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https://www.readbyqxmd.com/read/29351919/high-yield-of-pathogenic-germline-mutations-causative-or-likely-causative-of-the-cancer-phenotype-in-selected-children-with-cancer
#1
Illja Diets, Esmé Waanders, Marjolijn J L Ligtenberg, Diede van Bladel, Eveline J Kamping, Peter M Hoogerbrugge, Saskia Hopman, Maran J W Olderode-Berends, Erica H Gerkes, David Koolen, Carlo Marcelis, Gijs We Santen, Martine van Belzen, Dylan Mordaunt, Lesley McGregor, Elizabeth Thompson, Antonis Kattamis, Agata Pastorczak, Wojciech Mlynarski, Denisa Ilencikova, Anneke Vulto-van Silfhout, Thatjana Gardeitchik, E S J M de Bont, Jan Loeffen, Anja Wagner, Arjen R Mensenkamp, Roland P Kuiper, Nicoline Hoogerbrugge, Marjolijn Jongmans
PURPOSE: In many children with cancer and characteristics suggestive of a genetic predisposition syndrome, the genetic cause is still unknown. We studied the yield of pathogenic mutations by applying whole exome sequencing on a selected cohort of children with cancer. EXPERIMENTAL DESIGN: To identify mutations in known and novel cancer predisposing genes, we performed trio-based whole exome sequencing on germline DNA of 40 selected children and their parents. These children were diagnosed with cancer and had at least one of the following features: (1) intellectual disability and/or congenital anomalies, (2) multiple malignancies, (3) family history of cancer or (4) an adult type of cancer...
January 19, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29351307/doxycycline-modulates-vegf-a-expression-failure-of-doxycycline-inducible-lentivirus-shrna-vector-to-knockdown-vegf-a-expression-in-transgenic-mice
#2
Mari Merentie, Riina Rissanen, Line Lottonen-Raikaslehto, Jenni Huusko, Erika Gurzeler, Mikko P Turunen, Lari Holappa, Petri Mäkinen, Seppo Ylä-Herttuala
Vascular endothelial growth factor-A (VEGF-A) is the master regulator of angiogenesis, vascular permeability and growth. However, its role in mature blood vessels is still not well understood. To better understand the role of VEGF-A in the adult vasculature, we generated a VEGF-A knockdown mouse model carrying a doxycycline (dox)-regulatable short hairpin RNA (shRNA) transgene, which silences VEGF-A. The aim was to find the critical level of VEGF-A reduction for vascular well-being in vivo. In vitro, the dox-inducible lentiviral shRNA vector decreased VEGF-A expression efficiently and dose-dependently in mouse endothelial cells and cardiomyocytes...
2018: PloS One
https://www.readbyqxmd.com/read/29350840/a-phase-3-trial-of-mometasone-furoate-sinus-implants-for-chronic-sinusitis-with-recurrent-nasal-polyps
#3
Robert C Kern, J Pablo Stolovitzky, Stacey L Silvers, Ameet Singh, Jivianne T Lee, David M Yen, Alfred M C Iloreta, Francis P J Langford, Boris Karanfilov, Keith E Matheny, James W Stambaugh, Anna K Gawlicka
BACKGROUND: Topical intranasal corticosteroid sprays (INCSs) are standard treatment for nasal polyps (NPs), but their efficacy is reduced by poor patient compliance and impaired access of drug to the sinus mucosa. A corticosteroid-eluting sinus implant was designed to address these limitations in patients with recurrent polyposis after sinus surgery by delivering 1350 μg of mometasone furoate (MF) directly to the ethmoid sinus mucosa over approximately 90 days. METHODS: A randomized, sham-controlled, double-blind trial was undertaken in 300 adults with refractory chronic rhinosinusitis with NPs (CRSwNP), who were candidates for repeat surgery...
January 19, 2018: International Forum of Allergy & Rhinology
https://www.readbyqxmd.com/read/29349576/prep1-deficiency-affects-olfactory-perception-and-feeding-behavior-by-impairing-bdnf-trkb-mediated-neurotrophic-signaling
#4
Serena Ricci, Davide Viggiano, Ilaria Cimmino, Giuseppe Perruolo, Serena Cabaro, Antonietta Liotti, Francesca Fiory, Rosa Spinelli, Angelina Di Carlo, Francesco Beguinot, Pietro Formisano, Francesco Oriente
Prep1 is a homeodomain transcription factor which has an important role in hindbrain development. Prep1 expression is also kept in adult mouse brain and in particular within the olfactory bulbs. Moreover, many Prep1 neurons co-localize with Calbindin-positive periglomerular interneurons in olfactory glomerular layer. However, Prep1 function in this brain region is still unknown. In this study, we show that Prep1 hypomorphic heterozygous (Prep1 i/+ ) mice express low levels of protein and feature a 30% reduction of olfactory bulb area, compared to WT mice...
