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https://www.readbyqxmd.com/read/28088843/evaluating-surrogate-marker-information-using-censored-data
#1
Layla Parast, Tianxi Cai, Lu Tian
Given the long follow-up periods that are often required for treatment or intervention studies, the potential to use surrogate markers to decrease the required follow-up time is a very attractive goal. However, previous studies have shown that using inadequate markers or making inappropriate assumptions about the relationship between the primary outcome and surrogate marker can lead to inaccurate conclusions regarding the treatment effect. Currently available methods for identifying and validating surrogate markers tend to rely on restrictive model assumptions and/or focus on uncensored outcomes...
January 15, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28088788/dual-syk-jak-inhibition-overcomes-ibrutinib-resistance-in-chronic-lymphocytic-leukemia-cerdulatinib-but-not-ibrutinib-induces-apoptosis-of-tumor-cells-protected-by-the-microenvironment
#2
Ailin Guo, Pin Lu, Greg Coffey, Pamela Conley, Anjali Pandey, Y Lynn Wang
Ibrutinib (BTK inhibitor) has generated remarkable responses in CLL. However, the drug, to a large extent, does not cause cell death directly and does not eradicate CLL malignant clones. Inability to eradicate CLL has fostered resistance generation. Once patients become resistant, they do poorly with a median survival of 3-4 months. Novel therapeutic strategies are needed to prevent resistance, improve treatment outcome and ultimately cure the disease. Herein, we explore dual targeting of the BCR and JAK-STAT pathways with a novel single agent, cerdulatinib, which selectively inhibits both SYK (a BCR component) and JAK kinases...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28088772/thrombospondin-immune-regulation-and-the-kidney
#3
Claudio Ponticelli, Hans-Joachim Anders
Most therapeutic attempts to prevent the progression of kidney diseases have been based on interventions to inhibit the production of transforming growth factor-β (TGF-β). Thrombospondins (TSPs) play an important role in activating TGF-β. In the healthy kidney, two TSPs are expressed, TSP1 and TSP2, which exert contrasting effects. While TSP1 is a major activator of TGF-β in renal cells and exerts pro-inflammatory effects both in vitro and in vivo, TSP2 lacks the ability for TGF-β activation but regulates matrix remodeling and inflammation in experimental kidney disease...
January 14, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28088755/hispanic-mothers-beliefs-regarding-hpv-vaccine-series-completion-in-their-adolescent-daughters
#4
A M Roncancio, K K Ward, C C Carmack, B T Muñoz, F L Cribbs
Rates of human papillomavirus (HPV) vaccine series completion among adolescent Hispanic females in Texas in 2014 (∼39%) lag behind the Healthy People 2020 goal (80%). This qualitative study identifies Hispanic mothers' salient behavioral, normative and control beliefs regarding having their adolescent daughters complete the vaccine series. Thirty-two mothers of girls (aged 11-17) that had received at least one dose of the HPV vaccine, completed in-depth interviews. Six girls had received one dose of the HPV vaccine, 10 girls had received two doses, and 16 girls had received all three doses...
January 14, 2017: Health Education Research
https://www.readbyqxmd.com/read/28088741/prevalence-and-correlates-of-fentanyl-contaminated-heroin-exposure-among-young-adults-who-use-prescription-opioids-non-medically
#5
Alexandria Macmadu, Jennifer J Carroll, Scott E Hadland, Traci C Green, Brandon D L Marshall
BACKGROUND: The rate of overdose deaths caused by fentanyl-contaminated heroin (FCH) use is increasing rapidly in the United States. We examined risk factors for exposure to FCH and experiences with FCH use among young adult non-medical prescription opioids (NMPO) users. METHODS: We analyzed data from the Rhode Island Young Adult Prescription Drug Study (RAPiDS), which enrolled young adults aged 18 to 29 reporting prior 30day NMPO use between January 2015 and February 2016...
January 6, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088740/associations-between-adverse-childhood-experiences-student-teacher-relationships-and-non-medical-use-of-prescription-medications-among-adolescents
#6
Myriam Forster, Amy L Gower, Iris W Borowsky, Barbara J McMorris
OBJECTIVE: Few studies have investigated associations between adverse childhood experiences (ACE) and nonmedical use of prescription medication (NMUPM) in population-based samples of adolescents, and even fewer have examined whether promotive factors might buffer these effects. The present study assesses the direct effects of ACE and positive student-teacher relationships on NUMPD and whether positive student-teacher relationships moderate this association. DESIGN: Data were from the 2013 Minnesota Student Survey (MSS), an in-school survey administered every three years to students throughout Minnesota...
