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https://www.readbyqxmd.com/read/27933712/the-importance-of-mrna-structure-in-determining-the-pathogenicity-of-synonymous-and-non-synonymous-mutations-in-haemophilia
#1
N Hamasaki-Katagiri, B C Lin, J Simon, R C Hunt, T Schiller, E Russek-Cohen, A A Komar, H Bar, C Kimchi-Sarfaty
INTRODUCTION: Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for the generation of large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia is associated with inversions, deletions, insertions, nonsense and missense mutations. Both synonymous and non-synonymous mutations influence the base pairing of messenger RNA (mRNA), which can alter mRNA structure, cellular half-life and ribosome processivity/elongation...
December 9, 2016: Haemophilia: the Official Journal of the World Federation of Hemophilia
https://www.readbyqxmd.com/read/27932591/the-cellular-diversity-of-the-pedunculopontine-nucleus-relevance-to-behavior-in-health-and-aspects-of-parkinson-s-disease
#2
REVIEW
Ilse S Pienaar, Anthony Vernon, Philip Winn
The pedunculopontine nucleus (PPN) is a rostral brainstem structure that has extensive connections with basal ganglia nuclei and the thalamus. Through these the PPN contributes to neural circuits that effect cortical and hippocampal activity. The PPN also has descending connections to nuclei of the pontine and medullary reticular formations, deep cerebellar nuclei, and the spinal cord. Interest in the PPN has increased dramatically since it was first suggested to be a novel target for treating patients with Parkinson's disease who are refractory to medication...
December 7, 2016: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/27931680/reactivation-or-reinfection-in-adult-tuberculosis-is-that-the-question
#3
Pere-Joan Cardona
Looking at the chapter on "natural history" in any tuberculosis (TB) reference book, there is a kind of certainty regarding TB in adults. That is the concept of "post-primary" TB described as the reactivation of dormant bacilli hidden in an old lesion developed during infancy due to a type of local immunosuppression. Intriguingly, this concept involves at least two major uncertainties: how can dormant bacilli remain for such a long period, almost a lifetime, in an old lesion, taking into account granuloma dynamism; and what sort of local immunosuppression is the one that facilitates reactivation? The controversy between reactivation and exogenous reinfection as the cause of active TB started very soon in TB research...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27931210/ontological-security-and-connectivity-provided-by-pets-a-study-in-the-self-management-of-the-everyday-lives-of-people-diagnosed-with-a-long-term-mental-health-condition
#4
Helen Brooks, Kelly Rushton, Sandra Walker, Karina Lovell, Anne Rogers
BACKGROUND: Despite evidence that connecting people to relevant wellbeing-related resources brings therapeutic benefit, there is limited understanding, in the context of mental health recovery, of the potential value and contribution of pet ownership to personal support networks for self-management. This study aimed to explore the role of pets in the support and management activities in the personal networks of people with long-term mental health problems. METHODS: Semi-structured interviews centred on 'ego' network mapping were conducted in two locations (in the North West and in the South of England) with 54 participants with a diagnosis of a long-term mental health problem...
December 9, 2016: BMC Psychiatry
https://www.readbyqxmd.com/read/27928097/intestinal-immunity-and-gut-microbiota-in-atherogenesis
#5
Tomoya Yamashita
Atherosclerosis is a chronic inflammatory disease. Interventions targeting the inflammatory process could provide new strategies for preventing atherosclerotic cardiovascular diseases (CVD). Previously, we have reported that oral administration of anti-CD3 antibodies, or active vitamin D3, reduced atherosclerosis in mice via recruiting regulatory T cells and tolerogenic dendritic cells to the gut-associated lymphoid tissues. From this, it is reasonable to propose that the intestine could be a novel therapeutic target for prevention of atherosclerotic CVD...
