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https://www.readbyqxmd.com/read/29925096/inhibitors-in-hemophilia-b
#1
Cristina Santoro, Gabriele Quintavalle, Giancarlo Castaman, Erminia Baldacci, Antonietta Ferretti, Federica Riccardi, Annarita Tagliaferri
Hemophilia B (HB) is an X-linked bleeding disorder caused by deficiency of factor IX (FIX). Patients with the severe form (FIX <1%) account approximately for 30 to 45% of persons with HB and usually suffer from recurrent joint, soft-tissue, and muscle bleeds. The availability of safe plasma-derived and recombinant products has virtually abolished the risk of viral infections and the adoption of prophylactic regimens has attenuated the impact of hemophilic arthropathy. Therefore, the development of an inhibitor against FIX is currently the most serious complication that can still occur in the new generations of HB patients...
June 20, 2018: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/29925063/targeting-shp-1-2-and-ship-pathways-a-novel-strategy-for-cancer-treatment
#2
REVIEW
Wolfram C M Dempke, Peter Uciechowski, Klaus Fenchel, Timothy Chevassut
Well-balanced levels of tyrosine phosphorylation, maintained by the reversible and coordinated actions of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs), are critical for a wide range of cellular processes including growth, differentiation, metabolism, migration, and survival. Aberrant tyrosine phosphorylation, as a result of a perturbed balance between the activities of PTKs and PTPs, is linked to the pathogenesis of numerous human diseases, including cancer, suggesting that PTPs may be innovative molecular targets for cancer treatment...
June 20, 2018: Oncology
https://www.readbyqxmd.com/read/29925031/influence-of-pulsed-electric-fields-and-mitochondria-cytoskeleton-interactions-on-cell-respiration
#3
Ishan Goswami, Justin B Perry, Mitchell E Allen, David A Brown, Michael R von Spakovsky, Scott S Verbridge
Pulsed electric fields with microsecond pulse width (μsPEFs) are used clinically; namely, irreversible electroporation/Nanoknife is used for soft tissue tumor ablation. The μsPEF pulse parameters used in irreversible electroporation (0.5-1 kV/cm, 80-100 pulses, ∼100 μs each, 1 Hz frequency) may cause an internal field to develop within the cell because of the disruption of the outer cell membrane and subsequent penetration of the electric field. An internal field may disrupt voltage-sensitive mitochondria, although the research literature has been relatively unclear regarding whether such disruptions occur with μsPEFs...
June 19, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29924966/a-proteomic-variant-approach-provara-for-personalized-medicine-of-inherited-and-somatic-disease
#4
DarrenM Hutt, Salvatore Loguercio, Alexandre Rosa Campos, William E Balch
The advent of precision medicine for genetic diseases has been hampered by the large number of variants that cause familial and somatic disease, a complexity that is further confounded by the impact of genetic modifiers. To begin to understand differences in onset, progression and therapeutic response that exist among disease-causing variants, we present the proteomic variant approach (ProVarA), a proteomic method that integrates mass spectrometry with genomic tools to dissect the etiology of disease. To illustrate its value, we examined the impact of variation in cystic fibrosis (CF), where 2025 disease-associated mutations in the CF transmembrane conductance regulator (CFTR) gene have been annotated and where individual genotypes exhibit phenotypic heterogeneity and response to therapeutic intervention...
June 17, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29924791/-algorithm-of-treatment-policy-for-a-femoral-artery-false-aneurysm
#5
A A Fokin, K A Kireev
The purpose of the study was to elaborate an algorithm of treatment policy for post-puncture false aneurysms of the femoral artery (FAFA). The study was performed on the basis of the clinical material over 2014-2017 at the Regional Vascular Centre whose specialists have since 2017 been using the femoral arterial approach (FAA) only if the radial arteries are inaccessible for puncture or for inserting the endovascular tools and appliances. The obtained findings demonstrated that the number of coronary interventions performed with the use of the femoral arterial approach in patients presenting with acute coronary syndrome decreased from a total of 758 (100...
