Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,
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Σάββατο 2 Ιουνίου 2018
Siderophore-based biosensors and nanosensors; new approach on the development of diagnostic systems
Source:Biosensors and Bioelectronics, Volume 117
Author(s): Rahim Nosrati, Sadegh Dehghani, Bahareh Karimi, Meysam Yousefi, Seyed Mohammad Taghdisi, Khalil Abnous, Mona Alibolandi, Mohammad Ramezani
Siderophores are small organic compounds secreted by microorganisms under iron-depleted conditions which enhance the uptake of iron. Siderophores can play vital roles in ecology, agriculture, bioremediation, biosensor, and medicine. In recent years, the concept of siderophore-based biosensing devices has opened new horizons in high precision detection of various metal ions especially the iron, microorganisms, phosphopeptides, antibiotics as well pesticides. Once combined with nanomaterials, nano-scale siderophore systems provide powerful analytical platforms for detection of low concentration of metal ions and numerous pathogens. In this article, a brief overview of general aspects of siderophore is firstly discussed. In addition, a clear and concise review of recent advances of siderophore-based biosensors (siderosensor) and nanosensors are mainly discussed herein. Subsequently, future perspectives and challenges of siderophore-based sensors are discussed briefly.
https://ift.tt/2J7ReQ3
Correlation of IDH1 and B7H3 expression with prognosis of CRC patients
Source:European Journal of Surgical Oncology
Author(s): Jingyi Wu, Fang Wang, Xingxiang Liu, Ting Zhang, Fen Liu, Xiaosong Ge, Yong Mao, Dong Hua
BackgroundB7H3 is an immuno-stimulatory glycoprotein that is overexpressed in cancer. However, its functional contributions to cancer development and progression are not well understood. In several reports, it was demonstrated that B7H3 reprograms lipid metabolism and regulates glucose metabolism. Isocitrate dehydrogenase 1 (IDH1), a metabolic enzyme in the TCA cycle, its reaction product is involved in lipid synthesis. Thus, we aimed to identify a novel marker to predict the prognosis of CRC patients and to investigate the relationship between IDH1 and B7H3.MethodsWe analyzed IDH1 and B7H3 expression levels in 225 CRC specimens by immunochemistry. Moreover, in vitro studies were performed to demonstrate the correlation between IDH1 and B7H3.ResultsAmong 225 tissues, the positive rates of IDH1 and B7H3 were 37.8% (85/225) and 87.6% (197/225), respectively. In CRC samples, IDH1 significantly correlated with B7H3 expression (P = 0.044). Moreover, multivariate analyses revealed that high expression of both B7H3 and IDH1 and a high tumor grade were related to the prognosis of CRC patients. Kaplan-Meier survival analysis revealed that patients with co-expression of IDH1 and B7H3 had a poor overall survival. In SW480B7H3-EGFP cells, which highly express B7H3, IDH1 was up-regulated. Similarly, knockdown of B7H3 expression in Caco-2-shB7-H3 contributed to reduced IDH1 levels.ConclusionsAlthough IDH1 and B7H3 cannot be used as independent prognostic factors, co-expression of IDH1 and B7H3 significantly correlated with the prognosis of CRC patients and may serve as a combined predictive marker. Thus, the correlation between IDH1 and B7H3 has been proven in vivo and in vitro.
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Herbicides in vineyards reduce grapevine root mycorrhization and alter soil microorganisms and the nutrient composition in grapevine roots, leaves, xylem sap and grape juice
Abstract
Herbicides are increasingly applied in vineyards worldwide. However, not much is known on potential side effects on soil organisms or on the nutrition of grapevines (Vitis vinifera). In an experimental vineyard in Austria, we examined the impacts of three within-row herbicide treatments (active ingredients: flazasulfuron, glufosinate, glyphosate) and mechanical weeding on grapevine root mycorrhization; soil microorganisms; earthworms; and nutrient concentration in grapevine roots, leaves, xylem sap and grape juice. The three herbicides reduced grapevine root mycorrhization on average by 53% compared to mechanical weeding. Soil microorganisms (total colony-forming units, CFU) were significantly affected by herbicides with highest CFUs under glufosinate and lowest under glyphosate. Earthworms (surface casting activity, density, biomass, reproduction) or litter decomposition in soil were unaffected by herbicides. Herbicides altered nutrient composition in grapevine roots, leaves, grape juice and xylem sap that was collected 11 months after herbicide application. Xylem sap under herbicide treatments also contained on average 70% more bacteria than under mechanical weeding; however, due to high variability, this was not statistically significant. We conclude that interdisciplinary approaches should receive more attention when assessing ecological effects of herbicides in vineyard ecosystems.
