Amplification of F-Actin Disassembly and Cellular Repulsion by Growth Factor Signaling

Publication date: Available online 6 July 2017
Source:Developmental Cell
Author(s): Jimok Yoon, Sang Bum Kim, Giasuddin Ahmed, Jerry W. Shay, Jonathan R. Terman
Extracellular cues that regulate cellular shape, motility, and navigation are generally classified as growth promoting (i.e., growth factors/chemoattractants and attractive guidance cues) or growth preventing (i.e., repellents and inhibitors). Yet, these designations are often based on complex assays and undefined signaling pathways and thus may misrepresent direct roles of specific cues. Here, we find that a recognized growth-promoting signaling pathway amplifies the F-actin disassembly and repulsive effects of a growth-preventing pathway. Focusing on Semaphorin/Plexin repulsion, we identified an interaction between the F-actin-disassembly enzyme Mical and the Abl tyrosine kinase. Biochemical assays revealed Abl phosphorylates Mical to directly amplify Mical Redox-mediated F-actin disassembly. Genetic assays revealed that Abl allows growth factors and Semaphorin/Plexin repellents to combinatorially increase Mical-mediated F-actin disassembly, cellular remodeling, and repulsive axon guidance. Similar roles for Mical in growth factor/Abl-related cancer cell behaviors further revealed contexts in which characterized positive effectors of growth/guidance stimulate such negative cellular effects as F-actin disassembly/repulsion.

Teaser

Semaphorin/plexin signaling repels cellular growth and promotes actin disassembly. Surprisingly, Yoon et al. find that these effects are amplified by growth-promoting factors acting via Abl tyrosine kinase. These results reveal a role for chemoattractant cues in promoting the effects of chemorepellents and suggest complex interactions among growth-suppressing and -promoting pathways.


http://ift.tt/2tP1XWT

Evolution of the Oral Microbiome and Dental Caries

Abstract

Purpose of Review

Our paper reviews how dietary changes during human evolution have contributed to the increased incidence and prevalence of dental caries in modern populations by shifting the oral microbiome from a "healthy" to "carious" state. We addressed two questions: (1) what is the microbial difference between the states of health and caries, and (2) how has the development of an agricultural diet impacted the oral microbiome?

Recent Findings

The application of next-generation sequencing has revealed the complexity of the oral microbiome and lack of a simple compositional difference between health and caries. Genetic analysis of the oral microbiome from contemporary and ancient humans has shown that the introduction of agriculture was associated with increased frequency of caries-related bacteria and the evolution of the key carious pathogen, Streptococcus mutans.

Summary

The adoption of an agricultural diet has contributed to a modern rise in caries by changing the oral microbiome ecology. Identification of evolutionary factors that have influenced the oral microbiome in health and caries, and how the two states differ functionally, as opposed to compositionally, may help to reduce the current burden of caries.

http://ift.tt/2sN4bql

Cancer therapies and the problem of me too many

Publication date: Available online 6 July 2017
Source:Seminars in Oncology
Author(s): Tito Fojo




http://ift.tt/2sw7kGB

Liposomal honokiol induced lysosomal degradation of Hsp90 client proteins and protective autophagy in both gefitinib-sensitive and gefitinib-resistant NSCLC cells

Publication date: October 2017
Source:Biomaterials, Volume 141
Author(s): Jianhong Yang, Wenshuang Wu, Jiaolin Wen, Haoyu Ye, Hong Luo, Peng Bai, Minghai Tang, Fang Wang, Li Zheng, Shengyong Yang, Weimin Li, Aihua Peng, Li Yang, Li Wan, Lijuan Chen
Honokiol (HK), a natural chemical isolated from Mangnolia officinalis, has shown antitumorigenic activities when used to treat a variety of tumor cell lines. The mechanism of honokiol activity when used to treat gefitinib-sensitive and gefitinib-resistant non-small cell lung cancer (NSCLC) requires elucidation. Here, the presence of liposomal honokiol (LHK) induced apoptotic and antitumor activities in four xenograft models generated using NSCLC cell lines such as HCC827 (gefitinib-sensitive) and H1975 (gefitinib-resistant). Mechanistic studies revealed that LHK inhibited the Akt and Erk1/2, both EGFR signaling cascades effectors, by promoting degradation of HSP90 client proteins (HCP), including wild-type or mutant EGFR, Akt and C-Raf. Molecular biology assays showed that LHK induced HCP degradation through a lysosomal pathway, rather than the canonical proteasome protein degradation pathway. As a result of misfolded protein accumulation, LHK induced endoplasmic reticulum (ER) stress and autophagy. Inhibition of ER stress (with 4-phenylbutyrate) or autophagy (with small interfering RNA) reduced LHK-induced HCP degradations. Additionally, LHK induced autophagy showed a protective role for cancer cell as inhibition of autophagy in vitro and in vivo by autophagosome degradation inhibitors could promote the anticancer activity of LHK. LHK has been approved by the China Food and Drug Administration for first-in-human clinical trials in NSCLC. The current study will guide the design of future LHK clinical trials.



http://ift.tt/2tWWvls

Eruptive keratoacanthomas in tattoos

http://ift.tt/2tnRyk3

Characterization of CRF1 receptor antagonists with differential peripheral vs central actions in CRF challenge in rats

Publication date: Available online 6 July 2017
Source:Peptides
Author(s): Maiko Tanaka, Yoshiro Tomimatsu, Katsuya Sakimura, Yoshikazu Ootani, Yuu Sako, Takuto Kojima, Kazuyoshi Aso, Takahiko Yano, Keisuke Hirai
The aim of this study was to investigate peripheral and central roles of corticotropin-releasing factor (CRF) in endocrinological and behavioral changes. Plasma adrenocorticotropin (ACTH) concentration was measured as an activity of hypothalamic-pituitary-adrenal (HPA) axis. As behavioral changes, locomotion and anxiety behavior were measured after CRF challenge intravenously (i.v.) for the peripheral administration or intracerebroventricularly (i.c.v.) for the central administration. Plasma ACTH concentration was significantly increased by both administration routes of CRF; however, hyperlocomotion and anxiety behavior were induced only by the i.c.v. administration. In the drug discovery of CRF1 receptor antagonists, we identified two types of compounds, Compound A and Compound B, which antagonized peripheral CRF-induced HPA axis activation to the same extent, but showed different effects on the central CRF signal. These had similar in vitro CRF1 receptor binding affinities (15 and 10nM) and functional activities in reporter gene assay (15 and 9.5nM). In the ex vivo binding assays using tissues of the pituitary, oral treatment with Compound A and Compound B at 10mg/kg inhibited [¹²⁵I]-CRF binding, whereas in the assay using tissues of the frontal cortex, treatment of Compound A but not Compound B inhibited [¹²⁵I]-CRF binding, indicating that only Compound A inhibited central [¹²⁵I]-CRF binding. In the peripheral CRF challenge, increase in plasma ACTH concentration was significantly suppressed by both Compound A and Compound B. In contrast, Compound A inhibited the increase in locomotion induced by the central CRF challenge while Compound B did not. Compound A also reduced central CRF challenge-induced anxiety behavior and c-fos immunoreactivity in the cortex and the hypothalamic paraventricular nucleus. These results indicate that the central CRF signal, rather than the peripheral CRF signal would be related to anxiety and other behavioral changes, and CRF1 receptor antagonism in the central nervous system may be critical for identifying drug candidates for anxiety and mood disorders.



http://ift.tt/2uwt1rz

Filamin B: The next hotspot in skeletal research?

Publication date: Available online 6 July 2017
Source:Journal of Genetics and Genomics
Author(s): Qiming Xu, Nan Wu, Lijia Cui, Zhihong Wu, Guixing Qiu
Filamin B (FLNB) is a large dimeric actin-binding protein which crosslinks actin cytoskeleton filaments into a dynamic structure. Up to present, pathogenic mutations in FLNB are solely found to cause skeletal deformities, indicating the important role of FLNB in skeletal development. FLNB-related disorders are classified as spondylocarpotarsal synostosis (SCT), Larsen syndrome (LS), atelosteogenesis (AO), boomerang dysplasia (BD), and isolated congenital talipes equinovarus, presenting with scoliosis, short-limbed dwarfism, clubfoot, joint dislocation and other unique skeletal abnormalities. The formation of ossification center is opposite between SCT and LS, as SCT presents with premature fusion of carpal and tarsal bones, while LS shows supernumerary ossification centers of carpal or tarsal bones. Several mechanisms of FLNB mutations causing skeletal malformations have been proposed, including delay of ossification in long bone growth plate, reduction of bone mineral density (BMD), dysregulation of muscle differentiation, ossification of intervertebral disc (IVD), disturbance of proliferation, differentiation and apoptosis in chondrocytes, impair of angiogenesis, and hypomotility of osteoblast, chondrocyte and fibroblast. Interventions on FLNB-related diseases require prenatal surveillance by sonography, gene testing in high-risk carriers, and proper orthosis or orthopedic surgeries to correct malformations including scoliosis, cervical spine instability, large joint dislocation, and clubfoot. Gene and cell therapies in treating FLNB-related diseases are also promising but require further studies.



http://ift.tt/2twp6uQ

Therapeutic applications of histone deacetylase inhibitors in sarcoma

Publication date: Available online 6 July 2017
Source:Cancer Treatment Reviews
Author(s): Fan Tang, Edwin Choy, Chongqi Tu, Francis Hornicek, Zhenfeng Duan
Sarcomas are a rare group of malignant tumors originating from mesenchymal stem cells. Surgery, radiation and chemotherapy are currently the only standard treatments for sarcoma. However, their response rates to chemotherapy are quite low. Toxic side effects and multi-drug chemoresistance make treatment even more challenging. Therefore, better drugs to treat sarcomas are needed. Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are epigenetic modifying agents that can inhibit sarcoma growth in vitro and in vivo through a variety of pathways, including inducing tumor cell apoptosis, causing cell cycle arrest, impairing tumor invasion and preventing metastasis. Importantly, preclinical studies have revealed that HDIs can not only sensitize sarcomas to chemotherapy and radiotherapy, but also increase treatment responses when combined with other chemotherapeutic drugs. Several phase I and II clinical trials have been conducted to assess the efficacy of HDIs either as monotherapy or in combination with standard chemotherapeutic agents or targeted therapeutic drugs for sarcomas. Combination regimen for sarcomas appear to be more promising than monotherapy when using HDIs. This review summarizes our current understanding and therapeutic applications of HDIs in sarcomas.



http://ift.tt/2sw0KQq

Evolution of anti-HER2 therapies for cancer treatment

Publication date: Available online 6 July 2017
Source:Cancer Treatment Reviews
Author(s): Sagun Parakh, Hui K. Gan, Adam C. Parslow, Ingrid J.G. Burvenich, Antony W. Burgess, Andrew M. Scott
The development of HER2-directed monoclonal antibodies and tyrosine kinase inhibitors have provided benefits to cancer patients, as well as produced many insights into the biology of the ErbB receptor family. Current therapies based on ErbB family members have resulted in improved overall survival with associated improvements in quality of life for the cancer patients that respond to treatment. Compared to monotherapy using either two antibodies to block the HER2 receptor blockade or combinatorial approaches with HER2 antibodies and standard therapies has provided additional benefits. Despite the therapeutic success of existing HER2 therapies, personalising treatment and overcoming resistance to these therapies remains a significant challenge. The heterogeneous intra-tumoural HER2 expression and lack of fully predictive and prognostic biomarkers remain significant barriers to improving the use of HER2 antibodies. Imaging modalities using radiolabelled pertuzumab and trastuzumab allow quantitative assessment of intra-tumoural HER2 expression, HER2 antibody saturation and the success of different drug delivery systems to be assessed. Molecular imaging with HER2 antibodies has the potential to be a non-invasive, predictive and prognostic technique capable of influencing therapeutic decisions, predicting response and failure of treatments as well as providing insights into receptor recycling and signalling. Similarly, conjugating HER2 antibodies with novel toxic payloads or combining HER2 antibodies with cellular immunotherapy provide exciting new opportunities for the management of tumours overexpressing HER2. Future research will lead to higher therapeutic responses, lower toxicities and providing insight into the mechanisms of resistance to HER2-targeted treatments.



