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https://www.readbyqxmd.com/read/28655199/proteins-involved-in-endocytosis-are-upregulated-by-ageing-in-the-normal-human-brain-implications-for-the-development-of-alzheimer-s-disease
#1
Mouhamed Alsaqati, Rhian S Thomas, Emma J Kidd
The greatest risk factor for Alzheimer's disease (AD) is advanced age, but the reason for this association remains unclear. Amyloid-beta (Aβ) is produced from amyloid precursor protein (APP) primarily after APP is internalised by clathrin-mediated or clathrin-independent endocytosis. Changes in endocytosis in AD have been identified. We hypothesised that endocytic protein expression is altered during ageing, thus influencing the likelihood of developing AD by increasing Aβ production. We explored how levels of endocytic proteins, APP, its metabolites, secretase enzymes and tau varied with age in cortical brain samples from men of three age ranges (young (20-30), middle-aged (45-55) and old (70-90)) with no symptoms of dementia...
June 26, 2017: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/28655021/the-diagnosis-and-treatment-of-prostate-cancer-a-review
#2
Mark S Litwin, Hung-Jui Tan
Importance: Prostate cancer is the most common cancer diagnosis made in men with more than 160 000 new cases each year in the United States. Although it often has an indolent course, prostate cancer remains the third-leading cause of cancer death in men. Observations: When prostate cancer is suspected, tissue biopsy remains the standard of care for diagnosis. However, the identification and characterization of the disease have become increasingly precise through improved risk stratification and advances in magnetic resonance and functional imaging, as well as from the emergence of biomarkers...
June 27, 2017: JAMA: the Journal of the American Medical Association
https://www.readbyqxmd.com/read/28654861/aging-alters-mrna-expression-of-amyloid-transporter-genes-at-the-blood-brain-barrier
#3
Doreen Osgood, Miles C Miller, Arthur A Messier, Liliana Gonzalez, Gerald D Silverberg
Decreased clearance of potentially toxic metabolites, due to aging changes, likely plays a significant role in the accumulation of amyloid-beta (Aβ) peptides and other macromolecules in the brain of the elderly and in the patients with Alzheimer's disease (AD). Aging is the single most important risk factor for AD development. Aβ transport receptor proteins expressed at the blood-brain barrier are significantly altered with age: the efflux transporters lipoprotein receptor-related protein 1 and P-glycoprotein are reduced, whereas the influx transporter receptor for advanced glycation end products is increased...
May 19, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28654711/addressing-the-immunopathogenesis-of-atopic-dermatitis-advances-in-topical-and-systemic-treatment
#4
Lawrence F Eichenfield, Linda F Stein Gold
Several immunologic mediators-phosphodiesterase (PDE), interleukin (IL), small molecules, and Janus kinase-have been implicated in the pathogenesis of atopic dermatitis, and evidence has shown that blocking these mediators can help modify the disease process. Several new topical medications have been developed that target the enzyme PDE; crisaborole was recently approved by the US Food and Drug Administration (FDA) for the treatment of atopic dermatitis, and phase II studies have been completed on OPA-15406...
