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https://www.readbyqxmd.com/read/28728108/new-tacrine-dimers-with-antioxidant-linkers-as-dual-drugs-anti-alzheimer-s-and-antiproliferative-agents
#1
Jesús M Roldán-Peña, Daniel Alejandre-Ramos, Óscar López, Inés Maya, Irene Lagunes, José M Padrón, Luis Emiliano Peña-Altamira, Manuela Bartolini, Barbara Monti, Maria L Bolognesi, José G Fernández-Bolaños
We have designed a series of tacrine-based homo- and heterodimers that incorporate an antioxidant tether (selenoureido, chalcogenide) as new dual compounds: for the treatment of Alzheimer's disease and as antiproliferative agents. Symmetrical homodimers bearing a dichalcogenide or selenide-based tether, the best compounds in the series, were found to be strong and highly selective electric eel AChE inhibitors, with inhibition constants within the low nanomolar range. This high inhibitory activity was confirmed on recombinant human AChE for the most interesting derivatives...
June 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28728106/multipotent-ache-and-bace-1-inhibitors-for-the-treatment-of-alzheimer-s-disease-design-synthesis-and-bio-analysis-of-7-amino-1-4-dihydro-2h-isoquilin-3-one-derivates
#2
Xiong-Jie Zhao, Da-Min Gong, Yu-Ren Jiang, Dong Guo, Yao Zhu, You-Chao Deng
In this paper, the preparation of a new class of multi-target-directed ligands (MTDLs) based on a 7-amino-1,4-dihydro-2H-isoquilin-3-one, whose lead (compound I) showed promising properties in acetylcholinesterase (AChE) inhibitory activity [1], is described. The results of in vitro activities and molecular docking demonstrated that the target molecule (compounds 10a-n) with three parts of aromatic moieties and appropriate structural length can interact with aromatic residues in catalytic active site (CAS), peripheral anionic site (PAS) and the channel of AChE...
July 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28727985/comparative-study-and-analytical-verification-of-pcr-methods-for-the-diagnosis-of-congenital-chagas-disease
#3
Carolina Inés Cura, Juan Carlos Ramírez, Marcelo Rodríguez, Constanza Lopez-Albízu, Lucía Irazu, Karenina Scollo, Sergio Sosa-Estani
Congenital infection is currently the first cause of new cases of Chagas disease in Argentina and nonendemic areas worldwide. Its diagnosis is of utmost importance to guarantee curative treatment. To improve such diagnosis, a transfer process of PCR tests to the national laboratory network has been initiated. We performed a comparative study of four PCR assays [two end-point PCR and two duplex real-time quantitative PCR (qPCR) procedures] to detect Trypanosoma cruzi DNA in blood samples. Because satellite DNA and kinetoplastid DNA qPCR methods have the best performance and the use of two different molecular targets for confirmatory purposes has been recommended, these methods selected to perform the transfer process and, in consequence, subjected to an analytical verification protocol based on international guidelines...
July 17, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28727948/a-collaborative-network-based-approach-to-advance-women-s-depression-research-in-the-united-states-preliminary-findings
#4
Heather A Flynn, Catherine Spino, Constance Guille, Kristina M Deligiannidis, Pauline Maki, Jordan Jahnke, Katherine L Rosenblum, C Neill Epperson, Sandra J Weiss
OBJECTIVE: Translation of women's mental health research has yet to impact overall prevalence and burden of Mood Disorders in the United States. The lack of standard measures and methodological coordination across studies has contributed to the slow impact of research on outcomes. The primary aims of this project were to demonstrate the process by which multiple investigators, sites, and settings administered a standard women's mental health questionnaire within a new Women's Depression Network...
July 20, 2017: Journal of Women's Health
https://www.readbyqxmd.com/read/28727877/genetic-predisposition-to-breast-cancer-due-to-mutations-other-than-brca1-and-brca2-founder-alleles-among-ashkenazi-jewish-women
#5
Tom Walsh, Jessica B Mandell, Barbara M Norquist, Silvia Casadei, Suleyman Gulsuner, Ming K Lee, Mary-Claire King
Importance: Among Ashkenazi Jewish women, 3 mutations in BRCA1 and BRCA2 severely increase the risk of breast and ovarian cancer. However, among Ashkenazi Jewish patients with breast cancer who do not carry one of these founder mutations, the likelihood of carrying another pathogenic mutation in BRCA1 or BRCA2 or another breast cancer gene is not known. This information would be valuable to the patient and family for cancer prevention and treatment. Objective: To determine the frequency of cancer-predisposing mutations other than the BRCA1 and BRCA2 founder alleles among patients of Ashkenazi Jewish ancestry with breast cancer...
