and the prevalence of ptosis within the successful and unsuccessful groups. Results: In the overall sample of 88 eyes, clinical and digital MRD1 were not significantly different. Among eyes with successful Volk trials, significant differences in MRD1 measured by the 3 modalities were as follows: in the successful group, Volk MRD1 (3.05 mm) was significantly (p

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wvrjbg
via IFTTT

Haberland Syndrome Associated With Calvarial Exostosis.

No abstract available

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzCItF
via IFTTT

An Aesthetic Orbicularis Oculi Myectomy Technique for Blepharospasm: Use of Topical 5-Fluorouracil and Fibrin Sealant.

Purpose: To describe a modified technique of orbicularis oculi myectomy for refractory blepharospasm. This technique includes removal of orbicularis muscle, reformation of the eyelid crease and pretarsal platform using fibrin sealant (Tisseel), and topical 5-fluorouracil to reduce scar formation and improve aesthetic outcome. Methods: Retrospective chart review of 7 patients who underwent bilateral orbicularis oculi myectomy with our technique from 2013 to 2016. Outcome measures were postoperative botulinum toxin dose, frequency, duration between treatments, the amount of lagophthalmos, severity of dry eye, and patient satisfaction with aesthetic and functional outcome. Results: Patients who underwent the aesthetic myectomy technique had significantly decreased botulinum toxin use with relief of symptoms postoperatively. Only 1 of 7 patients experienced mild dry eye symptoms postoperatively, managed with artificial tears. All patients were satisfied with the aesthetic and functional outcome. Conclusions: The aesthetic myectomy technique provides effective treatment for blepharospasm with good functional and aesthetic outcome. (C) 2017 by The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc., All rights reserved.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wvD01I
via IFTTT

New dental clinic for SWAMS

The South West Aboriginal Medical Service has received a funding boost to establish a dental clinic to meet the health needs of the Noongar community.

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2wvkF4X
via IFTTT

SIDS (sudden infant death syndrome)

SIDS (sudden infant death syndrome): The sudden and unexpected death of a baby with no known illness, typically affecting sleeping infants between the ages of two weeks to six months. Infants with a brother or sister who died of SIDS; babies whose mothers used heroin, methadone, or cocaine during pregnancy; infants born weighing less than 4.4 pounds; children with an abnormal breathing pattern that includes long periods without taking a breath (apnea); and babies who sleep on their stomachs are at increased risk for SIDS.

Since babies who sleep on their stomachs are at least three times more likely to die of SIDS than babies who sleep on their backs, children's health authorities recommend always placing infants on their backs to sleep.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iOYRy6
via IFTTT

Young cancer patient's appointments canceled due to Hurricane Harvey - WTHR

Young cancer patient's appointments canceled due to Hurricane Harvey WTHR Hunter Bowman, a 12-year-old from Ludington, Michigan was set to go there for cancer treatment, but now things are up in the air. The 12-year-old was diagnosed with thyroid cancer when he was 9 years old, something that is rare in kids his age. "It ... and more »

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iPqV4s
via IFTTT

Structural properties of the intrinsically disordered, multiple calcium ion-binding otolith matrix macromolecule-64 (OMM-64)

Publication date: Available online 1 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Monika Poznar, Rafał Hołubowicz, Magdalena Wojtas, Jacek Gapiński, Ewa Banachowicz, Adam Patkowski, Andrzej Ożyhar, Piotr Dobryszycki
Fish otoliths are calcium carbonate biominerals that are involved in hearing and balance sensing. An organic matrix plays a crucial role in their formation. Otolith matrix macromolecule-64 (OMM-64) is a highly acidic, calcium-binding protein (CBP) found in rainbow trout otoliths. It is a component of high-molecular-weight aggregates, which influence the size, shape and polymorph of calcium carbonate in vitro. In this study, a protocol for the efficient expression and purification of OMM-64 was developed. For the first time, the complete structural characteristics of OMM-64 were described. Various biophysical methods were combined to show that OMM-64 occurs as an intrinsically disordered monomer. Under denaturing conditions (pH, temperature) OMM-64 exhibits folding propensity. It was determined that OMM-64 binds approximately 61 calcium ions with millimolar affinity. The folding-unfolding experiments showed that calcium ions induced the collapse of OMM-64. The effect of other counter ions present in trout endolymph on OMM-64 conformational changes was studied. The significance of disordered properties of OMM-64 and the possible function of this protein is discussed.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wvjq5G
via IFTTT

The Effect of Phosphorylation on the Salt-Tolerance-Related Functions of the Soybean Protein PM18, a Member of the Group-3 LEA Protein Family

Publication date: Available online 1 September 2017
Source:Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics
Author(s): Yun Liu, Meiyan Yang, Hua Cheng, Nan Sun, Simu Liu, Shuiming Li, Yong Wang, Yizhi Zheng, Vladimir N. Uversky
Enzymatically driven post-translated modifications (PTMs) usually happen within the intrinsically disordered regions of a target protein and can modulate variety of protein functions. Late embryogenesis abundant (LEA) proteins are a family of the plant intrinsically disordered proteins (IDPs). Despite their important roles in plant stress response, there is currently limited knowledge on the presence and functional and structural effects of phosphorylation on LEA proteins. In this study, we identified three phosphorylation sites (Ser⁹⁰, Tyr¹³⁶, and Thr²⁶⁶) in the soybean PM18 protein that belongs to the group-3 LEA proteins. In yeast expression system, PM18 protein increased the salt tolerance of yeast, and the phosphorylation of this protein further enhanced its protective function. Further analysis revealed that Ser⁹⁰ and Tyr¹³⁶ are more important than Thr²⁶⁶, and these two sites might work cooperatively in regulating the salt resistance function of PM18. The circular dichroism analysis showed that PM18 protein was disordered in aqueous media, and phosphorylation did not affect the disordered status of this protein. However, phosphorylation promoted formation of more helical structure in the presence of sodium dodecyl sulfate (SDS) or trifluoroethanol (TFE). Furthermore, in dedicated in vitro experiments, phosphorylated PM18 protein was able to better protect lactate dehydrogenase (LDH) from the inactivation induced by the freeze-thaw cycles than its un- or dephosphorylated forms. All these data indicate that phosphorylation may have regulatory effects on the stress-tolerance-related function of LEA proteins. Therefore, further studies are needed to shed more light on functional and structural roles of phosphorylation in LEA proteins.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzLnMp
via IFTTT

Humanization of JAA-F11, a Highly Specific Anti-Thomsen-Friedenreich Pancarcinoma Antibody and In Vitro Efficacy Analysis

JAA-F11 is a highly specific mouse monoclonal to the Thomsen-Friedenreich Antigen (TF-Ag) which is an alpha-O-linked disaccharide antigen on the surface of ~80% of human carcinomas, including breast, lung, colon, bladder, ovarian, and prostate cancers, and is cryptic on normal cells. JAA-F11 has potential, when humanized, for cancer immunotherapy for multiple cancer types. Humanization of JAA-F11, was performed utilizing complementarity determining regions grafting on a homology framework. The objective herein is to test the specificity, affinity and biology efficacy of the humanized JAA-F11 (hJAA-F11).

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gyy7kC
via IFTTT

Up-regulation of Biglycan is Associated with Poor Prognosis and PTEN Deletion in Patients with Prostate Cancer

Biglycan (BGN), a proteoglycan of the extracellular matrix, is included in mRNA signatures for prostate cancer aggressiveness. To understand the impact of BGN on prognosis and its relationship to molecularly defined subsets, we analyzed BGN expression by immunohistochemistry on a tissue microarray containing 12,427 prostate cancers. Seventy-eight percent of 11,050 interpretable cancers showed BGN expression, which was considered as low intensity in 47.7% and as high intensity in 31.1% of cancers.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eNuSlE
via IFTTT

The Volume of Three-Dimensional Cultures of Cancer Cells In Vitro Influences Transcriptional Profile Differences and Similarities with Monolayer Cultures and Xenografted Tumors

Improving the congruity of preclinical models with cancer as it is manifested in humans is a potential way to mitigate the high attrition rate of new cancer therapies in the clinic. In this regard, three-dimensional (3D) tumor cultures in vitro have recently regained interest as they have been acclaimed to have higher similarity to tumors in vivo than to cells grown in monolayers (2D). To identify cancer functions that are active in 3D rather than in 2D cultures, we compared the transcriptional profiles (TPs) of two non-small cell lung carcinoma cell lines, NCI-H1650 and EBC-1 grown in both conditions to the TP of xenografted tumors.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gxxxUg
via IFTTT

Evaluation of the Response of Intracranial Xenografts to VEGF Signaling Inhibition Using Multiparametric MRI

Vascular endothelial growth factor A (VEGF-A) is considered one of the most important factors in tumor angiogenesis, and consequently, a number of therapeutics have been developed to inhibit VEGF signaling. Therapeutic strategies to target brain malignancies, both primary brain tumors, particularly in pediatric patients, and metastases, are lacking, but targeting angiogenesis may be a promising approach. Multiparametric MRI was used to investigate the response of orthotopic SF188luc pediatric glioblastoma xenografts to small molecule pan-VEGFR inhibitor cediranib and the effects of both cediranib and cross-reactive human/mouse anti-VEGF-A antibody B20-4.1.1 in intracranial MDA-MB-231 LM2–4 breast cancer xenografts over 48 hours.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eNC94V
via IFTTT

