Residential Proximity to Gasoline Stations and Risk of Childhood Leukemia

<span class="paragraphSection"><div class="boxTitle">Abstract</div>Significant elevations in the risk of childhood leukemia have been associated with environmental exposure to gasoline; aromatic hydrocarbons from refinery pollution, petroleum waste sites, and mobile sources (automobile exhaust); paints, paint products, and thinners; and secondary cigarette smoke in the home. These higher risks have also been associated with parental exposure to benzene, gasoline, motor vehicle–related jobs, painting, and rubber solvents. These exposures and jobs have 1 common chemical exposure—benzene, a recognized cause of acute leukemia in adults—and raise the question of whether children represent a subpopulation in which a higher risk of leukemia is associated with very low level exposure to environmental benzene.</span>

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The crosstalk between Wnt/β-catenin signaling pathway with DNA damage response and oxidative stress: implications in cancer therapy

Publication date: Available online 11 January 2017
Source:DNA Repair
Author(s): Ansar Karimaian, Maryam Majidinia, Hossein Bamazadeh-baghi, Bahman Yousefi
DNA repair is essential for maintaining genomic integrity in cells. The dependence of cancer cell survival on proper DNA repair provides an opportunity to treat defective tumors by DNA damaging agents. Not only Wnt signaling has important functions in controlling gene expression, as well as cell polarity, adhesion and behavior, it also highly interacts with DNA damage response (DDR) in different levels. Furthermore, oxidative stress, which is responsible for majority of DNA lesions, affects Wnt signaling in different ways. A better understanding of the cross-talk between these pathways and events could provide strategies for treatment of cancer cells with deficient DNA repair capacity. As such, we will give a brief overview of the importance of the DNA repair machinery, signaling mechanisms of Wnt/β-catenin pathway, and DDR. We will further review the interactions between Wnt signaling and DDR, and the impact of oxidative stress on Wnt signaling. Finally, Wnt signaling is discussed as a potential treatment strategy for cancer.



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Teaching Radiology to Medical Students—There Is a Need for Change to Better Prepare Students for Clinical Practice

Publication date: Available online 10 January 2017
Source:Academic Radiology
Author(s): Brian M. Moloney, Christine E. McCarthy, Dara Byrne, Terri P. McVeigh, Michael J. Kerin, Peter A. McCarthy
Rationale and ObjectivesDeriving maximum benefit from radiology rotations in medical schools is challenging. Lack of education on appropriate imaging renders students feeling unprepared. This study compares the ability of undergraduate medical students to identify appropriate radiological investigations, both at the beginning and end of their final year of education, to those of residents in their first year of clinical practice.Materials and MethodsTwelve scenarios were extracted from the American College of Radiology's Appropriateness Criteria (ACR-AC) and a questionnaire was generated. One topic was selected from each of the 10 sections in the diagnostic section and two from the interventional section. The questionnaire was distributed to three groups. Group A was composed of medical students at the beginning of final year. Group B was composed of medical students at the end of final year. Group C was composed of residents at the end of their first year of clinical practice. Radiology residents were surveyed to assess familiarity with the ACR-AC among trainees in Ireland.ResultsThe total cohort included 160 participants. Group C (n = 35) performed significantly better than group A (n = 72) and group B (n = 53). There was no statistical difference in the mean scores achieved by group A and group B. Sixteen (73%) of 22 radiology trainees were familiar with the ACR-AC.ConclusionsA minimal improvement in the knowledge of medical students in requesting radiological investigations over the course of the final medical year, yet a significant impact of a relatively short period of "on-the-job" learning in the clinical setting, was indicated. Emphasis on education on appropriateness may offer an improvement in the utilization of radiology services and improve patient care.



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Immunohistochemical Approach for the Diagnosis of a Liver Mass on Small Biopsy Specimens

Publication date: Available online 11 January 2017
Source:Human Pathology
Author(s): Won-Tak Choi, Rageshree Ramachandran, Sanjay Kakar
Well-differentiated hepatocellular carcinoma (HCC) shares overlapping histological features with benign hepatocellular lesions, including hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) in non-cirrhotic liver, and with high-grade dysplastic nodule (HGDN) in cirrhotic liver. Several metastatic tumors, such as neuroendocrine tumor, renal cell carcinoma, adrenocortical carcinoma, melanoma, and epithelioid angiomyolipoma, can be indistinguishable from HCC on histologic grounds. Since this distinction has important therapeutic implications, judicious use of immunohistochemical markers plays an important role in establishing an accurate diagnosis, especially when limited material of tumor is available on cell block or a small core biopsy. This review describes commonly used immunohistochemical markers used in the diagnosis of HCC, highlighting advantages and disadvantages of each marker, and suggests appropriate immunohistochemical panels for specific clinicopathologic situations.



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FOXO1 downregulation is associated with worse outcome in bladder cancer and adds significant prognostic information to p53 overexpression

Publication date: Available online 11 January 2017
Source:Human Pathology
Author(s): Josep Lloreta, Alba Font-Tello, Núria Juanpere, Albert Frances, Marta Lorenzo, Lara Nonell, Silvia de Muga, Ivonne Vázquez, Lluís Cecchini, Silvia Hernández-Llodrà
Nuclear FOXOs mediate cell cycle arrest and promote apoptosis. FOXOs and p53 could have similar effects as tumor suppressor genes. In spite of extensive literature, little is known about the role of FOXO1 and its relationship with p53 status in bladder cancer. Expression of FOXO1 and p53 were analyzed by immunohistochemistry in 162 urothelial carcinomas (UC). Decreased FOXO1 expression, p53 overexpression and the combination FOXO1 downregulation/p53 overexpression were strongly associated with high grade (P=.030; P=.017; P=.004, respectively), high stage (P=.0001; P<.0001; P<.0001, respectively) or both (P=.0004; P<.0001; P<.0001, respectively). In the overall series of cases, p53 overexpression was associated with tumor progression (HR=3.18, 95% CI 1.19–8.48 P=.02), but this association was even stronger if having any alteration in any of the two genes was considered (HR=3.51, 95% CI 1.34–9.21 P=.01). Having both FOXO1 downregulation and p53 overexpression was associated with disease recurrence (HR=2.75, 95% CI 1.06–7.13 P=.03). In the analysis of the different subgroups, having any alteration in any of the two genes was associated with progression in low grade (P=.005) and pTa (P=.006) tumors. Finally, the combined FOXO1 downregulation/p53 overexpression was associated with disease recurrence specifically in high grade (P=.04) and in pT1 stage tumors (P=.007). Adding FOXO1 expression to the immunohistochemical analysis of p53 can provide relevant prognostic information on progression and recurrence of bladder cancer. It may be particularly informative on the risk of progression in the more indolent and on the risk of recurrence in the more aggressive tumors.



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Overexpression of Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is associated with tumor aggressiveness and poor prognosis in patients with invasive ductal breast carcinoma

Publication date: Available online 10 January 2017
Source:Human Pathology
Author(s): Min Xiao, QingYong Xu, Chun Lou, Yu Qin, XiaoMing Ning, TianBo Liu, XuHai Zhao, ShuSheng Jia, YuanXi Huang
Tumor necrosis factor-α-induced protein 8 (TNFAIP8), a transcription factor NF-κB-inducible, antiapoptotic and oncogenic molecule, is associated with prognosis of several human malignancies. However, the relationship between TNFAIP8 and the prognosis of the invasive ductal carcinoma (IDC) of the breast remains unclear. TNFAIP8 expression was evaluated using real-time PCR and Western blot analysis in 20 fresh IDC tissues, and immunohistochemical analysis in 351 paraffin-embedded IDC tissues. Real-time PCR and Western blot analysis demonstrated that both TNFAIP8 mRNA and protein were upregulated in IDC tissues compared with the paired adjacent noncancerous tissues. Immunohistochemistry revealed that TNFAIP8 expression was significantly correlated with some clinicopathological factors, including axillary lymph node metastasis (P=.001), advanced TNM stage (P<.001), high histological grade (P<.001), molecular subtype (P<.001), and postoperative recurrence (P<.001). Univariate and multivariate logistic regression analyses demonstrated that TNFAIP8 overexpression was strongly associated with axillary lymph node metastasis (odds ratio, 1.818; 95%CI, 1.167–2.832; P=.008). Moreover, Kaplan–Meier analysis indicated that IDC patients with high TNFAIP8 expression had a shorter survival time than those with low TNFAIP8 expression, and multivariate analysis indicated that TNFAIP8 was an independent prognostic for overall survival and disease-free survival in IDC (P=.041 and P=.020, respectively). Therefore, TNFAIP8 overexpression may contribute to tumor progression, and it may be a novel prognostic biomarker for the patients with IDC.



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Phospholipase D mRNA expression and clinical role in high-grade serous carcinoma

Publication date: Available online 11 January 2017
Source:Human Pathology
Author(s): Keren Harel-Dassa, Saul Yedgar, Claes G. Tropé, Ben Davidson, Reuven Reich
This objective of this study was to analyze the expression and clinical role of phospholipase D (PLD) in high-grade serous carcinoma (HGSC). PLD1 and PLD2 isoform expression was studied in 125 HGSC specimens (73 effusions, 28 ovarian tumors, 24 solid metastases) using quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR). Expression levels were analyzed for association with clinicopathologic parameters, including chemoresponse, and survival. PLD1 and PLD2 isoforms were found in the majority of specimens at all anatomic sites and their levels were strongly positively related (P<.001 for effusions and solid lesions). PLD2 mRNA expression was significantly higher in effusions compared to both carcinomas in the ovary and solid metastases (P<.001). Higher levels of both isoforms were associated with higher CA 125 levels at diagnosis (P<.001) and higher PLD2 mRNA levels in effusions were associated with unfavorable response to chemotherapy (P=.021). Expression levels of the studied isoforms were unrelated to the levels of previously studied mRNAs that form part of the phospholipase A2 pathway or to survival. The present study provides the first evidence of PLD expression in HGSC and suggests a role for in mediating progression to effusions and chemoresistance in this cancer.