July 20, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28727774/inhibitors-of-mycobacterium-marinum-virulence-identified-in-a-dictyostelium-discoideum-host-model
#6
Hajer Ouertatani-Sakouhi, Sébastien Kicka, Gianpaolo Chiriano, Christopher F Harrison, Hubert Hilbi, Leonardo Scapozza, Thierry Soldati, Pierre Cosson
Tuberculosis remains one of the major threats to public health worldwide. Given the prevalence of multi drug resistance (MDR) in Mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. Inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. In this study, we used a Dictyostelium discoideum host model to assess virulence of Mycobacterium marinum and to identify compounds inhibiting mycobacterial virulence...
2017: PloS One
https://www.readbyqxmd.com/read/28727714/3d-morphometric-analysis-of-normal-sacroiliac-joints-a-new-classification-of-surface-shape-variation-and-the-potential-implications-in-pain-syndromes
#7
Mary Kristen Jesse, Christopher Kleck, Adam Williams, Brian Petersen, Deborah Glueck, Kimberly Lind, Vikas Patel
BACKGROUND: Normal sacroiliac (SI) joints vary widely in shape, and it is unclear whether SI joint morphology plays a role in the development of pain. To answer this question, we used 3D-CT surface rendering to image healthy study participants and used the resulting images to develop a classification system for SI joint morphology. In a case-control study comparing health research participants to patients with SI pain, we assessed whether the classification of SI joint morphology was associated with pain...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727700/therapeutic-role-of-placebo-evolution-of-a-new-paradigm-in-understanding-research-and-clinical-practice
#8
Laxmaiah Manchikanti, Mark V Boswell, Alan D Kaye, Standiford Helm Ii, Joshua A Hirsch
Research into interventional techniques in managing chronic spinal pain continues to be challenging, mystifying, confusing, and biased. Insight, or lack thereof, into placebo and nocebo phenomena contributes mightily to these difficulties. Unfortunately, placebo-nocebo responses are the subject of numerous controversies and challenges from not only a research perspective, but also clinical perspective. While interventionalists consider the biggest threat to interventional pain management research is inappropriate and outdated interpretation of the data, a greater problem is the misuse of the placebo response in research, with the declaration that all and everything as a placebo effect: with a misinterpretation of the nature of the placebo the, associated conclusions can be inaccurate...
July 2017: Pain Physician
https://www.readbyqxmd.com/read/28727668/comprehensive-cardiac-rehabilitation-for-secondary-prevention-after-transient-ischemic-attack-or-mild-stroke-psychological-profile-and-outcomes
#9
Peter L Prior, Vladimir Hachinski, Richard Chan, Karen Unsworth, Sharon Mytka, Michael Harnadek, Christina OʼCallaghan, Neville Suskin
PURPOSE: Having previously reported that comprehensive cardiac rehabilitation (CCR) is effective for secondary prevention post-transient ischemic attack (TIA)/mild nondisabling stroke (MNDS), we present psychometric findings for the same sample that elucidate subacute TIA/MNDS psychological outcomes and test whether CCR would be independently associated with psychological improvements. METHODS: In this prospective cohort trial patients with ≥1 risk factor, recruited from a stroke prevention clinic within 12 months (mean = 11...
July 19, 2017: Journal of Cardiopulmonary Rehabilitation and Prevention
https://www.readbyqxmd.com/read/28727644/cariprazine-specificity-profile-in-the-treatment-of-acute-schizophrenia-a-meta-analysis-and-meta-regression-of-randomized-controlled-trials
#10
Filippo Corponi, Alessandro Serretti, Stuart Montgomery, Chiara Fabbri
Cariprazine is a new dopamine D2 and D3 receptor partial agonist antipsychotic. Meta-analytic evidence of efficacy in acute schizophrenia and specific groups of patients is lacking. We carried out a meta-analysis in patients with acute schizophrenia to evaluate the efficacy of cariprazine over placebo and active comparators in overall symptoms, positive and negative symptoms and quality of life. Low and high (≥6 mg/day) doses were tested separately. The possible effect of clinical-demographic modulators was also tested...
