Κυριακή, 18 Φεβρουαρίου 2018

Glucagon-like peptide 2 decreases osteoclasts by stimulating apoptosis dependent on nitric oxide synthase

Abstract

Objectives

Glucagon-like peptide 2 (GLP2) is involved in the regulation of energy absorption and metabolism. Despite the importance of the GLP2 signalling mechanisms on osteoclast, little has been studied on how GLP2 works during osteoclastogenesis.

Materials and Methods

RAW264.7 cells were infected with rLV-Green-GLP2. The induction of osteoclasts was performed by RANKL. TRAP were detected by RT-PCR, Western blotting and staining. Total nitric oxide and total NOS activity were measured. Cells apoptosis was detected by Hoest33258 and Annix V staining. Animal test, chromatin immunoprecipitation (CHIP), co-immunoprecipitation(IP) and luciferase reporter assay were also performed.

Results

We indicate that GLP2 is associated with osteoporosis-related factors in aged rats, including BALP, TRAP, IL6, TNFα, Nitric Oxide (NO), iNOS, calcitonin and occludin. Moreover, GLP2 is demonstrated to result in negative action during proliferation of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts. Furthermore, GLP2 decreases osteoclasts induced from monocyte/macrophage cells RAW264.7 as well as the serum TRAP activity in aged rats. Mechanistic investigations reveal GLP2 enhances the expression of iNOS through stimulating the activity of TGFβ-Smad2/3 signalling in osteoclasts. In particular, inhibition of TGFβ fully abrogates this function of GLP2 in osteoclasts. Strikingly, overexpression of GLP2 significantly increases the product of nitric oxide via iNOS which promotes apoptosis of osteoclasts by decreasing bcl2 or increasing caspase3. Thereby, the ability of GLP2 to regulate apoptosis depends on TGFβ-Smad2/3-iNOS-NO signalling pathway since total NOS inhibitor L-NMMA specifically inhibits the actions by GLP2.

Conclusions

GLP2 induces apoptosis via TGFβ-Smad2/3 signalling, which contributes to the inhibition of the proliferation of osteoclasts and which may provide potential therapeutic targets for the treatment of osteoporosis.



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Evaluation and application of prebiotic and probiotic ingredients for development of ready to drink tea beverage

Abstract

Ready-to-drink (RTD) ice tea is a ready prepared tea, produced from green and black tea originating from same plant Camellia sinensis. The objective of this study was to determine the effect of prebiotics [galacto-oligosaccharide (GOS), fructo-oligosaccharide (FOS), and inulin] or synbiotic ingredients (GOS, FOS, inulin, and Lactobacillus acidophilus) on the sensory properties and consumer acceptability of RTD. The quality of green tea extract (GTE) and black tea extract (BTE) was improved with pretreatment of cellulase and pectinase enzymes. The combined enzymatic extraction amplified total extractives up to 76% in GTE and 72% in BTE. Total polyphenol was found to be enhanced to 24% in GTE and 19% in BTE. GTE was further selected for development of RTD in two different formats; synbiotic RTD and prebiotic RTD premix and analyzed for sensory attributes (colour, aroma, taste, and acceptability). Synbiotic RTD was also evaluated for stability over a period of 28 days at 4 °C. Synbiotic RTD developed an unpleasant flavor and aroma during the shelf life. Premix format of RTD developed using spray drying was reconstituted and found to be functionally and sensorially acceptable.



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IJMS, Vol. 19, Pages 611: The Role of the Estrogen Pathway in the Tumor Microenvironment

IJMS, Vol. 19, Pages 611: The Role of the Estrogen Pathway in the Tumor Microenvironment

International Journal of Molecular Sciences doi: 10.3390/ijms19020611

Authors: Natalie Rothenberger Ashwin Somasundaram Laura P. Stabile

Estrogen receptors are broadly expressed in many cell types involved in the innate and adaptive immune responses, and differentially regulate the production of cytokines. While both genomic and non-genomic tumor cell promoting mechanisms of estrogen signaling are well characterized in multiple carcinomas including breast, ovarian, and lung, recent investigations have identified a potential immune regulatory role of estrogens in the tumor microenvironment. Tumor immune tolerance is a well-established mediator of oncogenesis, with increasing evidence indicating the importance of the immune response in tumor progression. Immune-based therapies such as antibodies that block checkpoint signals have emerged as exciting therapeutic approaches for cancer treatment, offering durable remissions and prolonged survival. However, only a subset of patients demonstrate clinical response to these agents, prompting efforts to elucidate additional immunosuppressive mechanisms within the tumor microenvironment. Evidence drawn from multiple cancer types, including carcinomas traditionally classified as non-immunogenic, implicate estrogen as a potential mediator of immunosuppression through modulation of protumor responses independent of direct activity on tumor cells. Herein, we review the interplay between estrogen and the tumor microenvironment and the clinical implications of endocrine therapy as a novel treatment strategy within immuno-oncology.



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Our cities are driving evolution and it’s not all bad news

Urbanisation may be overrunning our planet, but in his book Darwin Comes to Town, evolutionary biologist Menno Schilthuizen seeks – and finds – the positives

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Long haul with a free conscience

Gone West is offering travellers and businesses a simple way to reduce their carbon footprints

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Our cities are driving evolution and it’s not all bad news

Urbanisation may be overrunning our planet, but in his book Darwin Comes to Town, evolutionary biologist Menno Schilthuizen seeks – and finds – the positives

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Long haul with a free conscience

Gone West is offering travellers and businesses a simple way to reduce their carbon footprints

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Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation

Publication date: Available online 18 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Jun-Xia Zhang, Xin-Liang Qu, Peng Chu, Du-Jiang Xie, Lin-Lin Zhu, Yue-Lin Chao, Li Li, Jun-Jie Zhang, Shao-Liang Chen
Uncoupled endothelial nitric oxide synthase (eNOS) produces O2 instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O2 production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O2 burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O2 releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis.



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Convergence of BOLD and ERP Measures of Neural Reactivity to Emotional Faces in Children and Adolescents with and without Anxiety Disorders

Publication date: Available online 17 February 2018
Source:Biological Psychology
Author(s): Nóra Bunford, Autumn Kujawa, Kate D. Fitzgerald, Christopher S. Monk, K. Luan Phan
The neural bases of emotion are commonly measured using blood-oxygen-level-dependent (BOLD) signal and the late positive potential (LPP) event-related potential (ERP) component, but rarely together in the same individuals. Despite evidence of developmental changes in processing socio-emotional signals (e.g., faces) as reflected by both BOLD and LPP indices of brain maturation, the literature on the correspondence between these measures is limited to healthy adults, leaving questions regarding such correspondence across development and in clinical populations unaddressed. We examined the relationship between BOLD and LPP during an emotional face processing task in a large sample of youth (N = 70; age 7–19 years) with and without anxiety disorders, and tested whether BOLD signal in regions corresponding to LPP may account for age-related decreases in LPP. Greater activation in bilateral inferior frontal gyrus (IFG)/orbitofrontal gyrus (OFG), left supplementary motor area, right superior parietal lobule, and bilateral amygdala correlated with enhanced LPP to emotional faces in both anxious and healthy youth. Older youth exhibited reduced activation in bilateral IFG/OFG and bilateral amygdala, as well as reduced LPP. Decreased right IFG/OFG activation mediated the association between age and LPP. These findings support correspondence between these measures and need for multi-method approaches and indicate that age-related decreases in LPP may be driven, in part, by decreased IFG/OFG activation.



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EEG phase states at stimulus onset in a variable-ISI Go/NoGo task: Effects on ERP components

Publication date: Available online 17 February 2018
Source:Biological Psychology
Author(s): Robert J. Barry, Jack S. Fogarty, Frances M. De Blasio, Diana Karamacoska
Previous EEG-ERP dynamics studies found non-random “preferred” EEG phases at stimulus onset in a fixed interstimulus interval (ISI) equiprobable auditory Go/NoGo paradigm, with substantial effects on ERP components. Here we changed to a variable ISI task to prevent/reduce preferential phase occurrence. Discrete Fourier transforms decomposed prestimulus EEG at Cz for each trial to calculate the phase of different frequencies at stimulus onset; we combined these into the delta, theta, alpha, and beta bands, and then sorted trials into phase quartiles for each. ERPs from the raw EEG, assessed using temporal Principal Components Analyses, were examined as a function of phase at stimulus onset. Preferential phase occurrence was reduced as predicted, but random phase substantially impacted component amplitudes. For example, negativity in delta enhanced Go and NoGo P3b; and in theta reduced NoGo but not Go P3b. Overall, EEG phases at stimulus onset support differential cognitive processing in this two-choice task.



