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Genevieve M Weir, Olga Hrytsenko, Tara Quinton, Neil L Berinstein, Marianne M Stanford, Marc Mansour
BACKGROUND: Future cancer immunotherapies will combine multiple treatments to generate functional immune responses to cancer antigens through synergistic, multi-modal mechanisms. In this study we explored the combination of three distinct immunotherapies: a class I restricted peptide-based cancer vaccine, metronomic cyclophosphamide (mCPA) and anti-PD-1 treatment in a murine tumor model expressing HPV16 E7 (C3). METHODS: Mice were implanted with C3 tumors subcutaneously...
2016: Journal for Immunotherapy of Cancer
Andrew J Tatem, Peng Jia, Dariya Ordanovich, Michael Falkner, Zhuojie Huang, Rosalind Howes, Simon I Hay, Peter W Gething, David L Smith
BACKGROUND: Malaria remains a problem for many countries classified as malaria free through cases imported from endemic regions. Imported cases to non-endemic countries often result in delays in diagnosis, are expensive to treat, and can sometimes cause secondary local transmission. The movement of malaria in endemic countries has also contributed to the spread of drug resistance and threatens long-term eradication goals. Here we focused on quantifying the international movements of malaria to improve our understanding of these phenomena and facilitate the design of mitigation strategies...
October 21, 2016: Lancet Infectious Diseases
Naren P Tallapragada
In August 2015, Turing Pharmaceuticals acquired the marketing rights to Daraprim (pyrimethamine), a drug used to treat parasitic infections like malaria and toxoplasmosis. Soon after, Turing caused an uproar when it announced that it would raise the price per tablet of Daraprim from [Formula: see text], a 5500% price hike for a drug that has been on the market for over 60 years and off patent since the 1970s. Old, off-patent drugs are becoming increasingly expensive; Daraprim is the archetypal example. Turing had the power to set a high price for Daraprim because the drug's limited patient population, the absence of competing manufacturers, and a lack of therapeutic alternatives all created an effective monopoly...
April 2016: Journal of Law and the Biosciences
Giovanni Milito, Giorgio Lisi, Elena Aronadio, Michela Campanelli, Dario Venditti, Simona Grande, Michele Grande
BACKGROUNDS: Hemorrhoidectomy is considered the gold standard and the most effective and definitive treatment for grades 3 or 4 haemorrhoids, and Milligan-Morgan's and Ferguson's procedures are the most widely used techniques throughout the world. The aim of the study is to present our surgical technique using LigasureTM vessel sealing, focus on technical aspects and surgical tricks showing our results with a huge number of patients and a long-term follow-up. METHODS: Between June 2001 and June 2014 at the University Hospital of Tor Vergata, Rome, Italy, 1000 patients were selected to underwent LigaSureTM hemorrhoidectomy for III and IV degree haemorrhoids...
October 21, 2016: Minerva Gastroenterologica e Dietologica
Zhong Liu, Cheng Zhang, Alireza Khodadadi-Jamayran, Lam Dang, Xiaosi Han, Kitai Kim, Hu Li, Rui Zhao
Neural stem cells (NSCs) have the capacity to differentiate into neurons, astrocytes, and oligodendrocytes, and therefore represent a promising donor tissue source for treating neurodegenerative diseases and repairing injuries of the nervous system. However, it remains unclear how canonical microRNAs (miRNAs), the subset of miRNAs requiring the Drosha-Dgcr8 microprocessor and the type III RNase Dicer for biogenesis, regulate NSCs. In this study, we established and characterized <i>Dgcr8</i><sup>-/-</sup> NSCs from conditionally <i>Dgcr8</i>-disrupted mouse embryonic brain...
October 20, 2016: Stem Cells and Development
Mandy Beyer, Nicole Kiweler, Siavosh Mahboobi, Oliver H Krämer
Histone deacetylases (HDACs) catalyze the deacetylation of lysine residues in their target proteins. This biochemical modification can have profound effects on the functions of these proteins and a dysregulation of HDAC activity contributes to severe diseases, including neoplastic transformation. In the following chapter, we present a strategy that allows to distinguish between the inhibition of the class I HDACs HDAC1, 2, and 3 and of the class IIb HDAC HDAC6. This method is based on Western blot and relies on the detection of hyperacetylated substrates of class I or class IIb HDACs in lysates from cells that were treated with histone deacetylase inhibitors (HDACi)...
2017: Methods in Molecular Biology
Firas El Chaer, Dimpy P Shah, Roy F Chemaly
Cytomegalovirus (CMV) infection is a significant complication in hematopoietic cell transplantation (HCT) recipients. Four antiviral drugs are used for preventing or treating CMV: ganciclovir, valganciclovir, foscarnet, and cidofovir. With prolonged and repeated use of these drugs, CMV can become resistant to standard therapy, resulting in increased morbidity and mortality, especially in HCT recipients. Antiviral drug resistance should be suspected when CMV viremia (DNAemia or antigenemia) fails to improve or continue to increase after 2 weeks of appropriately dosed and delivered antiviral therapy...