July 19, 2017: International Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28727617/granulosa-cell-tumors-novel-predictors-of-recurrence-in-early-stage-patients
#11
Sharif Sakr, Eman Abdulfatah, Sumi Thomas, Zaid Al-Wahab, Rafic Beydoun, Robert Morris, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay
Granulosa cell tumors (GCTs) comprise 2% to 5% of ovarian neoplasms, with unpredictable patterns of recurrence. The HER family, GATA4, and SMAD3 genes are reportedly involved in GCT proliferation and apoptosis and may serve as new predictors of recurrence. The aim of the study was to evaluate novel predictors of recurrence in GCT from a large single institution cohort. Patients diagnosed with GCTs (n=125) between 1975 and 2014 were identified. Clinicopathologic parameters were obtained and immunohistochemical evaluation was performed of calretinin, inhibin, HER2, CD56, SMAD3, and GATA4...
May 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28727604/preclinical-development-of-ebi-005-an-il-1-receptor-1-inhibitor-for-the-topical-ocular-treatment-of-ocular-surface-inflammatory-diseases
#12
Joseph Kovalchin, Bracken King, Allyson Masci, Elizabeth Hopkins, Jeremy Fry, Jay Hou, Christian Li, Kelly Tenneson, Steve Weber, Gary Wolfe, Kathy Collins, Eric S Furfine
OBJECTIVE: Topical interleukin (IL)-1 receptor (R)1 blockade is therapeutically active in reducing signs and symptoms of dry eye disease. Herein, we describe in vitro and in vivo nonclinical Investigational New Drug (IND)-enabling studies of EBI-005, a novel protein chimera of IL-1β and IL-1 receptor antagonist (IL-1Ra or anakinra) that potently binds IL-1R1 and blocks signaling. These studies provide an assessment of receptor affinity, drug bioavailability, immunogenic response, safety, and tolerability in mice and rabbits...
July 18, 2017: Eye & Contact Lens
https://www.readbyqxmd.com/read/28727570/hyperosmotic-stress-stimulates-autophagy-via-polycystin-2
#13
Daniel Peña-Oyarzun, Rodrigo Troncoso, Catalina Kretschmar, Cecilia Hernando, Mauricio Budini, Eugenia Morselli, Sergio Lavandero, Alfredo Criollo
Various intracellular mechanisms are activated in response to stress, leading to adaptation or death. Autophagy, an intracellular process that promotes lysosomal degradation of proteins, is an adaptive response to several types of stress. Osmotic stress occurs under both physiological and pathological conditions, provoking mechanical stress and activating various osmoadaptive mechanisms. Polycystin-2 (PC2), a membrane protein of the polycystin family, is a mechanical sensor capable of activating the cell signaling pathways required for cell adaptation and survival...
July 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28727498/new-perspectives-regarding-the-antiviral-effect-of-vitamin-a-on-norovirus-using-modulation-of-gut-microbiota
#14
Heetae Lee, GwangPyo Ko
Gut microbiota has been revealed to play an important role in various health conditions, and recent studies have suggested the modulation of gut microbiota as a therapeutic strategy. There is no effective treatment for norovirus infection, though vitamin A has been suggested to have an antiviral effect in an epidemiological study. We demonstrated that vitamin A significantly inhibited murine norovirus replication. Vitamin A supplementation significantly increased the abundance of Lactobacillus sp. during norovirus infection, which played a crucial role in antiviral efficacy, inhibiting murine norovirus...
July 20, 2017: Gut Microbes
https://www.readbyqxmd.com/read/28727481/leucocyte-and-platelet-rich-fibrin-l-prf-as-a-regenerative-medicine-strategy-for-the-treatment-of-refractory-leg-ulcers-a-prospective-cohort-study
#15
Nelson R Pinto, Matias Ubilla, Yelka Zamora, Verónica Del Rio, David M Dohan Ehrenfest, Marc Quirynen
Chronic wounds (VLU: venous leg ulcer, DFU: diabetic foot ulcer, PU: pressure ulcer, or complex wounds) affect a significant proportion of the population. Despite appropriate standard wound care, such ulcers unfortunately may remain open for months or even years. The use of leukocyte- and platelet-rich fibrin (L-PRF) to cure skin ulcers is a simple and inexpensive method, widely used in some countries but unknown or neglected in most others. This auto-controlled prospective cohort study explored and quantified accurately for the first time the adjunctive benefits of topical applications of L-PRF in the management of such refractory ulcers in a diverse group of patients...