http://ift.tt/2svWyjL

Variability in gut microbiota response to an inulin-type fructan prebiotic within an in vitro three-stage continuous colonic model system

Publication date: Available online 6 July 2017
Source:Bioactive Carbohydrates and Dietary Fibre
Author(s): G. Healey, R. Murphy, C. Butts, L. Brough, D. Rosendale, P. Blatchford, H. Stoklosinski, J. Coad
Gut microbiota have a major influence on human health and disease. Dietary interventions have been shown to beneficially modulate the gut microbiota and improve health; however, it appears there is large inter-individual variability in gut microbiota responsiveness to dietary interventions. We aimed to determine whether different fermentable carbohydrate content media, mimicking Western and Prudent style dietary patterns, influence gut microbiota response to an inulin-type fructan prebiotic using an in vitro three-stage continuous colonic model system. We demonstrated that the addition of an inulin-type fructan prebiotic led to shifts in the organic acid concentrations and bacterial taxa in both the low (LF) and high fermentable carbohydrate (HF) gut models. The shifts that occurred after the addition of the prebiotic significantly differed between the LF and HF gut models. Acetate increased in the HF gut models but decreased in the LF gut models (p=0.021). The increases that occurred in Firmicutes (p=0.026), Lactobacillus (p=0.045) and Mitsuokella (p=0.012) were significantly greater in the HF gut models. Megasphaera (p=0.033) and an unknown genus of Enterobacteriaceae (p=0.011) decreased in the LF gut models but increased in the HF gut models. The reduction in an unknown genus of Lachnospiraceae (other) was significant greater in LF gut models (p=0.040). Additionally, large inter- and intra-donor variability in gut microbiota responsiveness to the prebiotic were demonstrated. This study demonstrates that media with different fermentable carbohydrate contents caused variability in gut microbiota responsiveness to an inulin-type fructan prebiotic; however, these results will need to be replicated in an in vivo study.



http://ift.tt/2tSwbYU

Low molar excess of 4-oxo-2-nonenal and 4-hydroxy-2-nonenal promote oligomerization of alpha-synuclein through different pathways

Publication date: Available online 6 July 2017
Source:Free Radical Biology and Medicine
Author(s): Leire Almandoz-Gil, Hedvig Welander, Elisabet Ihse, Payam Emami Khoonsari, Sravani Musunuri, Christofer Lendel, Jessica Sigvardson, Mikael Karlsson, Martin Ingelsson, Kim Kultima, Joakim Bergström
Aggregated alpha-synuclein is the main component of Lewy bodies, intraneuronal inclusions found in brains with Parkinson's disease and dementia with Lewy bodies. A body of evidence implicates oxidative stress in the pathogenesis of these diseases. For example, a large excess (30:1, aldehyde:protein) of the lipid peroxidation end products 4-oxo-2-nonenal (ONE) or 4-hydroxy-2-nonenal (HNE) can induce alpha-synuclein oligomer formation. The objective of the study was to investigate the effect of these reactive aldehydes on alpha-synuclein at a lower molar excess (3:1) at both physiological (7.4) and acidic (5.4) pH. As observed by size-exclusion chromatography, ONE rapidly induced the formation of alpha-synuclein oligomers at both pH values, but the effect was less pronounced under the acidic condition. In contrast, only a small proportion of alpha-synuclein oligomers were formed with low excess HNE-treatment at physiological pH and no oligomers at all under the acidic condition. With prolonged incubation times (up to 96h), more alpha-synuclein was oligomerized at physiological pH for both HNE and ONE. As determined by Western blot, ONE-oligomers were more SDS-stable and to a higher-degree cross-linked as compared to the HNE-induced oligomers. However, as shown by their greater sensitivity to proteinase K treatment, ONE-oligomers, exhibited a less compact structure than HNE-oligomers. As indicated by mass spectrometry, ONE modified most Lys residues, whereas HNE primarily modified the His50 residue and fewer Lys residues, albeit to a higher degree than ONE. Taken together, our data show that the aldehydes ONE and HNE can modify alpha-synuclein and induce oligomerization, even at low molar excess, but to a higher degree at physiological pH and seemingly through different pathways.

Graphical abstract

http://ift.tt/2svTdRL

Rifampicin-induced injury in HepG2 cells is alleviated by TUDCA via increasing bile acid transporters expression and enhancing the Nrf2-mediated adaptive response

Publication date: Available online 6 July 2017
Source:Free Radical Biology and Medicine
Author(s): Weiping Zhang, Lihong Chen, Hui Feng, Wei Wang, Yi Cai, Fen Qi, Xiaofang Tao, Jun Liu, Yujun Shen, Xiaofei Ren, Xi Chen, Jianming Xu, Yuxian Shen
Bile acid transporters and the nuclear factor erythroid 2-related factor (Nrf-2)-mediated adaptive response play important roles in the development of drug-induced liver injury (DILI). However, little is known about the contribution of the adaptive response to rifampicin (RFP)-induced cell injury. In this study, we found RFP decreased the survival rate of HepG2 cells and increased the levels of lactate dehydrogenase (LDH), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), γ-glutamyl-transferase (γ-GT), total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), total bile acid (TBA) and adenosine triphosphate (ATP) in the cell culture supernatants in both a concentration- and a time-dependent manner. RFP increased the expression levels of bile acid transporter proteins and mRNAs, such as bile salt export pump (BSEP), multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 2 (MRP2), Na⁺/taurocholate cotransporter (NTCP), organic anion transporting protein 2 (OATP2), organic solute transporter β (OSTβ) and Nrf2. Following the transient knockdown of Nrf2 and treatment with RFP, the expression levels of the BSEP, MDR1, MRP2, NTCP, OATP2 and OSTβ proteins and mRNAs were decreased to different degrees. Moreover, the cell survival was decreased, whereas the LDH level in the cell culture supernatant was increased. Overexpression of the Nrf2 gene produced the opposite effects. Treatment with tauroursodeoxycholic acid (TUDCA) increased the expression levels of the bile acid transporters and Nrf2, decreased the expression levels of glucose-regulated protein 78 (GRP78), PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP-homologous protein (CHOP), and inhibited RFP-induced oxidative stress. Moreover, TUDCA reduced cell apoptosis, increased cell survival and decreased the levels of LDH, ALT, AST, AKP, γ-GT, TBIL, DBIL, IBIL, TBA and ATP in the cell culture supernatant. Therefore, TUDCA alleviates RFP-induced injury in HepG2 cells by enhancing bile acid transporters expression and the Nrf2-mediated adaptive response.

Graphical abstract

http://ift.tt/2svS2BO

Examining a role for PKG Iα oxidation in the pathogenesis of cardiovascular dysfunction during diet-induced obesity

Publication date: Available online 6 July 2017
Source:Free Radical Biology and Medicine
Author(s): Olena Rudyk, Philip Eaton
BackgroundProtein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state. Diet-induced obesity is associated with NOS uncoupling, which may in part contribute to the associated cardiovascular dysfunction due to exacerbated PKG Iα disulfide oxidation to the disulfide state. This is a rational hypothesis because PKG Iα oxidation is known to significantly contribute to heart failure that arises from chronic myocardial oxidative stress.Methods and ResultsBovine arterial endothelial cells (BAECs) or smooth muscle cells (SMCs) were exposed to drugs that uncouple NOS. These included 1,3-bis(2-chloroethyl)−1-nitrosourea (BCNU) which promotes its S-glutathiolation, 4-diamino-6-hydroxy-pyrimidine (DAHP) which inhibits guanosine-5'-triphosphate-cyclohydrolase 2 to prevent BH4 synthesis or methotrexate (MTX) which inhibits the regeneration of BH4 from BH2 by dihydrofolate reductase. While all the drugs mentioned above induced robust PKG Iα disulfide dimerization in cells, exposure of BAECs to NOS inhibitor L-NMMA did not. Increased PKG Iα disulfide formation occurred in hearts and aortae from mice treated in vivo with DAHP (10mM in a drinking water for 3 weeks). Redox-dead C42S PKG Iα knock-in (KI) mice developed less pronounced cardiac posterior wall hypertrophy and did not develop cardiac dysfunction, assessed by echocardiography, compared to the wild-type (WT) mice after chronic DAHP treatment. WT or KI mice were then subjected to a diet-induced obesity protocol by feeding them with a high fat Western-type diet (RM 60% AFE) for 27 weeks, which increased body mass, adiposity, plasma leptin, resistin and glucagon levels comparably in each genotype. Obesity-induced hypertension, assessed by radiotelemetry, was mild and transient in the WT, while the basally hypertensive KI mice were resistant to further increases in blood pressure increase following high fat feeding. Although the obesogenic diet caused mild cardiac dysfunction in the WT but not the KI mice, gross changes in myocardial structure monitored by echocardiography were not apparent in either genotype. The level of cyclic guanosine monophosphate (cGMP) was decreased in the aortae of WT and KI mice following high fat feeding. PKG Iα oxidation was not evident in the hearts of WT mice fed a high fat diet.ConclusionsDespite robust evidence for PKG Iα oxidation during NOS uncoupling in cell models, it is unlikely that PKG Iα oxidation occurs to a significant extent in vivo during diet-induced obesity and so is unlikely to mediate the associated cardiovascular dysfunction.

