Δευτέρα 25 Απριλίου 2016

Multipolar force fields and their effects on solvent dynamics around simple solutes.

The performance of multipole (MTP) and point charge (PC) force fields in classical molecular dynamics (MD) simulations of condensed-phase systems for both equilibrium and dynamical quantities is compared. MTP electrostatics provides an improved description of the anisotropic electrostatic potential, which is especially important to describe key, challenging interactions, such as lone pairs, π-interactions, and hydrogen bonds. These chemical environments are probed by focusing on the hydration properties of two molecules: N-methylacetamide and phenyl bromide. Both, equilibrium and dynamical, quantities are affected by the quality of the electrostatic model. The alteration of the first solvation shell in MTP simulations is validated by comparing with lifetimes and correlation times of solute-solvent interactions from experiment. The improved dynamical behavior found in the MTP simulations—observed for molecules parametrized using very different protocols—suggests that a systematic improvement of both equilibrium and dynamical quantities when using MTP electrostatics is possible.

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Coupled protein-ligand dynamics in truncated hemoglobin N from atomistic simulations and transition networks.

The nature of ligand motion in proteins is difficult to characterize directly using experiment. Specifically, it is unclear to what degree these motions are coupled.; All-atom simulations are used to sample ligand motion in truncated Hemoglobin N. A transition network analysis including ligand- and protein-degrees of freedom is used to analyze the microscopic dynamics.; Clustering of two different subsets of MD trajectories highlights the importance of a diverse and exhaustive description to define the macrostates for a ligand-migration network. Monte Carlo simulations on the transition matrices from one particular clustering are able to faithfully capture the atomistic simulations. Contrary to clustering by ligand positions only, including a protein degree of freedom yields considerably improved coarse grained dynamics. Analysis with and without imposing detailed balance agree closely which suggests that the underlying atomistic simulations are converged with respect to sampling transitions between neighboring sites.; Protein and ligand dynamics are not independent from each other and ligand migration through globular proteins is not passive diffusion.; Transition network analysis is a powerful tool to analyze and characterize the microscopic dynamics in complex systems. This article is part of a Special Issue entitled Recent developments of molecular dynamics.

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Kernel density estimation-based solution of the nuclear Schrodinger equation

Solving the time-dependent Schrödinger equation for nuclear motion remains a challenge. Despite novel approaches based on Bohmian mechanics, the long-time stability and generalization to multiple dimensions remains an open question. In the present work a method based on an ensemble of classical particles instead of a wave function is employed to evolve the system. Quantum effects are introduced through forces derived from the quantum potential Q and the necessary derivatives are obtained from a density estimate using kernel density estimation. Application of the procedure to typical 1- and 2-dimensional problems yields good agreement with numerically exact solutions and favourable scaling with the number of particles is found.

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Quantum-Chemistry Based Calibration of the Alkali Metal Cation Series (Li+-Cs+) for Large-Scale Polarizable Molecular Mechanics/Dynamics Simulations

The alkali metal cations in the series Li(+)-Cs(+) act as major partners in a diversity of biological processes and in bioinorganic chemistry. In this article, we present the results of their calibration in the context of the SIBFA polarizable molecular mechanics/dynamics procedure. It relies on quantum-chemistry (QC) energy-decomposition analyses of their monoligated complexes with representative O-, N-, S-, and Se- ligands, performed with the aug-cc-pVTZ(-f) basis set at the Hartree-Fock level. Close agreement with QC is obtained for each individual contribution, even though the calibration involves only a limited set of cation-specific parameters. This agreement is preserved in tests on polyligated complexes with four and six O- ligands, water and formamide, indicating the transferability of the procedure. Preliminary extensions to density functional theory calculations are reported.

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Gesammelte Schriften von Gotteserfahrungen



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Synthesis of New Alkylated Mononucleotide Analogues and Their Repair Proficiency by the Prokaryotic DNA Repair Protein AlkB

We describe the synthesis of a variety of new alkylated mononucleotides and examine their repair proficiency with the prokaryotic direct DNA repair protein AlkB. A comparison of rates of repair among the different substrates supports the currently accepted radical mechanism.

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Rock music and hearing loss - to quote Who singer Roger Daltrey: "We’re all going deaf. We’re all wearing hearing aids"

From the interview:

How’s your hearing?

My hearing’s dreadful. We’re all going deaf. We’re all wearing hearing aids. No it’s true. I suggest to everybody over the age of 50 that have been going to loud concerts for years and years and years, go and have your hearing tested. You’d be surprised what you’re missing. It’s unbelievable. Most people over the age of 60 are lip-reading. (Jokes) And it’s all our fault!

How do you keep your voice in shape?

If you don’t use it, you lose it, simple as that. And too many of our generation they think they’ve made it and they come off the road for four or five years and don’t sing and before they know it the muscles that you need to be there for you, to hit the notes, have disappeared. And you can get them back. But sometimes you leave it too long and it’s gone forever.

How do you keep your famous body in shape?

I do about 20 minutes in the gym these days. Hardly anything. I’m getting lazier and lazier. I do a lot of walking. I love to walk. Five miles a day I average.





References:

Daltrey happy to be on the road again http://buff.ly/1SoUpMs
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Cuticle and subsurface ornamentation of intact plant leaf epidermis under confocal and superresolution microscopy

ABSTRACT

Plant cuticle micromorphology is an invaluable tool in modern ecology and paleoecology. It has expanded our knowledge of systematic relationships among diverse plant groups and can be used to identify fossil plants. Furthermore, fossil plant leaf micromorphology is used for reconstructing past environments, most notably for estimating atmospheric CO2 concentration. Here we outline a new protocol for imaging plant cuticle for archival and paleoecological applications. Traditionally, both modern reference and fossil samples undergo maceration with subsequent imaging via environmental SEM, widefield fluorescence, or light microscopy. In this paper, we demonstrate the capabilities of alternative preparation and imaging methods using confocal and superresolution microscopy with intact leaf samples. This method produces detailed three-dimensional images of surficial and subsurface structures of the intact leaf. Multiple layers are captured simultaneously, which previously required independent maceration and microtome steps. We compared clearing agents (chloral hydrate, KOH, and Visikol); mounting media (Eukitt and Hoyer's); fluorescent stains (periodic acid Schiff, propidium iodide); and confocal vs. superresolution microscopes. We conclude that Eukitt is the best medium for long-term preservation and imaging. Because of nontoxicity and ease of procurement, Visikol made for the best clearing agent. Staining improves contrast and under most circumstances PAS provided the clearest images. Supperresolution produced higher clarity images than traditional confocal, but the information gained was minimal. This new protocol provides the botanical and paleobotanical community an alternative to traditional techniques. Our proposed workflow has the net benefit of being more efficient than traditional methods, which only capture the surface of the plant epidermis. Microsc. Res. Tech., 2016. © 2016 Wiley Periodicals, Inc.



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IJMS, Vol. 17, Pages 619: Glycated Albumin versus Glycated Hemoglobin as a Glycemic Indicator in Diabetic Patients on Peritoneal Dialysis

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Compared with glycated hemoglobin (HbA1c), glycated albumin (GA) is superior in estimating glycemic control in diabetic patients on hemodialysis (HD). However, the better index for assessment of glycemic control in diabetic patients on peritoneal dialysis (PD) and the impact of protein loss on GA are unknown. Twenty diabetic patients on HD were matched by age, sex, and baseline postprandial plasma glucose (PG) levels to 20 PD patients. PG, HbA1c, GA, and serum albumin levels were measured for six months. Protein loss in PD patients was estimated by measuring the protein concentration in the peritoneal dialysate and by 24 h urine collection. Although PG and HbA1c did not differ significantly between the groups, the PD group had significantly lower GA (17.8% versus 20.8%, p < 0.001) and GA/HbA1c ratio (2.95% versus 3.45%, p < 0.0001) than the HD group. Although the PG level correlated significantly with the GA levels in both groups, it was not correlated with the HbA1c levels in both groups. HbA1c level was negatively associated with erythropoiesis-stimulating agent (ESA) dose in both groups, whereas GA was not significantly associated with serum albumin, hemoglobin concentration, ESA dose, and protein loss. Multiple regression analysis identified GA as the only independent factor associated with PG in PD patients. Our results suggested that GA was not significantly associated with protein loss, hemoglobin, serum albumin, and ESA dose. Although GA might underestimate glycemic status, it provided a significantly better measure for estimating glycemic control than HbA1c, even in PD patients.

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IJMS, Vol. 17, Pages 617: New Is Old, and Old Is New: Recent Advances in Antibiotic-Based, Antibiotic-Free and Ethnomedical Treatments against Methicillin-Resistant Staphylococcus aureus Wound Infections

Staphylococcus aureus is the most common pathogen of wound infections. Thus far, methicillin-resistant S. aureus (MRSA) has become the major causative agent in wound infections, especially for nosocomial infections. MRSA infections are seldom eradicated by routine antimicrobial therapies. More concerning, some strains have become resistant to the newest antibiotics of last resort. Furthermore, horizontal transfer of a polymyxin resistance gene, mcr-1, has been identified in Enterobacteriaceae, by which resistance to the last group of antibiotics will likely spread rapidly. The worst-case scenario, “a return to the pre-antibiotic era”, is likely in sight. A perpetual goal for antibiotic research is the discovery of an antibiotic that lacks resistance potential, such as the recent discovery of teixobactin. However, when considering the issue from an ecological and evolutionary standpoint, it is evident that it is insufficient to solve the antibiotic dilemma through the use of antibiotics themselves. In this review, we summarized recent advances in antibiotic-based, antibiotic-free and ethnomedical treatments against MRSA wound infections to identify new clues to solve the antibiotic dilemma. One potential solution is to use ethnomedical drugs topically. Some ethnomedical drugs have been demonstrated to be effective antimicrobials against MRSA. A decline in antibiotic resistance can therefore be expected, as has been demonstrated when antibiotic-free treatments were used to limit the use of antibiotics. It is also anticipated that these drugs will have low resistance potential, although there is only minimal evidence to support this claim to date. More clinical trials and animal tests should be conducted on this topic.