2018: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29924776/-results-of-endovascular-treatment-of-obstructive-lesions-of-veins-of-the-iliofemoral-segment
#6
A V Pokrovskiĭ, I M Ignat'ev, E G Gradusov
OBJECTIVE: The purpose of the study was to assess the immediate and remote results of endovascular treatment of obstructive lesions of the veins of the iliofemoral segment. PATIENTS AND METHODS: We performed balloon angioplasty and stenting for iliofemoral venous thrombosis in a total of 75 patients. Of these, 60 patients were subjected to stenting of post-thrombotic obstructions and 15 patients underwent stenting of non-thrombotic obstructive lesions of the iliac veins (for May-Thurner syndrome - in 11, for extravasal tumour-induced compression and cicatricial stenosis - in 4)...
2018: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29924773/-gene-mediated-induction-of-angiogenesis-in-inoperable-patients-with-atherosclerosis-and-diabetes-mellitus
#7
R E Kalinin, I A Suchkov, R V Deev, N D Mzhavanadze, A A Krylov
Analysed in the article are the results of a comprehensive approach to treatment of patients presenting with lower limb critical ischaemia and diabetes mellitus by means of gene-induced angiogenesis. The study comprised a total of 65 patients found to have an ill-suited for surgical reconstruction peripheral arterial bed and undergoing conservative therapy. The patients were divided into two groups. The Study Group patients additionally to the conventional conservative therapy received 2 intramuscular injections of therapeutic agent Neovasculgen at a course dose of 2...
2018: Angiologii︠a︡ i Sosudistai︠a︡ Khirurgii︠a︡, Angiology and Vascular Surgery
https://www.readbyqxmd.com/read/29924461/short-term-external-counterpulsation-augments-cerebral-blood-flow-and-tissue-oxygenation-in-chronic-cerebrovascular-occlusive-disease
#8
Eva E Buschmann, Philipp Hillmeister, Anja Bondke Persson, David S Liebeskind, Lea Schlich, Robert Kamenzky, Andreas Busjahn, Ivo R Buschmann, Peter Bramlage, Andreas Hetzel, Matthias Reinhard
BACKGROUND: External counterpulsation improves cerebral perfusion velocity in acute stroke and may stimulate collateral artery growth. However, whether (non-acute) at-risk patients with high-grade carotid artery disease may benefit from counterpulsation needs to be validated. METHODS: Twenty-eight patients (71±6.5 years, 5 women) with asymptomatic unilateral chronic severe ICA stenosis (>70%) or occlusion were randomized to receive 20 min active counterpulsation followed by sham treatment or vice versa...
June 20, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
https://www.readbyqxmd.com/read/29924455/igg4-related-disease-review-of-the-histopathologic-features-differential-diagnosis-and-therapeutic-approach
#9
REVIEW
Jacob R Bledsoe, Emanuel Della-Torre, Lucrezia Rovati, Vikram Deshpande
Immunoglobulin G4-related disease (IgG4-RD) is an uncommon disorder that demonstrates characteristic clinicopathologic features including sclerosing lesions with storiform fibrosis, increased IgG4+ plasma cells with an increased IgG4+/IgG+ plasma cell ratio, obliterative phlebitis, and often an increased serum IgG4 level. This review summarizes the characteristic histopathologic and clinical features of IgG4-RD with detailed discussion of the histopathologic characteristics of the most commonly involved anatomic sites...
June 2018: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/29924359/identification-of-aspergillus-and-mucorales-in-formalin-fixed-paraffin-embedded-tissue-samples-comparison-of-specific-and-broad-range-fungal-qpcr-assays
#10
J Springer, I McCormick Smith, S Hartmann, R Winkelmann, D Wilmes, O Cornely, J Kessel, J Löffler, V Rickerts
Establishing the etiology of invasive fungal infections is important to guide therapeutic options and for epidemiologic purposes. Formalin-fixed, paraffin-embedded (FFPE) tissue specimens from patients with proven invasive fungal infections are valuable to determine the etiology of systemic fungal infections. We compared different polymerase chain reaction (PCR) amplification strategies from FFPE tissue blocks to identify agents of invasive fungal infections. We found that specific PCR assays show superior sensitivity in the identification of DNA of Mucorales and Aspergillus and mixed infections caused by both as compared to broad-range PCR assays...