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Renal involvement in Lysinuric protein intolerance: contribution of pathology to assessment of heterogeneity of renal lesions

Publication date: Available online 11 January 2017
Source:Human Pathology
Author(s): Emmanuel Estève, Pauline Krug, Aurélie Hummel, Jean-Baptiste Arnoux, Olivia Boyer, Anais Brassier, Pascale de Lonlay, Vincent Vuiblet, Stéphanie Gobin, Rémi Salomon, Christine Piètrement, Jean-Paul Bonnefont, Aude Servais, Louise Galmiche
Lysinuric protein intolerance (LPI) is a rare autosomal recessive disease caused by mutations in the SLC7A7 gene encoding the light subunit of a cationic amino acid transporter. Symptoms mimic primary urea cycle defects but dysimmune symptoms are also described. Renal involvement in LPI was first described in the 1980's. In 2007, it appeared that it could concern as much as 75% of LPI patients and could lead to end stage renal disease. The most common feature is proximal tubular dysfunction and nephrocalcinosis but glomerular lesions are also reported. However, very little is known regarding histological lesions associated with LPI. We gathered every kidney biopsy of LPI proven patient in our highly specialized pediatric and adult institution. Clinical, biological and histological informations were analyzed. Five LPI patients underwent kidney biopsy in our institution between 1986 and 2015. Clinically, 4/5 presented with proximal tubular dysfunction and 3/5 with nephrotic range proteinuria. Histology showed unspecific tubulointerstitial lesions and nephrocalcinosis in 3/5 biopsies and marked peritubular capillaritis in one child. Glomerular lesions were heterogeneous: lupus like-full house membranoproliferative glomerulonephritis (MPGN) in one child evolved towards monotypic IgG1kappa MPGN sensitive to immunomodulators. One patient presented with glomerular non AA non AL amyloidosis. Renal biopsy is particularly relevant in LPI presenting with glomerular symptoms for which variable histological lesions can be responsible, implying specific treatment and follow up.



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Development of delineation for the left anterior descending coronary artery region in left breast cancer radiotherapy: An optimized organ at risk

Publication date: Available online 10 January 2017
Source:Radiotherapy and Oncology
Author(s): Jie Lee, Kai-Lung Hua, Shih-Ming Hsu, Jhen-Bin Lin, Chou-Hsien Lee, Kuo-Wei Lu, Kun-Yao Dai, Xu-Nian Huang, Jun-Zhao Huang, Meng-Hao Wu, Yu-Jen Chen
Background and purposeThe left anterior descending coronary artery (LAD) and diagonal branches (DBs) are blurred on computed tomography (CT). We aimed to define the LAD region (LADR) with adequate inclusion of the LAD and DBs and contouring consistency.Methods and materialsThe LADR was defined using coronary CT angiograms. The inclusion ratio was used to assess the LAD and DBs inclusion by the LADR. Four radiation oncologists delineated the LAD and LADR, using contrast-enhanced CT of 15 patients undergoing left breast radiotherapy. The Sørensen–Dice similarity index (DSI), Jaccard similarity index (JSI), and Hausdorff distance (HD) were calculated to assess similarity. The mean dose (Dmean) and maximum dose (Dmax) to the LAD and LADR were calculated to compare consistency. Correlations were evaluated using Pearson's correlation coefficient.ResultsThe inclusion ratio of the LAD by the LADR was 96%. The mean DSI, JSI, and HD values were respectively 27.9%, 16.7%, and 0.42mm for the LAD, and 83.1%, 73.0%, and 0.18mm for the LADR. The Dmean between the LAD and LADR were strongly correlated (r=0.93).ConclusionDelineation of the LADR significantly improved contouring similarity and consistency for dose reporting. This could optimize dose estimation for breast radiotherapy.



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On-going Mechanical Damage from Mastication Drives Homeostatic Th17 Cell Responses at the Oral Barrier

Publication date: Available online 10 January 2017
Source:Immunity
Author(s): Nicolas Dutzan, Loreto Abusleme, Hayley Bridgeman, Teresa Greenwell-Wild, Tamsin Zangerle-Murray, Mark E. Fife, Nicolas Bouladoux, Holly Linley, Laurie Brenchley, Kelly Wemyss, Gloria Calderon, Bo-Young Hong, Timothy J. Break, Dawn M.E. Bowdish, Michail S. Lionakis, Simon A. Jones, Giorgio Trinchieri, Patricia I. Diaz, Yasmine Belkaid, Joanne E. Konkel, Niki M. Moutsopoulos
Immuno-surveillance networks operating at barrier sites are tuned by local tissue cues to ensure effective immunity. Site-specific commensal bacteria provide key signals ensuring host defense in the skin and gut. However, how the oral microbiome and tissue-specific signals balance immunity and regulation at the gingiva, a key oral barrier, remains minimally explored. In contrast to the skin and gut, we demonstrate that gingiva-resident T helper 17 (Th17) cells developed via a commensal colonization-independent mechanism. Accumulation of Th17 cells at the gingiva was driven in response to the physiological barrier damage that occurs during mastication. Physiological mechanical damage, via induction of interleukin 6 (IL-6) from epithelial cells, tailored effector T cell function, promoting increases in gingival Th17 cell numbers. These data highlight that diverse tissue-specific mechanisms govern education of Th17 cell responses and demonstrate that mechanical damage helps define the immune tone of this important oral barrier.

Teaser

The signals regulating immunity at the gingiva, a key oral barrier, remain unclear. Dutzan et al. show that oral barrier Th17 cells are induced in response to mastication rather than commensal colonization, identifying physiologic mechanical damage as a unique tissue-specific cue conditioning local immunity and inflammation at the oral barrier.


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Lymphocyte Circadian Clocks Control Lymph Node Trafficking and Adaptive Immune Responses

Publication date: Available online 10 January 2017
Source:Immunity
Author(s): David Druzd, Olga Matveeva, Louise Ince, Ute Harrison, Wenyan He, Christoph Schmal, Hanspeter Herzel, Anthony H. Tsang, Naoto Kawakami, Alexei Leliavski, Olaf Uhl, Ling Yao, Leif Erik Sander, Chien-Sin Chen, Kerstin Kraus, Alba de Juan, Sophia Martina Hergenhan, Marc Ehlers, Berthold Koletzko, Rainer Haas, Werner Solbach, Henrik Oster, Christoph Scheiermann
Lymphocytes circulate through lymph nodes (LN) in search for antigen in what is believed to be a continuous process. Here, we show that lymphocyte migration through lymph nodes and lymph occurred in a non-continuous, circadian manner. Lymphocyte homing to lymph nodes peaked at night onset, with cells leaving the tissue during the day. This resulted in strong oscillations in lymphocyte cellularity in lymph nodes and efferent lymphatic fluid. Using lineage-specific genetic ablation of circadian clock function, we demonstrated this to be dependent on rhythmic expression of promigratory factors on lymphocytes. Dendritic cell numbers peaked in phase with lymphocytes, with diurnal oscillations being present in disease severity after immunization to induce experimental autoimmune encephalomyelitis (EAE). These rhythms were abolished by genetic disruption of T cell clocks, demonstrating a circadian regulation of lymphocyte migration through lymph nodes with time-of-day of immunization being critical for adaptive immune responses weeks later.

Graphical abstract

Teaser

Lymphocyte trafficking through lymph nodes and lymph is an important immune surveillance mechanism of the body. Druzd et al. (2017) demonstrate that this trafficking occurs in a circadian manner and that adaptive immune responses are also time-of-day dependent and are ablated when circadian clock function is lost in T cells.


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Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women

Publication date: Available online 10 January 2017
Source:Immunity
Author(s): Christina Gosmann, Melis N. Anahtar, Scott A. Handley, Mara Farcasanu, Galeb Abu-Ali, Brittany A. Bowman, Nikita Padavattan, Chandni Desai, Lindsay Droit, Amber Moodley, Mary Dong, Yuezhou Chen, Nasreen Ismail, Thumbi Ndung'u, Musie S. Ghebremichael, Duane R. Wesemann, Caroline Mitchell, Krista L. Dong, Curtis Huttenhower, Bruce D. Walker, Herbert W. Virgin, Douglas S. Kwon
Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4⁺ T cells compared to those with Lactobacillus crispatus-dominant communities. We identified specific bacterial taxa linked with reduced (L. crispatus) or elevated (Prevotella, Sneathia, and other anaerobes) inflammation and HIV infection and found that high-risk bacteria increased numbers of activated genital CD4⁺ T cells in a murine model. Our results suggest that highly prevalent genital bacteria increase HIV risk by inducing mucosal HIV target cells. These findings might be leveraged to reduce HIV acquisition in women living in sub-Saharan Africa.

Graphical abstract

Teaser

The potential impact of cervicovaginal bacteria on HIV susceptibility is not well-defined. Gosmann et al. (2017) identify anaerobic cervicovaginal bacterial communities and specific taxa highly prevalent in young healthy South African women that increase their HIV risk. These findings might be leveraged to reduce HIV acquisition in women.


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Dermoscopy of giant juvenile xanthogranuloma

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Je-Ho Mun, Jungyoon Ohn, Kyu Han Kim




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Table of Contents

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1





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Editorial Board

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1





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Dermoscopy, reflectance confocal microscopy, and high-definition optical coherence tomography in the diagnosis of generalized argyria

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Elisa Cinotti, Bruno Labeille, Catherine Douchet, Frédéric Cambazard, Jean-Luc Perrot




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Parallel globules on the ridges caused by transepidermal elimination of melanocytic nests: A new dermoscopic pattern of acral melanoma

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Giovanni Ghigliotti, Elena De Col, Franco Rongioletti




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Dermoscopy of adenoma sebaceum

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Biswanath Behera, Rashmi Kumari, Debasis Gochhait, Arjuna Babu Sathya, Devinder Mohan Thappa




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Peripilar hair casts

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Lucía Campos-Muñoz, Alejandro Fueyo-Casado, Carmen Carranza-Romero, Elena Gonzalez-Guerra, Eduardo López-Bran




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Dermoscopic characteristics of a cutaneous histiocytic sarcoma in a young patient

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Ines Escandell, Maria Dolores Ramon, Sara Sánchez, Liria Terradez, Esperanza Jorda




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Title Page

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1





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Dermoscopic features of a solitary fibrofolliculoma on the left cheek

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Maressa C. Criscito, Euphemia W. Mu, Shane A. Meehan, David Polsky, Iris Kopeloff




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Dermoscopy of cutaneous involvement by multiple myeloma

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Emi Dika, Giulia Maria Ravaioli, Paola Tacchetti, Elena Zamagni, Pier Alessandro Fanti, Simone Ribero, Cosimo Misciali, Annalisa Patrizi




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Acral persistent papular mucinosis (APPM): Dermoscopy of an uncommon disease

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Cristián Navarrete-Dechent, Shirin Bajaj, Ashfaq Marghoob, Sergio González, Alejandra Jaque




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Diagnosing squamous cell carcinoma of the lip using dermoscopy

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): A. Tülin Güleç




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Familial outbreak of eruptive pseudoangiomatosis with dermoscopic and histopathologic correlation