March 2017: Seminars in Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/28654634/emergence-of-met-hyper-amplification-at-progression-to-met-and-braf-inhibition-in-colorectal-cancer
#5
Daniele Oddo, Giulia Siravegna, Annunziata Gloghini, Claudio Vernieri, Benedetta Mussolin, Federica Morano, Giovanni Crisafulli, Rosa Berenato, Giorgio Corti, Chiara Costanza Volpi, Michela Buscarino, Monica Niger, Philip D Dunne, Giuseppe Rospo, Emanuele Valtorta, Alice Bartolini, Giovanni Fucà, Simona Lamba, Antonia Martinetti, Maria Di Bartolomeo, Filippo de Braud, Alberto Bardelli, Filippo Pietrantonio, Federica Di Nicolantonio
BACKGROUND: Combined MET and BRAF inhibition showed clinical benefit in a patient with rectal cancer carrying BRAF(V600E) and MET amplification. However after 4 months, acquired resistance emerged and the patient deceased shortly after disease progression. The mechanism of resistance to this drug combination is unknown. METHODS: We analysed plasma circulating tumour DNA obtained at progression by exome sequencing and digital PCR. MET gene and mRNA in situ hybridisation analyses in two bioptic specimens obtained at progression were used to confirm the plasma data...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28654633/chemotherapy-with-radiotherapy-influences-time-to-development-of-radiation-induced-sarcomas-a-multicenter-study
#6
A Y Zhang, I Judson, C Benson, J S Wunder, I Ray-Coquard, R J Grimer, R Quek, E Wong, A B Miah, P C Ferguson, A Dufresne, J Y H Teh, M Stockler, M H N Tattersall
BACKGROUND: An increasing number and proportion of cancer patients with apparently localised disease are treated with chemotherapy and radiation therapy in contemporary oncology practice. In a pilot study of radiation-induced sarcoma (RIS) patients, we demonstrated that chemotherapy was associated with a reduced time to development of RIS. We now present a multi-centre collaborative study to validate this association. METHODS: This was a retrospective cohort study of RIS cases across five large international sarcoma centres between 1 January 2000 to 31 December 2014...
June 27, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28654574/capecitabine-and-celecoxib-as-a-promising-therapy-for-thymic-neoplasms
#7
Kevin Wood, Elizabeth Byron, Linda Janisch, Ravi Salgia, Manish R Sharma
OBJECTIVES: For patients with unresectable or metastatic thymic epithelial neoplasms, few therapy options are available and outcomes are poor. This case series demonstrates that the combination of capecitabine and celecoxib may be a promising therapeutic option for these patients. MATERIALS AND METHODS: The current report describes the outcomes of 5 patients with thymic neoplasms treated on a drug-drug interaction study of capecitabine and celecoxib in patients with advanced solid malignancies (NCT01705106) conducted at the University of Chicago, plus a sixth patient treated with the same regimen outside of the protocol...
June 26, 2017: American Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28654473/regenerative-rehabilitation-combining-stem-cell-therapies-and-activity-dependent-stimulation
#8
Chet T Moritz, Fabrisia Ambrosio
The number of clinical trials in regenerative medicine is burgeoning, and stem cell/tissue engineering technologies hold the possibility of becoming the standard of care for a multitude of diseases and injuries. Advances in regenerative biology reveal novel molecular and cellular targets, with potential to optimize tissue healing and functional recovery, thereby refining rehabilitation clinical practice. The purpose of this review is to (1) highlight the potential for synergy between the fields of regenerative medicine and rehabilitation, a convergence of disciplines known as regenerative rehabilitation; (2) provide translational examples of regenerative rehabilitation within the context of neuromuscular injuries and diseases; and (3) offer recommendations for ways to leverage activity dependence via combined therapy and technology, with the goal of enhancing long-term recovery...
July 2017: Pediatric Physical Therapy
https://www.readbyqxmd.com/read/28654472/the-past-present-and-future-of-neurorehabilitation-from-nustep-through-iv-step-and-beyond
#9
Susan R Harris, Carolee J Winstein
PURPOSES: To present the history and aims of the STEP conferences; describe the interdependence of prevention, prediction, plasticity, and participation; reflect on where we stand today regarding those 4 Ps; and discuss how future neurorehabilitation should look for individuals with movement disorders. KEY POINTS: Physical therapists have focused primarily on tertiary prevention, emphasizing primary/secondary prevention far less. Predicting optimal response to intervention is essential for primary prevention...
July 2017: Pediatric Physical Therapy
https://www.readbyqxmd.com/read/28654444/lichenoid-dermatitis-of-the-vulva-diagnosis-and-differential-diagnosis-for-the-gynecologic-pathologist
#10
Marc R Lewin, Ryan W Hick, Maria A Selim
Inflammatory processes affecting the vulva may present a unique challenge due to location specific changes. Different factors are behind the intricacy in the presentation of vulvar dermatoses. First, the vulva is lined by different epithelia (hair-bearing keratinized epithelium, modified mucosa, and mucosa). Furthermore, among other factors, this organ is exposed to friction, occlusion, and trauma. Lastly, as there is a tendency to look for health care advice at an advanced stage of the disease, the lesion may be modified by secondary changes due to self-treatment...
