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Amar Patel, Lawrence Fong
Immunotherapies have emerged as a revolutionary modality for cancer treatment, and a variety of immune-based approaches are currently being investigated in the field of prostate cancer. Despite the 2010 approval of sipuleucel-T, subsequent progress in prostate cancer immunotherapy development has been limited by disappointing results with novel vaccination approaches and by prostate cancer's general resistance to immune checkpoint blockade. Nevertheless, there remains strong preclinical and clinical evidence to suggest that prostate cancer is a susceptible target for immune therapies...
March 15, 2018: Oncology (Williston Park, NY)
Werner de Cruppé, Max Geraedts
STUDY AIM: The minimum volume standards for hospitals in Germany, in force since 2004, provide four exemptions for non-complying hospitals. This study investigates the extent and importance of these exemptions for complex procedures on the oesophagus and pancreas for all non-complying hospitals and for the revised minimum volume regulations in force since the beginning of 2018. METHOD: Longitudinal, descriptive analyses of data on minimum volume standards and their exemptions for complex procedures on the oesophagus and pancreas, as presented by the hospital quality report cards of the reporting years from 2006 to 2014...
March 16, 2018: Zentralblatt Für Chirurgie
Michael Platten, David A Reardon
Strategies to empower the immune system to successfully attack cancers, including vaccination approaches, adaptive T cell therapies, and immune checkpoint modulators, have recently achieved remarkable success across a spectrum of cancer indications. Nonetheless, with rare exception, only a minority of patients with a given type of cancer respond to an immunotherapeutic when administered as single-agent therapy. Although under extensive laboratory and clinical investigation, the role of these approaches for glioma patients remains to be determined...
February 2018: Seminars in Neurology
Julie J Miller, Wolfgang Wick
The majority of World Health Organization grade II and grade III gliomas harbor heterozygous mutations in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1), and tumors with an IDH wild-type status show molecular features of a glioblastoma and simply may constitute a separate disease entity. This discovery has led to a profound shift in the way that gliomas are classified and, consequently, how treatment decisions are made. We will review the current understanding of IDH- mutant gliomagenesis and the preclinical models being used to investigate the underlying biology of these tumors and to explore new therapeutic options for these patients...
February 2018: Seminars in Neurology
Maria Martinez-Lage, Felix Sahm
The updated 2016 WHO classification of Central Nervous System tumors introduced a novel concept of neuropathology diagnostics. Molecular parameters are now included into the definition of several entities. This evolution from a previously purely histology-based classification to an integrated approach of histology and genetic characteristics has implications in daily diagnostic and clinical practice. Both the spectrum of diagnostic workup demanded from the neuropathologist and the range of relevant markers to be considered by clinicians and clinical investigators have increased...
February 2018: Seminars in Neurology
Caroline Charette, Krista L Best, Emma M Smith, William C Miller, François Routhier
Background: Mobility limitations represent the third most prevalent cause of disability, affecting more than 1.9 million community-dwelling Canadians. Walking aids are often prescribed to reduce the impacts of mobility impairments. There are limited data on walking aids since 2004. Objective: The objective of this study was to investigate the prevalence of walking aid use in Canada and to explore demographic characteristics among users of walking aids. Design: The design used was a secondary analysis of a cross-sectional national survey...
March 14, 2018: Physical Therapy
Michelle M Valdez, Maureen Liwanag, Charles Mount, Rechell Rodriguez, Elisea Avalos-Reyes, Andrew Smith, David Collette, Michael Starsiak, Richard Green
Introduction: Inefficiencies in the command approval process for publications and/or presentations negatively impact DoD Graduate Medical Education (GME) residency programs' ability to meet ACGME scholarly activity requirements. A preliminary review of the authored works approval process at Naval Medical Center San Diego (NMCSD) disclosed significant inefficiency, variation in process, and a low level of customer satisfaction. In order to facilitate and encourage scholarly activity at NMCSD, and meet ACGME requirements, the Executive Steering Council (ESC) chartered an interprofessional team to lead a Lean Six Sigma (LSS) Rapid Improvement Event (RIE) project...
