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Πέμπτη 23 Φεβρουαρίου 2017

Higher Dihydrotestosterone Is Associated with the Incidence of Lung Cancer in Older Men

Abstract

Advancing age is associated with increased cancer incidence, but the role of sex hormones as risk predictors for common cancers in older men remains uncertain. This study was performed to assess associations of testosterone (T), dihydrotestosterone (DHT) and estradiol (E2), with incident prostate, lung and colorectal cancer in community-dwelling older men. Plasma T, DHT and E2 were assayed using liquid chromatography-mass spectrometry between 2001 and 2004 in 3690 men. Cancer outcomes until 20 June 2013 were ascertained using data linkage. Analyses were performed using proportional hazards competing-risks models, and adjustments were made for potential confounding factors including smoking status. Results are expressed as subhazard ratios (SHR). There were 348, 107 and 137 cases of prostate, lung and colorectal cancers respectively during a median of 9.1-year follow-up. Mean T was comparable in current and non-smokers, whilst mean DHT was lower in ex- and current smokers compared to non-smokers. After adjusting for confounders including smoking, higher T or DHT was associated with an increased incidence of lung cancer (SHR = 1.30, 95% CI 1.06–1.60; p = 0.012 per 1 SD increase in T and SHR = 1.29, 95% CI 1.08–1.54; p = 0.004 for DHT). Sex hormones were not associated with prostate or colorectal cancer. In older men, higher T or DHT predict increased incidence of lung cancer over the next decade. Sex hormones are not associated with incident prostate or colorectal cancer. Further studies are warranted to determine if similar associations of sex hormones with lung cancer are present in other populations and to investigate potential underlying mechanisms.



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Omega-3 fatty acids as adjunctive treatment for bexarotene-induced hypertriglyceridaemia in patients with cutaneous T-cell lymphoma

Summary

Background

Bexarotene is an oral retinoid approved for treating cutaneous T-cell lymphoma (CTCL) in patients resistant to first-line systemic treatment. Hypertriglyceridaemia is an unavoidable adverse effect of bexarotene therapy, and requires monitoring because of the risk of developing pancreatitis. Therefore, prophylactic hypolipidaemic therapy, usually with a fibrate alone, is required for preventing bexarotene-induced hypertriglyceridaemia. Despite these measures, a large number of patients develop very severe hypertriglyceridaemia.

Aim

To assess the lipid metabolism changes before and after the use of a combination of omega-3 fatty acids (n-3 FA) plus fenofibrate compared with fenofibrate alone as a more effective lipid-lowering therapy in patients with CTCL treated with bexarotene.

Methods

From January 2005 to January 2013, we analysed all 25 patients with CTCL treated with bexarotene. The first 18 consecutively enrolled patients received fenofibrate alone as a lipid-lowering therapy, and the next 7 consecutively enrolled patients received a combination of fenofibrate and n-3 FA.

Results

Data for all 25 consecutive patients with CTCL treated with bexarotene were evaluated. Of these, 24 patients (96%) developed hypertriglyceridaemia despite the hypolipidaemic therapy, with this being very severe (> 11.2 mmol/L) in 20% of the cases. Of the 18 patients receiving fenofibrate alone, 5 (28%) developed very severe hypertriglyceridaemia, compared with none of the 7 patients treated with the n-3 FA combination.

Conclusions

Our results suggest that the n-3 FA combination may be more effective than fibrate alone for preventing bexarotene-induced hypertriglyceridaemia.



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Protective Effect of SFE-CO2 of Ligusticum chuanxiong Hort Against d-Galactose-Induced Injury in the Mouse Liver and Kidney

Rejuvenation Research , Vol. 0, No. 0.


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Evaluation of impact of an external breast shield (FlexiShield) in electronic brachytherapy for breast IORT: A phantom study

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Publication date: Available online 23 February 2017
Source:Brachytherapy
Author(s): Yongbok Kim, Jason Wei-Yeong Huynh, Victor J. Gonzalez
PurposeTo investigate Axxent (iCAD, Inc., San Jose, CA) electronic brachytherapy balloon deformation and its dosimetric impact because of an external flexible shield (FlexiShield [FS]; iCAD, Inc.).Methods and MaterialsProstheses breast tissue phantom overlaid three spherical balloon applicators to simulate three clinical scenarios depending on minimum skin-to-balloon surface spacing (SS): balloon with SS of 2 cm, 1 cm, and balloon with 1 cm SS and touching the chest wall. Two sets of megavoltage CT (MVCT) scans were obtained with or without FS for 15 different sizes of balloons. For 45 pairs of MVCT scans, balloon deformation was measured in superior–inferior (dSI) dimension on coronal and sagittal planes and anterior–posterior (dAP) and lateral (dLAT) dimensions on the equatorial plane of balloon. SS was also compared. A treatment plan was made on each MVCT scan. Doses at four balloon surface points and skin were compared. Conformity index value was also compared to evaluate three-dimensional dose distribution. Clinically, 20 Gy was prescribed to the surface of balloon.ResultsBalloon deformation was observed with compression in SI and AP dimensions and expansion in lateral dimension. Average SI compression was 0.5 mm. Average dLat - dAP was 2.4 mm, which resulted in elevated point doses at AP dimension by 10.8% of prescribed dose and reduced point doses at lateral dimension by 4.6%. FS decreased SS by 1.8 mm, increasing skin dose by 1.2 Gy, on average. Conformity index value was decreased from 0.922 to 0.908, on average.ConclusionsThis phantom study demonstrates that use of skin shielding during breast intraoperative radiation therapy can cause balloon deformation and SS reduction, resulting in dosimetric changes that are disregarded in current practice.



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Prostate MRI for brachytherapists: Anatomy and technique

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Publication date: Available online 23 February 2017
Source:Brachytherapy
Author(s): A.M. Venkatesan, R.J. Stafford, C. Duran, P.D. Soni, A. Berlin, P.W. McLaughlin
PurposeTo present an overview of mp MRI techniques necessary for high-resolution imaging of prostate.MethodsWe summarize examples from our clinical experience and concepts from the current literature that illustrate normal prostate anatomy on multiparametric MRI (mp MRI).ResultsOur experience regarding optimal mp MRI image acquisition is provided, as well as a summary of prostate and periprostatic anatomy and anatomical variants that pose challenges for BT.Conclusionsmp MRI provides unparalleled assessment of the prostate and periprostatic anatomy, making it the most appropriate imaging modality to facilitate prostate BT treatment planning, implantation, and followup. This work provides an introduction to prostate mp MR imaging, anatomy, and anatomical variants essential for successful integration mp MRI into prostate brachytherapy practice.



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Common Carotid Artery Diameter, Blood Flow Velocity and Wave Intensity Responses at Rest and during Exercise in Young Healthy Humans: A Reproducibility Study

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Publication date: Available online 23 February 2017
Source:Ultrasound in Medicine & Biology
Author(s): Nicola Pomella, Eurico Nestor Wilhelm Neto Wilhelm, Christina Kolyva, José González-Alonso, Mark Rakobowchuk, Ashraf W. Khir
The aim of this study was to assess the reproducibility of non-invasive, ultrasound-derived wave intensity (WI) in humans at the common carotid artery. Common carotid artery diameter and blood velocity of 12 healthy young participants were recorded at rest and during mild cycling, to assess peak diameter, change in diameter, peak velocity, change in velocity, time derivatives, non-invasive wave speed and WI. Diameter, velocity and WI parameters were fairly reproducible. Diameter variables exhibited higher reproducibility than corresponding velocity variables (intra-class correlation coefficient [ICC] = 0.79 vs. 0.73) and lower dispersion (coefficient of variation [CV] = 5% vs. 9%). Wave speed had fair reproducibility (ICC = 0.6, CV = 16%). WI energy variables exhibited higher reproducibility than corresponding peaks (ICC = 0.78 vs. 0.74) and lower dispersion (CV = 16% vs. 18%). The majority of variables had higher ICCs and lower CVs during exercise. We conclude that non-invasive WI analysis is reliable both at rest and during exercise.



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Biochemical Basis for Increased Activity of Ebola Glycoprotein in the 2013–16 Epidemic

Publication date: Available online 23 February 2017
Source:Cell Host & Microbe
Author(s): May K. Wang, Sun-Young Lim, Soo Mi Lee, James M. Cunningham
Ebola virus (EBOV) infection is characterized by sporadic outbreaks caused by zoonotic transmission. Fixed changes in amino acid sequence, such as A82V in the EBOV glycoprotein (GP) that occurred early in the 2013–16 epidemic, are suspected to confer a selective advantage to the virus. We used biochemical assays of GP function to show that A82V, as well as a polymorphism in residue 544 identified in other outbreaks, enhances infection by decreasing the threshold for activation of membrane fusion activity triggered by the host factors cathepsin B and Niemann-Pick C1. Importantly, the increase in infectivity comes with the cost of decreased virus stability. Thus, emergence of a virus GP with altered properties that can affect transmission and virulence may have contributed to the severity and scope of the 2013–16 EBOV epidemic.

Graphical abstract

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Teaser

A fixed A82V polymorphism in the EBOV glycoprotein that occurred early in the 2013–16 epidemic is suspected to confer a selective advantage. Wang et al. show that A82V and another polymorphism from other outbreaks confers increased EBOV infectivity and decreased host entry factor dependency, at the cost of decreased virus stability.


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Salmonella enterica Remodels the Host Cell Endosomal System for Efficient Intravacuolar Nutrition

Publication date: Available online 23 February 2017
Source:Cell Host & Microbe
Author(s): Viktoria Liss, A. Leoni Swart, Alexander Kehl, Natascha Hermanns, Yuying Zhang, Deepak Chikkaballi, Nathalie Böhles, Jörg Deiwick, Michael Hensel
Salmonella enterica is a facultative intracellular pathogen that survives and proliferates in the Salmonella-containing vacuole (SCV), yet how these vacuolar bacteria acquire nutrition remains to be determined. Intracellular Salmonella convert the host endosomal system into an extensive network of interconnected tubular vesicles, of which Salmonella-induced filaments (SIFs) are the most prominent. We found that membranes and lumen of SIFs and SCVs form a continuum, giving vacuolar Salmonella access to various types of endocytosed material. Membrane proteins and luminal content rapidly diffuse between SIFs and SCVs. Salmonella in SCVs without connection to SIFs have reduced access to endocytosed components. On a single-cell level, Salmonella within the SCV-SIF continuum were found to exhibit higher metabolic activity than vacuolar bacteria lacking SIFs. Our data demonstrate that formation of the SCV-SIF continuum allows Salmonella to bypass nutritional restriction in the intracellular environment by acquiring nutrients from the host cell endosomal system.

Graphical abstract

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Teaser

The intracellular proliferation of the vacuolar pathogen Salmonella enterica depends on conversion of the host endosomal system into a network of interconnected tubular vesicles. Liss et al. use single-cell analyses to reveal a role for this tubular network in conveying nutrients from the host endosomal system to vacuolar bacteria.