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Educate patients to recognise signs and symptoms of potential infection during neutropenia: https://t.co/oVSh4B2C3u https://t.co/fFy2DWxtP8

Educate patients to recognise signs and symptoms of potential infection during neutropenia: https://t.co/oVSh4B2C3u https://t.co/fFy2DWxtP8

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6-Shogaol induces caspase-independent paraptosis in cancer cells via proteasomal inhibition

Publication date: Available online 17 February 2018
Source:Experimental Cell Research
Author(s): Divya Nedungadi, Anupama Binoy, Nanjan Pandurangan, Sanjay Pal, Bipin G. Nair, Nandita Mishra
An α, β-unsaturated carbonyl compound of ginger, 6-Shogaol (6S), induced extensive cytoplasmic vacuolation and cell death in breast cancer cell (MDA-MB-231) and non-small lung cancer (A549) cells. In the presence of autophagic inhibitors the cells continued to exhibit cytoplasmic vacuolation and cell death clearly distinguishing it from the classic autophagic process. 6S induced death did not exhibit the characteristic apoptotic features like caspase cleavage, phosphatidyl serine exposure and DNA fragmentation. The immunofluorescence with the Endoplasmic Reticulum (ER) resident protein, calreticulin indicated that the vacuoles were of ER origin, typical of paraptosis. This was supported by the increase in level of microtubule associated protein light chain 3B (LC3 I and LC3 II) and polyubiquitin binding protein, p62. The level of ER stress markers like polyubiquitinated proteins, Bip and CHOP also consistently increased. We have found that 6S inhibits the 26S proteasome. The proteasomal inhibitory activity was elucidated by a) molecular docking of 6S onto the active site of β5 subunit and b) reduced fluorescence by the fluorogenic substrate of the chymotrypsin-like subunit. In conclusion these studies demonstrate for the first time that proteasomal inhibition by 6S induces cell death via paraptosis. So 6-shogaol may act as a template for anti-cancer lead discovery against the apoptosis resistant cancer cells.



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Ras protein's role in spreading cancer

Protein systems, such as Ras, make up the complex signaling pathways that control whether a cell divides or, in some cases, becomes cancerous and metastasizes into other regions of the body. For example, 98 percent of pancreatic cancers show Ras protein...

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Studying mitosis' structure to understand the inside of cancer cells

Cell division is an intricately choreographed ballet of proteins and molecules that divide the cell. During mitosis, microtubule-organizing centers (MTOCs) assemble the spindle fibers that separate the copying chromosomes of DNA. While scientists are...

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A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration.

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A multifaceted coating on titanium dictates osteoimmunomodulation and osteo/angio-genesis towards ameliorative osseointegration.

Biomaterials. 2018 Feb 06;162:154-169

Authors: Bai L, Du Z, Du J, Yao W, Zhang J, Weng Z, Liu S, Zhao Y, Liu Y, Zhang X, Huang X, Yao X, Crawford R, Hang R, Huang D, Tang B, Xiao Y

Abstract
A multifaceted coating for hard tissue implants, with favorable osteogenesis, angiogenesis, and osteoimmunomodulation abilities, would be of great value since it could improve osseointegration and alleviate prosthesis loosening. However, to date there are few coatings that fully satisfy these criteria. Herein we describe a microporous TiO2 coating decorated with hydroxyapatite (HA) nanoparticles that is generated by micro-arc oxidation of pure titanium (Ti) and followed annealing. By altering the annealing temperature, it is possible to simultaneously tune the coating's physical (morphology and wettability) and chemical (composites and crystallinity) properties. A coating produced with micro-arc oxidization (MAO) with an annealing temperature of 650 °C (MAO-650) exhibits numerous favorable physicochemical properties, such as hybrid micro-nano morphology, superhydrophilicity, and highly crystalline HA nanoparticles. In vitro experiments reveal that the MAO-650 coating not only supports proliferation and differentiation of both osteoblasts and endothelial cells, but also inhibits the inflammatory response of macrophages and enables a favorable osteoimmunomodulation to facilitate osteo/angio-genesis. In vivo evaluation mirrors these results, and shows that the MAO-650 coating results in ameliorative osseointegration when compared with the pristine MAO coating. These data highlight the profound effect of surface physicochemical properties on the regulation of osteo/angio-genesis and osteoimmunomodulation in the enhancement of osseointegration.

PMID: 29454274 [PubMed - as supplied by publisher]



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Associations of household renovation materials and periods with childhood asthma, in China: A retrospective cohort study.

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Associations of household renovation materials and periods with childhood asthma, in China: A retrospective cohort study.

Environ Int. 2018 Feb 14;113:240-248

Authors: Zhang J, Sun C, Liu W, Zou Z, Zhang Y, Li B, Zhao Z, Deng Q, Yang X, Zhang X, Qian H, Sun Y, Sundell J, Huang C

Abstract
BACKGROUND: Childhood asthma is prevalent in China. However, there is a lack of evidence on whether household renovation, including the materials used and the periods, are associated with the disease.
OBJECTIVES: To investigate the associations between household decoration materials and renovation periods, and childhood asthma and its related symptoms.
METHODS: During 2010-2012, a retrospective cohort study was initiated in seven cities of China, and 40,010 children, aged 3-6 years, were recruited. Data on demographics, health status, and home decoration conditions were collected using a parent-administered questionnaire. Two-level (city-child) logistic regression analyses with adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were performed to show the target associations. Sensitivity analysis was performed by stratifying data for children in the southern and northern cities.
RESULTS: Children whose homes underwent renovation or the addition of new furniture within 1 year before pregnancy, during pregnancy, at age 0-1 year, and after age 1 year had significantly (p < 0.05) higher prevalence of childhood asthma and its related symptoms. The use of solid wood floors and wallpaper had significant associations (cement: AOR, 95% CI: 1.59, 1.17-2.17; lime: AOR, 95% CI: 1.31, 1.00-1.71) with an increased risk of lifetime asthma. Household renovation and the addition of new furniture during pregnancy had significant associations with lifetime asthma (renovation: AOR, 95% CI: 1.23, 1.01-1.51); lifetime wheeze (renovation: AOR, 95% CI: 1.21, 1.05-1.39; furniture: AOR, 95% CI: 1.24, 1.14-1.36), current wheeze (renovation: AOR, 95% CI, 1.21 1.05-1.40; furniture: AOR, 95% CI: 1.23, 1.12-1.34), and current dry cough (renovation: AOR, 95% CI: 1.41, 1.23-1.63; furniture: AOR, 95% CI: 1.28, 1.17-1.41). Similar associations were found between the addition of new furniture during early childhood and lifetime asthma and its related symptoms. Except for the association between lifetime wheeze and flooring materials, the studied associations were generally stronger among children from the northern cities.
CONCLUSIONS: We confirmed that using cellulose based materials in home decoration and renovation, and adding new furniture during early childhood and pregnancy could be risk factors for childhood asthma. The association between household decoration during early childhood and childhood asthma may be stronger in the northern cities of China.

PMID: 29454245 [PubMed - as supplied by publisher]



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Making space work: Staff socio-spatial practices in a paediatric outpatient department.

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Making space work: Staff socio-spatial practices in a paediatric outpatient department.

Health Place. 2018 Feb 14;50:146-153

Authors: Water T, Wrapson J, Reay S, Ford K

Abstract
Studies of the characteristics of therapeutic landscapes have become common in medical geography. However, there is limited analysis of how therapeutic landscapes are produced. Based upon the qualitative theoretical thematic analysis of focus group data, this study examined the spatial work carried out by healthcare practitioners in a paediatric outpatients' department, turning unsatisfactory space into a therapeutic place. The study highlights the spatial strategies employed by staff to mitigate socio-spatial deficiencies in the healthcare environment. Staff perceived the task of making space work as an integral part of their duty of care to patients and an important facet of their professional identity. This study concludes that many of the spatial aspects of health care practice are often taken for granted. However this may hide the crucial role that health professionals have in producing places that heal.

PMID: 29454242 [PubMed - as supplied by publisher]



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Effect-based trigger values for in vitro and in vivo bioassays performed on surface water extracts supporting the environmental quality standards (EQS) of the European Water Framework Directive.

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Effect-based trigger values for in vitro and in vivo bioassays performed on surface water extracts supporting the environmental quality standards (EQS) of the European Water Framework Directive.

Sci Total Environ. 2018 Feb 14;628-629:748-765

Authors: Escher BI, Aїt-Aїssa S, Behnisch PA, Brack W, Brion F, Brouwer A, Buchinger S, Crawford SE, Du Pasquier D, Hamers T, Hettwer K, Hilscherová K, Hollert H, Kase R, Kienle C, Tindall AJ, Tuerk J, van der Oost R, Vermeirssen E, Neale PA

Abstract
Effect-based methods including cell-based bioassays, reporter gene assays and whole-organism assays have been applied for decades in water quality monitoring and testing of enriched solid-phase extracts. There is no common EU-wide agreement on what level of bioassay response in water extracts is acceptable. At present, bioassay results are only benchmarked against each other but not against a consented measure of chemical water quality. The EU environmental quality standards (EQS) differentiate between acceptable and unacceptable surface water concentrations for individual chemicals but cannot capture the thousands of chemicals in water and their biological action as mixtures. We developed a method that reads across from existing EQS and includes additional mixture considerations with the goal that the derived effect-based trigger values (EBT) indicate acceptable risk for complex mixtures as they occur in surface water. Advantages and limitations of various approaches to read across from EQS are discussed and distilled to an algorithm that translates EQS into their corresponding bioanalytical equivalent concentrations (BEQ). The proposed EBT derivation method was applied to 48 in vitro bioassays with 32 of them having sufficient information to yield preliminary EBTs. To assess the practicability and robustness of the proposed approach, we compared the tentative EBTs with observed environmental effects. The proposed method only gives guidance on how to derive EBTs but does not propose final EBTs for implementation. The EBTs for some bioassays such as those for estrogenicity are already mature and could be implemented into regulation in the near future, while for others it will still take a few iterations until we can be confident of the power of the proposed EBTs to differentiate good from poor water quality with respect to chemical contamination.

PMID: 29454215 [PubMed - as supplied by publisher]



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HSF4 transcriptional regulates HMOX-1 expression in HLECs.

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HSF4 transcriptional regulates HMOX-1 expression in HLECs.