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Carlos Gustavo Wambier, Mark Aaron Cappel, Tayza Katelline Danilau Ostroski, Mário Rodrigues Montemor Netto, Sarah Perillo de Farias Wambier, Bruna Lais Santos de Jesus, Eurico Arruda




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Secukinumab sustains early patient-reported outcome benefits through 1 year: Results from 2 phase III randomized placebo-controlled clinical trials comparing secukinumab with etanercept

Publication date: Available online 10 January 2017
Source:Journal of the American Academy of Dermatology
Author(s): Bruce Strober, Alice B. Gottlieb, Bintu Sherif, Patrick Mollon, Isabelle Gilloteau, Lori McLeod, Todd Fox, Margaret Mordin, Ari Gnanasakthy, Charis Papavassilis, Mark G. Lebwohl
BackgroundPsoriasis is a chronic condition with negative impact on patients' quality of life that most often requires lifelong effective and safe treatment.ObjectiveThis analysis focused on the effect of secukinumab treatment on patient-reported health-related quality of life as assessed by the Dermatology Life Quality Index (DLQI) in patients with moderate to severe psoriasis.MethodsThe proportion of subjects achieving DLQI score 0/1 response at week 24, time to DLQI score 0/1 response, and sustained DLQI score 0/1 response up to week 52 were compared between secukinumab and etanercept.ResultsOf 1470 subjects, 1144 received secukinumab and 326 received etanercept. DLQI score 0/1 response rates were significantly higher for secukinumab than for etanercept at week 24. The median time to DLQI score 0/1 response was significantly shorter for secukinumab versus etanercept (12 vs 24 weeks; P < .01). The majority of secukinumab-treated subjects achieved DLQI score 0/1 response at week 24 and sustained it through week 52 along with a 90% to 100% reduction in the Psoriasis Area and Severity Index total score response.LimitationsPlacebo comparisons are limited during the maintenance period because of rerandomization at week 12.ConclusionSecukinumab treatment provided faster and greater sustained improvements in quality of life than etanercept over 52 weeks, consistent with greater clinical response.



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Solitary angiokeratoma with Meyerson phenomenon

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): André Oliveira, Jorge Cardoso, Iris Zalaudek




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A case of onychomatricoma: Classic clinical, dermoscopic, and nail-clipping histologic findings

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Lauren Goldlust Okon, Nazanin Saedi, Laurel Schwartz, Jason B. Lee




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Desmoplastic trichilemmoma dermoscopically mimicking molluscum contagiosum

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Cristián Navarrete-Dechent, Pablo Uribe, Sergio González




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Acral pseudolymphomatous angiokeratoma of children with rainbow pattern: A mimicker of Kaposi sarcoma

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Víctor Hugo Pinos León, Jennyfer Daniela Granizo Rubio




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The anal groove sign: The use of dermatoscopy for identification of Ixodes ticks

Publication date: February 2017
Source:Journal of the American Academy of Dermatology, Volume 76, Issue 2, Supplement 1
Author(s): Deirdre M. Connolly, Jason B. Lee




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Nasopharyngeal carriage of respiratory pathogens in Warao Amerindians: significant relationship with stunting.

Related Articles

Nasopharyngeal carriage of respiratory pathogens in Warao Amerindians: significant relationship with stunting.

Trop Med Int Health. 2017 Jan 10;:

Authors: Verhagen LM, Hermsen M, Rivera-Olivero IA, Sisco MC, de Jonge MI, Hermans PW, de Waard JH

Abstract
OBJECTIVE: To assess risk factors for nasopharyngeal carriage of pathogens in geographically isolated Warao Amerindians in Venezuela.
METHODS: In this point prevalence survey, nasopharyngeal swabs were obtained from 1064 Warao Amerindians: 504 children aged 0 - 4 years, 227 children aged 5 - 10 years, and 333 caregivers. Written questionnaires were completed to obtain information on demographics and environmental risk factors. Anthropometric measurements were performed in children aged 0 - 4 years.
RESULTS: Carriage rates of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis were 51%, 7%, 1%, and 13% respectively. Crowding index, method of cooking, and tobacco exposure were not associated with increased carriage. In multivariable analysis, an increase in height-for-age Z score (i.e. improved chronic nutritional status) was associated with decreased odds of S. pneumoniae colonization (OR 0.76, 95% CI 0.70 - 0.83).
CONCLUSIONS: Better knowledge of demographic and environmental risk factors facilitates better understanding of the dynamics of colonization with respiratory pathogens in an Amerindian population. Poor chronic nutritional status was associated with increased pathogen carriage in children <5 years of age. The high rates of stunting generally observed in indigenous children may fuel the acquisition of respiratory pathogens that can lead to respiratory and invasive disease. This article is protected by copyright. All rights reserved.

PMID: 28072501 [PubMed - as supplied by publisher]

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Competitive failure analysis on tensile fracture of laser-deposited material for martensitic stainless steel

Publication date: 15 March 2017
Source:Materials & Design, Volume 118
Author(s): Shaopeng Wei, Gang Wang, Jianchao Yu, Yiming Rong
Sufficient mechanical properties of deposited materials are needed in remanufacturing applications to guarantee the functionality and reliability of repaired parts. The present paper described the tensile fracture behavior of laser-deposited FV520B martensitic stainless steel comprehensively based on evolution of the microstructure and mechanical property. The samples were fabricated by laser hot-wire deposition. The fracture behavior of the deposited samples was characterized using a specially designed uniaxial tension testing approach and investigated on the grain size, microhardness profile, residual stresses and precipitate distribution. The results show that the tensile fracture occurred at the position with high fluctuating microhardness caused by the multi-layer laser heating. Three tensile fracture patterns of deposited material were found: interfacial fracture, heat affected zone (HAZ) fracture and HAZ/interface hybrid fracture. They result from the competitive failure between microvoid coalescence in the heat affected zone and interfacial cracking in the clad layer/HAZ interface. Grain refinement and dissolution of precipitates occurred in heat affected zone, leading to a decrease of strength and increase of toughness.

Graphical abstract

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The effect of ultrasonic impact treatment on the deformation behavior of commercially pure titanium under uniaxial tension

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): A.V. Panin, M.S. Kazachenok, A.I. Kozelskaya, R.R. Balokhonov, V.A. Romanova, O.B. Perevalova, Yu I. Pochivalov
The deformation behavior of commercially pure titanium specimens subjected to surface hardening by ultrasonic impact treatment followed by uniaxial tension was investigated experimentally and numerically. The microstructure of the ultrasonically treated ~100μm thick surface layer undergoing uniaxial tension was revealed, using transmission electron microscopy and electron backscatter diffraction. Non-equiaxed 100–200nm α-Ti grains composed of 2nm diameter TiC and Ti2C nanoparticles, ω- and α″-phase crystallites were found in the 10μm thick uppermost layer. Fine and coarse α-Ti grains containing dislocations and twins were observed at depths of 20 and 50μm below the specimen surface, respectively. A non-crystallographic deformation (shear banding) mechanism at work in the nanostructured surface layer of the specimens under study was revealed. The evolution of shear bands was studied by the finite difference method, with the fine-grained structure being explicitly accounted for in the calculations. Shear band self-organization was described, using the energy balance approach similar to that based on Griffith's energy balance criterion for brittle fracture. The tensile deformation of the hardened layer lying at a depth of 50μm was implemented by the glide of dislocations and growth of deformation twins induced by preliminary ultrasonic impact treatment.

Graphical abstract

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Enhanced nucleation and refinement of eutectic Si by high number-density nano-particles in Al–10Si–0.5Sb alloys

Publication date: 5 March 2017
Source:Materials & Design, Volume 117
Author(s): Fengxiang Guo, Wei Wang, Wenhui Yu, Yong Zhang, Shaopeng Pan, Zhonghai Zhou, Dan Liu, Jingyu Qin, Yao Wang, Xuelei Tian
The mechanism of refinement of eutectic Si with Sb additions in an Al–10wt.% Si alloy is studied. The increased holding time designates a transition of the eutectic nucleation temperature from a decreased value to an increased one, accompanied by a morphological transformation of eutectic Si from lamellar to a shorter, rod-like shape. By ab initio molecular dynamics simulation, the chemical short-range order of −0.002 demonstrates weak affinity in the Al–Sb pair, which does not favor the existence of AlSb clusters in the melts. Sb–Sb segregation and the Sb–Si repulsive force are revealed, which promote the formation of Al-enriched precursors and the accumulation of Si atoms adjacent to precursors, inducing precursor nucleation. Continuous attachment of precursors and individual Si atoms during Si growth results in the high number-density nano-particles and suppresses the formation of twin grains within eutectic Si.

Graphical abstract

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Exosome-SIRPα, a CD47 blockade increases cancer cell phagocytosis

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Eunee Koh, Eun Jung Lee, Gi-Hoon Nam, Yeonsun Hong, Eunji Cho, Yoosoo Yang, In-San Kim
CD47, a "don't eat me" signal, is over-expressed on the surface of most tumors that interacts with signal regulatory protein α (SIRPα) on phagocytic cells. By engaging SIRPα, CD47 limits the ability of macrophages to engulf tumor cells, which acts as a major phagocytic barrier. In this study, we developed an exosome-based immune checkpoint blockade that antagonizes the interaction between CD47 and SIRPα. These exosomes harboring SIRPα variants (SIRPα-exosomes) were sufficient to induce remarkably augmented tumor phagocytosis, lead to prime effective anti-tumor T cell response. Given that clustering of native CD47 provides a high binding avidity to ligate dimerized SIRPα on macrophage, nature-derived exosomes could be appreciable platform to antagonize CD47. Disruption of CD47-SIRPα interaction by SIRPα-exosomes leads to an increase in cells being engulfed by macrophages and a concomitant inhibition of tumor growth in tumor-bearing mice. Moreover, SIRPα-exosomes therapy promotes an intensive T cell infiltration in syngeneic mouse models of cancer, raising the possibility of CD47-targeted therapies to unleash both an innate and adaptive anti-tumor response. Note that very small amount of exosomal SIRPα proteins could effectively lead to phagocytic elimination of tumor cells both in vitro and in vivo. Our results suggest that superlative exosome-based platform has broad potential to maximize the therapeutic efficacy of membrane-associated protein therapeutics.