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Stop the Eye Rolling.

Author: P., Marcy
Page: 13


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Speaking Up for Patients.

Author: Holder, Jacqueline RN
Page: 13


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It's Time to Earn the Public's Trust.

Author: Kennedy, Maureen Shawn MA, RN, FAAN
Page: 7


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Just a Nurse, or a Bedside Leader?.

Author: Costanzo, Amy J. MSN, RN-BC
Page: 11


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Reducing SIDS.

Author: Fife, Patricia MPA, RN
Page: 13


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Stop the Eye Rolling.

Author: Moffa, Nurse
Page: 13


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Stop the Eye Rolling.

Author: H-J., Paul
Page: 13


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Stop the Eye Rolling.

Author: L.G., Stormy
Page: 13


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VA Grants Most APRNs Full Practice Authority.

Author: Sofer, Dalia
Page: 14


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Benefits of Kangaroo Care for Premature Babies Continue into Young Adulthood.

Author: Stockwell, Serena
Page: 15


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NewsCAP: More nurse training results in fewer pressure ulcers in German hospitals.

Author:
Page: 15


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Rollback of Michigan's Motorcycle Helmet Law Results in More Head Injuries.

Author: Halpern, Lucy Wang
Page: 16


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NewsCAP: New Web site allows consumer comparisons of rehabilitation facilities.

Author:
Page: 16


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NewsCAP: A new vaccine against Ebola may be effective and safe to use in an outbreak.

Author:
Page: 16


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Inadequate Handwashing Practices in Childcare Facilities.

Author: Potera, Carol
Page: 17


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Rural Pregnant Women and Newborns Hit Hard by Opioid Crisis.

Author: Stockwell, Serena
Page: 17


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Trends in U.S. Health Care.

Author:
Page: 18


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Do NPs Need Postgraduate Residencies?.

Author: Nelson, Roxanne
Page: 19-20


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AJN On the Cover.

Author: Szulecki, Diane associate editor
Page: 21


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AJN On the Web.

Author:
Page: 21


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In situ heart valve tissue engineering using a bioresorbable elastomeric implant – From material design to 12 months follow-up in sheep

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Jolanda Kluin, Hanna Talacua, Anthal I.P.M. Smits, Maximilian Y. Emmert, Marieke C.P. Brugmans, Emanuela S. Fioretta, Petra E. Dijkman, Serge H.M. Söntjens, Renée Duijvelshoff, Sylvia Dekker, Marloes W.J.T. Janssen-van den Broek, Valentina Lintas, Aryan Vink, Simon P. Hoerstrup, Henk M. Janssen, Patricia Y.W. Dankers, Frank P.T. Baaijens, Carlijn V.C. Bouten
The creation of a living heart valve is a much-wanted alternative for current valve prostheses that suffer from limited durability and thromboembolic complications. Current strategies to create such valves, however, require the use of cells for in vitro culture, or decellularized human- or animal-derived donor tissue for in situ engineering. Here, we propose and demonstrate proof-of-concept of in situ heart valve tissue engineering using a synthetic approach, in which a cell-free, slow degrading elastomeric valvular implant is populated by endogenous cells to form new valvular tissue inside the heart. We designed a fibrous valvular scaffold, fabricated from a novel supramolecular elastomer, that enables endogenous cells to enter and produce matrix. Orthotopic implantations as pulmonary valve in sheep demonstrated sustained functionality up to 12 months, while the implant was gradually replaced by a layered collagen and elastic matrix in pace with cell-driven polymer resorption. Our results offer new perspectives for endogenous heart valve replacement starting from a readily-available synthetic graft that is compatible with surgical and transcatheter implantation procedures.

Graphical abstract

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Orthogonal near-infrared upconversion co-regulated site-specific O2 delivery and photodynamic therapy for hypoxia tumor by using red blood cell microcarriers

Publication date: May 2017
Source:Biomaterials, Volume 125
Author(s): Peiyuan Wang, Xiaomin Li, Chi Yao, Wenxing Wang, Mengyao Zhao, Ahmed Mohamed El-Toni, Fan Zhang
Pre-existing hypoxia in tumors can result in an inadequate oxygen supply during photodynamic therapy (PDT), which in turn hampers photodynamic efficacy. To overcome this problem, we developed an orthogonal near-infrared upconversion controlled red blood cell (RBC) microcarriers to selectively deliver O2 in hypoxia area. Moreover, this RBC microcarriers are able to overcome a series of complex biological barriers which include transporting across the inflamed endothelium, evading mononuclear phagocyte system, reducing reticuloendothelial system uptake. Based on these abilities, RBC microcarriers have efficient tumors accumulation and are capable of delivery a large amount of O2 for PDT under near-infrared (NIR) irradiation to realize effective solid tumor eradication.

Graphical abstract

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Sensitivity of various body indices and visceral adiposity index in predicting metabolic syndrome among Chinese patients with adult growth hormone deficiency

Abstract

Aim

Adult growth hormone deficiency (AGHD) refers to decreased secretion of growth hormones in the adults, which is associated with increased clustering of conventional cardiovascular risk factors such as central obesity, insulin resistance and dyslipidemia. Metabolic syndrome (MetS), a recognized risk factor of cardiovascluar diseases, shares some clinical features. Given that the prevalence of MetS is on the rise in patients with AGHD, and that cardiovascular disease (CVD) is an important cause of morbidity and mortality in that population, the alternative, simple, non-invasive methods of assessing MetS among this population are needed. This study aims to determine the sensitivity of five anthropometric indices [Body mass index (BMI), Waist circumference (WC), Waist-to-hip ratio (WHR), Waist-to-height ratio (WHtR) and Visceral adiposity index (VAI)] in predicting metabolic syndrome in Chinese population-based patients with adult growth hormone deficiency.

Materials and methods

A total of 96 Chinese patients with adult growth hormone deficiency were included in this study. They were compared with equal number of apparently healthy persons with similar characteristics (matched with age and gender) to the previous group. Anthropometric measurements including weight, height, serum lipids indices, blood pressure (BP), fasting plasma glucose (FPG), WC were measured. BMI, WHR, WHtR, and VAI were calculated.

Results and discussion

AGHD patients with MetS had higher WC (91.00 ± 8.28 vs 78.01 ± 7.12), BMI (24.95 ± 2.91 VS 23.30 ± 2.80), WHR (0.92 ± 0.06 VS 0.87 ± 0.07), WHtR (0.53 ± 0.06 VS 0.47 ± 0.05), VAI [(5.59 (4.02, 7.55) VS 1.69 (0.87, 3.05)] levels in comparison to those without MetS. Meantime WC, BMI, WHR, WHtR, VAI was positively correlated to MetS components. ROC curve for participants with AGHD showed that VAI had the highest SS of 92% (BMI 0.812; WHR 0.706; WHtR 0.902; VAI 0.920, respectively) for prediction of MetS in AGHD. The optimal cutoff values for different adiposity markers in predicting MetS were as follows: WC (79.65), BMI (23.46); WHR (0.89); WHtR (0.54); VAI (2.29).

Conclusion

In conclusion, our study showed all adiposity measures of interest present themselves as easy and practical tools for use in population studies and clinical practice for evaluating MetS in AGDH and VAI was identified as the best in Chinese AGHD patients among them.



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Multidisciplinary Management of Breast Cancer During Pregnancy

Background.

Although breast cancer during pregnancy (BCDP) is rare (occurring with only 0.4% of all BC diagnoses in female patients aged 16–49 years), management decisions are challenging to both the patient and the multidisciplinary team.

Materials and Methods.

Experts in breast cancer at the University of North Carolina conducted a targeted literature search regarding the multidisciplinary treatment approaches to BCDP: medical, surgical, and radiation oncology. Supportive care, including antiemetic agents, and imaging approaches were also reviewed.

Results.

Review of the literature revealed key points in the management of BCDP. Surgical management is similar to that in nonpregnant patients; pregnant patients may safely undergo breast-conserving surgery. Recommendations should be tailored to the individual according to the clinical stage, tumor biology, genetic status, gestational age, and personal preferences. Anthracycline-based chemotherapy can be safely initiated only in the second and third trimesters. The rate of congenital abnormalities in children exposed to chemotherapy is similar to the national average (approximately 3%). Dosing of chemotherapy should be similar to that in the nonpregnant patient (i.e., actual body surface area). Antihuman epidermal growth factor receptor 2 therapy, radiation, and endocrine treatment are contraindicated in pregnancy and lactation. Care should include partnership with obstetricians. The literature regarding prognosis of BCDP is mixed.

Conclusion.

To maximize benefit and minimize risk to the mother and fetus, an informed discussion with the patient and her medical team should result in an individualized treatment plan, taking into account the timing of the pregnancy and the stage and subtype of the breast cancer. Because BCDP is rare, it is essential to collect patient data in international registries. The Oncologist 2017;22:1–11

Implications for Practice.

Breast cancer during pregnancy is a major ethical and professional challenge for both the patient and the multidisciplinary treatment team. Although the oncologic care is based on that of the non-pregnant breast cancer patient, there are many challenges from regarding the medical, surgical and radiation oncology and obstetrical aspects of care that need to be considered to deliver the safest and best treatment plan to both the mother and developing fetus.



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Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome

Background.

Several risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far.

Patients and Methods.

A retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method.

Results.

Two hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 x Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%–50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively.

Conclusion.

In stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:000–000

Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine neoplasms is affected by several risk factors, including the proliferative index Ki67, extension of liver metastases, and the presence of distant extra-abdominal lesions. A risk score that combines these variables may help physicians dealing with these diseases to plan the optimal therapeutic approach and follow-up program.



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Escalating Health Care Expenditures in Cancer Decedents Last Year of Life: A Decade of Evidence from a Retrospective Population-Based Cohort Study in Taiwan

Background.

No population-based longitudinal studies on end-of-life (EOL) expenditures were found for cancer decedents.

Methods.

This population-based, retrospective cohort study examined health care expenditures from 2001 to 2010 among 339,546 Taiwanese cancer decedents' last year of life. Individual patient-level data were linked from administrative datasets. Health care expenditures were converted from Taiwan dollars to U.S. dollars by health-specific purchasing power parity conversions to account for different health-purchasing powers. Associations of patient, physician, hospital, and regional factors with EOL care expenditures were evaluated by multilevel linear regression model by generalized estimating equation method.

Results.