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IJMS, Vol. 17, Pages 615: TNFSF15 Inhibits Blood Retinal Barrier Breakdown Induced by Diabetes

Tumor necrosis factor superfamily 15 (TNFSF15) is an endogenous neovascularization inhibitor and an important negative regulator of vascular homeostasis. This study aimed to explore the potential role of TNFSF15 in diabetic retinopathy. Vitreous TNFSF15 and VEGF levels in proliferative diabetic retinopathy (PDR) patients were detected by ELISA. Retinal expression of TNFSF15 and the content of tight junction proteins (TJPs) in rats were detected by immunohistochemistry and Western blot, respectively. The blood retinal barrier (BRB) permeability was evaluated using Evans Blue (EB) dye. The TNFSF15/VEGF ratio was decreased in the vitreous fluid of patients with PDR relative to the controls, even though the expression levels of TNFSF15 were higher. TNFSF15 was dramatically decreased one month later after diabetes induction (p < 0.001), and then increased three months later and thereafter. TNFSF15 treatment significantly protected the BRB in the diabetic animals. Diabetes decreased TJPs levels in the retina, and these changes were inhibited by TNFSF15 treatment. Moreover, TNFSF15 decreased activation of VEGF both in mRNA and protein levels caused by diabetes. These results indicate that TNFSF15 is an important inhibitor in the progression of DR and suggest that the regulation of TNFSF15 shows promise for the development of diabetic retinopathy treatment strategies.

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quality of care; +22 new citations

22 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2016/04/25

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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Erratum to: Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization?

Erratum to: Significance of endothelial progenitor cells (EPC) for tumorigenesis of head and neck squamous cell carcinoma (HNSCC): possible marker of tumor progression and neovascularization?

Clin Oral Investig. 2016 Apr 23;

Authors: Ziebart T, Blatt S, Günther C, Voelxen N, Pabst A, Sagheb K, Kühl S, Lambrecht T

PMID: 27108343 [PubMed - as supplied by publisher]



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Direct perturbation of neural integrator by bilateral galvanic vestibular stimulation.

Direct perturbation of neural integrator by bilateral galvanic vestibular stimulation.

Med Biol Eng Comput. 2016 Apr 23;

Authors: Hong K, Shim HM, Goh M, Jang SY, Lee S, Kim KS

Abstract
Caloric vestibular stimulation (CVS) and galvanic vestibular stimulation (GVS) act primarily on the peripheral vestibular system. Although the electrical current applied during GVS is thought to flow through peripheral vestibular organs, some current may spread into areas within the central nervous system, particularly when the bilateral galvanic vestibular stimulation (bGVS) method is used. According to Alexander's law, the magnitude of nystagmus increases with eccentric gaze movement, due to the function of the neural integrator (NI); thus, if the information for vestibular stimulation corresponds to Alexander's law, the peripheral vestibular organ is stimulated. Therefore, it would appear that if CVS results comply with Alexander's law, and bGVS results do not, the sites stimulated by bGVS are not perfectly located in the peripheral vestibular area. In our experiments on normal human subjects, the magnitude of nystagmus under CVS increased with rising gaze eccentricity in the direction that the magnitude of the nystagmus increases, and this change was found to follow Alexander's law. However, in the case of nystagmus under bGVS, results did not follow Alexander's law. In addition, study of the influences of bGVS at different current intensities on nystagmus magnitude showed that bGVS at 5 mA distorted nystagmus magnitude more than at 3 mA, which suggests bGVS acts not only on the peripheral vestibular nerves, but also on some areas of the central nervous system, particularly the NI. According to our experiments, bGVS directly affects neural integrator function.

PMID: 27108289 [PubMed - as supplied by publisher]



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Integrin αvβ3 Expression in Tongue Squamous Carcinoma Cells Cal27 Confers Anticancer Drug Resistance Through Loss of pSrc(Y418).

Integrin αvβ3 Expression in Tongue Squamous Carcinoma Cells Cal27 Confers Anticancer Drug Resistance Through Loss of pSrc(Y418).

Biochim Biophys Acta. 2016 Apr 20;

Authors: Stojanović N, Brozovic A, Majhen D, Bosnar MH, Fritz G, Osmak M, Ambriović-Ristov A

Abstract
Integrins play key roles in the regulation of tumor cell adhesion, migration, invasion and sensitivity to anticancer drugs. In the present study we investigate the mechanism of resistance of tongue squamous carcinoma cells Cal27 with de novo integrin αvβ3 expression to anticancer drugs. Cal27-derived cell clones, obtained by transfection of plasmid containing integrin subunit β3 cDNA, as compared to control cells demonstrate: expression of integrin αvβ3; increased expression of integrin αvβ5; increased adhesion to fibronectin and vitronectin; resistance to cisplatin, mitomycin C, doxorubicin and 5-fluorouracil; increased migration and invasion, increased amount of integrin-linked kinase (ILK) and decreased amounts of non-receptor tyrosine kinase (Src) and pSrc(Y418). Knockdown of ILK and integrin β5 in cells expressing integrin αvβ3 ruled out their involvement in drug resistance. Opposite, Src knockdown in Cal27 cells which led to a reduction in pSrc(Y418), as well as treatment with the pSrc(Y418) inhibitors dasatinib and PP2, conferred resistance to all four anticancer drugs, indicating that the loss of pSrc(Y418) is responsible for the observed effect. We identified differential integrin signaling between Cal27 and integrin αvβ3-expressing cells. In Cal27 cells integrin αv heterodimers signal through pSrc(Y418) while this is not the case in integrin αvβ3-expressing cells. Finally, we show that dasatinib counteracts the effect of cisplatin in two additional head and neck squamous cell carcinoma (HNSCC) cell lines Cal33 and Detroit562. Our results suggest that pSrc(Y418) inhibitors, potential drugs for cancer therapy, may reduce therapeutic efficacy if combined with chemotherapeutics, and might not be recommended for HNSCC treatment.

PMID: 27108184 [PubMed - as supplied by publisher]



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International Pediatric ORL Group (IPOG) laryngomalacia consensus recommendations.

International Pediatric ORL Group (IPOG) laryngomalacia consensus recommendations.

Int J Pediatr Otorhinolaryngol. 2016 Apr 7;

Authors: Carter J, Rahbar R, Brigger M, Chan K, Cheng A, Daniel SJ, De Alarcon A, Garabedian N, Hart C, Hartnick C, Jacobs I, Liming B, Nicollas R, Pransky S, Richter G, Russell J, Rutter MJ, Schilder A, Smith RJ, Strychowsky J, Ward R, Watters K, Wyatt M, Zalzal G, Zur K, Thompson D

Abstract
OBJECTIVE: To provide recommendations for the comprehensive management of young infants who present with signs or symptoms concerning for laryngomalacia.
METHODS: Expert opinion by the members of the International Pediatric Otolaryngology Group (IPOG).
RESULTS: Consensus recommendations include initial care and triage recommendations for health care providers who commonly evaluate young infants with noisy breathing. The consensus statement also provides comprehensive care recommendations for otolaryngologists who manage young infants with laryngomalacia including: evaluation and treatment considerations for commonly debated issues in laryngomalacia, initial work-up of infants presenting with inspiratory stridor, treatment recommendations based on disease severity, management of the infant with feeding difficulties, post-surgical treatment management recommendations, and suggestions for acid suppression therapy.
CONCLUSION: Laryngomalacia care consensus recommendations are aimed at improving patient-centered care in infants with laryngomalacia.

PMID: 27107728 [PubMed - as supplied by publisher]



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[Acantholytic squamous cell carcinoma of larynx as an uncommon variant of squamous cell carcinoma].

[Acantholytic squamous cell carcinoma of larynx as an uncommon variant of squamous cell carcinoma].

Kulak Burun Bogaz Ihtis Derg. 2016 May-Jun;26(3):176-80

Authors: Tiken EE, Çolpan Öksüz D, Batur Ş, Uzel EK, Öz B, Öz F, Uzel Ö, Turkan S

Abstract
Acantholytic squamous cell carcinoma is an uncommon variant of squamous cell carcinoma. Acantholytic squamous cell carcinoma occurs in the sun-exposed areas of the skin and lip. It is rarely observed in the respiratory and digestive tract and may present more aggressively. The incidence of distant metastases of squamous cell head and neck cancers is low and the lungs are the most common metastatic sites. Metastasis to the soft tissue, skin, and adrenal glands from the laryngeal region is very uncommon. In this article, we report a 58-year-old female case who underwent postoperative radiation therapy with the diagnosis of acantholytic squamous cell carcinoma of the larynx and developed metastasis to the soft tissue and adrenal gland at the early period.

PMID: 27107606 [PubMed - as supplied by publisher]



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Pectoralis major myofascial interposition flap prevents postoperative pharyngocutaneous fistula in salvage total laryngectomy.

Pectoralis major myofascial interposition flap prevents postoperative pharyngocutaneous fistula in salvage total laryngectomy.