NF-κB p65 Overexpression Promotes Bladder Cancer Cell Migration via FBW7-Mediated Degradation of RhoGDIα Protein

BACKGROUND: Since invasive bladder cancer (BC) is one of the most lethal urological malignant tumors worldwide, understanding the molecular mechanisms that trigger the migration, invasion, and metastasis of BC has great significance in reducing the mortality of this disease. Although RelA/p65, a member of the NF-kappa B transcription factor family, has been reported to be upregulated in human BCs, its regulation of BC motility and mechanisms have not been explored yet. METHODS: NF-κBp65 expression was evaluated in N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)–induced high invasive BCs by immunohistochemistry staining and in human BC cell lines demonstrated by Western Blot.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gxxhEM
via IFTTT

The Antitumor Activity of IMGN529, a CD37-Targeting Antibody-Drug Conjugate, Is Potentiated by Rituximab in Non-Hodgkin Lymphoma Models

Naratuximab emtansine (IMGN529) is an investigational antibody-drug conjugate consisting of a CD37-targeting antibody conjugated to the maytansine-derived microtuble disruptor, DM1. IMGN529 has shown promising preclinical and clinical activity in non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Due to the aggressive nature of the disease, DLBCL is often treated with combination therapies to maximize clinical outcomes; therefore, we investigated the potential of combining IMGN529 with both standard-of-care and emerging therapies against multiple oncology-relevant targets and pathways.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2grakzm
via IFTTT

Teoria dei giochi e scienza della complessità: doppio appuntamento per la Lake Como School - CiaoComo.it

CiaoComo.it

Teoria dei giochi e scienza della complessità: doppio appuntamento per la Lake Como School CiaoComo.it L'obiettivo è quello di analizzare i recenti progressi in un campo di ricerca che offre diversi argomenti, dalla classificazione dei sistemi, alla valutazione del potere effettivo degli agenti, compreso il comportamento dei membri, elementi casuali ...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iQ3OGZ
via IFTTT

Phase II basket trial of perifosine monotherapy for recurrent gynecologic cancer with or without PIK3CA mutations

Summary

Objective Perifosine exhibits anti-tumor activity by inhibiting AKT phosphorylation. The purpose of this phase II basket trial was to evaluate the efficacy and safety of perifosine monotherapy for ovarian, endometrial, and cervical cancers. Methods Recurrent or persistent ovarian, endometrial, or cervical cancer patients were assigned to PIK3CA wild-type or mutant groups. Each patient received 600 mg oral perifosine on day 1 followed by a maintenance dose of 100 mg daily. The primary endpoint was disease control rate; secondary endpoints included response rate, progression-free survival, overall survival, and safety. Immunohistochemical staining and targeted sequencing were used to explore new biomarkers in such patients. Results Sixteen and 5 ovarian, 17 and 7 endometrial, and 18 and 8 cervical cancer patients with PIK3CA wild-type and mutant, respectively, were enrolled. Disease control rates (wild-type/mutant) were 12.5/40.0%, 47.1/14.3%, and 11.1/25.0% in ovarian, endometrial, and cervical cancer, respectively. The most common grade 3/4 toxicities were anemia (22.5%) and anorexia (11.3%). Immunohistochemical staining revealed that the disease control rate in patients with negative phosphatase and tensin homolog (PTEN) expression was 50.0%, and the odds ratio of positive to negative patients was 0.24 in all patients. Conclusions Perifosine monotherapy showed good tolerability but expected efficacy was not achieved. Modest efficacy was demonstrated in ovarian cancer patients with PIK3CA mutations and endometrial cancer patients with PIK3CA wild-type; no difference was observed between PIK3CA wild-type and mutant in cervical cancer. Absence of PTEN expression may be predictive of clinical efficacy with perifosine monotherapy.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gxc91v
via IFTTT

Quantitative Mass Spectrometry Reveals Food Intake-Induced Neuropeptide Level Changes in Rat Brain: Functional Assessment of Selected Neuropeptides as Feeding Regulators [Research]

Endogenous neuropeptides are important signaling molecules that function as regulators of food intake and body weight. Previous work has shown that neuropeptide gene expression levels in a forebrain reward site, the nucleus accumbens (NAc), were changed by feeding. In order to directly monitor feeding-induced changes in neuropeptide expression levels within the NAc, we employed a combination of cryostat dissection, heat stabilization, neuropeptide extraction and label-free quantitative neuropeptidomics via a liquid chromatography-high resolution mass spectrometry platform. Using this methodology, we described the first neuropeptidome in NAc and discovered that feeding caused the expression level changes of multiple neuropeptides derived from different precursors, especially proSAAS-derived peptides such as Big LEN, PEN and little SAAS. We further investigated the regulatory functions of these neuropeptides derived from the ProSAAS family by performing an intra-NAc microinjection experiment using the identified ProSAAS neuropeptides, 'Big-LEN' and 'PEN'. Big LEN significantly increased rats' food and water intake, whereas both big LEN and PEN affected other behaviors including locomotion, drinking and grooming. In addition, we quantified the feeding-induced changes of peptides from hippocampus, hypothalamus and striatum to reveal the neuropeptide interplay among different anatomical regions. In summary, our study demonstrated neuropeptidomic changes in response to food intake in the rat NAc and other key brain regions. Importantly, the microinfusion of ProSAAS peptides into NAc revealed that they are behaviorally active in this brain site, suggesting the potential utility of these peptides as therapeutics for eating disorders.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wrvvum
via IFTTT

A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis [Research]

Perilipin 2 (PLIN2) is a lipid-droplet protein that is up-regulated in alcoholic steatosis and associated with hepatic accumulation of ceramides, bioactive lipids implicated in alcoholic liver disease pathogenesis. The specific role of ceramide synthetic enzymes in the regulation of PLIN2 and promotion of hepatocellular lipid accumulation is not well understood. We examined the effects of pharmacologic ceramide synthesis inhibition on hepatic PLIN2 expression, steatosis, and glucose and lipid homeostasis in mice with alcoholic steatosis and in ethanol-incubated human hepatoma VL17A cells. In cells, pharmacologic inhibition of ceramide synthase reduced lipid accumulation by reducing PLIN2 RNA stability. The subtype ceramide synthase (CerS)6 was specifically up-regulated in experimental alcoholic steatosis in vivo and in vitro and was up-regulated in zone 3 hepatocytes in human alcoholic steatosis. In vivo ceramide reduction by inhibition of de novo ceramide synthesis reduced PLIN2 and hepatic steatosis in alcohol-fed mice, but only de novo synthesis inhibition, not sphingomyelin hydrolysis, improved glucose tolerance and dyslipidemia. These findings implicate CerS6 as a novel regulator of PLIN2 and suggest that ceramide synthetic enzymes may promote the earliest stage of alcoholic liver disease, alcoholic steatosis.—Williams, B., Correnti, J., Oranu, A., Lin, A., Scott, V., Annoh, M., Beck, J., Furth, E., Mitchell, V., Senkal, C. E., Obeid, L., Carr, R. M. A novel role for ceramide synthase 6 in mouse and human alcoholic steatosis.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wrj01U
via IFTTT

De novo digenic mutations of telomere-associated proteins and inflammasomes initiate many chronic human diseases: a hypothesis [Hypothesis]

Many age-related human diseases have inflammatory components of uncertain causes. It has been proposed that some may be initiated or sustained by doubly mutated immune cells that have both inappropriately activated inflammasomes and enhanced replicative potential. Genes of cells that express mutant TERT and NLRP3 proteins are presumed to be at increased risk for mutagenesis because they reside in subtelomeric regions of chromatin that are deficient in DNA repair mechanisms. Expanded clones of proinflammatory cells can occur throughout one's lifetime and could represent an alternative explanation for some forms of pathologic scarring that are now attributed to truncated telomeres.—Marchesi, V. T. De novo digenic mutations of telomere-associated proteins and inflammasomes initiate many chronic human diseases: a hypothesis.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wqRDow
via IFTTT

PLA2 and ENPP6 may act in concert to generate phosphocholine from the matrix vesicle membrane during skeletal mineralization [Hypothesis]