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Scholar : Journal of Oral Science Research, Year 2018, Issue 05 -New Issue Alert.
Scholar : Journal of Clinical Otorhinolaryngology Head and Neck Surgery, Year 2018, Issue 10 -New Issue Alert.
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Scholar : chinese Journal of Practical Stomatology, Year 2018, Issue 03 -New Issue Alert.
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The effect of anthropogenic activities on the phosphorus-buffering intensity of the two contrasting rivers in northern China
Abstract
The phosphorus (P)-buffering ability of suspended particulate matter (SPM) from the Ziya River Mainstream (ZRM) and the Luanhe River (LR) of northern China was investigated in this study. Forty samples of SPM from the ZRM and LR were collected in October and November of 2016. The ZRM has slow flow and poor water quality, while the LR has fast flow and reasonably good water quality. Under a scanning electron microscope, the SPM from the ZRM had a more complex microstructure than that from the LR, perhaps because of the slower flow and heavier pollution in the ZRM. P fractions in both SPM and water samples were determined using standard measurement and testing program methods. The equilibrium P concentration was used to determine the influence of SPM on soluble reactive P (SRP) concentrations. These SRP fractions were used to evaluate the P-buffering intensity of the two rivers. Differences in SPM microstructure resulted in the SPM from ZRM having a stronger P-buffering ability than the LR, making SPM an effective vector for SRP. Anthropogenic activities likely contributed to the differences in both microstructures of the SPM and P-buffering intensity of the rivers. A conceptual model was developed to show how anthropogenic activities influence the P-buffering intensity of the two rivers. As far as we know, this is the first time that the P-buffering intensity has been compared between two rivers that have been severely impacted by anthropogenic activities. Our findings provide an important reference for similar rivers worldwide.
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Is skewed income distribution good for environmental quality? A comparative analysis among selected BRICS countries
Abstract
A large number of studies have examined the linkage between income inequality and environmental quality at the individual country levels. This study attempts to examine the linkage between the two factors for the individual BRICS economies from a comparative perspective, which is scarce in the literature. It examines the selected countries (Brazil, India, China and South Africa) by endogenising the patterns of primary energy consumption (coal use and petroleum use), total primary energy consumption, economic growth, and urbanisation as key determining factors in CO2 emission function. The long-run results based on ARDL bounds testing revealed that income inequality leads to increase in CO2 emissions for Brazil, India and China, while the same factor leads to reduction in CO2 emissions for South Africa. However, it observes that while coal use increases CO2 emissions for India, China and South Africa, it has no effect for Brazil. In contrast, the use of petroleum products contributes to CO2 emissions in Brazil, while the use of the same surprisingly results in reduction of carbon emissions in South Africa, India and China. The findings suggest that given the significance of income inequality in environmental pollution, the policy makers in these emerging economies have to take into consideration the role of income inequality, while designing the energy policy to achieve environmental sustainability.
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Phthalate exposure as a risk factor for hypertension
Abstract
Phthalates are ubiquitous in environment. Hypertension is a major risk factor for cardiovascular diseases. Phthalate exposure is associated with hypertension in multiple studies. This review aims to summarize the scientific literature on associations between phthalate exposure and hypertension and discuss the mechanisms in the relationship. We identified and reviewed original articles published to March 2018, using PubMed and Web of Science to search the terms "phthalate(s)," "phthalic acid," "blood pressure," "high blood pressure," "hypertension," "prehypertension," and "cardiovascular disease." Findings were summarized based on the relevance to the themes, including presentation of main phthalates and their major metabolites as well as associations of phthalate exposure with blood pressure in epidemiological and experimental studies. We identified ten population-based investigations and five toxicological experiments. Epidemiological data underscored a possible correlation between phthalate exposure and hypertension in adults, whereas individual study in children stands on the opposite. Experimental studies mainly targeted the increasing effect of phthalates on blood pressure. This review suggested some underlying mechanisms of phthalate-associated hypertension. Considering the current evidence, phthalate might be risk factors of hypertension. However, the effect of phthalate exposure in early life on blood pressure in later life or adulthood is still unclear. Well-designed longitudinal and molecular mechanism studies are indispensable.