January 18, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29349021/arthroscopic-repair-of-medial-transtendinous-rotator-cuff-tears
#5
Brian J Kelly, Larry D Field
Rotator cuff tears are extremely common in the adult population, and medial transtendinous rotator cuff tears, although rare, have recently been reported in the literature. These tears are almost always traumatic, which is a common indication for surgical management. It is necessary to consider these tears as a distinct subset when planning for rotator cuff repair because traditional repair techniques would overtension the tendon, increasing the risk for failure of the repair. The objective of this Technical Note is to describe an arthroscopic repair technique for these tears that avoids overtensioning the rotator cuff while still using repair techniques that are familiar to the arthroscopic shoulder surgeon...
December 2017: Arthroscopy Techniques
https://www.readbyqxmd.com/read/29347878/the-effect-of-aging-on-the-mis-perception-of-intentionality-an-erp-study
#6
R Pasion, C Fernandes, A R Gonçalves, F Ferreira-Santos, R Páscoa, F Barbosa, J Marques-Teixeira
Despite the accumulated knowledge on moral decision-making in the early stages of development, empirical evidence is still limited in the old-aged adults. The current study contributes to unveil the neural correlates of judgments of moral transgressions as a function of aging, by examining the temporal dynamics of neural activation elicited by intentional and accidental harmful actions in three groups of healthy participants: young adults (18-35), adults (40-55), and older adults (60-75). Older adults were slower and less accurate in rating intentionality, compared to the younger groups...
January 18, 2018: Social Neuroscience
https://www.readbyqxmd.com/read/29347812/reevaluation-of-the-impact-of-methicillin-resistance-on-outcomes-in-patients-with-staphylococcus-aureus-bacteremia-and-endocarditis
#7
Eun-Jeong Joo, Dong Ah Park, Cheol-In Kang, Doo Ryeon Chung, Jae-Hoon Song, Sang Moo Lee, Kyong Ran Peck
Background/Aims: Methicillin-resistant Staphylococcus aureus (MRSA) is highly prevalent in hospitals, and has recently emerged in the community. The impact of methicillin-resistance on mortality and medical costs for patients with S. aureus bacteremia (SAB) requires reevaluation. Methods: We searched studies with SAB or endocarditis using electronic databases including Ovid-Medline, Embase-Medline, and Cochrane Library, as well as five local databases for published studies during the period January 2000 to September 2011...
January 20, 2018: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/29346517/does-telomere-length-indicate-biological-physical-and-cognitive-health-among-older-adults-evidence-from-the-health-and-retirement-study
#8
Lauren Brown, Yuan Zhang, Colter Mitchel, Jennifer Ailshire
Telomere length (TL) has been suggested as a biomarker that can indicate individual variability in the rate of aging. Yet, it remains unclear whether TL is related to recognized indicators of health in an aging, older nationally representative sample. We examine whether TL is associated with 15 biological, physical and cognitive markers of health among older adults ages 54+. TL was assayed from saliva using quantitative PCR (T/S ratio) in the 2008 Health and Retirement Study (n=4,074). We estimated probability of high risk levels across indictors of health by TL and age-singly and jointly...
January 16, 2018: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/29346414/reliability-of-plasma-polar-metabolite-concentrations-in-a-large-scale-cohort-study-using-capillary-electrophoresis-mass-spectrometry
#9
Sei Harada, Akiyoshi Hirayama, Queenie Chan, Ayako Kurihara, Kota Fukai, Miho Iida, Suzuka Kato, Daisuke Sugiyama, Kazuyo Kuwabara, Ayano Takeuchi, Miki Akiyama, Tomonori Okamura, Timothy M D Ebbels, Paul Elliott, Masaru Tomita, Asako Sato, Chizuru Suzuki, Masahiro Sugimoto, Tomoyoshi Soga, Toru Takebayashi
BACKGROUND: Cohort studies with metabolomics data are becoming more widespread, however, large-scale studies involving 10,000s of participants are still limited, especially in Asian populations. Therefore, we started the Tsuruoka Metabolomics Cohort Study enrolling 11,002 community-dwelling adults in Japan, and using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry. The CE-MS method is highly amenable to absolute quantification of polar metabolites, however, its reliability for large-scale measurement is unclear...