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Editorial board

Publication date: March 2017
Source:Biomaterials, Volume 120





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Point-of-Care Ultrasound Diagnosis of Posterior Sternoclavicular Joint Dislocation

Publication date: Available online 10 January 2017
Source:The Journal of Emergency Medicine
Author(s): Rachel R. Bengtzen, Ryan C. Petering
BackgroundPosterior sternoclavicular dislocations can be challenging diagnostically, as traumatic force often happens to the lateral shoulder rather than directly to the sternoclavicular joint. Shoulder radiographs do not illustrate the sternoclavicular joint well, and can miss the diagnosis. This injury, however, has the potential for life-threatening complications due to proximity of mediastinal structures that might also be injured.Case ReportThe following case illustrates a delayed diagnosis of posterior sternoclavicular dislocation. It also shows how point-of-care ultrasound can diagnose a dislocation, confirm persistence of a dislocation diagnosis when patients are transported from a referring facility, as well as educate the patient and family.Why Should an Emergency Physician Be Aware of This?Point-of-care ultrasound can be used to rapidly diagnose posterior sternoclavicular dislocations and to provide patients education about their injury.



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Bilateral multifocal upper extremity atypical granular cell tumors presenting as long-standing right wrist and left hand masses in a 15 year old African American female

Abstract

Granular cell tumor (GrCT) is a benign nerve sheath tumor. Atypical and malignant variants of GrCT are rare but have been well described. We report a case of multifocal symmetric atypical GrCT in the bilateral hand/wrists of a 15 year old African American female. The initial clinical impression for both masses were favored to be ganglion cysts. Ultrasound findings of both masses revealed hypoechoic soft tissue lesions with some internal echogenicity favoring complex cysts. On excision, both masses were histologically circumscribed, lobulated, and attached to tendon. Large epithelioid cells with abundant granular eosinophilic cytoplasm arranged in syncytial cords and trabeculae percolated through collagen. Many cells had pleomorphism and/or prominent nucleoli. Mitotic figures, spindling, high N:C ratio, and necrosis were absent. Both masses showed diffuse S100 protein but negative desmin and pancytokeratin expression. Ki-67 index was 1-2%. p53 was positive in 5-10% of nuclei. Both masses met criteria for atypical (but not malignant) GrCT. Our case shows that atypical GrCT may be not only multifocal but also symmetric. We speculate that migration of defective neural crest stem cells along both upper limb buds during embryogenesis may have allowed these essentially identical tumors to arise in similar locations bilaterally simultaneously.

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“Microbiological findings and antibacterial therapy in Stevens-Johnson syndrome/Toxic Epidermal Necrolysis patients from a Swedish Burn Center”

ABSTRACT

Background

Superimposed infections/sepsis are the major cause of morbidity/mortality in Stevens-Johnson syndrome/Toxic Epidermal Necrolysis (SJS/TEN). It is a delicate balance between avoiding new pharmaceuticals and prophylactically treat an incipient infection. The objective of this study was to investigate the rates and types of infection-microbials and antibiotics involved in SJS/TEN patients.

Methods

Microbiology and clinical data were collected for SJS/TEN patients admitted to our Burn Centre from January 2010 through January 2016.

Results

A total of 24 patients were admitted over the study period. There were 303 bacterial cultures taken whereof 113 (37.3%) were positive (median of 4.4 per patient). Twenty-two (91.7%) patients had at least one positive sample recorded. Fifteen (62.5%) patients had a confirmed episode of sepsis with skin being the most common source of colonization (77.8%). Eleven (45.8%) patients received empiric antibiotic therapy at referral facility/prior to admission to our Centre. Patients who grew a higher number of different species were significantly less likely to have received early empiric antimicrobial therapy (P < .001).

Conclusions

Secondary bacterial infection and sepsis were a highly common finding in our patient population. Despite the risk of resistance and further immunological provocation, empirical antibiotic treatment might have a place in clinical management.

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Angiotropic syringomatous carcinoma

Abstract

Syringomatous carcinoma (SC) is a slow-growing malignant skin tumor that usually affects the face or scalp. An 83-year-old female developed SC on the sole, a rare location. Histopathologically, numerous ducts with few keratinizing cysts were seen in the upper dermis, and cords, strands, and nests with sclerotic stroma were seen in the deep dermis and subcutis. In addition to the perineural and intraneural invasion of the tumor, the tumor cells had also invaded the vessel walls. There was no intravasation of tumor cells or interruption of the endothelium. Because melanoma with vascular wall invasion without intravasation of melanoma cells or interruption of the endothelium has been called angiotropic melanoma, we termed the present tumor angiotropic SC. Tumor cells showed wide local invasion.

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GATA3 EXPRESSION AND ITS RELATIONSHIP WITH CLINICOPATHOLOGICAL PARAMETERS IN INVASIVE BREAST CARCINOMAS

Publication date: Available online 10 January 2017
Source:Pathology - Research and Practice
Author(s): A. Cakir, I. Isik Gonul, O. Ekinci, B. Cetin, M. Benekli, O. Uluoglu
GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p<0.0001), nuclear grade (p=0.001), histological grade (p=0.001), tumor necrosis (p=0.001), stromal lymphocytic response (p<0.01), nipple invasion (p=0.01), metastasis (p=0.03), vimentin (p=0.0003), EGFR (p=0.015) and CK14 (p=0.001) expressions; and directly associated with ER (p<0.0001) and progesterone receptor (PR) (p<0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p<0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p=0.001 and p=0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells.



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Concurrent MET copy number gain and KRAS mutation is a poor prognostic factor in pancreatobiliary subtype ampullary cancers

Publication date: Available online 11 January 2017
Source:Pathology - Research and Practice
Author(s): Mi Jung Kwon, Jeong Won Kim, Jang Yong Jeon, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Kyueng-Whan Min, Ji-Young Choe, Hye Kyung Lee
Hepatocyte growth factor (HGF) and MET are candidates of targeted therapies for cancer patients. Although MET and HGF are commonly expressed in biliary tract cancers, their expression and gene copy number status and their association with KRAS mutations have not been investigated in pancreatobiliary-type ampullary adenocarcinomas (A-ACs), one of the aggressive periampullary cancers. MET and HGF expressions and MET copy number status were examined by performing immunohistochemistry (IHC) and silver in situ hybridization (SISH) in 62 surgically resected, paraffin-embedded tumors, respectively. High MET and HGF protein expressions were detected in 24 (38.7%) and 15 (24.2%) tumors. High MET expression was associated with KRAS mutation. However, there were no associations of high MET/HGF expression alone with other clinicopathological feature or survival. MET SISH positivity was detected in 19 tumors (30.6%), where 84.2% were due to high trisomy or polysomy and only 3 cases (15.8%) were MET gene amplification. The overall MET protein overexpression was well correlated with MET SISH positivity. The concurrent MET SISH positivity and KRAS mutation, not each alone, was an independent poor prognostic factor of disease-free survival only in pancreatobiliary subtype of A-ACs, but not in intestinal subtype.Concurrent MET SISH positivity and KRAS mutation may predict a high risk of recurrence in pancreatobiliary subtype of A-ACs, indicating those markers could be potent candidates for a new therapeutic target in this cancer type. MET IHC can be used as a reliable tool screening for MET copy number status in ampullary cancers.



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Editorial for December JCD

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Issue Information - TOC

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BJD Snippet

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Cosmetics, Vol. 4, Pages 5: Contact Allergy to Castor Oil, but Not to Castor Wax

Ricinus communis (castor) seed oil (CAS 8001-79-4), a vegetable oil extracted from the seeds of Ricinus communis, is widely used in cosmetics and pharmaceuticals, and may be a cause of allergic contact dermatitis from these products. We present two patients with allergic contact dermatitis from cosmetics containing castor oil, in whom a correct diagnosis was achieved by patch testing castor oil 'as is'. PEGylated and/or hydrogenated derivatives (the latter formerly also available from patch test allergen suppliers) and/or cosmetics containing these specific derivatives did not result in contact allergy or allergic contact dermatitis. This observation might be relevant for the manufacturing of cosmetics and pharmaceuticals. In the future, further research into the allergenicity of castor oil and its numerous derivatives, and their optimal patch test concentrations, may be desirable.

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Recent advances in nanomaterial-based biosensors for antibiotics detection

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Lingyi Lan, Yao Yao, Jianfeng Ping, Yibin Ying
Antibiotics are able to be accumulated in human body by food chain and may induce severe influence to human health and safety. Hence, the development of sensitive and simple methods for rapid evaluation of antibiotic levels is highly desirable. Nanomaterials with excellent electronic, optical, mechanical, and thermal properties have been recognized as one of the most promising materials for opening new gates in the development of next-generation biosensors. This review highlights the current advances in the nanomaterial-based biosensors for antibiotics detection. Different kinds of nanomaterials including carbon nanomaterials, metal nanomaterials, magnetic nanoparticles, up-conversion nanoparticles, and quantum dots have been applied to the construction of biosensors with two main signal-transducing mechanisms, i.e. optical and electrochemical. Furthermore, the current challenges and future prospects in this field are also included to provide an overview for future research directions.



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Fabrication strategies, sensing modes and analytical applications of ratiometric electrochemical biosensors

Publication date: 15 May 2017
Source:Biosensors and Bioelectronics, Volume 91
Author(s): Hui Jin, Rijun Gui, Jianbo Yu, Wei Lv, Zonghua Wang
Previously developed electrochemical biosensors with single-electric signal output are probably affected by intrinsic and extrinsic factors. In contrast, the ratiometric electrochemical biosensors (RECBSs) with dual-electric signal outputs have an intrinsic built-in correction to the effects from system or background electric signals, and therefore exhibit a significant potential to improve the accuracy and sensitivity in electrochemical sensing applications. In this review, we systematically summarize the fabrication strategies, sensing modes and analytical applications of RECBSs. First, the different fabrication strategies of RECBSs were introduced, referring to the analytes-induced single- and dual-dependent electrochemical signal strategies for RECBSs. Second, the different sensing modes of RECBSs were illustrated, such as differential pulse voltammetry, square wave voltammetry, cyclic voltammetry, alternating current voltammetry, electrochemiluminescence, and so forth. Third, the analytical applications of RECBSs were discussed based on the types of target analytes. Finally, the forthcoming development and future prospects in the research field of RECBSs were also highlighted.