October 19, 2016: Blood
Cheng-Chao Ruan, Yan Li, Yu Ma, Ding-Liang Zhu, Ping-Jin Gao
OBJECTIVE: Previous studies have indicated that adiponectin (APN) protects against hypertension-related cardiovascular disease. However, whether APN is involved in the regulation of hypertensive renal damage remains unclear. The present study aimed to elucidate how APN regulates renal epithelial to mesenchymal transdifferentiation (EMT) in desoxycorticosterone (DOCA)-salt hypertensive mice. DESIGN AND METHOD: Male APN knockout (APNKO) mice and wild-type (WT) C57BL/6 littermates were sc infused with DOCA pellet (50 mg for 21 day release)...
September 2016: Journal of Hypertension
Bishoy M Faltas, Davide Prandi, Scott T Tagawa, Ana M Molina, David M Nanus, Cora Sternberg, Jonathan Rosenberg, Juan Miguel Mosquera, Brian Robinson, Olivier Elemento, Andrea Sboner, Himisha Beltran, Francesca Demichelis, Mark A Rubin
Chemotherapy-resistant urothelial carcinoma has no uniformly curative therapy. Understanding how selective pressure from chemotherapy directs the evolution of urothelial carcinoma and shapes its clonal architecture is a central biological question with clinical implications. To address this question, we performed whole-exome sequencing and clonality analysis of 72 urothelial carcinoma samples, including 16 matched sets of primary and advanced tumors prospectively collected before and after chemotherapy. Our analysis provided several insights: (i) chemotherapy-treated urothelial carcinoma is characterized by intra-patient mutational heterogeneity, and the majority of mutations are not shared; (ii) both branching evolution and metastatic spread are very early events in the natural history of urothelial carcinoma; (iii) chemotherapy-treated urothelial carcinoma is enriched with clonal mutations involving L1 cell adhesion molecule (L1CAM) and integrin signaling pathways; and (iv) APOBEC-induced mutagenesis is clonally enriched in chemotherapy-treated urothelial carcinoma and continues to shape the evolution of urothelial carcinoma throughout its lifetime...
October 17, 2016: Nature Genetics
Shedra A Snipes, Sharon P Cooper, Eva M Shipp
OBJECTIVE: This paper describes how perceived discrimination shapes the way Latino farmworkers encounter injuries and seek out treatment. METHODS: After 5 months of ethnographic fieldwork, 89 open-ended, semi-structured interviews were analyzed. NVivo was used to code and qualitatively organize the interviews and field notes. Finally, codes, notes, and co-occurring dynamics were used to iteratively assess the data for major themes. RESULTS: The primary source of perceived discrimination was the "boss" or farm owner...
October 17, 2016: Journal of Agromedicine
D Lelic, I W D Fischer, A E Olesen, C D Mørch, F G Arguissain, J A B Manresa, A Dahan, A M Drewes
Severe pain is often treated with opioids. Antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) have also shown a pain relieving effect, but for both SNRI and opioids the specific mode of action in humans remains vague. This study investigated how oxycodone and venlafaxine affect spinal and supraspinal pain processing. Twenty volunteers were included in this randomized cross-over study comparing five-day treatment with venlafaxine, oxycodone and placebo. As a proxy of the spinal pain transmission, the nociceptive withdrawal reflex (NWR) to electrical stimulation on the sole of the foot was recorded at the tibialis anterior muscle before and after five days of treatment...
October 17, 2016: European Journal of Neuroscience
Mathieu F Chevalier, Céline Didier, Pierre-Marie Girard, Maria E Manea, Pauline Campa, Françoise Barré-Sinoussi, Daniel Scott-Algara, Laurence Weiss
Early events during primary HIV infection (PHI) are thought to influence disease outcome. Although a growing body of evidence suggests a beneficial role of HIV-specific CD4 help in HIV infection, it is unclear how early viral replication, systemic immune activation, and antiretroviral therapy (ART) may shape CD4 T-cell responses during PHI, and whether HIV-specific CD4 responses contribute to the high immune activation observed in PHI. Twenty-seven patients with early PHI were included in a prospective longitudinal study and 12 of them received ART after enrollment...
2016: Frontiers in Immunology
Dominique L Doster, Amanda R Jensen, Sina Khaneki, Troy A Markel
Intestinal ischemia is a devastating intraabdominal emergency that often necessitates surgical intervention. Mortality rates can be high, and patients who survive often have significant long-term morbidity. The implementation of traditional medical therapies to prevent or treat intestinal ischemia have been sparse over the last decade, and therefore, the use of novel therapies are becoming more prevalent. Cellular therapy using mesenchymal stromal cells is one such treatment modality that is attracting noteworthy attention in the scientific community...