Mineralization is a key process in the formation of bone and cartilage in vertebrates, involving the deposition of calcium and phosphate containing hydroxyapatite (HA) mineral within a collagenous matrix. Inorganic phosphate (P_i) accumulation within matrix vesicles (MVs) is a fundamental stage in the precipitation of HA, with PHOSPHO1 being identified as the principal enzyme acting to produce P_i. PHOSPHO1 is a dual-specific phosphocholine/phosphoethanolamine phosphatase enriched in mineralizing cells and within MVs. However, the source and mechanism by which PHOSPHO1 substrates are formed before mineralization have not been determined. Here, we propose that 2 enzymes—phospholipase A2 (PLA₂) and ectonucleotide pyrophophatase/phosphodiesterase 6 (ENPP6)—act in sequence upon phosphatidylcholine found in MV membranes to produce phosphocholine, which PHOSPHO1 can hydrolyze to liberate P_i. This hypothesis is supported by evidence that both enzymes are expressed in mineralizing cells and data showing that phosphatidylcholine is broken down in MVs during mineralization. Therefore, PLA₂ and ENPP6 activities may represent a key step in the mineralization process. Further functional studies are urgently required to examine their specific roles in the initiation of skeletal mineralization.—Stewart, A. J., Leong, D. T. K., Farquharson, C. PLA₂ and ENPP6 may act in concert to generate phosphocholine from the matrix vesicle membrane during skeletal mineralization.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iQg9La
via IFTTT

Mechanism for the inhibition of the cAMP dependence of HCN ion channels by the auxiliary subunit TRIP8b [Neurobiology]

TRIP8b, an accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels, alters both the cell surface expression and cyclic nucleotide dependence of these channels. However, the mechanism by which TRIP8b exerts these dual effects is still poorly understood. Besides binding to the carboxy-terminal tripeptide of HCN channels, TRIP8b also binds directly to the cyclic nucleotide-binding domain (CNBD). That interaction, which requires a small central portion of TRIP8b termed TRIP8bcore, is both necessary and sufficient for reducing the cAMP-dependent regulation of HCN channels. Here, using fluorescence anisotropy, we report that TRIP8b binding to the CNBD of HCN2 channels decreases the apparent affinity of cAMP for the CNBD. We explored two possible mechanisms for this inhibition. A noncompetitive mechanism in which TRIP8b inhibits the conformational change of the CNBD associated with cAMP regulation and a competitive mechanism in which TRIP8b and cAMP compete for the same binding site. To test these two mechanisms, we used a combination of fluorescence anisotropy, bio-layer interferometry, and double electron-electron resonance (DEER) spectroscopy. Fitting these models to our fluorescence anisotropy binding data revealed that, surprisingly, the TRIP8b-dependent reduction of cAMP binding to the CNBD can largely be explained by partial competition between TRIP8b and cAMP. On the basis of these findings, we propose that TRIP8b competes with a portion of the cAMP binding site or distorts the binding site by making interactions with the binding pocket, thus acting predominantly as a competitive antagonist that inhibits the cyclic-nucleotide dependence of HCN channels.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iRv1ZV
via IFTTT

Two independent but synchronized G{beta}{gamma} subunit-controlled pathways are essential for trailing-edge retraction during macrophage migration [Cell Biology]

Chemokine-induced directional cell migration is a universal cellular mechanism and plays crucial roles in numerous biological processes, including embryonic development, immune system function, and tissue remodeling and regeneration. During the migration of a stationary cell, the cell polarizes, forms lamellipodia at the leading edge (LE), and triggers the concurrent retraction of the trailing edge (TE). During cell migration governed by inhibitory G protein (Gi)−coupled receptors (GPCRs), G protein Gβγ (Gβγ) subunits control the LE signaling. Interestingly, TE retraction has been linked to the activation of the small GTPase Ras homolog family member A (RhoA), activated by the Gα12/13 pathway. However, it is not clear how the activation of Gi−coupled GPCRs at the LE orchestrates the TE retraction in RAW264.7 macrophages. Here, using an optogenetic approach involving an opsin to activate the Gi-pathway in defined subcellular regions of RAW cells, we show that in addition to their LE activities, free Gβγ subunits also govern TE retraction by operating two independent, yet synchronized, pathways. The first pathway involves RhoA activation, which prevents dephosphorylation of the myosin light chain (MLC), allowing actomyosin contractility to proceed. The second pathway activates phospholipase Cβ (PLCββ) and induces MLC phosphorylation to enhance actomyosin contractility through increasing cytosolic calcium. We further show that both of these pathways are essential, and inhibition of either one is sufficient to abolish the Gi−coupled GPCR−governed TE retraction and subsequent migration of RAW cells.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ewGVXB
via IFTTT

The calcium-binding protein ALG-2 regulates protein secretion and trafficking via interactions with MISSL and MAP1B [Cell Biology]

Mobilization of intracellular calcium is essential for a wide range of cellular processes including signal transduction, apoptosis, and vesicular trafficking. Several lines of evidence have suggested that apoptosis-linked gene 2 (ALG-2, also known as PDCD6), a calcium-binding protein, acts as a calcium sensor linking calcium levels with efficient vesicular trafficking, especially at the endoplasmic reticulum (ER)-to-Golgi transport step. However, how ALG-2 regulates these processes remains largely unclear. Here, we report that MAPK1-interacting and spindle-stabilizing (MISS)-like (MISSL), a previously uncharacterized protein, interacts with ALG-2 in a calcium-dependent manner. Live-cell imaging revealed that upon a rise in intracellular calcium levels, GFP-tagged MISSL (GFP-MISSL) dynamically relocalizes in a punctate pattern and colocalizes with ALG-2. MISSL knockdown caused disorganization of the components of the ER exit site, the ER-Golgi intermediate compartment, and Golgi. Importantly, knockdown of either MISSL or ALG-2 attenuated the secretion of secreted alkaline phosphatase (SEAP), a model secreted cargo protein, with similar reductions in secretion by single- and double-protein knockdowns, suggesting that MISSL and ALG-2 act in the same pathway to regulate the secretion process. Furthermore, ALG-2 or MISSL knockdown delayed ER-to-Golgi transport of procollagen type I. We also found that ALG-2 and MISSL interact with microtubule-associated protein 1B (MAP1B) and that MAP1B knockdown reverts the reduced secretion of SEAP caused by MISSL or ALG-2 depletion. These results suggest that a change in the intracellular calcium level plays a role in regulation of the secretory pathway via interaction of ALG-2 with MISSL and MAP1B.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iNCKI4
via IFTTT

Negatively charged residues in the first extracellular loop of the L-type CaV1.2 channel anchor the interaction with the CaV{alpha}2{delta}1 auxiliary subunit [Molecular Biophysics]

Voltage-gated L-type CaV1.2 channels in cardiomyocytes exist as heteromeric complexes. Co-expression of CaVα2δ1 with CaVβ /CaVα1 proteins reconstitutes the functional properties of native L-type currents but the interacting domains at the CaV1.2/CaVα2δ1 interface are unknown. Here, a homology-based model of CaV1.2 identified protein interfaces between the extracellular domain of CaVα2δ1 and the extracellular loops of the CaVα1 protein in repeats I (IS1S2, IS5S6), II (IIS5S6), and III (IIIS5S6). Insertion of a 9-residue hemagglutinin epitope in IS1S2, but not in IS5S6 or in IIS5S6, prevented the co-immunoprecipitation of CaV1.2 and CaVα2δ1. IS1S2 contains a cluster of three conserved negatively charged residues Glu-179, Asp-180, and Asp-181, that could contribute to non-bonded interactions with CaVα2δ1. Substitutions of CaV1.2 Asp-181 impaired the co-immunoprecipitation of CaVβ / CaV1.2 with CaVα2δ1 and the CaVα2δ1-dependent shift in voltage-dependent activation gating. In contrast, single substitutions in CaV1.2 in neighboring positions in the same loop (179, 180, 182, 183 and 184) did not significantly alter the functional upregulation of CaV1.2 whole-cell currents. However, a negatively charged residue at position 180 was necessary to convey the CaVα2δ1-mediated shift in the activation gating. We also found a more modest contribution from the positively charged Arg-1119 in the extracellular pore region in repeat III of CaV1.2. We conclude that CaV1.2 Asp-181 anchors the physical interaction that facilitates the CaVα2δ1-mediated functional modulation of CaV1.2 currents. By stabilizing the first extracellular loop of CaV1.2, CaVα2δ1 may upregulate currents by promoting conformations of the voltage sensor that are associated with the channel's open state

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ewFF6D
via IFTTT

A histone-mimicking interdomain linker in a multi-domain protein modulates multivalent histone binding [Molecular Biophysics]

N-terminal histone tails are subject to many posttranslational modifications that are recognized by and interact with designated reader domains in histone-binding proteins. BROMO domain adjacent to zinc finger 2B (BAZ2B) is a multi-domain histone-binding protein that contains two histone reader modules, a plant homeodomain (PHD) and a bromodomain (BRD), linked by a largely disordered linker. While previous studies have reported a specificity of the PHD domain for the unmodified N-terminus of histone H3 and of the BRD domain for H3 acetylated at Lys-14 (H3K14ac), the exact mode of H3 binding by BAZ2B and its regulation are underexplored. Here, using isothermal titration calorimetry (ITC) and NMR spectroscopy, we report that acidic residues in the BAZ2B PHD domain are essential for H3 binding and that BAZ2B PHD-BRD establishes a polyvalent interaction with H3K14ac. Furthermore, we provide evidence that the disordered interdomain linker modulates the histone-binding affinity by interacting with the PHD domain. In particular, lysine-rich stretches in the linker, which resemble the positively charged N-terminus of histone H3, reduce the binding affinity of the PHD finger toward the histone substrate. Phosphorylation, acetylation, or poly(ADP-ribosyl)ation of the linker residues may thereby act as a cellular mechanism to transiently tune BAZ2B histone-binding affinity. Our findings further support the concept of interdomain linkers serving a dual role in substrate binding by appropriately positioning the adjacent domains and by electrostatically modulating substrate binding. Moreover, inhibition of histone binding by a histone-mimicking interdomain linker represents another example of regulation of protein-protein interactions by intramolecular mimicry.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iPGs4f
via IFTTT