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Pancreatic Struma with Papillary Thyroid Carcinoma: a Diagnostic Dilemma

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Decreased TAp63 and ΔNp63 mRNA Levels in Most Human Pituitary Adenomas Are Correlated with Notch3/Jagged1 Relative Expression

Abstract

Despite recent advances in molecular genetics, the pituitary adenoma initiation, development, progress, and the molecular basis of their unique features are still poorly understood. In this sense, it is proposed that stem cell could be involved in pituitary adenoma tumorigenesis. It is suggested that TP63 has important functions in stem cells, and it may have interplay of TP63 and Notch and its ligand Jagged in this process. This study aimed to evaluate the distinct expression of TP63 isoforms (TAp63 and ΔNp63), as well as its correlation with Notch3 receptor and its ligand Jagged1 in human pituitary adenomas at the messenger RNA (mRNA) level. We included 77 pituitary adenoma tumor samples from patients who underwent surgical resection. The expression levels of TP63 isoforms (TAp63 and ΔNp63) and Notch3 and its ligand Jagged1 were evaluated by qRT-PCR using isoform-specific primers. We also evaluated proliferation index immunohistochemically using KI-67 antibody. The expression levels were associated with clinical outcomes, as age, gender, tumor size, and tumor subtype. In summary, we found that mRNA expression of both TP63 isoforms decreased in pituitary adenomas compared with normal pituitary control. On the other hand, there was an increase of relative Notch3 and Jagged1 mRNA expression in the majority of examined samples. The mRNA expression of three genes evaluated was correlated and statistically significantly. There was no significant association between gene expression and the analyzed clinical data. The current study has provided the first time evidence that Tap63 and ΔNp63 isoforms are underexpressed in most pituitary adenomas. These results are correlated with Notch3 and its ligand Jagged1 overexpression, corroborating previous studies pointing its antagonistic interactions.

http://ift.tt/2j5jQuU

Muscarinic acetylcholine receptor-mediated tight junction opening is involved in epiphora in late phase of submandibular gland transplantation

Abstract

Submandibular gland (SMG) autotransplantation is an effective therapy for treating severe dry eye syndrome. However, epiphora occurs in more than 40% of patients 6 months after operation. We previously found that muscarinic acetylcholine receptor (mAChR) plays a crucial role in regulating SMG secretion partially through the modulation on tight junction (TJ)-based paracellular pathway. Therefore, the present study aimed to investigate the possible involvement of mAChR and TJ in a rabbit long-term model of SMG transplantation. We found that SMG secretion was significantly increased on postoperative days 90 and 180, which imitated epiphora observed in the patients with SMG transplantation. Although the mRNA expression and fluorescence intensity of M1 and M3 mAChR subtypes were reversed to control levels on postoperative days 30, 90, and 180, the content of β-arrestin2, but not β-arrestin1, was gradually decreased after transplantation, which suggests that mAChR may be hypersensitive in late phase of SMG transplantation. The width of acinar TJs was enlarged and fluorescence intensity of F-actin in peri-apicolateral membranes were remarkably increased on postoperative days 90 and 180. Topical treatment with atropine gel significantly reduced SMG secretion, TJ width, as well as F-actin intensity in peri-apicolateral membranes on postoperative days 180. Moreover, in a perfused rabbit SMG, carbachol increased salivary secretion, enlarged TJ width, and induced F-actin rearrangement, whereas these responses were inhibited by atropine pretreatment. Taken together, our findings suggest that the hypersensitive mAChR may contribute to epiphora in late phase of SMG transplantation through modulating TJ-based paracellular permeability.

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The use of modified ride-on cars to maximize mobility and improve socialization-a group design

Publication date: Available online 10 January 2017
Source:Research in Developmental Disabilities
Author(s): Hsiang-Han Huang, Chia-Ling Chen
AimTo examine the effects of ride-on car (ROC) training versus conventional therapy on mobility and social function in young children with disabilities in a hospital-based environment.Methods and proceduresTwenty young children with disabilities, aged 1–3 years, were recruited. The treatment group (n=10) received ROC training of 2h/session, 2 sessions/week for a total of 9 weeks in the hospital environment. The control group (n=10) received conventional therapy alone. Assessments included the Chinese version of the Pediatric Evaluation of Disability Inventory and the Parenting Stress Index.Outcomes and resultsAfter a 9-week intervention, the treatment group showed improvements in mobility and social function, whereas the control group showed improvements in social function alone. Four children in the treatment group had clinically meaningful changes in mobility and 3 in social function, as compared to 2 and 1, respectively, in the control group.Conclusions and implicationsThis is the first group study that demonstrated the potential benefits of ROC training on mobility and social function in young children with disabilities in the hospital environment. Future studies should include a larger sample size to detect any differences between ROC training and conventional therapy.



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Family adaptation to cerebral palsy in adolescents: A European multicenter study

Publication date: Available online 10 January 2017
Source:Research in Developmental Disabilities
Author(s): Audrey Guyard, Susan I. Michelsen, Catherine Arnaud, Jerome Fauconnier
Background and aimFactors promoting family adaptation to child's disability are poorly studied together. The aim of the study was to describe the family adaptation to disability and to identify determinants associated with using a global theoretical model.Materials and methods286 families of teenagers [13–17 years] with cerebral palsy (CP) from 4 European disability registers were included and visited at home. Face to face interviews were performed in order to measure parental distress, perceived impact in various dimensions of family life, family resources and stressors. Relationships were modelled with structural equations.Results31.8% of parents living with an adolescent with CP showed clinically significant high stress requiring professional assistance. The main stressors were the level of motor impairment and behavioural disorders in adolescent. A good family functioning was the best protective factor. Respite in care and a parents' positive attitude were significantly related to less parental distress. Material support, socioeconomical level, marital status or parental qualifications did not appear to be significant protector factors.ConclusionsParticular attention must be paid not only on physical condition but also on adolescent psychological problems to improve family adaptation. Families at risk of experiencing severe distress should be targeted early and proactive caregiver interventions on the whole family should be performed.What this paper addsFamily is a dynamic system: facing disability, it tries to recover its balance with available resources and its perception of the situation. Literature highlights potential stressors and protecting factors that could affect the disabled child's family adaptation but few papers study a global model including most of these factors. This study validated a global theoretical model of family adaptation to disability at adolescence. It identified behaviour disorders and motor impairment level as main stressors, family functioning as the largest protecting factors, and equipment and financial support as non significant protective factors.



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Exposure of luminous marine bacteria to low-dose gamma-radiation

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): N.S. Kudryasheva, A.S. Petrova, D.V. Dementyev, A.A. Bondar
The study addresses biological effects of low-dose gamma-radiation. Radioactive ¹³⁷Cs-containing particles were used as model sources of gamma-radiation. Luminous marine bacterium Photobacterium phosphoreum was used as a bioassay with the bioluminescent intensity as the physiological parameter tested. To investigate the sensitivity of the bacteria to the low-dose gamma-radiation exposure (≤250 mGy), the irradiation conditions were varied as follows: bioluminescence intensity was measured at 5, 10, and 20°С for 175, 100, and 47 h, respectively, at different dose rates (up to 4100 μGy/h). There was no noticeable effect of gamma-radiation at 5 and 10°С, while the 20°С exposure revealed authentic bioluminescence inhibition. The 20°С results of gamma-radiation exposure were compared to those for low-dose alpha- and beta-radiation exposures studied previously under comparable experimental conditions. In contrast to ionizing radiation of alpha and beta types, gamma-emission did not initiate bacterial bioluminescence activation (adaptive response). As with alpha- and beta-radiation, gamma-emission did not demonstrate monotonic dose-effect dependencies; the bioluminescence inhibition efficiency was found to be related to the exposure time, while no dose rate dependence was found. The sequence analysis of 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose gamma radiation. The exposure time that caused 50% bioluminescence inhibition was suggested as a test parameter for radiotoxicity evaluation under conditions of chronic low-dose gamma irradiation.

Graphical abstract

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Wet deposition and soil content of Beryllium – 7 in a micro-watershed of Minas Gerais (Brazil)

Publication date: April 2017
Source:Journal of Environmental Radioactivity, Volumes 169–170
Author(s): Alexander D. Esquivel L, Rubens M. Moreira, Roberto Pellacani G. Monteiro, Anômora A. Rochido Dos Santos, Jimena Juri Ayub, Diego L. Valladares
Beryllium-7 (⁷Be) is a natural radionuclide of cosmogenic origin, normally used as a tracer for several environmental processes; such as soil redistribution, sediment source discrimination, atmospheric mass transport, and trace metal scavenging from the atmosphere. In this research the content of ⁷Be in soil, its seasonal variation throughout the year and its relationship with the rainfall regime in the Mato Frio creek micro-watershed was investigated, to assess its potential use in estimating soil erosion. The ⁷Be content in soil shows a marked variation throughout the year. Minimum ⁷Be values were observed in the dry season (from April to September) and were between 7 and 14 times higher in the rainy season (from October to March). The seasonal oscillations in ⁷Be soil content could be explained by the asymmetric rainfall regime. A highly linear relationship between rainfall amount and ⁷Be deposition was observed in rain water. A good agreement between ⁷Be soil content and ⁷Be atmospheric deposition was noticed, mainly in wet months. ⁷Be penetration in soil reaches a 5 cm depth, this could be explained by the soil type in the region. The soils are Acrisol type, characterized by low pH values and clay illuviation in deeper layers of the soil. In some regions of Brazil special attention should be paid if this radionuclide will be used as soil erosion tracer, taking into account the soil origin and its particular properties.



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Fifth Terrestrial Radioisotopes in Environment – International Conference on Environmental Protection (TREICEP)

Publication date: Available online 11 January 2017
Source:Journal of Environmental Radioactivity
Author(s): Tibor Kovács, Sheldon Landsberger




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TAF15-ZNF384 fusion gene in childhood mixed phenotype acute leukemia

Publication date: Available online 10 January 2017
Source:Cancer Genetics
Author(s): Li Yao, Jiannong Cen, Jinlan Pan, Dandan Liu, Yong Wang, Zixing Chen, Changgeng Ruan, Suning Chen




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Tracking fluorescent components of dissolved organic matter from soils in large-scale irrigated area

Abstract

Combination of fluorescence excitation-emission matrix spectroscopy with parallel factor analysis (PARAFAC) and principal component analysis (PCA) was engaged to track fluorescent components of dissolved organic matter (DOM) extracted from soils, to seek potential factors, and to reveal their correlations with physico-chemical properties of soils. Soil samples at different depths were collected in Hetao irrigated area of Inner Mongolia, China. Five fluorescent components (C1 to C5) were identified by PARAFAC modeling of DOM extracted from the soil samples. C1 was referred as fulvic-like fluorescent component, by which DOM was dominated in the whole soil samples. C2 was associated with salinity and agriculture, which was similar to marine humic-like fluorescent component. C3 was assigned as traditional humic-like fluorescent component. The three components were of the terrestrial origin. C4 was involved in tryptophan-like fluorescent component, which was autochthonous productions of biological degradation. C5 might be a polycyclic aromatic hydrocarbon contaminant, which could be relative to anthropogenic sources of pesticides. The C1, C2, and C3 were the potential factors of characterizing DOM fractions using PCA on fluorescent components and physico-chemical parameters. Moreover, DOM might restrained by exchangeable sodium percentage, and its formation and decomposition might be influenced by soil moisture.