Gene. 2018 Feb 14;:

Authors: Liao S, Qu Z, Li L, Zhou B, Gao M, Huang M, Li D

Abstract
The major causes for cataract formation are free radicals, which are neutralized by the endogenous antioxidants. However, how the human lens clean these harmful free radicals is still unclear. Transcriptional factor heat shock factor 4 (HSF4) is a cataract-causing gene and plays important roles during lens development. Here we show that HMOX-1, an anti-oxidase, is a bona fide transcriptional target gene of HSF4 in HLECs (human lens epithelial cells). HSF4 directly binds to the HSE element in HMOX-1 promoter to mediate its mRNA transcription and protein accumulation. The HSE element located at the region of -389 bp to -362 bp upstream from the TSS (transcription start site), which is critical for HMOX-1 transcriptional activation. Furthermore, knockdown of HSF4 by siRNA inhibited HMOX-1 expression. Thus, these data revealed a novel transcription target of HSF4 and provided new insights into anti-oxidation regulation in lens and age-related cataract.

PMID: 29454088 [PubMed - as supplied by publisher]



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Looking for capacities rather than vulnerabilities: The moderating effect of health assets on the associations between adverse social position and health.

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Looking for capacities rather than vulnerabilities: The moderating effect of health assets on the associations between adverse social position and health.

Prev Med. 2018 Feb 14;:

Authors: Roy M, Levasseur M, Doré I, St-Hilaire F, Michallet B, Couturier Y, Maltais D, Lindström B, Généreux M

Abstract
To increase capacities and control over health, it is necessary to foster assets (i.e. factors enhancing abilities of individuals or communities). Acting as a buffer, assets build foundations for overcoming adverse conditions and improving health. However, little is known about the distribution of assets and their associations with social position and health. In this study, we documented the distribution of health assets and examined whether these assets moderate associations between adverse social position and self-reported health. A representative population-based cross-sectional survey of adults in the Eastern Townships, Quebec, Canada (n = 8737) was conducted in 2014. Measures included assets (i.e. resilience, sense of community belonging, positive mental health, social participation), self-reported health (i.e. perceived health, psychological distress), and indicators of social position. Distribution of assets was studied in relation to gender and social position. Logistic regressions examined whether each asset moderated associations between adverse social position and self-reported health. Different distributions of assets were observed with different social positions. Women were more likely to participate in social activities while men were more resilient. Resilience and social participation were moderators of associations between adverse social position (i.e. living alone, lower household income) and self-reported health. Having assets contributes to better health by increasing capacities. Interventions that foster assets and complement current public health services are needed, especially for people in unfavorable situations. Health and social services decision-makers and practitioners could use these findings to increase capacities and resources rather than focusing primarily on preventing diseases and reducing risk factors.

PMID: 29454078 [PubMed - as supplied by publisher]



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Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex in depressive episodes of patients with Major Depressive Disorder, Bipolar Disorder I, and Major Depressive with Alcohol Use Disorders.

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Add-on high frequency deep transcranial magnetic stimulation (dTMS) to bilateral prefrontal cortex in depressive episodes of patients with Major Depressive Disorder, Bipolar Disorder I, and Major Depressive with Alcohol Use Disorders.

Neurosci Lett. 2018 Feb 14;:

Authors: Rapinesi C, Kotzalidis GD, Ferracuti S, Girardi N, Zangen A, Sani G, Raccah RN, Girardi P, Pompili M, Casale AD, Sapienza Centre for Research on Personalised Mental Health

Abstract
BACKGROUND: Dorsolateral prefrontal cortex (DLPFC) is critically involved in mood and alcohol use disorders.
OBJECTIVE: We aimed to investigate the safety of intervention with add-on bilateral prefrontal high-frequency deep transcranial magnetic stimulation (dTMS) and between-group differences in treatment response in patients with different types of depressive episodes, including major depressive episodes in the course of major depressive disorder (MDD), bipolar disorder, type I (BD-I), and MDD with alcohol use disorder (MDAUD).
METHODS: We conducted a 6-month open-label study, involving 82 patients with DSM-5 Depressive Episode. Of these, 41 had diagnosis of MDD, 20 BD-I, and 21 MDAUD. All patients received standard drug treatment and add-on dTMS over the bilateral DLPFC with left prevalence for four weeks, with five sessions in each week. We rated mood state with the Hamilton Depression Rating Scale (HDRS) at baseline, one-month, and six-month follow-up visits.
RESULTS: Mean total HDRS scores dropped from 22.8 (SD = 5.9) at baseline to 10.4 (SD = 3.6) at 1 month, to 10.0 (SD = 4.5) at 6 months, while response/remission were 70.73% (N = 58) and 19.51% (N = 16) at 1 month and 76.83% (N = 63) and 32.93% (27) at 6 months, respectively, with no between-group differences. No patient experienced any side effects.
CONCLUSIONS: High-frequency DLPFC dTMS was well tolerated and did not significantly differ on improvement of depression in MDD, BD-I, and MDAUD.

PMID: 29454034 [PubMed - as supplied by publisher]



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Predicting Cognitive Decline with Deep Learning of Brain Metabolism and Amyloid Imaging.

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Predicting Cognitive Decline with Deep Learning of Brain Metabolism and Amyloid Imaging.

Behav Brain Res. 2018 Feb 14;:

Authors: Choi H, Jin KH, Alzheimer’s Disease Neuroimaging Initiative

Abstract
For effective treatment of Alzheimer's disease (AD), it is important to identify subjects who are most likely to exhibit rapid cognitive decline. We aimed to develop an automatic image interpretation system based on a deep convolutional neural network (CNN) which can accurately predict future cognitive decline in mild cognitive impairment (MCI) patients using flurodeoxyglucose and florbetapir positron emission tomography (PET). PET images of 139 patients with AD, 171 patients with MCI and 182 normal subjects obtained from Alzheimer's Disease Neuroimaging Initiative database were used. Deep CNN was trained using 3-dimensional PET volumes of AD and normal controls as inputs. Manually defined image feature extraction such as quantification using predefined region-of-interests was unnecessary for our approach. Furthermore, it used minimally processed images without spatial normalization which has been commonly used in conventional quantitative analyses. Cognitive outcome of MCI subjects was predicted using this network. The prediction accuracy of the conversion of mild cognitive impairment to AD was compared with the conventional feature-based quantification approach. Accuracy of prediction (84.2%) for conversion to AD in MCI patients outperformed conventional feature-based quantification approaches. ROC analyses revealed that performance of CNN-based approach was significantly higher than that of the conventional quantification methods (p < 0.05). Output scores of the network were strongly correlated with the longitudinal change in cognitive measurements (p < 0.05). These results show the feasibility of deep learning as a practical tool for developing predictive neuroimaging biomarker.

PMID: 29454006 [PubMed - as supplied by publisher]



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GATA3 acetylation at K119 by CBP inhibits cell migration and invasion in lung adenocarcinoma.

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GATA3 acetylation at K119 by CBP inhibits cell migration and invasion in lung adenocarcinoma.

Biochem Biophys Res Commun. 2018 Feb 14;:

Authors: Li X, Jin J, Yang S, Xu W, Meng X, Deng H, Zhan J, Gao S, Zhang H

Abstract
GATA3 is a transcriptional factor involved in the development of multiple organs. Post translational modifications of GATA3 are critical to its function. Here, we report that GATA3 interacts with and is acetylated by the acetyltransferase CBP. Class I deacetylases HDAC1, HDAC2 and HDAC3 deacetylate GATA3. The major acetylated site of GATA3 in lung adenocarcinoma cells was determined at lysine 119 (AcK119). Functionally, GATA3-acetylation mimics K119Q mutant was found to inhibit lung adenocarcinoma cell migration and invasion with concomitant downregulation of EMT-controlling transcriptional factors Slug, Zeb1 and Zeb2. Taken together, we demonstrated that GATA3 acetylation at lysine 119 by CBP hinders the migration and invasion of lung adenocarcinoma cells.

PMID: 29453984 [PubMed - as supplied by publisher]



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Preclinical evaluation of a semi-automated and rapid commercial electrophoresis assay for von Willebrand factor multimers.

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Preclinical evaluation of a semi-automated and rapid commercial electrophoresis assay for von Willebrand factor multimers.

J Clin Lab Anal. 2018 Feb 17;:

Authors: Pikta M, Zemtsovskaja G, Bautista H, Nouadje G, Szanto T, Viigimaa M, Banys V

Abstract
BACKGROUND: The von Willebrand factor (VWF) multimer test is required to correctly subtype qualitative type 2 von Willebrand disease (VWD). The current VWF multimer assays are difficult, nonstandardized, and time-consuming. The purpose of this study was to evaluate the clinical utility of the commercial VWF multimer kit by Sebia (Lisses, France), an electrophoresis technique yielding same-day results.
METHODS: Ten healthy volunteer plasma samples, in-house reference plasma (IRP) and commercial normal plasma (CNP) samples, 10 plasma samples from patients with a known VWD type, 1 hemophilia A plasma sample, and 7 external quality assurance (EQA) samples were analyzed using the commercial VWF multimer kit. Additional coagulation testing included measurements of VWF antigen (VWF:Ag), VWF activity (VWF:Ac), and FVIII activity (FVIII:C).
RESULTS: The CNP results revealed a relative loss of the highest molecular weight multimers; therefore, IRP was preferred as the reference sample. The interpretations of 10 patients with a known VWD type could be successfully reproduced and agreed with previous VWF multimer results. In all EQA surveys, the multimer results and final VWD diagnosis agreed with expert opinion.
CONCLUSIONS: The VWF multimer assay by Sebia is easy to perform and can be successfully implemented in any clinical laboratory for second-stage evaluation of VWD. The resolution power of multimer distribution is adequate to correctly classify VWD types 1, 2A, 2B, and 3.

