Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com

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Σάββατο 13 Μαΐου 2017

Crystal structure and mechanical properties of a new ternary phase in Mg-Zn-Y alloy solidified under high pressure

Publication date: 15 September 2017
Source:Journal of Alloys and Compounds, Volume 717
Author(s): Wei Jiang, Chunming Zou, Haw-Tyng Huang, Zheng Ran, Zunjie Wei
A new ternary phase, Mg64.093±0.004Zn15.355±0.002Y20.552±0.005 (at. %) was found in a Mg-Zn-Y alloy prepared by high pressure solidification. A full set of crystal structure parameters including the atomic coordinates of this new phase were determined using X-ray diffraction with Rietveld refinement and electron probe micro-analysis. Furthermore, the mechanical properties of this phase, including the Young's modulus and hardness were reported by nanoindentation test. Theoretical elastic constants, bulk modulus, shear modulus, Young's modulus, Poisson's ratio of this phase were calculated by first-principles. Results indicate that this phase is a ductile materials phase.

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Stable isotope ratio and elemental composition parameters in combination with discriminant analysis classification model to assign country of origin to commercial vegetables – A preliminary study

Publication date: October 2017
Source:Food Control, Volume 80
Author(s): Anja Mahne Opatić, Marijan Nečemer, Sonja Lojen, Rajko Vidrih
Recently, increased public attention has been paid to the geographical authentication of food, including vegetables, which are considered to be one of the major health-promoting components in a balanced diet. The purpose of the present study was to investigate the suitability of the use of isotopic compositions of light elements (δ13C, δ15N, δ18O, δ34S) in combination with multi-elemental fingerprinting (P, S, Cl, K, Ca, Mn, Fe, Zn, Br, Rb, Sr) to provide rapid, robust and inexpensive screening methods for distinguishing lettuce, sweet pepper, and tomato samples according to their given country of origin (i.e., Slovenia, Austria, Spain, Morocco, Italy, Greece), and thus ensuring their traceability in terms of their authenticity. The classification efficiency of the proposed multivariate statistical models using supervised pattern-recognition analysis, namely multivariate discriminant analysis, was sufficient for rapid and robust screening purpose. The predictions of the suggested discriminant analysis models per kind using cross-validation leave-one-out were 86.2%, 71.1% and 74.4% for lettuce, sweet pepper and tomato, respectively. The first use of the proposed methodology on vegetable samples on European and Mediterranean scales provides a valuable and necessary contribution to the development and implementation of a new national surveillance system that can be used to trace the geographical origins of vegetables.



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Preparation and characterization of magnetic biosorbent based on oil palm empty fruit bunch fibers, cellulose and Ceiba pentandra for heavy metal ions removal

Publication date: 15 October 2017
Source:Industrial Crops and Products, Volume 105
Author(s): S. Daneshfozoun, M.A. Abdullah, B. Abdullah
This study prepared, characterized and developed agro-based magnetic biosorbents (AMBs) from Ceiba pentandra (RKF), oil palm empty fruit bunches (EFB) and celluloses (CEL) extracted from EFB, using a novel, simple and cost-effective preparation technique for the removal of Pb(II), Cu(II), Zn(II), Mn(II) and Ni(II) ions from aqueous solutions. There has been no report on the methods to prepare and the use of magnetic biosorbent based on these biomaterials. The morphological, chemical and magnetic characterization suggested successful preparation of AMBs with good dispersion of magnetic nanoparticles on the surface of the base materials with clear magnetic properties. Optimum sorption was achieved between pH 5–7, and increase in initial ion concentration and solution temperature resulted in increased ion uptake. AMBs regeneration was successfully performed for 5 adsorption/desorption cycles. The magnetic biosorbent based on kapok showed the best Pb(II) removal efficiency of 99.4% and 49mg/g adsorption capacity compared to 98.2% for cellulose and 97.7% for EFB. The magnetic biosorbents exhibited 10.3% higher removal efficiency than the raw sorbents.



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On the eutectoid transformation behavior of the Ti-Zn system and its metastable phases

Publication date: 25 September 2017
Source:Journal of Alloys and Compounds, Volume 718
Author(s): D.A. Brice, P. Samimi, I. Ghamarian, Y. Liu, M.Y. Mendoza, M.J. Kenney, R.F. Reidy, M. Garcia-Avila, P.C. Collins
To date, Zn has not been used as an alloying addition in structural Ti alloys. The main obstacle has been the disparity between their melting and vaporization temperatures. A novel processing technique was developed to create a Ti-Zn compound. The equilibrium phases and microstructures were studied by electron microscopy and x-ray diffraction techniques. Results show the presence of pearlitic domains of α-Ti (hexagonal closed packed crystal structure) and Ti2Zn (body center tetragonal structure) in regions that have a near eutectoid composition. Solutionizing and water quenching results in the formation of martensite along with intermetallic laths, suggesting that the eutectoid transformation is active.

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Ventilator Management of Bronchopleural Fistula Secondary to Methicillin-Resistant Staphylococcus aureus Necrotizing Pneumonia in a Pregnant Patient with Systemic Lupus Erythematosus

Managing mechanical ventilation in patient with bronchopleural fistula with coexisting acute respiratory distress syndrome is a challenging situation for the intensivist. We are reporting a case of a pregnant patient with systemic lupus erythematosus on immunosuppressive medications who developed methicillin-resistant Staphylococcus aureus necrotizing pneumonia complicated by bronchopleural fistula and acute respiratory distress syndrome.

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Role for RIF1-Interacting Partner DDX1 in BLM Recruitment to DNA Double-Strand Breaks

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Publication date: Available online 13 May 2017
Source:DNA Repair
Author(s): Lei Li, Ho-Yin Poon, Matthew R. Hildebrandt, Elizabeth A. Monckton, Devon R. Germain, Richard P. Fahlman, Roseline Godbout
Human Rap1-interacting factor 1 (RIF1) is an important player in the repair of DNA double strand breaks (DSBs). RIF1 acts downstream of 53BP1, with well-documented roles in class switch recombination in B-cells and inhibition of end resection initiation in BRCA1-defective cells. Here, we report that DEAD Box 1 (DDX1), a RNA helicase also implicated in DSB repair, interacts with RIF1, with co-localization of DDX1 and RIF1 observed throughout interphase. Recruitment of DDX1 to DSBs is dependent on RIF1, with RIF1 depletion abolishing DDX1-mediated facilitation of homologous recombination at DSBs. As previously demonstrated for RIF1, DDX1 is also required for chromatin loading of Bloom syndrome helicase (BLM) to ionizing radiation-induced DSBs, a RIF1-related activity that is independent of 53BP1. We show that DDX1 and RIF1 have different nucleic acid requirements for accumulation at DSBs, with RNA-DNA hybrids required for DDX1 accrual at DSBs, and single-strand RNA required for accumulation of RIF1 at these sites. Our data suggest both convergent and divergent roles for RIF1 in DSB repair, and may help to explain why RIF1 depletion does not fully mimic 53BP1 ablation in the restoration of homologous recombination defects in BRCA1-deficent cells.



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Five-year outcomes of an oropharynx-directed treatment approach for unknown primary of the head and neck

Publication date: July 2017
Source:Oral Oncology, Volume 70
Author(s): Kenneth Shung Hu, Waleed Fouad Mourad, Mauricio E. Gamez, Wilson Lin, Adam Saul Jacobson, Mark Stephen Persky, Mark L. Urken, Bruce E. Culliney, Zujun Li, Theresa Nguyen Tran, Stimson Pryor Schantz, Juskaran Chadha, Louis Benjamin Harrison
PurposeSquamous cell carcinoma of unknown primary (SCCHNUP) is commonly treated with comprehensive radiation to the laryngopharynx and bilateral necks. In 1998, we established a departmental policy to treat SCCHNUP with radiation directed to the oropharynx and bilateral neck.MethodsFrom 1998–2011, 60 patients were treated – N1: 18%, N2: 75% and N3: 7%. 82% underwent neck dissection. 55% received IMRT and 62% underwent concurrent chemoradiotherapy.ResultsAt median follow-up of 54months, 5 patients failed regionally and 4 emerged with a primary (tongue base, hypopharynx and thoracic esophagus). Five-year rates of regional control, primary emergence, distant metastasis, disease-free survival and overall survival were 90%, 10%, 20%, 72% and 79%, respectively. The 5year rate of primary emergence in a non-oropharynx site was 3%.ConclusionThis is the first demonstration that an oropharynx-directed approach yields low rates of primary emergence in SCCHNUP with excellent oncologic outcomes.



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Macrophage polarization differs between apical granulomas, radicular cysts, and dentigerous cysts

Abstract

Objectives

Apical periodontitis can appear clinically as apical granulomas or radicular cysts. There is evidence that immunologic factors are involved in the pathogenesis of both pathologies. In contrast to radicular cysts, the dentigerous cysts have a developmental origin. Macrophage polarization (M1 vs M2) is a main regulator of tissue homeostasis and differentiation. There are no studies comparing macrophage polarization in apical granulomas, radicular cysts, and dentigerous cysts.

Materials and methods

Forty-one apical granulomas, 23 radicular cysts, and 23 dentigerous cysts were analyzed in this study. A tissue microarray (TMA) of the 87 consecutive specimens was created, and CD68-, CD11c-, CD163-, and MRC1-positive macrophages were detected by immunohistochemical methods. TMAs were digitized, and the expression of macrophage markers was quantitatively assessed.

Results

Radicular cysts are characterized by M1 polarization of macrophages while apical granulomas show a significantly higher degree of M2 polarization. Dentigerous cysts have a significantly lower M1 polarization than both analyzed periapical lesions (apical granulomas and radicular cysts) and accordingly, a significantly higher M2 polarization than radicular cysts. Macrophage cell density in dentigerous cysts is significantly lower than in the periapical lesions.

Conclusions

The development of apical periodontitis towards apical granulomas or radicular cysts might be directed by macrophage polarization. Radicular cyst formation is associated with an increased M1 polarization of infiltrating macrophages. In contrast to radicular cysts, dentigerous cysts are characterized by a low macrophage infiltration and a high degree of M2 polarization, possibly reflecting their developmental rather than inflammatory origin.

Clinical relevance

As M1 polarization of macrophages is triggered by bacterial antigens, these results underline the need for sufficient bacterial clearance during endodontic treatment to prevent a possible M1 macrophage-derived stimulus for radicular cyst formation.