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Risk assessment of agriculture impact on the Frío River watershed and Caño Negro Ramsar wetland, Costa Rica

Abstract

The Caño Negro Ramsar wetland is a conservation area of great natural and societal value, located in the lower part of the Frío River watershed in the north of Costa Rica. Its aquatic ecosystems may be considered vulnerable to pollution due to recent changes in land use toward agriculture. In 2011 and 2012, quarterly sampling was done at ten sites located in the middle and lower sections of the Frío River Basin that pass through crop areas and later drain into Caño Negro wetland. Pesticide residues, nitrates, sediment concentrations, and diversity of benthic macroinvertebrates and fish biomarkers were studied in the selected sites. Additionally, risk of toxicity was calculated in two different ways: (1) by using a ratio of MEC to hazard concentrations threshold for 5% of species (HC₅) to calculate a risk quotient (RQ), and (2) by using a ratio of MEC to available ecotoxicity data of native fish and cladocera for diazinon and ethoprophos, to obtain a risk quotient for native species (RQns). Results indicated that three out of the ten sites (rivers Thiales, Mónico, and Sabogal) showed variable levels of pollution including six different active ingredients (a.i.) of pesticide formulations (herbicides ametryn, bromacil, and diuron; insecticides cypermethrin, diazinon, and ethoprophos). Moreover, potential adverse effects on fishes in Thiales and Mónico rivers were indicated by cholinesterase (ChE) inhibition and glutathione S-transferase (GST) enhancement. Risk evaluations indicated pesticide residues of ametryn, bromacil, and ethoprophos to be exceeding the limits set by MTR, also RQ was high (>1) in 70% of the positive samples for diuron (most frequently found pesticide in water samples), cypermethrin, diazinon, and ethoprophos, and RQns was high for diazinon. Therefore, these substances might be of major concern for the ecological health of aquatic ecosystems in the middle basin of the Frío River. The most critical site was Mónico River, which had the highest pollution (75% detection samples with 3–5 a.i.) and highest calculated risk (RQ > 1 in 75% of the samples). This is also the river that most directly drains into the protected wetland. Even though pesticide pollution in this area is not as severe as in other parts of Costa Rica, it is imperative that measures are taken, particularly in the surroundings of Mónico River, in order to diminish and mitigate possible detrimental effects to biota in Caño Negro Ramsar Site.

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Practice Makes Perfect: Correlations Between Prior Experience in High-level Athletics and Robotic Surgical Performance Do Not Persist After Task Repetition

Publication date: Available online 10 January 2017
Source:Journal of Surgical Education
Author(s): Kevin Shee, Fady M. Ghali, Elias S. Hyams
ObjectiveRobotic surgical skill development is central to training in urology as well as in other surgical disciplines. Here, we describe a pilot study assessing the relationships between robotic surgery simulator performance and 3 categories of activities, namely, videogames, musical instruments, and athletics.DesignA questionnaire was administered to preclinical medical students for general demographic information and prior experiences in surgery, videogames, musical instruments, and athletics. For follow-up performance studies, we used the Matchboard Level 1 and 2 modules on the da Vinci Skills Simulator, and recorded overall score, time to complete, economy of motion, workspace range, instrument collisions, instruments out of view, and drops. Task 1 was run once, whereas task 2 was run 3 times.SettingAll performance studies on the da Vinci Surgical Skills Simulator took place in the Simulation Center at Dartmouth-Hitchcock Medical Center.ParticipantsAll participants were medical students at the Geisel School of Medicine. After excluding students with prior hands-on experience in surgery, a total of 30 students completed the study.ResultsWe found a significant correlation between athletic skill level and performance for both task 1 (p = 0.0002) and task 2 (p = 0.0009). No significant correlations were found for videogame or musical instrument skill level. Students with experience in certain athletics (e.g., volleyball, tennis, and baseball) tended to perform better than students with experience in other athletics (e.g., track and field). For task 2, which was run 3 times, this association did not persist after the third repetition due to significant improvements in students with low-level athletic skill (levels 0-2).ConclusionsOur study suggests that prior experience in high-level athletics, but not videogames or musical instruments, significantly influences surgical proficiency in robot-naive students. Furthermore, our study suggests that practice through task repetition can overcome initial differences that may be related to a background in athletics. These novel relationships may have broader implications for the future recruitment and training of robotic surgeons and may warrant further investigation.



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Mitigating cadmium accumulation in greenhouse lettuce production using biochar

Abstract

Greenhouse experiments were conducted to investigate the influence of rice straw biochar (RSB) on soil cadmium (Cd) availability and accumulation in lettuce. The RSB was applied either in bands or broadcast in the test site of four greenhouses with soil Cd concentrations ranging from 1.70–3.14 μg g⁻¹. Biochar doses applied in bands were half of those broadcast. The Cd levels in the shoots of lettuce were observed to be reduced by up to 57% with increasing RSB application rate (0, 6, 12, 18 t ha⁻¹). Following RSB application, shoot Cd concentrations of lettuce were reduced to below the Chinese threshold value set for food, and hazard quotients for Cd associated with vegetable consumption were reduced from 0.70–1.11 to 0.42–0.65. A decrease in soil bulk density (11%) and increases in water holding capacity (16%), available phosphorus (30%), available potassium (197%), and lettuce yield (15%) were observed after RSB application. Multiple linear regression analysis suggested that the soil extractable Cd level (but not biomass dilution) and soil bulk density, as influenced by RSB addition, were the dominant contributors to the shoot Cd levels in lettuce and lettuce yield, respectively. These results highlight the potential for RSB to mitigate the phytoaccumulation of Cd and thereby to reduce human exposure from vegetable consumption. Application of biochar in band, rather than broadcasting over the entire area, represents an opportunity to halve the biochar cost while retaining a good remediation effect.

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Microbial flora analysis for the degradation of beta-cypermethrin

Abstract

In the Xinjiang region of Eurasia, sustained long-term and continuous cropping of cotton over a wide expanse of land is practiced, which requires application of high levels of pyrethroid and other classes of pesticides—resulting in high levels of pesticide residues in the soil. In this study, soil samples were collected from areas of long-term continuous cotton crops with the aim of obtaining microbial resources applicable for remediation of pyrethroid pesticide contamination suitable for the soil type and climate of that area. Soil samples were first used to culture microbial flora capable of degrading beta-cypermethrin using an enrichment culture method. Structural changes and ultimate microbial floral composition during enrichment were analyzed by high-throughput sequencing. Four strains capable of degrading beta-cypermethrin were isolated and preliminarily classified. Finally, comparative rates and speeds of degradation of beta-cypermethrin between relevant microbial flora and single strains were determined. After continuous subculture for 3 weeks, soil sample microbial flora formed a new type of microbial flora by rapid succession, which showed stable growth by utilizing beta-cypermethrin as the sole carbon source (GXzq). This microbial flora mainly consisted of Pseudomonas, Hyphomicrobium, Dokdonella, and Methyloversatilis. Analysis of the microbial flora also permitted separation of four additional strains; i.e., GXZQ4, GXZQ6, GXZQ7, and GXZQ13 that, respectively, belonged to Streptomyces, Enterobacter, Streptomyces, and Pseudomonas. Under culture conditions of 37 °C and 180 rpm, the degradation rate of beta-cypermethrin by GXzq was as high as 89.84% within 96 h, which exceeded that achieved by the single strains GXZQ4, GXZQ6, GXZQ7, and GXZQ13 and their derived microbial flora GXh.

http://ift.tt/2jhLC57

Efficient photo–catalytic degradation of malachite green using nickel tungstate material as photo–catalyst

Abstract

The present study focused on the evaluation of photo-catalytic and photo–electrochemical properties of the photo–catalyst based on nickel tungstate material prepared by a nitrate method through the degradation of malachite green (MG) dye's. The effect of catalyst loading and dye concentration was examined. Physico–chemical, optical, electrical, electrochemical, and photo–electrochemical properties of the prepared material were analyzed by X-ray diffraction (XRD), fourier transform–infrared spectroscopy (FTIR), BET analysis, optical reflectance diffuse (DR), scanning electron microscopy (SEM/EDX), electrical conductivity, cyclic voltammetry (CV), current intensity, mott–shottky, and nyquist. XRD revealed the formation of monoclinic structure with a small particle size. BET surface area of the sample was around 10 m²/g. The results show that the degradation of MG was more than 80%, achieved after 3 h of irradiation at pH 4.6 and with a catalyst loading of 75 mg. Also, it was found that the dye photo–degradation obeyed the pseudo-first order kinetic via Langmuir Hinshelwood model.

http://ift.tt/2j4U9uq

Improved slant drilling well for in situ remediation of groundwater and soil at contaminated sites

Abstract

Soil contamination has become a crucial issue in urban redevelopment. Japan has many contaminated sites on which manufacturing has been conducted over several decades. Site holders are now under pressure to manage chemical contamination; however, the use of heavy machinery is difficult in remedial operations on restricted sites, especially where there are still working factories. The slant well is a potentially useful technique in such settings, but its use is technically challenging because of the need for high drilling accuracy and the difficulty in sealing the slanted bores. In this study, we investigated an improved technique for slant drilling that can be used around existing structures to treat contaminated soil and groundwater. A key to this novel approach was the use of water-swelling materials as sealants. Research at a test site investigated the accuracy of drilling. Tracer tests were also conducted using sodium chloride and urea. The improved slant borings showed a deviation of less than 2% from the target bore. The spread of the two tracers at different depths was demonstrated. The proposed technique provides a useful approach to the treatment of brownfield sites in countries where in situ remediation has not yet been undertaken.

http://ift.tt/2j4V1PN

Comparative toxicity of nano ZnO and bulk ZnO towards marine algae Tetraselmis suecica and Phaeodactylum tricornutum

Abstract

The wide use of ZnO nanoparticles in a number of products implies an increasing release into the marine environment, resulting in the need to evaluate the potential effects upon organisms, and particularly phytoplankton, being at the base of the throphic chain. To this aim, dose–response curves for the green alga Tetraselmis suecica and the diatom Phaeodactylum tricornutum derived from the exposure to nano ZnO (100 nm) were evaluated and compared with those obtained for bulk ZnO (200 nm) and ionic zinc. The toxic effects to both algae species were reported as no observable effect concentration (NOEC) of growth inhibition and as 1, 10, and 50% effect concentrations (EC1, EC10, and EC50). The toxicity decreased in the order nano ZnO > Zn²⁺ > bulk ZnO. EC50 values for nano ZnO were 3.91 [3.66–4.14] mg Zn/L towards the green microalgae and 1.09 [0.96–1.57] mg Zn/L towards the diatom, indicating a higher sensitivity of P. tricornutum. The observed diverse effects can be ascribed to the interaction occurring between different algae and ZnO particles. Due to algae motility, ZnO particles were intercepted in different phases of aggregation and sedimentation processes, while algae morphology and size can influence the level of entrapment by NP aggregates.