December 7, 2016: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/27928009/influence-of-plasma-cell-niche-factors-on-the-recruitment-and-maintenance-of-irf4hi-plasma-cells-and-plasmablasts-in-vaccinated-siv-infected-rhesus-macaques-with-low-and-high-viremia
#6
Julia M Shaw, Leia K Miller-Novak, Venkatramanan Mohanram, Katherine McKinnon, Thorsten Demberg, Diego A Vargas-Inchaustegui, David Venzon, Marjorie Robert-Guroff
: In a recent study, we found protection following SIV exposure correlated with rectal plasma cell frequency in vaccinated female rhesus macaques. We sought to determine if these same macaques maintained high mucosal plasma cell frequencies post-infection and if this translated to reduced viremia. Although delayed SIV acquisition did not predict subsequent viral control, alterations existed in the distribution of plasma cells and plasmablasts between macaques that exhibited high or low viremia...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27927641/genetic-architecture-distinguishes-systemic-juvenile-idiopathic-arthritis-from-other-forms-of-juvenile-idiopathic-arthritis-clinical-and-therapeutic-implications
#7
Michael J Ombrello, Victoria L Arthur, Elaine F Remmers, Anne Hinks, Ioanna Tachmazidou, Alexei A Grom, Dirk Foell, Alberto Martini, Marco Gattorno, Seza Özen, Sampath Prahalad, Andrew S Zeft, John F Bohnsack, Norman T Ilowite, Elizabeth D Mellins, Ricardo Russo, Claudio Len, Maria Odete E Hilario, Sheila Oliveira, Rae S M Yeung, Alan M Rosenberg, Lucy R Wedderburn, Jordi Anton, Johannes-Peter Haas, Angela Rosen-Wolff, Kirsten Minden, Klaus Tenbrock, Erkan Demirkaya, Joanna Cobb, Elizabeth Baskin, Sara Signa, Emily Shuldiner, Richard H Duerr, Jean-Paul Achkar, M Ilyas Kamboh, Kenneth M Kaufman, Leah C Kottyan, Dalila Pinto, Stephen W Scherer, Marta E Alarcón-Riquelme, Elisa Docampo, Xavier Estivill, Ahmet Gül, Carl D Langefeld, Susan Thompson, Eleftheria Zeggini, Daniel L Kastner, Patricia Woo, Wendy Thomson
OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of conditions unified by the presence of chronic childhood arthritis without an identifiable cause. Systemic JIA (sJIA) is a rare form of JIA characterised by systemic inflammation. sJIA is distinguished from other forms of JIA by unique clinical features and treatment responses that are similar to autoinflammatory diseases. However, approximately half of children with sJIA develop destructive, long-standing arthritis that appears similar to other forms of JIA...
December 7, 2016: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/27927043/allopurinol-insights-from-studies-of-dose-response-relationships
#8
Richard O Day, Diluk R W Kannangara, Sophie L Stocker, Jane E Carland, Kenneth M Williams, Garry G Graham
Gout is the most common inflammatory arthritis in men and is increasingly prevalent. Allopurinol is very effective at reducing plasma urate concentrations to a level sufficient to dissolve monosodium urate crystals. However, many patients fail to achieve a sufficient therapeutic response to allopurinol. Areas covered: This review covers the metabolism and pharmacokinetics of allopurinol and its active metabolite, oxypurinol and how these factors affect the plasma concentrations of urate at initiation and during long-term therapy with allopurinol...
December 7, 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27926950/c6-and-c7-substituted-3-4-dihydro-2-1h-quinolinones-as-inhibitors-of-monoamine-oxidase
#9
L Meiring, J Petzer, A Petzer
Purpose Monoamine oxidase (MAO) inhibitors are considered to be useful therapeutic agents and isoform specific inhibitors are employed for the treatment of depression and Parkinson's disease. MAO inhibitors are also under investigation for the treatment of disorders ranging from Alzheimer's disease, prostate cancer and certain cardiomyopathies. While a number of irreversible MAO inhibitors are available in the clinic, reversible inhibitors, particularly of the MAO-B isoform are still being developed. Based on our interest in discovering reversible inhibitors with specificity for MAO-B, we have recently reported that, among a series of 10 3,4-dihydro-2(1H)-quinolinone derivatives, are high potency MAO-B inhibitors, with a number of homologues displaying good selectivities for MAO-B over the MAO-A isoform...
December 7, 2016: Drug Research
https://www.readbyqxmd.com/read/27926600/supporting-rural-women-during-pregnancy-baby-beep-nurses
#10
Emily C Evans, Linda F C Bullock
PURPOSE: The aim of this study was to characterize nursing care provided by the research nurses from the Baby Behavioral Educational Enhancement of Pregnancy (Baby BEEP) study as they delivered a telephone social support intervention to low-income, pregnant women in the Midwestern United States. STUDY DESIGN AND METHODS: This was a descriptive qualitative study that used Peplau's Theory of Interpersonal Relations to frame and interpret the analysis. RESULTS: Research nurses from the Baby BEEP study found a novel way to reach a vulnerable population through weekly telephone interactions...