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Approach to Severe Cutaneous Adverse Drug Reactions

Opinion Statement

Severe cutaneous adverse drug reactions (SCARs) can occur at any age and can be life threatening, although some drugs have been more frequently reported than others. The spectrum of SCARs includes acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome (DiHS) or hypersensitivity syndrome (HSS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Immediate withdrawal of the offending drug is the mainstay treatment in SCARs, and rechallenge often leads to recurrent reactions. Cross reactivity and multiple sensitivities have also been reported. The identification of the offending medication at the onset of the disease is therefore essential to avoid future exposures to the same or chemically related compounds. Various algorithms can be useful to identify the culprit drug in the acute stage. Delayed onset from the initiation of treatment differs in the various clinical entities. Therefore, a prompt, accurate diagnosis is crucial for proper identification of the offending agent. After resolution of the disease, cutaneous tests and in vitro tests can be useful for confirmation of drug causality and investigation of possible cross-reactivity. SCARs are rare diseases, given the incidence is extremely low. Multidisciplinary and international teams are required to study these diseases. Further research is needed to fully understand etiopathogenesis and for the development of specific treatments.



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Hypoxia-based strategies for regenerative dentistry—Views from the different dental fields

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Publication date: September 2017
Source:Archives of Oral Biology, Volume 81
Author(s): Anna Sonja Müller, Klara Janjić, Bledar Lilaj, Michael Edelmayer, Hermann Agis
The understanding of the cell biological processes underlying development and regeneration of oral tissues leads to novel regenerative approaches. Over the past years, knowledge on key roles of the hypoxia-based response has become more profound. Based on these findings, novel regenerative approaches for dentistry are emerging, which target cellular oxygen sensors. These approaches include hypoxia pre-conditioning and pharmacologically simulated hypoxia. The increase in studies on hypoxia and hypoxia-based strategies in regenerative dentistry highlights the growing attention to hypoxia's role in regeneration and its underlying biology, as well as its application in a therapeutic setting.In this narrative review, we present the current knowledge on the role of hypoxia in oral tissues and review the proposed hypoxia-based approaches in different fields of dentistry, including endodontics, orthodontics, periodontics, and oral surgery.



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Chromane isolated from leaves of Dillenia indica improves the neuronal dysfunction in STZ-induced diabetic neuropathy

Publication date: Available online 13 May 2017
Source:Journal of Ethnopharmacology
Author(s): Navpreet Kaur, Lalit Kishore, Randhir Singh
Ethnopharmacological relevanceAccording to the Indian traditional medicine, Dillenia indica L. has shown therapeutic efficacy in various diseases. Fruits and leaves of the plant possess anti-oxidant and anti-inflammatory properties. Reactive oxygen species, formation of advanced glycation end products (AGEs) and apoptosis are implicated in the pathogenesis of diabetic neuropathy.Aim of the studyThe aim of the present study was to explore the effect of D. indica and its isolate, chromane (CR), on thermal and mechanical hyperalgesia, allodynia, MNCV and oxidative-nitrosative stress in streptozotocin-induced experimental diabetes.Material and MethodsDiabetes was induced by intraperitoneal administration of Streptozotocin (STZ; 65mg/kg) for the development of diabetic neuropathy. Chronic treatment with DAE (100, 200 and 400mg/kg, p.o.) and CR (5 and 10mg/kg, p.o.) for 30 days was started from the 60th day of STZ administration. Development of neuropathy was evident from a marked hyperalgesia and allodynia; reduced MNCV associated with increased formation of AGEs and reactive oxygen species.Resultssignificantly attenuated behavioral and biochemical changes associated with diabetic neuropathy. Present study suggested that DAE and CR ameliorated hyperglycemia and diabetic neuropathic pain via modulation of oxidative-nitrosative stress and reduction in AGEs formation in the diabetic rats.ConclusionThus D. indica might be beneficial in chronic diabetics, ameliorate the progression of diabetic neuropathy and may also find application in diabetic neuropathic pain.

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Coordinated regulation of IFITM1, 2 and 3 genes by an IFN-responsive enhancer through long-range chromatin interactions

Publication date: Available online 13 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Ping Li, Ming-Lei Shi, Wen-Long Shen, Zhang Zhang, De-Jian Xie, Xiang-Yuan Zhang, Chao He, Yan Zhang, Zhi-Hu Zhao
Interferon-induced transmembrane protein (IFITM) 1, 2 and 3 are a family of interferon (IFN)-induced transmembrane proteins that block entry of a broad spectrum of pathogens. However, the transcriptional regulation of these genes, especially whether there exists any enhancers and their roles during the IFN induction process remain elusive. Here, combining episomal luciferase reporter assay and in vivo genome editing, we identified an IFNβ-responsive enhancer located 35kb upstream of IFITM3 gene promoter upregulating the IFNβ-induced expression of IFITM1, 2 and 3 genes, thus contributing to IFNβ-mediated resistance to influenza A virus (IAV) infection. The enhancer was first identified and verified by data mining and luciferase reporter assay. Then we showed that signal transducers and activators of transcription (STAT) 1 bound to the enhancer after the treatment of IFNβ and was indispensable for the enhancer activity. Next, CRISPR-Cas9 mediated in vivo truncation of the enhancer considerably decreased both IFNβ and IAV-induced expression of IFTIM1, 2 and 3 in HEK293 cells. Furthermore, chromosome conformation capture revealed that the IFITM1, 2 and 3 genes physically clustered together and constitutively looped to the distal enhancer through long-range interactions in both HEK293 and A549 cells, providing structural basis for coordinated regulation of IFITM1, 2 and 3 by IFNβ. Finally, we showed that in vivo truncation of the enhancer impaired IFNβ-induced resistance to IAV infection. These findings expand our understanding of the mechanisms underlying the transcriptional regulation of IFITM1, 2 and 3 expression and its ability to mediate IFN-β signaling.



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Cell-surface G-protein-coupled receptors for tumor-associated metabolites: A direct link to mitochondrial dysfunction in cancer

Publication date: Available online 13 May 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer
Author(s): Bojana Ristic, Yangzom D. Bhutia, Vadivel Ganapathy
Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of mitochondrial function is one of the most significant changes that occurs in tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and epigenetics. In particular, three mitochondrial enzymes are inactivated in cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3-hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to regulation via acetylation/deacetylation. SIRT3, the predominant mitochondrial deacetylase, directly targets these enzymes for deacetylation and maintains their optimal catalytic activity. SIRT3 is a tumor suppressor, and deacetylation of these enzymes contributes to its biological function. PDH catalyzes the oxidative decarboxylation of pyruvate into acetyl CoA, SDH oxidizes succinate into fumarate, and HMGCS2 controls the synthesis of the ketone body β-hydroxybutyrate. As the activities of these enzymes are decreased in cancer, tumor cells accumulate lactate and succinate but produce less amounts of β-hydroxybutyrate. Apart from their role in cellular energetics, these metabolites function as signaling molecules via specific cell-surface G-protein-coupled receptors. Lactate signals via GPR81, succinate via GPR91, and β-hydroxybutyrate via GPR109A. In addition, lactate activates hypoxia-inducible factor HIF1α and succinate promotes DNA methylation. GPR81 and GPR91 are tumor promoters, and increased production of lactate and succinate as their agonists drives tumorigenesis by enhancing signaling via these two receptors. In contrast, GPR109A is a tumor suppressor, and decreased synthesis of β-hydroxybutyrate as its agonist suppresses signaling via this receptor, thus attenuating the tumor-suppressing function of GPR109A. In parallel with the opposing changes in lactate/succinate and β-hydroxybutyrate levels, tumor cells upregulate GPR81 and GPR91 but downregulate GPR109A. As such, these three metabolite receptors play a critical role in cancer and represent a new class of drug targets with selective antagonists of GPR81 and GPR91 for cancer treatment and agonists of GPR109A for cancer prevention.



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Disparities in cancer stage at diagnosis and survival of Aboriginal and non-Aboriginal South Australians

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Publication date: June 2017
Source:Cancer Epidemiology, Volume 48
Author(s): David Banham, David Roder, Dorothy Keefe, Gelareh Farshid, Marion Eckert, Margaret Cargo, Alex Brown
Background/AimThis study tested the utility of retrospectively staging cancer registry data for comparing stage and stage-specific survivals of Aboriginal and non-Aboriginal people. Differences by area level factors were also explored.MethodsThis test dataset comprised 950 Aboriginal cases and all other cases recorded on the South Australian cancer registry with a 1977–2010 diagnosis. A sub-set of 777 Aboriginal cases diagnosed in 1990–2010 were matched with randomly selected non-Aboriginal cases by year of birth, diagnostic year, sex, and primary site of cancer. Competing risk regression summarised associations of Aboriginal status, stage, and geographic attributes with risk of cancer death.ResultsAboriginal cases were 10 years younger at diagnosis, more likely to present in recent diagnostic years, to be resident of remote areas, and have primary cancer sites of head & neck, lung, liver and cervix. Risk of cancer death was associated in the matched analysis with more advanced stage at diagnosis. More Aboriginal than non-Aboriginal cases had distant metastases at diagnosis (31.3% vs 22.0, p<0.001). After adjusting for stage, remote-living Aboriginal residents had higher risks of cancer death than Aboriginal residents of metropolitan areas. Non-Aboriginal cases had the lowest risk of cancer death.ConclusionRetrospective staging proved to be feasible using registry data. Results indicated more advanced stages for Aboriginal than matched non-Aboriginal cases. Aboriginal people had higher risks of cancer death, which persisted after adjusting for stage, and applied irrespective of remoteness of residence, with highest risk of death occurring among Aboriginal people from remote areas.



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Dupilumab Improves General Health-Related Quality-of-Life in Patients with Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized, Controlled Phase 3 Clinical Trials

Abstract

Introduction

Patients with moderate-to-severe atopic dermatitis (AD) report a multidimensional disease burden that includes impaired health-related quality-of-life (HRQoL). Changes in overall health status and specific dimensions that contribute to HRQoL were evaluated in adults with moderate-to-severe AD who participated in phase 3 clinical trials of dupilumab, which is a fully human monoclonal antibody that inhibits signaling of cytokines IL-4 and IL-13.

Methods

Two dupilumab phase 3 clinical trials of identical design included the 5-dimension 3-level EuroQol (EQ-5D) as a measure of HRQoL. EQ-5D data from the two trials were pooled in an analysis that, using analysis of covariance, compared subcutaneous dupilumab 300 mg once weekly (qw) or every 2 weeks (q2w) versus placebo for EQ-5D utility score change from baseline overall and for clinical responders. The proportions of patients who reported different levels of problems on the individual dimension of the EQ-5D were also compared by treatment group.

Results

Patients (n = 1379) were 57.9% male with a mean (SD) age of 38.3 (14.3) years; baseline EQ-5D utility scores ranged from 0.611 to 0.629 across treatment groups. EQ-5D least squares mean change from baseline at week 16 was 0.031 with placebo, and was significantly greater with dupilumab qw (0.207) and q2w (0.210) (both P < 0.0001), which exceeded the minimal clinically important difference and resulted in scores that approached population norms. Changes from baseline among patients who achieved AD clinical response were greater than changes among the total population. Improvements were driven by the individual EQ-5D dimensions with the greatest burden at baseline (i.e., pain/discomfort, anxiety/depression and usual activities).