January 6, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088739/the-effects-of-rurality-on-substance-use-disorder-diagnosis-a-multiple-groups-latent-class-analysis
#7
Billy Brooks, Matthew McBee, Robert Pack, Arsham Alamian
BACKGROUND: Rates of accidental overdose mortality from substance use disorder (SUD) have risen dramatically in the United States since 1990. Between 1999 and 2004 alone rates increased 62% nationwide, with rural overdose mortality increasing at a rate 3 times that seen in urban populations. Cultural differences between rural and urban populations (e.g., educational attainment, unemployment rates, social characteristics, etc.) affect the nature of SUD, leading to disparate risk of overdose across these communities...
January 6, 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/28088721/modeling-biosolids-drying-through-a-laminated-hydrophobic-membrane
#8
Solmaz Marzooghi, Chunjian Shi, Steven K Dentel, Paul T Imhoff
The adaptation of the membrane distillation process as a low-cost and sustainable approach to biosolids drying and stabilization is investigated, which may have application in container-based sanitation systems proposed in low-income urban regions. Three-layer laminated, breathable, hydrophobic membranes enclose the biosolids, facilitating drying but preventing transport of contaminants. The membranes used in this process are non-wetting with pore spaces that only allow vapor transport. Water vapor can be expelled due to a moderate vapor pressure gradient...
December 29, 2016: Water Research
https://www.readbyqxmd.com/read/28088711/surgery-for-chronic-mesh-infection-occurred-10-years-after-sacrectomy-mesh-resection-and-mesentric-leaf-repair-a-case-report
#9
Makoto Koyama, Yusuke Miyagawa, Yuta Yamamoto, Masato Kitazawa, Akira Suzuki, Satoshi Ishizone, Shinichi Miyagawa
INTRODUCTION: Sacrectomy to treat malignant tumors is often results in large pelvic defects to require reconstruction, using a prosthetic mesh. Importance is to avoid its direct contact of mesh with intestine to prevent adhesion between them. PRESENTATION OF CASE: An 83-year old woman who was diagnosed with a mesh infection caused by a small bowel penetration 10 years after sacrectomy combined with mesh reconstruction for chordoma. In the first operation, because of incomplete re-peritonealization due to a large defect in the retroperitoneum, a mesh unavoidably was compelled to contact with the small intestine...
October 26, 2016: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28088707/dna-sensing-and-immune-responses-in-cancer-therapy
#10
REVIEW
Jian Qiao, Haidong Tang, Yang-Xin Fu
The identification of critical DNA sensors and their pathways has led to revealing the central role of DNA sensing in immune system. It has been initially demonstrated that DNA sensing and immune responses have high impacts on the development and prevention of infection and inflammatory. In addition to toll-like receptor pathways, there is now also emerging evidence that cytosolic enzyme cyclic GMP-AMP synthase (cGAS) is essential for the recognition of not only pathogen-derived DNA but also tumor DNA for innate sensing...
January 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28088700/chlorogenic-acid-ameliorated-concanavalin-a-induced-hepatitis-by-suppression-of-toll-like-receptor-4-signaling-in-mice
#11
Yinglin Yuan, Xia Gong, Li Zhang, Rong Jiang, Junxia Yang, Bin Wang, Jingyuan Wan
Chlorogenic acid (CGA), one of the most abundant dietary polyphenolic compounds, has been reported to exhibit anti-inflammatory ability. However, the hepatoprotective effects and molecular mechanisms of CGA on concanavalin A (Con A)-induced hepatitis have not been explored. In the present study, we found that pretreatment with CGA dose-dependently inhibited the elevation of plasma aminotransferases and alleviated hepatic pathological damage as well as hepatocyte apoptosis in Con A-exposed mice. Additionally, CGA markedly suppressed the production of serum tumor necrosis factor (TNF)-α and interferon (IFN)-γ, alleviated the infiltration of hepatic macrophages, neutrophils, and activated CD4(+) T lymphocytes in Con A-primed mice...