Graphical abstract

http://ift.tt/2svH6nQ

Connexin43, but not connexin30, contributes to adult neurogenesis in the dentate gyrus

Publication date: Available online 6 July 2017
Source:Brain Research Bulletin
Author(s): Jiong Zhang, Stephanie Griemsmann, Zhou Wu, Radoslaw Dobrowolski, Klaus Willecke, Martin Theis, Christian Steinhäuser, Peter Bedner
The subgranular zone of the dentate gyrus represents a niche in which radial glia (RG)-like cells generate new neurons throughout postnatal life in the mammalian brain. Previous data showed that RG-like cells are coupled through gap junction channels, primarily formed by connexin43 (Cx43) and Cx30, and that the expression of these proteins is required for adult neurogenesis in the hippocampus. However, their individual function and underlying mechanisms remain unclear. Here we demonstrate that Cx43, but not Cx30, is crucial for adult neurogenesis. To assess whether Cx43-dependent intercellular coupling between RG-like cells or rather channel-independent interactions of the protein regulate neurogenesis, mice bearing a Cx43 point mutation (Cx43G138R) in RG-like cells and protoplasmic astrocytes cells were employed, which was expected to cause channel closure without affecting the trafficking of the protein to the membrane. We confirmed the disruption of coupling between RG-like cells and astrocytes in the hippocampus of Cx43G138R mice. Proliferative activity and neurogenesis in the DG were significantly decreased in the mutant mouse line, indicating that functional Cx43 channels are essential for proper adult neurogenesis. The fate of proliferating cells in the DG was not affected by Cx43 mutation as revealed by 5-bromo-2-deoxyuridine (BrdU) incorporation assays. Together, these findings suggest that adult neurogenesis in the hippocampus does not require Cx30 but channel-dependent functions of Cx43.



http://ift.tt/2svOIXf

Transitions in Prognostic Awareness Among Terminally Ill Cancer Patients in Their Last 6 Months of Life Examined by Multi‐State Markov Modeling

AbstractBackground.Developing accurate prognostic awareness, a cornerstone of preference‐based end‐of‐life (EOL) care decision‐making, is a dynamic process involving more prognostic‐awareness states than knowing or not knowing. Understanding the transition probabilities and time spent in each prognostic‐awareness state can help clinicians identify trigger points for facilitating transitions toward accurate prognostic awareness. We examined transition probabilities in distinct prognostic‐awareness states between consecutive time points in 247 cancer patients' last 6 months and estimated the time spent in each state.Methods.Prognostic awareness was categorized into four states: (a) unknown and not wanting to know, state 1; (b) unknown but wanting to know, state 2; (c) inaccurate awareness, state 3; and (d) accurate awareness, state 4. Transitional probabilities were examined by multistate Markov modeling.Results.Initially, 59.5% of patients had accurate prognostic awareness, whereas the probabilities of being in states 1–3 were 8.1%, 17.4%, and 15.0%, respectively. Patients' prognostic awareness generally remained unchanged (probabilities of remaining in the same state: 45.5%–92.9%). If prognostic awareness changed, it tended to shift toward higher prognostic‐awareness states (probabilities of shifting to state 4 were 23.2%–36.6% for patients initially in states 1–3, followed by probabilities of shifting to state 3 for those in states 1 and 2 [9.8%–10.1%]). Patients were estimated to spend 1.29, 0.42, 0.68, and 3.61 months in states 1–4, respectively, in their last 6 months.Conclusion.Terminally ill cancer patients' prognostic awareness generally remained unchanged, with a tendency to become more aware of their prognosis. Health care professionals should facilitate patients' transitions toward accurate prognostic awareness in a timely manner to promote preference‐based EOL decisions.Implications for Practice.Terminally ill Taiwanese cancer patients' prognostic awareness generally remained stable, with a tendency toward developing higher states of awareness. Health care professionals should appropriately assess patients' readiness for prognostic information and respect patients' reluctance to confront their poor prognosis if they are not ready to know, but sensitively coach them to cultivate their accurate prognostic awareness, provide desired and understandable prognostic information for those who are ready to know, and give direct and honest prognostic information to clarify any misunderstandings for those with inaccurate awareness, thus ensuring that they develop accurate and realistic prognostic knowledge in time to make end‐of‐life care decisions.

http://ift.tt/2uwENCv

Spectrophotometric analysis of the effectiveness of a novel in-office laser-assisted tooth bleaching method using Er,Cr:YSGG laser

Abstract

The purpose of this in vitro study was to compare the effectiveness of a novel Er,Cr:YSGG laser-assisted in-office tooth bleaching method with a conventional method by spectrophotometric analysis of the tooth color change. Furthermore, the influence of the application time of the bleaching gel on the effectiveness of the methods and the maintenance of the results 7 days and 1 month after the treatments were also evaluated. Twenty-four bovine incisors were stained and randomly distributed into four groups. Group 1 specimens received an in-office bleaching treatment with 35% H₂O₂ for 2 × 15 min. Group 2 specimens received the same treatment but with extended application time (2 × 20 min). In Group 3, the same in-office bleaching procedure (2 × 15 min) was carried out as that in Group 1, using Er,Cr:YSGG laser irradiation for 2 × 15 s on each specimen to catalyze the reaction of H₂O₂ breakdown. Group 4 specimens received the same bleaching treatment as Group 3 but with extended application time (2 × 20 min). Er,Cr:YSGG laser-assisted tooth bleaching treatment is more effective than the conventional treatment regarding color change of the teeth. Application time of the bleaching agent may influence the effectiveness of the methods. The color change of the tested treatments decreases after 7 days and 1 month. The clinical relevance of this study is that this novel laser-assisted bleaching treatment may be more advantageous in color change and application time compared to the conventional bleaching treatment.

http://ift.tt/2tn6TRS

Impact of air masses on the distribution of 210Pb in the southeast of Iberian Peninsula air

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): E. Chham, F. Piñero-García, P. González-Rodelas, M.A. Ferro-García
The current research has been developed in the southern of the Iberian Peninsula in order to better understand the atmospheric processes and also the influence of the air masses origin and pathways in the transport of ²¹⁰Pb-aerosols in the atmosphere. Simultaneous measurements of the radionuclides ⁷Be and ²¹⁰Pb on airborne have been routinely carried out at Granada (Spain 37.177N, 3.598 W, 687 m a.s.l.) from 2010 to 2014. The long term monitoring evolution on ²¹⁰Pb is discussed in this study and also the useful ratio ⁷Be/²¹⁰Pb.The maximum monthly activity concentration for ²¹⁰Pb at ground level in Granada was detected during summer and early autumn (September), whereas minimum activity was measured in the winter. The monthly mean activity concentration for ²¹⁰Pb was 617.8 ± 33.0 μBq·m⁻³. The results show that the annual average ²¹⁰Pb concentrations in samples collected during the same period were almost constant.The lowest activity concentration for ²¹⁰Pb are associated with maritime air masses coming from Atlantic and Norwest of Spain, while the highest activity concentrations for this radiotracers were positively correlated with the arrival of mineral dust linked to continental air masses coming from Mediterranean, Africa and Local area. The concentrations values show a nice agreement with the relevant reported results.



http://ift.tt/2tXm5GZ

Atmospheric tritium concentrations under influence of AREVA NC La Hague reprocessing plant (France) and background levels

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): O. Connan, D. Hébert, L. Solier, D. Maro, G. Pellerin, C. Voiseux, M. Lamotte, P. Laguionie
In-air tritium measurements were conducted around the AREVA NC La Hague reprocessing plant, as well as on other sites that are not impacted by the nuclear industry in northwest of France. The results indicate that the dominant tritium form around the AREVA site is HT (86%). HT and HTO levels are lower than 5 and 1 Bq. m⁻³ for hourly samples taken in the plume. No tritiated organic molecules (TOM) were detected. 26 measurement campaigns were performed and links were established between near-field ⁸⁵Kr, HT and HTO activities. Environmental measurements are in line with those taken at the discharge stack, and tend to demonstrate that there are no rapid changes in the tritium forms released. Out of the influence of any nuclear activities, the levels measured were below 13 mBq.m⁻³ for HT and 5 mBq.m⁻³ for HTO (<0.5 Bq. L⁻¹). HTO level in air seems to be influenced by HTO activities in surrounding seawater.



http://ift.tt/2uvXTsn

Distribution of heavy metals around the Barakah nuclear power plant in the United Arab Emirates

Abstract

Inductively coupled plasma emission spectroscopy was used to measure the concentrations of heavy metals in 58 samples collected from the Barakah nuclear power plant (BNPP) area, UAE. The grain size distribution was symmetric, but the samples ranged from fine to coarse sand. The inverse relationship between grain size and heavy metal contaminations was validated. The pre-operational average heavy metal contaminations around the BNPP were 0.03, 0.40, 1.2, 2.05, 1.66, 1.6, 5.9, 7.3, 7, 8.8, 60, and 2521 ppm for Cd, Mo, Co, Cu, Pb, As, Zn, Ni, V, Cr, Mn, and Fe, respectively. The spatial distribution was more compact in the south compared to the north, with less severe contaminations in the east and west. The negative geoaccumulation indices suggest an uncontaminated area, and the BNPP has minor enrichments. All concentrations were significantly below the safe limits set by the Dutch guidelines. The levels of heavy metals reported in the UAE were lower than levels reported in countries around the world.

http://ift.tt/2uQyt8e

Favorable effects of Myo-inositol, selenomethionine or their combination on the hydrogen peroxide-induced oxidative stress of peripheral mononuclear cells from patients with Hashimoto’s thyroiditis: preliminary in vitro studies

OBJECTIVE: The aim of this study was to assess whether blood mononuclear cells (PBMC) from Hashimoto's thyroiditis (HT) and control women, were protected from in vitro H2O2-induced oxidative stress after addition of antioxidants.

PATIENTS AND METHODS: PBMC, from 8 HT women and 3 healthy women (controls), were cultured in the presence of 200 µM H2O2 alone, with subsequent addition of myo-inositol (Myo) (0.25, 0.5, 1.0 µM), selenomethionine (SelMet) (0.25, 0.5, 1.0 µM), or their combination (0.25+0.25, 0.5+0.5, 1.0+1.0 µM). PBMC proliferation, vitality, genotoxicity (Comet score) and secretion in the medium of the chemokines CXCL10 [IP10], CCL2 e CXCL9 [MIG] were the indices measured.

RESULTS: PBMC proliferation was decreased by H2O2 alone, and it decreased further and dose-dependently in either group (greatest decrease with Myo+SelMet in HT). H2O2 alone decreased vitality by 5% in controls and 10% in the HT group, but vitality was rescued by the three additions. The addition of H2O2 alone increased the Comet score at +505% above baseline in controls and +707% in HT women. In either group, each addition dose-dependently contrasted genotoxicity. Concentrations of chemokines in the medium were increased by H2O2 alone, and in HT women more than in controls. Each addition dose-dependently decreased these concentrations in either group, and often below baseline levels, with Myo+SelMet being the most potent addition (up to approximately -80% of baseline).

CONCLUSIONS: The tested antioxidants exert beneficial effects on PBMC exposed in vitro to H2O2-induced oxidative stress in both control and HT women. Particularly, the association Myo+SelMet is the most effective. After the demonstration of a favorable in vitro outcomes in a large cohort of HT patients, we could predict favorable in vivo outcomes given by the same supplement. Thus, one can select HT patients with a high chance of benefit from supplementation.

L'articolo Favorable effects of Myo-inositol, selenomethionine or their combination on the hydrogen peroxide-induced oxidative stress of peripheral mononuclear cells from patients with Hashimoto's thyroiditis: preliminary in vitro studies sembra essere il primo su European Review.

http://ift.tt/2tMlvLC

Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis

Sleep disturbances and dementia are two common and significant health problems in older adults. Investigations suggest that sleep disturbances might increase the risk of dementia. The aim of the present study was to systematically review and meta-analyze the predictive roles of overall sleep disturbances, their subtypes (e.g., insomnia, sleep disordered breathing [SDB]), and other sleep problems (e.g., excessive daytime sleepiness, sleep-related movement disorder, circadian rhythm sleep disorder, and nonspecific sleep problems) in incident all-cause dementia and Alzheimer's disease (AD) and vascular dementia subtypes.

http://ift.tt/2uw6T0p

Influence of relative humidity on heterogeneous reactions of O3 and O3/SO2 with soot particles: Potential for environmental and health effects

Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Xiang He, Shufeng Pang, Jiabi Ma, Yunhong Zhang
The heterogeneous reactions of soot particles with O3 and the mixture of O3 and SO2 were studied as a function of relative humidities (RHs). The reactions were followed in real time using microscopic Fourier transform infrared (micro-FTIR) spectrometer to obtain kinetic data. The results show that the ketone (CO) group is the main product of the O3/soot reaction, and the sulfate is identified on the surface of soot particles in the presence of O3/SO2. Both reactions are sensitive to RHs and surrounding water significantly promotes the proceeding of the heterogeneous reactions. For the O3/soot reaction, the pseudo-first-order rate constant increases from 3.2 × 10⁻⁴ s⁻¹ to 7.1 × 10⁻⁴ s⁻¹ with increasing RH in the range of 1%–82%. When O3 and SO2 exist simultaneously during the reaction, the reaction rate and uptake coefficient are all enhanced by about an order of magnitude as the RH increases from 1% to 83%. The high productions of the ketone and sulfate on soot surface are of highly hydrophilic, which play a key role in environmental effect under humid environment. The possible reaction mechanism speculates that products of aromatic carbonyls and dihydrofuran species on soot particles will be more harmful to human health.