Mean annual EOL care expenditures for Taiwanese cancer decedents increased from 2000 to 2010 from U.S. $49,591 to U.S. $68,773, respectively, with one third of spending occurring in the patients' last month. Increased EOL care expenditures were associated with male gender, younger age, being married, diagnosed with hematological malignancies and cancers other than lung, gastric, and hepatic-pancreatic cancers, and dying within 7–24 months of diagnosis. Patients spent less at EOL when they had higher comorbidities and metastatic disease, died within 6 months of diagnosis, were under care of oncologists, gastroenterologists, and intensivists, and received care at a teaching hospital with more terminally ill cancer patients. Higher EOL care expenditures were associated with greater EOL care intensity at the primary hospital and regional levels.

Conclusion.

Taiwanese cancer decedents consumed considerable National Health Insurance disbursements at EOL, totaling more than was consumed in six developed non-U.S. countries surveyed in 2010. To slow increasing cost and improve EOL cancer care quality, interventions to ensure appropriate EOL care provision should target hospitals and clinicians less experienced in providing EOL care and those who tend to provide aggressive EOL care to high-risk patients. The Oncologist 2017;22:1–10

Implications for Practice.

Cancer-care costs are highest during the end-of-life (EOL) period for cancer decedents. This population-based study longitudinally examined EOL expenditures for cancer decedents. Mean annual EOL-care expenditures for Taiwanese cancer decedents increased from U.S. $49,591 to U.S. $68,773 from the year 2000 to 2010, with one third of spending in patients' last month and more than for six developed non-U.S. countries surveyed in 2010. To slow the increasing cost of EOL-cancer care, interventions should target hospitals/clinicians less experienced in providing EOL care, who tend to provide aggressive EOL care to high-risk patients, to avoid the physical suffering, emotional burden, and financial costs of aggressive EOL care.



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FDA Approval Summary: Nivolumab in Advanced Renal Cell Carcinoma After Anti-Angiogenic Therapy and Exploratory Predictive Biomarker Analysis

On November 23, 2015, the U.S. Food and Drug Administration approved nivolumab (OPDIVO, Bristol-Myers Squibb Company) for patients with advanced renal cell carcinoma (RCC) who have received prior anti-angiogenic therapy. The approval was based on efficacy and safety data demonstrated in an open-label, randomized study of 821 patients with advanced RCC who progressed after at least one anti-angiogenic therapy. Patients were randomized to nivolumab or everolimus and followed for disease progression. The primary end point was overall survival. Subsequent therapies, including everolimus for patients who developed progressive disease on the nivolumab arm, were allowed, but no cross-over was permitted. The median overall survival was 25.0 months on the nivolumab arm and 19.6 months on everolimus arm (hazard ratio: 0.73; 95% confidence interval: 0.60–0.89). The confirmed response rates were 21.5% versus 3.9%; median durations of response were 23.0 versus 13.7 months, and median times to response were 3.0 versus 3.7 months in the nivolumab and everolimus arms, respectively. A statistically significant improvement in progression-free survival was not observed in this trial. The safety profile of nivolumab in renal cell cancer was similar to that in other disease settings. However, the incidence of immune-mediated nephritis appeared to be higher in patients with RCC. The Oncologist 2017;22:1–7

Implications for Practice: The overall benefit/risk profile demonstrated in trial CA209025 supported the approval of nivolumab as an additional treatment option for patients with advanced renal cell carcinoma after anti-angiogenic therapy. The use of nivolumab in patients who had received vascular endothelial growth factor-targeted therapy resulted in a 5.4 month improvement in median overall survival compared with the everolimus arm. This difference is statistically significant and clinically meaningful.



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Targeting NK-cell checkpoints for cancer immunotherapy

Publication date: April 2017
Source:Current Opinion in Immunology, Volume 45
Author(s): Aura Muntasell, Maria C Ochoa, Luna Cordeiro, Pedro Berraondo, Ascension López-Díaz de Cerio, Mariona Cabo, Miguel López-Botet, Ignacio Melero
Natural Killer (NK) cells are cytotoxic lymphocytes specialized in early defense against virus-infected and transformed cells. NK-cell function is regulated by activating and inhibitory surface receptors recognizing their ligands on transformed cells. Modulation of NK numbers and/or function by a variety of agents such as cytokines and monoclonal antibodies may result in enhanced anti-tumor activity. Recombinant cytokines (i.e., IL-15 and IL-2), antibodies blocking inhibitory receptors (i.e., KIR, NKG2A and TIGIT) and agonists delivering signals via CD137, NKG2D and CD16 stand out as the most suitable opportunities. These agents can be used to potentiate NKcell- mediated antibody-dependent cellular cytotoxicity (ADCC) against antibody-coated tumor cells, offering potential for multiple combinatorial immunotherapy strategies against cancer.



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Global and local investigations of the electrochemical behavior the T6 heat treated Mg–Zn–RE magnesium alloy thixo-cast

Publication date: 31 May 2017
Source:Applied Surface Science, Volume 405
Author(s): Zbigniew Szklarz, Magdalena Bisztyga, Halina Krawiec, Lidia Lityńska-Dobrzyńska, Łukasz Rogal
The influence of semi-solid metal processing (SSM called also as thixoforming) of ZE41A magnesium alloy on the electrochemical behavior in 0.1M NaCl solution was investigated. To describe the corrosion behavior of ZE41A alloy, the electrochemical measurements were conducted in global and local scale for two types of specimens: (1) ingot-feedstock, (2) specimen after thixoforming and T6 treatment. The heat treatment and thixoforming significantly improved mechanical properties of ZE41A alloy. The global corrosion potential is slightly higher for treated sample what is related to the presence of Zr–Zn nanoparticles distributed in solid solution. The corrosion behavior differences between feedstock and thixo-cast after T6 samples are also visible in local scale, what has been revealed by using microcapillary technique. However there is no improvement in corrosion behavior after treatment. Corrosion morphology of the treated sample indicate higher susceptibility to pitting and filiform corrosion. Corrosion rate is also slightly higher.



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Fluid origin and migration of the Huangshaping W–Mo polymetallic deposit, South China: Geochemistry and 40Ar/39Ar geochronology of hydrothermal K-feldspars

Publication date: June 2017
Source:Ore Geology Reviews, Volume 86
Author(s): Huan Li, Kotaro Yonezu, Koichiro Watanabe, Thomas Tindell
The Huangshaping deposit is a world-class W–Mo–Pb–Zn–Cu polymetallic deposit that formed during the Jurassic magmatic event in the central Nanling region, South China. In order to reveal the three-dimensional development of mineralization and alteration in this complicated fluid-rock system, four typical hydrothermal K-feldspar samples were collected from potassic alteration zones at different elevation levels around main W–Mo ore bodies, followed by precise trace element analysis and 40Ar/39Ar dating. The results show that these K-feldspars have a pronounced lanthanide tetrad effect with high contents of Ga, Ta, Nb, U, Y and HREE but low concentrations of Ba, Sr, Eu and Zr, suggesting a hydrothermal origin. Additionally, correlation between the Ca/Cl/K ratios and the apparent ages suggest that metasomatic fluids played an important role in the formation of the hydrothermal K-feldspars. The plateau 40Ar/39Ar ages which represent the timing of potassic alteration vary from 152.9±0.5 to 154.3±0.6Ma, spatially showing younger trends from north to south and from shallow to deep. These dates correspond to the previous published molybdenite Re–Os data variations in different elevation levels, which record the mineralization event with relatively older ages ranging from 153.8 to 159.4Ma. Combined with the spatial relation analysis among samples, the fluid migration rates associated with the mineralization and alteration are calculated at 10–100mMa−1. Thus, we propose a fluid downward migration model for the Huangshaping polymetallic deposit.

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Hydrogenolysis of glycerol over Ni, Cu, Zn, and Zr supported on H-beta

Publication date: 1 June 2017
Source:Chemical Engineering Journal, Volume 317
Author(s): Amit Kant, Yingxin He, Abbas Jawad, Xin Li, Fateme Rezaei, Joseph D. Smith, Ali A. Rownaghi
A series of transition metal oxides (e.g., Ni, Cu, Zn, and Zr) were supported on H-beta with loading of 5–20wt% via wet impregnation. These catalysts were evaluated in the hydrogenolysis of glycerol under aqueous conditions at different reaction temperatures (150–250°C), times (5–15h) and H2 pressures (300–1200psi). The results from characterization of materials by XRD, FT-IR, N2 sorption and NH3-TPD together with the results from the activity test allowed further understanding of the role of transition metals and acid sites on hydrogenolysis of glycerol. The H-beta was found to contain higher Brønsted acidity and catalyst activity compared to those supported metal catalysts. It was found that the acidic properties of the H-Beta zeolite and metal content play a significant role on the final product distribution. The major product over bare H-beta and Zr/H-beta was 1-proponal, while the concentration of 1,2-propanediol and 1,3-propanediol increased significantly by the incorporation of a second metal oxide. A high 1,3-propanediol selectivity of 14% was obtained over the H-beta supported Ni-Zr catalyst at 73% glycerol conversion. The selectivity of 1,2-propanediol and 1,3-propanediol were decreased at higher reaction temperature and time.

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Alzheimer's disease neuropathologic change, Lewy body disease, and vascular brain injury in clinic- and community-based samples

Publication date: May 2017
Source:Neurobiology of Aging, Volume 53
Author(s): Willa D. Brenowitz, C. Dirk Keene, Stephen E. Hawes, Rebecca A. Hubbard, W.T. Longstreth, Randy L. Woltjer, Paul K. Crane, Eric B. Larson, Walter A. Kukull
We examined the relationships between Alzheimer's disease neuropathologic change (ADNC), Lewy body disease (LBD), and vascular brain injury (VBI) in 2 large autopsy samples. Because findings may differ between study populations, data came from U.S. Alzheimer's Disease Centers contributing to the National Alzheimer's Coordinating Center (n = 2742) and from the population-based Adult Changes in Thought study (n = 499). Regardless of study population, over 50% of participants with ADNC had co-occurring LBD or VBI; the majority of whom had a clinical AD dementia diagnosis prior to death. Overlap of pathologies was similar between studies, especially after standardizing to the distribution of age and dementia status in the Adult Changes in Thought population. LBD, but not VBI, was positively associated with ADNC in both studies. Interestingly, cortical LBD was more common in those with intermediate ADNC compared to low or high ADNC, especially in the National Alzheimer's Coordinating Center (p < 0.001). High prevalence of co-occurring neuropathologies among older adults with dementia has implications for accurate diagnosis of dementia etiologies and development of disease-modifying strategies.