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Spent MgO-carbon refractory bricks as a material for permeable reactive barriers to treat a nickel- and cobalt-contaminated groundwater
Abstract
Spent magnesia (MgO)-carbon refractory bricks were repurposed as a permeable reactive barrier reactive media to treat a nickel (5 mg l−1)- and cobalt (0.3 mg l−1)-contaminated groundwater. MgO has been used for decades as a heavy metal precipitating agent as it hydrates and buffers the pH in a range of 8.5–10 associated with the minimum solubility of various divalent metals. The contaminated groundwater site's conditions are typical of contaminated neutral drainage with a pH of 6 as well as high concentrations of iron (220 mg l−1) and sulphates (2500 mg l−1). Using synthetic contaminated water, batch and small-scale column tests were performed to determine the treatment efficiency and longevity. The increase and stabilization of the pH at 10 observed during the tests are associated with the hydration and dissolution of the MgO and promoted the removal not only of a significant proportion of the contaminants but also of iron. During the column test, this accumulation of precipitates over time clogged and passivated the MgO resulting in a loss of chemical performance (pH lowering, metal breakthrough) after 210 pore volumes of filtration. Precipitation also affected the hydraulic conductivity values which dropped from 2.3·10−3 to 4.2·10−4 m s−1 at the end of test. Saturation indices and XRD analyses suggest the precipitates formed are likely composed of goethite as well as iron, cobalt and nickel hydroxides. Recycled MgO-C refractory bricks were demonstrated to be an efficient reactive material for the removal of Co and Ni, but careful considerations should be taken of the potential clogging and passivation phenomena given particular physicochemical conditions.
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Targeted reversal and phosphorescence lifetime imaging of cancer cell metabolism via a theranostic rhenium(I)-DCA conjugate
Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Jing Yang, Qian Cao, Hang Zhang, Liang Hao, Danxia Zhou, Zhenji Gan, Zhiwei Li, Ye-Xiang Tong, Liang-Nian Ji, Zong-Wan Mao
Cancer cell metabolism is quite different from normal cells. Targeting cancer metabolism and untuning the tumor metabolic machine has emerged as a promising strategy for cancer therapy. We have developed a multi-functional Re-dca conjugate (Re-dca 2) by conjugating the metabolic modulator dichloroacetate (DCA) to mitochondria-targeted rhenium(I) complex, allowing its efficient penetration into cancer cells and selective accumulation in mitochondria, thus achieving the cancer cell metabolism reversal from glycolysis to glucose oxidation at pharmacologically relevant DCA doses. Mechanism studies confirm the inhibition effect of Re-dca 2 on the activity of pyruvate dehydrogenase kinase (PDK) and capture the metabolic reversal window in Re-dca 2 treated NCI-1229 cells at the early stage of drug treatment, resulting in selective killing of malignant cells cocultured with normal cells, significant inhibition of cancer cell metastasis and invasion, as well as excellent anti-angiogenesis activities in zebrafish embryos. By comparison, DCA-free Re(I) analogue is also investigated under the same conditions. Although this analogue also exhibits cytotoxicity due to the Re(I) core, metabolic reversal is not induced by this analogue and its anti-metastasis activity is much lower than Re-dca 2, indicating the synergistic effect of Re(I) core and DCA moiety on cancer therapy. In vivo anti-cancer investigations also indicate that the mitochondria-targeted Re-dca 2 can effectively inhibit the tumor growth without affecting the body weight of nude mice, and the therapeutic effect is much better than the DCA-free Re(I) analogue 2a. Simultaneously, the O2-sensitive phosphorescent lifetimes of Re-dca 2 can be utilized for PLIM imaging of intracellular oxygen consumption, thus reflecting the Re-dca 2 induced glycolysis-to-glucose oxidation reversal at the early drug treatment stage. The excellent phosphorescence of Re-dca 2 can also be utilized for real-time tracking of mitochondrial morphological changes during treatment. In a word, rational design of phosphorescent metallodrug and metabolic modulator conjugates for synergistic treatment is a promising strategy for simultaneous untuning and tracking tumor metabolic machine, thus providing new clues for cancer therapy and mechanisms.
Graphical abstract
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The study of relationships between pKa value and siRNA delivery efficiency based on tri-block copolymers
Publication date: September 2018
Source:Biomaterials, Volume 176
Author(s): Lili Du, Changrong Wang, Lingwei Meng, Qiang Cheng, Junhui Zhou, Xiaoxia Wang, Deyao Zhao, Jianhua Zhang, Liandong Deng, Zicai Liang, Anjie Dong, Huiqing Cao
Tri-block copolymers have exhibited great potentials in small interfering RNA (siRNA) therapeutics. To reveal structure-activity relationships, we here synthesized a series of tri-block copolymers with different hydrophobic segments, PEG-PAMA-P(C6Ax-C7Ay-DPAz-DBAm) (EAAS) and PEG-PDAMAEMA-P(C6Ax-C7Ay-DPAz-DBAm) (EDAS), termed from EAASa to EAASh and EDASa to EDASh, with pKa ranging from 5.2 to 7.0. Our data showed that the better gene silencing efficiency was located in pKa of 5.8–6.2, which was contributed from higher endosomal escape observed with confocal images and hemolysis assay. EAASc, the leader polymer, showed excellent gene knockdown at w/w ratio of 14.5 on HepG2 (89.94%), MDA-MB-231 (92.45%), 293A (83.06%), and Hela cells (80.27%), all better than lipofectamine 2000. Besides, EAASc mediated effective gene silencing in tumor when performed peritumoral injection. This work found out that polymers with pKa ranging from 5.8 to 6.2 were efficient in siRNA delivery, which provided an optimization strategy for siRNA delivery systems, especially for tri-block copolymers.