Graphical abstract

http://ift.tt/2tnbAuQ

Quantifying the uncertainties of China's emission inventory for industrial sources: From national to provincial and city scales

Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Yu Zhao, Yaduan Zhou, Liping Qiu, Jie Zhang
A comprehensive uncertainty analysis was conducted on emission inventories for industrial sources at national (China), provincial (Jiangsu), and city (Nanjing) scales for 2012. Based on various methods and data sources, Monte-Carlo simulation was applied at sector level for national inventory, and at plant level (whenever possible) for provincial and city inventories. The uncertainties of national inventory were estimated at −17–37% (expressed as 95% confidence intervals, CIs), −21–35%, −19–34%, −29–40%, −22–47%, −21–54%, −33–84%, and −32–92% for SO2, NOX, CO, TSP (total suspended particles), PM10, PM2.5, black carbon (BC), and organic carbon (OC) emissions respectively for the whole country. At provincial and city levels, the uncertainties of corresponding pollutant emissions were estimated at −15–18%, −18–33%, −16–37%, −20–30%, −23–45%, −26–50%, −33–79%, and −33–71% for Jiangsu, and −17–22%, −10–33%, −23–75%, −19–36%, −23–41%, −28–48%, −45–82%, and −34–96% for Nanjing, respectively. Emission factors (or associated parameters) were identified as the biggest contributors to the uncertainties of emissions for most source categories except iron & steel production in the national inventory. Compared to national one, uncertainties of total emissions in the provincial and city-scale inventories were not significantly reduced for most species with an exception of SO2. For power and other industrial boilers, the uncertainties were reduced, and the plant-specific parameters played more important roles to the uncertainties. Much larger PM10 and PM2.5 emissions for Jiangsu were estimated in this provincial inventory than other studies, implying the big discrepancies on data sources of emission factors and activity data between local and national inventories. Although the uncertainty analysis of bottom-up emission inventories at national and local scales partly supported the "top-down" estimates using observation and/or chemistry transport models, detailed investigations and field measurements were recommended for further improving the emission estimates and reducing the uncertainty of inventories at local and regional scales, for both industrial and other sectors.



http://ift.tt/2tmLuse

Multi-year application of WRF-CAM5 over East Asia-Part II: Interannual variability, trend analysis, and aerosol indirect effects

Publication date: September 2017
Source:Atmospheric Environment, Volume 165
Author(s): Yang Zhang, Kai Wang, Jian He
Following a comprehensive evaluation of WRF-CAM5 in Part I, Part II describes analyses of interannual variability, multi-year variation trends, and the direct, indirect, and total effects of anthropogenic aerosols. The interannual variations of chemical column and surface concentrations, and ozone (O3)/particulate matter (PM) indicators are strongly correlated to anthropogenic emission changes. Despite model biases, the model captures well the observed interannual variations of temperature at 2-m, cloud fraction, shortwave cloud forcing, downwelling shortwave radiation, cloud droplet number concentration, column O3, and column formaldehyde (HCHO) for the whole domain. While the model reproduces the volatile organic compound (VOC)-limited regimes of O3 chemistry at sites in Hong Kong, Taiwan, Japan, South Korea, and from the Acid Deposition Monitoring Network in East Asia (EANET) and the degree of sulfate neutralization at the EANET sites, it has limited capability in capturing the interannual variations of the ratio of O3 and nitrogen dioxide (O3/NO2) and PM chemical regime indicators, due to uncertainties in the emissions of precursors for O3 and secondary PM, the model assumption for ammonium bisulfate (NH4HSO4) as well as lack of gas/particle partitioning of total ammonia and total nitrate. While the variation trends in multi-year periods in aerosol optical depth and column concentrations of carbon monoxide, sulfur dioxide, and NO2 are mainly caused by anthropogenic emissions, those of major meteorological and cloud variables partly reflect feedbacks of chemistry to meteorological variables. The impacts of anthropogenic aerosol indirect effects either dominate or play an important role in the aerosol total effects for most cloud and chemical predictions, whereas anthropogenic aerosol direct effects influence most meteorological and radiation variables. The direct, indirect, and total effects of anthropogenic aerosols exhibit a strong interannual variability in 2001, 2006, and 2011.



http://ift.tt/2sSlAc3

Suction drains in aesthetic breast implant exchange are associated with surgical site infections: A retrospective cohort study

Surgical site infection (SSI) following aesthetic breast implant exchange occurs in up to 2% of procedures. The effect of suction drains on SSI risk in these cases remains controversial. The goal of this study was to assess SSI risk in the presence of suction drains after aesthetic exchange of breast implants.

http://ift.tt/2tmJDne

A systematic review of the influence of burying or not burying Kirschner wires on infection rates following fixation of upper extremity fractures

Fractures of the upper extremity are common with bones in the hand most frequently fractured. Hand fractures are typically seen in men of working age, distal radius fractures in an older population following a fall and supracondylar fractures in children.1 Kirschner wire (K-wire) fixation is the most common method of surgical fixation. One of the key decisions is whether to bury or not to bury the wire ends. Current popular opinion suggests that buried wires reduce infection rates. However, burying wires still retains a risk of erosion through the skin with subsequent pin site infection.

http://ift.tt/2sS1Q8s

Perioperative Antibiotic Use in Diabetic Patients: A Retrospective Review of 670 Surgeries

Carpal tunnel syndrome (CTS) has a high incidence in diabetic patients, with a reported incidence up to 21%. In severe cases of CTS, patients may undergo carpal tunnel release (CTR) surgery, which involves risk of infection and other complications. Some physicians provide prophylactic antibiotics to decrease risk of infection. Our study examines the effects of prophylactic antibiotic use, especially in a high-risk, diabetic population.

http://ift.tt/2tmT8CC

A Negative Pressure Wound Therapy for complex infected cranial defects overlying dura mater: An effective and safe procedure

Despite rare, large cranial infected defects involving dura mater are challenging for practicians. Many patients are poor candidates for immediate reconstruction because of original pathology, comorbidities or previous radiotherapy. Recently, few authors have reported the use of negative pressure wound therapy (NPWT) in association with a first-step debridement surgery with encouraging results (1-2). In our institution, when immediate reconstruction is not feasible, a standardized reproducible two-steps procedure has been established.

http://ift.tt/2sSjUzj

Multimarker study of the effects of antifouling biocide on benthic organisms: results using Perna viridis as candidate species

Abstract

Toxic effects of continuous low dose application of the antifouling biocide chlorine on marine benthic organisms were monitored using transplanted green mussels (Perna viridis) and a suite of biomarkers. Caged mussels were deployed in chlorinated and non-chlorinated sections of the cooling system of an operating electric power plant. Biomarkers indicative of general stress, oxidative stress (superoxide dismutase and catalase), and DNA integrity, along with expression of stress proteins, were studied to assess the effects. Deterioration in condition index with corresponding increase in DNA strand breaks was indicative of chlorine stress. Superoxide dismutase enzyme did not show any particular trend, but catalase activity was high during the initial days of exposure at the chlorinated site; later, it became almost equal to that at the control site. Similarly, expressions of stress proteins (HSP60, HSP70, HSP22, GSTS1, and CYP4) showed bell-shaped pattern during the period of study. Positive correlation among the endpoints indicated the utility of the multimarker approach to monitor the effects of continuous low dose chlorination on mussels.

http://ift.tt/2tmRMYR

Emission characteristics of toxic pollutants from an updraft fixed bed gasifier for disposing rural domestic solid waste

Abstract

Gasification has gained advantage as an effective way to dispose domestic solid waste in mountainous rural of China. However, its toxic emissions such as PCDD/Fs and heavy metals, as well as their potential environmental risks, were not well studied in engineering application. In this study, an updraft fixed bed gasifier was investigated by field sampling analysis. Results showed that low toxic emissions (dust, SO₂, NOx, HCl, CO, H₂S, NH₃, PCDD/Fs and heavy metals) in the flue gas were achieved when the rural solid waste was used as feedstock. The mass distribution of heavy metals showed that 94.00% of Pb, 80.45% of Cu, 78.00% of Cd, 77.31% of Cr, and 76.25% of As were remained in residual, whereas 86.58% of Hg was found in flue gas. The content of PCDD/Fs in the flue gas was 0.103 ngI-TEQ·Nm⁻³, and the total emission factor of PCDD/Fs from the gasifier was 50.04 μgI-TEQ·t-waste⁻¹, among which only 0.04 μgI-TEQ·t-waste⁻¹ was found in the flue gas. The total output of PCDD/Fs was1.89 times as high as input, indicting the updraft fixed bed gasifier increased emission of PCDD/Fs during the treatment domestic solid waste. In addition, the distribution characteristics of PCDD/Fs congeners reflected that PCDD/Fs was mainly generated in the gasification process rather than the stage of flue gas cleaning, suggesting the importance to effectively control the generation of PCDD/Fs within the gasifier chamber in order to obtain a low PCDD/Fs emission level.

http://ift.tt/2sS3K9m

Insectifugal and insecticidal potentials of two tropical botanical essential oils against cowpea seed bruchid

Abstract

Essential oils (EO) obtained from Xylopia parviflora root bark and Hoslundia opposita leaf via hydro distillation were analysed by GC-MS and evaluated for their insectifugal (repellent) and insecticidal activities against cowpea seed bruchid (Callosbruchus maculatus Fabricius), a cosmopolitan pest of cowpea seeds. X. parviflora was predominated by sesquiterpenes (59.57%), with the main compounds being β-himachalene (22.68%), 1,7,7,Trimethylbicyclo[2.2.1]hept-5-en-2-ol (19.68%), β-elemene (14.41%), 5(1H)-Azulenone, 2,4,6,7,8,8a–hexahydro-3,8-dimethyl-4-(1-methylethylidene)-(85-cis)- (12.38%) and (−)-α-parasinsen (8.34%). The predominant compounds in H. opposita EO were 1,8-cineole (61.15%), followed by α-terpineol (16.81%) and β-phellandrene (13.25%). Percentage repellence at application rates of 0.66–1.32 μl/cm² (46.93–73.07%) was significantly (p < 0.05) higher than that of control (17.73%). RD₅₀ (repellence dose for 50% of treated adults) for H. opposita (0.43 μl/cm²) was not significantly different from the value for X. parviflora (0.60 μl/cm²). Although higher percentage of male mortality than female mortality was observed due to topical application of the EOs, the disparity was not significant. The results of correlation of the chemical groups of the EOs with the insectifugal activity indicate that the observed bioactivity was due to the synergistic effects of the chemical groups. The two EOs are therefore recommended for incorporation into bruchid protection schemes in the tropics.