Conclusion

In adults with moderate-to-severe AD, dupilumab resulted in improvements in HRQoL that were statistically significant relative to placebo and were clinically meaningful.

Funding

Sanofi and Regeneron Pharmaceuticals, Inc.

Trial registration

ClinicalTrials.gov identifiers, NCT02277743 and NCT02277769, EudraCT Numbers 2014-001198-15 and 2014-002619-40.



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Working memory and attentional bias on reinforcing efficacy of food

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Publication date: 1 September 2017
Source:Appetite, Volume 116
Author(s): Katelyn A. Carr, Leonard H. Epstein
Reinforcing efficacy of food, or the relationship between food prices and purchasing, is related to obesity status and energy intake in adults. Determining how to allocate resources for food is a decision making process influenced by executive functions. Attention to appetitive cues, as well as working memory capacity, or the ability to flexibly control attention while mentally retaining information, may be important executive functions involved in food purchasing decisions. In two studies, we examined how attention bias to food and working memory capacity are related to reinforcing efficacy of both high energy-dense and low energy-dense foods. The first study examined 48 women of varying body mass index (BMI) and found that the relationship between attentional processes and reinforcing efficacy was moderated by working memory capacity. Those who avoid food cues and had high working memory capacity had the lowest reinforcing efficacy, as compared to those with low working memory capacity. Study 2 systematically replicated the methods of study 1 with assessment of maintained attention in a sample of 48 overweight/obese adults. Results showed the relationship between maintained attention to food cues and reinforcing efficacy was moderated by working memory capacity. Those with a maintained attention to food and high working memory capacity had higher reinforcing efficacy than low working memory capacity individuals. These studies suggest working memory capacity moderated the relationship between different aspects of attention and food reinforcement. Understanding how decision making process are involved in reinforcing efficacy may help to identify future intervention targets.



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Lack of negative autocorrelations of daily food intake on successive days challenges the concept of the regulation of body weight in humans

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Publication date: 1 September 2017
Source:Appetite, Volume 116
Author(s): David A. Levitsky, Ji Eun Raea Limb, Lua Wilkinson, Anna Sewall, Yingyi Zhong, Ammar Olabi, Jean Hunter
According to most theories, the amount of food consumed on one day should be negatively related to intake on subsequent days. Several studies have observed such a negative correlation between the amount consumed on one day and the amount consumed two to four days later. The present study attempted to replicate this observation by re-examining data from a previous study where all food ingested over a 30-day observation period was measured. Nine male and seven female participants received a vegan diet prepared, dispensed, and measured in a metabolic unit. Autocorrelations were performed on total food intake consume on one day and that consumed one to five days later. A significant positive correlation was detected between the weight of food eaten on one day and on the amount consumed on the following day (r = 0.29, 95% CI [0.37, 0.20]). No correlation was found between weights of food consumed on one day and up to twelve days later (r = 0.09, 95% CI [0.24, −0.06]), (r = 0.11, 95% CI [0.26, −0.0.26]) (r = 0.02, 95% CI [0.15, −0.7]) (r = −0.08, 95% CI [0.11, −0.09]). The same positive correlation with the previous day's intake was observed at the succeeding breakfast but not at either lunch or dinner. However, the participants underestimated their daily energy need resulting in a small, but statistically significant weight loss. Daily food intake increased slightly (13 g/day), but significantly, across the 30-day period. An analysis of the previous studies revealed that the negative correlations observed by others was caused by a statistical artifact resulting from normalizing data before testing for the correlations. These results, when combined with the published literature, indicate that there is little evidence that humans precisely compensate for the previous day's intake by altering the amount consumed on subsequent days. Moreover, the small but persistent increase in food intake suggests that physiological mechanisms that affect food intake operate more subtly and over much longer periods of time than the meal or even total daily intake.



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LDH inhibition impacts on heat shock response and induces senescence of hepatocellular carcinoma cells

Publication date: 15 July 2017
Source:European Journal of Pharmaceutical Sciences, Volume 105
Author(s): Marcella Manerba, Lorenza Di Ianni, Marzia Govoni, Marinella Roberti, Maurizio Recanatini, Giuseppina Di Stefano
In normal cells, heat shock response (HSR) is rapidly induced in response to a variety of harmful conditions and represents one of the most efficient defense mechanism. In cancer tissues, constitutive activation converts HSR into a life-threatening process, which plays a major role in helping cell survival and proliferation. Overexpression of heat shock proteins (HSPs) has been widely reported in human cancers and was found to correlate with tumor progression. Hepatocellular carcinoma is one of the conditions in which HSR activation was shown to have the highest clinical significance.Transcription of HSPs is induced by HSF-1, which also activates glycolytic metabolism and increases the expression of LDH-A, the master regulator of the Warburg effect. In this paper, we tried to explore the relationship between HSR and LDH-A. In cultured hepatocellular carcinoma cells, by using two enzyme inhibitors (oxamate and galloflavin), we found that the reduction of LDH-A activity led to decreased level and function of the major HSPs involved in tumorigenesis. Galloflavin (a polyphenol) also inhibited the ATPase activity of two of the examined HSPs. Finally, hindering HSR markedly lowered the alpha-fetoprotein cellular levels and induced senescence.Specific inhibitors of single HSPs are currently under evaluation in different neoplastic diseases. However, one of the effects usually observed during treatment is a compensatory elevation of other HSPs, which decreases treatment efficacy. Our results highlight a connection between LDH and HSR and suggest LDH inhibition as a way to globally impact on this tumor promoting process.

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Evaluating the predictability of the in vitro transfer model and in vivo rat studies as a surrogate to investigate the supersaturation and precipitation behaviour of different Albendazole formulations for humans

Publication date: 15 July 2017
Source:European Journal of Pharmaceutical Sciences, Volume 105
Author(s): Aaron Ruff, René Holm, Edmund S. Kostewicz
The present study investigated the ability of the in vitro transfer model and an in vivo pharmacokinetic study in rats to investigate the supersaturation and precipitation behaviour of albendazole (ABZ) relative to data from a human intestinal aspiration study reported in the literature. Two lipid based formulation systems, a hydroxypropyl-β-cyclodextrin (HPβCD) solution and the addition of a crystallization inhibitor (HPMC-E5) on the behaviour of ABZ was investigated. These formulations were investigated to represent differences in their ability to facilitate supersaturation within the small intestine. Overall, both the in vitro transfer model and the in vivo rat study were able to rank order the formulations (as aqueous suspension±HPMC<Lipid based formulations<HPβCD-solution) in accordance with the observations in the human aspiration study. The results therefore demonstrated that both the in vivo rat model and the in vitro transfer model could reflect the performance of the ABZ formulations in the human study. Whilst the rat was able to provide information on the overall plasma exposure, through the use of the in vitro transfer model, a more mechanistic understanding of the supersaturation and precipitation behaviour of ABZ using the different formulation strategies, could be attained.

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Neutrophil Extracellular Traps are associated with disease severity and microbiota diversity in Chronic Obstructive Pulmonary Disease

Neutrophil extracellular traps are associated with disease severity and loss of microbiota diversity in COPD, suggesting a role in disease pathogenesis and progression.

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Intratympanic steroid delivery by an indwelling catheter in refractory severe sudden sensorineural hearing loss

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Publication date: Available online 13 May 2017
Source:Auris Nasus Larynx
Author(s): Diego Zanetti, Federica Di Berardino, Nader Nassif, Luca Oscar Redaelli De Zinis
ObjectiveMany studies over the last decade showed favorable outcomes with intratympanic (IT) steroid treatment, alone as salvage treatment or in combination with conventional systemic therapy (ST). However, in severe to profound sensorineural hearing loss resistant to ST, the optimal infusion mode, the type and concentration of the solution, the preferable drug, its total amount, and the duration and fractionation of the treatment are still debated. Aim of the study was to investigate the feasibility and the outcomes of a direct and constant IT delivery of dexamethasone (DEX) by means of a new indwelling catheter.MethodsA prospective case-control study in a tertiary referral university hospital. Ninety-nine subjects treated with ST only and 28 with additional IT DEX have been included in the study. A 4 Fr catheter inserted in a sub-annular fashion with a minimal postero-inferior tympanotomy through and endocanalar approach under local anesthesia. DEX 4mg/ml delivered daily, up to 7 days. Daily bone and air-conducted pure tone and speech audiometry were performed with a follow-up at 1, 3, 6 months after treatment.ResultsTwenty-one out of 28 patients (75%) refractory to ST gained on average 24.0dB±20.5dB HL after IT-DEX, compared to 35.4% (average 6.7dB±16.6dB HL) of those receiving only medical ST (p<0.001). No significant side effects were noted.ConclusionIn severe to profound sudden deafness refractory to conventional ST, the daily perfusion of 4mg/ml DEX through an intratympanic catheter is an easy, well accepted procedure that enables patients to receive a drug in the middle ear in a repeatable or sustained form, with minimal discomfort and a partial rescue (67.86%) and a speech recognition gain of 39%.



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Severely infected pneumoceles of the frontal sinus in patients with mental retardation and brain atrophy treated by endoscopic sinus surgery

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Publication date: Available online 13 May 2017
Source:Auris Nasus Larynx
Author(s): Ichiro Tojima, Hirotaka Kikuoka, Takao Ogawa, Takeshi Shimizu
We herein present three cases of abnormally expanded frontal sinuses (pneumoceles) with severe infection in patients with mental retardation and brain atrophy. Two patients previously underwent laryngotracheal separation surgery, and bacteriological examinations of purulent nasal discharge revealed infections caused by drug-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As conservative medical treatments were ineffective, all three patients were treated by computed tomography-guided endoscopic sinus surgery. This navigation system is useful for safer surgery in the area of anatomic deformity. The clinical findings, possible etiologies and surgical treatment of these cases are discussed.



http://ift.tt/2qhqWOy

Mechanisms of Immune Tolerance in Leukemia and Lymphoma

Publication date: Available online 13 May 2017
Source:Trends in Immunology
Author(s): Emily K. Curran, James Godfrey, Justin Kline
The mechanisms through which immune responses are generated against solid cancers are well characterized and knowledge of the immune evasion pathways exploited by these malignancies has grown considerably. However, for hematological cancers, which develop and disseminate quite differently than solid tumors, the pathways that regulate immune activation or tolerance are less clear. Growing evidence suggests that, while numerous immune escape pathways are shared between hematological and solid malignancies, several unique pathways are exploited by leukemia and lymphoma. Below we discuss immune evasion mechanisms in leukemia and lymphoma, highlighting key differences from solid tumors. A more complete characterization of the mechanisms of immune tolerance in hematological malignancies is critical to inform the development of future immunotherapeutic approaches.



http://ift.tt/2qhreVv

Intratympanic steroid delivery by an indwelling catheter in refractory severe sudden sensorineural hearing loss