PMID: 29453814 [PubMed - as supplied by publisher]



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Testing the Grossman model of medical spending determinants with macroeconomic panel data.

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Testing the Grossman model of medical spending determinants with macroeconomic panel data.

Eur J Health Econ. 2018 Feb 16;:

Authors: Hartwig J, Sturm JE

Abstract
Michael Grossman's human capital model of the demand for health has been argued to be one of the major achievements in theoretical health economics. Attempts to test this model empirically have been sparse, however, and with mixed results. These attempts so far relied on using-mostly cross-sectional-micro data from household surveys. For the first time in the literature, we bring in macroeconomic panel data for 29 OECD countries over the period 1970-2010 to test the model. To check the robustness of the results for the determinants of medical spending identified by the model, we include additional covariates in an extreme bounds analysis (EBA) framework. The preferred model specifications (including the robust covariates) do not lend much empirical support to the Grossman model. This is in line with the mixed results of earlier studies.

PMID: 29453763 [PubMed - as supplied by publisher]



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U-tube based near-surface environmental monitoring in the Shenhua carbon dioxide capture and storage (CCS) project.

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U-tube based near-surface environmental monitoring in the Shenhua carbon dioxide capture and storage (CCS) project.

Environ Sci Pollut Res Int. 2018 Jan 27;:

Authors: Li Q, Song R, Shi H, Ma J, Liu X, Li X

Abstract
The CO2 injected into deep formations during implementation of carbon dioxide (CO2) capture and storage (CCS) technology may leak and migrate into shallow aquifers or ground surfaces through a variety of pathways over a long period. The leaked CO2 can threaten shallow environments as well as human health. Therefore, almost all monitoring programs for CCS projects around the world contain near-surface monitoring. This paper presents a U-tube based near-surface monitoring technology focusing on its first application in the Shenhua CCS demonstration project, located in the Ordos Basin, Inner Mongolia, China. First, background information on the site monitoring program of the Shenhua CCS demonstration project was provided. Then, the principle of fluid sampling and the monitoring methods were summarized for the U-tube sampler system, and the monitoring data were analyzed in detail. The U-tube based monitoring results showed that the U-tube sampler system is accurate, flexible, and representative of the subsurface fluid sampling process. The monitoring indicators for the subsurface water and soil gas at the Shenhua CCS site indicate good stratification characteristics. The concentration level of each monitoring indicator decreases with increasing depth. Finally, the significance of this near-surface environmental monitoring technology for CO2 leakage assessments was preliminarily confirmed at the Shenhua CCS site. The application potential of the U-tube based monitoring technology was also demonstrated during the subsurface environmental monitoring of other CCS projects.

PMID: 29453717 [PubMed - as supplied by publisher]



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Occurrence and assessment of the risk of ultraviolet filters and light stabilizers in Victorian estuaries.

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Occurrence and assessment of the risk of ultraviolet filters and light stabilizers in Victorian estuaries.

Environ Sci Pollut Res Int. 2018 Feb 16;:

Authors: Allinson M, Kameda Y, Kimura K, Allinson G

Abstract
This reconnaissance study was undertaken to examine the occurrence of common ultraviolet filters (UVF) and light stabilizers (UVLS), and preservatives in four different estuaries in Port Philip Bay, Victoria, for the first time. In total, 11 UV filters, 10 UV stabilizers, 12 preservatives and a metabolite, and one fragrance were screened in grab samples of water and sediment using a combination of solid phase extraction and gas and liquid chromatography mass spectrometry measurement techniques. In that context, 16 of the UVF and UVLS and 5 of the preservatives screened were observed in water and/or sediment samples. There are no marine water quality guideline values for any of the fragrances, preservatives and UV filters and light stabilizers in Australia's current national water quality guidelines, so potential risk was assessed using the risk quotient (RQ) and toxic unit (TU) concepts. In that context, only two chemicals (OC and EHMC) had both an RQ above 1 and a log10TU above - 3, suggesting that few of the screened chemicals would have posed an individual, short-term risk to organisms in the waters studied at the time of sampling. However, the detection of common UV filters, such as 4MBC, EHMC, OC and the common preservatives 2-PE, MP, and PB in these Victorian estuaries highlights that the existence of personal care products in the environment is not just an issue for more densley populated countries in the northern hemisphere, but also potentially of concern in Australia. And, in that context, more sampling campaigns in Port Philip Bay are of paramount importance to assess the potential risk posed by these compounds to aquatic ecosystems.

PMID: 29453716 [PubMed - as supplied by publisher]



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Prevalence of DSM-5 Autism Spectrum Disorder Among School-Based Children Aged 3-12 Years in Shanghai, China.

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Prevalence of DSM-5 Autism Spectrum Disorder Among School-Based Children Aged 3-12 Years in Shanghai, China.

J Autism Dev Disord. 2018 Feb 16;:

Authors: Jin Z, Yang Y, Liu S, Huang H, Jin X

Abstract
We estimated the prevalence of ASD in a population-based sample comprising children aged 3-12 years (N = 74,252) in Shanghai. This included a high-risk group sampled from special education schools and a low-risk group randomly sampled from general schools. First, we asked parents and then teachers to complete the Social Communication Questionnaire for participating children. Children who screened positive based on both parental and teachers' reports were comprehensively assessed. ASD was identified based on DSM-5 criteria. We identified 711 children as being at-risk for ASD, of which 203 were identified as ASD cases. The prevalence of ASD was 8.3 per 10,000, which is likely an underestimate, given that 81.6% of the children diagnosed with ASD had IQs below 40. This is the first report on the prevalence of ASD according to DSM-5 in China.

PMID: 29453711 [PubMed - as supplied by publisher]



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Reliability of cartilage digestion and FDA-EB fluorescence staining for the detection of chondrocyte viability in osteochondral grafts.

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Reliability of cartilage digestion and FDA-EB fluorescence staining for the detection of chondrocyte viability in osteochondral grafts.

Cell Tissue Bank. 2018 Feb 16;:

Authors: Qi J, Cao F, Han Y, Xie D, Song H, Chen B, Zhou L

Abstract
The purpose of this study is to evaluate the reliability of cartilage digestion and fluorescein diacetate-ethidium bromide (FDA-EB) fluorescence staining for the detection of chondrocyte viability in osteochondral grafts. Sixteen fresh osteochondral grafts were harvested from pig knee condyles, and the articular cartilage tissue was preserved. Each cartilage graft was cut into two 70-µm thick pieces and randomly allocated to Group A or Group B. The cell viability of Group A was detected using FDA-EB fluorescence staining of the digested cartilage, and the viability of Group B was detected with FDA-EB fluorescence staining of cartilage sections. Comparisons of chondrocyte viability and correlation analyses of the two groups were performed using the paired sample t test and Pearson correlation test, respectively. No significant difference was found in the chondrocyte viability between Groups A and B (p > 0.05), and a strong correlation was observed (r = 0.70, p < 0.05). Therefore, cartilage digestion with FDA-EB fluorescence staining is a reliable method for detecting chondrocyte viability in osteochondral grafts.

PMID: 29453700 [PubMed - as supplied by publisher]



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18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging.

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18F-FPYBF-2, a new F-18 labelled amyloid imaging PET tracer: biodistribution and radiation dosimetry assessment of first-in-man 18F-FPYBF-2 PET imaging.

Ann Nucl Med. 2018 Feb 16;:

Authors: Nishii R, Higashi T, Kagawa S, Okuyama C, Kishibe Y, Takahashi M, Okina T, Suzuki N, Hasegawa H, Nagahama Y, Ishizu K, Oishi N, Kimura H, Watanabe H, Ono M, Saji H, Yamauchi H

Abstract
OBJECTIVE: Recently, a benzofuran derivative for the imaging of β-amyloid plaques, 5-(5-(2-(2-(2-18F-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)- N-methylpyridin-2-amine (18F-FPYBF-2) has been validated as a tracer for amyloid imaging and it was found that 18F-FPYBF-2 PET/CT is a useful and reliable diagnostic tool for the evaluation of AD (Higashi et al. Ann Nucl Med, http://ift.tt/2o3WU0L , 2018). The aim of this study was to assess the biodistribution and radiation dosimetry of diagnostic dosages of 18F-FPYBF-2 in normal healthy volunteers as a first-in-man study.
METHODS: Four normal healthy volunteers (male: 3, female: 1; mean age: 40 ± 17; age range 25-56) were included and underwent 18F-FPYBF-2 PET/CT study for the evaluation of radiation exposure and pharmacokinetics. A 10-min dynamic PET/CT scan of the body (chest and abdomen) was performed at 0-10 min and a 15-min whole-body static scan was performed six times after the injection of 18F-FPYBF-2. After reconstructing PET and CT image data, individual organ time-activity curves were estimated by fitting volume of interest data from the dynamic scan and whole-body scans. The OLINDA/EXM version 2.0 software was used to determine the whole-body effective doses.
RESULTS: Dynamic PET imaging demonstrated that the hepatobiliary and renal systems were the principal pathways of clearance of 18F-FPYBF-2. High uptake in the liver and the gall bladder, the stomach, and the kidneys were demonstrated, followed by the intestines and the urinary bladder. The ED for the adult dosimetric model was estimated to be 8.48 ± 1.25 µSv/MBq. The higher absorbed doses were estimated for the liver (28.98 ± 12.49 and 36.21 ± 15.64 µGy/MBq), the brain (20.93 ± 4.56 and 23.05 ± 5.03µ Gy/MBq), the osteogenic cells (9.67 ± 1.67 and 10.29 ± 1.70 µGy/MBq), the small intestines (9.12 ± 2.61 and 11.12 ± 3.15 µGy/MBq), and the kidneys (7.81 ± 2.62 and 8.71 ± 2.90 µGy/MBq) for male and female, respectively.
CONCLUSIONS: The ED for the adult dosimetric model was similar to those of other agents used for amyloid PET imaging. The diagnostic dosage of 185-370 MBq of 18F-FPYBF-2 was considered to be acceptable for administration in patients as a diagnostic tool for the evaluation of AD.