2018: PloS One
https://www.readbyqxmd.com/read/29346023/fertility-preservation-in-pediatric-oncology-patients-new-perspectives
#10
Chiara Gertosio, Mariasole Magistrali, Paola Musso, Cristina Meazza, Mauro Bozzola
Over the past 30 years, advances in antineoplastic treatment led to a significant increase in the survival of patients with childhood cancer. In Europe and the United States, 82% of children, adolescents, and young adults survive 5 years from the cancer diagnosis and the majority achieves long-term survival into adulthood. The impact of cancer therapy on fertility is related to the age of the patient and to the duration, dose/intensity, and type of treatment. Exposure to chemotherapy or to radiation to gonads or pituitary brings long-term complications of cancer-directed therapies that include effects on reproductive capacity...
January 18, 2018: Journal of Adolescent and Young Adult Oncology
https://www.readbyqxmd.com/read/29345225/indications-for-the-surgical-management-of-benign-goiter-in-adults
#11
Detlef K Bartsch, Markus Luster, Heinz J Buhr, Dietmar Lorenz, Christoph-Thomas Germer, Peter E Goretzki
BACKGROUND: Thyroidectomy is still three to six times more common in Germany than in the USA, Great Britain, and the Scandinavian countries. Thus, the question is often asked whether thyroidectomy in Germany is being performed for the correct indications. METHODS: This review is based on studies and guidelines containing information on the indications for surgery in benign goiter and Graves' disease; these publications were retrieved by a systematic literature search in the Medline and Cochrane Library databases (1990-2016)...
January 8, 2018: Deutsches Ärzteblatt International
https://www.readbyqxmd.com/read/29345102/the-mycobiota-of-the-sand-fly-phlebotomus-perniciosus-involvement-of-yeast-symbionts-in-uric-acid-metabolism
#12
Elena Martin, Ilaria Varotto Boccazzi, Leone De Marco, Gioia Bongiorno, Matteo Montagna, Luciano Sacchi, Priscilla Mensah, Irene Ricci, Luigi Gradoni, Claudio Bandi, Sara Epis
The knowledge of the fungal mycobiota of arthropods, including the vectors of human and animal diseases, is still limited. Here, we investigated the mycobiota associated with the sand fly Phlebotomus perniciosus, the main vector of leishmaniasis in the western Mediterranean area, by a culture-dependent approach (microbiological analyses and sequencing of the 26S rRNA gene), internal transcribed spacer (ITS) rRNA amplicon-based next-generation sequencing, fluorescence in situ hybridisation (FISH), and genome sequencing of the dominant yeast species...
January 18, 2018: Environmental Microbiology
https://www.readbyqxmd.com/read/29344645/targeted-disruption-of-adenosine-kinase-in-myeloid-monocyte-cells-increases-osteoclastogenesis-and-bone-resorption-in-mice
#13
Qiuying Ye, Ge Li, Shuhua Liu, Yalun Guan, Yunfeng Li, Jinling Li, Huanhuan Jia, Xuejiao Li, Qingnan Li, Ren Huang, Hui Wang, Yu Zhang
Adenosine kinase (ADK) serves an important role in intracellular adenosine clearance via phosphorylating adenosine to AMP. The role of adenosine and its receptors in the maintenance of bone homeostasis is well studied, particularly in osteoclastogenesis and bone resorption; however, the function of ADK in bone metabolism is still unclear. In the present study, utilizing the cre/floxp recombination system, mice with conditional loss of ADK function in myeloid monocyte cells were used to assess the effect of ADK deficiency on bone metabolism...
January 17, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29344620/association-of-depression-with-mortality-in-older-adults-undergoing-transcatheter-or-surgical-aortic-valve-replacement
#14
Laura M Drudi, Matthew Ades, Sena Turkdogan, Caroline Huynh, Sandra Lauck, John G Webb, Nicolo Piazza, Giuseppe Martucci, Yves Langlois, Louis P Perrault, Anita W Asgar, Marino Labinaz, Andre Lamy, Nicolas Noiseux, Mark D Peterson, Rakesh C Arora, Brian R Lindman, Melissa Bendayan, Rita Mancini, Amanda Trnkus, Dae H Kim, Jeffrey J Popma, Jonathan Afilalo
Importance: Depression is increasingly recognized as a risk factor for adverse outcomes in cardiovascular disease. However, little is known about depression in older adults undergoing transcatheter (TAVR) or surgical (SAVR) aortic valve replacement. Objective: To determine the prevalence of depression and its association with all-cause mortality in older adults undergoing TAVR or SAVR. Design, Setting, and Participants: This preplanned analysis of the Frailty Aortic Valve Replacement (FRAILTY-AVR) prospective cohort study included 14 centers in 3 countries from November 15, 2011, through April 7, 2016...