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Anthropogenic CO 2 emissions from a megacity in the Yangtze River Delta of China
Abstract
Anthropogenic CO2 emissions from cities represent a major source contributing to the global atmospheric CO2 burden. Here, we examined the enhancement of atmospheric CO2 mixing ratios by anthropogenic emissions within the Yangtze River Delta (YRD), China, one of the world's most densely populated regions (population greater than 150 million). Tower measurements of CO2 mixing ratios were conducted from March 2013 to August 2015 and were combined with numerical source footprint modeling to help constrain the anthropogenic CO2 emissions. We simulated the CO2 enhancements (i.e., fluctuations superimposed on background values) for winter season (December, January, and February). Overall, we observed mean diurnal variation of CO2 enhancement of 23.5~49.7 μmol mol−1, 21.4~52.4 μmol mol−1, 28.1~55.4 μmol mol−1, and 29.5~42.4 μmol mol−1 in spring, summer, autumn, and winter, respectively. These enhancements were much larger than previously reported values for other countries. The diurnal CO2 enhancements reported here showed strong similarity for all 3 years of the study. Results from source footprint modeling indicated that our tower observations adequately represent emissions from the broader YRD area. Here, the east of Anhui and the west of Jiangsu province contributed significantly more to the anthropogenic CO2 enhancement compared to the other sectors of YRD. The average anthropogenic CO2 emission in 2014 was 0.162 (± 0.005) mg m−2 s−1 and was 7 ± 3% higher than 2010 for the YRD. Overall, our emission estimates were significantly smaller (9.5%) than those estimated (0.179 mg m−2 s−1) from the EDGAR emission database.
https://ift.tt/2JncJM1
A novel diindolylmethane analog, 1,1-bis(3’-indolyl)-1-(p-chlorophenyl) methane, inhibits the tumor necrosis factor-induced inflammatory response in primary murine synovial fibroblasts through a Nurr1-dependent mechanism
Source:Molecular Immunology, Volume 101
Author(s): Maryam F. Afzali, Katriana A. Popichak, Lindsey H. Burton, Anna L. Klochak, William J. Wilson, Stephen Safe, Ronald B. Tjalkens, Marie E. Legare
The progression of rheumatoid arthritis involves the thickening of the synovial lining due to the proliferation of fibroblast-like synoviocytes (FLS) and infiltration by inflammatory cells. Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine involved in progression of the disease. Under rheumatoid conditions, FLS express the tumor necrosis factor (TNF)-recognition complex (TNFR1, TNFR2, VCAM-1 and ICAM-1), which induces local macrophage activation and leads to downstream nuclear factor κB (NF-κB) signaling. The NF-κB-regulated inflammatory gene, cyclooxygenase (COX), increases synthesis of prostaglandins that contribute to the propagation of inflammatory damage within the joint. Because the nuclear orphan receptor, NR4A2 (Nurr1), can negatively regulate NF-κB-dependent inflammatory gene expression in macrophages, we postulated that activation of this receptor by the Nurr1 ligand 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) would modulate inflammatory gene expression in synovial fibroblasts by inhibiting NF-κB. Treatment with C-DIM12 suppressed TNFα-induced expression of adhesion molecules and NF-κB regulated genes in primary synovial fibroblasts including vascular adhesion molecule 1 (VCAM-1), PGE2 and COX-2. Immunofluorescence studies indicated that C-DIM12 did not prevent translocation of p65 and stabilized nuclear localization of Nurr1 in synovial fibroblasts. Knockdown of Nurr1 expression by RNA interference prevented the inhibitory effects of C-DIM12 on inflammatory gene expression, indicating that the anti-inflammatory effects of this compound are Nurr1-dependent. Collectively, these data suggest that this receptor may be a viable therapeutic target in RA.