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Hormone deprivation alters mitochondrial function and lipid profile in the hippocampus

Mitochondrial dysfunction is a common hallmark in aging. In the female, reproductive senescence is characterized by loss of ovarian hormones, many of whose neuroprotective effects converge upon mitochondria. The functional integrity of mitochondria is dependent on membrane fatty acid and phospholipid composition, which are also affected during aging. The effect of long-term ovarian hormone deprivation upon mitochondrial function and its putative association with changes in mitochondrial membrane lipid profile in the hippocampus, an area primarily affected during aging and highly responsive to ovarian hormones, is unknown. To this aim, Wistar adult female rats were ovariectomized or sham-operated. Twelve weeks later, different parameters of mitochondrial function (O2 uptake, ATP production, membrane potential and respiratory complex activities) as well as membrane phospholipid content and composition were evaluated in hippocampal mitochondria. Chronic ovariectomy reduced mitochondrial O2 uptake and ATP production rates and induced membrane depolarization during active respiration without altering the activity of respiratory complexes. Mitochondrial membrane lipid profile showed no changes in cholesterol levels but higher levels of unsaturated fatty acids and a higher peroxidizability index in mitochondria from ovariectomized rats. Interestingly, ovariectomy also reduced cardiolipin content and altered cardiolipin fatty acid profile leading to a lower peroxidizability index. In conclusion, chronic ovarian hormone deprivation induces mitochondrial dysfunction and changes in the mitochondrial membrane lipid profile comparable to an aging phenotype. Our study provides insights into ovarian hormone loss-induced early lipidomic changes with bioenergetic deficits in the hippocampus that may contribute to the increased risk of Alzheimer's disease and other age-associated disorders observed in postmenopause.



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A putative role for anti-Mullerian hormone (AMH) in optimising ovarian reserve expenditure

The mammalian ovary has a finite supply of oocytes, which are contained within primordial follicles where they are arrested in a dormant state. The number of primordial follicles in the ovary at puberty is highly variable between females of the same species. Females that enter puberty with a small ovarian reserve are at risk of a shorter reproductive lifespan, as their ovarian reserve is expected to be depleted faster. One of the roles of anti-Müllerian hormone (AMH) is to inhibit primordial follicle activation, which slows the rate at which the ovarian reserve is depleted. A simple interpretation is that the function of AMH is to conserve ovarian reserve. However, the females with the lowest ovarian reserve and the greatest risk of early reserve depletion have the lowest levels of AMH. In contrast, AMH apparently strongly inhibits primordial follicle activation in females with ample ovarian reserve, for reasons that remain unexplained. The rate of primordial follicle activation determines the size of the developing follicle pool, which in turn, determines how many oocytes are available to be selected for ovulation. This review discusses the evidence that AMH regulates the size of the developing follicle pool by altering the rate of primordial follicle activation in a context-dependent manner. The expression patterns of AMH across life are also consistent with changing requirements for primordial follicle activation in the ageing ovary. A potential role of AMH in the fertility of ageing females is proposed herein.



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Mechanisms for PACAP-induced prolactin gene expression in grass carp pituitary cells

In mammals, pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic hormone with diverse functions but its role in prolactin (PRL) regulation is highly controversial. To shed light on Prl regulation by PACAP in fish model, grass carp pituitary cells was used as a model to examine the receptor specificity and signal transduction for PACAP modulation of prl gene expression in the carp pituitary. Using RT-PCR, PACAP-selective PAC1 receptor was detected in carp lactotrophs. In carp pituitary cells, nanomolar doses of PACAP, but not VIP, could elevate Prl secretion and protein production with concurrent rise in prl mRNA and these stimulatory effects were blocked by PACAP antagonist but not VIP antagonist. PACAP-induced prl mRNA expression could be mimicked by activating adenylate cyclase (AC), increasing cAMP level by cAMP analog, or increasing intracellular Ca2+ ([Ca2+]i) by Ca2+ ionophore/voltage-sensitive Ca2+ channel (VSCC) activator. PACAP-induced prl gene expression, however, was attenuated/abolished by suppressing cAMP production, inhibiting PKA activity, blocking [Ca2+]i mobilization and VSCC activation, calmodulin (CaM) antagonism, and inactivation of JNK and CaM Kinase II (CaMK-II). Similar sensitivity to CaM, JNK, and CaMK-II blockade was also noted by substituting cAMP analog for PACAP as the stimulant for prl mRNA expression. These results, as a whole, provide evidence for the first time that (i) PACAP activation of PAC1 receptor expressed in carp lactotrophs could induce Prl synthesis and secretion, and (ii) Prl production induced by PACAP was mediated by upregulation of prl gene expression, presumably via functional coupling of cAMP/PKA-, Ca2+/CaM-, and MAPK-dependent cascades.



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Reduced metabolism in the hypothalamus of the anorectic anx/anx mouse

The anorectic anx/anx mouse exhibits a mitochondrial complex I dysfunction that is related to aberrant expression of hypothalamic neuropeptides and transmitters regulating food intake. Hypothalamic activity, i.e. neuronal firing and transmitter release, is dependent on glucose utilization and energy metabolism. To better understand the role of hypothalamic activity in anorexia, we assessed carbohydrate and high-energy phosphate metabolism, in vivo and in vitro, in the anx/anx hypothalamus. In the fasted state, hypothalamic glucose uptake in the anx/anx mouse was reduced by ~50% of that seen in wild-type (wt) mice (P < 0.05). Under basal conditions, anx/anx hypothalamus ATP and glucose 6-P contents were similar to those in wt hypothalamus, whereas phosphocreatine was elevated (~2-fold; P < 0.001) and lactate was reduced (~35%; P < 0.001). The anx/anx hypothalamus had elevated total AMPK (~25%; P < 0.05) and GLUT4 (~60%; P < 0.01) protein contents, whereas GLUT1 and GLUT3 were similar to that of wt hypothalamus. Interestingly, the activation state of AMPK (ratio of phosphorylated AMPK/total AMPK) was significantly decreased in hypothalamus of the anx/anx mouse (~60% of that in wt; P < 0.05). Finally, during metabolic stress (ischemia), accumulation of lactate (measure of glycolysis) and IMP and AMP (breakdown products of ATP) were ~50% lower in anx/anx vs wt hypothalamus. These data demonstrate that carbohydrate and high-energy phosphate utilization in the anx/anx hypothalamus are diminished under basal and stress conditions. The decrease in hypothalamic metabolism may contribute to the anorectic behavior of the anx/anx mouse, i.e. its inability to regulate food intake in accordance with energy status.



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Tissue thyroid hormone metabolism is differentially regulated during illness in mice

Illness induces major modifications in central and peripheral thyroid hormone (TH) metabolism, so-called nonthyroidal illness syndrome (NTIS). As a result, organ-specific changes in local TH availability occur depending on the type and severity of illness. Local TH availability is of importance for the regulation of the tissue-specific TH target genes and determined by the interplay between deiodinating enzymes, TH transport and TH receptor (TR) expression. In the present study, we evaluated changes in TH transport, deiodination and TR expression, the resulting tissue TH concentrations and the expression of TH target genes in liver and muscle in three animal models of illness. We induced (1) acute systemic inflammation by intraperitoneal injection of bacterial endotoxin (LPS), (2) chronic local inflammation by a turpentine injection in the hind limb and (3) severe pneumonia and sepsis by intranasal inoculation with Streptococcus pneumoniae. We found that all aspects of peripheral TH metabolism are differentially regulated during illness, depending on the organ studied and severity of illness. In addition, tissue TH concentrations are not equally affected by the decrease in serum TH concentrations. For example, the decrease in muscle TH concentrations is less severe than the decrease observed in liver. In addition, despite lower TH concentrations in muscle in all three models, muscle T3 action is differentially affected. These observations help to understand the complex nature of the nonthyroidal illness syndrome.



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Skeletal muscle insulin resistance: role of mitochondria and other ROS sources

At present, obesity is one of the most important public health problems in the world because it causes several diseases and reduces life expectancy. Although it is well known that insulin resistance plays a pivotal role in the development of type 2 diabetes mellitus (the more frequent disease in obese people) the link between obesity and insulin resistance is yet a matter of debate. One of the most deleterious effects of obesity is the deposition of lipids in non-adipose tissues when the capacity of adipose tissue is overwhelmed. During the last decade, reduced mitochondrial function has been considered as an important contributor to 'toxic' lipid metabolite accumulation and consequent insulin resistance. More recent reports suggest that mitochondrial dysfunction is not an early event in the development of insulin resistance, but rather a complication of the hyperlipidemia-induced reactive oxygen species (ROS) production in skeletal muscle, which might promote mitochondrial alterations, lipid accumulation and inhibition of insulin action. Here, we review the literature dealing with the mitochondria-centered mechanisms proposed to explain the onset of obesity-linked IR in skeletal muscle. We conclude that the different pathways leading to insulin resistance may act synergistically because ROS production by mitochondria and other sources can result in mitochondrial dysfunction, which in turn can further increase ROS production leading to the establishment of a harmful positive feedback loop.



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High fat feeding unmasks variable insulin responses in male C57BL/6 mouse substrains

Mouse models are widely used for elucidating mechanisms underlying type 2 diabetes. Genetic background profoundly affects metabolic phenotype; therefore, selecting the appropriate model is critical. Although variability in metabolic responses between mouse strains is now well recognized, it also occurs within C57BL/6 mice, of which several substrains exist. This within-strain variability is poorly understood and could emanate from genetic and/or environmental differences. To better define the within-strain variability, we performed the first comprehensive comparison of insulin secretion from C57BL/6 substrains 6J, 6JWehi, 6NJ, 6NHsd, 6NTac and 6NCrl. In vitro, glucose-stimulated insulin secretion correlated with Nnt mutation status, wherein responses were uniformly lower in islets from C57BL/6J vs C57BL/6N mice. In contrast, in vivo insulin responses after 18 weeks of low fat feeding showed no differences among any of the six substrains. When challenged with a high-fat diet for 18 weeks, C57BL/6J substrains responded with a similar increase in insulin release. However, variability was evident among C57BL/6N substrains. Strikingly, 6NJ mice showed no increase in insulin release after high fat feeding, contributing to the ensuing hyperglycemia. The variability in insulin responses among high-fat-fed C57BL/6N mice could not be explained by differences in insulin sensitivity, body weight, food intake or beta-cell area. Rather, as yet unidentified genetic and/or environmental factor(s) are likely contributors. Together, our findings emphasize that caution should be exercised in extrapolating data from in vitro studies to the in vivo situation and inform on selecting the appropriate C57BL/6 substrain for metabolic studies.



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Four Cases of Pediatric Deep-Seated/Subcutaneous Pyogenic Granuloma: Review of Literature and Differential Diagnosis

ABSTRACT

Background

Pyogenic granulomas are benign, reactive, typically superficial vascular lesions that can be idiopathic or arise secondary to trauma, underlying vascular malformations, infections, physiologic or pathologic endocrine changes, and hormone therapy. Deep-seated/subcutaneous pyogenic granulomas (DSPG) are rarely seen in any age group. Pediatric DSPGs can be a clinical and pathologic challenge because these lesions mimic other vascular lesions, including kaposiform hemangioendothelioma, infantile hemangiomas, and vascular malformations.

Methods

Retrospective search of DSPG excised at Cincinnati Children's Hospital Medical center between June 2010 and June 2011 was conducted. Clinical information was obtained from patient charts and histologic slides were retrieved and reviewed.