http://ift.tt/2tmAgE6

Chrysotile and rock wool fibers induce chromosome aberrations and DNA damage in V79 lung fibroblast cells

Abstract

According to global estimates, at least 107,000 people die each year from asbestos-related lung cancer, mesothelioma, and asbestosis resulting from occupational exposure. Chrysotile accounts for approximately 90% of asbestos used worldwide. Artificial substitutes can also be cytotoxic to the same degree as chrysotile. But only a few researchers focused on their genetic effects and mutagenicity information which is useful in evaluating the carcinogenicity of chemicals. In this study, chrysotile from Mangnai, Qinghai, China, and an artificial substitute, rock wool fiber were prepared as suspensions and were tested at concentrations of 50, 100, and 200 μg/ml in V79 lung fibroblasts. Chromosome aberrations were detected by micronucleus assay after exposure for 24 h, and DNA damage were estimated by single cell gel electrophoresis after exposure for 12, 24, or 48 h. According to the results, chrysotile and rock wool fibers caused micronuclei to form in a dose-dependent manner in V79 cells; olive tail moment values increased in a dose- and time-dependent manner. When V79 cells were exposed to a concentration of 200 μg/ml, the degree of DNA damage induced by chrysotile fibers was greater than rock wool fibers. Our study suggests that both chrysotile and rock wool fibers could induce chromosome aberrations and DNA damage. These materials are worthy of further study.

http://ift.tt/2sSyG9b

Interrelationship between silicon, aluminum, and elements associated with tissue metabolism and degenerative processes in degenerated human intervertebral disc tissue

Abstract

There is a growing body of evidence concerning the significant role of silicon in development and composition of both connective and bone tissue. Bio-essential silicon shows strong chemical and biological affinity to aluminum, which is toxic and biologically inessential element. The presence of silicon was confirmed in a variety of tissues; however, it has never been examined in intervertebral disc tissue, neither in healthy nor in degenerated one. In this paper, for the first time in the literature, we present the content of silicon in the degenerated intervertebral disc tissue. We also compared the results of silicon analysis with aluminum values in degenerated intervertebral disc tissue in humans. We used chemometric methods to find correlations and similarities between silicon, aluminum, and elements associated with tissue metabolism (Mg) and degenerative processes (Zn and Cu). The presence of silicon was confirmed in all 30 samples harvested from 22 patients operated on due to degenerative changes. Its concentration was within the range of 5.37–12.8 μg g⁻¹ d.w., with the mean concentration of 7.82 μg g⁻¹ d.w. The analysis showed significant correlation between Si and both Al and Mg and weak or negative correlation with Zn and Cu, where the latter was probably the result of degenerative processes. Although silicon is considered essential in glycosaminoglycan and collagen synthesis in connective tissue, it did not show any correlation nor similarities with elements reflecting changes associated with the degenerative process of the intervertebral disc. Silicon showed significant correlation with aluminum, similar to those observed in other human tissues.

http://ift.tt/2tmpaPi

Water footprint and carbon footprint of the energy consumption in sunflower agroecosystems

Abstract

The aims of this study were to assess the energy requirements, carbon footprint, and water footprint of sunflower production in Kermanshah province, western Iran. Data were collected from 70 sunflower production agroecosystems which were selected based on random sampling method in summer 2012. Results indicated that total input and output energy in sunflower production were 26,973.87 and 64,833.92 MJha⁻¹, respectively. The highest share of total input energy in sunflower agroecosystems was recorded for electricity power, N fertilizer, and diesel fuel with 35, 19, and 17%, respectively. Also, energy use efficiency, water footprint, greenhouse gas (GHG) emission, and carbon footprint were calculated as 2.40, 3.41 m³ kg⁻¹, 2042.091 kg CO_2eqha⁻¹, and 0.875 kg CO_2eqkg⁻¹, respectively. 0.18 of sunflower water footprint was related to green water footprint and the remaining 82% was related to blue water footprint. Also, the highest share of carbon footprint was related to electricity power (nearby 80%). Due to the results of this study, reducing use of fossil fuel and non-renewable energy resource and application of sufficient irrigation systems by efficient use of water resource are essential in order to achieve low carbon footprint, environmental challenges, and also sustainability of agricultural production systems.

http://ift.tt/2sSErUy

Sediment bacterial communities in a eutrophic lake influenced by multiple inflow-rivers

Abstract

Sediment bacterial communities are sensitive to environmental fluctuations, particularly external input sources. Studying the relationships between bacterial community distribution and the estuarine environment is critical for understanding the river-lake confluence ecosystem and the effect of inflow-rivers on lakes. In the present study, bacterial communities from the sediments of 14 estuaries and four pelagic sites of the Taihu Lake were investigated via high-throughput sequencing. The results demonstrated that Delta-, Beta-, and Gamma-proteobacteria, Acidobacteria, Nitrospira, Bacilli, Anaerolineae, and Actinobacteria were the major classes in sediment bacterial communities of the Taihu Lake. In general, the inflow-rivers of different pollution types have distinctly different influences on sediment bacterial communities of the lake. The bacterial community composition and physicochemical properties of pelagic sites were closer to those of the estuaries of western region which was polluted by serious industrial and agricultural pollution. The bacterial community diversity of estuaries was lower than those of pelagic sites. Spearman correlation analysis indicated that α-diversity of the bacterial community was significantly correlated with C/N, total nitrogen, and total carbon in estuarine sediments. Redundancy analysis revealed that the variance in bacterial community composition was also significantly associated with C/N (24.9%) followed by total phosphorus (15.8%), nitrite (7.2%), and nitrate (7.7%) among different estuaries. This study provides a reference to understand the influence of inflow-rivers on the lake ecosystem, which offered a basic guidance for maintaining the ecological system and protecting the water environment of lacustrine basin.

http://ift.tt/2tmR11H

Effect of pH and polypropylene beads in hybrid water treatment process of alumina ceramic microfiltration and PP beads with air back-flushing and UV irradiation

Abstract

For advanced water treatment, effects of pH and pure polypropylene (PP) beads packing concentration on membrane fouling and treatment efficiency were observed in a hybrid process of alumina ceramic microfiltration (MF; pore size 0.1 μm) and pure PP beads. Instead of natural organic matters and fine inorganic particles in natural water source, a quantity of humic acid (HA) and kaolin was dissolved in distilled water. The synthetic feed flowed inside the MF membrane, and the permeated water contacted the PP beads fluidized in the gap of the membrane and the acryl module case with outside UV irradiation. Periodic air back-flushing was performed to control membrane fouling during 10 s per 10 min. The membrane fouling resistance (R _f) was the maximum at 30 g/L of PP bead concentration. Finally, the maximum total permeated volume (V _T) was acquired at 5 g/L of PP beads, because flux maintained higher all through the operation. The treatment efficiency of turbidity was almost constant, independent of PP bead concentration; however, that of dissolved organic materials (DOM) showed the maximal at 50 g/L of PP beads. The R _f increased as increasing feed pH from 5 to 9; however, the maximum V_T was acquired at pH 6. It means that the membrane fouling could be inhibited at low acid condition. The treatment efficiency of turbidity increased a little, and that of DOM increased from 73.6 to 75.7% as increasing pH from 5 to 9.

http://ift.tt/2sS3HKI

Fish as bioindicators for trace element pollution from two contrasting lakes in the Eastern Rift Valley, Kenya: spatial and temporal aspects

Abstract

Lake Turkana and Lake Naivasha are two freshwater lakes in the Kenyan Rift Valley that differ significantly in water chemistry and anthropogenic influence: Lake Turkana is believed to be rather pristine and unpolluted, but a previous study has shown rather high levels of Li, Zn, and Cd in the migratory fish species Hydrocynus forskahlii, questioning this pristine status. Lake Naivasha is heavily influenced by agricultural activity in its catchment area and by direct water use, and high levels of metal pollutants have been reported in fish. This study presents the distribution of nine important trace elements in liver and muscle of the nonmigratory red belly tilapia Tilapia zillii from Lake Turkana and from Lake Naivasha (before and after a significant rise in water level due to as yet not fully understood reasons). In addition, trace element levels in the common carp Cyprinus carpio from Lake Naivasha are presented. Metal concentrations measured in the liver and muscle of T. zillii collected in Lake Turkana confirm the pristine status of the study site, but contrast with the results obtained for the migratory H. forskahlii. Comparing T. zillii from the two lakes reveals a clear difference in accumulation patterns between essential and nonessential trace elements: physiologically regulated essential elements are present in a very similar range in fish from both lakes, while levels of nonessential metals reflect short- or long-term exposure to those elements. The comparison of trace element concentrations in the fish samples from Lake Naivasha showed lower levels of most trace elements after the significant increase of the water level. This study demonstrates that fish are valuable bioindicators for evaluating trace element pollution even in contrasting lakes as long as the way-of-life habits of the species are taken into account.

http://ift.tt/2tmIcoJ

Assessment of the potential health risks of heavy metals in soils in a coastal industrial region of the Yangtze River Delta

Abstract

Soil heavy metal contamination is a serious environmental problem. Human beings may be directly exposed to heavy metals in soils through the inhalation of soil particles, dermal contact, and oral ingestion, which can seriously threaten health. This study assesses the health risks associated with heavy metals in soils by determining the concentrations of eight heavy metals (Cr, Pb, Cd, Hg, As, Cu, Zn, and Ni) based on 2051 surface-soil samples collected from the southern Yangtze River Delta of China. The mean concentrations were higher than the corresponding background values in Zhejiang Province and China as a whole, indicating an accumulation of heavy metals. The health risk assessment suggests that the non-carcinogenic and carcinogenic risks in the study area were not significant. The non-carcinogenic risk for children was the highest, followed by those for adults and seniors; the non-carcinogenic risk for the entire population was less than 1.0, the predetermined threshold. Carcinogenic risk for adults was the highest, followed by those for seniors and children; a few sample points had a value larger than the threshold of 1.0E−04. Arsenic represented the greatest contribution to non-carcinogenic and carcinogenic risk. Meanwhile, ingestion of heavy metals in soil was the main exposure pathway for carcinogenic risk, followed by inhalation and dermal exposure. The spatial method of Getis-Ord was used to identify hot spots of health risk. Hot spots with high hazard index (HI) and total carcinogenic risk (TCR) for children, adults, and seniors were mainly distributed in core urban areas, such as Jiangbei, Haishu, Yinzhou, Jiangdong, and the urban areas of some other counties, which coincided with industrial, mining, and urban areas of the study area and were strongly influenced by anthropogenic activities. These results provide a basis for heavy metal control in soil, source identification, and environment management in the Yangtze River Delta and other rapidly developing industrial regions in China.

http://ift.tt/2sRZff0

Targeting FGFR in Squamous Cell Carcinoma of the Lung

Abstract

Unlike for adenocarcinomas of the lung, no molecular targeted therapies have yet been developed for squamous cell lung cancers, because targetable oncogenic aberrations are scarce in this tumor type. Recent discoveries have established that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in cancer development by supporting tumor angiogenesis and cancer cell proliferation via different mechanisms. Through comprehensive genomic studies, aberrations in the FGF pathway have been identified in various tumor types, including squamous cell lung cancer, making FGF receptor (FGFR) a potentially druggable target in this malignancy. Several multi-targeted tyrosine kinase inhibitors include FGFR in their target spectrum and a number of these compounds have been approved for clinical use in different cancers. Novel agents selectively targeting FGFRs have been developed and are currently under investigation in clinical trials, showing promising results. This article reviews FGFR aberrations and the clinical data involving selective and multikinase FGFR inhibitors in squamous cell lung cancer.