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Morphological and ultrastructural changes in the placenta of the diabetic pregnant Egyptian women
Source:Acta Histochemica
Author(s): Nabila Yousef Abdelhalim, Mohammed Hany Shehata, Hanan Nabih Gadallah, Walaa Mohamed Sayed, Aref Ali Othman
Diabetes mellitus (DM) is a chronic metabolic disease in which the body fails to produce enough insulin or increased tissue resistance to insulin. The diabetes may have profound effects on placental development and function. This study was designed to detect the placental changes in pregnancy associated with DM comparing these changes with normal placenta. The study was carried out on sixty full-term placentae; divided into three equal groups; control group (group I): placentae of normal pregnancy, uncontrolled diabetes (group II): placentae from pregnant women whose blood glucose is poorly controlled during pregnancy. Controlled diabetes (group III): includes placentae from diabetic women whose blood glucose is controlled during pregnancy. The placentae from group II tend to be heavier and exhibited immaturity of villi, villous edema, fibrosis, excessive syncytial knots formation and infarctions. In addition to, fibrinoid necrosis, increased thickness of vasculosyncytial membrane, syncytial basement membrane, microvillous abnormalities and vascular endothelial changes were demonstrated. The syncytial multivesicular knots were present in placentae of group II. The nuclei within these syncytial knots display condensed chromatin, either dispersed throughout the nucleus or in the form of dense peripheral clumps with and numerous cytoplasmic vacuoles. The syncytial basement membrane showed focal areas of increase in its thickness and irregularity. Villous cytotrophoblasts showed increased number and activity in the form of numerous secretory granules, abundant dilated RER, larger distorted mitochondria. Villous vessels showed various degrees of abnormalities in the form of endothelial cell enlargement, folding, thickening and protrusion of their luminal surfaces into vascular lumen making it narrower in caliber. In placentae of group III, most of these abnormalities decreased. In most of placentae of group III, the VSM appeared nearly normal in thickness and showed nearly normal composition of one layer of syncytiotrophoblastic cells, one layer of smooth, regular capillary endothelium and the space between them. Mild microvillous abnormalities were noted in few placentae as they appeared short and blunted with mild decrease in their number per micron. The electron picture of syncytial knots appeared nearly normal containing aggregations of small, condensed hyperchromatic nuclei, minimal vacuoles could be seen in the cytoplasm of syncytial knots. Syncytial basement membrane appeared regular and nearly normal in its thickness and composition coming in direct contact with fetal blood capillaries but mild abnormalities were noted in the basement membrane in few placentae as increased its thickness and deposition of fibers or fibrinoid. Regarding cytotrophoblasts in the terminal villi of placentae with controlled diabetes, these cells appeared nearly normal. They were scattered beneath the syncytium and were active containing mitochondria, rough endoplasmic reticulum, free ribosomes and a large nucleus with fine dispersed chromatin. The vascular ultrastructural pattern in terminal villi of placentae of this group showed no significant abnormalities and was normally distributed in the villous tree. The luminal surface of the vascular endothelium appeared regular smooth in the majority of placentae of this group. The endothelial cells appeared connected to each other with tight junctions. It could be concluded that whether if long-term diabetes is controlled or not, placentae of diabetic mother showed a variety of significant histological structural changes seen more frequently than in the placentae of pregnant women without diabetes.
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Association of telomere length with general cognitive trajectories: a meta-analysis of four prospective cohort studies
Source:Neurobiology of Aging, Volume 69
Author(s): Yiqiang Zhan, Mark S. Clements, Rosebud O. Roberts, Maria Vassilaki, Brooke R. Druliner, Lisa A. Boardman, Ronald C. Petersen, Chandra A. Reynolds, Nancy L. Pedersen, Sara Hägg
To investigate the association of telomere length (TL) with trajectories of general cognitive abilities, we used data on 5955 participants from the Sex Differences in Health and Aging Study and the Swedish Adoption/Twin Study of Aging in Sweden, and the Mayo Clinic Study of Aging, and the Health and Retirement Study in the United States. TL was measured at baseline, while general cognitive ability was assessed repeatedly up to 7 occasions. Latent growth curve models were used to examine the associations. One standard deviation increase of TL was associated with 0.021 unit increase (95% confidence interval [CI]: 0.001, 0.042) of standardized mean general cognitive ability. After controlling for sex, the point estimate remained similar (0.019) with a wider CI (95% CI: −0.002, 0.039). The association was attenuated with adjustment for educational attainment (0.009, 95% CI: −0.009, 0.028). No strong evidence was observed for the association of TL and decline in general cognitive ability. Longer TL was associated with higher general cognitive ability levels in the age-adjusted models but not in the models including all covariates, nor with cognitive decline.
https://ift.tt/2Lh5VwR
Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis
Source:European Journal of Cancer, Volume 98
Author(s): Matthew N. Mills, George Q. Yang, Daniel E. Oliver, Casey L. Liveringhouse, Kamran A. Ahmed, Amber G. Orman, Christine Laronga, Susan J. Hoover, Nazanin Khakpour, Ricardo L.B. Costa, Roberto Diaz
BackgroundTriple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC.MethodsA total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan–Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome.ResultsMBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC.Conclusion(s)Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments.