Results

Of the 106 cases of pyogenic granuloma, four (3.8%) were diagnosed as DSPG. We report the details of those four cases and compare them to the other pediatric DSPG cases reported in the literature. We also review the histologic differential diagnosis of DSPG in pediatric population.

Conclusion

Our results suggest that these lesions may not be as rare as inferred by literature, but, rather, underdiagnosed.



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Looking back and to the future: Are we improving ‘cure’ in non-small cell lung cancer?

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Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): David Walder, Mary O'Brien
In surgical series, cancer-free survival at 5 years is often referred to as a cure. In recent years, attempts to improve cure rates in non-small cell lung cancer (NSCLC) have focussed on earlier diagnosis through cost-effective screening programs. Systemic therapies have historically added only a small benefit to overall survival in both the adjuvant and palliative setting. However, in the last two decades, the development of new treatment options has added incremental improvements in NSCLC survival rates. Patients with a targetable sensitising mutation including epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase rearrangements have significantly better prognosis, and many will survive beyond 5 years. Immunotherapy is an effective treatment in selected patients with NSCLC and is set to cause another leap in 5 year survival rates. Although these patients are not free from disease, survival at 5 years may become the more important end-point as NSCLC becomes seen as a chronic oncological disease.



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Surgically treated oesophageal cancer developed in a radiated field: Impact on peri-operative and long-term outcomes

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Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Sheraz R. Markar, Caroline Gronnier, Arnaud Pasquer, Alain Duhamel, Hélène Behal, Jérémie Théreaux, Johan Gagnière, Gil Lebreton, Cécile Brigand, Bernard Meunier, Denis Collet, Christophe Mariette
BackgroundThe objectives of this study were to compare peri-operative and long-term outcomes from oesophageal cancer (EC) (i) that arose in a previously radiated field (ECRF) versus primary (PEC) and among ECRF patients and (ii) radiotherapy-induced (RIEC) versus non-radiotherapy–induced EC (NRIEC).MethodsData were collected from 30 European centres from 2000 to 2010. Two thousand four hundred eighty nine EC patients surgically treated were included in the PEC group and 136 in the ECRF group, NRIEC group (n = 61) and RIEC group (n = 75). Propensity score matching analyses were used to compensate for differences in baseline characteristics.ResultsCompared to the PEC group, the ECRF group was characterised by less use of neoadjuvant chemoradiotherapy (0% versus 29.5%; P < 0.001), less pathological stage III/IV (31.6% versus 39.2%, P = 0.036), greater incidence of R1/2 margins (21.3% versus 10.9%; P < 0.001), increased in-hospital mortality (14.0% versus 7.1%; P = 0.003) and overall morbidity (68.4% versus 56.4%, P = 0.006). After matching, 5-year overall (28.8% versus 50.5%; hazard ratio [HR] = 1.53, 95% confidence interval [CI]: 1.15–2.04; P = 0.003) and event-free (32.2% versus 42.5%; HR = 1.56, 95% CI: 1.18–2.05; P = 0.002) survivals were significantly reduced in the ECRF group. There were no significant differences in incidence or pattern of tumour recurrence. Comparing RIEC and NRIEC groups, there were no significant differences in short- or long-term outcomes before and after matching.ConclusionsECRF is associated with poorer long-term survival related to a reduced utilisation of neoadjuvant chemoradiotherapy and an increased incidence of tumour margin involvement at surgery. Outcomes appear to be dictated by the limitations related to previous radiotherapy administration more than the radiotherapy-induced carcinogenesis.



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Survival of patients with melanoma brain metastasis treated with stereotactic radiosurgery and active systemic drug therapies

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Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Ee Siang Choong, Serigne Lo, Martin Drummond, Gerald B. Fogarty, Alexander M. Menzies, Alexander Guminski, Brindha Shivalingam, Kathryn Clarke, Georgina V. Long, Angela M. Hong
IntroductionWith new systemic therapies demonstrating activity in melanoma brain metastasis, most of the previously reported stereotactic radiosurgery (SRS) data are superseded. In this study, we report the outcomes (overall survival [OS] and brain control [BC]) and identify factors that associate with such outcomes in the era of modern systemic therapy.MethodA total of 108 patients treated with SRS from 2010 to 2015 were included. Systemic treatment use within 6 weeks of SRS was noted. OS was defined as time from SRS to death or last follow-up, and BC was defined as absence of any active intracranial disease during follow-up. Univariate and multivariate Cox proportional hazard analyses were performed on clinico-pathological prognostic features associated with OS and BC.ResultsThe median age was 64.3 years, and the median follow-up was 8.6 months. Seventy-nine (73.1%) patients received systemic treatment. The median OS were as follows: anti-CTLA4 – 7.5 months (95% CI: 4.4–15.6), anti-PD1 – 20.4 months (95% CI: 8.8 – N/A) and BRAF inhibitor (BRAFi) ± MEK inhibitor (MEKi) – 17.8 months (95% CI: 11.8 – N/A). Median BC was as follows: anti-CTLA4 – 7.5 months (95% CI: 4.0–15.6), anti-PD1 – 12.7 months (95% CI: 5.5 – N/A) and BRAFi ± MEKi – 12.7 months (95% CI: 8.3–18.5). In multivariate analysis, age and type of systemic therapy were strongly associated with OS. Age, Eastern Cooperative Oncology Group performance status, Graded Prognostic Assessment (GPA) score, and presence of symptoms were associated with BC.ConclusionsFavourable outcomes are seen in patients treated with SRS and with the best survival seen in patients treated with anti-PD1. Known independent prognostic factors for survival such as age and performance status and GPA score remain relevant in this setting.



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The number of extranodal sites assessed by PET/CT scan is a powerful predictor of CNS relapse for patients with diffuse large B-cell lymphoma: An international multicenter study of 1532 patients treated with chemoimmunotherapy

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Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Tarec Christoffer El-Galaly, Diego Villa, Thomas Yssing Michaelsen, Martin Hutchings, Nabegh George Mikhaeel, Kerry J. Savage, Laurie H. Sehn, Sally Barrington, Jakob W. Hansen, Daniel Smith, Kirsty Rady, Karen J. Mylam, Thomas S. Larsen, Staffan Holmberg, Maja B. Juul, Sabrina Cordua, Michael R. Clausen, Kristina B. Jensen, Hans E. Johnsen, John F. Seymour, Joseph M. Connors, Peter de Nully Brown, Martin Bøgsted, Chan Y. Cheah
PurposeDevelopment of secondary central nervous system involvement (SCNS) in patients with diffuse large B-cell lymphoma is associated with poor outcomes. The CNS International Prognostic Index (CNS-IPI) has been proposed for identifying patients at greatest risk, but the optimal model is unknown.MethodsWe retrospectively analysed patients with diffuse large B-cell lymphoma diagnosed between 2001 and 2013, staged with PET/CT and treated with R-CHOP(-like) regimens. Baseline clinicopathologic characteristics, treatments, and outcome data were collected from clinical databases and medical files. We evaluated the association between candidate prognostic factors and modelled different risk models for predicting SCNS.ResultsOf 1532 patients, 62 (4%) subsequently developed SCNS. By multivariate analysis, disease stage III/IV, elevated serum LDH, kidney/adrenal and uterine/testicular involvement were independently associated with SCNS. There was a strong correlation between absolute number of extranodal sites and risk of SCNS; the 144 patients (9%) with >2 extranodal sites had a 3-year cumulative incidence of SCNS of 15.2% (95% confidence interval [CI] 9.2–21.2%) compared with 2.6% (95% CI 1.7–3.5) among those with ≤2 sites (P < 0.001). The 3-year cumulative risks of SCNS for CNS-IPI defined risk groups were 11.2%, 3.1% and 0.4% for high-, intermediate- and low-risk patients, respectively. All risk models analysed had high negative predictive values, but only modest positive predictive values.ConclusionsPatients with >2 extranodal sites or high-risk disease according to the CNS-IPI should be considered for baseline CNS staging. Clinical risk prediction models suffer from limited positive predictive ability, highlighting the need for more sensitive biomarkers to identify patients at highest risk of this devastating complication.



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Does axillary lymph node dissection impact survival in patients with breast cancer and isolated tumour cells or micrometastasis in sentinel node?

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Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): Mina M.G. Youssef, Diane Cameron, Sisse Olsen, Douglas Ferguson




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Letter to the Editor regarding the paper by Park et al., Extra-gain of HER2-positive cases through HER2 reassessment in primary and metastatic sites in advanced gastric cancer with initially HER2-negative primary tumours: Results of GASTric cancer HER2 reassessment study 1 (GASTHER1)

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Publication date: April 2017
Source:European Journal of Cancer, Volume 75
Author(s): A. Ieni, G. Angelico, P. Zeppa, G. Tuccari




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Knowledge, attitude, and practice towards ergonomics among undergraduates of Faculty of Dentistry, Tanta University, Egypt

Abstract

Ergonomics is the scientific study of people and their working environment. Dentistry is a profession that generally produces various musculoskeletal disorders. If ergonomic principles are applied in the field of dentistry, it helps to prevent occupational ergonomic health hazards and provides more comfort to the dentist and patient. To assess knowledge, attitudes, and practice of ergonomics during routine dental procedures among undergraduates of Faculty of Dentistry, Tanta University, cross-sectional study was conducted among dental students of Tanta University during the year 2015–2016 using a predesigned selfadministered questionnaire. Knowledge, attitude, and practice were assessed by 16, 5, and 6 questions, respectively. The study included 479 dental students, of them, 291 (60.8%) were females, 359 (74.9%) were from urban areas, and 359 students (74.9%) were 22 years old and below. Only one quarter of the students had good knowledge whereas nearly half of the students (48.9%) had fair knowledge concerning ergonomics. Out of the participants, 84.8% had positive attitudes and 95.4% had poor practice of ergonomics. Only 48.9% of the studied students had fair knowledge regarding ergonomics; also 5% only of students practice it. But about 84.8% of students have a positive attitude towards studying ergonomics. Dental students need to ensure involving ergonomics in the routine dental practice. This may be achieved via addition of ergonomics in their curriculum.