January 17, 2018: JAMA Cardiology
https://www.readbyqxmd.com/read/29344357/examining-the-effectiveness-of-a-cognitive-intervention-to-improve-cognitive-function-in-a-population-of-older-adults-living-with-hiv-a-pilot-study
#15
Judy A Frain, Ling Chen
Objective: The purpose of this randomized-controlled pilot study was to explore the effectiveness of a home-based computerized cognitive training intervention in improving cognitive function in a population of older adults with mild cognitive impairment who are living with HIV. Methods: In all, 24 participants were enrolled in this study. All study participants were impaired [defined as Montreal Cognitive Assessment (MoCA) score < 26]; 12 were randomly assigned to a computer-training intervention group and 12 to a control group...
January 2018: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/29344090/overexpression-of-the-proneural-transcription-factor-ascl1-in-chronic-lymphocytic-leukemia-with-a-t-12-14-q23-2-q32-3
#16
Theodora Malli, Melanie Rammer, Sabrina Haslinger, Jonathan Burghofer, Sonja Burgstaller, Hans-Christian Boesmueller, Renate Marschon, Wolfgang Kranewitter, Martin Erdel, Sabine Deutschbauer, Gerald Webersinke
Background: Translocations of the IGH locus on 14q32.3 are present in about 8% of patients with chronic lymphocytic leukemia (CLL) and contribute to leukemogenesis by deregulating the expression of the IGH-partner genes. Identification of these genes and investigation of the downstream effects of their deregulation can reveal disease-causing mechanisms. Case presentation: We report on the molecular characterization of a novel t(12;14)(q23.2;q32.3) in CLL. As a consequence of the rearrangement ASCL1 was brought into proximity of the IGHJ-Cμ enhancer and was highly overexpressed in the aberrant B-cells of the patient, as shown by qPCR and immunohistochemistry...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29343131/safety-and-tolerability-of-plecanatide-in-patients-with-chronic-idiopathic-constipation-long-term-evidence-from-an-open-label-study
#17
Charles F Barish, Patrick Griffin
OBJECTIVE: This multicenter, fixed-dose, open-label study evaluated the long-term safety and tolerability of once-daily oral plecanatide for the treatment of adults with chronic idiopathic constipation (CIC). METHODS: Eligible patients completed a phase 2b or phase 3 double-blind study of plecanatide, or had not previously been treated with plecanatide. Enrolled patients received plecanatide (3 or 6 mg) for up to 72 weeks. Safety and tolerability were assessed by the incidence, nature, and severity of spontaneously reported treatment-emergent adverse events (TEAEs)...
January 17, 2018: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/29343085/a-lack-of-systemic-absorption-following-the-repeated-application-of-topical-quetiapine-in-healthy-adults
#18
Bryce Kayhart, Maria I Lapid, Sarah Nelson, Julie L Cunningham, Virginia H Thompson, Jonathan G Leung
In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia...
January 1, 2018: American Journal of Hospice & Palliative Care
https://www.readbyqxmd.com/read/29342934/exploring-positive-survivorship-experiences-of-indigenous-australian-cancer-patients
#19
Laura Tam, Gail Garvey, Judith Meiklejohn, Jennifer Martin, Jon Adams, Euan Walpole, Michael Fay, Patricia Valery
Amongst Indigenous Australians, "cancer" has negative connotations that detrimentally impact upon access to cancer care services. Barriers to accessing cancer services amongst Indigenous Australians are widely reported. In contrast, factors that facilitate this cohort to successfully navigate cancer care services ("enablers") are scarcely reported in the literature. Through qualitative interviews, this article examines factors that assist Indigenous Australians to have positive cancer experiences. Semi-structured interviews were conducted with twelve adult Indigenous oncology patients recruited from a tertiary hospital in Queensland, Australia during 2012-2014...
January 15, 2018: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29342921/rna-targeted-therapies-and-amyotrophic-lateral-sclerosis
#20
REVIEW
Stéphane Mathis, Gwendal Le Masson
Amyotrophic lateral sclerosis (ALS) is a fatal motor disease in adults. Its pathophysiology remains mysterious, but tremendous advances have been made with the discovery of the most frequent mutations of its more common familial form linked to the C9ORF72 gene. Although most cases are still considered sporadic, these genetic mutations have revealed the role of RNA production, processing and transport in ALS, and may be important players in all ALS forms. There are no disease-modifying treatments for adult human neurodegenerative diseases, including ALS...
January 15, 2018: Biomedicines
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