Eur Arch Otorhinolaryngol. 2016 Apr 23;

Authors: Anschütz L, Nisa L, Elicin O, Bojaxhiu B, Caversaccio M, Giger R

Abstract
Pharyngocutaneous fistula (PCF) is the most cumbersome complication after salvage total laryngectomy (STL) in patients who have been previously irradiated for laryngeal or hypopharyngeal cancer. To assess the fistula rate, risk factors and effects of primary closure with and without pectoralis major myofascial interposition flap (PMMIF) on fistula formation, we conducted a retrospective review. We identified 48 patients from 2004 to 2013 who underwent STL after failure of primary curative (chemo)radiotherapy in laryngeal or hypopharyngeal cancer. Details of risk factors for PCF formation, other postoperative complications and general outcome data were analyzed. Ten (20.8 %) out of 48 patients underwent STL with PMMIF closure. Patient and tumor features were not different between the groups with or without PMMIF closure. PCF rates were 0 and 42.1 % in patients with and without PMMIF, respectively (p = 0.002). Other operative complications were similar. We identified prior neck irradiation to be a risk factor for fistula formation (p = 0.04). Patients without PCF had a statistically significant reduction of average hospital stay (20 vs. 56 days; p = 0.001). Analysis of fistula management revealed 50 % of PCF to be closed secondarily by a pectoralis major myocutaneous flap. Over one-third of fistulae persisted despite attempted surgical closure in some cases. PMMIF is useful to prevent PCF in STL following (chemo)radiotherapy. Neck irradiation during primary treatment is a risk factor for PCF formation.

PMID: 27107580 [PubMed - as supplied by publisher]



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Mandibular melanotic neuroectodermal tumor of infancy: a role for neoadjuvant chemotherapy.

Mandibular melanotic neuroectodermal tumor of infancy: a role for neoadjuvant chemotherapy.

Eur Arch Otorhinolaryngol. 2016 Apr 23;

Authors: Maroun C, Khalifeh I, Alam E, Akl PA, Saab R, Moukarbel RV

Abstract
Melanotic Neuroectodermal Tumor of Infancy (MNTI) is a rare, locally aggressive neoplasm with a predilection for the head and neck area, most commonly occurring in the maxilla. The vast majority of treatment modalities for all cases of MNTI to date have involved surgical intervention only, with just 9.6 % involving some sort of chemotherapy, radiotherapy, or a combination of the prior mentioned modalities. There is very limited information available regarding the use of neoadjuvant chemotherapy, due to its rare nature. In this report, a 4 month old girl presented to our clinic with a chief complaint of a large oral mass of about 2.5 months in duration. Intraoral examination showed an oral mass arising from the lingual aspect of inferior alveolar ridge with extensive mandibular invasion. The patient received three cycles of vincristine, Adriamycin, and cyclophosphamide as neodajuvant therapy. Upon completion, the tumor had decreased significantly in size. The patient was then scheduled for surgery and underwent surgical resection of the tumor. We were able to obtain adequate shrinkage of the tumor to allow better resectability, easier surgical access and a more minimally invasive approach with no lip split and a smaller neck incision. In conclusion, we have reported an extremely rare case of MNTI of the mandible that was successfully treated with neoadjuvant chemotherapy and surgical resection. This approach was advantageous to minimize the chance of recurrence and improve resectability in particularly large tumors, while maximizing functional outcomes and minimizing deformity.

PMID: 27107579 [PubMed - as supplied by publisher]



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Dieci cose che fanno bene al tuo seno - Glamour.it


Glamour.it

Dieci cose che fanno bene al tuo seno
Glamour.it
Progetti un'estate all'insegna di micro bikini scollature audaci, nude look? O vuoi semplicemente prenderti cura al meglio della tua femminilità? Ecco tutto quello che c'è da sapere per assicurarsi un decolleté sano, ben curato e ad alto tasso di fascino!



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Post-transcriptional control of the mammalian circadian clock: implications for health and disease.

Post-transcriptional control of the mammalian circadian clock: implications for health and disease.

Pflugers Arch. 2016 Apr 23;

Authors: Preußner M, Heyd F

Abstract
Many aspects of human physiology and behavior display rhythmicity with a period of approximately 24 h. Rhythmic changes are controlled by an endogenous time keeper, the circadian clock, and include sleep-wake cycles, physical and mental performance capability, blood pressure, and body temperature. Consequently, many diseases, such as metabolic, sleep, autoimmune and mental disorders and cancer, are connected to the circadian rhythm. The development of therapies that take circadian biology into account is thus a promising strategy to improve treatments of diverse disorders, ranging from allergic syndromes to cancer. Circadian alteration of body functions and behavior are, at the molecular level, controlled and mediated by widespread changes in gene expression that happen in anticipation of predictably changing requirements during the day. At the core of the molecular clockwork is a well-studied transcription-translation negative feedback loop. However, evidence is emerging that additional post-transcriptional, RNA-based mechanisms are required to maintain proper clock function. Here, we will discuss recent work implicating regulated mRNA stability, translation and alternative splicing in the control of the mammalian circadian clock, and its role in health and disease.

PMID: 27108448 [PubMed - as supplied by publisher]



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Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically.

Obstructive sleep apnea and Fuhrman grade in patients with clear cell renal cell carcinoma treated surgically.

World J Urol. 2016 Apr 23;

Authors: Vilaseca A, Nguyen DP, Vertosick EA, Corradi RB, Musquera M, Pérez M, Fossati N, Sjoberg DD, Farré R, Almendros I, Montserrat JM, Benfante NE, Hakimi AA, Skanderup AJ, Russo P, Alcaraz A, Touijer KA

Abstract
PURPOSE: To assess the association between obstructive sleep apnea (OSA) and Fuhrman grade in patients with clear cell renal cell carcinoma (ccRCC). As secondary endpoints, we studied its association with tumor size, metastasis-free survival (MFS) and cancer-specific survival (CSS).
METHODS: We reviewed the databases of two tertiary care centers, identifying 2579 patients who underwent partial or radical nephrectomy for ccRCC between 1991 and 2014. Descriptive statistics were used to compare pathologic variables between patients with and without OSA. Linear and logistic regression models were used to assess the association of OSA with Fuhrman grade and tumor size. A Cox proportional hazards model was used to determine OSA association with MFS and CSS. A pathway analysis was performed on a cohort with available gene expression data.
RESULTS: In total, 172 patients (7 %) had self-reported OSA at diagnosis. More patients with OSA had high Fuhrman grade compared to those without OSA [51 vs. 38 %; 13 % risk difference; 95 % confidence interval (CI), 5-20 %; p = 0.003]. On multivariable analysis, the association remained significant (OR 1.41; 95 % CI 1.00-1.99; p = 0.048). OSA was not associated with tumor size (p > 0.5), MFS (p = 0.5) or CSS (p = 0.4). A trend toward vascular endothelial growth factor pathway enrichment was seen in OSA patients (p = 0.08).
CONCLUSIONS: OSA is associated with high Fuhrman grade in patients undergoing surgery for ccRCC. Pending validation of this novel finding in further prospective studies, it could help shape future research to better understand etiological mechanisms associated.

PMID: 27108420 [PubMed - as supplied by publisher]



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The impact of dexamethasone and prednisone on sleep in children with acute lymphoblastic leukemia.

The impact of dexamethasone and prednisone on sleep in children with acute lymphoblastic leukemia.

Support Care Cancer. 2016 Apr 23;

Authors: Daniel LC, Li Y, Kloss JD, Reilly AF, Barakat LP

Abstract
PURPOSE: Corticosteroids can affect sleep patterns, mood, and behavior. Two of the most commonly prescribed corticosteroids in acute lymphoblastic leukemia (ALL), dexamethasone and prednisone, may impact sleep differently, but no research has compared these medications in children. The current study tested the hypothesis that dexamethasone and prednisone differentially affect sleep in children with ALL to understand how these medications contribute to health-related quality of life (HRQL).
METHODS: Parents of 81 children 3-12 years old in maintenance therapy for ALL completed a baseline measure of child sleep (dexamethasone n = 55, prednisone n = 26), and 61 parents returned 28 days of child sleep diaries starting the first day of a 5-day steroid course (dexamethasone n = 43, prednisone n = 18). Parents also completed measures of HRQL and fatigue on the last day of steroids and the last day of the month.
RESULTS: At baseline, parents reported more sleep disturbances in children taking dexamethasone than prednisone. Across the month, children taking dexamethasone experienced poorer sleep quality compared to children taking prednisone. During corticosteroid treatment, children taking dexamethasone also experienced more night awakenings than children taking prednisone. Sleep variables accounted for almost half of the variance in HRQL during time off steroids and also significantly contributed to fatigue during the corticosteroids course and time off corticosteroids.
CONCLUSIONS: Sleep is an essential component of HRQL in children taking corticosteroids, and the impact on sleep is more pronounced in children taking dexamethasone compared to prednisone. Screening for sleep disturbances and offering brief interventions to manage steroid-related sleep disruptions may improve HRQL.

PMID: 27108263 [PubMed - as supplied by publisher]



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Stem Cell Factor (SCF) is a putative biomarker of antidepressant response.

Stem Cell Factor (SCF) is a putative biomarker of antidepressant response.

J Neuroimmune Pharmacol. 2016 Apr 23;

Authors: Benedetti F, Poletti S, Hoogenboezem TA, Locatelli C, Ambrée O, de Wit H, Wijkhuijs AJ, Mazza E, Bulgarelli C, Vai B, Colombo C, Smeraldi E, Arolt V, Drexhage HA

Abstract
Growth factors involved in neurogenesis and neuroplasticity could play a role in biological processes that drive depression recovery. Combined total sleep deprivation and morning light therapy (TSD + LT) can acutely reverse depressive symptoms, thus allowing to investigate the neurobiological correlates of antidepressant response. We tested if changes on plasma levels of Brain Derived Neurotrophic Factor (BDNF), S100 calcium binding protein B (S100-B), Stem Cell Factor (SCF), Insulin-like Growth Factor-Binding Protein 2 (IGFBP-2), Epidermal Growth Factor (EGF), Platelet-Derived Growth Factor-BB (PDGF-BB), and Vascular Endothelial Growth Factor (VEGF) are associated with response to TSD + LT in 26 inpatients affected by a major depressive episode in the course of bipolar disorder. Regional grey matter (GM) volumes were assessed at baseline, and BOLD fMRI neural responses to a moral valence decision task were recorded before and after treatment. 61.5 % of patients responded to treatment. SCF plasma levels increased significantly more in responders, and correlated with GM volumes in frontal and parietal cortical areas. The pattern of change of SCF also associated with both GM volumes and changes of BOLD fMRI neural responses in the anterior cingulate and medial prefrontal cortex. SCF is both a hematopoietic growth factor and a neurotrophic factor, involved in neuron-neuron and neuron-(micro) glia interactions, fostering neuronal growth and an anti-inflammatory milieu. We correlated SCF levels with antidepressant response and with functional and structural MRI measures in cortical areas that are involved in the cognitive generation and control of affect. SCF may be a candidate growth factor that contributes to neurotrophic and immune effects that are involved in the process of remission/recovery from depression.