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Effects of straw and biochar amendments on aggregate stability, soil organic carbon, and enzyme activities in the Loess Plateau, China

Abstract

Soil from the Loess Plateau of China is typically low in organic carbon and generally has poor aggregate stability. Application of organic amendments to these soils could help to increase and sustain soil organic matter levels and thus to enhance soil aggregate stability. A field experiment was carried out to evaluate the effect of the application of wheat straw and wheat straw-derived biochar (pyrolyzed at 350–550 °C) amendments on soil aggregate stability, soil organic carbon (SOC), and enzyme activities in a representative Chinese Loess soil during summer maize and winter wheat growing season from 2013 to 2015. Five treatments were set up as follows: no fertilization (CK), application of inorganic fertilizer (N), wheat straw applied at 8 t ha−1 with inorganic fertilizer (S8), and wheat straw-derived biochar applied at 8 t ha−1 (B8) and 16 t ha−1 (B16) with inorganic fertilizer, respectively. Compared to the N treatment, straw and straw-derived biochar amendments significantly increased SOC (by 33.7–79.6%), microbial biomass carbon (by 18.9–46.5%), and microbial biomass nitrogen (by 8.3–38.2%), while total nitrogen (TN) only increased significantly in the B16 plot (by 24.1%). The 8 t ha−1 straw and biochar applications had no significant effects on soil aggregation, but a significant increase in soil macro-aggregates (>2 mm) (by 105.8%) was observed in the B16 treatment. The concentrations of aggregate-associated SOC increased by 40.4–105.8% in macro-aggregates (>2 mm) under straw and biochar amendments relative to the N treatment. No significant differences in invertase and alkaline phosphatase activity were detected among different treatments. However, urease activity was greater in the biochar treatment than the straw treatment, indicating that biochar amendment improved the transformation of nitrogen in the soil. The carbon pool index and carbon management index were increased with straw and biochar amendments, especially in the B16 treatment. In conclusion, application of carbonized crop residue as biochar, especially at a rate of 16 t ha−1, could be a potential solution to recover the depleted SOC and enhance the formation of macro-aggregates in Loess Plateau soils of China.



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Effects on heavy metal accumulation in freshwater fishes: species, tissues, and sizes

Abstract

Three fish species (Carassius auratus, Pelteobagrus fulvidraco, and Squaliobarbus curriculus) were collected from Xiang River near Changsha City, Southern China. The concentrations of heavy metals including arsenic (As), cadmium (Cd), copper (Cu), iron (Fe), manganese (Mn), lead (Pb), and zinc (Zn) in the muscle, gill, and liver of three species were determined by the inductively coupled plasma mass spectrometry method. One-way analysis of variance (ANOVA) was introduced to determine the significant variations (p < 0.05) of heavy metals. Livers were found to accumulate Cd and Cu due to the metallothionein proteins. High levels of Mn and Pb in the gills indicated that the main uptake pathway of these heavy metals was from the water. The carnivorous species, P. fulvidraco, was found to accumulate the highest levels of toxic elements (As, Cd, and Pb), while relatively high concentrations of nutrient elements (Cu, Fe, Mn, and Zn) were accumulated in omnivorous species (C. auratus and S. curriculus). According to the results of Pearson's correlation analysis, there were few significant relationships at p < 0.01 level between the concentrations of the analyzed elements and the fish sizes. The results of risk assessment indicated that exposure to the toxic heavy metals from fish muscle consumption posed no non-carcinogenic health risk to local inhabitants.



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Mechanical ventilator as a major cause of infection and drug resistance in intensive care unit

Abstract

Ventilator-associated pneumonia (VAP) is the most frequent infection in intensive care units (ICU). It is associated with high rates of long morbidity and mortality. Management of a case of VAP is often said to add $40,000 to hospital costs USA. All these data directed our interest to study the etiology, risk factors, and antibiotic susceptibility patterns of VAP in ICU of Tanta University Hospital. This study included 36 cases of VAP. Endotracheal aspirates were obtained from all cases and microbiologically analyzed. Samples were collected over 1 year. Forty-two strains were isolated from 28 cases, while eight cases showed no bacterial growth. The most frequent organism was Staphylococcus aureus (30.95%), followed by Acinetobacter baumannii and Pseudomonas aeruginosa (21.43% for each), and the least common was Staphylococcus epidermidis (2.38%). Multi-drug resistance was detected in (50%) of the isolated bacteria in this study. Imipenem, amikacin, linezolid, vancomycin, and levofloxacin are recommended to be the most effective drugs in management of VAP. VAP is a serious problem in ICU carrying many risks for the patient live. Regimens of empirical treatment should take in consideration the update in the bacterial etiology and antibiotic susceptibility patterns of VAP.



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Interactional effect of cerium and manganese on NO catalytic oxidation

Abstract

To preferably catalyze the oxidation of NO to NO2 in diesel after-treatment system, a series of CeO2-MnOx composite oxides was supported on silica-alumina material by the co-impregnation method. The maximum conversion of NO of the catalyst with a Ce/Mn weight ratio of 5:5 was improved by around 40%, compared to the supported manganese-only or cerium-only sample. And its maximum reaction rate was 0.056 μmol g−1 s−1 at 250 °C at the gas hourly space velocity of 30,000 h−1. The experimental results suggested that Ce-Mn solid solution was formed, which could modulate the valence state of cerium and manganese and exhibit great redox properties. Moreover, the strong interaction between ceria and manganese resulted in the largest desorption amount of strong chemical oxygen and oxygen vacancies, leading to the maximum Oα area ratio of 62.26% from the O 1s result. These effective oxygen species could be continually transferred to the surface, leading to the best NO catalytic activity of 5Ce5Mn/SA catalyst.

Graphical abstract


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Photooxidation of herbicide amitrole in the presence of fulvic acid

Abstract

Fulvic acid (Henan ChangSheng Corporation) photoinduced degradation of non-UVA-absorbing herbicide amitrole (3-amino-1,2,4-triazole, AMT) as a way for its removal from polluted water was investigated in details. It was shown that the main primary species generated by fulvic acid under UVA radiation, triplet state and hydrated electron, are not directly involved in the herbicide degradation. AMT decays in reactions with secondary intermediates, reactive oxygen species, formed in reactions of the primary ones with dissolved oxygen. Singlet oxygen is responsible for 80% of herbicide oxidation, and OH and O2−• radicals—for the remaining 20% of AMT. It was found that quantum yield of AMT photodegradation (ϕ 365nm) decreases linearly from 2.2 × 10−3 to 1.2 × 10−3 with the increase of fulvic acid concentration from 1.1 to 30 mg L−1. On the contrary, the increase of AMT concentration from 0.8 to 25 mg L−1 leads to practically linear growth of ϕ 365nm value from 1.8 × 10−4 to 4 × 10−3. Thus, the fulvic acid exhibits a good potential as UVA photooxidizer of organic pollutants sensitive to the singlet oxygen (ϕ 532nm(1O2) = 0.025 at pH 6.5).



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Research on magnetic separation for complex nickel deep removal and magnetic seed recycling

Abstract

This study investigated the deep removal of complex nickel from simulated wastewater using magnetic separation and magnetic seed recycling. Nano-magnetite (Fe3O4) was used as the magnetic seed. The flocculant applied was N,N-bis-(dithiocarboxy) ethanediamine (EDTC), a highly efficient heavy metal chelating agent included in dithiocarbamate (DTC). Important investigated parameters included hydraulic retention time, magnetic seed dosage, and magnetic field strength. The study also explored the magnetic flocculation mechanism involved in the reaction. The result indicated that the residual Ni concentration was reduced to less than 0.1 mg/L from the initial concentration of 50 mg/L under optimal conditions. Magnetic seed recovery reached 76.42% after a 3-h stirring period; recycled magnetic seeds were analyzed using scanning electron microscope (SEM) and X-ray diffraction (XRD). The zeta potential results illustrated that magnetic seeds firmly combined with flocs when the pH ranged from 6.5 to 7.5 due to the electrostatic attraction. When the pH was less than 7, magnetic seeds and EDTC were also combined due to electrostatic attraction. Particle size did affect microfloc size; it decreased microfloc size and increased floc volume through magnetic seed loading. The effective binding sites between flocs and magnetic seeds increased when adding the magnetic seeds. This led the majority of magnetic flocs to be integrated with the magnetic seeds, which served as a nucleus to enhance the flocculation property and ultimately improve the nickel complex removal rate.



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The effects of endophytic bacterium SaMR12 on Sedum alfredii Hance metal ion uptake and the expression of three transporter family genes after cadmium exposure

Abstract

A hydroponic experiment was conducted to investigate the effects of an endophytic bacterium SaMR12 on Sedum alfredii Hance metal ion accumulation, chlorophyll concentration, and the expression of three metal transporter families, zinc-regulated transporters, iron-regulated transporter-like protein (ZIP); natural resistance-associated macrophage protein; and heavy metal ATPase (HMA) at different Cd treatment levels. The results showed that at relatively low Cd conditions (≤25 μM), SaMR12 demonstrated a 19.5–27.5% increase in Fe, a 46.7–90.7% increase in Zn, and a 7.9–43.7% increase in Cu content in the shoot and elevated expression of SaIRT1, SaZIP3, SaHMA2, and SaNramp3 in the shoot and SaZIP1, SaHMA2, SaNramp1, and SaNramp3 in the root. At high Cd conditions (100 and 400 μM), SaMR12 demonstrated a 16.4–18.5% increase in leaf chlorophyll concentration, a 18.9–23.2% increase in Fe, and a 15.4–17.5% increase in Mg content in the shoot and elevated expression of SaZIP3, SaNramp6, SaHMA2, and SaHMA3 in the shoot and SaZIP3, SaNarmp1, SaNarmp3, and SaNarmp6 in the root. These results indicated that SaMR12 can elevate essential metal ion uptake and regulate the expression of transport genes to promote plant growth and enhance Cd tolerance and uptake to improve Cd accumulation up to 118–130%.



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Association of urinary cadmium with risk of diabetes: a meta-analysis

Abstract

The association between urinary cadmium and diabetes risk remains controversial. PubMed, Web of Science, China National Knowledge Infrastructure, and Wanfang Data updated on 21 June 2016 were searched for eligible publications. Pooled odds ratio (OR) with 95% confidence interval (CI) of diabetes for highest versus lowest level of urinary cadmium was calculated by using fixed-effect model or random-effect model. Dose-response relationship between urinary cadmium and diabetes was estimated by restricted cubic spline. A total of nine studies with 28,691 participants were included in this meta-analysis. The pooled OR of diabetes for the highest versus lowest level of urinary cadmium was 1.02 (95% CI, 1.00, 1.05; I 2 = 42.3%). In subgroup analysis, the ORs were 1.02 (95% CI 1.00, 1.05; I 2 = 0.9%) for studies conducted in Asia and 1.11 (95% CI 0.88, 1.41; I 2 = 86.3%) in America. For dose-response analysis, a linear relationship was found between urinary cadmium and the risk of diabetes (P for nonlinear = 0.5856). For every l μg/g creatinine increment of urinary cadmium, the risk of diabetes increased by 16% (1.16, 95% CI 1.08, 1.25). This meta-analysis suggests that cadmium exposure might be significantly associated with prevalence of diabetes, but large prospective studies are needed to confirm this finding.