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The chiral nature of the enhanced interrogation programme
Source:Aggression and Violent Behavior
Author(s): Myles Balfe
The United States suffered a catastrophic attack on September 11th 2001. The response to these killings, by the United States and its allies, was extremely forceful. As part of this response, US security institutions, and the health professionals who worked for them, developed an 'enhanced interrogation', or torture, programme to acquire intelligence from detainees in their custody. The enhanced interrogation programme has been described as a 'conflicted' phenomenon. This article considers in detail precisely why the enhanced interrogation programme, and the role of health professionals in it, can be said to be conflicted. The article identifies a number of reasons, including: the ambiguous and divided nature of the violence used in it; the dual roles that health professionals played in the enhanced interrogation initiative as healers and interrogators; professional division over the programme's ethics and effectiveness; the serious and negative impacts that the programme had on interrogators as well as detainees; and its split legacies. Underlying these individual reasons is the sense that the enhanced interrogation initiative was 'doubled', something that often pulled in two opposing dimensions simultaneously, and could be interpreted in divergent ways. The article concludes with a reiteration of the reasons why torture is ethically and effectively wrong.
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Synthesis of Sulfadiazinyl acyl/aryl thiourea derivatives as calf intestinal alkaline phosphatase inhibitors, Pharmacokinetic properties, Lead optimization, Lineweaver-Burk plot evaluation and Binding analysis
Publication date: Available online 2 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Sajid-ur-Rehman, Aamer Saeed, Gufran Saddique, Pervaiz Ali Channar, Fayaz Ali Larik, Qamar Abbas, Mubashir Hassan, Hussain Raza, Tanzeela Abdul Fattah, Sung-Yum Seo
To seek the new medicinal potential of sulfadiazine drug, the free amino group of sulfadiazine was exploited to obtain acyl/aryl thioureas using simple and straightforward protocol. Acyl/aryl thioureas are well recognized bioactive pharmacophore containing moieties. A new series (4a-4j) of sulfadiazine derived acyl/aryl thioureas was synthesized and characterized through spectroscopic and elemental analysis. The synthesized derivatives 4a-4j were subjected to calf intestinal alkaline phosphatase (CIAP) activity. The derivative 4a-4j showed better inhibition potential compared to standard monopotassium phosphate (MKP). The compound 4c exhibited higher potential in the series with IC50 0.251±0.012µM (standard KH2PO4 4.317±0.201µM). Lineweaver-Burk plots revealed that most potent derivative 4c inhibition CIAP via mixed type pathway. Pharmacological investigations showed that synthesized compounds 4a-4j obey Lipinsk's rule. ADMET parameters evaluation predicted that these molecule show significant lead like properties with minimum possible toxicity and can serve as templates in drug designing. The synthetic compounds show none mutagenic and irritant behavior. Molecular docking analysis showed that compound 4c interacts with Asp273, His317 and Arg166 amino acid residues.
Graphical abstract
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Design, synthesis, and biological evaluation of novel biphenyl-4-carboxamide derivatives as orally available TRPV1 antagonists
Publication date: Available online 2 June 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Hiromasa Oka, Koichi Yonezawa, Akio Kamikawa, Kazuhiro Ikegai, Norio Asai, Shohei Shirakami, Satoshi Miyamoto, Toshihiro Watanabe, Tetsuo Kiso, Yukihiro Takemoto, Seiji Tamura, Takahiro Kuramochi
A new series of transient receptor potential vanilloid type 1 (TRPV1) antagonists were designed and synthesized from N-(3-hydroxyphenyl)-2-(piperidin-1-ylmethyl)biphenyl-4-carboxamide hydrochloride (8). SAR studies identified (R)-N-(1-methyl-2-oxo-1,2,3,4-tetrahydro-7-quinolyl)-2-[(2-methylpyrrolidin-1-yl)methyl]biphenyl-4-carboxamide hydrochloride (ASP8370, 7), as a compound with high aqueous solubility, satisfactory stability in human liver microsomes, and reduced CYP3A4 inhibition. ASP8370 was selected as a clinical development candidate with significant ameliorative effects on neuropathic pain. SAR studies also revealed the structural mechanisms underlying the switching between TRPV1 antagonism and agonism.
Graphical abstract
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Implementation of enhanced cognitive behaviour therapy (CBT-E) for adults with anorexia nervosa in an outpatient eating-disorder unit at a public hospital
Abstract
Background
Anorexia nervosa (AN) in adults is difficult to treat, and no current treatment is supported by robust evidence. A few studies, most of which were performed by highly specialized research units, have indicated that enhanced cognitive behaviour therapy (CBT-E) for eating disorders can be effective. However, the dropout rate is high and the evidence from non-research clinical units is sparse.