PMID: 27108110 [PubMed - as supplied by publisher]



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[Prevalence and initial management of overactive bladder in France: A cross-sectional study].

[Prevalence and initial management of overactive bladder in France: A cross-sectional study].

Prog Urol. 2016 Apr 20;

Authors: Cornu JN, Amarenco G, Bruyere F, Chartier-Kastler E, Fatton B, Grise P, Haab F, Bourouina R

Abstract
AIMS: To determine the prevalence of overactive bladder (OAB) syndrome in France and gather data about initial patient trajectories in the healthcare system.
METHODS: A dedicated questionnaire (41 questions) has been sent to a 12,000 sample of people representative of the global population. The following data were investigated: social and demographic features, medical history, Urinary Symptom Profile questionnaire, bother, history of symptoms, care seeking and treatments received. Patient were considered having OAB in case if presenting at least two episodes of urgency per week, or being under treatment of OAB. OAB prevalence was the main outcome, and associated factors were characterized by univariate and multivariate analysis.
RESULTS: Based on 8842 available questionnaires, the global prevalence of OAB was estimated to be 14.4%. Prevalence was significantly higher in women, older age groups, as well as obesity, irritable bowel syndrome, urinary tract infections, enuresia, constipation, anxiety/depression, neurological diseases, sleep apnea syndrome, asthma, chronic obstructive pulmonary disease, diabetes and hypertension. Only 34.6% of patients with OAB had visited a health practitioner for this problem. General practitioners were most frequently implicated in patient primary care and evaluation. Seventy-two percent of patients with OAB had had additional investigations (mostly a urine culture) and only 6% of patients had to complete a bladder diary. The most frequent treatment option was oral antimuscarinics. Physical therapy and rehabilitation have been prescribed in 26% of cases, as well as dietary advice.
CONCLUSIONS: OAB is a frequent syndrome. Its prevalence increases with age, and OAB frequently concern elderly frail people with many other associated diseases.
LEVEL OF EVIDENCE: 3.

PMID: 27108102 [PubMed - as supplied by publisher]



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Postoperative Analgesia in a Prolonged Continuous Interscalene Block Versus Single-Shot Block in Outpatient Arthroscopic Rotator Cuff Repair: A Prospective Randomized Study.

Postoperative Analgesia in a Prolonged Continuous Interscalene Block Versus Single-Shot Block in Outpatient Arthroscopic Rotator Cuff Repair: A Prospective Randomized Study.

Arthroscopy. 2016 Apr 20;

Authors: Malik T, Mass D, Cohn S

Abstract
PURPOSE: To compare the analgesic efficacy of 3-day continuous interscalene brachial plexus block versus a single-shot block for arthroscopic rotator cuff repair.
METHODS: Eighty-five patients scheduled for arthroscopic rotator cuff repair were randomly assigned to either the single-shot group (SSG) or continuous interscalene brachial block group (CG). Patients in the SSG received 2.5 mg/kg of 0.5% bupivacaine up to 25 mL; the CG received the same dose as a loading dose via catheter followed by an infusion of 0.125% bupivacaine at 5 mL/h and a patient-controlled bolus of 5 mL hourly for 72 hours. Follow-up after discharge was with telephone calls over the next 3 days. Pain was measured on a visual analog scale. Also measured were sleep disturbance, number of opioid doses taken, adverse effects, and level of patient satisfaction.
RESULTS: The median rest pain scores on the 3 days of follow-up measured on a scale of 0 to 10 (with 10 equal to greatest pain) were 0, 0, and 3 in the CG compared with 4, 4, and 3 in the SSG (P < .001) for days 1, 2, and 3, respectively. The median maximum scores were 2, 2, and 4 in the CG compared with 8, 7, and 6 in the SSG (P < .001) for the same time period.
CONCLUSION: A 3-day continuous interscalene brachial plexus block provides better analgesia than a single-shot block. Sleep patterns were better, and less opioid was needed after arthroscopic rotator cuff repair in patients given a continuous plexus block.
LEVEL OF EVIDENCE: Level I, prospective randomized study.

PMID: 27107906 [PubMed - as supplied by publisher]



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JCM, Vol. 5, Pages 49: Treatment of Established Status Epilepticus

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.

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Weltanschauung als Erzählkultur. Zur Konstruktion von Religion und Sozialismus in Staatsbürgerkundeschulbüchern der DDR

Die Dissertation Weltanschauung als Erzählkultur untersucht das Verhältnis von Religion und Sozialismus in Staatsbürgerkundebüchern der DDR. Besondere Bedeutung erhält dabei die Frage nach der Rolle von Erzählungen für die Konstruktion einer sozialistischen Erinnerungskultur: Welche Geschichten wurden in den Lehrbüchern einer sich als nicht religiös verstehenden Moral und Ethik erzählt, um diese zu begründen und zu illustrieren? Das Schulbuch spiegelt sowohl das offiziell genehmigte Wissen über Weltanschauung als auch die Strategien, mit denen der Sozialismus grundlegend als Weltanschauung entworfen werden sollte. Die Umsetzung dieses Anliegens wird in zwei Schritten nachvollzogen: Was wurde als sozialistische Weltanschauung präsentiert (Inhalt)? Wie wurde es präsentiert (Form)? Wie die Untersuchung der Form aufzeigt, sollte die ,Wirksamkeit’ des Sozialismus über Arbeiterheldengeschichten, die Schilderung selbstlosen Handelns einfacher Bürger zum Wohl des Sozialismus oder Geschichten von lebenslangen Freundschaften belegt werden. Literarischen Texteinschüben kam eine Sonderrolle zu. Sie sollten zeigen, dass Sozialismus einen eigenen Wert bildet, der auf den Menschen zurückwirkt. Literatur wurde zur Wirklichkeitsaussage, die die Erfahrungs-, Erinnerungs- und Redehoheit über den Sozialismus erhielt.Die sozialistische Erinnerungskultur war als Erzählkultur gestaltet, in der die persönliche Erlebbarkeit und Wirksamkeit des Sozialismus über Geschichten und damit über fiktionale Textstrukturen bezeugt werden sollte. Dass diese Strukturen bisweilen als religiös interpretiert wurden, zeigt die wissenschaftliche Debatte überSozialismus als Religion. Die Untersuchung bezieht hier klar Stellung: Aus religionswissenschaftlicher Perspektive stellt sich die Frage, ob Sozialismus ,tatsächlich’ eine Religion sei, so nicht. Narrative Muster wie jenes der erlebnisbasierten charakterlichen Wandlung sagen zunächst nichts über Inhalte aus. Ihre Struktur ist nicht per se religiös, sondern narrativ: Sie laden den Leser zur Bedeutungsgebung ein.

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Rationalismus ist nicht alles. Rezension zu Johannes Fischer: Verstehen statt Begründen. Warum es in der Ethik um mehr als nur um Handlungen geht. Stuttgart 2012.



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Erratum to: Informed consent, and an ethico-legal framework for paediatric observational research and biobanking: the experience of an Italian birth cohort study



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Cells, Vol. 5, Pages 20: Role of Intermediate Filaments in Vesicular Traffic

Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, such as the organization of microtubules and microfilaments, the regulation of nuclear structure and activity, the control of cell cycle and the regulation of signal transduction pathways. Furthermore, a number of intermediate filament proteins have been involved in the acquisition of tumorigenic properties. Over the last years, a strong involvement of intermediate filament proteins in the regulation of several aspects of intracellular trafficking has strongly emerged. Here, we review the functions of intermediate filaments proteins focusing mainly on the recent knowledge gained from the discovery that intermediate filaments associate with key proteins of the vesicular membrane transport machinery. In particular, we analyze the current understanding of the contribution of intermediate filaments to the endocytic pathway.

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Watch Dr Enrique Ocio describing novel agents before and after stem cell transplantation for myeloma: https://t.co/soVVWyBVij

Watch Dr Enrique Ocio describing novel agents before and after stem cell transplantation for myeloma: https://t.co/soVVWyBVij

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Biosensors, Vol. 6, Pages 18: Current-Induced Transistor Sensorics with Electrogenic Cells

The concepts of transistor recording of electroactive cells are considered, when the response is determined by a current-induced voltage in the electrolyte due to cellular activity. The relationship to traditional transistor recording, with an interface-induced response due to interactions with the open gate oxide, is addressed. For the geometry of a cell-substrate junction, the theory of a planar core-coat conductor is described with a one-compartment approximation. The fast electrical relaxation of the junction and the slow change of ion concentrations are pointed out. On that basis, various recording situations are considered and documented by experiments. For voltage-gated ion channels under voltage clamp, the effects of a changing extracellular ion concentration and the enhancement/depletion of ion conductances in the adherent membrane are addressed. Inhomogeneous ion conductances are crucial for transistor recording of neuronal action potentials. For a propagating action potential, the effects of an axon-substrate junction and the surrounding volume conductor are distinguished. Finally, a receptor-transistor-sensor is described, where the inhomogeneity of a ligand–activated ion conductance is achieved by diffusion of the agonist and inactivation of the conductance. Problems with regard to a development of reliable biosensors are mentioned.