June 19, 2018: Medical Mycology: Official Publication of the International Society for Human and Animal Mycology
https://www.readbyqxmd.com/read/29924341/molecular-and-clinicopathologic-heterogeneity-of-intracranial-tumors-mimicking-extraskeletal-myxoid-chondrosarcoma
#11
Julia Velz, Abbas Agaimy, Karl Frontzek, Marian Christoph Neidert, Oliver Bozinov, Ulrich Wagner, Christine Fritz, Roland Coras, Silvia Hofer, Beata Bode-Lesniewska, Elisabeth Rushing
Primary intracranial neoplasms with features of extraskeletal myxoid chondrosarcomas (EMC) are extremely rare and poorly characterized tumors with only ∼12 cases described, the majority lacking molecular confirmation. There is an urgent need for the integration of molecular studies for correct subclassification of these tumors in order to predict clinical behavior, guide therapeutic decision-making, and provide novel targets for therapy. Clinical and pathologic data of 3 intracranial EMC-like myxoid neoplasms were retrospectively reviewed...
June 18, 2018: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/29924302/role-of-proteoglycans-and-glycosaminoglycans-in-duchenne-muscular-dystrophy
#12
Laurino Carmen, Vadala Maria, Julio Cesar Morales-Medina, Annamaria Vallelunga, Beniamino Palmieri, Tommaso Iannitti
Duchenne Muscular dystrophy (DMD) is an inherited fatal X-linked myogenic disorder with a prevalence of 1 in 3500 male live births. It affects voluntary muscles, and heart and breathing muscles. DMD is characterised by continuous degeneration and regeneration cycles resulting in extensive fibrosis and a progressive reduction in muscle mass. Since the identification of a reduction in dystrophin protein as the cause of this disorder, numerous innovative and experimental therapies, focusing on increasing the levels of dystrophin, have been proposed, but the clinical improvement has been unsatisfactory...
June 19, 2018: Glycobiology
https://www.readbyqxmd.com/read/29924299/the-rasopathy-family-consequences-of-germline-activation-of-the-ras-mapk-pathway
#13
Mylène Tajan, Romain Paccoud, Sophie Branka, Thomas Edouard, Armelle Yart
Noonan syndrome (NS; Mendelian Inheritance in Men (MIM) ♯163950) and related syndromes (Noonan syndrome with multiple lentigines (NS-ML, formerly called LEOPARD syndrome; MIM ♯151100), Noonan-like syndrome with loose anagen hair (NS-LAH; MIM ♯607721), Costello syndrome (CS; MIM ♯218040), Cardio-Facio-Cutaneous syndrome (CFCS; MIM ♯115150), type I Neurofibromatosis (NF1; MIM ♯162200), and Legius syndrome (LS; MIM ♯611431)) are a group of related genetic disorders, associating distinctive facial features, cardiopathies, growth and skeletal abnormalities, developmental delay/mental retardation, and tumor predisposition...
June 18, 2018: Endocrine Reviews
https://www.readbyqxmd.com/read/29924242/treatment-of-cutaneous-leishmaniasis-with-thermotherapy-in-brazil-an-efficacy-and-safety-study
#14
Sheila Viana Castelo Branco Gonçalves, Carlos Henrique Nery Costa
BACKGROUND: Pentavalent antimonials remain as the standard drugs in the treatment of cutaneous leishmaniosis. The high cost, difficult administration, long treatment time, toxicity and increasing morbidity are factors that limit the use of these drugs. OBJECTIVES: To describe the response to radiofrequency thermotherapy in the treatment of localized cutaneous leishmaniasis in Brazil, and to evaluate its safety and tolerability. METHODS: We conducted a non-comparative open trial with a total of 15 patients confirmed to have cutaneous leishmaniasis on parasitological examination...
June 2018: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29924221/tazarotene-gel-with-narrow-band-uvb-phototherapy-a-synergistic-combination-in-psoriasis
#15
Surabhi Dayal, Rajiv Kaura, Priyadarshini Sahu, Vijay Kumar Jain
BACKGROUND: Narrow-band UVB (NB-UVB) has been shown to be one of the most effective treatment modalities for psoriasis. Tazarotene, a known effective anti-psoriatic modality, when combined with NB-UVB may enhance the therapeutic success. OBJECTIVE: To study clinical efficacy and safety of combination of NB-UVB with topical tazarotene 0.05% gel in psoriasis. METHOD: Thirty patients with plaque psoriasis having symmetrical lesions were enrolled for 12 weeks...