This underlines the need to take into account the peculiarity of the biological system in the assessment of NP toxicity.

http://ift.tt/2jhPqU5

Evaluation of 2D resistivity imaging technique for delineating subsurface seepage of hydrocarbon-contaminated water southeast of Karbala city, Iraq

Abstract

2D imaging technique was applied in (8) transects near a pit of contaminated water near contaminated well southeast of Karbala city, Iraq. Each transect was 30 m long with 1 m electrode spacing. Data acquisition was fulfilled by using Wenner electrode array. The resistivity of water-contaminated zone is found less than 3Ω.m and the top dry zone recorded relatively high resistivity (more than 170Ω.m). It is found that the greatest amount of seepage was found moving towards northeast direction coincided with groundwater movement direction, whereas there was no movement towards northwest and southeast directions and restricted on the closest areas to the pit location. The outcomes suggested that the 2D imaging technique is a successful and powerful tool in separating contaminated zone from clear one and in detecting underground seepage depth and moving direction.

http://ift.tt/2j5feov

Determination of cytostatic drugs in Besòs River (NE Spain) and comparison with predicted environmental concentrations

Abstract

The number of cytostatic drugs used in cancer treatments is wide and increases every year; therefore, tools have been developed to predict their concentration in the environment to prioritize those for monitoring studies. In the present study, the predicted environmental concentrations (PECs) were calculated according to consumption data in Catalonia (NE Spain) for 2014. According to PECs and to the most widely reported compounds, 19 cytostatics were monitored in two sampling campaigns performed along the Besòs River. A total of seven drugs were detected at levels between 0.5 and 656 ng L⁻¹. PEC and measured environmental concentrations (MECs) were compared in order to validate PECs. The PEC/MEC ratio presented a good agreement between predicted and measured concentrations confirming the PEC estimations. Mycophenolic acid, prioritized as the compound with the highest PEC, was detected at the highest concentrations (8.5–656 ng L⁻¹) but showed no risk for aquatic organisms (risk quotient <1) considering acute toxicity tests performed in Daphnia magna.

http://ift.tt/2jhPnYc

Assessment of metal contamination in the Hun River, China, and evaluation of the fish Zacco platypus and the snail Radix swinhoei as potential biomonitors

Abstract

The Hun River is a major tributary of the Liao River in the northeast area of China and provides drinking water for 23 million local residents. This study was designed to assess the severity of metal contamination in the Hun River and the potential use of indigenous organisms (the fish Zacco platypus and the snail Radix swinhoei) as biomonitors of metal contamination. Water, sediment, and the native fish and snails were collected at four sampling sites that differed in their physicochemical characteristics and their contamination levels. The samples were analyzed for Cd, Cr, Cu, Ni, Pb, and Zn by ICP-MS. The results showed that although the overall potential ecological risks of the metals were low at our sampling sites, Cd posed a noteworthy ecological risk. Strong correlations were obtained between Cd concentrations in the organisms and in the environment. The results indicated that Z. platypus and R. swinhoei can be useful biomonitoring species for assessing Cd contamination. Biomonitoring with the snail may be most effective when focused on the gonad/digestive tissue (because of the high metal accumulation there), but further work is needed to confirm this.

http://ift.tt/2jhTq6X

Hydroxy-Carboxylic Acid Receptor Actions in Metabolism

Publication date: Available online 10 January 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Stefan Offermanns
Lactic acid, the ketone body 3-hydroxy-butyric acid, also known as β-hydroxybutyrate, and the β-oxidation intermediate 3-hydroxy-octanoic acid are hydroxy-carboxylic acids (HCAs) that serve as intermediates of energy metabolism. However, they also regulate cellular functions, in part by directly activating the G protein-coupled receptors HCA1/GPR81, HCA2/GPR109A, and HCA3/GPR109B. During the past decade, it has become clear that HCA receptors help to maintain homeostasis under changing metabolic and dietary conditions, by controlling metabolic, immune, and other body functions. Work based on genetic mouse models and synthetic ligands of HCA receptors has, in addition, shown that members of this receptor family can serve as targets for the prevention and therapy of diseases such as metabolic and inflammatory disorders.



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Cardiac Lymphatics – A New Avenue for Therapeutics?

Publication date: Available online 10 January 2017
Source:Trends in Endocrinology & Metabolism
Author(s): Taina Vuorio, Annakaisa Tirronen, Seppo Ylä-Herttuala
Recent progress in lymphatic vessel biology and in novel imaging techniques has established the importance of the lymphatic vasculature as part of the cardiovascular system. The lymphatic vessel network regulates many physiological processes important for heart function such as fluid balance, transport of extravasated proteins, and trafficking of immune cells. Therefore, lymphangiogenic therapy could be beneficial in the treatment of cardiovascular diseases, for example by improving reverse cholesterol transport (RCT) from atherosclerotic lesions or by resolving edema and fibrosis after myocardial infarction. In this review we first describe recent findings on the development and function of cardiac lymphatic vessels, and subsequently focus on the prospects of pro- and anti-lymphangiogenic therapies in cardiovascular diseases.



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Early-phase trial demonstrates shrinkage in pediatric neural tumors

In an early-phase clinical trial of a new oral drug, selumetinib, children with the common genetic disorder neurofibromatosis type 1 (NF1) and plexiform neurofibromas, tumors of the peripheral nerves, tolerated selumetinib and, in most cases, responded to it with tumor shrinkage.

http://ift.tt/2huW9uH

Cellular Immunotherapy Targets a Common Human Cancer Mutation

In a study of an immune therapy for colorectal cancer that involved a single patient, researchers identified a method for targeting the cancer-causing protein produced by a mutant form of the KRAS gene.

http://ift.tt/2gEcGcQ

No Safe Level of Smoking: Even low-intensity smokers are at increased risk of earlier death

People who consistently smoked an average of less than one cigarette per day over their lifetimes had a 64 percent higher risk of earlier death than people who never smoked.

http://ift.tt/2gM6K4A

NCI collaborates with Multiple Myeloma Research Foundation

The National Cancer Institute (NCI) announced a collaboration with the Multiple Myeloma Research Foundation (MMRF) to incorporate MMRF's wealth of genomic and clinical data on the disease into the NCI Genomic Data Commons (GDC), a publicly available database.

http://ift.tt/2duYdD4

NCI embraces scientific road map to achieve Cancer Moonshot goals

National Cancer Institute Acting Director Douglas Lowy, M.D., today accepted, with revisions that reflect NCAB's discussion, the recommendations of a Blue Ribbon Panel (BRP) on 10 approaches most likely to make a decade's worth of progress against cancer in five years, a key goal of the White House Cancer Moonshot.

http://ift.tt/2ihRNYp

Oxygen can impair cancer immunotherapy in mice

Researchers have identified a mechanism in mice by which anticancer immune responses are inhibited within the lungs, a common site of metastasis for many cancers.

http://ift.tt/2ieVhI0

Uncovering a new principle in chemotherapy resistance in breast cancer

A laboratory study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.

http://ift.tt/2ieGywG

International collaboration to create new cancer models to accelerate research

An international project to develop a large, globally accessible bank of new cancer cell culture models for the research community launched today.

http://ift.tt/2ihRrB2

NCI launches largest-ever study of breast cancer genetics in black women

The Breast Cancer Genetic Study in African-Ancestry Populations initiative is a collaborative research project that will identify genetic factors that may underlie breast cancer disparities. It is the largest study ever to investigate how genetic and biological factors contribute to breast cancer risk among black women.

http://ift.tt/2ieXfry

Significant expansion of data available in the Genomic Data Commons

The recently launched Genomic Data Commons will get a dramatic increase in the power and utility of its resources with the signing today of a data sharing agreement between the NCI and Foundation Medicine, Inc. (FMI), a molecular information company.

http://ift.tt/2dFcSuO

Beyond the Paradigm: Combining Mass Spectrometry and Nuclear Magnetic Resonance for Metabolomics

Publication date: Available online 11 January 2017
Source:Progress in Nuclear Magnetic Resonance Spectroscopy
Author(s): Darrell D. Marshall, Robert Powers
Metabolomics is undergoing tremendous growth and is being employed to solve a diversity of biological problems from environmental issues to the identification of biomarkers for human diseases. Nuclear magnetic resonance (NMR) and mass spectrometry (MS) are the analytical tools that are routinely, but separately, used to obtain metabolomics data sets due to their versatility, accessibility, and unique strengths. NMR requires minimal sample handling without the need for chromatography, is easily quantitative, and provides multiple means of metabolite identification, but is limited to detecting the most abundant metabolites (⩾ 1 μM). Conversely, mass spectrometry has the ability to measure metabolites at very low concentrations (femtomolar to attomolar) and has a higher resolution (∼10³-10⁴) and dynamic range (∼10³-10⁴), but quantitation is a challenge and sample complexity may limit metabolite detection because of ion suppression. Consequently, liquid chromatography (LC) or gas chromatography (GC) is commonly employed in conjunction with MS, but this may lead to other sources of error. As a result, NMR and mass spectrometry are highly complementary, and combining the two techniques is likely to improve the overall quality of a study and enhance the coverage of the metabolome. While the majority of metabolomic studies use a single analytical source, there is a growing appreciation of the inherent value of combining NMR and MS for metabolomics. An overview of the current state of utilizing both NMR and MS for metabolomics will be presented.