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Viruses, Vol. 8, Pages 107: Development of a Triple-Color Pseudovirion-Based Assay to Detect Neutralizing Antibodies against Human Papillomavirus

Pseudovirion-based neutralization assay is considered the gold standard method for evaluating the immune response to human papillomavirus (HPV) vaccines. In this study, we developed a multicolor neutralization assay to simultaneously detect the neutralizing antibodies against different HPV types. FluoroSpot was used to interpret the fluorescent protein expression instead of flow cytometry. The results of FluoroSpot and flow cytometry showed good consistency, with R2 > 0.98 for the log-transformed IC50 values. Regardless of the reporter color, the single-, dual-, and triple-color neutralization assays reported identical results for the same samples. In low-titer samples from naturally HPV-infected individuals, there was strong agreement between the single- and triple-color assays, with kappa scores of 0.92, 0.89, and 0.96 for HPV16, HPV18, and HPV58, respectively. Good reproducibility was observed for the triple-color assay, with coefficients of variation of 2.0%–41.5% within the assays and 8.3%–36.2% between the assays. Three triple-color systems, HPV16-18-58, HPV6-33-45, and HPV11-31-52, were developed that could evaluate the immunogenicity of a nonavalent vaccine in three rounds of the assay. With the advantages of an easy-to-use procedure and less sample consumption, the multiple-color assay is more suitable than classical assays for large sero-epidemiological studies and clinical trials and is more amenable to automation.

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Viruses, Vol. 8, Pages 117: Glutamic Acid Residues in HIV-1 p6 Regulate Virus Budding and Membrane Association of Gag

The HIV-1 Gag p6 protein regulates the final abscission step of nascent virions from the cell membrane by the action of its two late (l-) domains, which recruit Tsg101 and ALIX, components of the ESCRT system. Even though p6 consists of only 52 amino acids, it is encoded by one of the most polymorphic regions of the HIV-1 gag gene and undergoes various posttranslational modifications including sumoylation, ubiquitination, and phosphorylation. In addition, it mediates the incorporation of the HIV-1 accessory protein Vpr into budding virions. Despite its small size, p6 exhibits an unusually high charge density. In this study, we show that mutation of the conserved glutamic acids within p6 increases the membrane association of Pr55 Gag followed by enhanced polyubiquitination and MHC-I antigen presentation of Gag-derived epitopes, possibly due to prolonged exposure to membrane bound E3 ligases. The replication capacity of the total glutamic acid mutant E0A was almost completely impaired, which was accompanied by defective virus release that could not be rescued by ALIX overexpression. Altogether, our data indicate that the glutamic acids within p6 contribute to the late steps of viral replication and may contribute to the interaction of Gag with the plasma membrane.

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Clinical relevance of molecular diagnosis in pet allergy

Abstract

We describe the pattern of sensitisation to pet IgE components and its association with clinical symptoms.

159 consecutive patients with rhinitis/asthma sensitised to dog, cat, and horse were recruited. Specific IgE to whole extracts and to pet recombinant allergens were performed. Only 5% of patients were monosensitised to animal allergens.

Specific IgE to Can f 1 was significantly associated with persistent rhinitis, Can f 2 with asthma diagnosis, Can f 3 with moderate/severe rhinitis (M/S-R) and asthma diagnosis (AD), and Can f 5 with persistent and M/S-R. Positive IgE to Fel d 2 was significantly associated with M/S-R and AD, Equ c 1 with M/S-R and Equ c 3 with persistent rhinitis, AD and severe asthma. Sensitisation to ≥2 molecules or to pet albumins was associated with more severe respiratory symptoms. Molecular diagnosis in patients with pet allergy may also help clinicians to predict clinical symptoms and their severity.

This article is protected by copyright. All rights reserved.



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Acupuncture for Dyspnea in Lung Cancer: Results of a Feasibility Trial

Purpose. Dyspnea is a common and distressing symptom for patients with lung cancer (LC) because of disease burden, therapy toxicity, and comorbid illnesses. Acupuncture is a centuries-old therapy with biological plausibility for relief of dyspnea in this setting. This pilot study aimed to evaluate the feasibility and preliminary effectiveness of acupuncture for dyspnea among patients with LC. Methods. Eligible patients had a diagnosis of LC and clinically significant dyspnea without a clear organic cause. The treatment consisted of 10 weekly acupuncture sessions, with a follow-up visit 4 weeks after therapy. The primary outcome was dyspnea severity as measured using a validated Numerical Rating Scale (NRS) of 0 to 10 (10 being "most severe shortness of breath imaginable"). Results. We enrolled 12 patients in the study. The median age was 64.5 years; 66.7% of the patients were female, and 66.7% were Caucasians. Among those enrolled, 10 (83.3%) were able to complete all 10 acupuncture sessions. Acupuncture was well tolerated; adverse events were mild and self-limited. Mean (SD) dyspnea scores on the NRS improved from 6.3 (1.7) at baseline to 3.6 (1.9; P = .003) at the end of treatment and 3.2 (2.3; P = .008) at follow-up. Fatigue and quality of life also improved significantly with acupuncture (P < .05). Conclusion. Among patients with LC, acupuncture was well tolerated and exhibited promising preliminary beneficial effects in the treatment of dyspnea, fatigue, and quality of life. Performing a trial in this population appears feasible.



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A looming water crisis demands creative thinking

Water may look like a local resource but is actually a global commons that requires a joined-up plan to distribute fairly

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Die Medien der Religion

Das Verhältnis von Religion und Medien ist eines der zentralen Probleme der Religionsgeschichte. Wie schon in früheren Zeiten, aber vermehrt im beginnenden 21. Jahrhundert wird der gesellschaftliche Diskurs über Religion insgesamt durch Massenmedien geprägt und gestaltet. Der Band versammelt Sondierungen von Religionswissenschaftlerinnen und Religionswissenschaftlern in diesem innovativen Forschungsfeld anlässlich einer Tagung der Schweizerischen Gesellschaft für Religionswissenschaft im Jahr 2009. Die untersuchten Medien reichen vom Geld über Printmedien und Kleidung bis hin zu Comics und Internet.

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...und schuf sie als Mann und Frau. Ethische Herausforderungen transidenter Individualität aus theologischer Perspektive

Die christliche Theologie, insbesondere die systematische, hat größere Schwierigkeitendamit, sich dem Phänomen Trans*identität zu nähern. Das zeigt sich schon daran, dass zwar Debatten über lesbische, schwule und queere Menschen im Allgemeinen geführt werden, die deutschsprachige protestantische Theologie transidente Individuen jedoch vernachlässigt. In meinem Artikel erläutere ich die begrifflichen Schwierigkeiten, die zu dieser Vernachlässigung führen. Meine These ist, dass einerseits die Verbindung von Sexualität und Sünde einen Grund dafür darstellt. Andererseits haben diese Schwierigkeiten auch mit dem Phänomen selbst zu tun, das auch ein gendertheoretisch informiertes theologisches Sprechen in Schwierigkeiten bringt. In einem weiteren Teil erläutere ich grundlegende Prinzipien einer nicht diskriminierenden theologischen Ethik, die in der Lage sein soll, mit Trans*identität umzugehen. Die Begriffe Individualität und Liebe spielen dabei eine fundamentale Rolle. Zusammen mit einer analytischen Verwendung des Begriffs der Sünde können sie als Ressourcen der theologischen Tradition verstanden werden, die eine Verantwortungsethik theologischen wie säkularen Zuschnitts mit diesem Fokus bereichern.

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Der steinerne Beweis. Geschichtstheologische Überlegungen zur Zerstörung des Jerusalemer Tempels in den Reden gegen die Juden von Johannes Chrysostomus

Die Zerstörung des Jerusalemer Tempels im Jahre 70 hat in der Sicht von Johannes Chrysostomus (349-407) nicht nur dem jüdischen Opferkult ein Ende, sondern auch die Tora ausser Kraft gesetzt. Die Ruinen in der Stadt sind dafür der steinerne Beweis. In diesem Kontext wird verständlich, dass Kaiser Julian (361-363) mit seinem Versuch, den Tempel wieder zu errichten, die Christen im höchsten Mass verunsicherte. Rund zwanzig Jahre später hielt Johannes Chrysostomus in Antiochien, der syrischen Metropole, seine Reden gegen die Juden, in denen er wortmächtig den Beweis antreten wollte, dass der Tempel nie wieder erstehen würde. Seine Reden zeigen aber vor allem die Problematik jeder theologischen Argumentation mit der Geschichte.

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A looming water crisis demands creative thinking

Water may look like a local resource but is actually a global commons that requires a joined-up plan to distribute fairly

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Retrospective analysis of bevacizumab-induced hypertension and clinical outcome in patients with colorectal cancer and lung cancer

Abstract

Bevacizumab(Avastin®), a humanized therapeutic monoclonal antibody that targets vascular endothelial growth factor, is widely used in cancer treatment. Patients who are treated with bevacizumab have an increased risk of developing systemic hypertension. However, the relationship between bevacizumab-induced hypertension and clinical outcome remains unclear. We aimed to evaluate the effect of bevacizumab-induced hypertension in terms of prognosis in patients with colorectal cancer and non-small cell lung cancer. The study included 632 patients, 317 patients with non-small cell lung cancer and 315 patients with colorectal cancer. All patients were treated with bevacizumab in combination with standard chemotherapy protocols, between April 2007 and December 2014. Blood pressure was measured before each treatment cycle. In the patient group with colorectal cancer, treated with bevacizumab, Grade 2–3 hypertension was present in 27.6%. In hypertensive patients with colorectal cancer, median overall survival was 42.6 months, compared with 20.6 months for normotensive patients in this group (= 0.00071). In the patient group with non-small cell lung cancer, treated with bevacizumab, Grade 2–3 hypertension was present in 20.5%. In hypertensive patients with non-small cell lung cancer, median overall survival was 43.0 months, compared with 26.3 months for normotensive patients in this group (= 0.00451). Patients who developed hypertension during treatment with bevacizumab for colorectal cancer and non-small cell lung cancer had significantly prolonged overall survival when compared with normotensive patients. Bevacizumab-induced hypertension may represent a biomarker for clinical benefit in cancer patients treated with bevacizumab.