January 2017: MCN. the American Journal of Maternal Child Nursing
https://www.readbyqxmd.com/read/27926532/novel-parp1-2-inhibitor-mefuparib-hydrochloride-elicits-potent-in-vitro-and-in-vivo-anticancer-activity-characteristic-of-high-tissue-distribution
#11
Jin-Xue He, Meng Wang, Xia-Juan Huan, Chuan-Huizi Chen, Shan-Shan Song, Ying-Qing Wang, Xue-Mei Liao, Cun Tan, Qian He, Lin-Jiang Tong, Yu-Ting Wang, Xiao-Hua Li, Yi Su, Yan-Yan Shen, Yi-Ming Sun, Xin-Ying Yang, Yi Chen, Zhi-Wei Gao, Xiao-Yan Chen, Bing Xiong, Xiu-Lian Lu, Jian Ding, Chun-Hao Yang, Ze-Hong Miao
The approval of poly(ADP-ribose) polymerase (PARP) inhibitor AZD2281 in 2014 marked the successful establishment of the therapeutic strategy targeting homologous recombination repair defects of cancers in the clinic. However, AZD2281 has poor water solubility, low tissue distribution and relatively weak in vivo anticancer activity, which appears to become limiting factors for its clinical use. In this study, we found that mefuparib hydrochloride (MPH) was a potent PARP inhibitor, possessing prominent in vitro and in vivo anticancer activity...
December 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27926382/prediction-of-anti-cancer-drug-response-by-kernelized-multi-task-learning
#12
Mehmet Tan
MOTIVATION: Chemotherapy or targeted therapy are two of the main treatment options for many types of cancer. Due to the heterogeneous nature of cancer, the success of the therapeutic agents differs among patients. In this sense, determination of chemotherapeutic response of the malign cells is essential for establishing a personalized treatment protocol and designing new drugs. With the recent technological advances in producing large amounts of pharmacogenomic data, in silico methods have become important tools to achieve this aim...
October 2016: Artificial Intelligence in Medicine
https://www.readbyqxmd.com/read/27925188/a-human-3d-in-vitro-model-to-assess-the-relationship-between-osteoporosis-and-dissemination-to-bone-of-breast-cancer-tumour-cells
#13
F Salamanna, V Borsari, S Brogini, P Torricelli, S Cepollaro, M Cadossi, M Fini
Despite consistent improvements in diagnostic and therapeutic strategies for breast cancer, up to 40% of patients will develop bone metastases. To reduce the morbidity and complications related with bone metastases, it is imperative to reduce their etiological factors. Osteoporosis, being characterized by a sudden estrogen deficiency, may provide a favorable condition for bone metastasis. This work, using a humanized 3D in vitro model, aims at evaluating the relationship between osteoporosis and breast cancer-derived bone metastases...
December 7, 2016: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/27924643/risk-of-infections-using-anti-tnf-agents-in-rheumatoid-arthritis-psoriatic-arthritis-and-ankylosing-spondylitis-a-systematic-review-and-meta-analysis
#14
Silvia Minozzi, Stefanos Bonovas, Theodore Lytras, Valentina Pecoraro, Marien González-Lorenzo, Anan Judina Bastiampillai, Eugenia Maria Gabrielli, Andrea Carlo Lonati, Lorenzo Moja, Michela Cinquini, Valentina Marino, Andrea Matucci, Giuseppe Maria Milano, Giuliano Tocci, Raffaele Scarpa, Delia Goletti, Fabrizio Cantini
Five anti-tumor necrosis factor (anti-TNF) agents have received regulatory approval for use in rheumatology: adalimumab, golimumab, infliximab, certolizumab, and etanercept. Apart from their well-documented therapeutic value, it is still uncertain to what extent they are associated with an increased risk of infectious adverse events. Areas covered: We conducted a systematic review and meta-analysis of published randomized studies to determine the effect of anti-TNF drugs on the occurrence of infectious adverse events (serious infections; tuberculosis; opportunistic infections; any infection)...
December 2016: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/27924341/structure-activity-relationship-of-novel-macrocyclic-biased-apelin-receptor-agonists
#15
Alexandre Murza, Xavier Sainsily, Jérôme Côté, Laurent Bruneau-Cossette, Élie Besserer-Offroy, Jean-Michel Longpré, Richard Leduc, Robert Dumaine, Olivier Lesur, Mannix Auger-Messier, Philippe Sarret, Éric Marsault
Apelin is the endogenous ligand for the G protein-coupled receptor APJ and exerts a key role in regulating cardiovascular functions. We report herein a novel series of macrocyclic analogues of apelin-13 in which the N- and C-terminal residues as well as the macrocycle composition were chemically modified to modulate structure-activity relationships on the APJ receptor. To this end, the binding affinity and the ability to engage G protein-dependent and G protein-independent signalling pathways of the resulting analogues were assessed...