July 20, 2017: Platelets
https://www.readbyqxmd.com/read/28727416/in-situ-electrochemical-sensing-and-real-time-monitoring-live-cells-based-on-freestanding-nanohybrid-paper-electrode-assembled-from-3d-functionalized-graphene-framework
#16
Yan Zhang, Jian Xiao, Qi-Ying Lv, Lu Wang, Xulin Dong, Muhammad Asif, Jinghua Ren, Wenshan He, Yimin Sun, Fei Xiao, Shuai Wang
In this work, we develop a new type of freestanding nanohybrid paper electrode assembled from 3D ionic liquid (IL) functionalized graphene framework (GF) decorated by gold nanoflowers (AuNFs), and explore its practical application in in-situ electrochemical sensing of live breast cell samples by real-time tracking biomarker H2O2 released from cells. The AuNFs modified IL functionalized GF (AuNFs/IL-GF) was synthesized via a facile and efficient dopamine assisted one-pot self-assembly strategy. The as-obtained nanohybrid assembly exhibits a typical 3D hierarchical porous structure, where the highly active electrocatalyst AuNFs are well dispersed on IL-GF scaffold...
July 20, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28727373/new-concept-for-treating-female-stress-urinary-incontinence-with-radiofrequency
#17
Patrícia Lordelo, Andrea Vilas Boas, Danielle Sodré, Amanda Lemos, Sibele Tozetto, Cristina Brasil
PURPOSE: To evaluate the clinical response and adverse effects of radiofrequency on the urethral meatus in the treatment of stress urinary incontinence in women. MATERIALS AND METHODS: This phase one study included ten women with Stress Urinary Incontinence (SUI). The evaluation consisted of 1 hour Pad tests to quantify urine loss and to assess the degree of procedure satisfaction by using the Likert scale. To evaluate safety, we observed the number of referred side effects...
June 14, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/28727359/-stroke-prevention-in-patients-with-atrial-fibrillation
#18
Gaia Sirimarco, Lorenz Hirt, Roman Sztajzel, Fabienne Perren
Oral anticoagulation with vitamin K antagonists (VKA) was the cornerstone of stroke prevention in atrial fibrillation (AF). This review article presents the state of the art, with regard to the treatment options developed over the past few years, the new oral anticoagulants (NOAC). A search in PubMed for relevant published studies has been performed. Dabigatran and apixaban were superior to warfarin to reduce stroke risk or systemic embolism ; dabigatran, rivaroxaban and edoxaban were non-inferior. All NOAC are globally non-inferior to warfarin for stroke prevention in non-valvular AF and they have a superior safety profile, with a reduced intracranial bleeding risk...
April 26, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28727344/-to-where-and-until-when-handle-the-osteoporosis
#19
Brigitte Uebelhart, Serge Ferrari
Estrogen replacement therapy, selective modulators of the estrogen receptor (SERMs), bisphophonates and denosumab are antiresorptive therapies which can be used for several years. Teriparatide is still the only bone forming agent available, its use is limited to 24 months. Except the absence of new fragility fractures, there is no well defined target in the treatment of osteoporosis. Nevertheless persistence of high fracture risk (prevalent fractures and/or low BMD) on therapy indicates to maintain or intensify the treatment...
April 19, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28727341/-use-of-trabecular-bone-score-as-a-complementary-approach-to-dxa-for-fracture-risk-assessment-in-clinical-practice
#20
Didier Hans, Enisa Shevroja, Olivier Lamy
Physicians can assess the risk of fracture based on bone density (BMD) and several risk factors. Some of them and BMD are incorporated into FRAX, an assessment tool that estimates the 10-years probability of fracture. BMD didn't take into account the microarchitecture. TBS is a texture parameter related to bone microarchitecture. A low TBS is associated with a history of fracture and the incidence of new fracture independently of BMD, clinical risk factors and FRAX. TBS is yet integrated in the FRAX tool, and this effect is of greatest utility for individuals who are close to an intervention threshold...
April 19, 2017: Revue Médicale Suisse
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