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Advanced treatment of municipal secondary effluent by catalytic ozonation using Fe 3 O 4 -CeO 2 /MWCNTs as efficient catalyst

Abstract

The advanced treatment of municipal secondary effluent was performed by catalytic ozonation using Fe3O4-CeO2/MWCNTs as catalyst. The experimental results showed that in catalytic ozonation system, the removal efficiency of soluble COD was more than 46% after 30 min reaction, and about 36% of effluent organic matters (EfOMs) were mineralized, which was four times higher than that in single ozonation system. Moreover, proteins, humic acids, and UV254 decreased obviously after 30 min reaction, but polysaccharides did not significantly decrease. In catalytic ozonation system, the ozone utilization increased, which is favorable for the degradation of EfOM. The organic compounds and alkalinity were the main hydroxyl radical consumers in municipal secondary effluent. The catalytic ozonation process was also effective for the degradation of two target micropollutants (sulfamethazine and carbamazepine). The catalyst could be stable after five-time reuse for catalytic ozonation of effluent.



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Mercury health risk assessment among a young adult Lebanese population

Abstract

Mercury (Hg) exposure represents a significant public health concern at a global level. This study aims at assessing Hg exposure and risk among Lebanese young adults based on Hg biomonitoring and seafood intake. A group of 166 young adults were administered a questionnaire to assess Hg exposure and were asked to provide a hair sample. Risk assessment was performed: (1) using the US Environmental Protection Agency Hazard Quotient (HQ) model based on fish intake and previously studied local fish Hg concentrations, and (2) by determining the total hair Hg concentration (THHg) using continuous flow-chemical vapor generation atomic absorption spectrometry. Differences in THHg across demographic and exposure subgroups were tested using t test or ANOVA. Correlations between THHg concentrations, fish consumption, and HQ were determined by computing Pearson's r. Higher THHg correlated with higher consumption of Mediterranean rabbitfish/spinefoots (r = 0.27; p = 0.001) and geographical location (p < 0.001) in the bivariate analysis, and remained significant in the adjusted multivariable linear regression model (geographical location: ß = 0.255, 95%CI 0.121–0.388; rabbitfish/spinefoots consumption: ß = 0.016, 95%CI 0.004–0.027). No significant correlations were found between HQ and THHg. In conclusion, this is the first study examining hair Hg levels and fish consumption in a young adult Lebanese population. Our findings constitute valuable baseline data for a local fish advisory and Hg monitoring.



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Attempts to minimize nitrogen oxide emission from diesel engine by using antioxidant-treated diesel-biodiesel blend

Abstract

The study represents a comprehensive analysis of engine exhaust emission variation from a compression ignition (CI) diesel engine fueled with diesel-biodiesel blends. Biodiesel used in this investigation was produced through transesterification procedure from Moringa oleifera oil. A single cylinder, four-stroke, water-cooled, naturally aspirated diesel engine was used for this purpose. The pollutants from the exhaust of the engine that are monitored in this study are nitrogen oxide (NO), carbon monoxide (CO), hydrocarbon (HC), and smoke opacity. Engine combustion and performance parameters are also measured together with exhaust emission data. Some researchers have reported that the reason for higher NO emission of biodiesel is higher prompt NO formation. The use of antioxidant-treated biodiesel in a diesel engine is a promising approach because antioxidants reduce the formation of free radicals, which are responsible for the formation of prompt NO during combustion. Two different antioxidant additives namely 2,6-di-tert-butyl-4-methylphenol (BHT) and 2,2′-methylenebis(4-methyl-6-tert-butylphenol) (MBEBP) were individually dissolved at a concentration of 1% by volume in MB30 (30% moringa biodiesel with 70% diesel) fuel blend to investigate and compare NO as well as other emissions. The result shows that both antioxidants reduced NO emission significantly; however, HC, CO, and smoke were found slightly higher compared to pure biodiesel blends, but not more than the baseline fuel diesel. The result also shows that both antioxidants were quite effective in reducing peak heat release rate (HRR) and brake-specific fuel consumption (BSFC) as well as improving brake thermal efficiency (BTE) and oxidation stability. Based on this study, antioxidant-treated M. oleifera biodiesel blend (MB30) can be used as a very promising alternative source of fuel in diesel engine without any modifications.



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Effect of ferrous sulfate and nitrohumic acid neutralization on the leaching of metals from a combined bauxite residue

Abstract

Bauxite residue neutralization is intended to open opportunities for revegetation and reuse of the residue. Ferrous sulfate (FS) and nitrohumic acid (NA) were two kinds of materials studied for pH reduction of the residue from 10.6 to 8.3 and 8.1, respectively. The effects of FS and NA on the leaching of metals from a combined bauxite residue were investigated by using sequential and multiple extraction procedures. Neutralization with FS and NA restricted the leaching of Al, V, and Pb from the residue but promoted the leaching of Fe, Cu, Mn, and Ni, consistent with the changes in the potentially mobile fractions. With the exceptions of Pb and Ni, leaching of metals increased during a 10-day extraction period. However, the maximum leaching of Al, V, Pb, Fe, Cu, Mn, and Ni from neutralized bauxite residue were 0.46 mg/L, 59.3, 12.9, 167, 95.3, 15.5, and 14.5 μg/L, respectively, which were under the corresponding limits in the National Standard (GB/T 14848-93). Although it is necessary to consider the continued leaching of metals during neutralization, both maximum and accumulation leaching concentrations of metals from a combined bauxite residue were too low to pose a potential environmental risk.



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Polycyclic aromatic hydrocarbons in the leaves of twelve plant species along an urbanization gradient in Shanghai, China

Abstract

Plants, particularly their leaves, play an important role in filtering both gas-phase and particle-phase polycyclic aromatic hydrocarbons (PAHs). However, many studies have focused on the accumulation and adsorption functions of plant leaves, possibly underestimating the effects that plants have on air quality. Therefore, eight tree species from different locations in Shanghai were selected to assess PAH filtering (via adsorption and capture) using washed and unwashed plant leaves. The differences in the total PAH contents in the washed leaves were constant for the different species across the different sampling sites. The PAH levels decreased in the following order: industrial areas > traffic areas > urban areas > background area. The PAH compositions in the different plant leaves were dominated by fluorene (Fle), phenanthrene (Phe), anthracene (Ant), chrysene (Chr), fluoranthene (Flu), and pyrene (Pyr); notably, Phe accounted for 49.4–76.7% of the total PAHs. By comparing the PAH contents in the washed leaves with the PAH contents in the unwashed leaves, Pittosporum tobira (P. tobira), Ginkgo biloba (G. biloba), and Platanus acerifolia (P. acerifolia) were found to be efficient species for adsorbing PAHs, while Osmanthus fragrans (O. fragrans), Magnolia grandiflora (M. grandiflora), and Prunus cerasifera Ehrh. (P. cerasifera Ehrh.) were efficient species for capturing PAHs. The efficiencies of the plant leaves for the removal of PAHs from air occurred in the order of low molecular weight > medium molecular weight > high molecular weight PAHs.



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Editorial Board and Contents

Publication date: March 2017
Source:Trends in Immunology, Volume 38, Issue 3





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Classical and non-classical causes of GH deficiency in adults

Publication date: Available online 23 February 2017
Source:Best Practice & Research Clinical Endocrinology & Metabolism
Author(s): F. Tanriverdi, F. Kelestimur
Growth hormone deficiency (GHD) can develop due to a variety of conditions, and may occur either as isolated or multiple pituitary hormone deficiencies. It has been previously demonstrated that GH is one of the most frequent hormonal deficiencies in adult patients with hypopituitarism. The most frequent classical causes of adult-onset GHD (AO-GHD) are pituitary adenomas and/or their treatment. However, during the last decade an increasing number of studies from different parts of the world have revealed that non-tumoural causes of hypopituitarism are more common than previously known. Therefore, in this review our aim is to briefly summarize the classical and non-classical acquired causes of GHD in adults.



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Breast Tomosynthesis

Publication date: Available online 23 February 2017
Source:Radiologic Clinics of North America
Author(s): Sarah M. Friedewald

Teaser

Digital breast tomosynthesis (DBT) is rapidly becoming the new standard of care for breast cancer screening. DBT has improved on the limitations of traditional digital mammography by increasing cancer detection and decreasing false-positive examinations. Interpretation of DBT is slightly different than digital mammography and therefore experience with the technology is paramount to achieve best performance. Examples of malignancies that should be recalled and benign findings that are safely called as benign are provided in this article. Additionally, practical interpretation methods and implementation protocols are explained.


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“A Rare Cause of Quadriparesis.”

Publication date: Available online 23 February 2017
Source:Pediatric Neurology
Author(s): Nidheesh Cheeyancheri Chencheri, Pawan Subhash Kashyape




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Haut Conseil de la santé publique. Avis relatif à l’utilisation des vaccins quadrivalents inactivés contre la grippe saisonnière (septembre 2016)

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Publication date: Available online 23 February 2017
Source:Revue des Maladies Respiratoires
Author(s): Haut Conseil de la santé publique




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Erratum to “Pharmacological treatment optimization for stable chronic obstructive pulmonary disease. Proposals from the Société de pneumologie de langue française” [Rev. Mal. Respir. 33 (2016) 911–936]

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Publication date: Available online 23 February 2017
Source:Revue des Maladies Respiratoires
Author(s): M. Zysman, F. Chabot, P. Devillier, B. Housset, C. Morelot-Panzini, N. Roche




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External Beam Radiation Therapy or Brachytherapy With or Without Short Course Neoadjuvant Androgen Deprivation Therapy: Results of a Multi-Center, Prospective Study of Quality of Life

Publication date: Available online 22 February 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Hiram Alberto Gay, Martin G. Sanda, Jingxia Liu, Ningying Wu, Daniel A. Hamstra, John T. Wei, Rodney L. Dunn, Eric A. Klein, Howard M. Sandler, Christopher S. Saigal, Mark S. Litwin, Deborah A. Kuban, Larry Hembroff, Meredith M. Regan, Peter Chang, Jeff M. Michalski
PurposeThe long-term effects of neoadjuvant androgen deprivation therapy (NADT) with radiation therapy on participant-reported health-related quality of life (HRQOL) have not been characterized in prospective multi-center studies. We evaluated HRQOL for 2 years among participants undergoing radiation therapy (RT) with or without NADT for newly diagnosed, early-stage prostate cancer.MethodsWe analyzed longitudinal cohort data from the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment Consortium to ascertain the HRQOL trajectory of men receiving NADT with external beam radiation therapy (EBRT) or brachytherapy (BT). HRQOL was measured with the EPIC-26 questionnaire at 2, 6, 12, and 24 months after the initiation of NADT. We used Chi-square or Fisher's Exact test to compare the shift percentages between groups that did or did not receive NADT. Analyses were conducted at the two-sided 5% significance level.ResultsFor subjects receiving EBRT, questions regarding the ability to have an erection, ability to reach an orgasm, quality of erections, frequency of erections, ability to function sexually, and lack of energy were in a significantly worse dichotomized category for the patients receiving NADT. Comparing baseline versus 24 months, 24%, 23%, and 30% of participants receiving EBRT plus NADT shifted to the worse dichotomized category for the ability to reach an orgasm, quality of erections, and ability to function sexually compared to 14%, 13% and 16% in the EBRT group, respectively.ConclusionCompared to baseline, at 2 years participants receiving NADT plus EBRT compared with EBRT alone had worse HRQOL, as measured by the ability to reach orgasms, quality of erections, and ability to function sexually. However, there was no difference in the ability to have an erection, frequency of erections, overall sexual function, hot flashes, breast tenderness/enlargement, feeling depressed, lack of energy or change in body weight. The improved survival in intermediate and high-risk patients receiving ADT and EBRT necessitates pre-treatment counseling of the HRQOL impact of ADT and EBRT.