Many studies over the last decade showed favorable outcomes with intratympanic (IT) steroid treatment, alone as salvage treatment or in combination with conventional systemic therapy (ST). However, in severe to profound sensorineural hearing loss resistant to ST, the optimal infusion mode, the type and concentration of the solution, the preferable drug, its total amount, and the duration and fractionation of the treatment are still debated. Aim of the study was to investigate the feasibility and the outcomes of a direct and constant IT delivery of dexamethasone (DEX) by means of a new indwelling catheter.

http://ift.tt/2rcZfWx

Severely infected pneumoceles of the frontal sinus in patients with mental retardation and brain atrophy treated by endoscopic sinus surgery

We herein present three cases of abnormally expanded frontal sinuses (pneumoceles) with severe infection in patients with mental retardation and brain atrophy. Two patients previously underwent laryngotracheal separation surgery, and bacteriological examinations of purulent nasal discharge revealed infections caused by drug-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As conservative medical treatments were ineffective, all three patients were treated by computed tomography-guided endoscopic sinus surgery.

http://ift.tt/2qe94WY

Intratympanic steroid delivery by an indwelling catheter in refractory severe sudden sensorineural hearing loss

Many studies over the last decade showed favorable outcomes with intratympanic (IT) steroid treatment, alone as salvage treatment or in combination with conventional systemic therapy (ST). However, in severe to profound sensorineural hearing loss resistant to ST, the optimal infusion mode, the type and concentration of the solution, the preferable drug, its total amount, and the duration and fractionation of the treatment are still debated. Aim of the study was to investigate the feasibility and the outcomes of a direct and constant IT delivery of dexamethasone (DEX) by means of a new indwelling catheter.

http://ift.tt/2rcZfWx

Severely infected pneumoceles of the frontal sinus in patients with mental retardation and brain atrophy treated by endoscopic sinus surgery

We herein present three cases of abnormally expanded frontal sinuses (pneumoceles) with severe infection in patients with mental retardation and brain atrophy. Two patients previously underwent laryngotracheal separation surgery, and bacteriological examinations of purulent nasal discharge revealed infections caused by drug-resistant bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. As conservative medical treatments were ineffective, all three patients were treated by computed tomography-guided endoscopic sinus surgery.

http://ift.tt/2qe94WY

Component Resolved Diagnosis in Hymenoptera Anaphylaxis

Abstract

Purpose of Review

Hymenoptera anaphylaxis is one of the leading causes of severe allergic reactions and can be fatal. Venom-specific immunotherapy (VIT) can prevent a life-threatening reaction; however, confirmation of an allergy to a Hymenoptera venom is a prerequisite before starting such a treatment. Component resolved diagnostics (CRD) have helped to better identify the responsible allergen.

Recent Findings

Many new insect venom allergens have been identified within the last few years. Commercially available recombinant allergens offer new diagnostic tools for detecting sensitivity to insect venoms. Additional added sensitivity to nearly 95% was introduced by spiking yellow jacket venom (YJV) extract with Ves v 5. The further value of CRD for sensitivity in YJV and honey bee venom (HBV) allergy is more controversially discussed. Recombinant allergens devoid of cross-reactive carbohydrate determinants often help to identify the culprit venom in patients with double sensitivity to YJV and HBV. CRD identified a group of patients with predominant Api m 10 sensitization, which may be less well protected by VIT, as some treatment extracts are lacking this allergen.

Summary

The diagnostic gap of previously undetected Hymenoptera allergy has been decreased via production of recombinant allergens. Knowledge of analogies in interspecies proteins and cross-reactive carbohydrate determinants is necessary to distinguish relevant from irrelevant sensitizations.



http://ift.tt/2qdchpB

Component Resolved Diagnosis in Hymenoptera Anaphylaxis

Abstract

Purpose of Review

Hymenoptera anaphylaxis is one of the leading causes of severe allergic reactions and can be fatal. Venom-specific immunotherapy (VIT) can prevent a life-threatening reaction; however, confirmation of an allergy to a Hymenoptera venom is a prerequisite before starting such a treatment. Component resolved diagnostics (CRD) have helped to better identify the responsible allergen.

Recent Findings

Many new insect venom allergens have been identified within the last few years. Commercially available recombinant allergens offer new diagnostic tools for detecting sensitivity to insect venoms. Additional added sensitivity to nearly 95% was introduced by spiking yellow jacket venom (YJV) extract with Ves v 5. The further value of CRD for sensitivity in YJV and honey bee venom (HBV) allergy is more controversially discussed. Recombinant allergens devoid of cross-reactive carbohydrate determinants often help to identify the culprit venom in patients with double sensitivity to YJV and HBV. CRD identified a group of patients with predominant Api m 10 sensitization, which may be less well protected by VIT, as some treatment extracts are lacking this allergen.

Summary

The diagnostic gap of previously undetected Hymenoptera allergy has been decreased via production of recombinant allergens. Knowledge of analogies in interspecies proteins and cross-reactive carbohydrate determinants is necessary to distinguish relevant from irrelevant sensitizations.



http://ift.tt/2qdchpB

E-cigarette liquids: Constancy of content across batches and accuracy of labeling

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Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Jean-François Etter, Aurélie Bugey
AimsTo assess whether bottles of refill liquids for e-cigarettes were filled true to label, whether their content was constant across two production batches, and whether they contained impurities.MethodsIn 2013, we purchased on the Internet 18 models from 11 brands of e-liquids. We purchased a second sample of the same models 4months later. We analyzed their content in nicotine, anabasine, propylene glycol, glycerol, ethylene glycol and diethylene glycol, and tested their pH.ResultsThe median difference between the nicotine value on the labels and the nicotine content in the bottles was 0.3mg/mL (range −5.4 to +3.5mg/mL, i.e. −8% to +30%). For 82% of the samples, the actual nicotine content was within 10% of the value on the labels. All models contained glycerol (median 407mg/mL), and all but three models contained propylene glycol (median 650mg/mL). For all samples, levels of anabasine, ethylene glycol and diethylene glycol were below our limits of detection. The pH of all the e-liquids was alkaline (median pH=9.1; range 8.1 to 9.9). The measured content of two batches of the same model varied by a median of 0% across batches for propylene glycol, 1% for glycerol, 0% for pH, and 0.5% for nicotine (range −15% to +21%; 5th and 95th percentiles: −15% and +10%).ConclusionsThe nicotine content of these e-liquids matched the labels on the bottles, and was relatively constant across production batches. The content of propylene glycol and glycerol was also stable across batches, as was the pH.



http://ift.tt/2rdPB6y

The social exigencies of the gateway progression to the use of illicit drugs from adolescence into adulthood

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Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Roy Otten, Chung Jung Mun, Thomas J. Dishion
BackgroundThere is limited empirical integration between peer clustering theory and the Gateway framework. The goal of the present study was to test the hypothesis that friendship associations partly predict gateway escalations in the use of drugs from adolescence to adulthood.MethodThis longitudinal study analyzed 3 waves of data from a community sample of 711 male and female participants without a history of illicit drug use reporting drug use at age 17, 22, and 27. Substance use assessments including tobacco, alcohol, cannabis, onset and abuse/dependence tendency of illicit drugs other than cannabis (i.e., cocaine, methamphetamine, and opiates), and friends' reported use of illicit drugs. Structural equation modeling was used to test the hypothesized model.ResultsParticipants' cannabis use level at age 17 was positively associated with perceived friends' drug use at age 22, which in turn predicted participants' onset of illicit drug use between ages 22 and 27. Moreover, progression of tobacco use throughout age 17 to 22 was associated with an increased onset of illicit drug use between ages 22 and 27. Apart for an effect of cannabis use at age 22 on abuse and dependence tendency to various drugs at age 28, results were similar.ConclusionsDuring this period of development, the availability and selection of drug-using friends contributes to the progression to potentially more rewarding and damaging illicit drugs. These findings suggest the need to attend to the peer ecology in prevention and support the common practice of using abstaining peers in treatment for drug dependence.



http://ift.tt/2qEmPPz

The relationship between social desirability bias and self-reports of health, substance use, and social network factors among urban substance users in Baltimore, Maryland

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Publication date: October 2017
Source:Addictive Behaviors, Volume 73
Author(s): Carl A. Latkin, Catie Edwards, Melissa A. Davey-Rothwell, Karin E. Tobin
BackgroundSocial desirability response bias may lead to inaccurate self-reports and erroneous study conclusions. The present study examined the relationship between social desirability response bias and self-reports of mental health, substance use, and social network factors among a community sample of inner-city substance users.MethodsThe study was conducted in a sample of 591 opiate and cocaine users in Baltimore, Maryland from 2009 to 2013. Modified items from the Marlowe-Crowne Social Desirability Scale were included in the survey, which was conducted face-to-face and using Audio Computer Self Administering Interview (ACASI) methods.ResultsThere were highly statistically significant differences in levels of social desirability response bias by levels of depressive symptoms, drug use stigma, physical health status, recent opiate and cocaine use, Alcohol Use Disorders Identification Test (AUDIT) scores, and size of social networks. There were no associations between health service utilization measures and social desirability bias. In multiple logistic regression models, even after including the Center for Epidemiologic Studies Depression Scale (CES-D) as a measure of depressive symptomology, social desirability bias was associated with recent drug use and drug user stigma. Social desirability bias was not associated with enrollment in prior research studies.ConclusionsThese findings suggest that social desirability bias is associated with key health measures and that the associations are not primarily due to depressive symptoms. Methods are needed to reduce social desirability bias. Such methods may include the wording and prefacing of questions, clearly defining the role of "study participant," and assessing and addressing motivations for socially desirable responses.



http://ift.tt/2rdMrjb

The acceptability and tolerability of nasal douching in children with allergic rhinitis: A systematic review

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Publication date: July 2017
Source:International Journal of Pediatric Otorhinolaryngology, Volume 98
Author(s): Nelson Gutiérrez-Cardona, Paula Sands, Graham Roberts, Jane S. Lucas, Woolf Walker, Rami Salib, Andrea Burgess, Hasnaa Ismail-Koch
BackgroundAllergic rhinitis (AR) is a significant issue in children. Treatment options include allergen avoidance, pharmacotherapy and immunotherapy. The use of nasal saline douching (NSD) in children has recently gained acceptability. However, there is limited data regarding the acceptability and tolerability of NSD in children with AR.MethodsA search was conducted using Medline and Embase databases from January 1946 until June 2015 on the use of NSD in children aged 4–12 years with AR. All publications identified that assessed the beneficial effects, acceptability and tolerability were included.Results40 studies were analyzed. Data varied considerably in terms of saline solutions used, modality of application, participant numbers, study design, follow up and outcomes. Factors that appear to influence the acceptability and tolerability of NSD include parental and health professionals' preconceptions, and characteristics of the solution.ConclusionsNasal saline douching appears to be effective, being accepted and tolerated in the majority of children (78–100%). NSD has a significant positive impact on the quality of life in children with allergic rhinitis. When used as an adjunctive treatment having mainly a cleansing property, NSD potentiates the effects and may reduce the dose required of AR medications. Among the principal factors that influence the acceptability and tolerability of NSD are the child's age, delivery system and method, and tonicity. Nasal saline douching provides an accessible, low cost, low morbidity, easy to use treatment in children with allergic rhinitis.



http://ift.tt/2rdLQ0W

Nurse-led counselling and replacement therapy is effective for smoking cessation in oral cancer patients



http://ift.tt/2qciqm4

Breast augmentation combined with a transposed glandular flap for prevention and correction of lower pole deformities

Abstract

Background

Lower pole deformities constitute the most complex problem encountered during and after breast augmentation. If the procedure is not accurately planned, the choice of techniques to correct lower pole deformity intraoperatively can be limited, leading to the possibility of additional scarring or the necessity of a second surgery.