January 12, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28088671/melatonin-attenuates-titanium-particle-induced-osteolysis-via-activation-of-wnt-%C3%AE-catenin-signaling-pathway
#12
Zichuan Ping, Xuanyang Hu, Liangliang Wang, Jiawei Shi, Yunxia Tao, Xiexing Wu, Zhenyang Hou, Xiaobin Guo, Wen Zhang, Huilin Yang, Yaozeng Xu, Zhirong Wang, Dechun Geng
: Wear debris-induced inhibition of bone regeneration and extensive bone resorption were common features in peri-prosthetic osteolysis (PPO). Here, we investigated the effect of melatonin on titanium particle-stimulated osteolysis in a murine calvariae model and mouse-mesenchymal-stem cells (mMSCs) culture system. Melatonin inhibited titanium particle-induced osteolysis and increased bone formation at osteolytic sites, confirmed by radiological and histomorphometric data. Furthermore, osteoclast numbers decreased dramatically in the low- and high-melatonin administration mice, as respectively, compared with the untreated animals...
January 11, 2017: Acta Biomaterialia
https://www.readbyqxmd.com/read/28088642/anti-rage-antibody-selectively-blocks-acute-systemic-inflammatory-responses-to-lps-in-serum-liver-csf-and-striatum
#13
Juciano Gasparotto, Camila Tiefensee Ribeiro, Rafael Calixto Bortolin, Henrique Schaan Fernandes, Alexsander Alves Teixeira, Marcelo Otavio Rodrigues Guasselli, Crepin Aziz Jose O Agani, Natália Cabral Souza, Mateus Grings, Guilhian Leipnitz, Henrique Mautone Gomes, Matheus Augusto de Bittencourt Pasquali, Peter R Dunkley, Phillip W Dickson, José Claudio Fonseca Moreira, Daniel Pens Gelain
Systemic inflammation induces transient or permanent dysfunction in the brain by exposing it to soluble inflammatory mediators. The receptor for advanced glycation endproducts (RAGE) binds to distinct ligands mediating and increasing inflammatory processes. In this study we used an LPS-induced systemic inflammation model in rats to investigate the effect of blocking RAGE in serum, liver, cerebrospinal fluid (CSF) and brain (striatum, prefrontal cortex, ventral tegmental area and substantia nigra). Intraperitoneal injection of RAGE antibody (50 μg/kg) was followed after 1h by a single LPS (5 mg/kg) intraperitoneal injection...
January 11, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28088609/leukemia-inhibitory-factor-impairs-structural-and-neurochemical-development-of-rat-visual-cortex-in-vivo
#14
Maren Engelhardt, Graziella di Cristo, Jochen Grabert, Silke Patz, Lamberto Maffei, Nicoletta Berardi, Petra Wahle
Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocortical projection neurons of the lateral geniculate nucleus, and tecto-thalamic projection neurons of the superior colliculus, and cortical layer IV spiny stellates and layer VI pyramidal neurons. Here, we report that P12-20 LIF infusion inhibits somatic maturation of pyramidal neurons and of all interneuron types in vivo...
January 11, 2017: Molecular and Cellular Neurosciences
https://www.readbyqxmd.com/read/28088586/a-case-control-study-of-risk-sources-for-severe-fever-with-thrombocytopenia-syndrome-in-hubei-province-china
#15
Xuesen Xing, Xuhua Guan, Li Liu, Junqiang Xu, Guoming Li, Jianbo Zhan, Gongping Liu, Xiaoqing Jiang, Xingfu Shen, Yongzhong Jiang, Yang Wu, Hao Zhang, Jing Huang, Fan Ding, Sha Sha, Man Liu, Faxian Zhan
BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS), an emerging infectious disease caused by a novel bunyavirus, was discovered in rural areas of Central China in 2009. METHODS: A case-control study based on hospital data was applied to detect the potential risk sources for SFTS in SFTS-endemic counties in Hubei Province. Cases were defined as hospitalized SFTSV confirmed patients. Controls were randomly selected from non-SFTSV patients in the same hospital ward within 2 weeks of inclusion of the cases, and they were matched by age (+/- 5 years) and gender according to 1:2 matching condition...