December 7, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27924018/disgenet-a-comprehensive-platform-integrating-information-on-human-disease-associated-genes-and-variants
#16
Janet Piñero, Àlex Bravo, Núria Queralt-Rosinach, Alba Gutiérrez-Sacristán, Jordi Deu-Pons, Emilio Centeno, Javier García-García, Ferran Sanz, Laura I Furlong
The information about the genetic basis of human diseases lies at the heart of precision medicine and drug discovery. However, to realize its full potential to support these goals, several problems, such as fragmentation, heterogeneity, availability and different conceptualization of the data must be overcome. To provide the community with a resource free of these hurdles, we have developed DisGeNET (http://www.disgenet.org), one of the largest available collections of genes and variants involved in human diseases...
October 19, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923701/prognostic-significance-of-repeat-biopsy-in-lupus-nephritis-histopathologic-worsening-and-a-short-time-between-biopsies-is-associated-with-significantly-increased-risk-for-end-stage-renal-disease-and-death
#17
Cristina Arriens, Sixia Chen, David R Karp, Ramesh Saxena, Kamalanathan Sambandam, Eliza Chakravarty, Judith A James, Joan T Merrill
BACKGROUND/PURPOSE: Approximately half of patients with systemic lupus erythematosus (SLE) develop lupus nephritis (LN), a major cause of morbidity and early mortality in that disease. Prolonged renal inflammation is associated with irreversible kidney damage which confers a 30% risk of end stage renal disease (ESRD), making early, aggressive treatment mandatory. Failure to achieve therapeutic response or recurrence of renal flare often prompts repeat biopsy. However, the role of repeat biopsy in determining long-term renal prognosis remains controversial...
December 3, 2016: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/27923046/mitochondria-and-caspases-tune-nmnat-mediated-stabilization-to-promote-axon-regeneration
#18
Li Chen, Derek M Nye, Michelle C Stone, Alexis T Weiner, Kyle W Gheres, Xin Xiong, Catherine A Collins, Melissa M Rolls
Axon injury can lead to several cell survival responses including increased stability and axon regeneration. Using an accessible Drosophila model system, we investigated the regulation of injury responses and their relationship. Axon injury stabilizes the rest of the cell, including the entire dendrite arbor. After axon injury we found mitochondrial fission in dendrites was upregulated, and that reducing fission increased stabilization or neuroprotection (NP). Thus axon injury seems to both turn on NP, but also dampen it by activating mitochondrial fission...
December 6, 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27922982/mir-21-is-overexpressed-in-hydatidiform-mole-tissues-and-promotes-proliferation-migration-and-invasion-in-choriocarcinoma-cells
#19
Ya-Xin Wang, Jiu-Ru Zhao, Yue-Ying Xu, Wei-Bin Wu, Hui-Juan Zhang
OBJECTIVE: The aims of this study were to make clear whether miR-21 was dysregulated in hydatidiform mole (HM) tissues and choriocarcinoma (CCA) cells, to elucidate whether aberrant miR-21 expression would affect the function of CCA cells, and to find out whether there was a relationship between miR-21 and AKT, PDCD4, and PTEN in CCA cells. METHODS: Fresh and formalin-fixed, paraffin-embedded trophoblastic tissues (normal first trimester placentas and HMs) were retrieved from the biobank in the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University...
December 3, 2016: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/27922681/cxcr4-promotes-cisplatin-resistance-of-non-small-cell-lung-cancer-in-a-cyp1b1-dependent-manner
#20
Songping Xie, Zhenbo Tu, Jie Xiong, Ganjun Kang, Lina Zhao, Weidong Hu, Haiyan Tan, Kingsley Miyanda Tembo, Qianshan Ding, Xinzhou Deng, Jie Huang, Qiuping Zhang
Chemoresistance is the main cause of treatment failure and high mortality in advanced lung cancer. Cisplatin, an important chemotherapeutic agent for lung cancer, has been observed to show enormously reduced chemotherapeutic efficacy owing to the development of chemoresistance. CXCR4, a stromal-derived-factor-1 specific chemokine receptor, is highly expressed in non-small cell lung cancer (NSCLC) tissues and participates in cancer progression by regulating cell growth, apoptosis or invasion. In this study, we therefore investigated whether CXCR4 plays a role in the cisplatin associated resistance in NSCLC...
December 2, 2016: Oncology Reports
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