Methods

Volume deficiencies of the lower pole after implant placement, such as flatness and double bubble, are indications for the proposed technique. A glandular flap is created by bisecting the lower pole of the gland and is transposed inwards and downwards to fill the deficient area. It is not necessary to fix the flap in place.

Results

Between January 2011 and December 2014, 30 patients underwent breast augmentation or augmentation-mastopexy combined with a transposed glandular flap. A desired lower pole was achieved in all the cases. No major complications were observed.

Conclusions

The transposed glandular flap herein described was proven to be useful to correct volume deficiencies of the lower pole after implant placement in cases of primary and secondary cases of breast augmentation.

Level of Evidence: Level IV, therapeutic study



http://ift.tt/2raQQCH

Component Resolved Diagnosis in Hymenoptera Anaphylaxis

Abstract

Purpose of Review

Hymenoptera anaphylaxis is one of the leading causes of severe allergic reactions and can be fatal. Venom-specific immunotherapy (VIT) can prevent a life-threatening reaction; however, confirmation of an allergy to a Hymenoptera venom is a prerequisite before starting such a treatment. Component resolved diagnostics (CRD) have helped to better identify the responsible allergen.

Recent Findings

Many new insect venom allergens have been identified within the last few years. Commercially available recombinant allergens offer new diagnostic tools for detecting sensitivity to insect venoms. Additional added sensitivity to nearly 95% was introduced by spiking yellow jacket venom (YJV) extract with Ves v 5. The further value of CRD for sensitivity in YJV and honey bee venom (HBV) allergy is more controversially discussed. Recombinant allergens devoid of cross-reactive carbohydrate determinants often help to identify the culprit venom in patients with double sensitivity to YJV and HBV. CRD identified a group of patients with predominant Api m 10 sensitization, which may be less well protected by VIT, as some treatment extracts are lacking this allergen.

Summary

The diagnostic gap of previously undetected Hymenoptera allergy has been decreased via production of recombinant allergens. Knowledge of analogies in interspecies proteins and cross-reactive carbohydrate determinants is necessary to distinguish relevant from irrelevant sensitizations.



http://ift.tt/2qdchpB

Component Resolved Diagnosis in Hymenoptera Anaphylaxis

Abstract

Purpose of Review

Hymenoptera anaphylaxis is one of the leading causes of severe allergic reactions and can be fatal. Venom-specific immunotherapy (VIT) can prevent a life-threatening reaction; however, confirmation of an allergy to a Hymenoptera venom is a prerequisite before starting such a treatment. Component resolved diagnostics (CRD) have helped to better identify the responsible allergen.

Recent Findings

Many new insect venom allergens have been identified within the last few years. Commercially available recombinant allergens offer new diagnostic tools for detecting sensitivity to insect venoms. Additional added sensitivity to nearly 95% was introduced by spiking yellow jacket venom (YJV) extract with Ves v 5. The further value of CRD for sensitivity in YJV and honey bee venom (HBV) allergy is more controversially discussed. Recombinant allergens devoid of cross-reactive carbohydrate determinants often help to identify the culprit venom in patients with double sensitivity to YJV and HBV. CRD identified a group of patients with predominant Api m 10 sensitization, which may be less well protected by VIT, as some treatment extracts are lacking this allergen.

Summary

The diagnostic gap of previously undetected Hymenoptera allergy has been decreased via production of recombinant allergens. Knowledge of analogies in interspecies proteins and cross-reactive carbohydrate determinants is necessary to distinguish relevant from irrelevant sensitizations.



http://ift.tt/2qdchpB

Dysregulated Lymphoid Cell Populations in Mouse Models of Systemic Lupus Erythematosus

Abstract

Biases in the distribution and phenotype of T, B, and antigen-presenting cell populations are strongly connected to mechanisms of disease development in mouse models of systemic lupus erythematosus (SLE). Here, we describe longitudinal changes in lymphoid and antigen-presenting cell subsets in bone marrow, blood and spleen from two lupus-prone strains (MRL/lpr and B6.Sle1.Sle2.Sle3 tri-congenic mice), and how they integrate in our present understanding of the pathogenesis of the disease. In particular, we focus on (autoreactive) T cell activation patterns in lupus-prone mice. Break of T cell tolerance to chromatin constituents (histone peptides) is key to the development of the disease and is related to T cell intrinsic defects, contributed by genetic susceptibility factors and by extrinsic amplificatory mechanisms, in particular over-stimulation by antigen-presenting cells. We also describe shifts in B cell sub-populations, going from skewed immature B cell populations as an indication of disturbed central and peripheral tolerance checkpoints, to enriched long-lived plasma cells, which are key to persistent autoantibody production in the disease. B cell activation mechanisms in SLE are both T cell-dependent (break of tolerance and production of specific autoantibodies) and -independent (polyclonal B cell activation, production of autoantibodies by long-lived plasma cells). By providing a comprehensive evaluation of B and T cell surface markers in two major mouse models of SLE and a description of their changes before and after disease onset, this review illustrates how the study of lymphoid cell phenotype delivers key information regarding pathogenic pathways and supplies tools to assess the beneficial effects of novel therapeutic interventions.



http://ift.tt/2qE4Us8

Calcium Signaling: From Normal B Cell Development to Tolerance Breakdown and Autoimmunity.

Abstract

Maintenance of self-tolerance of auto-reactive lymphocytes is a fundamental mechanism to prevent the onset of autoimmune diseases. Deciphering the mechanisms involved in the deregulations leading to tolerance disruption and autoimmunity is still a major area of interest to identify new therapeutic targets and options. Ca2+ signaling plays a major role in B cell normal development and is therefore finely tuned by B cell receptor (BCR)-dependent and independent pathways. Developmental changes in the characteristics of BCR-dependent Ca2+ signals as well as the modulation of basal intracellular concentration ([Ca2+]i) contribute strongly to self-tolerance maintaining mechanisms responsible for the physical or functional elimination of autoreactive B cells such as clonal deletion, receptor editing, and anergy. Implication of Ca2+ signals in B tolerance mechanisms mainly occurs through the specific activation of transcriptional programs depending on the amplitude, shape, and duration of Ca2+ signals. A large number of studies reported Ca2+ signaling defects in autoimmune pathology such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary Sjӧgren's syndrome (pSS). However, the precise nature of the molecular events responsible for these deregulations is not fully understood. Moreover, the demonstration of a direct correlation between Ca2+ signaling defects and tolerance disruption is still lacking. The recent identification of proteins involved in B cell Ca2+ signals such as ORAI, stromal interaction molecule and transient receptor potential is opening new horizons for understanding Ca2+ signaling defects observed in autoimmune diseases and for proposing potentially new therapeutic solutions. This review aims to present an overview of the developmental evolution of BCR dependent Ca2+ signaling and to place this signaling pathway in the context of mechanisms involved in tolerance maintenance and breakdown.



http://ift.tt/2rdGJ0O

Inactivation of the KSRP gene modifies collagen antibody induced arthritis

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Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Rudolf Käfer, Katharina Schrick, Lisa Schmidtke, Evelyn Montermann, Dominika Hobernik, Matthias Bros, Ching-Yi Chen, Hartmut Kleinert, Andrea Pautz
The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted to analyze its importance for the development of autoimmune diseases.We chose collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease mouse model in which neutrophils and macrophages constitute the main effector cell populations. We compared arthritis induction in wild type (WT) and KSRP−/− mice and paws were taken for histological sections and qPCR analysis. Furthermore, we determined the frequencies of spleen immune cells by flow cytometry. Cytokine levels in spleen cell supernatants were determined by cytometric bead array analyses (CBA).After CAIA induction we unexpectedly observed in WT animals much stronger swelling of the paws than in KSRP−/− mice. In accordance, histological staining of paw sections of KSRP−/− animals revealed much lower frequencies of infiltrating immune cells in the joints compared to WT animals. Furthermore, CAIA-treatment resulted in reduced expression of several inflammatory factors (like CXCL-1, iNOS, TNF-α and S100A8) as well as immune cell marker genes (e.g. LFA-1, CD68, Ly6G) in the joints of KSRP−/− mice.Spleen cells of KSRP−/− mice showed lower frequencies of myeloid cells. On cytokine level IFN-γ production was increased in spleen cells of KSRP−/− mice compared to WT samples.These data surprisingly suggest that the absence of KSRP protects against the induction of inflammatory arthritis.



http://ift.tt/2qErd16

Inactivation of the KSRP gene modifies collagen antibody induced arthritis

S01615890.gif

Publication date: July 2017
Source:Molecular Immunology, Volume 87
Author(s): Rudolf Käfer, Katharina Schrick, Lisa Schmidtke, Evelyn Montermann, Dominika Hobernik, Matthias Bros, Ching-Yi Chen, Hartmut Kleinert, Andrea Pautz
The KH type splicing regulatory protein (KSRP) is a nucleic acid binding protein, which negatively regulates the stability and/or translatability of many mRNA species encoding immune-relevant proteins. As KSRP is expressed in immune cells including T and B cells, neutrophils, macrophages and dendritic cells, we wanted to analyze its importance for the development of autoimmune diseases.We chose collagen antibody-induced arthritis (CAIA) as an appropriate autoimmune disease mouse model in which neutrophils and macrophages constitute the main effector cell populations. We compared arthritis induction in wild type (WT) and KSRP−/− mice and paws were taken for histological sections and qPCR analysis. Furthermore, we determined the frequencies of spleen immune cells by flow cytometry. Cytokine levels in spleen cell supernatants were determined by cytometric bead array analyses (CBA).After CAIA induction we unexpectedly observed in WT animals much stronger swelling of the paws than in KSRP−/− mice. In accordance, histological staining of paw sections of KSRP−/− animals revealed much lower frequencies of infiltrating immune cells in the joints compared to WT animals. Furthermore, CAIA-treatment resulted in reduced expression of several inflammatory factors (like CXCL-1, iNOS, TNF-α and S100A8) as well as immune cell marker genes (e.g. LFA-1, CD68, Ly6G) in the joints of KSRP−/− mice.Spleen cells of KSRP−/− mice showed lower frequencies of myeloid cells. On cytokine level IFN-γ production was increased in spleen cells of KSRP−/− mice compared to WT samples.These data surprisingly suggest that the absence of KSRP protects against the induction of inflammatory arthritis.



http://ift.tt/2qErd16

Mechanisms of Resistance to JAK2 Inhibitors in Myeloproliferative Neoplasms

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Publication date: Available online 13 May 2017
Source:Hematology/Oncology Clinics of North America
Author(s): Sara C. Meyer

Teaser

Myeloproliferative neoplasms are driven by activated JAK2 signaling due to somatic mutations in JAK2, the thrombopoietin receptor MPL or the chaperone calreticulin in hematopoietic stem/progenitor cells. JAK2 inhibitors have been developed, but despite clinical benefits, they do not signficantly reduce the mutant clone. Loss of response to JAK2 inhibitors occurs and several mechanisms of resistance, genetic and functional, have been identified. Resistance mutations have not been reported in MPN patients suggesting incomplete target inhibition. Alternative targeting of JAK2 by HSP90 inhibitors or type II JAK2 inhibition overcomes resistance to current JAK2 inhibitors. Additional combined therapy approaches are currently being evaluated.