PMID: 29453681 [PubMed - as supplied by publisher]



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Changes in medicine prescription following a medication review in older high-risk patients with polypharmacy.

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Changes in medicine prescription following a medication review in older high-risk patients with polypharmacy.

Int J Clin Pharm. 2018 Feb 17;:

Authors: Hurmuz MZM, Janus SIM, van Manen JG

Abstract
Background The more (inappropriate) drugs a patient uses, the higher the risk of drug related problems. To reduce these risks, medication reviews can be performed. Objective To report changes in the prescribed number of (potentially inappropriate) drugs before and after performing a medication review in high-risk polypharmacy patients. A secondary objective was to study reasons for continuing potentially inappropriate drugs (PIDs). Setting Dutch community pharmacy and general medical practice. Methods A retrospective longitudinal intervention study with a pre-test/post-test design and follow-up of 1 week and 3 months was performed. The study population consisted of 126 patients with polypharmacy and with additional risk for drug related problems that underwent a medication review in five community pharmacies. The medication review was performed by the pharmacist in close cooperation with the general practitioner of each corresponding patient. Main outcome measure Number of (potentially inappropriate) drugs, and appropriateness of prescribed medicines. Results The average number of drugs a patient used 1 day before the review was 8.7 (SD = 2.9), which decreased (p < 0.05) to 8.3 (SD = 2.7) 1 week after the review, and to 8.4 (SD = 2.6) 3 months after the review. The average number of PIDs was initially 0.6 (SD = 0.8) per patient and decreased to 0.4 (SD = 0.6, p < 0.05). Twenty-two of the 241 initial drug changes (9%) were deprescribed during follow-up. Registered reasons for continuing PIDs are clinical or patients' preferences. Conclusions Performing medication reviews in polypharmacy patients seems useful to continue at least in high-risk patients in The Netherlands. The time-consuming reviews could be limited to patients who are willing to change their medication.

PMID: 29453677 [PubMed - as supplied by publisher]



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Proteomic and genomic responses of plants to nutritional stress.

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Proteomic and genomic responses of plants to nutritional stress.

Biometals. 2018 Feb 16;:

Authors: Kerry RG, Mahapatra GP, Patra S, Sahoo SL, Pradhan C, Padhi BK, Rout JR

Abstract
Minerals or trace elements in small amount are essential nutrients for every plant, but when the internal concentration exceeds the threshold, these essential elements do create phytotoxicity. Plant responses to elemental stresses are very common due to different anthropogenic activities; however it is a complex phenomenon with individual characteristics for various species. To cope up with the situation, a plant produces a group of strategies both in proteomic and genomic level to overcome it. Controlling the metal stress is known to activate a multigene response resulting in the changes in various proteins, which directly affects almost all biological processes in a living cell. Therefore, proteomic and genomic approaches can be useful for elucidating the molecular responses under metal stress. For this, it is tried to provide the latest knowledge and techniques used in proteomic and genomic study during nutritional stress and is represented here in review form.

PMID: 29453655 [PubMed - as supplied by publisher]



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Immunohistochemical Biomarkers in Pituitary Pathology.

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Immunohistochemical Biomarkers in Pituitary Pathology.

Endocr Pathol. 2018 Feb 16;:

Authors: Asa SL, Mete O

Abstract
Pituitary pathology is one area of endocrine pathology that is highly dependent on immunohistochemistry. There is a wide range of disorders that occur in and around the sella turcica, and the distinction of tumor-like lesions from neoplasms requires careful evaluation. The diagnosis, prognosis, and predictive features of neoplasms in the sellar region are all dependent on the application and interpretation of biomarkers of cell differentiation, hormonal activity, subcellular morphology, and proliferation. As in hematopathology, the number of biomarkers has increased dramatically and continues to increase. Fortunately, some of the biomarkers provide information that was initially dependent on electron microscopy; therefore, the need for this additional technology has been reduced to only rare unusual tumors. In this review, we provide a simple approach to understanding the importance of the various biomarkers that are used to ensure the correct diagnosis and provide the treating clinicians with tools to guide appropriate patient management and surveillance.

PMID: 29453601 [PubMed - as supplied by publisher]



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A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy.

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A Microvascularized Tumor-mimetic Platform for Assessing Anti-cancer Drug Efficacy.

Sci Rep. 2018 Feb 16;8(1):3171

Authors: Pradhan S, Smith AM, Garson CJ, Hassani I, Seeto WJ, Pant K, Arnold RD, Prabhakarpandian B, Lipke EA

Abstract
Assessment of anti-cancer drug efficacy in in vitro three-dimensional (3D) bioengineered cancer models provides important contextual and relevant information towards pre-clinical translation of potential drug candidates. However, currently established models fail to sufficiently recapitulate complex tumor heterogeneity. Here we present a chip-based tumor-mimetic platform incorporating a 3D in vitro breast cancer model with a tumor-mimetic microvascular network, replicating the pathophysiological architecture of native vascularized breast tumors. The microfluidic platform facilitated formation of mature, lumenized and flow-aligned endothelium under physiological flow recapitulating both high and low perfused tumor regions. Metastatic and non-metastatic breast cancer cells were maintained in long-term 3D co-culture with stromal fibroblasts in a poly(ethylene glycol)-fibrinogen hydrogel matrix within adjoining tissue chambers. The interstitial space between the chambers and endothelium contained pores to mimic the "leaky" vasculature found in vivo and facilitate cancer cell-endothelial cell communication. Microvascular pattern-dependent flow variations induced concentration gradients within the 3D tumor mass, leading to morphological tumor heterogeneity. Anti-cancer drugs displayed cell type- and flow pattern-dependent effects on cancer cell viability, viable tumor area and associated endothelial cytotoxicity. Overall, the developed microfluidic tumor-mimetic platform facilitates investigation of cancer-stromal-endothelial interactions and highlights the role of a fluidic, tumor-mimetic vascular network on anti-cancer drug delivery and efficacy for improved translation towards pre-clinical studies.

PMID: 29453454 [PubMed - in process]



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A novel combination of bortezomib, lenalidomide, and clarithromycin produced stringent complete response in refractory multiple myeloma complicated with diabetes mellitus – clinical significance and possible mechanisms: a case report

In general, dexamethasone is a required component drug in various combination chemotherapies for treating multiple myeloma, and its efficacy has been widely recognized. However, administration of dexamethasone...

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STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy.

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STINGel: Controlled release of a cyclic dinucleotide for enhanced cancer immunotherapy.

Biomaterials. 2018 Feb 06;163:67-75

Authors: Leach DG, Dharmaraj N, Piotrowski SL, Lopez-Silva TL, Lei YL, Sikora AG, Young S, Hartgerink JD

Abstract
Recent advancements in the field of immunotherapy have yielded encouraging results for the treatment of advanced cancers. Cyclic dinucleotides (CDNs) are a powerful new class of immunotherapy drugs known as STING (Stimulator of Interferon Genes) agonists, currently in clinical trials. However, previous studies of CDNs in murine cancer models have required multiple injections, and improve survival only in relatively nonaggressive tumor models. Therefore, we sought to improve the efficacy of CDN immunotherapy by developing a novel biomaterial we call "STINGel." STINGel is an injectable peptide hydrogel that localizes and provides controlled release of CDN delivery, showing an 8-fold slower release rate compared to a standard collagen hydrogel. The carrier hydrogel is a positively charged, MultiDomain Peptide (MDP) which self-assembles to form a nanofibrous matrix and is easily delivered by syringe. The highly localized delivery of CDN from this nanostructured biomaterial affects the local histological response in a subcutaneous model, and dramatically improves overall survival in a challenging murine model of head and neck cancer compared to CDN alone or CDN delivered from a collagen hydrogel. This study demonstrates the feasibility of biomaterial-based immunotherapy platforms like STINGel as strategies for increasing the efficacy of CDN immunotherapies.

PMID: 29454236 [PubMed - as supplied by publisher]



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Management of Skull Base Tumors in the Obstetric Population: a Case Series.

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Management of Skull Base Tumors in the Obstetric Population: a Case Series.