Graphical abstract

http://ift.tt/2ibOsvv

Molecular biomarkers to predict response to neoadjuvant chemotherapy for bladder cancer

Publication date: Available online 11 January 2017
Source:Cancer Treatment Reviews
Author(s): Consuelo Buttigliero, Marcello Tucci, Francesca Vignani, Giorgio V. Scagliotti, Massimo Di Maio
Cystectomy is the gold standard for treatment of localized muscle-invasive bladder cancer. However, about 50% of patients develop metastases within 2 years after cystectomy and subsequently die for the disease. Neoadjuvant cisplatin-based chemotherapy before cystectomy improves the overall survival in patients with muscle-invasive bladder cancer, and pathological response to neoadjuvant treatment (downstaging to ⩽pT1 at cystectomy) is a strong predictor of better disease-specific survival. Nevertheless, some patients do not benefit from neoadjuvant therapy. The identification of reliable biomarkers that could enable the clinicians to identify patients who will really benefit from neoadjuvant chemotherapy is a major issue. This approach could lead to individualized therapy, in order to optimize the chance of response, avoiding the impact of neoadjuvant treatment on quality of life and the delay of cystectomy in non-responder patients. However, no molecular predictive biomarkers have shown clinical utility.This paper aims to review currently available data about biomarkers predictive of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer.



http://ift.tt/2iEdK1r

Robust Estimation of Carotid Artery Wall Motion Using the Elasticity-based State-space Approach

Publication date: Available online 10 January 2017
Source:Medical Image Analysis
Author(s): Zhifan Gao, Huahua Xiong, Xin Liu, Heye Zhang, Dhanjoo Ghista, Wanqing Wu, Shuo Li
The dynamics of the carotid artery wall has been recognized as a valuable indicator to evaluate the status of atherosclerotic disease in the preclinical stage. However, it is still a challenge to accurately measure this dynamics from ultrasound images. This paper aims at developing an elasticity-based state-space approach for accurately measuring the two-dimensional motion of the carotid artery wall from the ultrasound imaging sequences. In our approach, we have employed a linear elasticity model of the carotid artery wall, and converted it into the state space equation. Then, the two-dimensional motion of carotid artery wall is computed by solving this state-space approach using the H∞ filter and the block matching method. In addition, a parameter training strategy is proposed in this study for dealing with the parameter initialization problem. In our experiment, we have also developed an evaluation function to measure the tracking accuracy of the motion of the carotid artery wall by considering the influence of the sizes of the two blocks (acquired by our approach and the manual tracing) containing the same carotid wall tissue and their overlapping degree. Then, we have compared the performance of our approach with the manual traced results drawn by three medical physicians on 37 healthy subjects and 103 unhealthy subjects. The results have showed that our approach was highly correlated (Pearson's correlation coefficient equals 0.9897 for the radial motion and 0.9536 for the longitudinal motion), and agreed well (width the 95% confidence interval is 89.62 μm for the radial motion and 387.26 μm for the longitudinal motion) with the manual tracing method. We also compared our approach to the three kinds of previous methods, including conventional block matching methods, Kalman-based block matching methods and the optical flow. Altogether, we have been able to successfully demonstrate the efficacy of our elasticity-model based state-space approach (EBS) for more accurate tracking of the 2-dimensional motion of the carotid artery wall, towards more effective assessment of the status of atherosclerotic disease in the preclinical stage.

Graphical abstract

http://ift.tt/2iey74i

A Framework for Analysis of Linear Ultrasound Videos to Detect Fetal Presentation and Heartbeat

Publication date: Available online 10 January 2017
Source:Medical Image Analysis
Author(s): M.A. Maraci, C.P. Bridge, R. Napolitano, A. Papageorghiou, J.A. Noble
Confirmation of pregnancy viability (presence of fetal cardiac activity) and diagnosis of fetal presentation (head or buttock in the maternal pelvis) are the first essential components of ultrasound assessment in obstetrics. The former is useful in assessing the presence of an on-going pregnancy and the latter is essential for labour management. We propose an automated framework for detection of fetal presentation and heartbeat from a predefined free-hand ultrasound sweep of the maternal abdomen. Our method exploits the presence of key anatomical sonographic image patterns in carefully designed scanning protocols to develop, for the first time, an automated framework allowing novice sonographers to detect fetal breech presentation and heartbeat from an ultrasound sweep. The framework consists of a classification regime for a frame by frame categorization of each 2D slice of the video. The classification scores are then regularized through a conditional random field model, taking into account the temporal relationship between the video frames. Subsequently, if consecutive frames of the fetal heart are detected, a kernelized linear dynamical model is used to identify whether a heartbeat can be detected in the sequence. In a dataset of 323 predefined free-hand videos, covering the mother's abdomen in a straight sweep, the fetal skull, abdomen, and heart were detected with a mean classification accuracy of 83.4%. Furthermore, for the detection of the heartbeat an overall classification accuracy of 93.1% was achieved.

Graphical abstract

http://ift.tt/2iepDKw

Remarks about “A pediatric patient of hemorrhagic acute transverse myelitis”

Publication date: Available online 11 January 2017
Source:Brain and Development
Author(s): Daniele Coraci, Valter Santilli, Silvia Giovannini, Luca Padua




http://ift.tt/2j4x4YL

Reply to the remarks about “A pediatric patient of hemorrhagic acute transverse myelitis”

Publication date: Available online 11 January 2017
Source:Brain and Development
Author(s): Masataka Fukuoka, Ichiro Kuki, Hisashi Kawawaki, Kiyohiro Kim, Yuka Hattori, Hitomi Tsuji, Asako Horino, Megumi Nukui, Shin Okazaki




http://ift.tt/2jhnUWJ

Bilateral blepharoptosis in a juvenile

Publication date: Available online 10 January 2017
Source:Brain and Development
Author(s): Hiroshi Yamaguchi, Tsukasa Tanaka, Daisaku Toyoshima, Azusa Maruyama, Akihiro Ichinose, Hiroaki Nagase
In adults, aponeurotic blepharoptosis is the most common type of ptosis. However, myogenic ptosis is the predominant cause, and bilateral aponeurotic ptosis is very rare among children. Here, we report a previously healthy 10-year-old Japanese girl with bilateral aponeurotic blepharoptosis who presented initially with bilateral blepharoptosis for about 4years. This case report shows that history taking and careful observation of the patient lead to an accurate diagnosis, and aponeurotic ptosis should be considered in the differential diagnosis of bilateral blepharoptosis among children.



http://ift.tt/2j4bWlt

Epigenetic modifications and epigenetic based medication implementations of autoimmune diseases

Publication date: March 2017
Source:Biomedicine & Pharmacotherapy, Volume 87
Author(s): Majid Ahmadi, Tohid Gharibi, Sanam Dolati, Davood Rostamzadeh, Saeed Aslani, Behzad Baradaran, Vahid Younesi, Mehdi Yousefi
Recent genome-wide association studies have documented a number of genetic variants to explain mechanisms underlying autoimmune diseases. However, the precise etiology of autoimmune diseases remains largely unknown. Epigenetic mechanisms like alterations in the post-translational modification of histones and DNA methylation may potentially cause a breakdown of immune tolerance and the perpetuation of autoreactive responses. Recently, several studies both in experimental models and clinical settings proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in autoimmune diseases, in some cases based on mechanistical observations. Epigenetic therapy already being employed in hematopoietic malignancies may also be associated with beneficial effects in autoimmune diseases. In this review, we will discuss on what we know and expect about the treatment of autoimmune disease based on epigenetic aberrations.



http://ift.tt/2iDTwoC

Clinical effectiveness of low-level laser treatment on peripheral somatosensory neuropathy

Abstract

Peripheral sensory neuropathy treatment is one of the common treatment problems and causes morbidity and mortality in people suffering from that. Although treatment depends on the underlying cause of the condition, nevertheless, in some cases, there is no cure for it, and it requires palliative and symptomatic treatment. In laboratory studies, low-level laser has been effective in the nerves protection and restoration. The aim of this article is to investigate the clinical efficacy of low-level laser on improvement of the peripheral somatosensory neuropathy. Search in the articles published up to 30 October 2015 (full text and abstracts) in databases PubMed (Medline), Cochrane library, Physiotherapy Evidence Database was performed. The studies of low-level laser trials on patients with peripheral neuropathy were carried out and evaluated in terms of the exclusion criteria. There are 35 articles among which 10 articles had the intended and required criteria. 1, 3, and 6 articles study the patients with diabetes, neuropathy caused by trauma, and carpal tunnel syndrome, respectively. In six studies, laser led to a reduction in sensory impairment and improvement of the physiological function of the sensory nerves. In these articles, lasers (Diode, GaAlAs, He-Ne) had wavelength range 660–860 nm, radiation power 20–250 mW, energy density 0.45–70 J/cm². The intervention sessions range was 6–21 times and patient follow-up was 0–6 months. According to the results of these studies, low-level laser therapy can improve sensory function in patients with peripheral somatosensory neuropathy, although little research have not been done, laser treatment regimens are varied and do not recommend a specific treatment protocol. It seems it requires more research to sum up better, particularly in relation to diabetes.

http://ift.tt/2jh3Cwn

Clinical Thyroidology for the Public – Highlighted Article

From Clinical Thyroidology for the Public: Hypothyroidism (underactive thyroid) is very common, especially in women and is diagnosed most of the time by an increased TSH level. Read More….

The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.

http://ift.tt/2jh9XIl

BDNF gene delivery mediated by neuron-targeted nanoparticles is neuroprotective in peripheral nerve injury

Publication date: March 2017
Source:Biomaterials, Volume 121
Author(s): Cátia D.F. Lopes, Nádia P. Gonçalves, Carla P. Gomes, Maria J. Saraiva, Ana P. Pêgo
Neuron-targeted gene delivery is a promising strategy to treat peripheral neuropathies. Here we propose the use of polymeric nanoparticles based on thiolated trimethyl chitosan (TMCSH) to mediate targeted gene delivery to peripheral neurons upon a peripheral and minimally invasive intramuscular administration. Nanoparticles were grafted with the non-toxic carboxylic fragment of the tetanus neurotoxin (HC) to allow neuron targeting and were explored to deliver a plasmid DNA encoding for the brain-derived neurotrophic factor (BDNF) in a peripheral nerve injury model. The TMCSH-HC/BDNF nanoparticle treatment promoted the release and significant expression of BDNF in neural tissues, which resulted in an enhanced functional recovery after injury as compared to control treatments (vehicle and non-targeted nanoparticles), associated with an improvement in key pro-regenerative events, namely, the increased expression of neurofilament and growth-associated protein GAP-43 in the injured nerves. Moreover, the targeted nanoparticle treatment was correlated with a significantly higher density of myelinated axons in the distal stump of injured nerves, as well as with preservation of unmyelinated axon density as compared with controls and a protective role in injury-denervated muscles, preventing them from denervation. These results highlight the potential of TMCSH-HC nanoparticles as non-viral gene carriers to deliver therapeutic genes into the peripheral neurons and thus, pave the way for their use as an effective therapeutic intervention for peripheral neuropathies.



http://ift.tt/2ibqHPt