March 14, 2018: Military Medicine
Marco Armando, Corrado Sandini, Maelle Chambaz, Marie Schaer, Maude Schneider, Stephan Eliez
Converging evidence suggests that psychosis emerges from the complex interaction of genetic and environmental factors. Stressful life events (SLEs) play a prominent role in combination with coping strategies and with a dysfunctional hypothalamus-pituitary-adrenal axis (HPAA). It has been proposed that the framework of schizotypy might help disentangle the interaction between genetic and environmental factors in the pathogenesis of psychosis. Similarly, 22q11.2 deletion syndrome (22q11DS) is considered as a genetic model of psychosis vulnerability...
March 14, 2018: Schizophrenia Bulletin
Charles Cole, Ashley Byrne, Anna E Beaudin, E Camilla Forsberg, Christopher Vollmers
RNA-sequencing (RNA-seq) is a powerful technique to investigate and quantify entire transcriptomes. Recent advances in the field have made it possible to explore the transcriptomes of single cells. However, most widely used RNA-seq protocols fail to provide crucial information regarding transcription start sites. Here we present a protocol, Tn5Prime, that takes advantage of the Tn5 transposase-based Smart-seq2 protocol to create RNA-seq libraries that capture the 5' end of transcripts. The Tn5Prime method dramatically streamlines the 5' capture process and is both cost effective and reliable...
March 14, 2018: Nucleic Acids Research
Anna M Hammersmith
Purpose: Parents' and children's lives are interwoven over the life course. Parents' positivity and negativity toward children relate to children's and parents' transitions, although the nature of this relationship is unclear. This study investigated the extent to which transitions-like those tied to residence, unions, employment, parenthood, and health-related to parents' positivity and negativity. Method: This study used the Health and Retirement Study's Psychosocial Survey from 2006 and 2010 to examine how parents' and children's transitions related to parents' positivity and negativity toward children...
March 14, 2018: Gerontologist
Daniella C Parravano, Daniel A Ciampi, Erich T Fonoff, Bernardo Monaco, Jessie Navarro, Lin T Yeng, Manoel J Teixeira, Clement Hamani
BACKGROUND: Motor cortex stimulation (MCS) is routinely used for the treatment of chronic neuropathic pain but its effect on quality of life remains uncertain. OBEJCTIVE: To systematically review the published literature on MCS and quality of life and report the effects of this therapy in a series of patients prospectively followed in our center. METHODS: The systematic literature review was conducted using the search words "motor cortex stimulation and pain and neurosurgery" and "motor cortex stimulation and pain and quality of life...
March 14, 2018: Neurosurgery
Huanhuan Hu, Naoko Sasaki, Takayuki Ogasawara, Satsue Nagahama, Shamima Akter, Keisuke Kuwahara, Takeshi Kochi, Masafumi Eguchi, Ikuko Kashino, Taizo Murakami, Makiko Shimizu, Akihiko Uehara, Makoto Yamamoto, Tohru Nakagawa, Toru Honda, Shuichiro Yamamoto, Ai Hori, Chihiro Nishiura, Hiroko Okazaki, Teppei Imai, Akiko Nishihara, Toshiaki Miyamoto, Kentaro Tomita, Isamu Kabe, Tetsuya Mizoue, Naoki Kunugita, Seitaro Dohi
Introduction: We aimed to determine the prospective association of smoking status, smoking intensity, and smoking cessation with the risk of hearing loss in a large Japanese cohort. Methods: The cohort study included 50195 employees, who were aged 20-64 years and free of hearing loss at baseline. Participants were followed up for a maximum of 8 years. Pure-tone audiometric testing was performed annually to identify hearing loss at 1 and 4 kHz. Cox proportional hazards regression models were used to investigate the association between smoking and hearing loss...
March 14, 2018: Nicotine & Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco
Farnaz Foolad, Brandie D Taylor, Samuel A Shelburne, Cesar A Arias, Samuel L Aitken
VRE are associated with ∼1300 deaths per year in the USA. Recent literature suggests that daptomycin, a cyclic lipopeptide antibiotic with concentration-dependent bactericidal activity, is the preferred treatment option for VRE bacteraemia, yet the optimal dosing strategy for this indication has not been established. In vitro evidence suggests that higher-than-labelled doses of daptomycin are required to optimally treat VRE bacteraemia and to inhibit the development of resistance. However, concern of dose-dependent toxicities, notably increases in creatine phosphokinase and the development of rhabdomyolysis, are a barrier to initiating high-dose schemes in clinical practice...