Proteolytic Processing of Lysyl Oxidase like-2 in the Extracellular Matrix is Required for Crosslinking of Basement Membrane Collagen IV [Enzymology]

Lysyl oxidase like 2 (LOXL2) is an enzyme secreted into the extracellular matrix that crosslinks collagens by mediating oxidative deamination of lysine residues. Our previous work demonstrated that this enzyme crosslinks the 7S domain, a structural domain that stabilizes collagen IV scaffolds in the basement membrane. In spite of its relevant role in extracellular matrix biosynthesis, little is known about the structural requirements of LOXL2 that enable collagen IV crosslinking. In this study, we demonstrate that LOXL2 is processed extracellularly by serine proteases, generating a 65 kDa form lacking the first two Scavenger Receptors Cysteine Rich domains. Site-specific mutagenesis to prevent proteolytic processing generated a full-length enzyme that is active in vitro towards a soluble substrate, but fails to crosslink insoluble collagen IV within the extracellular matrix. In contrast, the processed form of LOXL2 binds to collagen IV and crosslinks the 7S domain. Together, our data demonstrate that proteolytic processing is an important event that allows LOXL2-mediated crosslinking of basement membrane collagen IV.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ewUQN8
via IFTTT

Facial Nerve Clinic to Provide Comprehensive Personalized Care - Newswise (press release)

Facial Nerve Clinic to Provide Comprehensive Personalized Care Newswise (press release) The program will treat patients with facial nerve paralysis or weakness caused by Bell's palsy, Ramsay-Hunt Syndrome, facial nerve tumors, cancer treatment, ear disease, acoustic neuromas, facial trauma, temporal bone trauma, parotid surgery, ...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iRGMzw
via IFTTT

Table of Contents

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iQuMOn
via IFTTT

Editorial Board

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2ewUGFw
via IFTTT

Venous thromboembolism and hyperhomocysteinemia as first manifestation of pernicious anemia: a case series

Hyperhomocysteinemia has been suspected of favoring thrombosis. Several case–control studies and even a meta-analysis have confirmed a link between venous thrombosis and hyperhomocysteinemia. Homocysteine is d...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2erEpy7
via IFTTT

Inhibition of lysozyme amyloidogenesis by phospholipids. Focus on long-chain dimyristoylphosphocholine

Publication date: Available online 1 September 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Slavomira Ponikova, Jana Kubackova, Zuzana Bednarikova, Jozef Marek, Erna Demjen, Andrea Antosova, Andrej Musatov, Zuzana Gazova
BackgroundProtein amyloid aggregation is an important pathological feature of a group of different degenerative human diseases called amyloidosis. We tested effect of two phospholipids, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) on amyloid aggregation of hen egg white (HEW) lysozyme in vitro.MethodsEffect of phospholipids was investigated using spectroscopic techniques (fluorescence and CD spectroscopy), atomic force microscopy and image analysis.ResultsPhospholipids DMPC and DHPC are able dose-dependently inhibit lysozyme fibril formation. The length of the phospholipid tails and different structural arrangement of the phospholipid molecules affect inhibitory activity; long-chain DMPC inhibits fibrillization more efficiently. Interestingly, interference of DMPC with lysozyme amyloid fibrils has no effect on their morphology or amount.ConclusionsPhospholipid molecules have significant effect on lysozyme amyloid fibrillization. We suggest that inhibitory activity is due to the interference of phospholipids with lysozyme leading to the blocking of the intermolecular protein interactions important for formation of the cross-β structure within the core of the fibrils. The higher inhibitory activity of DMPC is probably due to adsorption of protein molecules on the liposome surfaces which caused decrease of species needed for fibrillization. Interaction of the phospholipids with formed fibrils is not sufficient enough to interrupt the bonds in β-sheets which are required for destroying of amyloid fibrils.General significanceThe obtained results contribute to a better understanding of the effect of phospholipids on amyloid fibrillization of the lysozyme. The data suggest that DMPC and DHPC phospholipids represent agents able to modulate lysozyme amyloid aggregation.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vSu1Wr
via IFTTT

Protein Phosphorylation and Its Role in the Regulation of Annexin A2 Function

Publication date: Available online 1 September 2017
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Ann Kari Grindheim, Jaakko Saraste, Anni Vedeler
BackgroundAnnexin A2 (AnxA2) is a multifunctional protein involved in endocytosis, exocytosis, membrane domain organisation, actin remodelling, signal transduction, protein assembly, transcription and mRNA transport, as well as DNA replication and repair.Scope of ReviewThe current knowledge of the role of phosphorylation in the functional regulation of AnxA2 is reviewed. To provide a more comprehensive treatment of this topic, we also address in depth the phosphorylation process in general and discuss its possible conformational effects. Furthermore, we discuss the apparent limitations of the methods used to investigate phosphoproteins, as exemplified by the study of AnxA2.Major ConclusionsAnxA2 is subjected to complex regulation by post-translational modifications affecting its cellular functions, with Ser11, Ser25 and Tyr23 representing important phosphorylation sites. Thus, Ser phosphorylation of AnxA2 is involved in the recruitment and docking of secretory granules, the regulation of its association with S100A10, and sequestration of perinuclear, translationally inactive mRNP complexes. By contrast, Tyr phosphorylation of AnxA2 regulates its role in actin dynamics and increases its association with endosomal compartments. Modification of its three main phosphorylation sites is not sufficient to discriminate between its numerous functions. Thus, fine-tuning of AnxA2 function is mediated by the joint action of several post-translational modifications.General SignificanceAnxA2 participates in malignant cell transformation, and its overexpression and/or phosphorylation is associated with cancer progression and metastasis. Thus, tight regulation of AnxA2 function is an integral aspect of cellular homeostasis. The presence of AnxA2 in cancer cell-derived exosomes, as well as the potential regulation of exosomal AnxA2 by phosphorylation or other PTMs, are topics of great interest.

Graphical abstract

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wrbSmf
via IFTTT

Private Equity Investments in Health Care Practices

Private equity funds are generally prohibited from owning entities that employ licensed professionals and may not invest directly in medical or dental practices in many states because of laws that prohibit the corporate practice of medicine and fee-splitting between licensed professionals and nonprofessionals. This article was published in the August 31, 2017 issue of Middle Market Growth, a weekly newsletter published by Association of Corporate Growth .

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2gwhC8H
via IFTTT

Total reference air kerma can accurately predict isodose surface volumes in cervix cancer brachytherapy. A multicenter study

Publication date: Available online 1 September 2017
Source:Brachytherapy
Author(s): Karen S. Nkiwane, Else Andersen, Jerome Champoudry, Astrid de Leeuw, Jamema Swamidas, Jacob Lindegaard, Richard Pötter, Christian Kirisits, Kari Tanderup
PurposeTo demonstrate that V60 Gy, V75 Gy, and V85 Gy isodose surface volumes can be accurately estimated from total reference air kerma (TRAK) in cervix cancer MRI-guided brachytherapy (BT).Methods and Materials60 Gy, 75 Gy, and 85 Gy isodose surface volumes levels were obtained from treatment planning systems (VTPS) for 239 EMBRACE study patients from five institutions treated with various dose rates, fractionation schedules and applicators. An equation for estimating VTPS from TRAK was derived. Furthermore, a surrogate Point A dose (Point A*) was proposed and tested for correlation with V75 Gy.ResultsPredicted volumes Vpred = 4965 (TRAK/dref) 3/2 + 170 (TRAK/dref) − 1.5 gave the best fit to VTPS. The difference between VTPS and predicted volumes was 0.0% ± 2.3%. All volumes were predicted within 10%. The prediction was valid for (1) high-dose rate and pulsed dose rate, (2) intracavitary vs. intracavitary/interstitial applicators, and (3) tandem-ring, tandem-ovoid, and mold. Point A* = 14 TRAK was converted to total EQD2 and showed high correlation with V75 Gy.ConclusionsTRAK derived Isodose surface volumes may become a tool for assessment of treatment intensity. Furthermore, surrogate Point A^∗ doses can be applied for both intracavitary and intracavitary/interstitial BT and can be used to compare treatments across fractionation schedules.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gwRvhG
via IFTTT

Cetuximab with radiotherapy as an alternative treatment for advanced squamous cell carcinoma of the temporal bone