January 11, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28088582/ripk1-protects-hepatocytes-from-kupffer-cells-mediated-tnf-induced-apoptosis-in-mouse-models-of-pamp-induced-hepatitis
#16
Aveline Filliol, Claire Piquet-Pellorce, Céline Raguénès-Nicol, Sarah Dion, Muhammad Farooq, Catherine Lucas-Clerc, Peter Vandenabeele, Mathieu J M Bertrand, Jacques Le Seyec, Michel Samson
BACKGROUND & AIMS: The severity of liver diseases is exacerbated by the death of hepatocytes, which can be induced by the sensing of Pathogen Associated Molecular Patterns (PAMPs) derived from the gut microbiota. The molecular mechanisms regulating these cell death pathways are poorly documented. In this study, we investigated the role of the Receptor Interacting Protein Kinase 1 (RIPK1), a protein known to regulate cell fate decisions, in the death of hepatocytes using two in vivo models of PAMP-induced hepatitis...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28088580/grand-round-anticoagulation-in-chronic-liver-disease
#17
REVIEW
Ameet Dhar, Benjamin H Mullish, Mark R Thursz
In this Grand Round, we first present a case of a man with decompensated liver disease who subsequently developed a fatal pulmonary embolism, having not been prescribed prophylactic anticoagulation to prevent venous thromboembolic disease. We go on to discuss the burden of thrombotic disease in those with chronic liver disease, before a more detailed discussion regarding the current evidence, safety data, and clinical dilemmas regarding the use of anticoagulation in patients with chronic liver disease, as well as discussing potential future directions within this field...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28088579/the-microrna-449-family-inhibits-tgf-%C3%AE-mediated-liver-cancer-cell-migration-by-targeting-sox4
#18
Maria Sandbothe, Reena Buurman, Nicole Reich, Luisa Greiwe, Beate Vajen, Engin Gürlevik, Vera Schäffer, Marlies Eilers, Florian Kühnel, Alejandro Vaquero, Thomas Longerich, Stephanie Roessler, Peter Schirmacher, Michael P Manns, Thomas Illig, Brigitte Schlegelberger, Britta Skawran
BACKGROUND & AIMS: Modulation of microRNA expression is considered for treatment of hepatocellular carcinoma (HCC). Therefore, we characterized the epigenetically regulated microRNA-449 family (miR-449a, miR-449b, miR-449c) with regards to its functional effects and target genes in HCC. METHODS: After transfection of miR-449a, miR-449b, and/or miR-449c, tumor-relevant functional effects were analyzed using in vitro assays and a xenograft mouse model. Binding specificities, target genes, and regulated pathways of each microRNA were identified by microarray analyses...
January 11, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28088560/role-of-comorbidities-and-in-hospital-complications-in-short-term-status-epilepticus-outcome
#19
Marco Belluzzo, Giovanni Furlanis, Lara Stragapede, Fabrizio Monti
OBJECTIVE: pre-morbid patient conditions and hospitalization complications possibly play a role in status epilepticus short-term outcome, although evidence is incomplete and non-conclusive. The study's aim was to define whether comorbidities and in-hospital complications arising after status epilepticus affect its prognosis. METHODS: A retrospective single center study was carried out. All selected patients were adults presenting an EEG-proven status epilepticus episode between 2003 and 2014...
December 30, 2016: Clinical Neurology and Neurosurgery
https://www.readbyqxmd.com/read/28088535/neurobiological-consequences-of-juvenile-stress-a-gabaergic-perspective-on-risk-and-resilience
#20
REVIEW
Anne Albrecht, Iris Müller, Ziv Ardi, Gürsel Çalışkan, David Gruber, Sebastian Ivens, Menahem Segal, Joachim Behr, Uwe Heinemann, Oliver Stork, Gal Richter-Levin
ALBRECHT, A., MÜLLER, I., ARDI, Z., ÇALIŞKAN, G., GRUBER, D., IVENS, S., SEGAL, M., BEHR, J., HEINEMANN, U., STORK, O., and RICHTER-LEVIN, G. Neurobiological consequences of juvenile stress: a GABAergic perspective on risk and resilience. NEUROSCI BIOBEHAV REV XXX-XXX, 2016. - Childhood adversity is among the most potent risk factors for developing mood and anxiety disorders later in life. Therefore, understanding how stress during childhood shapes and rewires the brain may optimize preventive and therapeutic strategies for these disorders...
January 11, 2017: Neuroscience and Biobehavioral Reviews
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