October 10, 2016: Cytotherapy
Chikezie I Eseonu, Karim ReFaey, Jordina Rincon-Torroella, Oscar Garcia, Gary S Wand, Roberto Salvatori, Alfredo Quinones-Hinojosa
OBJECTIVE: The transition from microscopic to a fully endoscopic transsphenoidal surgery requires a surgeon to assess how the change in technique will affect the extent of tumor resection (EOR), outcomes, and complications. We compared a single surgeon's experience transitioning from one technique to the other, and examined the operative outcomes and EOR between microscopic versus endoscopic transsphenoidal surgery. METHODS: Retrospective data analysis of adult patients who were treated surgically for a pituitary adenoma between August 2005 and May 2015 by a single neurosurgeon, who was originally trained and practiced in the microscopic transsphenoidal approach...
October 11, 2016: World Neurosurgery
Adan Z Becerra, Christopher T Aquina, Supriya G Mohile, Mohamedtaki A Tejani, Maria J Schymura, Francis P Boscoe, Zhaomin Xu, Carla F Justiniano, Courtney I Boodry, Alex A Swanger, Katia Noyes, John R Monson, Fergal J Fleming
BACKGROUND: There is a paucity of literature quantifying the extent to which time to adjuvant chemotherapy for stage III colon cancer patients varies between individual surgeons, medical oncologists, and hospitals. METHODS: A retrospective cohort study was conducted by merging the New York State Cancer Registry with the Statewide Planning & Research Cooperative System and Medicare claims to identify stage III colon cancer patients from 2004 to 2009 who underwent resection and received adjuvant chemotherapy...
October 13, 2016: Annals of Surgical Oncology
Bradley C Carthon, Emmanuel S Antonarakis
Despite the numerous regulatory approvals for prostate cancer, metastatic prostate cancer remains a huge burden for men worldwide. In an exciting development, James et al. recently published data from the Systemic Therapy in Advanced or Metastatic Prostate Cancer: Evaluation of Drug Efficacy: a multi-stage multi-arm randomised control trial (STAMPEDE). This is an innovative multi-arm multi-stage (MAMS) trial that has utilized one control arm and several comparator arms in order to provide evidence for the inclusion of therapies beyond standard androgen deprivation alone...
September 2016: Translational Cancer Research
Eugene Kobyliansky, Dmitry Torchinsky, Leonid Kalichman, David Karasik
BACKGROUND: To our knowledge, there are no experimental studies that have addressed the effects of starvation on the maintenance of telomere length. Two epidemiologic studies that have addressed this topic gave controversial results. OBJECTIVE: We characterized leukocyte telomere length (LTL) in a Chuvash population that was comprised of survivors of the mass famine of 1922-1923 and in these survivors' descendants. DESIGN: The tested cohort consisted of native Chuvash men (n = 687) and women (n = 647) who were born between 1909 and 1980 and who resided in small villages in the Chuvash Republic of the Russian Federation...
October 12, 2016: American Journal of Clinical Nutrition
Rosario Musumeci, Enrico Calaresu, Jolanda Gerosa, Davide Oggioni, Simone Bramati, Patrizia Morelli, Ida Mura, Andrea Piana, Bianca Maria Are, Clementina Elvezia Cocuzza
Linezolid is the main representative of the oxazolidinones, introduced in 2000 in clinical practice to treat severe Gram-positive infections. This compound inhibits protein synthesis by binding to the peptidyl transferase centre of the 50S bacterial ribosomal subunit. The aim of this study was to characterize 12 clinical strains of linezolid-resistant Staphylococcus spp. isolated in Northern Italy. All isolates of Staphylococcus spp. studied showed a multi-antibiotic resistance phenotype. In particular, all isolates showed the presence of the mecA gene associated with SSCmec types IVa, V or I...
September 13, 2016: New Microbiologica
Torben Esser, Gerburg Keilhoff, Uwe Ebmeyer
OBJECTIVE: Our asphyxia cardiac arrest (ACA) rat model is well established. The original model was designed in the 1990(th) using halothane and nitrous oxide for pre-insult anesthesia. Because of its hepato-toxicity and its potential to induce severe liver failures, halothane is no longer used in clinical anesthesia for several years. In order to minimize the health risk for our laboratory staff as well as to keep the experimental settings of our model on a clinically oriented basis we decided to replace halothane by sevoflurane...
October 7, 2016: Brain Research
Antonio Ruggiero, Andrea Cuculo, Antonio Centola, Giulio Campanale, Dolores Russo, Antonio Gaglione, Matteo Di Biase, Natale Daniele Brunetti, Fernando Alfonso, Marcos García-Guimaraes, Javier Cuesta, Gonzalo Navarrete, Teresa Bastante, Jacqueline Saw
No abstract text is available yet for this article.
October 10, 2016: EuroIntervention
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