Publication date: Available online 1 September 2017
Source:Auris Nasus Larynx
Author(s): Koji Ebisumoto, Kenji Okami, Masashi Hamada, Daisuke Maki, Akihiro Sakai, Kosuke Saito, Fukuko Shimizu, Shoji Kaneda, Masahiro Iida
The prognosis of advanced temporal bone cancer is poor, because complete surgical resection is difficult to achieve. Chemoradiotherapy is one of the available curative treatment options; however, its systemic effects on the patient restrict the use of this treatment. A 69-year-old female (who needed peritoneal dialysis) presented at our clinic with T4 left external auditory canal cancer and was treated with cetuximab plus radiotherapy (RT). The primary lesion showed complete response. The patient is currently alive with no evidence of disease two years after completion of the treatment and does not show any late toxicity. This is the first advanced temporal bone cancer patient treated with RT plus cetuximab. Cetuximab plus RT might be a treatment alternative for patients with advanced temporal bone cancer.



from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2ewpHcK
via IFTTT

Poliposi nasosinusale. Rinosinusite cronica con polipi

Publication date: September 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 3
Author(s): P. Bonfils, P. Halimi, A.-L. Gaultier, Q. Lisan
La poliposi nasosinusale (chronic rhinosinusitis with polyps nella letteratura anglosassone) è una rinosinusite cronica bilaterale caratterizzata dallo sviluppo di polipi nelle cavità nasosinusali. La sua prevalenza è stimata, nella popolazione generale, pari a circa il 4%. La poliposi nasosinusale può essere associata ad alcune malattie come la fibrosi cistica, la discinesia ciliare, le immunodeficienze e l'intolleranza all'aspirina e ai farmaci antinfiammatori non steroidei (FANS). Deriva da un'infiammazione cronica della mucosa nasosinusale dove l'infiltrazione eosinofila è uno dei marker della malattia. Ma la sua fisiopatologia rimane ancora sconosciuta. Sono state sviluppate, nel corso degli ultimi trent'anni, numerose teorie che coinvolgono in particolare l'infezione micotica e il ruolo delloStaphylococcus aureus. La sintomatologia della poliposi è dominata dall'ostruzione nasale e dall'anosmia e da un minimo grado di rinorrea posteriore. È la forma di rinosinusite diffusa che compromette di più la qualità della vita. La triade di Widal (triade di Samter) associa tipicamente poliposi nasosinusale, asma e intolleranza all'aspirina e ai FANS. La prevalenza dell'asma è elevata nella poliposi nasosinusale; la ricerca di asma o di iperreattività bronchiale non specifica deve essere sistematica davanti ad ogni paziente con una poliposi. Il trattamento è sempre medico, eventualmente completato da un intervento chirurgico. I trattamenti medici si basano sui corticosteroidi, sia locali che sistemici. La chirurgia della poliposi si basa su una videochirurgia endonasale generalmente effettuata sotto controllo endoscopico. I criteri di selezione dei pazienti per la chirurgia sono dominati dall'importanza dei sintomi e dalla resistenza ai trattamenti medici.



from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2gxCIDr
via IFTTT

Actinomicosi cervicofacciale

Publication date: September 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 3
Author(s): A. Loth-Bouketala, J. Graziani, N. Fakhry
L'actinomicosi è una malattia rara causata da batteri anaerobi e filamentosi, gli Actinomyces, che si presenta sotto forma di tumefazione sottocutanea, infiammatoria e, il più delle volte, cronica. L'actinomicosi può avere diverse sedi, ma la regione cervicofacciale è quella il più delle volte colpita. Alcuni fattori favoriscono l'insorgenza di questa malattia (immunodepressione, trauma orale). La presentazione clinica è aspecifica e la diagnosi è spesso ritardata. Il quadro clinico può suggerire una patologia tumorale oppure una tubercolosi. L'evoluzione clinica può portare a una fistolizzazione cutanea della tumefazione. La valutazione tramite esami strumentali e del sangue è poco specifica. I campioni batteriologici e anatomopatologici (citopuntura, biopsie, evacuazione del pus) confermano la diagnosi. Per trattare l'actinomicosi è proposta un'antibioticoterapia, talvolta associata a un trattamento chirurgico.



from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2eNI7Tj
via IFTTT

Anatomia del nervo faciale

Publication date: September 2017
Source:EMC - Otorinolaringoiatria, Volume 16, Issue 3
Author(s): J. Barbut, F. Tankéré, I. Bernat
Il nervo faciale è al centro della pratica quotidiana in oto-rino-laringoiatria. La sua singolare fisiologia e la sua patologia fanno di questo paio di nervi cranici un soggetto appassionante in cui alcuni si sono specializzati. La precisa conoscenza della sua anatomia, il cui percorso è tortuoso e presenta molte relazioni con altri elementi nobili, è un prerequisito indispensabile per il suo approccio, sia in chirurgia cervicale che in quella otologica che in quella neuro-otologica. Gli autori cominciano con il discutere i principi fondamentali dell'embriologia del secondo arco branchiale per aiutare la comprensione dell'anatomia e delle possibili variazioni del tragitto e dei rapporti del nervo faciale. Di seguito è descritta dettagliatamente l'anatomia descrittiva del nervo faciale. Lo studio inizia con la genesi del messaggio nervoso a livello corticale con le afferenze per i nuclei centrali. Viene, poi, descritto il tragitto intracranico del nervo, dal suo prcorso intrapontino al suo tragitto intrapetroso, passando attraverso la sua porzione nell'angolo pontocerebellare. Infine, sono presentate le divisioni intraparotidee precisando i diversi muscoli che innervano. Un punto importante è costituito dai diversi rami nervosi collaterali intra- ed extrapetrosi. Viene spiegata anche l'anatomia funzionale descrivendo le funzioni e i tragitti dei diversi rami collaterali del nervo insieme alle origini e alle terminazioni dei componenti vegetativi, sensitivi e sensoriali del nervo. Infine, un capitolo è dedicato alle variazioni anatomiche del tragitto del nervo la cui conoscenza è indispensabile per limitare i rischi di paralisi facciale iatrogena durante la dissecazione del nervo.



from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2gwzWhM
via IFTTT

Hydroxyl-Group-Dominated Graphite Dots Reshape Laser Desorption/Ionization Mass Spectrometry for Small Biomolecular Analysis and Imaging

ACS Nano

DOI: 10.1021/acsnano.7b05328

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iPPUVc
via IFTTT

High-Speed “4D” Computational Microscopy of Bacterial Surface Motility

ACS Nano

DOI: 10.1021/acsnano.7b04738

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2iPA6lr
via IFTTT

Oregon Woman Suspected of Faking Cancer May Lose License - U.S. News & World Report

KOIN.com

Oregon Woman Suspected of Faking Cancer May Lose License U.S. News & World Report TUALATIN, Ore. (AP) — The Oregon State Board of Nursing may suspend the license of a Tualatin woman suspected of profiting financially by faking a cancer diagnosis. Jenifer Gaskin announced in 2014 that she had been diagnosed with thyroid cancer. Woman suspected of faking cancer may lose nursing licenseKOIN.com all 2 news articles »

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eMYSOu
via IFTTT

Dry Mouth - Doctor NDTV

Dry Mouth Doctor NDTV Dry mouth is the condition of not having enough saliva, or spit, to keep the mouth wet. The dental term "xerostomia" means dryness of the mouth due to a decreased function of the glands that produce saliva. It can cause difficulties in tasting, chewing ...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eNijXv
via IFTTT

Downregulation of GPR155 as a prognostic factor after curative resection of hepatocellular carcinoma

Molecular biomarkers capable of predicting recurrence patterns and prognosis are helpful for risk stratification and providing appropriate treatment to patients with hepatocellular carcinoma (HCC). In this stu...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vyUVaF
via IFTTT

A change in the study evaluation paradigm reveals that larynx preservation compromises survival in T4 laryngeal cancer patients

Larynx preservation (LP) is recommended for up to low-volume T4 laryngeal cancer as an evidence-based treatment option that does not compromise survival. However, a reevaluation of the current literature raise...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wv3aSe
via IFTTT

Down-regulation of miRNA-148a and miRNA-625-3p in colorectal cancer is associated with tumor budding

MiRNAs are often deregulated in colorectal cancer and might function as tumor suppressors or as oncogenes. They participate in controlling key signaling pathways involved in proliferation, invasion and apoptos...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzGdjL
via IFTTT

Effectiveness of PIVKA-II in the detection of hepatocellular carcinoma based on real-world clinical data

Protein Induced by Vitamin K Absence or Antagonist-II (PIVKA-II) is an efficient biomarker specific for hepatocellular carcinoma (HCC). Some researchers have proved that levels of PIVKA-II reflect HCC oncogene...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wuU5sy
via IFTTT

In memoriam: Dr. Robert William McCarley

Dr. Robert William McCarley, Professor of Psychiatry, was a world-renowned leader in the fields of sleep and schizophrenia research, and a past President of the Sleep Research Society. He passed away on May 27th, 2017 at the age of 79. Dr. McCarley's scientific pursuits and contributions have been recognized nationally and internationally. He was the recipient of many prestigious awards throughout his career including the Distinguished Scientist Award and the Mary A. Carskadon Outstanding Educator Award from the Sleep Research Society, the William C.