http://ift.tt/2tX5hjh

Potential toxic trace element (PTE) contamination in Baoji urban soil (NW China): spatial distribution, mobility behavior, and health risk

Abstract

Rapid urbanization and industrialization may cause increased exposure levels to potential toxic trace elements (PTEs) and associated health risks for population living in cities. The main objectives of this study are to investigate systematically the occurrence, source, fate, and risk of PTE contamination from industrial influence in Baoji urban soil. Seven PTE levels (Pb, Zn, Cu, Cr, V, Sb, and As) were surveyed in 50 composite samples from Baoji urban soil by wavelength dispersive X-ray fluorescence spectrometry. Results reveal that the long-term industrial activities have increased PTEs Pb (409.20 mg/kg mean value), Cu (107.19 mg/kg mean value), Zn (374.47 mg/kg mean value), and Sb (26.00 mg/kg mean value) to enrich in urban soil at the different extents. The same results concur with the significant similarity of spatial distribution patterns of Pb, Zn, Cu, and Sb (slightly similar distribution) interpolated by GIS, implying a considerable Pb, Zn, Cu, and Sb contamination pool in urban soil disturbance from local metallic industrial activities. Whereas As in study area mainly controls parent material leaching and therefore has natural sources. Cr and V with the heterogeneous spatial distributions are possibly inclined to coal combustion sources. Those conclusions are also confirmed by the results of multivariate analysis. The chemical forms of PTEs fractionated by BCR three-stage sequential extraction procedure show that Pb and Cu are highly associated to the reducible phase (62.55 and 36.41%, respectively). However, Zn is highly associated to the oxidizable phase (33.68%), and a significant concentration is associated to acid and water extractable fractionation of 15.93% for Zn and 34.40% for Pb. In contrast, As, Cr, V, and Sb are mainly bound to the residual phase (>65% for all elements) with low concentrations retained to water extractable fractionation. The health risk assessed by a new classification Modified Integrate Risk Assessment Code (MI-RAC) reveals that the Pb poses the extremely high risk for human health than others. The results of PTE leaching in organic acids (artificial chelating agent and LMMOAs) indicate that low pH and more carboxyl groups of organic acid can quickly increase the PTEs release from soil and induce more mobility. By comparison, DTPA and EDTA are the effective extractant for Pb and Sb. The leaching kinetics of most PTEs are best described with the Elovich equation model and which involve the ligand exchange (LE) and ligand-enhanced dissolution (LED) two major process. It is a conclusion that long-term metallic industrial activities would accelerate the PTE accumulations in Baoji urban soil and enhance their mobility in a local scale. The considerable mobility and extremely high risk of Pb in Baoji ecoenvironment should be paid more attentions, and the phytoremediation with organic acid leaching assistant could be used to reduce total metal content of multiPTE contaminants in Baoji soils. The research will give the scientific knowledge for controlling the pollution of PTEs in urban soil and can be used as guidance to control the soil pollution in similar cities worldwide.

http://ift.tt/2tvmltS

Heavy metals in sands of sandboxes: health risk associated with their quantities and form of occurrence in some spas of Poland

Abstract

The authors dealt with some hazardous elements, i.e. As, Cd, Co, Cr, Cu, Ni, Pb and Zn, contained in sands of the sandboxes localized in playgrounds of seven spas in southern Poland (CEE). The following determinations were made: the total contents of metals, the most mobile metals (water-leachable fraction) and the metals available to plants and organisms (CaCl₂- and EDTA-extractable fractions). The totals of the metals are below the upper limits of the values recommended for soils of the protected areas (type A). The mobility of the metals is low: the forms leachable with water range from 0.7% of the total content (TC) of Pb to 13.4% TC of Cd. The forms available to living organisms contain considerably higher quantities of the metals: from 2.3% TC of Ni to 22.6% TC of As in CaCl₂-extractable fractions and from 0.7% TC of Cr to 82% TC of As in EDTA-extractable fractions. An assessment of the health risk indicates that children are exposed to the metals present in the sandboxes mostly due to inadvertent swallowing of "dirt" from their hands. The highest are the HQ_ingestion indexes of As and Cr, both for the 3-year-old permanent spa residents (5.74E−02 and 1.71E−02, respectively) and the spa visitors of the same age (7.47E−03 and 2.22E−03, respectively) and the 6-year-old residents (4.31E−02 and 1.28E−02, respectively) and visitors (5.60E−03 and 1.66E−03, respectively). The health risk indexes HI in the case of non-cancerogenic substances for children 3 and 6 years old are for spa residents, 9.59E−02 and 7.19E−02, respectively, and for children visitors, who are exposed to environmental factors for a much shorter time than the residents, 1.25E−02 and 9.35E−03, respectively. All the risk indexes have their values significantly below 1, which proves the lack of deleterious effects resulting from the exposition of children to the elements considered. The children of both age groups, exposed to the cancerogenic substances, are endangered mainly by As. The risk values of the cancerogenic As for 3- and 6-year-old children residents are 1.27E−06 and 1.90E−06, respectively, and for children visitors of the same ages 1.65E−07 and 2.47E−07, respectively. These values are significantly lower than a permissible level of "1∙10E-05" and means that also in this case, the health risk is minimal. The risk values calculated for the remaining metals are much lower and follow the sequence Cr > Co > Cd. However, an adverse impact of some sand-contained pollutants that are attributed to the motor traffic (Cu, Zn, Ni, Cr, Co and Pb) and low emissions (mainly As and Cd) has been established in the spa resorts in question.

http://ift.tt/2tvFSKk

Occurrence and risk assessment of phthalate esters (PAEs) in agricultural soils of the Sanjiang Plain, northeast China

Abstract

This study looks at the pollution status of six priority control phthalate esters (PAEs) under different cultivation of agricultural soils in the Sanjiang Plain, northeast China. Results show the total concentration of PAEs ranged from 162.9 to 946.9 μg kg⁻¹ with an average value of 369.5 μg kg⁻¹. PAE concentrations in three types of cultivated soils exhibited decreasing order paddy field (532.1 ± 198.1 μg kg⁻¹) > vegetable field (308.2 ± 87.5 μg kg⁻¹) > bean field (268.2 ± 48.3 μg kg⁻¹). Di-(2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) were the most abundant PAEs congeners. Compared with previous studies, agricultural soils in the Sanjiang Plain showed relatively low contamination levels. Anthropogenic activities such as cultivation practices and industrial emissions were associated with the distribution pattern of PAEs. Furthermore, human health risks of PAEs were estimated and the non-cancer risk shown negligible but carcinogenic risk of DEHP exceeded the threshold limits value. PAE contaminants originated from cultivation practices and intense anthropogenic activities result in placing the agricultural soils under a potential risk to human health and also to ecosystems in the Sanjiang Plain. Therefore, the contamination status of PAEs in agricultural soil and potential impacts on human health should attract considerable attention.

http://ift.tt/2sLGbDR

Missed Case Feedback and Quality Assurance Conferences in Radiology Resident Education: A Survey of United States Radiology Program Directors

Publication date: Available online 6 June 2017
Source:Current Problems in Diagnostic Radiology
Author(s): Anne E. Gill, Philip K. Wong, Mark E. Mullins, Amanda S. Corey, Brent P. Little
Rationale and ObjectivesDiagnostic Radiology (DR) residents typically generate preliminary reports for imaging examinations, but few publications discuss feedback regarding missed or misinterpreted findings. Our goal was to determine the practices of United States DR residencies with respect to missed case feedback, including the role of Quality Assurance (QA) conferences.Materials and MethodsA 23-item survey containing multiple-choice questions and several free text fields was created and hosted on SurveyMonkey^R. An invitation to complete the survey was sent via email to all DR Program Directors (PDs) or representatives. Responses were tabulated and analyzed using SurveyMonkey^R analytic tools and Microsoft Excel.Results188 PDs or representatives were emailed, resulting in 45 survey responses. Common types of missed case feedback included resident QA case conferences (81%), resident self review of cases (72%), discussion during readout at the end of shift (70%), and faculty-resident meetings (67%). A minority of programs reported using automated methods of resident feedback, such as PACS integration or automated emails. Most resident QA conferences were held monthly (64%). Typical formats of conferences included informal discussion (43%), formal presentation (30%), or case conferences (30%). The majority (78%) of respondents rated resident missed case feedback mechanisms at their institution as at least "good".ConclusionDR residencies use a variety of mechanisms to provide feedback to residents regarding missed or misinterpreted cases, including QA conferences. Although several possibilities for improvement in feedback mechanisms were highlighted by survey responses, most respondents had a favorable view of their program's feedback processes.



http://ift.tt/2tRLnFN

A meta-analysis of the relationship between ataxia-telangiectasia mutated gene polymorphisms and lung cancer susceptibility

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Yanling Xu, Peng Gao, Xuejiao Lv, Lin Zhang, Wei Li, Jie Zhang
PurposeThis study aimed to analyze the relationship between ataxia-telangiectasia mutated (ATM) gene polymorphisms and lung cancer susceptibility using a meta-analysis.MethodsA literature search of the PubMed and EMBASE databases was performed using keywords such as "ATM gene" and "lung cancer," and the deadline "October 15 (th), 2016." After extracting relevant details, each selected literature was evaluated for quality according to the Newcastle–Ottawa Scale (NOS) scores, and Hardy–Weinberg equilibrium and heterogeneity tests were performed. Odds ratios (ORs) and 95% confidence interval (CI) were evaluated using R 3.12 software.ResultsEight eligible studies, published from 2004 to 2013, were identified. The NOS scores of these ranged from 5 to 7. The allele genetic model (OR=1.15; 95% CI, 1.01–1.31); additive genetic model (OR=1.44; 95% CI, 1.09–1.90); recessive genetic model (OR=1.48; 95% CI, 1.16–1.88); and dominant genetic model (OR=1.50; 95% CI, 1.16–1.93) of rs664143 (A>G) were found to be significantly different. For rs664677 (C>T), significant differences were found in the additive genetic model (OR=1.26, 95% CI, 1.01–1.55) and recessive genetic model (OR=1.31; 95% CI, 1.09–1.57). However, the other 2 genetic models (rs609429, rs664982) did not show significant differences.ConclusionThe polymorphisms rs664143 and rs664677 of ATM are associated with lung cancer occurrence.



http://ift.tt/2tvi3m1

A 55-year-old Female with Leukoencephalopathy with Cerebral Calcifications and Cysts: Case Report and Radiopathologic Description

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Jorge Novo, Diana Lin, Megan Shanks, Mehmet Kocak, Leonidas Arvanitis
Adult-onset leukoencephalopathies with increased cerebral volume can present a potentially challenging diagnosis for the pathologist. We present the case of a patient with a rare adult-onset disease called Leukoencephalopathy with cerebral Calcifications and Cysts (LCC). A 55-year-old woman with a history of morning headaches, mild memory loss, diabetes, and hypertension presented to the emergency department with acute onset altered mental status. CT scan revealed multiple small hypodense lesions in the white matter with calcifications in the bilateral cerebral hemispheres, basal ganglia, pons, and cerebellar hemispheres. MRI showed multiple complex/hemorrhagic cystic lesions with partial enhancement in addition to calcifications bilaterally in the frontotemporal white matter, pons, and cerebellar hemispheres, and diffuse white matter signal abnormality. The differential diagnosis included chronic infection, chronic thromboembolic disease, and neoplasm. The biopsy revealed extensive geode-like mineralization as well as smaller calcifications (calcospherites) with associated sclerosis, Rosenthal fibers, angiomatous proliferation of blood vessels with thrombosis and microbleeds. We discuss the differential diagnosis, radiologic and detailed histologic features of LCC.