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Utilidad y versatilidad del colgajo en isla de la arteria supraclavicular en reconstrucción de cabeza y cuello

Publication date: Available online 13 May 2017
Source:Acta Otorrinolaringológica Española
Author(s): José A. González-García, Carlos M. Chiesa-Estomba, Jon A. Sistiaga, Ekhiñe Larruscain, Leire Álvarez, Xabier Altuna
IntroducciónEl colgajo supraclavicular en isla es un colgajo rotacional pediculado que puede presentar ciertas ventajas en reconstrucción de cabeza y cuello en pacientes donde una reconstrucción microvascularizada no sea factible o aconsejable.Material y métodosPresentamos nuestra experiencia durante el año 2016 en 5 casos con la aplicación de este colgajo, como alternativa a una reconstrucción microvascularizada tras resección de distintos tumores de cabeza y cuello. En 2 casos se utilizó para reconstrucción del faringostoma quirúrgico tras laringectomía total con faringectomía parcial. En un caso para reconstrucción facial lateral tras resección parcial de temporal. En un caso para reconstrucción de un defecto cutáneo tras laringectomía total ampliada y en otro para cobertura cutánea tras el cierre primario de una fístula faringocutánea. No hubo complicaciones del colgajo y el resultado final fue satisfactorio en todos los casos.ResultadosEl colgajo supraclavicular en isla presenta una utilidad y es muy versátil en reconstrucciones de cabeza y cuello. El tiempo quirúrgico en pacientes de riesgo se reducirá respecto a colgajos libres microvascularizados. Su técnica quirúrgica es relativamente sencilla y se adapta perfectamente a reconstrucciones mucosas o cutáneas.ConclusiónEl colgajo supraclavicular en isla es una opción recomendable en reconstrucción de cabeza y cuello, su uso parece estar incrementándose y supone una alternativa segura y sobre todo rápida a los colgajos libres microvascularizados en pacientes seleccionados.IntroductionThe supraclavicular island flap is a rotational pedicled flap and may have some advantages in head and neck reconstruction compared with free-tissue transfer when this kind of reconstruction is not affordable or recommended.Material and methodsWe present our experience during the year 2016 in the application of the supraclavicular island flap in five cases as an alternative to microvascular reconstruction in several defects after resection of head and neck tumours. In two patients, the flap was used to close the surgical pharyngostoma after total laryngectomy with partial pharyngectomy. In one patient, it was used in lateral facial reconstruction after partial resection of the temporal bone. In one case, it was used to close a skin defect after total laryngectomy with prelaryngeal tissue extension. And in the last case to close a neck skin defect after primary closure of a pharyngo-cutaneous fistula. There were no flap complications, and the result was satisfactory in all cases.ResultsThe supraclavicular artery island flap is useful and versatile in head and neck reconstruction. Operating room time in aged patients or those with comorbidities will be reduced compared to free flaps. The surgical technique is relatively easy and can be used for skin and mucosal coverage.ConclusionThe supraclavicular island flap could be a recommended option in head and neck reconstruction, its use seems to be increasing and provides a safe and time-saving option to free flaps in selected patients.



http://ift.tt/2pw2SdM

Multi-Modal Classification of Neurodegenerative Disease by Progressive Graph-Based Transductive Learning

Publication date: Available online 13 May 2017
Source:Medical Image Analysis
Author(s): Zhengxia Wang, Xiaofeng Zhu, Ehsan Adeli, Yingying Zhu, Feiping Nie, Brent Munsell, Dinggang Shen, Guorong Wu
Graph-based transductive learning (GTL) is a powerful machine learning technique that is used when sufficient training data is not available. In particular, conventional GTL approaches first construct a fixed inter-subject relation graph that is based on similarities in voxel intensity values in the feature domain, which can then be used to propagate the known phenotype data (i.e., clinical scores and labels) from the training data to the testing data in the label domain. However, this type of graph is exclusively learned in the feature domain, and primarily due to outliers in the observed features, may not be optimal for label propagation in the label domain. To address this limitation, a progressive GTL (pGTL) method is proposed that gradually finds an intrinsic data representation that more accurately aligns imaging features with the phenotype data. In general, optimal feature-to-phenotype alignment is achieved using an iterative approach that: (1) refines inter-subject relationships observed in the feature domain by using the learned intrinsic data representation in the label domain, (2) updates the intrinsic data representation from the refined inter-subject relationships, and (3) verifies the intrinsic data representation on the training data to guarantee an optimal classification when applied to testing data. Additionally, the iterative approach is extended to multi-modal imaging data to further improve pGTL classification accuracy. Using Alzheimer's disease and Parkinson's disease study data, the classification accuracy of the proposed pGTL method is compared to several state-of-the-art classification methods, and the results show pGTL can more accurately identify subjects, even at different progression stages, in these two study data sets.

Graphical abstract

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Dual-core Steered Non-rigid Registration for Multi-modal Images via Bi-directional Image Synthesis

Publication date: Available online 13 May 2017
Source:Medical Image Analysis
Author(s): Xiaohuan Cao, Jianhua Yang, Yaozong Gao, Yanrong Guo, Guorong Wu, Dinggang Shen
In prostate cancer radiotherapy, computed tomography (CT) is widely used for dose planning purposes. However, because CT has low soft tissue contrast, it makes manual contouring difficult for major pelvic organs. In contrast, magnetic resonance imaging (MRI) provides high soft tissue contrast, which makes it ideal for accurate manual contouring. Therefore, the contouring accuracy on CT can be significantly improved if the contours in MRI can be mapped to CT domain by registering MRI with CT of the same subject, which would eventually lead to high treatment efficacy. In this paper, we propose a bi-directional image synthesis based approach for MRI-to-CT pelvic image registration. First, we use patch-wise random forest with auto-context model to learn the appearance mapping from CT to MRI domain, and then vice versa. Consequently, we can synthesize a pseudo-MRI whose anatomical structures are exactly same with CT but with MRI-like appearance, and a pseudo-CT as well. Then, our MRI-to-CT registration can be steered in a dual manner, by simultaneously estimating two deformation pathways: 1) one from the pseudo-CT to the actual CT and 2) another from actual MRI to the pseudo-MRI. Next, a dual-core deformation fusion framework is developed to iteratively and effectively combine these two registration pathways by using complementary information from both modalities. Experiments on a dataset with real pelvic CT and MRI have shown improved registration performance of the proposed method by comparing it to the conventional registration methods, thus indicating its high potential of translation to the routine radiation therapy.

Graphical abstract

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Ageing kinetics and strength of airborne-particle abraded 3Y-TZP ceramics

Publication date: Available online 12 May 2017
Source:Dental Materials
Author(s): Jasna Cotič, Peter Jevnikar, Andraž Kocjan
ObjectiveThe combined effects of alumina airborne-particle abrasion and prolonged in vitro ageing on the flexural strength of 3Y-TZP ceramic have been studied. The aim was to identify the different effects on the surface and subsurface regions that govern the performance of this popular bioceramic known for its susceptibility to low-temperature degradation (LTD).MethodsAs-sintered or airborne-particle abraded 3Y-TZP discs were subjected to ageing at 134°C for up to 480h. Biaxial flexural strength was measured and the relative amount of monoclinic phase determined using X-ray diffraction. The transformed zone depth (TZD) was observed on cross-sections with scanning electron microscopy coupled with a focused ion beam. Segmented linear regression was used to analyze the flexural strength and TZD as functions of the ageing time.ResultsA two-step linear ageing kinetics was detected in airborne-particle abraded specimens, reflecting the different microstructures through which the LTD proceeds into the bulk. A 10μm thick altered zone under the abraded surface was involved in both the surface strengthening and the increased ageing resistance. When the zone was annihilated by the LTD, the strength of the ceramic specimens and the speed of LTD returned to the values measured before abrasion. Even at prolonged ageing times, the strength of abraded groups was not lower than that of as-sintered groups.SignificanceBoth the ageing kinetics and the flexural strength were prominently affected by airborne-particle abrasion, which altered the subsurface microstructure and phase composition. Airborne-particle abrasion was not harmful to the 3Y-TZP ceramics' stability.

Graphical abstract

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PLGA nanoparticles as chlorhexidine-delivery carrier to resin-dentin adhesive interface

Publication date: Available online 12 May 2017
Source:Dental Materials
Author(s): Balasankar Meera Priyadarshini, Kakran Mitali, Thong Beng Lu, Harish K. Handral, Nileshkumar Dubey, Amr S. Fawzy
ObjectiveTo characterize and deliver fabricated CHX-loaded PLGA-nanoparticles inside micron-sized dentinal-tubules of demineralized dentin-substrates and resin-dentin interface.MethodsNanoparticles fabricated by emulsion evaporation were assessed in-vitro by different techniques. Delivery of drug-loaded nanoparticles to demineralized dentin substrates, interaction with collagen matrix, and ex-vivo CHX-release profiles using extracted teeth connected to experimental setup simulating pulpal hydrostatic pressure were investigated. Furthermore, nanoparticles association/interaction with a commercial dentin-adhesive applied to demineralized dentin substrates were examined.ResultsThe results showed that the formulated nanoparticles demonstrated attractive physicochemical properties, low cytotoxicity, potent antibacterial efficacy, and slow degradation and gradual CHX release profiles. Nanoparticles delivered efficiently inside dentinal-tubules structure to sufficient depth (>10μm) against the simulated upward pulpal hydrostatic-pressure, even after bonding-resins infiltration and were attached/retained on collagen-fibrils. These results verified the potential significance of this newly introduced drug-delivery therapeutic strategy for future clinical applications and promote for a new era of future dental research.SignificanceThis innovative drug-delivery strategy has proven to be a reliable method for delivering treatments that could be elaborated for other clinical applications in adhesive and restorative dentistry.