World Neurosurg. 2018 Feb 14;:

Authors: Priddy BH, Otto BA, Carrau RL, Prevedello DM

Abstract
BACKGROUND: Neoplasms rarely present during pregnancy. However, increase in plasma volume, hormone release induced growth, and tumor hypervascularity, can cause rapid symptoms. These range from not requiring intervention to necessitating emergent operations.
OBJECTIVE: We describe an algorithm for the management of symptomatic neoplasm in the obstetric population, and provide recommendations regarding surgical indications and timing.
METHODS: Patients who presented to a skull base clinic from 2010-2016 at large tertiary care hospital were reviewed to identify patients who presented with a skull base tumor during pregnancy.
RESULTS: Our cohort comprises ten women with skull base tumors during pregnancy. Four presented symptoms that required emergent skull base surgery, six underwent surgery after delivery or continued surveillance. All patients were found to have WHO Grade I or II meningioma or schwannomas. There were no maternal complications. Through this experience, a management algorithm was created.
CONCLUSION: Management of a symptomatic tumor during pregnancy requires balancing the potential to cure the mother and to harm the fetus. Trimester of pregnancy is the most critical factor in evaluating the need for urgent management. Surgery during the second trimester is the optimal time, as it is associated with the least risk for spontaneous abortion or preterm birth. The first and third trimesters are associated with increased risk of miscarriage and preterm labor respectively. Induction of labor for preterm delivery, followed by surgery, may be appropriate in early third trimester. Nonetheless, any pregnant woman with an emergent presentation should be offered surgery, regardless of trimester.

PMID: 29454125 [PubMed - as supplied by publisher]



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Activation of NLRX1-mediated autophagy accelerates the ototoxic potential of cisplatin in auditory cells.

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Activation of NLRX1-mediated autophagy accelerates the ototoxic potential of cisplatin in auditory cells.

Toxicol Appl Pharmacol. 2018 Feb 14;:

Authors: Yin H, Yang Q, Cao Z, Li H, Yu Z, Zhang G, Sun G, Man R, Wang H, Li J

Abstract
To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member ×1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus. We found that NLRX1 expression was increased concurrent with the increase of autophagy activation in HEI-OC1 cells under the cisplatin insult. NLRX1 overexpression led to the amount of accumulation of autophagsomes in HEI-OC1 cells in normal condition and a higher activation of autophagy concurrent with cell injury in HEI-OC1 cells treated with cisplatin, whereas, NLRX1 silencing decreased the activation level of autophagy concurrent with increased cell viability in HEI-OC1 cells treated with cisplatin. Mechanistic studies showed that NLRX1 potentiated mitochondrial-derived ROS generation in response to cisplatin exposure. Inhibition of ROS generation significantly prevented autophagy activation and apoptosis both in HEI-OC1cells and cochlear explants treated with cisplatin. The findings from this work reveal that NLRX1 sensitizes auditory cells in vitro to cisplatin-induced ototoxity via autophagic cell death pathway, providing another strategy against cisplatin-induced ototoxity.

PMID: 29454061 [PubMed - as supplied by publisher]



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TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors.

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TriCurin, a synergistic formulation of curcumin, resveratrol, and epicatechin gallate, repolarizes tumor-associated macrophages and triggers an immune response to cause suppression of HPV+ tumors.

Cancer Immunol Immunother. 2018 Feb 16;:

Authors: Mukherjee S, Hussaini R, White R, Atwi D, Fried A, Sampat S, Piao L, Pan Q, Banerjee P

Abstract
Our earlier studies reported a unique potentiated combination (TriCurin) of curcumin (C) with two other polyphenols. The TriCurin-associated C displays an IC50 in the low micromolar range for cultured HPV+ TC-1 cells. In contrast, because of rapid degradation in vivo, the TriCurin-associated C reaches only low nano-molar concentrations in the plasma, which are sub-lethal to tumor cells. Yet, injected TriCurin causes a dramatic suppression of tumors in TC-1 cell-implanted mice (TC-1 mice) and xenografts of Head and Neck Squamous Cell Carcinoma (HNSCC) cells in nude/nude mice. Here, we use the TC-1 mice to test our hypothesis that a major part of the anti-tumor activity of TriCurin is evoked by innate and adaptive immune responses. TriCurin injection repolarized arginase1high (ARG1high), IL10high, inducible nitric oxide synthaselow (iNOSlow), IL12low M2-type tumor-associated macrophages (TAM) into ARG1low, IL10low, iNOShigh, and IL12high M1-type TAM in HPV+ tumors. The M1 TAM displayed sharply suppressed STAT3 and induced STAT1 and NF-kB(p65). STAT1 and NF-kB(p65) function synergistically to induce iNOS and IL12 transcription. Neutralizing IL12 signaling with an IL12 antibody abrogated TriCurin-induced intra-tumor entry of activated natural killer (NK) cells and Cytotoxic T lymphocytes (CTL), thereby confirming that IL12 triggers recruitment of NK cells and CTL. These activated NK cells and CTL join the M1 TAM to elicit apoptosis of the E6+ tumor cells. Corroboratively, neutralizing IL12 signaling partially reversed this TriCurin-mediated apoptosis. Thus, injected TriCurin elicits an M2→M1 switch in TAM, accompanied by IL12-dependent intra-tumor recruitment of NK cells and CTL and elimination of cancer cells.

PMID: 29453519 [PubMed - as supplied by publisher]



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Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.

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Basal Cell Carcinoma in Cases with or without Xeroderma Pigmentosum.

JNMA J Nepal Med Assoc. 2017 Oct-Dec;56(208):432-437

Authors: Ghartimagar D, Ghosh A, Shrestha SR, Shrestha S, Thapa S, Narasimhan R, Talwar OP

Abstract
INTRODUCTION: Basal cell carcinoma is the most common form of cancer in humans and comprises the vast majority of skin cancers. It predominantly affects fair-skinned individuals, and its incidence is rapidly increasing. The objective of the study is to identify the epidemiology, its topography and different histological subtypes of basal cell carcinoma in patients with or without Xeroderma Pigmentosum.
METHODS: A cross-sectional descriptive study was conducted at Manipal Teaching Hospital, Pokhara from Jan 2009 to Dec 2016. Ethical approval was taken from MEMG/IRC/GA. The study included patients with a confirmed diagnosis of basal cell carcinoma irrespective of their age and sex.
RESULTS: This study showed 77 individuals with 91 biopsies of BCC including 5 cases of Xeroderma Pigmentosum. The predominant histological subtype was nodular with 41 (53.94%) cases, followed by the 14 (18.42%) cases of pigmented and 10 (13.15%) cases baso-squamous subtype. The most frequent sites of involvement were the head and neck, with predominance in the nasal and orbital region. The mean age was 57.68 years but the basal cell carcinoma in cases of Xeroderma Pigmentosum was seen more in younger age groups. There were 43 (55.84 %) male patients and 34 (44.16 %) female patients with a male to female ratio of 1.26:1.
CONCLUSIONS: Nodular and pigmented varieties were the most frequent subtypes with nose being the commonest site of involvement. Basal cell carcinomas in cases of Xeroderma Pigmentosum were noted in younger age group with multiple lesions.

PMID: 29453475 [PubMed - in process]



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Recurrent epistaxis leading to diagnosis of primary sinonasal melanoma.

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Recurrent epistaxis leading to diagnosis of primary sinonasal melanoma.

BMJ Case Rep. 2018 Feb 16;2018:

Authors: Tawagi K, Akaraz-Avedissian R, Burman-Solovyeva I

Abstract
A 48-year-old man presented to urgent care with recurrent epistaxis over 6 months. Initially, nosebleeds were controlled with packing or cautery. Ultimately, he was referred to ear, nose and throat department and underwent nasal endoscopy which revealed polypoid tissue. A biopsy of the polyp showed non-specific inflammation with no evidence of malignancy. Follow-up maxillofacial CT revealed a large mass lesion in the right maxillary sinus, right nasal fossa, much of the ethmoids and right sphenoid, with destruction of adjacent bony structures. MRI revealed a mass in the right nasal cavity with extension into the ethmoid and anterior sphenoid sinus, anterior cranial fossa and medial orbits. Staging CT discovered metastatic disease in the adrenal glands and lymphadenopathy in the neck. The patient underwent endoscopic sinus surgery with debulking and tissue diagnosis of malignant melanoma. He completed radiation therapy to sinus and was subsequently enrolled in a clinical trial. Most recent imaging revealed complete metabolic response on positron emission tomography.

PMID: 29453209 [PubMed - in process]



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Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss.

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Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss.

J Med Genet. 2018 Feb 16;:

Authors: Gao X, Yuan YY, Lin QF, Xu JC, Wang WQ, Qiao YH, Kang DY, Bai D, Xin F, Huang SS, Qiu SW, Guan LP, Su Y, Wang GJ, Han MY, Jiang Y, Liu HK, Dai P

Abstract
Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder.Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL).Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism.Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) - a protein that functions in the Jak/ STAT pathway- are associated with ADNSHL Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level.ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.

PMID: 29453195 [PubMed - as supplied by publisher]



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Skull metastasis revealing a renal tumor: A case report and review of the literature.

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Skull metastasis revealing a renal tumor: A case report and review of the literature.

Int J Surg Case Rep. 2018 Feb 10;43:56-60

Authors: Badri M, Gader G, Bahri K, Zammel I

Abstract
BACKGROUND: Renal cell carcinomas represent 85% of malignant renal tumors. Typically, the tumor remains asymptomatic a long time before the appearance of urologic clinical signs. In some cases, metastasis can precede the manifestations of the primary tumor. Different sites are potential metastatic localizations for renal tumors, including skull metastases who represent a very rare location.
CASE DESCRIPTION: We report the case of a 65-year-old man presented after the appearance of a skull mass. This tumefaction developed and had progressively grown up during 9 months. Neurological examination was normal. Brain imaging showed a soft tissue lesion in the left parietal bone with marked osteolysis. Peroperative was found a huge oval-shape hemorrhagic and firm mass associated with scalp invasion and bone destruction that was totally resected. Histopathology revealed renal cell carcinoma (RCC). Pelvic and abdominal CT scan was performed, revealing a large mass on the left kidney with irregular contours and poor definition. The patient was then transferred to urology where he underwent nephrectomy. The patient went then through adjuvant chemotherapy. Clinical and radiological follow up of 12 months did not bring to light tumor recurrence.
CONCLUSIONS: Although metastases to the head and neck occur infrequently, they should be considered when evaluating any unusual subcutaneous mass in the head and neck. RCC should not be discounted when sites as unlikely as the calvaria are evaluated. Treatment of metastatic renal cell carcinoma is complex, and the optimal regimen for achieving a lasting response without severe toxicity has not yet been defined.