http://ift.tt/2tv8m7l

Prognostic value of IMP3 expression as a determinant of chemosensitivity in triple-negative breast cancer

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Ryuji Ohashi, Maoka Sangen, Shigeki Namimatsu, Keiko Yanagihara, Koji Yamashita, Takashi Sakatani, Hiroyuki Takei, Zenya Naito
Triple negative breast cancer (TNBC) has an aggressive phenotype and poor prognosis. Neoadjuvant chemotherapy (NAC) is often used to treat TNBC, but some patients are resistant to NAC. We postulated that a subpopulation of TNBC cells expressing IMP3, an oncofetal protein, could be resistant to NAC, contributing to the poor prognosis. We investigated immunohistochemical expression of IMP3 in 42 TNBC patients who underwent NAC in association with clinical outcomes. The patients were divided into IMP3 positive (+) (n=19) and negative (−) (n=23) groups. High Ki67 positivity was detected in 13 patients of the IMP3+group and 8 cases in the IMP3 − group (p=0.03). While 9 patients in the IMP3 − group (39%) were responders, the majority of the IMP3+patients (84.2%) were non-responders (p=0.01). In a Cox proportional hazard model, IMP3 expression was independently associated with poor NAC response and clinical outcomes (p=0.03 and 0.046, respectively). The IMP3+group showed a tendency toward shorter overall survival compared to the IMP3 − group with marginal significance (p=0.07). These findings suggest that IMP3+tumor cells contributed to the poor clinical outcomes by exerting a chemoresistance to NAC, and that IMP3 expression has prognostic value as a biomarker for chemosensitivity and overall survival in TNBC.



http://ift.tt/2sLh1Fm

Thymosin beta-4 overexpression correlates with high-risk groups in gastric gastrointestinal stromal tumors: a retrospective analysis by immunohistochemistry

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Sevinç Şahin, Ozgur Ekinci, Selda Seçkin, Ayse Dursun
BackgroundThymosin beta-4 (Tβ4) is a protein that is linked to a number of important biological actions and recently tumor progression and poor prognosis of some tumors. The aim of this study was to evaluate Tβ4 expression in gastric GISTs and correlate with some clinicopathological characteristics related with prognosis and clinical outcome in order to add further data to the current literature.MethodsTβ4 antibody was applied to the 4μm-thick paraffin sections of 57 gastric GISTs by immunohistochemistry.ResultsTβ4 expression was found to be directly corrrelated with higher risk groups, tumor size, mitotic count, cellularity, and necrosis while it was inversely correlated with overall survival (OS) by univariate analysis (p=0.000, p=0.001, p=0.000, p=0.025, p=0.023, and p=0.042, respectively). The direct association between Tβ4 expression and risk groups were also supported by multivariate analysis (p=0.000, β=0.497, t=4.374).ConclusionOverexpression of Tβ4 was found to be related with predictive characteristics for tumor progression and adverse prognosis. Thus, we suggest that overexpression of Tβ4 might play a role in the progression of gastric GISTs and might be used as a potential prognostic tool as well as a target for novel therapies.



http://ift.tt/2tvbzn4

Extraskeletal Aneurysmal Bone Cyst: Report of a Case and Review of the Literature

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Liurka V. Lopez, Michael G. Rodriguez, Gene P. Siegal, Shi Wei
Aneurysmal bone cyst (ABC) is an expansile cystic lesion that may affect any bone of the skeleton. Although exceedingly rare, lesions with histomorphologic characteristics of an ABC have reportedly originated within soft tissue. Extraskeletal ABC may mimic a variety of benign and malignant lesions and can be confused with other more common or rare giant cell-rich tumors of soft tissue, especially myositis ossificans. Clinical, radiological and histologic correlation is crucial in reaching the correct diagnosis. Cytogenetic and/or molecular genetic analysis is a useful adjunct in diagnosing these exquisitely rare lesions. Here we report a case of an ABC arising in an extraskeletal site and provide a comprehensive review of literature on this rare entity.



http://ift.tt/2sLnMY0

Morphological characteristics of fatal pediatric hand, foot and mouth disease: a clinicopathological study with related receptors of EV71

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Yong-yao Gu, Ke Shi, Sha Yao, Xia Yang, Yu-hui Liu, Lan Tang, Yi-wu Dang, Gang Chen, Zhen-bo Feng, Hong-bo Pan
ObjectiveTo investigate the pathological features of fatal pediatric hand foot and mouth disease (HFMD).MethodsThe histopathological features of HFMD were first summarized from literatures, and then confirmed by in-house autopsies. Furthermore, immunohistochemistry was conducted to detect the distribution and expression level of two enterovirus 71 (EV71) receptors scavenger receptor class B, member 2 (SCARB2), and P-selectin glycoprotein ligand-1 (PSGL1) in the samples of autopsies.ResultsThe main symptoms of HFMD included hand and foot rashes, as well as oral herpes. The fatal HFMD patients had typical histopathological change in the central nervous system, such as encephaledema and encephalitis. As for respiratory system, the fatal HFMD patients suffered acute pulmonary edema and congestion. SCARB2 positive signaling was distributed equally in bronchial and bronchiolar epithelial cells, alveolar epithelial cells and inflammatory cells of all HFMD patients, healthy children and adults without significant difference. PSGL-1 dispersed in bronchial and bronchiolar epithelial cells of healthy adults, but no PSGL-1 expression was detected in HFMD patients and healthy children.ConclusionsBoth of the central nervous and respiratory systems may be involved in the fatal HFMD patients. The EV71 receptor PSGL-1 might play essential parts in the pathogenesis of fatal HFMD, however, the hypothesis needs to be further investigated.



http://ift.tt/2tvtFWb

Prognostic significance of lactate dehydrogenase B according to histologic type of non-small-cell lung cancer and its association with serum lactate dehydrogenase

Publication date: Available online 6 July 2017
Source:Pathology - Research and Practice
Author(s): Young Wha Koh, Su Jin Lee, Seong Yong Park
Lactate dehydrogenase B (LDHB) expression and the level of serum LDH were involved in tumor progression. Correlations between these parameters and their prognostic significance were not assessed in non-small cell lung cancer (NSCLC). We evaluated LDHB expression by immunohistochemical method and serum LDH in 243 NSCLC patients treated with surgical resection [136 adenocarcinomas (ADCs), 89 squamous cell carcinomas (SqCCs) and 18 other type carcinomas]. Correlation between LDHB expression and serum LDH was assessed, and the prognostic significance was determined. LDHB expression was identified in 52% of SqCC and 55% of ADC tissue samples. LDHB-positive SqCC patients had a higher recurrence-free survival (RFS) rate than LDHB-negative patients (p=0.017). LDHB-positive and LDHB-negative patients showed similar RFS rates in ADCs (p=0.519). Multivariate analysis showed that LDHB expression was an independent risk factor in lung SqCCs (hazard ratio=0.393, p=0.028). A positive correlation was found between LDHB expression and serum LDH level (p=0.02). High LDHB expression is significantly associated with the level of serum LDH and better clinical outcomes in lung SqCC.



http://ift.tt/2sLlV5k

Enhanced anticancer activity of an intracellularly activatable nanomedicine based on GLYlated nanodiamond

Publication date: Available online 6 July 2017
Source:Diamond and Related Materials
Author(s): Wenjing Zhao, Shiguo Wei, Hemiao Zhao, Yingqi Li, Ruifang Wu, Juanjuan Wang
With the purpose of enriched drug-loading and controlled drug release, a lysozyme-actived nanodiamond-methotrexate prodrug (ND-PEG-GLY-MTX, NPGM) was designed based on ester linkage between glycidylated (GLYlated) nanodiamond and methotrexate (MTX). The resulting NPGM nanoparticles exhibited a high drug load capacity and excellent stability in the physiological environment. In vitro drug release profile demonstrated that MTX could be greatly released from NPGM nanoparticles in acidic environment containing lysozyme, implying the ester bond of NPGM was broken. Confocal microscope and flow cytometer showed that NPGM entered the cells via time, temperature-dependent, energy independent and caveolin-mediated endocytosis and laid in the lysosomes of the cell. Interestingly, the cytotoxicity of NPGM nanoparticles (OFF) in the extracellular medium could be acitived (ON) by lysozyme in lysosomes, due to cleavage of ester linkages when NPGM entered tumor cells. Furthermore, MTT assay and apoptosis detection uncovered that NPGM had better therapeutic effect than that of free MTX. The results show that the well-defined NPGM is a controlled release drug nanoplatform for tumor treatment and the NPGM will open the new nanodrugs window for a broad covalent coupling spectrum of anticancer agents.

Graphical abstract

http://ift.tt/2tmaGPn

Frontmatter

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: i-iii

http://ift.tt/2tmut19

High prevalence of organ specific autoantibodies in Indian type 1 diabetic patients

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 707-712

http://ift.tt/2sRWaLT

Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 713-718

http://ift.tt/2tmeDnc

Excessive weight gain in exclusively breast-fed infants

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 719-724

http://ift.tt/2sRVvtD

Comparison of Tanner staging of HIV-infected and uninfected girls at the University of Nigeria Teaching Hospital, Ituku/Ozalla, Enugu, Nigeria

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 725-729

http://ift.tt/2tmcEzb

Joint association of screen time and physical activity with anthropometric measures in Iranian children and adolescents: the weight disorders survey of the CASPIAN-IV study

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 731-738

http://ift.tt/2sRvSt7

Assessment of insulin like growth factor-1 and IGF binding protein-3 in healthy Indian girls from Delhi and their correlation with age, pubertal status, obesity and thyroid hormonal status

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 739-747

http://ift.tt/2tm66AF

Impact of discontinuation of growth hormone treatment on lipids and weight status in adolescents

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 749-757

http://ift.tt/2tmcE29

Clinical, biochemical and genetic features with nonclassical 21-hydroxylase deficiency and final height

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 759-766

http://ift.tt/2sRI5On

A combined approach to generate laboratory reference intervals using unbalanced longitudinal data

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 767-773

http://ift.tt/2tmuH8B

Clinical evaluation and mutational analysis of GALK and GALE genes in patients with galactosemia in Greece: one novel mutation and two rare cases

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 775-779

http://ift.tt/2sRIj8t

Pediatric toxic polycystic thyroid

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 781-784

http://ift.tt/2sRBFit

In utero virilization secondary to a maternal Krukenberg tumor: case report and review of literature

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 785-790

http://ift.tt/2tm1fPP

Postprandial hyperinsulinemic hypoglycemia in a child as a late complication of esophageal reconstruction

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 791-795

http://ift.tt/2sRvOJT

Long-term follow-up of a child with Klinefelter syndrome and achondroplasia from infancy to 16 years

Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 30
Issue: 7
Pages: 797-803

http://ift.tt/2tmaxvo

The Steinberg Centre for Simulation and Interactive Learning at McGill University