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2eNfC88
via IFTTT

Computational Sensitivity Investigation of Hydrogel Injection Characteristics for Myocardial Support

Publication date: Available online 1 September 2017
Source:Journal of Biomechanics
Author(s): Hua Wang, Christopher B. Rodell, Madonna E. Lee, Neville N. Dusaj, Joseph H. Gorman, Jason A. Burdick, Robert C. Gorman, Jonathan F. Wenk
Biomaterial injection is a potential new therapy for augmenting ventricular mechanics after myocardial infarction (MI). Recent in vivo studies have demonstrated that hydrogel injections can mitigate the adverse remodeling due to MI. More importantly, the material properties of these injections influence the efficacy of the therapy. The goal of the current study is to explore the interrelated effects of injection stiffness and injection volume on diastolic ventricular wall stress and thickness. To achieve this, finite element models were constructed with different hydrogel injection volumes (150 µL and 300 µL), where the modulus was assessed over a range of 0.1 kPa to 100 kPa (based on experimental measurements). The results indicate that a larger injection volume and higher stiffness reduce diastolic myofiber stress the most, by maintaining the wall thickness during loading. Interestingly, the efficacy begins to taper after the hydrogel injection stiffness reaches a value of 50kPa. This computational approach could be used in the future to evaluate the optimal properties of the hydrogel.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wZybkk
via IFTTT

Alterations of musculoskeletal models for a more accurate estimation of lower limb joint contact forces during normal gait: a systematic review

Publication date: Available online 1 September 2017
Source:Journal of Biomechanics
Author(s): F. Moissenet, L. Modenese, R. Dumas
Musculoskeletal modelling is a methodology used to investigate joint contact forces during a movement. High accuracy in the estimation of the hip or knee joint contact forces can be obtained with subject-specific models. However, construction of subject-specific models remains time consuming and expensive. The purpose of this systematic review of the literature was to identify what alterations can be made on generic (i.e. literature-based, without any subject-specific measurement other than body size and weight) musculoskeletal models to obtain a better estimation of the joint contact forces. The impact of these alterations on the accuracy of the estimated joint contact forces were appraised.The systematic search yielded to 141 articles and 24 papers were included in the review. Different strategies of alterations were found: skeletal and joint model (e.g. number of degrees of freedom, knee alignment), muscle model (e.g. Hill-type muscle parameters, level of muscular redundancy), and optimisation problem (e.g. objective function, design variables, constraints). All these alterations had an impact on joint contact force accuracy but it was not possible to highlight any trend defining which alteration had the largest impact.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wZy7B6
via IFTTT

In-vivo analysis of sternal angle, sternal and sternocostal kinematics in supine humans during breathing.

Publication date: Available online 1 September 2017
Source:Journal of Biomechanics
Author(s): Benoît Beyer, Véronique Feipel, Victor Sholukha, Laurence Chèze, Serge Van Sint Jan.
This paper aims at contributing to the understanding of the combination of in vivo sternum displacement, sternal angle variations and sternocostal joints (SCJ) kinematics of the seven first rib pairs over the inspiratory capacity (IC). Retrospective codified spiral-CT data obtained at total lung capacity (TLC), middle of inspiratory capacity (MIC) and at functional residual capacity (FRC) were used to compute kinematic parameters of the bones and joints of interest in a sample of 12 asymptomatic subjects. 3D models of rib, thoracic vertebra, manubrium and sternum were processed to determine anatomical landmarks (ALs) on each bone. These ALs were used to create local coordinate system and compute spatial transformation of ribs and manubrium relative to sternum, and sternum relative to thoracic vertebra. The rib angular displacements and associated orientation of rotation axes and joint pivot points (JPP), the sternal angle variations and the associated displacement of the sternum relative to vertebra were computed between each breathing pose at the three lung volumes. Results can be summarized as following: 1) sternum cephalic displacement ranged between 17.8 and 19.2 mm over the IC; 2) the sternal angle showed a mean variation of 4.4° ± 2.7° over the IC; 3) ranges of rib rotation relative to sternum decreased gradually with increasing rib level; 4) axes of rotation were similarly oriented at each SCJ; 5) JPP spatial displacements showed less variations at first SCJ compared to levels underneath; 6) linear relation was demonstrated between SCJ ROMs and sternum cephalic displacement over the IC.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xEboHO
via IFTTT

The upper and lower segments of subscapularis muscle have different roles in glenohumeral joint functioning

Publication date: Available online 31 August 2017
Source:Journal of Biomechanics
Author(s): Sangeeta Rathi, Nicholas F. Taylor, Rodney A. Green
Subscapularis muscle is divided into two independent segments, upper and lower (USUB and LSUB), but the role of each segment in glenohumeral functioning is unclear. We compared the electromyographic (EMG) activity of USUB and LSUB during a variety of shoulder movements, with and without an external translation force. Intramuscular electrodes were inserted in USUB and LSUB segments of 20 adults without pathology and EMG activity was measured in stabilization trials (with and without an anterior or posterior directed force at the humerus and isometric rotations) and two shoulder positions (shoulder neutral, abduction). Maximal voluntary isometric contraction (MVIC) trials were performed in abduction, internal and external rotation of the shoulder. In MVIC trials, USUB showed higher activity during internal rotation (p=0.03), whereas LSUB showed higher activity during external rotation (p<0.01). In stabilization trials, the interaction effects were significant for muscle segment×condition (p<0.01), and approached significance for muscle segment×position (p=0.06). In the neutral position, the pattern of activity for LSUB was similar to USUB. In the abducted position the LSUB, unlike USUB, was more active during external rotation (p=0.06) and also showed increased activity in response to the posterior directed force at the humerus (p=0.04). Our results suggest that USUB primarily acts asan agonist for internal rotation. In contrast LSUB was particularly active in external rotation in the abducted position and demonstrated increased EMG activity in response to the posteriorly directed force at the humerus in that position, suggesting more of a role in glenohumeral stabilization.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xEibRM
via IFTTT

Dynamic balance in persons with multiple sclerosis who have a falls history is altered compared to non-fallers and to healthy controls

Publication date: Available online 1 September 2017
Source:Journal of Biomechanics
Author(s): Alexander T. Peebles, Adam P. Bruetsch, Sharon G. Lynch, Jessie M. Huisinga
Around 60% of persons with multiple sclerosis (MS) experience falls, however the dynamic balance differences between those who fall and those who don't are not well understood. The purpose of this study is to identify distinct biomechanical features of dynamic balance during gait that are different between fallers with MS, non-fallers with MS, and healthy controls. 27 recurrent fallers with MS, 28 persons with MS with no falls history, and 27 healthy controls walked on a treadmill at their preferred speed for 3 minutes. The variability of trunk accelerations and the average and variability of minimum toe clearance, spatiotemporal parameters, and margin of stability were compared between groups. Fallers with MS exhibited a slower cautious gait compared to non-fallers and healthy controls, but had decreased anterior-posterior margin of stability and minimum toe clearance. Fallers walked with less locally stable and predictable trunk accelerations, and increased variability of step length, stride time, and both anterior-posterior and mediolateral margin of stability compared to non-fallers and healthy controls. The present work provides 7evidence that within a group of persons with MS, there are gait differences that are influenced by falls history. These differences indicate that in persons with MS who fall, the center of mass is poorly controlled through base of support placement and the foot is closer to the ground during swing phase relative to the non-fallers. These identified biomechanical differences could be used to evaluate dynamic balance in persons with MS and to help improve fall prevention strategies.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wZ1dRa
via IFTTT

Few young cancer survivors are up to date with HPV vaccines - Business Insider

Few young cancer survivors are up to date with HPV vaccines Business Insider HPV infections are the most common sexually transmitted disease in the U.S., and several subtypes of the virus are responsible for cancers of the cervix, vagina, penis, tongue, throat and anus, according to the Centers for Disease Control and Prevention.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wqUazh
via IFTTT

Arizona accuses Insys of fraudulent opioid marketing scheme - Business Insider

ExpressNewsline

Arizona accuses Insys of fraudulent opioid marketing scheme Business Insider The case is the latest to center on Subsys, an under-the-tongue spray intended for cancer patients that contains fentanyl, a highly addictive and regulated synthetic opioid. In December, federal prosecutors in Boston charged six former Insys executives ... Arizona files lawsuit against Chandler-based opioid company, accuses it of fraudulent practicesCronkite News Insys Accused by Arizona of Fraudulent Marketing Scheme with OpioidThe Chronicle of News all 43 news articles »