Thumbnail image of graphical abstract

The most common bevacizumab-related adverse event was hypertension. Patients who developed hypertension during treatment with bevacizumab for colorectal cancer and non-small lung cancer had significantly prolonged overall survival.



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Flow cytometry-based characterization of underlying clonal B and plasma cells in patients with light chain amyloidosis

Abstract

Systemic amyloid light chain (AL) amyloidosis is a life-threatening protein deposition disorder; however, effective therapy can dramatically improve the prognosis of AL patients. Therefore, accurate diagnosis of the underlying hematologic disease is important. Multi-parameter flow cytometry (MFC) is a reliable method to analyze lymphatic neoplasias and to detect even a small lymphatic clone. We analyzed the presence of clonal plasma cell (PC) and B cells in the bone marrow of 63 patients with newly diagnosed AL amyloidosis by MFC. We compared the results with the levels of monoclonal protein, the histopathology and cytogenetic results. As reference of light chain restriction, we used the immunohistochemical results of κ or λ positive amyloid deposits in various tissues. MFC identified underlying clonal lymphatic cells in all but two patients (61 of 63, 97%). Sixty-one patients harbored malignant PCs, whereas B-cell lymphomas were identified in two patients. Furthermore, MFC indicated at least one putative immunotherapeutical target (CD20, CD38, CD52, or SLAMF7) on malignant PCs in all but one patient. These results demonstrate that MFC is a reliable tool for an accurate diagnosis of the underlying hematologic disease and the detection of potential immunotherapeutical targets in patients with AL amyloidosis.

Thumbnail image of graphical abstract

Systemic amyloid light chain (AL) amyloidosis is a life-threatening protein deposition disorder and an accurate diagnosis of the underlying hematologic disease is important to provide effective therapy. We analyzed the presence of clonal plasma cell (PC) and B cells in the bone marrow of 63 patients with newly diagnosed AL-amyloidosis by multi-parameter flow cytometry (MFC). MFC identified underlying clonal lymphatic cells in all but two patients (61 of 63, 97%). Sixty-one patients harbored malignant PCs, whereas B-cell lymphomas were identified in two patients. These results demonstrate that MFC is a reliable tool for an accurate diagnosis of the underlying hematologic disease in patients with AL amyloidosis.



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Adherence to cancer screening guidelines in Australian survivors of allogeneic blood and marrow transplantation (BMT)

Abstract

Allogeneic Blood and Marrow Transplant (BMT) survivors are at high risk of secondary cancers. Although current guidelines endorse survivors following Country-specific general population screening recommendations to mitigate this risk, little is known about cancer screening adherence in Australian BMT survivors. We conducted a cross-sectional survey of 441 BMT survivors who were >1 year post transplant, to explore rates of screening for secondary cancers and to identify barriers to cancer screening recommendations. Survey instruments included the Sydney Post-BMT Survey, FACT-BMT, DASS 21, The Chronic Graft versus Host Disease (GVHD) Activity Assessment–Patient Self-Report (Form B), the Lee Chronic GVHD Symptom Scale, Fear of Cancer Recurrence Scale, and The Post Traumatic Growth Inventory. Fifty-seven percent of respondents were male, median age 54 years, and 40% were >6 years post-BMT. Rates of cancer screening adherence were as follows: cervical 63.4%, breast 53.3%, skin 52.4%, and bowel 32.3%. Older BMT survivors and those >2 years post transplant were more likely to undergo cancer screening. Improved quality of life was associated with screening for skin, breast, and cervical cancer. Fear of cancer recurrence negatively impacted on cervical screening. For those who had not undergone screening, the majority reported not being advised to do so by their treatment team. This study is the largest and most comprehensive to date exploring cancer screening adherence in BMT survivors in Australia. These data provide the basis for health service reform to better meet the needs of BMT survivors and provide evidence to support counseling and education of both patients and professionals.

Thumbnail image of graphical abstract

We conducted a cross-sectional survey of 441 Blood and Marrow Transplant (BMT) survivors who were >1 year post transplant, to explore rates of screening for secondary cancers and to identify barriers to adherence with cancer screening recommendations. Rates of cancer screening uptake were as follows: cervical 63.4%, breast 53.3%, skin 52.4%, and bowel 32.3%. Improved quality of life was associated with screening for skin, breast, and cervical cancer. Fear of cancer recurrence negatively impacted on cervical screening. For those who had not undergone screening, the majority reported not being advised to do so by their treatment team.



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Are parenting behaviors associated with child sleep problems during treatment for acute lymphoblastic leukemia?

Abstract

Sleep disturbance is a recognized common side effect in children treated for acute lymphoblastic leukemia (ALL). Although associated with treatment factors such as hospitalization and corticosteroids, sleep problems may also be influenced by modifiable environmental factors such as parenting behaviors. The purpose of this study was to examine sleep problems in children undergoing treatment for ALL compared to healthy children and whether parenting practices are associated with sleep difficulties. Parents of 73 children aged 2–6 years who were (1) in the maintenance phase of ALL treatment (ALL group, n = 43) or (2) had no major medical illness (healthy control group, n = 30) participated in the study. Parents completed questionnaires measuring their child's sleep behavior and their own parenting practices. Parents of children undergoing ALL treatment reported significantly more child sleep problems; 48% of children with ALL compared to 23% of healthy children had clinical levels of sleep disturbance. Parents of the ALL group also reported significantly more lax parenting practices and strategies associated with their child's sleep including co-sleeping, comforting activities, and offering food and drink in the bedroom. Results of multivariate regression analysis indicated that, after controlling for illness status, parent–child co-sleeping was significantly associated with child sleep difficulties. Strategies employed by parents during ALL treatment may be a potential modifiable intervention target that could result in improved child sleep behaviors. Future research aimed at developing and testing parenting interventions aimed to improve child sleep in the context of oncology treatment is warranted.

Thumbnail image of graphical abstract

This study examined sleep problems in children undergoing treatment for acute lymphoblastic leukemia (ALL) compared to healthy children and whether parenting practices are associated with sleep difficulties. Parents of children with ALL reported significantly more child sleep problems and parent–child co-sleeping was significantly associated with child sleep difficulties. Strategies employed by parents during ALL treatment may be a potential modifiable intervention target that could result in improved child quality of life.



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Circulating CD14+HLA-DR-/low myeloid-derived suppressor cells in leukemia patients with allogeneic hematopoietic stem cell transplantation: novel clinical potential strategies for the prevention and cellular therapy of graft-versus-host disease

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population that includes immature myeloid cells and the progenitor cells of macrophages, dendritic cells (DCs), monocytes, and neutrophils. The expansion and functional importance of MDSCs in patients with cancer and noncancer pathogenic conditions has been recognized. As a result, there has been growing interest in understanding their roles in acute graft-versus-host disease (aGVHD) after allogenetic hematopoietic stem cell transplantation (allo-HSCT). In order to evaluate possible effects of MDSCs on aGVHD development and clinical outcomes, this study systematically detected the dynamic changes of MDSCs accumulation in patients during the first 100 days after allo-HSCT, and investigated the levels of other cell types and relative cytokines during MDSCs accumulation. Results showed that accumulation of MDSCs in the graft and in peripheral blood when engraftment might contribute to patients' overall immune suppression and result in the successful control of severe aGVHD and long-term survival without influence on risk of recurrence after allo-HSCT. But MDSCs levels in the graft had more favorable predictive abilities. Furthermore, MDSCs proportion significantly increased in patients developing aGVHD after allo-HSCT. It might be caused by secondary inflammatory response, especially related to high concentrations of IL-6 and TNF-α. But this accumulation would not be able to counterbalance the aggravation of aGVHD and would not have influence on clinical outcomes and risk of relapse. Overall, MDSCs might be considered as potential new therapeutic option for aGVHD and achieve long-term immunological tolerance and survival.

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This study revealed that MDSCs might be considered as a novel prognostic factor in patients with allo-HSCT and potential new approaches to regulate transplant rejection and achieve the recipient host long-term acceptance and survival. The understanding of the activation and differentiation of MDSCs in human will help to develop inhibitors during their unwanted activity, such as preventing relapse, but also provide options for therapeutical intervention in aGVHD after allo-HSCT.



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Prognostic microRNA signatures derived from The Cancer Genome Atlas for head and neck squamous cell carcinomas

Abstract

Identification of novel prognostic biomarkers typically requires a large dataset which provides sufficient statistical power for discovery research. To this end, we took advantage of the high-throughput data from The Cancer Genome Atlas (TCGA) to identify a set of prognostic biomarkers in head and neck squamous cell carcinomas (HNSCC) including oropharyngeal squamous cell carcinoma (OPSCC) and other subtypes. In this study, we analyzed miRNA-seq data obtained from TCGA patients to identify prognostic biomarkers for OPSCC. The identified miRNAs were further tested with an independent cohort. miRNA-seq data from TCGA was also analyzed to identify prognostic miRNAs in oral cavity squamous cell carcinoma (OSCC) and laryngeal squamous cell carcinoma (LSCC). Our study identified that miR-193b-3p and miR-455-5p were positively associated with survival, and miR-92a-3p and miR-497-5p were negatively associated with survival in OPSCC. A combined expression signature of these four miRNAs was prognostic of overall survival in OPSCC, and more importantly, this signature was validated in an independent OPSCC cohort. Furthermore, we identified four miRNAs each in OSCC and LSCC that were prognostic of survival, and combined signatures were specific for subtypes of HNSCC. A robust 4-miRNA prognostic signature in OPSCC, as well as prognostic signatures in other subtypes of HNSCC, was developed using sequencing data from TCGA as the primary source. This demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.