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Psychiatric Patient Length of Stay in the Emergency Department Following Closure of a Public Psychiatric Hospital

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Publication date: Available online 13 May 2017
Source:The Journal of Emergency Medicine
Author(s): Ryan K. Misek, Ashley D. Magda, Samantha Margaritis, Robert Long, Erik Frost
BackgroundPsychiatric patient boarding in the emergency department (ED) is a ubiquitous problem associated with increased morbidity and mortality.ObjectiveWe evaluate the effect of closing a public psychiatric facility in a major metropolitan area on the ED length of stay (LOS) of psychiatric patients.MethodsThis was a retrospective chart review at two metropolitan EDs of all patients assessed to require inpatient psychiatric hospitalization. The time of arrival, time of disposition, time of transfer, insurance status, and accepting facility type were collected prior to and following the closure of a local inpatient psychiatric facility.ResultsWe analyzed a total of 1107 patients requiring inpatient psychiatric hospitalization, with 671 patients who presented prior to the closure of the closest public psychiatric facility and 436 patients that presented following the facility closure. Following hospital closure, patients with private insurance (620 min before, 771 min after) and Medicare/Medicaid (642 min before, 718 min after) had statistically significantly longer ED LOS, as well as patients transferred to a private psychiatric hospital (664 min prior, 745 min after). However, overall ED length of stay following hospital closure for transfer of all psychiatric patients requiring inpatient hospitalization was not found to be statistically significant (1017 min prior, 967 min after).ConclusionThere was a statistically significant increase in ED LOS for patients with private insurance, Medicare/Medicaid, and for those patients transferred to a private psychiatric facility following closure of a public mental health hospital; however, overall, ED LOS was not increased for patients transferred to an inpatient psychiatric facility. This study highlights the significant impact that the closure of a single inpatient psychiatric facility can have on nearby EDs. We hope to bring attention to the need for increased psychiatric services during a time when there is a nationwide trend toward the reduction of available inpatient psychiatric beds.



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An Unusual Case of Flank Pain: More Than Just an Inguinal Hernia

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Publication date: Available online 13 May 2017
Source:The Journal of Emergency Medicine
Author(s): Kareem S. Elsayed, Raymond J. Melder, Michael C. Nguyen




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Numtogenesis as a Mechanism for Development of Cancer

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Publication date: Available online 13 May 2017
Source:Seminars in Cancer Biology
Author(s): Keshav K. Singh, Aaheli Roy Choudhury, Hemant K. Tiwari
Transfer of genetic material from cytoplasmic organelles to the nucleus, an ongoing process, has implications in evolution, aging, and human pathologies such as cancer. The transferred mitochondrial DNA (mtDNA) fragments in the nuclear genome are called nuclear mtDNA or NUMTs. We have named the process numtogenesis, defining the term as the transfer of mtDNA into the nuclear genome, or, less specifically, the transfer of mitochondria or mitochondrial components into the nucleus. There is increasing evidence of the involvement of NUMTs in human biology and pathology. Although information pertaining to NUMTs and numtogenesis is sparse, the role of this aspect of mitochondrial biology to human cancers is apparent. In this review, we present available knowledge about the origin and mechanisms of numtogenesis, with special emphasis on the role of NUMTs in human malignancies. We describe studies undertaken in our laboratory and in others and discuss the influence of NUMTs in tumor initiation and progression and in survival of cancer patients. We describe suppressors of numtogenesis and evolutionary conserved mechanisms underlying numtogenesis in cancer. An understanding the emerging field of numtogenesis should allow comprehension of this process in various malignancies and other diseases and, more generally, in human health.



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Antioxidant polyphenols in cancer treatment: friend, foe or foil?

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Publication date: Available online 13 May 2017
Source:Seminars in Cancer Biology
Author(s): Gian Luigi Russo, Idolo Tedesco, Carmela Spagnuolo, Maria Russo
Cancer prevention can be probably obtained with easier, faster and less financial strains by pursuing educational programs aimed to induce changes in lifestyle, starting from dietary habits. In the past decades, observational and case-control studies tried to establish a functional relationship between cancer mortality and morbidity and diet. The field becomes even more intricate when scientists investigated which dietary components are responsible for the putative, protective effects of fruits and vegetables against cancer. A relevant part of the literature focused on the positive role of "antioxidant" compounds in foods, including polyphenols. The present review critically evaluate clinical and pre-clinical studies based on polyphenol administration, which contributed to support the concept, deeply rooted in the general population, that antioxidant polyphenols can fight cancer. The controversial and contradictory issues related to the pros and cons on the use of polyphenols against cancer reflect the confounding assumption that cancer treatment and cancer prevention may overlap. We conclude that a clear cut must be done between these two concepts and that the experimental approaches to investigate one or the other should be significantly different, starting from adequate and specifically selected cellular models.



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Supervised or unsupervised rehabilitation after total hip replacement provides similar improvements for patients: a randomised controlled trial

Publication date: Available online 12 May 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Corinne Coulter, Diana M. Perriman, Teresa M. Neeman, Paul N. Smith, Jennifer M. Scarvell
ObjectiveTo determine do patients do better with unsupervised home PT or in an outpatient setting Are the outcomes after a supervised (centre-based) and an independent (home-based) physical rehabilitation program delivered in the early post-discharge phase (<8weeks) equivalent in an adult THR population.SettingAcute care public hospital in the region, supporting a population of almost 540,000.DesignSingle blinded randomised controlled trial.ParticipantsAdult patients (n=98) after unilateral elective total hip replacement (THR) were randomly assigned to supervised/centre-based exercise (n=56) or unsupervised/home exercise (n=42) and followed 6 months post-surgery.InterventionThe supervised group attended a 4 week outpatient rehabilitation program supervised by a physiotherapist. The unsupervised group was given written and pictorial instructions to perform rehabilitation independently at home.Outcome measuresThe WOMAC, SF-36 mental and physical component scores(MCS and PCS) questionnaires, the UCLA activity rating and the Timed up and Go test (TUG).ResultsThere were no differences between groups for any measure. Overall differences between the adjusted means were: WOMAC 0.5 [-6.75, 5.73], SF-36 PCS 0.8 [-6.5 - 8.1], SF-36 MCS 1.7 [-4.1 - 7.4], UCLA 0.3 [5.19, 6.10] and TUG 0 secs [-1.4 - 1.3].ConclusionResults demonstrated that outcomes in response to rehabilitation after THR are clinically and statistically similar whether the program was supervised or not. The results suggest that early rehabilitation programs can be effectively delivered unsupervised in the home to low-risk patients discharged home after THR. However, the relative effect of late stage rehabilitation was not tested.



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Mindfulness is Associated with Treatment Response from Non-Pharmacological Exercise Interventions in Knee Osteoarthritis

Publication date: Available online 12 May 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Augustine C. Lee, William F. Harvey, Lori Lyn Price, Xingyi Han, Jeffrey B. Driban, John B. Wong, Mei Chung, Timothy E. McAlindon, Chenchen Wang
ObjectiveTo examine the association between baseline mindfulness and response from exercise interventions in knee osteoarthritis (OA).DesignCohort Study; Responder analysis of a clinical trial subsetSettingUrban tertiary care academic hospitalParticipants86 participants with symptomatic, radiographic knee OA (mean age, 60 years; 74% female; 48% white)Interventions12 weeks (twice per week) of Tai Chi or Physical Therapy exerciseMain Outcome Measure(s)Treatment response was defined using Osteoarthritis Research Society International criteria indicating meaningful improvements in the Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain, function, or Patient Global Assessment scores. At baseline, participants completed the Five Facet Mindfulness Questionnaire (FFMQ; mean total score ±SD: 142±17) and were grouped into three categories of total mindfulness: higher, medium, or lower. Relative risk (RR) ratios were used to compare treatment response across groups.ResultsParticipants with higher total mindfulness appeared to be 38% (95% CI: 1.05, 1.83) more likely to meet responder criteria than those with lower mindfulness. We found no significant difference between medium and lower mindfulness groups (RR=1.0; 95% CI: 0.69, 1.44). Among the 5 mindfulness facets, medium Acting-with–Awareness was 46% (95% CI: 1.09, 1.96) more likely to respond than lower Acting-with–Awareness, and higher Acting-with–Awareness was 34% more likely to respond, but this did not reach significance (95% CI: 0.97, 1.86).ConclusionsIn this study, higher mindfulness, primarily driven by its Acting-with-Awareness facet, was significantly associated with a greater likelihood of response to non-pharmacological exercise interventions in knee OA. This suggests that mindfulness-cultivating interventions may increase the likelihood of response from exercise.



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High resolution T2 MRI in the diagnosis of cerebellopontine angle and internal auditory canal lesions

Publication date: Available online 13 May 2017
Source:Clinical Imaging
Author(s): Jonathan T. Maslan, Christopher M. Lack, Michael Zapadka, Tyler G. Gasser, Eric Oliver
High resolution T2 magnetic resonance imaging (MRI) can provide exquisite detail of internal auditory canal (IAC) and cerebellopontine angle (CPA) lesions. In this retrospective case series, blinded imaging sequences were delivered to three radiologists and compared with previously archived clinical reads that were non-blinded and incorporated both T1+C and T2 sequences together. This article demonstrates high sensitivity and specificity for high resolution T2 MRI particularly with lesions >5mm. This suggests a role for high resolution T2 MRI as an initial screening sequence or as a surveillance sequence.



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Early neurosyphilis presenting with facial palsy and an oral ulcer in a patient who is human immunodeficiency virus positive: a case report

Neurosyphilis is the tertiary stage of Treponema pallidum infection that involves the central nervous system, which occurs within days or weeks after an initial syphilis infection, especially in immunocompromised...

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Early neurosyphilis presenting with facial palsy and an oral ulcer in a patient who is human immunodeficiency virus positive: a case report

Neurosyphilis is the tertiary stage of Treponema pallidum infection that involves the central nervous system, which occurs within days or weeks after an initial syphilis infection, especially in immunocompromised...

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Possible involvement of the lipoxygenase and leukotriene signaling pathways in cisplatin-mediated renal toxicity

Abstract

Purpose

The present study examined the possible involvement of the lipoxygenase (LOX) pathway in cisplatin (CPT)-induced nephrotoxicity.

Methods

Wistar albino rats were challenged with CPT IP injection (7.5 mg/kg) and were sacrificed after one week. Signs of renal dysfunction, including urea and creatinine clearance levels and renal histological structure, were investigated. Gene and protein expression levels of different LOX pathway enzymes and products, including 5-LOX, 12-LOX, 15-LOX, 5-LOX activating protein (FLAP), leukotriene A4 hydrolase (LTA4 hydrolase), leukotriene C4 synthase (LTC4 synthase), LTB4 receptor, and cysteinyl (cys) LT receptor types 1 and 2, were also determined in the kidneys using real-time PCR and western blotting, respectively. The serum and kidney levels of LTB4 and inflammatory markers were also estimated.