Teaser

We evaluated HRQOL for 2 years among 573 participants undergoing EBRT or BT with or without NADT for newly diagnosed, early-stage prostate cancer. At 2 years, participants receiving NADT plus EBRT compared to EBRT had a worse ability to reach an orgasm, erection quality, and ability to function sexually, while the ability to have an erection, frequency of erections, sexual function, hot flashes, breast tenderness, feeling depressed, lack of energy, and body weight did not reach significance.


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Differences in Ki67 expressions between pre- and post-neoadjuvant chemotherapy specimens might predict early recurrence of breast cancer

Publication date: Available online 23 February 2017
Source:Human Pathology
Author(s): Emi Tokuda, Yoshiya Horimoto, Atsushi Arakawa, Takanori Himuro, Koji Senuma, Katsuya Nakai, Mitsue Saito
The prognosis of breast cancer patients not obtaining a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC) is poorer than that of pCR patients. Identifying new prognostic factors for non-pCR patients is important because fractions of this population might benefit from novel adjuvant treatments currently under development. High Ki67 expression in remnant disease after NAC has been described as a poor prognostic factor. Studies have shown that a reduction in Ki67 expression is more often observed in good responders to chemotherapy. We hypothesised that the change in Ki67 expression might be useful for predicting patient outcomes and thus retrospectively examined pairs of biopsy and surgical specimens of breast tissue from individual patients. One hundred and sixteen patients with remnant invasive disease in the breast, who received NAC and underwent surgery at our institution, were retrospectively examined. Differences in Ki67 expression between pre- and post-NAC specimens were analysed in relation to patient outcomes. The mean Ki67 expression value after NAC was higher in patients who developed metastasis than in those without metastasis (P<.01). Tumours showing higher Ki67 expression in the surgical than in the biopsy specimen were more frequent in patients with metastasis (P<.01). This trend was more obvious in patients who developed metastasis within one year after surgery. Our results indicate that a difference in Ki67 expressions after versus before NAC might be an important predictor of early metastasis. Evaluating not only absolute Ki67 values, but also any changes in response to NAC, may improve the prediction of patient outcomes.



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Multi-Site Tumor Sampling (MSTS): A new tumor selection method to enhance intratumor heterogeneity detection

Publication date: Available online 23 February 2017
Source:Human Pathology
Author(s): José I. López, Jesús M. Cortés
Intratumor heterogeneity (ITH) is increasingly being recognized as a highly complex process with high clinical impact that deserves special attention from practicing pathologists. The value of the ITH detection depends on the correctness of the pathologist's sampling. The goal of this review is twofold. On the one hand, we provide a basic scientific context for the practical pathologist's perspective. On the other, we encourage pathologists to adopt a more scientific and up-to-date approach to a key component of their daily work, namely, how to sample a tumor for reliable histological and molecular analysis. In particular, we review the consecutive steps of an efficient alternative to traditional approaches for detecting ITH: multi-site tumor sampling. Notably, this type of sampling, based on a divide and conquer algorithm, is supported by scientific evidence showing its clinical applicability and practical advantages at no extra cost.



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Psoriasis et phénomène de Koebner inversé après tatouage

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Publication date: Available online 22 February 2017
Source:Annales de Dermatologie et de Vénéréologie
Author(s): N. Kluger, M.-H. Jegou




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Gradual Shift toward Healthier Eating Styles: National Nutrition Month

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3
Author(s): Lucille Beseler




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A Year of MyPlate, MyWins: Small Changes Add Up to Big Wins; Help Put Your Best Fork Forward

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3
Author(s): Kristen Booze, Brooke Hardison, Jackie Haven




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Table of Contents

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3





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The Effectiveness and Cost of Lifestyle Interventions Including Nutrition Education for Diabetes Prevention: A Systematic Review and Meta-Analysis

Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3
Author(s): Yu Sun, Wen You, Fabio Almeida, Paul Estabrooks, Brenda Davy
BackgroundType 2 diabetes is a significant public health concern. With the completion of the Diabetes Prevention Program, there has been a proliferation of studies attempting to translate this evidence base into practice. However, the cost, effectiveness, and cost-effectiveness of these adapted interventions is unknown.ObjectiveThe purpose of this systematic review was to conduct a comprehensive meta-analysis to synthesize the effectiveness, cost, and cost-effectiveness of lifestyle diabetes prevention interventions and compare effects by intervention delivery agent (dietitian vs non-dietitian) and channel (in-person vs technology-delivered).MethodsEnglish and full-text research articles published up to July 2015 were identified using the Cochrane Library, PubMed, Education Resources Information Center, CAB Direct, Science Direct, and Google Scholar. Sixty-nine studies met inclusion criteria. Most employed both dietary and physical activity intervention components (four of 69 were diet-only interventions). Changes in weight, fasting and 2-hour blood glucose concentration, and hemoglobin A1c were extracted from each article. Heterogeneity was measured by the I2 index, and study-specific effect sizes or mean differences were pooled using a random effects model when heterogeneity was confirmed.ResultsParticipants receiving intervention with nutrition education experienced a reduction of 2.07 kg (95% CI 1.52 to 2.62; P<0.001; I2=90.99%, 95% CI 88.61% to 92.87%) in weight at 12 months with effect sizes over time ranging from small (0.17, 95% CI 0.04 to 0.30; P=0.012; I2= 86.83%, 95% CI 80.42% to 91.14%) to medium (0.65, 95% CI 0.49 to 0.82; P<0.001; I2=98.75%, 95% CI 98.52% to 98.94). Effect sizes for 2-hour blood glucose and hemoglobin A1c level changes ranged from small to medium. The meta-regression analysis revealed a larger relative weight loss in dietitian-delivered interventions than in those delivered by nondietitians (full sample: –1.0 kg; US subsample: –2.4 kg), and did not find statistical evidence that the delivery channel was an important predictor of weight loss. The average cost per kilogram weight loss ranged from $34.06 over 6 months to $1,005.36 over 12 months. The cost of intervention per participant delivered by dietitians was lower than interventions delivered by non-dietitians, although few studies reported costs.ConclusionsLifestyle interventions are effective in reducing body weight and glucose-related outcomes. Dietitian-delivered interventions, compared with those delivered by other personnel, achieved greater weight reduction. No consistent trend was identified across different delivery channels.



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March 2017 People & Events

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3





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March 2017 New in Review

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3





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March 2017 Classified Advertisements

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3





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What Role Does Diet Play in the Management of Nickel Allergy?

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Publication date: March 2017
Source:Journal of the Academy of Nutrition and Dietetics, Volume 117, Issue 3
Author(s): Eleese Cunningham




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Response to antiseptic agents of periodontal pathogens in in vitro biofilms on titanium and zirconium surfaces

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Publication date: Available online 23 February 2017
Source:Dental Materials
Author(s): M.C. Sánchez, E. Fernández, A. Llama-Palacios, E. Figuero, D. Herrera, M. Sanz
ObjectiveThe aim of this study was to develop in vitro biofilms on SLA titanium (Ti-SLA) and zirconium oxide (ZrO2) surfaces and to evaluate the effect of antiseptic agents on the number of putative periodontal pathogenic species.MethodsAn in vitro biofilm model was developed on sterile discs of Ti-SLA and ZrO2. Three antiseptic agents [chlorhexidine and cetyl-pyridinium-chloride (CHX/CPC), essential oils (EEOOs) and cetyl-peridinium-chloride (CPC)] were applied to 72-h biofilms, immersing discs during 1min in the antiseptic solution, either with or without mechanical disruption. Viable bacteria [colony forming units (CFU/mL)] were measured by quantitative polymerase chain reaction (qPCR) combined with propidium monoazide. A generalized lineal model was constructed to determine the effect of the agents on the viable bacterial counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis and Fusobacterium nucleatum on each surface.ResultsThe exposure to each antiseptic solution resulted in a statistically significant reductions in the number of viable target species included in the in vitro multi-species biofilm, on both Ti-SLA and ZrO2 (p<0.001) which was of up to 2 orders for A. actinomycetemcomitans, for P. gingivalis 2 orders on Ti-SLA and up to 3 orders on ZrO2, and, for F. nucleatum up to 4 orders. No significant differences were found in counts of the tested bacteria between in vitro biofilms formed on both Ti-SLA and ZrO2, after topically exposure to the antimicrobial agents whether the application was purely chemical or combined with mechanical disruption.SignificanceA. actinomycetemcomitans, P. gingivalis and F. nucleatum responded similarly to their exposure to antiseptics when grown in multispecies biofilms on titanium and zirconium surfaces, in spite of the described structural differences between these bacterial communities.



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Living with ‘melanoma’…for a day: a phenomenological analysis of medical students’ simulated experiences

Abstract

Background

Despite the rising incidence of melanoma, medical students have progressively fewer opportunities to encounter patients with this important condition. Curricula tend to attach the greatest value to intellectual forms of learning. Compared to intellectual learning, however, experiential learning affords students deep insights about a condition. Doctors who experience ill health are more empathic towards patients. However opportunities to learn about cancer experientially are limited. Temporary transfer tattoos can simulate the ill health associated with melanoma. We reasoned that, if doctors who have been sick are more empathic, temporarily 'having' melanoma might have a similar effect.

Objectives

Explore the impact of wearing a melanoma tattoo on medical students' understanding of patienthood and attitudes towards patients with melanoma.

Methods

Ten fourth year medical students were recruited to a simulation. They wore a melanoma tattoo for 24 hours and listened to a patient's account of receiving their diagnosis. Data were captured using audio-diaries and face-to-face interviews, transcribed, and analysed phenomenologically using the template analysis method.

Results

There were four themes: 1) Melanoma simulation: opening up new experiences.

2) Drawing upon past experiences.3) A transformative introduction to patienthood.

4) Doctors in the making: seeing cancer patients in a new light.

Conclusions

By means of a novel simulation, medical students were introduced to lived experiences of having a melanoma. Such an inexpensive simulation can prompt students to reflect critically on the empathetic care of such patients in the future

This article is protected by copyright. All rights reserved.



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