PMID: 29453166 [PubMed - as supplied by publisher]



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Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in the dorsal cochlear nucleus.

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Effects of AUT00063, a Kv3.1 channel modulator, on noise-induced hyperactivity in the dorsal cochlear nucleus.

Hear Res. 2018 Feb 07;361:36-44

Authors: Glait L, Fan W, Stillitano G, Sandridge S, Pilati N, Large C, Alvaro G, Kaltenbach JA

Abstract
The purpose of this study was to test whether a Kv3 potassium channel modulator, AUT00063, has therapeutic potential for reversing noise-induced increases in spontaneous neural activity, a state that is widely believed to underlie noise-induced tinnitus. Recordings were conducted in noise exposed and control hamsters from dorsal cochlear nucleus (DCN) fusiform cells before and following intraperitoneal administration of AUT00063 (30 mg/kg). Fusiform cell spontaneous activity was increased in sound-exposed animals, approximating levels that were nearly 50% above those of controls. Administration of AUT00063 resulted in a powerful suppression of this hyperactivity. The first signs of this suppression began 13 min after AUT00063 administration, but activity continued to decline gradually until reaching a floor level which was approximately 60% of pre-drug baseline by 25 min after drug treatment. A similar suppressive effect of AUT00063 was observed in control animals, with onset of suppression first apparent at 13 min post-treatment, but continuing to decline toward a floor level that was 54% of pre-drug baseline and was reached 28 min after drug treatment. In contrast, no suppression of spontaneous activity was observed in animals given similar injections of vehicle (control) solution. The suppressive effect of AUT00063 was achieved without significantly altering heart rate and with minimal effects on response thresholds, supporting the interpretation that the reductions of hyperactivity were not a secondary consequence of a more general physiological suppression of the brain or auditory system. These findings suggest that Kv3 channel modulation may be an effective approach to suppressing spontaneous activity in the auditory system and may provide a future avenue for treatment of tinnitus resulting from exposure to intense sound.

PMID: 29453003 [PubMed - as supplied by publisher]



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Risk factors for platelet transfusion in glioblastoma surgery.

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Risk factors for platelet transfusion in glioblastoma surgery.

J Clin Neurosci. 2018 Feb 13;:

Authors: Lagman C, Sheppard JP, Romiyo P, Nguyen T, Prashant GN, Nagasawa DT, Liau LM, Yang I

Abstract
The objectives of this study are to identify risk factors for and to evaluate clinical outcomes of platelet transfusion in glioblastoma surgery. The medical records of adult patients who underwent craniotomy for glioblastoma resection at a single academic medical center were retrospectively reviewed. We stratified patients into 2 groups: those who were transfused at least 1 unit of platelets intraoperatively or postoperatively (no more than 7 days after surgery), and those who were not transfused with platelets. Through the use of a 1:3 matched cohort analysis, we compared complications, length of stay, discharge disposition, and mortality, across groups. One hundred and five consecutive adult patients were included in this study. Thirteen patients (12.38%) received platelet transfusions. Prior antiplatelet therapy (odds ratio [OR] 8.21, 95% confidence interval [CI]: 2.36-28.58), preoperative platelet count less than 200,000 cells/µL (OR 8.46, 95% CI: 2.16-33.22), and longer operative times (OR 1.73, 95% CI: 1.10-2.72) were significant risk factors for platelet transfusion. There were no significant differences in the outcomes of interest in the matched cohort analysis.

PMID: 29452964 [PubMed - as supplied by publisher]



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Three-dimensional printer-aided casting of soft, custom silicone boluses (SCSBs) for head and neck radiation therapy.

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Three-dimensional printer-aided casting of soft, custom silicone boluses (SCSBs) for head and neck radiation therapy.

Pract Radiat Oncol. 2017 Nov 11;:

Authors: Chiu T, Tan J, Brenner M, Gu X, Yang M, Westover K, Strom T, Sher D, Jiang S, Zhao B

Abstract
PURPOSE: Custom tissue compensators provide dosimetric advantages for treating superficial or complex anatomy, but currently available fabrication technology is expensive or impractical for most clinical operations and yields compensators that are difficult for patients to tolerate. We aimed to develop an inexpensive, clinically feasible workflow for generating patient-specific, soft, custom silicone boluses (SCSBs) for head-and-neck (HN) radiation therapy.
METHODS AND MATERIALS: We developed a method using 3-dimensional printed parts for generating SCSBs for the treatment of HN cancers. The clinical workflow for generation of SCSBs was characterized inclusive of patient simulation to treatment in terms of resource time and cost. Dosimetric properties such as percentage depth dose and dose profiles were measured for SCSBs using GaF films. Comprehensive measurements were also conducted on an HN phantom. SCSBs were generated and used for electron or photon based radiation treatments of 7 HN patients with lesions at nose, cheek, eye, or ears. In vivo dose measurements with optically simulated luminescence dosimeters were performed.
RESULTS: Total design and fabrication time from patient simulation to radiation treatment start required approximately 1 week, with fabrication constituting 1 to 2 working days depending on bolus surface area, volume, and complexity. Computed tomography and dosimetric properties of the soft bolus were similar to water. In vivo dose measurements on 7 treated patients confirmed that the dose deposition conformed to planned doses. Material costs were lower than currently available hard plastic boluses generated with 3-dimensional printing technology. All treated patients tolerated SCSBs for the duration of therapy.
CONCLUSIONS: Generation and use of SCSBs for clinical use is feasible and effective for the treatment of HN cancers.

PMID: 29452869 [PubMed - as supplied by publisher]



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Usefulness of reconstructed 3D images for cochlear implantation in a case with a facial nerve anomaly.

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Usefulness of reconstructed 3D images for cochlear implantation in a case with a facial nerve anomaly.

Auris Nasus Larynx. 2018 Feb 14;:

Authors: Nakamura K, Dias MS, Sasaki T, Sugimoto H, Hatano M, Ito M

Abstract
Facial nerve anomalies are a potential problem in patients with cochleovestibular malformations. A case of cochlear implant (CI) surgery in the presence of intra-temporalbone facial nerve bifurcation is presented. During the first surgery, the facial nerve bifurcation obscured the promontory and round window. It was difficult to perform cochleostomy because of the lack of landmarks of the basal turn of the cochlea, and the first surgical attempt at cochleostomy was abandoned. A repeat CT scan was performed after the first surgery with reconstructed 3D images of the temporal bone and the cochlea, and then the cochlea was successfully opened at revision surgery. Reconstructed 3D CT images were very useful to identify the site of cochleostomy in this case with such difficult temporal bone anatomy.

PMID: 29452830 [PubMed - as supplied by publisher]



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Single-Arm Phase 2 Trial of Elective Nodal Dose Reduction for Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck.

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Single-Arm Phase 2 Trial of Elective Nodal Dose Reduction for Patients With Locoregionally Advanced Squamous Cell Carcinoma of the Head and Neck.

Int J Radiat Oncol Biol Phys. 2017 Dec 28;:

Authors: Maguire PD, Neal CR, Hardy SM, Schreiber AM

Abstract
PURPOSE: To evaluate a novel chemoradiation therapy (CRT) regimen for patients with squamous cell carcinoma of the head and neck (SCCHN) incorporating a lower intensity modulated radiation therapy dose to electively treated neck lymph nodes than is currently standard.
METHODS AND MATERIALS: Eligible patients had locally advanced SCCHN of the oral cavity, oropharynx, larynx, or hypopharynx. The 7-week CRT course consisted of weekly cisplatin at 35 mg/m2 concurrently with sequential-boost intensity modulated radiation therapy: 36 Gy to high- and low-risk planning target volumes followed by a sequential boost to the high-risk planning target volume to 70 Gy. The primary endpoint was elective nodal failure. Secondary endpoints were survival, toxicity, feeding tube duration, and quality of life evaluated by the FACT-HN and QOL-RTI surveys.
RESULTS: Between 2011 and 2014, 54 patients were enrolled, 31 (57%) of whom had human papillomavirus (HPV)-positive disease. Of the patients, 35 (65%) had stage IVa disease. The median follow-up period for survivors was 36 months (range, 12-66 months). Elective nodal failure did not develop in any patient. The actuarial 3-year survival rate for the entire cohort was 91% (95% confidence interval [CI] 0.79-0.96); for the HPV-negative group, 85% (95% CI 0.61-0.95); and for the HPV-positive group, 96% (95% CI 0.77-0.99). Common grade 3 toxicities were dysphagia (79%), mucositis and/or stomatitis (41%), nausea (20%), xerostomia (13%), vomiting (11%), and neutropenia (10%). The median feeding tube duration was 142 days. Patient FACT-HN scores were higher at 3, 6, and 12 months versus at the end of treatment (P < .0001). Total FACT-HN scores returned to pretreatment baseline by 6 months. Overall QOL-RTI scores were lower from pretreatment to the end of treatment through 12 months (P = .0001).
CONCLUSIONS: This CRT regimen for patients with advanced SCCHN demonstrated the potential feasibility of reducing the elective dose to the neck, a topic that requires additional study in future clinical trials.