Results

CPT renal toxicity was established as the creatinine and urea clearance levels were significantly reduced, while the serum levels of creatinine and urea were markedly increased. We reported a considerable up-regulation in the mRNA and protein expression levels of 5-LOX, FLAP, 12-LOX, LTA4 hydrolase, LTC4 synthase, LTB4 receptor, and Cys LT receptor types 1 and 2, while 15-LOX expression did not significantly change in the CPT group. Additionally, LTB4 and inflammatory indicators in serum and renal levels were elevated significantly in the CPT group. Histopathological examination clearly showed the nephrotoxic changes in the renal tissues of CPT-challenged animals.

Conclusions

Our findings suggested, for the first time, the participation of LOX enzymes and products in the signaling pathway leading to CPT-associated nephrotoxicity, which could be the foundation stone for combining LOX pathway attenuators with CPT therapy to decrease CPT-associated renal toxicity.



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UGT1A1 polymorphisms with irinotecan-induced toxicities and treatment outcome in Asians with Lung Cancer: a meta-analysis

Abstract

Previous studies of irinotecan pharmacogenetics have shown that the UGT1A1*28 polymorphism has an effect on irinotecan (IRI)-induced toxicities in Caucasians. Yet compared with the UGT1A1*6 mutation, the UGT1A1*28 occurs at a much lower frequency in the Asians. Whether UGT1A1*6 and UGT1A1*28 are associated with IRI-induced neutropenia, diarrhea and IRI-based chemotherapy tumor response (TR) in Asians with lung cancer remains controversial. In this meta-analysis, we found a higher risk of neutropenia and diarrhea with IRI-based chemotherapy in Asians with lung cancer carrying the UGT1A1*6 polymorphism. However, UGT1A1*28 showed a weak correlation with diarrhea, but no significant correlation with neutropenia. Neither UGT1A1*6 nor UGT1A1*28 is associated with IRI-based chemotherapy TR. These data suggest that the UGT1A1*28 polymorphism may not be a suitable biomarker to predict IRI-induced toxicities and chemotherapy TR in Asians, while UGT1A*6 polymorphism is associated with a higher risk of IRI-induced neutropenia and diarrhea, but not IRI-based chemotherapy TR.



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Characterization of rainwater chemical composition after a Southeast Asia haze event: insight of transboundary pollutant transport during the northeast monsoon

Abstract

Open biomass burning in Peninsula Malaysia, Sumatra, and parts of the Indochinese region is a major source of transboundary haze pollution in the Southeast Asia. To study the influence of haze on rainwater chemistry, a short-term investigation was carried out during the occurrence of a severe haze episode from March to April 2014. Rainwater samples were collected after a prolonged drought and analyzed for heavy metals and major ion concentrations using inductively coupled plasma mass spectroscopy (ICP-MS) and ion chromatography (IC), respectively. The chemical composition and morphology of the solid particulates suspended in rainwater were examined using a scanning electron microscope coupled with energy-dispersive X-ray spectroscopy (SEM-EDS). The dataset was further interpreted using enrichment factors (EF), statistical analysis, and a back trajectory (BT) model to find the possible sources of the particulates and pollutants. The results show a drop in rainwater pH from near neutral (pH 6.54) to acidic (<pH 4.00) during the haze to non-haze transitional period, suggesting that the deposition rate of sulfate and nitrate in the atmosphere via the precipitation process was relatively lower compared to the mineral components. Zinc, nitrate, and calcium, which were the predominant elements in the first rainwater samples. Besides, the results of the SEM-EDS indicated that the zinc was possibly originated from anthropogenic activities which are consistent with the results obtained from EF. The BT model showed that pollutants transported from the mainland of Indo-China and the marine region in the South China Sea were responsible for the high pollution event in the study area. These findings can be useful in identifying contributions of pollutants from single or multiple sources in rainwater samples during haze episodes.



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Evaluation of various solvent systems for lipid extraction from wet microalgal biomass and its effects on primary metabolites of lipid-extracted biomass

Abstract

Microalgae have tremendous potential to grow rapidly, synthesize, and accumulate lipids, proteins, and carbohydrates. The effects of solvent extraction of lipids on other metabolites such as proteins and carbohydrates in lipid-extracted algal (LEA) biomass are crucial aspects of algal biorefinery approach. An effective and economically feasible algae-based oil industry will depend on the selection of suitable solvent/s for lipid extraction, which has minimal effect on metabolites in lipid-extracted algae. In current study, six solvent systems were employed to extract lipids from dry and wet biomass of Scenedesmus obliquus. To explore the biorefinery concept, dichloromethane/methanol (2:1 v/v) was a suitable solvent for dry biomass; it gave 18.75% lipids (dry cell weight) in whole algal biomass, 32.79% proteins, and 24.73% carbohydrates in LEA biomass. In the case of wet biomass, in order to exploit all three metabolites, isopropanol/hexane (2:1 v/v) is an appropriate solvent system which gave 7.8% lipids (dry cell weight) in whole algal biomass, 20.97% proteins, and 22.87% carbohydrates in LEA biomass.

Graphical abstract:

Lipid extraction from wet microalgal biomass and biorefianry approach


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Adsorption of terpenic compounds onto organo-palygorskite

Abstract

Essential oils from aromatic plants are currently mentioned as suitable tools for excellent protection of stored grains from insect pest attacks. The present work aimed to study the processes of the synthesis insecticidal formulation with clay. The active terpenic compounds of essential oil of Eucalyptus globulus (Eg) were fixed in the palygorskite by adsorption process. Two sample types of palygorskites were used: raw and organo-palygorskite. The palygorskite clays were characterized by different physicochemical techniques including X-ray diffraction (XRD), Fourier transform infrared (FTIR) analyses, thermogravimetric analysis (TG), differential thermal analysis (DTA), Brunauer-Emmet-Teller (BET), and scanning electron microscope (SEM). Results reveal that the raw clay has a fibrous structure with impurities essential calcite. These structures and physicochemical properties of raw palygorskite and organo-palygorskite give it the potential of material adsorbent. Results show that the adsorption capacity strongly depends on affinity between terpenic compounds and organic cations rather than on interlayer distance of organo-palygorskite. The highest adsorption capacity of terpenic compounds is acquired with palygorskite interlaced by didodecyldimethylammonium bromide (DDDMA). These results validated the potential utility of the Paly-DDDMA as adsorbent fibrous clay for the retention of terpenic compounds in application of environmental preservation.



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Decontamination of arsenic(V)-contained liquid phase utilizing Fe 3 O 4 /bone char nanocomposite encapsulated in chitosan biopolymer

Abstract

The application of a novel nanocomposite synthesized through the combination of Fe3O4 nanoparticles and bone char particles for the adsorption of As(V) ions in the aquatic medium was investigated. As-prepared nanocomposite was immobilized by using chitosan biopolymer. The characterization of the nanocomposite was performed via SEM, XRD, FT-IR, and BET together with the determination of zero-point charge of the adsorbent surface. As results, the obtained experimental data were fitted well with pseudo-first-order kinetic model (R2 = 0.997) and Langmuir isotherm model (R2 = 0.990) with the maximum adsorption capacity of about 112 μg/g. Increasing the dosage of nanocomposite and initial solute concentration led to increasing the adsorption capacity of As(V) ions, while decreasing the solution temperature resulted in the enhanced adsorption process. According to the results of thermodynamic study, the adsorption of As(V) ions onto the nanocomposite was spontaneous and exothermic in nature.



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Evaluation of carbofuran-mediated toxicity against human lymphocytes and red blood cells in simulated wastewater degraded by coagulation–flocculation

Abstract

Coagulation–flocculation in water treatment has been relied upon aluminum (Al) and iron (Fe) salts for treatment of contaminants present in source waters containing dissolved organic compounds. However, water quality deteriorates day by day which makes it urgent to improve the standards of the treatment procedure. Coagulation–flocculation–sedimentation performance of ferric chloride and alum was comparatively investigated for carbofuran treatment in simulated wastewater. Coagulation trails were performed in a jar test at several pH levels and coagulant doses to determine reduction efficiencies of carbofuran degradation and chemical oxygen demand (COD). Effect of carbofuran on proliferation, viability, and direct cytotoxicity was performed using human neuroblastoma cells U-87. Direct toxicity of carbofuran on human mononuclear cells and red blood cells (RBC) was also analyzed. Carbofuran and its derivatives were found to be relatively safe at low concentration (2–5 μM). However, at slightly higher concentration (8 μM), a moderate loss in viability and proliferative potential was observed. Taken together, these results suggest that carbofuran appears to be safe at moderate or low concentration with respect to viability of normal human lymphocytes and RBC.



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Biogeochemical controls on mercury methylation in the Allequash Creek wetland

Abstract

We measured mercury methylation potentials and a suite of related biogeochemical parameters in sediment cores and porewater from two geochemically distinct sites in the Allequash Creek wetland, northern Wisconsin, USA. We found a high degree of spatial variability in the methylation rate potentials but no significant differences between the two sites. We identified the primary geochemical factors controlling net methylmercury production at this site to be acid-volatile sulfide, dissolved organic carbon, total dissolved iron, and porewater iron(II). Season and demethylation rates also appear to regulate net methylmercury production. Our equilibrium speciation modeling demonstrated that sulfide likely regulated methylation rates by controlling the speciation of inorganic mercury and therefore its bioavailability to methylating bacteria. We found that no individual geochemical parameter could explain a significant amount of the observed variability in mercury methylation rates, but we found significant multivariate relationships, supporting the widely held understanding that net methylmercury production is balance of several simultaneously occurring processes.



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The effects of cadmium pulse dosing on physiological traits and growth of the submerged macrophyte Vallisneria spinulosa and phytoplankton biomass: a mesocosm study

Abstract

Pulse inputs of heavy metals are expected to increase with a higher frequency of extreme climate events (heavy rain), leading to stronger erosion of contaminated and fertilized farmland soils to freshwaters, with potentially adverse effects on lake ecosystems. We conducted a 5-month mesocosm study to elucidate the responses of the submerged macrophyte Vallisneria spinulosa and phytoplankton to four different doses of cadmium (Cd): 0 (control), 0.05, 0.5, and 5 g m−2 (CK, I, II, and III, respectively) under mesotrophic conditions. We found that total phosphorus concentrations were larger in the three Cd pulse treatments, whereas total nitrogen concentrations did not differ among the four treatments. The contents of chlorophyll a and soluble sugar in macrophyte leaves decreased in III, and total biomass, ramet number, plant height, and total stolon length of macrophytes were lower in both II and III. In contrast, abundances of the three main phytoplankton taxa—Cyanophyta, Chlorophyta, and Bacillariophyta—did not differ among treatments. Total phytoplankton biomass was, however, marginally lower in CK than in the Cd treatments. We conclude that exposure to strong Cd pulses led to significantly reduced growth of macrophytes, while no obvious effect appeared for phytoplankton.



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