Methods
This quality assessment project implemented CBT-E in an outpatient setting at a public hospital. Forty-four patients with AN started therapy. Each patient received at least 40 sessions of CBT-E over a 12-month period. Their body mass index (BMI) was recorded at baseline and after 3, 6 and 12 months. Reasons for not starting therapy or for leaving therapy prematurely were recorded.
Results
Half (n = 22) of the 44 patients who started outpatient CBT-E did not complete the treatment. In the remaining sample there was a large (and statistically significant) weight gain after 12 months. The percentage of patients achieving the target BMI of > 18.5 kg/m2 was 36.4, 50.0 and 77.3% after 3, 6 and 12 months, respectively.
Conclusions
This quality assessment project shows that it is possible to establish effective CBT-E in an outpatient eating-disorder unit at a public hospital. Although half of the patients did not complete CBT-E, the remaining patients achieved a significant increase in BMI at 1 year after the start of therapy.
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Medium- and Large-Sized Autologous Breast Reconstruction using a Fleur-de-lys Profunda Femoris Artery Perforator Flap Design: A Report Comparing Results with the Horizontal Profunda Femoris Artery Perforator Flap
J reconstr Microsurg
DOI: 10.1055/s-0038-1649508
Background The volume of the profunda femoris artery perforator (PAP) flap limits its indications to small- and medium-sized breast reconstructions after modified radical mastectomy for cancer. We report a modified PAP flap design, including not only a vertical extension that increases its volume but also the skin surface, which suits larger breasts requiring immediate or delayed breast reconstructions and compare the results with our horizontal skin paddle PAP flap experience. Patients and Methods In our center between November 2014 and November 2016, 51 consecutive patients underwent a PAP flap breast reconstruction following breast cancer. A retrospective analysis on the collected data was performed to compare 34 patients with a bra cup smaller than C who underwent 41 horizontal PAP flap procedures, with those (n = 17) of a bra cup greater than or equal to C who underwent 21 fleur-de-lys PAP flap procedures. Demographic, anthropometric, flap and surgical characteristics, postoperative complication rates, and hospital stay were compared between the two groups. Results The average flap weight was 480 g (range: 340–735 g) for the fleur-de-lys PAP flap group compared with 222 g (range: 187–325 g) for the horizontal PAP flap procedure (p < 0.001). The mean flap dimensions were 25 × 18 cm for the fleur-de-lys PAP flap group compared with 25 × 7 cm in the horizontal PAP flap group. No flap failure was observed in the fleur-de-lys PAP flap group compared with two flap failures secondary to venous thrombosis in the horizontal PAP flap group (NS). Three patients (14%) experienced delayed healing at the donor site compared with four patients (10%) in the horizontal PAP flap group (NS). Conclusion The fleur-de-lys skin paddle design not only allows an increase of the horizontal PAP flap volume, but also increases the skin surface, with an acceptable donor site morbidity. For medium- or large-sized breasts, the fleur-de-lys PAP flap seems to be ideal when a DIEP flap-based reconstruction is contraindicated.
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Effect of particle size on particulate matter emissions during biosolid char combustion under air and oxyfuel conditions
Publication date: 15 November 2018
Source:Fuel, Volume 232
Author(s): Sui Boon Liaw, Xujun Chen, Yun Yu, Mário Costa, Hongwei Wu
In an industrial scale furnace, solid fuels can be fired in a wide range of particle sizes. This study aims to investigate the effect of the particle size on particulate matter (PM) emissions during combustion under air and oxyfuel (30% O2/70% CO2) conditions. Biosolid chars prepared from the pyrolysis of three different biosolid particle sizes at 1300 °C were burned in a drop tube furnace. The experimental results indicate that a shift from small to large char particles leads to >55% reduction in PM1–10 emission when combustion occurs in air, likely due to less intense char fragmentation experienced by the large char particles. Such a reduction originates from a decrease in Mg, Ca, P, Si, Al and some trace elements (V, Co, Cu, Zn and Mn) release as PM1–10. In contrast, PM1 emission is not affected by the char particle size. However, under oxyfuel conditions, the PM1–10 emission from the small char particles is ∼65% of that released during combustion in air. In addition, the PM1–10 emission from large char particles only reduced by ∼27% when compared to that from small char particles. This observation is likely to result from the coalescence of ash particles to form PM with particle sizes >10 µm due to the increase surface mobility caused by repeated formation and decomposition of CaCO3 in the ash.