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Prognostic microRNA signatures were identified for head and neck cancers by analysis of public profiling data from The Cancer Genome Atlas (TCGA). This work demonstrates the power of using TCGA as a potential resource to develop prognostic tools for improving individualized patient care.



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Phase II evaluation of sunitinib in the treatment of recurrent or refractory high-grade glioma or ependymoma in children: a children's Oncology Group Study ACNS1021

Abstract

Sunitinib malate is a small multi-targeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor (KIT), which are highly expressed by some high-grade brain tumors. We conducted a phase II study to estimate the efficacy and further characterize the pharmacokinetics of sunitinib in pediatric patients with recurrent or refractory high-grade glioma (Stratum A) or ependymoma (Stratum B). This was a prospective, multicenter Phase II trial conducted through the Children's Oncology Group (ClinicalTrials.gov Identifier NCT01462695). Sunitinib, 15 mg/m2, was orally administered once daily for 4 weeks every 6 weeks. The safety and tolerability of sunitinib, an estimate of progression-free survival (PFS), analyses of sunitinib pharmacokinetics (PK) and pharmacodynamics modulation of plasma VEGF and VEGFR2 were also assessed. Thirty eligible patients (17 patients on Stratum A, 13 patients on Stratum B) were enrolled and 29 patients were evaluable for response. Sunitinib was reasonably well tolerated in children with recurrent ependymoma or high-grade glioma. Most adverse events were of mild-to-moderate severity and manageable with supportive treatment. While there was a statistically significant modulation of plasma VEGFR2 with sunitinib exposure, there were no sustained tumor responses. Both strata were closed at time of planned interim analysis as there was not sufficient efficacy associated with sunitinib in children with recurrent brain tumors. Sunitinib was well tolerated in children and young adults with recurrent high-grade glioma or ependymoma but had no single agent objective antitumor activity in these patients.

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This Phase II study of sunitinib reports the safety, tolerability and pharmacokinetic disposition in pediatric patients with recurrent high-grade glioma and ependymoma. While there was sufficient level of sunitinib in peripheral blood to modulate plasma vascular endothelial growth factor receptor (VEGFR)2, there were no sustained responses and no single agent activity in this patient cohort.



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God langtidsbeskyttelse av BCG-vaksine

BCG-vaksinen kan halvere risikoen for tuberkulose i en 40-årsperiode etter vaksinering.

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Δευτέρα 18 Απριλίου 2016

quality of care; +21 new citations

21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2016/04/18

PubMed comprises more than 24 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.



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IJMS, Vol. 17, Pages 586: Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population

ag

The single nucleotide polymorphisms (SNPs) related to both coronary heart disease (CHD) and ischemic stroke (IS) in Chinese individuals have not been identified definitely. This study was developed to evaluate the genetic susceptibility to CHD and IS on the chromosome 9p21 and the adenosine triphosphate (ATP)-binding cassette transporter A1 genes (ABCA1) in a Chinese Han population. Genotypes of the rs1333040, rs1333042, rs4977574, rs2066715 and rs2740483 SNPs were determined in 1134 unrelated patients (CHD, 565 and IS, 569) and 541 controls. The frequencies of the rs4977574 genotypes and alleles between CHD and control groups, and the rs2740483 genotypes and alleles between IS and control groups were different (p = 0.006–0.001). The subjects with rs1333042GG genotype and the carriers of the rs4977574G allele were associated with increased risk of CHD. The carriers of the rs4977574G allele were associated with increased risk of IS. However, the carriers of the rs2740483C allele had lower risk of IS than the non-carriers of the rs2740483C allele after controlling for potential confounders. The rs4977574GG-age (>60 year) interaction increased the risk of CHD (p = 0.022), whereas the rs2740483CG/CC-body mass index (>24 kg/m2) interaction decreased the risk of IS (p = 0.035). The interactions of rs1333040-rs1333042 on the risk of CHD and IS were relatively strong, whereas the interactions of rs1333040-rs1333042-rs2066715 and rs1333040-rs1333042-rs2066715-rs2740483 on the risk of CHD, and rs1333040-rs1333042-rs4977574 and rs1333040-rs1333042-rs4977574-rs2740483 on the risk of IS were relatively weak. These findings suggest that some common variants on the chromosome 9p21 and ABCA1 and their interactions may significantly modify the risk of CHD and IS independent of effects on serum lipid levels.

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Panniculectomy and Cystectomy: An Approach to the Morbidly Obese Patient

The obese patient undergoing radical cystectomy faces a unique set of challenges. We present the case of a 68-year-old gentleman who presented to our institution with Bacillus Calmette-Guerin refractory disease, a body mass index of 38.5, and a large pannus. The present paper describes our technique for performing radical cystectomy with ileal conduit urinary diversion and concomitant panniculectomy. We discuss the impact of obesity on patients undergoing radical cystectomy and how this may be mitigated by panniculectomy.

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Gigantomastia and Macroprolactinemia Responding to Cabergoline Treatment: A Case Report and Minireview of the Literature

Background. Macroprolactinemia is defined as predominance of high molecular weight prolactin forms in the circulation. Although macroprolactin is considered as a biologically inactive molecule, some authorities suggest treatment in symptomatic cases. Gigantomastia is defined as excess breast tissue and most cases in the literature were treated by surgical intervention. Case. A 44-year-old woman was admitted to our clinic with gigantomastia and galactorrhea. The patient had a demand for surgical therapy. In laboratory examination, she had hyperprolactinemia and macroprolactinemia. Pituitary imaging revealed 6 mm microadenoma in right side of the hypophysis. Since she was symptomatic, cabergolin treatment was started. Macroprolactin became negative, breast circumference decreased significantly, and galactorrhea resolved after treatment. Conclusion. Gigantomastia might be the presenting symptom in patients with macroprolactinemia. In these patients medical treatment with cabergoline may be used initially as an alternative to surgical approach.

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Effect of Alkaloids Isolated from Phyllodium pulchellum on Monoamine Levels and Monoamine Oxidase Activity in Rat Brain

Phyllodium pulchellum (P. pulchellum) is a folk medicine with a significant number of bioactivities. The aim of this study was to investigate the effects displayed by alkaloids fractions, isolated from the roots of P. pulchellum, on neurotransmitters monoamine levels and on monoamine oxidase (MAO) activity. Six alkaloids, which had indolealkylamine or β-carboline skeleton, were obtained by chromatographic technologies and identified by spectroscopic methods such as NMR and MS. After treatment with alkaloids of P. pulchellum, the reduction of DA levels (54.55%) and 5-HT levels (35.01%) in rat brain was observed by HPLC-FLD. The effect of alkaloids on the monoamines metabolism was mainly related to MAO inhibition, characterized by IC50 values of and  μg/mL for MAO-A and MAO-B, respectively. The acute toxicity indicated that P. pulchellum extract was nontoxic.

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Ultra-High and Near-Zero Refractive Indices of Magnetron Sputtered Thin-Film Metamaterials Based on TixOy

Metamaterials based on with ultra-high and near-zero refractive indices were obtained by DC magnetron sputtering. The data on refractive indices, extinction coefficients, film thickness, and band gaps, obtained by spectroscopic ellipsometry, showed very high potential of these materials as metamaterials. Phase analysis performed by XRD revealed the presence of titanium phases with lower titanium oxidation states resulting from high concentration of oxygen vacancies, which are crucial for such extraordinary jumps and drops of refractive indices. Numerous band gaps for direct and indirect electron transitions additionally confirmed unique properties of these materials.

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Th17 Cell Response in Mice following Motor Nerve Injury

An increased risk of ALS has been reported for veterans, varsity athletes, and professional football players. The mechanism underlying the increased risk in these populations has not been identified; however, it has been proposed that motor nerve injury may trigger immune responses which, in turn, can accelerate the progression of ALS. Accumulating evidence indicates that abnormal immune reactions and inflammation are involved in the pathogenesis of ALS, but the specific immune cells involved have not been clearly defined. To understand how nerve injury and immune responses may contribute to ALS development, we investigated responses of CD4+ T cell after facial motor nerve axotomy (FNA) at a presymptomatic stage in a transgenic mouse model of ALS (B6SJL ). mice, compared with WT mice, displayed an increase in the basal activation state of CD4+ T cells and higher frequency of Th17 cells, which were further enhanced by FNA. In conclusion, mice exhibit abnormal CD4+ T cell activation with increased levels of Th17 cells prior to the onset of neurological symptoms. Motor nerve injury exacerbates Th17 cell responses and may contribute to the development of ALS, especially in those who carry genetic susceptibility to this disease.

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Hyoid bone displacement as parameter for swallowing impairment in patients treated for advanced head and neck cancer.

Hyoid bone displacement as parameter for swallowing impairment in patients treated for advanced head and neck cancer.