PMID: 29452770 [PubMed - as supplied by publisher]



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Base of tongue cancer-is it tongue cancer located at the base of the tongue, or is it a type of lingual tonsil cancer? The perspective from a genomic analysis.

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Base of tongue cancer-is it tongue cancer located at the base of the tongue, or is it a type of lingual tonsil cancer? The perspective from a genomic analysis.

Int J Oral Maxillofac Surg. 2018 Feb 13;:

Authors: Kim K, Choi KY, Kim JH, Park IS, Rho YS, Lee DJ

Abstract
The aim of this study was to determine whether base of tongue (BOT) cancer is tongue cancer located at the base of the tongue or lingual tonsil cancer originating from tonsil tissue. This was a retrospective study using data from The Cancer Genome Atlas (TCGA). The genomic patterns of three primary cancers (BOT, oral tongue, and tonsil) were compared to determine their similarities and differences. Gene expression data (n=193; 26 BOT, 125 oral tongue, and 42 tonsil cases), copy number alteration data (n=142; 19 BOT, 96 oral tongue, and 27 tonsil cases), and somatic mutation data (n=187; 25 BOT, 122 oral tongue, and 40 tonsil cases) were analyzed using the t-test, heatmap analysis, and OncoPrint, respectively. Clinical information for the three tumour groups was included in the analyses. When using multiplatform analysis, BOT cancer showed nearly the same genomic pattern as tonsil cancer, but not oral tongue cancer. The χ2 test and survival analysis revealed that BOT cancer had the same clinical and survival patterns as tonsil cancer. In conclusion, BOT cancer showed a genomic pattern similar to that of tonsil cancer, but different to that of oral tongue cancer. Further prospective studies are warranted before the results of this study can be applied in a clinical setting.

PMID: 29452725 [PubMed - as supplied by publisher]



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Uptake and distribution of organo-iodine in deep-sea corals.

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Uptake and distribution of organo-iodine in deep-sea corals.

J Environ Radioact. 2018 Feb 13;:

Authors: Prouty NG, Roark EB, Mohon LM, Chang CC

Abstract
Understanding iodine concentration, transport, and bioavailability is essential in evaluating iodine's impact to the environment and its effectiveness as an environmental biogeotracer. While iodine and its radionuclides have proven to be important tracers in geologic and biologic studies, little is known about transport of this element to the deep sea and subsequent uptake in deep-sea coral habitats. Results presented here on deep-sea black coral iodine speciation and iodine isotope variability provides key information on iodine behavior in natural and anthropogenic environments, and its geochemical pathway in the Gulf of Mexico. Organo-iodine is the dominant iodine species in the black corals, demonstrating that binding of iodine to organic matter plays an important role in the transport and transfer of iodine to the deep-sea corals. The identification of growth bands captured in high-resolution scanning electron images (SEM) with synchronous peaks in iodine variability suggest that riverine delivery of terrestrial-derived organo-iodine is the most plausible explanation to account for annual periodicity in the deep-sea coral geochemistry. Whereas previous studies have suggested the presence of annual growth rings in deep-sea corals, this present study provides a mechanism to explain the formation of annual growth bands. Furthermore, deep-sea coral ages based on iodine peak counts agree well with those ages derived from radiocarbon (14C) measurements. These results hold promise for developing chronologies independent of 14C dating, which is an essential component in constraining reservoir ages and using radiocarbon as a tracer of ocean circulation. Furthermore, the presence of enriched 129I/127I ratios during the most recent period of skeleton growth is linked to nuclear weapons testing during the 1960s. The sensitivity of the coral skeleton to record changes in surface water 129I composition provides further evidence that iodine composition and isotope variability captured in proteinaceous deep-sea corals is a promising geochronometer as well as an emerging tracer for continental material flux.

PMID: 29452767 [PubMed - as supplied by publisher]



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IJMS, Vol. 19, Pages 610: The Antioxidant Content and Protective Effect of Argan Oil and Syzygium aromaticum Essential Oil in Hydrogen Peroxide-Induced Biochemical and Histological Changes

IJMS, Vol. 19, Pages 610: The Antioxidant Content and Protective Effect of Argan Oil and Syzygium aromaticum Essential Oil in Hydrogen Peroxide-Induced Biochemical and Histological Changes

International Journal of Molecular Sciences doi: 10.3390/ijms19020610

Authors: Meryem BAKOUR Najoua SOULO Nawal HAMMAS Hinde FATEMI Abderrazak ABOULGHAZI Amal TAROQ Abdelfattah ABDELLAOUI Noori AL-WAILI Badiaa LYOUSSI

Oxidative stress is an important etiology of chronic diseases and many studies have shown that natural products might alleviate oxidative stress-induced pathogenesis. The study aims to evaluate the effect of Argan oil and Syzygium aromaticum essential oil on hydrogen peroxide (H2O2)-induced liver, brain and kidney tissue toxicity as well as biochemical changes in wistar rats. The antioxidant content of Argan oil and Syzygium aromaticum essential oil was studied with the use of gas chromatography. The animals received daily by gavage, for 21 days, either distilled water, Syzygium aromaticum essential oil, Argan oil, H2O2 alone, H2O2 and Syzygium aromaticum essential oil, or H2O2 and Argan oil. Blood samples were withdrawn on day 21 for the biochemical blood tests, and the kidney, liver and brain tissue samples were prepared for histopathology examination. The results showed that the content of antioxidant compounds in Syzygium aromaticum essential oil is higher than that found in Argan oil. H2O2 increased level of blood urea, liver enzymes, total cholesterol, Low Density Lipoprotein (LDL-C), Triglycerides (TG) and Very Low Density Lipoprotein (VLDL), and decreased the total protein, albumin and High Density Lipoprotein-cholesterol (HDL-C). There was no significant effect on blood electrolyte or serum creatinine. The histopathology examination demonstrated that H2O2 induces dilatation in the central vein, inflammation and binucleation in the liver, congestion and hemorrhage in the brain, and congestion in the kidney. The H2O2-induced histopathological and biochemical changes have been significantly alleviated by Syzygium aromaticum essential oil or Argan oil. It is concluded that the Argan oil and especially the mixture of Argan oil with Syzygium aromaticum essential oil can reduce the oxidative damage caused by H2O2, and this will pave the way to investigate the protective effects of these natural substances in the diseases attributed to the high oxidative stress.



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Viruses, Vol. 10, Pages 88: Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells

Viruses, Vol. 10, Pages 88: Spindle-E Acts Antivirally Against Alphaviruses in Mosquito Cells

Viruses doi: 10.3390/v10020088

Authors: Margus Varjak Isabelle Dietrich Vattipally B. Sreenu Bethan Eluned Till Andres Merits Alain Kohl Esther Schnettler

Mosquitoes transmit several human- and animal-pathogenic alphaviruses (Togaviridae family). In alphavirus-infected mosquito cells two different types of virus-specific small RNAs are produced as part of the RNA interference response: short-interfering (si)RNAs and PIWI-interacting (pi)RNAs. The siRNA pathway is generally thought to be the main antiviral pathway. Although an antiviral activity has been suggested for the piRNA pathway its role in host defences is not clear. Knock down of key proteins of the piRNA pathway (Ago3 and Piwi5) in Aedes aegypti-derived cells reduced the production of alphavirus chikungunya virus (CHIKV)-specific piRNAs but had no effect on virus replication. In contrast, knock down of the siRNA pathway key protein Ago2 resulted in an increase in virus replication. Similar results were obtained when expression of Piwi4 was silenced. Knock down of the helicase Spindle-E (SpnE), an essential co-factor of the piRNA pathway in Drosophila melanogaster, resulted in increased virus replication indicating that SpnE acts as an antiviral against alphaviruses such as CHIKV and the related Semliki Forest virus (SFV). Surprisingly, this effect was found to be independent of the siRNA and piRNA pathways in Ae. aegypti cells and specific for alphaviruses. This suggests a small RNA-independent antiviral function for this protein in mosquitoes.



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IJERPH, Vol. 15, Pages 362: Disaster Reintegration Model: A Qualitative Analysis on Developing Korean Disaster Mental Health Support Model

IJERPH, Vol. 15, Pages 362: Disaster Reintegration Model: A Qualitative Analysis on Developing Korean Disaster Mental Health Support Model

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15020362

Authors: Yun-Jung Choi Hwa-Bok Choi Meaghan O’Donnell

This study sought to describe the mental health problems experienced by Korean disaster survivors, using a qualitative research method to provide empirical resources for effective disaster mental health support in Korea. Participants were 16 adults or elderly adults who experienced one or more disasters at least 12 months ago recruited via theoretical sampling. Participants underwent in-depth individual interviews on their disaster experiences, which were recorded and transcribed for qualitative analysis, which followed Strauss and Corbin’s (1998) Grounded theory. After open coding, participants’ experiences were categorized into 130 codes, 43 sub-categories and 17 categories. The categories were further analyzed in a paradigm model, conditional model and the Disaster Reintegration Model, which proposed potentially effective mental health recovery strategies for disaster survivors, health providers and administrators. To provide effective assistance for mental health recovery of disaster survivors, both personal and public resilience should be promoted while considering both cultural and spiritual elements.



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