June 2018: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29924218/erythrodermic-psoriasis-and-human-immunodeficiency-virus-association-and-therapeutic-challenges
#16
Fernando Valenzuela, Javier Fernández, Margarita Sánchez, Andrea Zamudio
Erythrodermic psoriasis is a rare but severe type of psoriasis that may be triggered by human immunodeficiency virus infection. We describe the case of a 65-year-old male patient with chronic psoriasis who presents an exacerbation of his condition over a period of two weeks. Because of the severity of his case and subsequent need for systemic therapy, human immunodeficiency virus enzyme immunoassay was performed and tested positive. He thus began antiretroviral therapy combined with acitretin, showing good clinical response after 8 weeks of treatment...
June 2018: Anais Brasileiros de Dermatologia
https://www.readbyqxmd.com/read/29924011/clinical-inertia-in-the-pharmacological-management-of-hypertension-a-systematic-review-and-meta-analysis
#17
Tal Milman, Raed A Joundi, Naif M Alotaibi, Gustavo Saposnik
BACKGROUND: Clinical Inertia is defined as "failure of health care providers to initiate or intensify therapy according to current guidelines". This phenomenon is gaining increasing attention as a major cause of clinicians' failure to adequately manage hypertension, thus leading to an increased incidence of cardiovascular events. We performed a systematic review and meta-analysis of randomized controlled trials to determine whether interventions aimed at reducing clinical inertia in the pharmacological treatment of hypertension improve blood pressure (BP) control...
June 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29923862/therapeutic-effects-of-topical-8-oxo-2-deoxyguanosine-on-ethanol-induced-ocular-chemical-injury-models
#18
Sang-Taek Im, Hee Yeon Kim, Jin Young Yoon, Joo Youn Oh, Mee Kum Kim, Myung-Hee Chung, Hae Jung Paik, Dong Hyun Kim
PURPOSE: To evaluate the therapeutic effects of topical 8-oxo-2'-deoxyguanosine (8-oxo-dG) on experimental ocular chemical injury models. METHODS: We created ocular chemical injury models with 8-week-old BALB/c mice (n = 70) by applying 100% ethanol; the mice were then treated with 8-oxo-dG eye drops 10 and 5 mg/mL and phosphate-buffered saline (PBS) twice daily. After 7 days, clinical findings such as corneal integrity, clarity, and neovascularization were assessed...
June 19, 2018: Cornea
https://www.readbyqxmd.com/read/29923861/optimized-protocol-for-regeneration-of-the-conjunctival-epithelium-using-the-cell-suspension-technique
#19
Marina Bertolin, Claudia Breda, Stefano Ferrari, Sara Ilse Van Acker, Nadia Zakaria, Enzo Di Iorio, Angelo Migliorati, Diego Ponzin, Barbara Ferrari, Zala Lužnik, Vanessa Barbaro
PURPOSE: To develop autologous tissue-engineered conjunctival epithelial sheets to be used as advanced therapy medicinal products for severe ocular surface disorders involving the conjunctiva. METHODS: Methods used aimed at 1) mapping the conjunctiva for identification of the stem cell location, 2) establishing proper cell culturing conditions, 3) identifying the proper scaffold, and 4) characterizing the conjunctival grafts better. For these purposes, immunostaining and PAS staining, serial cultivation of cells, and quantitative polymerase chain reaction ([INCREMENT]Np63α and MUC5AC) were performed...
June 19, 2018: Cornea
https://www.readbyqxmd.com/read/29923797/valproate-augments-niraparib-killing-of-tumor-cells
#20
Laurence Booth, Jane L Roberts, Rumeesa Rais, Andrew Poklepovic, Paul Dent
PARP1 inhibitors are approved therapeutic agents in ovarian carcinomas, and have clinical activity in some breast cancers. As a single agent, niraparib killed ovarian and mammary tumor cells via an ATM-AMPK-ULK1 pathway which resulted in mTOR inactivation and the formation of autophagosomes, temporally followed by autolysosome formation. In parallel, niraparib activated a CD95-FADD-caspase 8 pathway, and collectively these signals caused tumor cell death that was suppressed by knock down of Beclin1, ATG5, CD95, FADD or AIF; or by expression of c-FLIP-s, BCL-XL or dominant negative caspase 9...
June 20, 2018: Cancer Biology & Therapy
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