June 26, 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28654435/myasthenia-gravis-new-developments-in-research-and-treatment
#11
Amelia Evoli
PURPOSE OF REVIEW: Myasthenia gravis, a rare disorder of the neuromuscular transmission, is increasingly acknowledged as a syndrome more than as a single disease. This review summarizes recent advances in pathophysiology which confirm the disease heterogeneity, and may help find disease-targeted and patient-targeted therapies. RECENT FINDINGS: Antibodies to the acetylcholine receptor, the muscle-specific tyrosine kinase and the lipoprotein receptor protein 4, characterize disease subtypes with distinct clinical traits and immune-pathogenic mechanisms...
June 24, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28654132/henoch-sch%C3%A3-nlein-purpura-a-literature-review
#12
Liv Eline Hetland, Kjærsti Sørensen Susrud, Kim Hein Lindahl, Anette Bygum
Henoch-Schönlein purpura is the most common childhood vasculitis, but may also affect adults. This article reviews the literature since 2011 on advances in diagnosis, clinical disease manifestations, pathophysiology and treatment of Henoch-Schönlein purpura. The clinical manifestations are thought to arise from IgA depositions in blood vessel walls in the affected organs, mostly skin, gastrointestinal tract, joints and kidneys. Corticosteroids may be effective in rapid resolution of renal manifestations and treating joint and abdominal pain, but they are not proven effective for treating organ manifestations and complications, such as glomerulonephritis, bowel infarction or intussusception...
June 27, 2017: Acta Dermato-venereologica
https://www.readbyqxmd.com/read/28654031/treatment-of-ligament-constructs-with-exercise-conditioned-serum-a-translational-tissue-engineering-model
#13
Ann Lee-Barthel, Keith Baar, Daniel W D West
In vitro experiments are essential to understand biological mechanisms; however, the gap between monolayer tissue culture and human physiology is large, and translation of findings is often poor. Thus, there is ample opportunity for alternative experimental approaches. Here we present an approach in which human cells are isolated from human anterior cruciate ligament tissue remnants, expanded in culture, and used to form engineered ligaments. Exercise alters the biochemical milieu in the blood such that the function of many tissues, organs and bodily processes are improved...
June 11, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28654022/recent-advances-in-the-management-of-gastroenteropancreatic-neuroendocrine-tumors-insights-from-the-2017-asco-gastrointestinal-cancers-symposium
#14
Renuka Iyer, Alexandria T Phan, J Philip Boudreaux
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare malignancies that originate in the gastrointestinal system. GEP-NETs are typically indolent, but tumors known as "functional" secrete hormones that can lead to a complex of symptoms, including flushing, diarrhea, bronchospasm, and valvular heart disease. Management of patients with GEP-NETs requires a multidisciplinary approach, as treatment modalities include surgery, radiology, and pharmacotherapy. The available pharmacologic agents have increased in recently, and now include cytotoxic chemotherapies, somatostatin analogues, multitargeted tyrosine kinase inhibitors, mammalian target of rapamycin inhibitors, and radioisotopic radiotherapies...
April 2017: Clinical Advances in Hematology & Oncology: H&O
https://www.readbyqxmd.com/read/28653957/the-lifecycle-of-the-ebola-virus-in-host-cells
#15
REVIEW
Dong-Shan Yu, Tian-Hao Weng, Xiao-Xin Wu, Frederick X C Wang, Xiang-Yun Lu, Hai-Bo Wu, Nan-Ping Wu, Lan-Juan Li, Hang-Ping Yao
Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae. However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle...