Eur Arch Otorhinolaryngol. 2016 Apr 16;

Authors: Kraaijenga SA, van der Molen L, Heemsbergen WD, Remmerswaal GB, Hilgers FJ, van den Brekel MW

Abstract
Reduced hyoid displacement is thought to contribute to aspiration and pharyngeal residues in head and neck cancer (HNC) patients with dysphagia. To further study hyoid elevation and anterior excursion in HNC patients, this study reports on temporal/kinematic measures of hyoid displacement, with the additional goal to investigate correlations with clinical swallowing impairment. A single-blind analysis of data collected as part of a larger prospective study was performed at three time points before and after chemoradiotherapy. Twenty-five patients had undergone clinical swallowing assessments at baseline, 10-weeks, and 1-year post-treatment. Analysis of videofluoroscopic studies was done on different swallowing consistencies of varying amounts. The studies were independently reviewed frame-by-frame by two clinicians to assess temporal (onset and duration) and kinematic (anterior/superior movement) measures of hyoid displacement (ImageJ), laryngeal penetration/aspiration, and presence of vallecula/pyriform sinus residues. Patient-reported oral intake and swallowing function were also evaluated. Mean maximum hyoid displacement ranged from 9.4 mm (23 % of C2-4 distance) to 12.6 mm (27 %) anteriorly, and from 18.9 mm (41 %) to 24.9 mm (54 %) superiorly, depending on bolus volume and consistency. Patients with reduced superior hyoid displacement perceived significantly more swallowing impairment. No correlation between delayed or reduced hyoid excursion and aspiration or residue scores could be demonstrated. Hyoid displacement is subject to variability from a number of sources. Based on the results, this parameter seems not very valuable for clinical use in HNC patients with dysphagia.

PMID: 27086361 [PubMed - as supplied by publisher]



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Post traumatic deafness: a pictorial review of CT and MRI findings.

Post traumatic deafness: a pictorial review of CT and MRI findings.

Insights Imaging. 2016 Apr 16;

Authors: Maillot O, Attyé A, Boyer E, Heck O, Kastler A, Grand S, Schmerber S, Krainik A

Abstract
Hearing loss is a common functional disorder after trauma, and radiologists should be aware of the ossicular, labyrinthine or brain lesions that may be responsible. After a trauma, use of a systematic approach to explore the main functional components of auditory pathways is essential. Conductive hearing loss is caused by the disruption of the conductive chain, which may be due to ossicular luxation or fracture. This pictorial review firstly describes the normal 2-D and 3-D anatomy of the ossicular chain, including the incudo-malleolar and incudo-stapedial joints. The role of 3-D CT in the post-traumatic evaluation of injury to the temporal bone is then evaluated. In the case of sensorineural hearing loss, CT can detect pneumolabyrinth and signs of perilymphatic fistulae but fails to detect subtle lesions within the inner ear, such as labyrinthine haemorrhage or localized brain axonal damage along central auditory pathways. The role that MRI with 3-D-FLAIR acquisition plays in the detection of inner ear haemorrhage and post-traumatic lesions of the brain parenchyma that may lead to auditory agnosia is also discussed.
KEY POINTS: • The most common middle ear injuries are incudo-malleolar and incudo-stapedial joint luxation. • In patients with SNHL, CT can detect pneumolabyrinth or perilymphatic fistula • 3-D-FLAIR MRI appears the best sequence to highlight labyrinthine haemorrhage • Axonal damage and brain hematoma may lead to deafness.

PMID: 27085885 [PubMed - as supplied by publisher]



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Treatment of large tracheal defects after resection: Laryngotracheal release and tracheal replacement.

Treatment of large tracheal defects after resection: Laryngotracheal release and tracheal replacement.

Auris Nasus Larynx. 2016 Apr 14;

Authors: Kirschbaum A, Teymoortash A, Suárez C, Shah JP, Silver CE, Nixon I, Rinaldo A, Kowalski LP, Robbins KT, Ferlito A

Abstract
OBJECTIVE: Resection with direct tracheal or laryngotracheal anastomosis is the standard procedure employed for treatment of benign stenosis or occasionally primary or secondary tracheal malignancy.
DATA SOURCES: Literature review.
RESULTS: A tracheal anastomosis usually heals without complications provided that the ends being joined are adequately supplied with blood, an atraumatic suturing technique is used, and the anastomosis does not become infected. It is especially important that the anastomosis is not subjected to tension.
CONCLUSION: Various techniques of laryngeal and tracheal release serve to reduce the tension on the anastomosis by mobilizing and reducing the distance between the two segments to be approximated. These techniques can be used in different combinations depending on situation encountered during surgery. In cases where more than 50% of the tracheal length must be excised, prosthetic replacements, autologous tissue transfer and allografts are required. All present various problems. The use of tissue-engineering techniques utilizing autologous stem cells has opened new perspectives for tracheal replacement. Such procedures are still in an experimental state.

PMID: 27085818 [PubMed - as supplied by publisher]



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[HPV DNA genotyping: A study of anogenital, head and neck and skin cancers in a population from west Algerian. HPV detection in different cancers from an Algerian population].

[HPV DNA genotyping: A study of anogenital, head and neck and skin cancers in a population from west Algerian. HPV detection in different cancers from an Algerian population].

Bull Cancer. 2016 Apr 13;

Authors: Nahet A, Boublenza L, Hassaine H, Masdoua N, Prétet JL, Belglaiaa E, Mougin C

Abstract
OBJECTIVES: To investigate the prevalence of human papillomaviruses (HPV) in cancers located at different sites in patients from west Algerian and collected between 2010 and 2014.
MATERIAL AND METHODS: Extracted DNA from archival formaldehyde-fixed and paraffin-embedded tissues was provided from 39 anogenital cancers, 10 head and neck cancers and 36 skin cancers. The viral DNA was detected using the INNO-LiPA HPV Genotyping Extra(®) kit.
RESULTS: The prevalence of HPV was 100% in cervical cancers, 40% in vaginal cancers, 17% in vulvar cancers, 33% in anal cancers, 0% in tonsil and larynx cancers and 6.4% in skin squamous cell carcinoma. In cervical cancers, the most prevalent genotypes were HPV16 (52%) and HPV18 (12%) as single infection.
CONCLUSION: The overall results agree partially with literature. Extensive research is necessary to promote HPV vaccine to reduce in particular the burden of cervical cancer in Algeria.

PMID: 27085765 [PubMed - as supplied by publisher]



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Erratum to "Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: A nationwide population-based retrospective study in Taiwan" [Oral Oncology 56 (2016) 71-77].

Erratum to "Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: A nationwide population-based retrospective study in Taiwan" [Oral Oncology 56 (2016) 71-77].

Oral Oncol. 2016 Apr 13;

Authors: Kuo TJ, Leung CM, Chang HS, Wu CN, Chen WL, Chen GJ, Lai YC, Huang WC

PMID: 27085636 [PubMed - as supplied by publisher]



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Corrigendum to "Cetuximab activity in dysplastic lesions of the upper aerodigestive tract" [Oral Oncol. 53 (2016) 60-66].

Corrigendum to "Cetuximab activity in dysplastic lesions of the upper aerodigestive tract" [Oral Oncol. 53 (2016) 60-66].

Oral Oncol. 2016 Apr 13;

Authors: Khan Z, Epstein JB, Marur S, Boyd Gillespie M, Feldman L, Tsai HL, Zhang Z, Wang H, Sciubba J, Ferris RL, Grandis JR, Gibson M, Koch W, Tufano R, Westra W, Tsottles N, Ozawa H, Chung CH, Califano JA

PMID: 27085635 [PubMed - as supplied by publisher]



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Short-term culture of tumour slices reveals the heterogeneous sensitivity of human head and neck squamous cell carcinoma to targeted therapies.

Short-term culture of tumour slices reveals the heterogeneous sensitivity of human head and neck squamous cell carcinoma to targeted therapies.

BMC Cancer. 2016;16(1):273

Authors: Donnadieu J, Lachaier E, Peria M, Saidak Z, Dakpe S, Ikoli JF, Chauffert B, Page C, Galmiche A

Abstract
BACKGROUND: Despite recent progress, investigating the impact of targeted therapies on Head and Neck Squamous Cell Carcinoma (HNSCC) remains a challenge. We investigated whether short-term culture of tumour fragments would permit the evaluation of tumour sensitivity to targeted therapies at the individual level.
METHODS: We cultivated tumour slices prepared from 18 HNSCC tumour samples obtained during surgical resection. The samples were treated for 48 h with a panel of 8 targeted therapies directed against selected oncogenic transduction pathways. We analysed the cell proliferation index (CPI) of tumour cells using Ki67 labelling and the activation status of the RAF-MEK-ERK cascade through ERK phosphorylation analysis.
RESULTS: Fourteen tumours were successfully analysed after short-term culture of tumour samples, revealing a striking individual heterogeneity of HNSCC in terms of tumour cell sensitivity to targeted therapies. Using 50 % inhibition of CPI as threshold, sorafenib was shown to be active in 5/14 tumours. Cetuximab, the only approved targeted drug against HNSCC, was active in only 2/14 tumours. A more than 50 % inhibition was observed with at least one drug out of the eight tested in 10/14 tumours. Cluster analysis was carried out in order to examine the effect of the drugs on cell proliferation and the RAF-MEK-ERK cascade.
CONCLUSIONS: In vitro culture of tumour fragments allows for the evaluation of the effects of targeted therapies on freshly resected human tumours, and might be of value as a possible guide for the design of clinical trials and for the personalization of the medical treatment of HNSCC.

PMID: 27085492 [PubMed - as supplied by publisher]



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Sam Glover

Sam Glover grew up in a working class Jewish immigrant family in Belfast. He joined the merchant navy after qualifying from Queens University and travelled the world as a ship's doctor. He started...
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Charles Roger Wood

The youngest of five siblings, Roger Wood grew up in Buckinghamshire, where his father was a rural GP. He qualified at a time when all students helped in the blitz. After war service aboard a Royal...
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Ethel Mary Reddie

Ethel Mary Reddie’s fellow students at UCL included John Wing and Robin Skynner. At that time she does not seem to have considered a future in psychiatry, but she recalled having lectures in...
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