March 13, 2018: Journal of Antimicrobial Chemotherapy
Karishma S Furtado, Elizabeth L Budd, Xiangji Ying, Anna J deRuyter, Rebecca L Armstrong, Tahna L Pettman, Rodrigo S Reis, Pauline Sung-Chan, Zhaoxin Wang, Tahnee Saunders, Leonardo A Becker, Jianwei Shi, Long Sum Tabitha Mui, Ross C Brownson
Implementation of evidence-based practices can improve efficiency and effectiveness of public health efforts. Few studies have explored the political contextual factors that impact implementation of evidence-based non-communicable disease prevention (EBNCDP). This study aimed to do so in Australia, Brazil, China and the United States. Investigators conducted 10-13 qualitative, semi-structured interviews of public health practitioners working in functionally similar public health organizations in each country (total N = 50)...
March 14, 2018: Health Education Research
Peter Vegh, Muzlifah Haniffa
Application of single-cell genomics technologies has revolutionized our approach to study the immune system. Unravelling the functional diversity of immune cells and their coordinated response is key to understanding immunity. Single-cell transcriptomics technologies provide high-dimensional assessment of the transcriptional states of immune cells and have been successfully applied to discover new immune cell types, reveal haematopoietic lineages, identify gene modules dictating immune responses and investigate lymphocyte antigen receptor diversity...
March 14, 2018: Briefings in Functional Genomics
Matthew A Psioda, Joseph G Ibrahim
We consider the problem of Bayesian sample size determination for a clinical trial in the presence of historical data that inform the treatment effect. Our broadly applicable, simulation-based methodology provides a framework for calibrating the informativeness of a prior while simultaneously identifying the minimum sample size required for a new trial such that the overall design has appropriate power to detect a non-null treatment effect and reasonable type I error control. We develop a comprehensive strategy for eliciting null and alternative sampling prior distributions which are used to define Bayesian generalizations of the traditional notions of type I error control and power...
March 14, 2018: Biostatistics
Rika Fukumori, Yoji Masuda, Ayaka Takeuchi, Rina Yanai, Khurchabiling Atchalalt, Borjigin Sarentonglaga, Kazuko Ogata, Mio Yamaguchi, Asuka Hara, Akane Sato, Toshihisa Sugino, Yoshikazu Nagao
The aim of this study was to investigate how intra-duodenal infusions of fatty acids (FA) affect appetite-related gut peptides such as glucagon-like peptide-1 (GLP-1) and ghrelin in sheep. We hypothesized that these peptides can be highly reactive to unsaturated long-chain FA, because they are well known to decrease DMI. Four ewes were fitted with a duodenal cannula and a jugular vein catheter for a 6-h duodenal infusion of the nine FA (C8:0, C10:0, C12:0, C14:0, C16:0, C18:0, C18:1, C18:2, C18:3) and water (control)...
March 14, 2018: Journal of Animal Science
Steven M Falowski, Ashwini Sharan, James McInerney, Darren Jacobs, Lalit Venkatesan, Filippo Agnesi
BACKGROUND: Spinal cord stimulation (SCS) is a common intervention for managing intractable pain. Generally, leads are implanted in a minimally invasive procedure with verbal feedback regarding the location and nature of generated paresthesias by active stimulation; in this way their optimal location can be confirmed. However, lead placement under general anesthesia can have additional benefits. OBJECTIVE: To investigate the outcomes of awake vs asleep lead placement procedures...
March 14, 2018: Neurosurgery
Min Young Kim, Ji Sook Kim, Seung Han Son, Chang Su Lim, Hea Young Eum, Dae Hyun Ha, Mi Ae Park, Eun Jung Baek, Buom-Yong Ryu, Ho Chul Kang, Vladimir N Uversky, Chul Geun Kim
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis...
March 14, 2018: Nucleic Acids Research
Douglas P Beall, M R Chambers, Sam Thomas, John Amburgy, James R Webb, Bradly S Goodman, Devin K Datta, Richard W Easton, Douglas Linville, Sanjay Talati, John B Tillman
BACKGROUND: Osteoporotic and neoplastic vertebral compression fractures (VCF) are common and painful, threatening quality of life and increasing risk of morbidity and mortality. Balloon kyphoplasty is a percutaneous option for treating painful cancer- and osteoporosis-related VCFs, supported by 2 randomized trials demonstrating efficacy benefits of BKP over nonsurgical care. OBJECTIVE: To investigate 12-mo disability, quality of life, and safety outcomes specifically in a Medicare-eligible population, representing characteristic patients seen in routine clinical practice...
March 14, 2018: Neurosurgery
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