June 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28653888/dj-1-as-a-potential-biomarker-for-the-early-diagnosis-in-lung-cancer-patients
#16
Binbin Han, Jiwen Wang, Jia Gao, Shana Feng, Yu Zhu, Xuexiang Li, Ting Xiao, Jun Qi, Wei Cui
DJ-1 is a novel oncogene that can transform NIH3T3 cells in cooperation with the activated ras gene. DJ-1 appears to have its greatest effect on tumourigenesis, and it may have a greater impact on early-stage lung cancers. In this study, we proposed to investigate the clinical value of DJ-1 protein in the early diagnosis of lung cancer and compared its diagnostic value with other biomarkers. Preoperative serum DJ-1 levels were measured in 300 lung cancer patients and compared with benign pulmonary disease (n = 44) and healthy volunteers (n = 64)...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28653677/monitoring-immune-checkpoint-blockade-response-evaluation-and-biomarker-development
#17
REVIEW
Mizuki Nishino, Nikhil H Ramaiya, Hiroto Hatabu, F Stephen Hodi
Cancer immunotherapy using immune-checkpoint blockade (ICB) has created a paradigm shift in the treatment of advanced-stage cancers. The promising antitumour activity of monoclonal antibodies targeting the immune-checkpoint proteins CTLA-4, PD-1, and PD-L1 led to regulatory approvals of these agents for the treatment of a variety of malignancies. Patients might experience clinical benefits from treatment with these agents, despite unconventional patterns of tumour response that can be misinterpreted as disease progression, warranting a new, specific approach to evaluate responses to immunotherapy...
June 27, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28653675/periprostatic-adipose-inflammation-is-associated-with-high-grade-prostate-cancer
#18
A Gucalp, N M Iyengar, X K Zhou, D D Giri, D J Falcone, H Wang, S Williams, M D Krasne, I Yaghnam, B Kunzel, P G Morris, L W Jones, M Pollak, V P Laudone, C A Hudis, H I Scher, P T Scardino, J A Eastham, A J Dannenberg
BACKGROUND: Obesity, a cause of subclinical inflammation, is associated with increased risk of high-grade prostate cancer (PC) and poor outcomes. Whether inflammation occurs in periprostatic white adipose tissue (WAT), and contributes to the negative impact of obesity on PC aggressiveness, is unknown. METHODS: In a single-center, cross-sectional design, men with newly diagnosed PC undergoing radical prostatectomy were eligible for study participation. The primary objective was to examine the prevalence of periprostatic WAT inflammation defined by the presence of crown-like structures (CLS-P) as detected by CD68 immunohistochemistry...
June 27, 2017: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/28653667/appendectomy-and-the-risk-of-colectomy-in-ulcerative-colitis-a-national-cohort-study
#19
Pär Myrelid, Kalle Landerholm, Caroline Nordenvall, Thomas D Pinkney, Roland E Andersson
OBJECTIVES: Ulcerative colitis (UC) is a chronic inflammatory disease usually responding well to anti-inflammatory drugs but many patients will still need colectomy. Appendectomy is associated with a lower risk of later developing UC. We aimed to assess the longitudinal relationship between appendectomy, appendicitis, and disease course in UC patients. METHODS: A national cohort of UC patients with a diagnosis in 1964-2010 was identified from the Swedish National Patient Register that also provided information regarding appendicitis and/or appendectomy before or after the UC diagnosis...
June 27, 2017: American Journal of Gastroenterology
https://www.readbyqxmd.com/read/28653647/advances-in-progressive-supranuclear-palsy-new-diagnostic-criteria-biomarkers-and-therapeutic-approaches
#20
REVIEW
Adam L Boxer, Jin-Tai Yu, Lawrence I Golbe, Irene Litvan, Anthony E Lang, Günter U Höglinger
Progressive supranuclear palsy (PSP), previously believed to be a common cause of atypical parkinsonism, is now recognised as a range of motor and behavioural syndromes that are associated with a characteristic 4-repeat tau neuropathology. New research criteria that recognise early presentations of PSP and operationalise diagnosis of the full spectrum of clinical phenotypes have been reported. The Movement Disorders Society PSP diagnostic criteria include syndromes with few or mild symptoms that are suggestive of underlying PSP pathology and could provide an opportunity for earlier therapeutic interventions in the future...
July 2017: Lancet Neurology
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