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wuXOGs
via IFTTT

ASK1 in neurodegeneration

Publication date: Available online 1 September 2017
Source:Advances in Biological Regulation
Author(s): Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Chikako Harada, Takayuki Harada
Neurodegenerative diseases (NDDs) such as glaucoma, multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington's disease (HD) are characterized by the progressive loss of neurons, causing irreversible damage to patients. Longer lifespans may be leading to an increase in the number of people affected by NDDs worldwide. Among the pathways strongly impacting the pathogenesis of NDDs, oxidative stress, a condition that occurs because of an imbalance in oxidant and antioxidant levels, has been known to play a vital role in the pathophysiology of NDDs. One of the molecules activated by oxidative stress is apoptosis signal-regulating kinase 1 (ASK1), which has been shown to play a role in NDDs. ASK1 activation is regulated by multiple steps, including oligomerization, phosphorylation, and protein-protein interactions. In the oxidative stress state, reactive oxygen species (ROS) induce the dissociation of thioredoxin, a protein regulating cellular reduction and oxidation (redox), from the N-terminal region of ASK1, and ASK1 is subsequently activated by the oligomerization and phosphorylation of a critical threonine residue, leading to cell death. Here, we review experimental evidence that links ASK1 signaling with the pathogenesis of several NDDs. We propose that ASK1 may be a new point of therapeutic intervention to prevent or treat NDDs.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wuJA8P
via IFTTT

RasGRP3 controls cell proliferation and migration in papillary thyroid cancer by regulating the Akt-MDM2 pathway

Publication date: 30 October 2017
Source:Gene, Volume 633
Author(s): Wangwang Qiu, Xiaotian Xia, Zhongling Qiu, Minggao Guo, Zhili Yang
Accumulating evidence has shown that Ras guanylnucleotide releasing peptide 3 (RasGRP3) is up-regulated in several distinct cancer types; however, its role in papillary thyroid cancer (PTC) remains unclear. In this study, we demonstrate that RasGRP3 was overexpressed in PTC tissues and cell lines. Downregulation of RasGRP3 using small interfering (si) RNA significantly inhibited PTC cell proliferation and migration in vitro, and tumor growth in vivo, reflecting an oncogenic role of RasGRP3 in PTC. We subsequently identified that the expression of mouse double minute 2 homolog (MDM2) and phosphorylated Akt (p-Akt) was significantly decreased in RasGRP3-downregulated PTC cells. Overexpression of MDM2 attenuated the function of si-RasGRP3. Taken together, our data show that RasGRP3 exerts its oncogenic effect in PTC through Akt-mediated MDM2 activation. RasGRP3 may serve as a potential new therapeutic target for PTC.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzkacL
via IFTTT

Public data mining plus domestic experimental study defined involvement of the old-yet-uncharacterized gene matrix-remodeling associated 7 (MXRA7) in physiopathology of the eye

Publication date: 20 October 2017
Source:Gene, Volume 632
Author(s): Changkai Jia, Feng Zhang, Ying Zhu, Xia Qi, Yiqiang Wang
Matrix-remodeling associated 7 (MXRA7) gene was first reported in 2002 and named so for its co-expression with several genes known to relate with matrix-remodeling. However, not any studies had been intentionally performed to characterize this gene. We started defining the functions of MXRA7 by integrating bioinformatics analysis and experimental study. Data mining of MXRA7 expression in BioGPS, Gene Expression Omnibus and EurExpress platforms highlighted high level expression of Mxra7 in murine ocular tissues. Real-time PCR was employed to measure Mxra7 mRNA in tissues of adult C57BL/6 mice and demonstrated that Mxra7 was preferentially expressed at higher level in retina, corneas and lens than in other tissues. Then the inflammatory corneal neovascularization (CorNV) model and fungal corneal infections were induced in Balb/c mice, and mRNA levels of Mxra7 as well as several matrix-remodeling related genes (Mmp3, Mmp13, Ecm1, Timp1) were monitored with RT-PCR. The results demonstrated a time-dependent Mxra7 under-expression pattern (U-shape curve along timeline), while all other matrix-remodeling related genes manifested an opposite changes pattern (dome-shape curve). When limited data from BioGPS concerning human MXRA7 gene expression in human tissues were looked at, it was found that ocular tissue was also the one expressing highest level of MXRA7. To conclude, integrative assay of MXRA7 gene expression in public databank as well as domestic animal models revealed a selective high expression MXRA7 in murine and human ocular tissues, and its change patterns in two corneal disease models implied that MXRA7 might play a role in pathological processes or diseases involving injury, neovascularization and would healing.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wuHLbL
via IFTTT

Leptin siRNA promotes ovarian granulosa cell apoptosis and affects steroidogenesis by increasing NPY2 receptor expression

Publication date: 30 October 2017
Source:Gene, Volume 633
Author(s): Xiaomeng Ding, Xinxin Kou, Ye Zhang, Xiaoli Zhang, Guomei Cheng, Tianming Jia
Leptin has been found to be involved in the ovarian granulosa cell apoptosis and steroidogenesis. Loss of neuropeptide Y (NPY) can correct the obesity syndrome of mutant mice lacking of leptin (ob/ob). However, the association of NPY and leptin in ovarian granulosa cells and ovarian steroidogenesis has not been investigated. Here, C57BL/6J ob/ob mice and C57BL/6J (control) mice were intraperitoneally injected with PBS, leptin (0.4μg/g bodyweight) or BIIE0246 (NPY2 receptor [NPY2R] antagonist, 30μg/kg bodyweight) every day for 15days. We found that NPY2R mRNA expression in mouse ovary was suppressed by leptin treatment, but increased by leptin deficiency. Leptin or BIIE0246 treatment significantly increased E2, but notably decreased progesterone in both mice. A lower level of E2 and a higher level of progesterone was observed in ob/ob mice than in control mice. Further, we then knocked down leptin expression in human ovarian granulosa cells by siRNA transfection and treated the cells with DMSO or BIIE0246. In vitro experiments confirmed the findings in mice. siLeptin treatment decreased the secretion of E2, anti-Mullerian hormone (AMH), insulin-like growth factor (IGF)-1 and transforming growth factor (TGF)-β, and the cell proliferation, but increased the secretion of progesterone and cell apoptosis. Western blotting analysis of PCNA, Bcl-2 and Bax confirmed the results of cell proliferation and apoptosis. Activation of JAK2 and STAT3 was also suppressed by knocking down leptin. All the effects of siLeptin on ovarian granulosa cells were partially reversed by BIIE0246. In conclusion, knockdown of leptin significantly affected ovarian steroidogenesis and ovarian function through NPY. siLeptin transfection impaired the activation of JAK2/STAT3 and contributed to ovarian granulosa cell apoptosis partially through up-regulating NPY2R expression.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vytQVb
via IFTTT

Farm Exposure in Early Childhood is Associated with a Lower Risk of Severe Respiratory Illnesses

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vz3Poy
via IFTTT

Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen-related apple allergy

SLIT with recombinant Mal d 1 is a promising approach for the effective treatment of birch pollen-related apple allergy.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wuQwCE
via IFTTT

Elevated IgE levels are linked to faster relapse in omalizumab-discontinued chronic spontaneous urticaria patients

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eMOJRZ
via IFTTT

IL-12 and IL-7 synergise to control MAIT cell cytotoxic responses to bacterial infection

The mechanisms controlling the cytotoxic response of MAIT cells to NTHi infection are unknown. Our observations provide a new understanding of protective immune mechanisms and also potential new therapeutic opportunities to improve clinical outcome.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gwHNvP
via IFTTT

Long-term Benefits of Optimal Asthma Control in Pregnancy

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eMOshV
via IFTTT

Enhanced Plasmacytoid Dendritic Cell Antiviral Responses After Omalizumab

Omalizumab enhanced ex vivo antiviral IFNα responses and reduced pDC surface FcεRIα. Both effects were significantly associated with lower asthma exacerbation rate, highlighting a potential mechanism underlying the atopy-virus connection in promoting exacerbations of asthma.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gwHpNT
via IFTTT

Food diversity during the first year of life and allergic diseases until 15 years

Higher food diversity during the first year of life appears to decrease the risk of allergic sensitization to aeroallergens up to 15 years only among children with early skin symptoms in German birth cohort.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eMOCFZ
via IFTTT

Inhibition of IL-17–committed T cells in a murine psoriasis model by a vitamin D analogue

A better understanding of the means by which topical vitamin D analogues exert their therapeutic effect on psoriasis is of theoretical and practical importance.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gxGQUk
via IFTTT

Serum periostin, IgE and SE-IgE can be used as biomarkers to identify moderate to severe chronic rhinosinusitis with nasal polyps

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eMOk1R
via IFTTT

Tips On Writing An Essay

There are various types of composition prompts. As of this web site, you may discover the tips you should imbibe the best way to write the article and a few writing prompts which will help you develop skill. They could be essentially subjective essays. Composing an essay isn't merely collecting the numerous info and not […]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzBJJX
via IFTTT

LSI Keywords for SEO Semantic Indexing (LSI) Discussed

Considering the commanding verb term,"Discuss how," signifies the article must provide a procedure to follow, and it'll have to maintain chronological order consequently. So as to compose a high-quality dissertation article you should be convincing and can prove your claim regardless of what. Effectively answering the question, however, is much more probably after knowing what […]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vyUnl2
via IFTTT

Howto Produce A Focused Composition

You might need to do a bit of research to discover the solution. You'll must select a thesis, or principal idea which you need to prove. The composition needs to be connected to your product or niche. Exactly like in a written composition, you'll need to choose what you would like to explain or claim. […]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzjT9J
via IFTTT