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Photophysicochemical properties and photodynamic therapy activity of highly water-soluble Zn(II) phthalocyanines
Publication date: 5 October 2018
Source:Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, Volume 203
Author(s): David O. Oluwole, Fatma Aslıhan Sarı, Earl Prinsloo, Edith Dube, Abdulcelil Yuzer, Tebello Nyokong, Mine Ince
The syntheses of two zinc(II) phthalocyanines (ZnPcs) having either imidazole (ZnPc 1) or pyridiloxy (ZnPc 2) moieties as their macrocycle substituents are reported. Quaternization of the ZnPcs with methyl iodide afforded water soluble cationic phthalocyanines. The photophysical, photochemical properties and photodynamic therapy (PDT) activity of the ZnPcs were studied in solution. The fluorescence quantum yield and lifetime of ZnPc 1 were higher as compared to ZnPc 2. ZnPc 2 afforded higher triplet state (ΦT) and singlet oxygen quantum yields (ΦΔ) in comparison to ZnPc 1. The PDT activity of ZnPcs was investigated against human breast adenocarcinoma cells (MCF–7). The two compounds afforded a very minimal in vitro dark cytotoxicity with 85% viable cells at concentration ≤80 μM. On irradiation of the cells having the ZnPcs, ≥50% cell death was recorded for ZnPc 1 which was also evidenced by the cells photo–micrograph.
Graphical abstract
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A novel mutation in the proopiomelanocortin (POMC) gene of a Hispanic child: metformin treatment shows a beneficial impact on the body mass index
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Impact of a group-based treatment program on adipocytokines, oxidative status, inflammatory cytokines and arterial stiffness in obese children and adolescents
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Genetic analysis of three families with X-linked dominant hypophosphatemic rickets
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Clinical and molecular genetic characterization of two patients with mutations in the phosphoglucomutase 1 (PGM1) gene
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Issue: Ahead of print
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Frontmatter
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: i-iv
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Congenital hypothyroidism
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 595-596
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The etiologies and incidences of congenital hypothyroidism before and after neonatal TSH screening program implementation: a study in southern Thailand
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 609-617
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Current status of the congenital hypothyroidism neonatal screening program in Adana Province, Turkey
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 619-624
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Risk of hypoglycemia in youth with type 2 diabetes on insulin
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 625-630
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Metabolic risk factors in adolescent girls with type 1 diabetes
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 631-635
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Definition of reference ranges for β-isomerized carboxy-terminal telopeptide collagen type I for children and adolescents
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 637-640
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Brown adipose tissue in young adults who were born preterm or small for gestational age
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 641-647
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Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 655-663
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Initial presentations and associated clinical findings in patients with classical congenital adrenal hyperplasia
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 671-673
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Cardiac examination in children with Laron syndrome undergoing mecasermin therapy
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 675-679
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Exertional rhabdomyolysis in carbonic anhydrase 12 deficiency
Journal Name: Journal of Pediatric Endocrinology and Metabolism
Volume: 31
Issue: 6
Pages: 697-699
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Inhibition of biofilm formation by Cd2+ on Bacillus subtilis 1JN2 depressed its biocontrol efficiency against Ralstonia wilt on tomato
Source:Microbiological Research
Author(s): Wei Yang, Haixia Yan, Ji Zhang, Yuming Gao, Wei Xu, Jinshan Shang, Yuming Luo
Bacillus subtilis 1JN2 can serve as an effective biocontrol agent against Ralstonia wilt on tomato, but the efficiency of control depends on the levels of heavy metals in the rhizosphere soil. Here, we investigated how the heavy metal Cd2+ affects the biocontrol efficacy of B.subtilis 1JN2 on Ralstonia wilt. We found that low Cd2+ content of 2 mM or lower had no effects on the biofilm formation of 1JN2, while media containing 3 mM or higher Cd2+ levels inhibited biofilm formation. Interestingly, high concentration of Cd2+ (5 mM) showed inhibition of B.subtilis 1JN2 cell growth. We next tested the effects of Cd2+ on the colonization of 1JN2 by supplementing artificial Cd2+ in the tomato rhizosphere in a greenhouse setting. We found that 3 mM Cd2+ in the tomato rhizosphere inhibited the colonization of B.subtilis 1JN2, Only 103 CFU/mL 1JN2 was detected one week post treated with 107 CFU/mL but 105 CFU/mL could be detected without Cd2+ in the soil. The presence of Cd2+ had no effect on the colonization of Ralstonia solanacearum on tomato, but the biocontrol efficacy against Ralstonia wilt by 1JN2 decreased 54.2% when the soil contained 3 mM Cd2+ compared to the control without Cd2+. Taken together, we found that the failure of biofilm formation of Bacillus subtilis 1JN2 that affected by Cd2+ lead to the decrease of its biocontrol efficacy against Ralstonia wilt on tomato.
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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