Publication date: Available online 5 July 2017
Source:Journal of Surgical Education
Author(s): Carmen L. Mueller, Genevieve Cyr, Ilana Bank, Farhan Bhanji , Laura Birnbaum, Miriam Boillat, Marie-Eve Bolduc, Jeffrey Chankowsky, Evelyn Constantin, Beth-Ann Cummings, Rachel Fisher, Philippe Legault, N Hugo Marchand, Luis Monton, Teresa Rudkin, Bayane Sabsabi, Niki Soilis, Daniel Zigman, Rajesh Aggarwal
Simulation allows for learner-centered health professions training by providing a safe environment to practice and make mistakes without jeopardizing patient care. It was with this goal in mind that the McGill Medical Simulation Center was officially opened on September 14, 2006, as a partnership between McGill University, the Faculty of Medicine and its affiliated hospitals. Its mandate is to provide state-of-the-art facilities to support simulation-based medical and allied health education initiatives.Since its inception, the center, recently renamed the Steinberg Center for Simulation and Interactive Learning (SCSIL), has undergone a major expansion and logged more than 130,000 learner visits. Educational activities are offered at all levels of medical and allied health care training, and include standardized patient encounters, partial task trainers, multidisciplinary courses, and high-fidelity trainers, among many others. In addition to its educational mandate, the center also supports an active research program, programs to enhance collaboration with disciplines outside of health care to spur innovation, and community outreach initiatives.



http://ift.tt/2tvrS3y

Masthead

Publication date: July–August 2017
Source:Journal of Surgical Education, Volume 74, Issue 4





http://ift.tt/2sL9vu8

Personality Factors Associated With Resident Performance: Results From 12 Accreditation Council for Graduate Medical Education Accredited Orthopaedic Surgery Programs

Publication date: Available online 5 July 2017
Source:Journal of Surgical Education
Author(s): Donna Phillips, Kenneth A. Egol, Martine C. Maculatis, Kathryn S. Roloff, Alan M. Friedman, Brett Levine, Steven Garfin, Alexandra Schwartz, Robert Sterling, Thomas Kuivila, Steve J. Paragioudakis, Joseph D. Zuckerman
ObjectivesTo understand the personality factors associated with orthopedic surgery resident performance.DesignA prospective, cross-sectional survey of orthopedic surgery faculty that assessed their perceptions of the personality traits most highly associated with resident performance. Residents also completed a survey to determine their specific personality characteristics. A subset of faculty members rated the performance of those residents within their respective program on 5 dimensions. Multiple regression models tested the relationship between the set of resident personality measures and each aspect of performance; relative weights analyses were then performed to quantify the contribution of the individual personality measures to the total variance explained in each performance domain. Independent samples t-tests were conducted to examine differences between the personality characteristics of residents and those faculty identified as relevant to successful resident performance.SettingData were collected from 12 orthopedic surgery residency programs¹1 The full list of participating programs is available from the corresponding author upon request. throughout the United States. The level of clinical care provided by participating institutions varied.ParticipantsData from 175 faculty members and 266 residents across 12 programs were analyzed.ResultsThe personality features of residents were related to faculty evaluations of resident performance (for all, p < 0.01); the full set of personality measures accounted for 4%-11% of the variance in ratings of resident performance. Particularly, the characteristics of agreeableness, neuroticism, and learning approach were found to be most important for explaining resident performance. Additionally, there were significant differences between the personality features that faculty members identified as important for resident performance and the personality features that residents possessed.ConclusionPersonality assessments can predict orthopedic surgery resident performance. However, results suggest the traits that faculty members value or reward among residents could be different from the traits associated with improved resident performance.



http://ift.tt/2tuY0UQ

Table of Contents & Bacode

Publication date: July–August 2017
Source:Journal of Surgical Education, Volume 74, Issue 4





http://ift.tt/2sKSYXk

VIP induces the decidualization program and conditions the immunoregulation of the implantation process

Publication date: Available online 6 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Esteban Grasso, Soledad Gori, Daniel Paparini, Elizabeth Soczewski, Laura Fernández, Lucila Gallino, Gabriela Salamone, Gustavo Martinez, Marcela Irigoyen, Claudio Ruhlmann, Claudia Pérez Leirós, Rosanna Ramhorst
The decidualization process involves phenotype and functional changes on endometrial cells and the modulation of mediators with immunoregulatory properties as the vasoactive intestinal peptide (VIP). We investigate VIP contribution to the decidualization program and to immunoregulation throughout the human embryo implantation process. The decidualization of Human endometrial stromal cell line (HESC) with Medroxyprogesterone-dibutyryl-cAMP increased VIP/VPAC-receptors system. In fact, VIP could induce decidualization increasing differentiation markers (IGFBP1, PRL, KLF13/KLF9 ratio, CXCL12, CXCL8 and CCL2) and allowing Blastocyst-like spheroids (BLS) invasion in an in vitro model of embryo implantation. Focus on the tolerogenic effects, decidualized cells induced a semi-mature profile on maternal dendritic cells; restrained CD4⁺ cells recruitment while increased regulatory T-cells recruitment. Interestingly, the human blastocyst conditioned media from developmentally impaired embryos diminished the invasion and T-regulatory cells recruitment in these settings.These evidences suggest that VIP contributes to the implantation process inducing decidualization, allowing BLS invasion and favoring a tolerogenic micro-environment.



http://ift.tt/2suDm62

From gene to therapy in spinal and bulbar muscular atrophy: Are we there yet?

Publication date: Available online 5 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Maria Pennuto, Carlo Rinaldi
Abnormal polyglutamine expansions in the androgen receptor (AR) cause a muscular condition, known as Kennedy's disease or spinal and bulbar muscular atrophy (SBMA). The disease is transmitted in an X-linked fashion and is clinically characterized by weakness, atrophy and fasciculations of the limb and bulbar muscles as a result of a toxic gain-of-function of the mutant protein. Notably, affected males also show signs of androgen insensitivity, such as gynaecomastia and reduced fertility. The characterization of the natural history of the disease, the increasing understanding of the mechanism of pathogenesis and the elucidation of the functions of normal and mutant AR have offered a momentum for developing a rational therapeutic strategy for this disease. In this special issue on androgens and AR functions, we will review the molecular, biochemical, and cellular mechanisms underlying the pathogenesis of SBMA. We will discuss recent advances on therapeutic approaches and opportunities for this yet incurable disease, ranging from androgen deprivation, to gene silencing, to an expanding repertoire of peripheral targets, including muscle. With the advancement of these strategies into the clinic, it can be reasonably anticipated that the landscape of treatment options for SBMA and other neuromuscular conditions will change rapidly in the near future.



http://ift.tt/2tNA1CL

How MR1 Presents a Pathogen Metabolic Signature to Mucosal-Associated Invariant T (MAIT) Cells

Publication date: Available online 5 July 2017
Source:Trends in Immunology
Author(s): Hamish E.G. McWilliam, Jose A. Villadangos
Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes restricted by the antigen (Ag)-presenting molecule MHC class I (MHC I)-related protein 1 (MR1). The Ags presented by MR1 are vitamin B-related Ags (VitBAgs), 'building-block' metabolites of riboflavin that are synthesized by a range of microbes. MR1 presentation is thus a unique mechanism for the immune detection of a pathogen metabolic signature. While the full picture of how MR1 accomplishes this remains incomplete, recent data show that, unlike other MHC molecules, MR1 operates by a presentation-on-demand mechanism. In the absence of metabolite ligands MR1 is mostly stored in the endoplasmic reticulum (ER). Ligand binding leads to the formation of a Schiff-base bond between MR1 and its ligand, triggering a 'molecular switch' in MR1 that allows trafficking of the complexes to the cell surface. The complexes are subsequently internalized and mostly degraded irrespective of the affinity of the interaction between MR1 and its ligands. Here we review past and recent studies that have contributed to defining this pathway and propose new directions for a full understanding of the role and mechanisms of MR1 Ag presentation.



http://ift.tt/2sL8S3C

Mice under Caloric Restriction Self-Impose a Temporal Restriction of Food Intake as Revealed by an Automated Feeder System

Publication date: 5 July 2017
Source:Cell Metabolism, Volume 26, Issue 1
Author(s): Victoria A. Acosta-Rodríguez, Marleen H.M. de Groot, Filipa Rijo-Ferreira, Carla B. Green, Joseph S. Takahashi
Caloric restriction (CR) extends lifespan in mammals, yet the mechanisms underlying its beneficial effects remain unknown. The manner in which CR has been implemented in longevity experiments is variable, with both timing and frequency of meals constrained by work schedules. It is commonplace to find that nocturnal rodents are fed during the daytime and meals are spaced out, introducing prolonged fasting intervals. Since implementation of feeding paradigms over the lifetime is logistically difficult, automation is critical, but existing systems are expensive and not amenable to scale. We have developed a system that controls duration, amount, and timing of food availability and records feeding and voluntary wheel-running activity in mice. Using this system, mice were exposed to temporal or caloric restriction protocols. Mice under CR self-imposed a temporal component by consolidating food intake and unexpectedly increasing wheel-running activity during the rest phase, revealing previously unrecognized relationships among feeding, metabolism, and behavior.

Graphical abstract

Teaser

Acosta-Rodríguez et al. developed an automated feeding system that controls amount, duration, and timing of food availability and also records feeding and voluntary wheel-running activity in mice. They discover that calorie-restricted mice self-imposed a temporal component by consolidating food intake and unexpectedly increasing wheel-running activity during the rest phase.


http://ift.tt/2tm7Z04

Will Gut Microbiota Help Design the Next Generation of GLP-1-Based Therapies for Type 2 Diabetes?

Publication date: 5 July 2017
Source:Cell Metabolism, Volume 26, Issue 1
Author(s): Sandrine Paule Claus
Glucagon-like peptide one (GLP-1)-based therapies for reducing hyperglycemia in type 2 diabetic patients are efficient, though some individuals develop GLP-1 resistance. In a recent issue of Cell Metabolism, Grasset et al. (2017) demonstrated that GLP-1 sensitivity is modulated by gut bacteria through NO signaling in the enteric nervous system.

Teaser

Glucagon-like peptide one (GLP-1)-based therapies for reducing hyperglycemia in type 2 diabetic patients are efficient, though some individuals develop GLP-1 resistance. In a recent issue of Cell Metabolism, Grasset et al. demonstrated that GLP-1 sensitivity is modulated by gut bacteria through NO signaling in the enteric nervous system.


http://ift.tt/2tlN6m0

Fighting Fire with Fiber: Preventing T Cell Infiltration in Diabetes

Publication date: 5 July 2017
Source:Cell Metabolism, Volume 26, Issue 1
Author(s): Sydney Lavoie, Wendy S. Garrett
Diet can alter the gut microbiota and shift its production of metabolites, which affect systemic immune function. In Nature Immunology, Mariño et al. (2017) explore diet-gut microbiome interactions in type 1 diabetes and identify mechanisms by which short-chain fatty acids prevent T cell destruction of pancreatic β-cells.

Teaser

Diet can alter the gut microbiota and shift its production of metabolites, which affect systemic immune function. In Nature Immunology, Mariño et al. (2017) explore diet-gut microbiome interactions in type 1 diabetes and identify mechanisms by which short-chain fatty acids prevent T cell destruction of pancreatic β-cells.


http://ift.tt/2sRc4pQ