How to Compose a Radio Ad

I simply would like one to know the way much I enjoy your composing support. TopWritingService is here now to offer topnotch exceptional custom writings. Despite the fact that TopWritingService produces inexpensive premiums, the caliber of its providers never undergoes. Regrettably, there are many less-than- sincere publishing services online-which don't value it and don't have […]

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vz3ORw
via IFTTT

Antibodies, Vol. 6, Pages 12: Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality

Antibodies, Vol. 6, Pages 12: Functional, Biophysical, and Structural Characterization of Human IgG1 and IgG4 Fc Variants with Ablated Immune Functionality

Antibodies doi: 10.3390/antib6030012

Authors: Susan Tam Stephen McCarthy Anthony Armstrong Sandeep Somani Sheng-Jiun Wu Xuesong Liu Alexis Gervais Robin Ernst Dorina Saro Rose Decker Jinquan Luo Gary Gilliland Mark Chiu Bernard Scallon

Engineering of fragment crystallizable (Fc) domains of therapeutic immunoglobulin (IgG) antibodies to eliminate their immune effector functions while retaining other Fc characteristics has numerous applications, including blocking antigens on Fc gamma (Fcγ) receptor-expressing immune cells. We previously reported on a human IgG2 variant termed IgG2σ with barely detectable activity in antibody-dependent cellular cytotoxicity, phagocytosis, complement activity, and Fcγ receptor binding assays. Here, we extend that work to IgG1 and IgG4 antibodies, alternative subtypes which may offer advantages over IgG2 antibodies. In several in vitro and in vivo assays, the IgG1σ and IgG4σ variants showed equal or even lower Fc-related activities than the corresponding IgG2σ variant. In particular, IgG1σ and IgG4σ variants demonstrate complete lack of effector function as measured by antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and in vivo T-cell activation. The IgG1σ and IgG4σ variants showed acceptable solubility and stability, and typical human IgG1 pharmacokinetic profiles in human FcRn-transgenic mice and cynomolgus monkeys. In silico T-cell epitope analyses predict a lack of immunogenicity in humans. Finally, crystal structures and simulations of the IgG1σ and IgG4σ Fc domains can explain the lack of Fc-mediated immune functions. These variants show promise for use in those therapeutic antibodies and Fc fusions for which the Fc domain should be immunologically "silent".

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vSgNJm
via IFTTT

Enhancing Multifunctionalities of Transition-Metal Dichalcogenide Monolayers via Cation Intercalation

ACS Nano

DOI: 10.1021/acsnano.7b04880

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wrwISt
via IFTTT

Breast Mass Discovered in 49-Year-Old Patient

A 49-year-old woman develops a mass in her right breast, and a biopsy is obtained. (Source: CancerNetwork)

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vRIUbu
via IFTTT

Oregon woman suspected of faking cancer may lose license - San Francisco Chronicle

KOIN.com

Oregon woman suspected of faking cancer may lose license San Francisco Chronicle Jenifer Gaskin announced in 2014 that she had been diagnosed with thyroid cancer. A friend established a GoFundMe page that brought in more than $10,000. The friend later became suspicious and police could not find proof that Gaskin had been at the ... Woman suspected of faking cancer may lose nursing licenseKOIN.com all 2 news articles »

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2vzrp4F
via IFTTT

Growth curves for intracranial volume in normal Asian children fortify management of craniosynostosis

Craniosynostosis alters the morphology of cranial vault, prevents normal cranial growth, and can elevate intracranial pressure over time. Surgical goals in the event of craniosynostosis are to reduce intracranial pressure and to achieve aesthetic cranial contours, but the timing of such surgery is open to debate. Although excess intracranial pressure must be avoided, premature surgical interventions may necessitate secondary revisions. Also, direct attempts to measure intracranial pressure are invasive by design and thus may not be feasible in every case.

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2xE026Q
via IFTTT

Sponsoring Organizations and Liaisons

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2eMT9YR
via IFTTT

Table of Contents

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2gwuvj1
via IFTTT

Lay preferences for dentogingival esthetic parameters: A systematic review

Publication date: Available online 1 September 2017
Source:The Journal of Prosthetic Dentistry
Author(s): Stefano Del Monte, Kelvin I. Afrashtehfar, Elham Emami, Samer Abi Nader, Faleh Tamimi
Statement of problemAn objective definition of the characteristics that render a smile esthetically acceptable in the eye of laypeople is lacking.PurposeThe purpose of this systematic review was to identify, appraise, and synthesize the available evidence on the opinion of laypeople regarding the dentogingival characteristics that render a smile esthetically acceptable. The evidence was collected by surveying with standardized digitally modified smile images.Material and methodsFour databases were used to search English language studies published between January 1996 and December 2015. This was complemented by a manual search of 8 dental journals. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, 2 independent reviewers extracted the relevant characteristics of lay evaluators, the images evaluated, and the outcomes measure. Included studies were assessed in agreement with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Outcomes were treated as a continuous variable, and when more than 1 article provided information on a parameter, the weighted arithmetic mean was calculated.ResultsAfter 8851 articles were screened, 20 studies were included. Those studies addressed 20 different dentogingival esthetic parameters. The total number of participants interviewed was 3107. According to the Olmos classification, 6 studies had a high level of quality, and 14 studies had a moderate level of quality. The 2 reviewers agreed on all the quality assessments. In the articles reviewed, central incisors clearly played a key role in smile esthetics. Almost all dental, gingival, and occlusal parameters are related to the proportion, shape, and position of central incisors and their relation to the adjacent dental structures.ConclusionsThe present review provides the estimated thresholds of tolerability and ideal values of smile parameters determined by laypeople. This may guide clinicians in evidence-based diagnosis and the planning of dental esthetic treatments.



from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2eN1FHv
via IFTTT

The Essentials

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2gwoaUA
via IFTTT

Editorial Board

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2eMWcjK
via IFTTT

News and Notes

Publication date: September 2017
Source:The Journal of Prosthetic Dentistry, Volume 118, Issue 3





from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2iPMPEv
via IFTTT

Growth curves for intracranial volume in normal Asian children fortify management of craniosynostosis

Craniosynostosis alters the morphology of cranial vault, prevents normal cranial growth, and can elevate intracranial pressure over time. Surgical goals in the event of craniosynostosis are to reduce intracranial pressure and to achieve aesthetic cranial contours, but the timing of such surgery is open to debate. Although excess intracranial pressure must be avoided, premature surgical interventions may necessitate secondary revisions. Also, direct attempts to measure intracranial pressure are invasive by design and thus may not be feasible in every case.

from ! ORL Sfakianakis via paythelady.61 on Inoreader http://ift.tt/2xE026Q
via IFTTT

Increased Vascular Permeability in the Bone Marrow Microenvironment Contributes to Disease Progression and Drug Response in Acute Myeloid Leukemia

Publication date: Available online 1 September 2017
Source:Cancer Cell
Author(s): Diana Passaro, Alessandro Di Tullio, Ander Abarrategi, Kevin Rouault-Pierre, Katie Foster, Linda Ariza-McNaughton, Beatriz Montaner, Probir Chakravarty, Leena Bhaw, Giovanni Diana, François Lassailly, John Gribben, Dominique Bonnet
The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies. Moreover, induction chemotherapy failing to restore normal vasculature was associated with a poor prognosis. Inhibition of NO production reduced vascular permeability, preserved normal hematopoietic stem cell function, and improved treatment response in PDX.

Graphical abstract

Teaser

Passaro et al. show that acute myeloid leukemia, mainly via nitric oxide (NO), causes bone marrow vascular abnormalities and that failure to restore normal vasculature after induction chemotherapy is associated with a poor prognosis. Importantly, inhibition of NO production improves treatment response in vivo.


from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2eqNS8Q
via IFTTT

From Original Antigenic Sin to the Universal Influenza Virus Vaccine

Publication date: Available online 31 August 2017
Source:Trends in Immunology
Author(s): Carole Henry, Anna-Karin E. Palm, Florian Krammer, Patrick C. Wilson
Antibody responses are essential for protection against influenza virus infection. Humans are exposed to a multitude of influenza viruses throughout their lifetime and it is clear that immune history influences the magnitude and quality of the antibody response. The 'original antigenic sin' concept refers to the impact of the first influenza virus variant encounter on lifelong immunity. Although this model has been challenged since its discovery, past exposure, and likely one's first exposure, clearly affects the epitopes targeted in subsequent responses. Understanding how previous exposure to influenza virus shapes antibody responses to vaccination and infection is critical, especially with the prospect of future pandemics and for the effective development of a universal influenza vaccine.



from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2wqXavz
via IFTTT

John Cody launches final album after cancer takes singer's voice - CBC.ca

CBC.ca

John Cody launches final album after cancer takes singer's voice CBC.ca The Montreal-based, Hamilton, Ont.-raised musician was already battling a number of health problems when doctors discovered last spring that cancer had spread from his colon to his larynx. "My first question isn't why me or anything, it's how much time ...

from # All Medicine by Alexandros G. Sfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2gvD7GH
via IFTTT