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https://www.readbyqxmd.com/read/28651360/novel-reproductive-technologies-to-prevent-mitochondrial-disease
#1
Lyndsey Craven, Mao-Xing Tang, Gráinne S Gorman, Petra De Sutter, Björn Heindryckx
BACKGROUND: The use of nuclear transfer (NT) has been proposed as a novel reproductive treatment to overcome the transmission of maternally-inherited mitochondrial DNA (mtDNA) mutations. Pathogenic mutations in mtDNA can cause a wide-spectrum of life-limiting disorders, collectively known as mtDNA disease, for which there are currently few effective treatments and no known cures. The many unique features of mtDNA make genetic counselling challenging for women harbouring pathogenic mtDNA mutations but reproductive options that involve medical intervention are available that will minimize the risk of mtDNA disease in their offspring...
June 23, 2017: Human Reproduction Update
https://www.readbyqxmd.com/read/28648379/targeted-protein-degradation-from-chemical-biology-to-drug-discovery
#2
REVIEW
Philipp M Cromm, Craig M Crews
Traditional pharmaceutical drug discovery is almost exclusively focused on directly controlling protein activity to cure diseases. Modulators of protein activity, especially inhibitors, are developed and applied at high concentration to achieve maximal effects. Thereby, reduced bioavailability and off-target effects can hamper compound efficacy. Nucleic acid-based strategies that control protein function by affecting expression have emerged as an alternative. However, metabolic stability and broad bioavailability represent development hurdles that remain to be overcome for these approaches...
June 10, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28646963/spectrum-and-burden-of-dermatophytes-in-children
#3
Leila Ferguson, L Claire Fuller
Tinea capitis is the most important superficial fungal condition in children. It is often unrecognised but the presence of alopecia, scale and lymphadenopathy, especially in inner-city children should prompt investigation. An understanding of changing epidemiology and prevalence of causative organisms is important in deciding appropriate therapy. The use of diagnostic aids including dermoscopy is increasing and is reported to be helpful in identifying subtle signs. Trichophyton tonsurans accounts for the majority of cases in the UK and terbinafine is increasingly advocated as a safe and effective therapy...
June 2017: Journal of Infection
https://www.readbyqxmd.com/read/28646112/crispr-cas12a-assisted-recombineering-in-bacteria
#4
Mei-Yi Yan, Hai-Qin Yan, Gai-Xian Ren, Ju-Ping Zhao, Xiao-Peng Guo, Yi-Cheng Sun
Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a (Cpf1) has emerged as an effective genome editing tool in many organisms. Here, we developed and optimized a CRISPR-Cas12a assisted recombineering system to facilitate genetic manipulation in bacteria. Using this system, point mutations, deletions, insertions, and gene replacements can be easily generated on the chromosome or native plasmids in Escherichia coli, Yersinia pestis, and Mycobacterium smegmatis Because CRISPR-Cas12a-assisted recombineering does not require introduction of an antibiotic resistance gene into the chromosome to select for recombinants, it is an efficient approach for generating markerless and scarless mutations in bacteria...
June 23, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28645279/diabetes-care-in-a-complex-humanitarian-emergency-setting-a-qualitative-evaluation
#5
Adrianna Murphy, Michel Biringanine, Bayard Roberts, Beverley Stringer, Pablo Perel, Kiran Jobanputra
BACKGROUND: Evidence is urgently needed from complex emergency settings to support efforts to respond to the increasing burden of diabetes mellitus (DM). We conducted a qualitative study of a new model of DM health care (Integrated Diabetic Clinic within an Outpatient Department [IDC-OPD]) implemented by Médecins Sans Frontières (MSF) in Mweso Hospital in eastern Democratic Republic of Congo (DRC). We aimed to explore patient and provider perspectives on the model in order to identify factors that may support or impede it...
June 23, 2017: BMC Health Services Research
https://www.readbyqxmd.com/read/28644739/treatment-of-hepatitis-c-with-new-fixed-dose-combinations
#6
Vicente Soriano
The advent of oral direct-acting antivirals (DAA) has revolutionized the hepatitis C virus (HCV) therapeutic landscape providing cure rates over 90%. However, a subset of patients remains at higher risk for treatment failure, including those infected with: i) genotype 3 and cirrhosis; ii) resistance-associated substitutions (RAS) occurring either as natural polymorphisms or selected after prior DAA failure; and iii) poor drug adherence associated with social disabilities (homeless, psychiatric illnesses, injection drug use, alcoholism, etc...
June 23, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28642928/effect-of-curing-and-silanizing-on-composite-repair-bond-strength-using-an-improved-micro-tensile-test-method
#7
Sigfus Thor Eliasson, Jon E Dahl
Objectives: To evaluate the micro-tensile repair bond strength between aged and new composite, using silane and adhesives that were cured or left uncured when new composite was placed. Methods: Eighty Filtek Supreme XLT composite blocks and four control blocks were stored in water for two weeks and thermo-cycled. Sandpaper ground, etched and rinsed specimens were divided into two experimental groups: A, no further treatment and B, the surface was coated with bis-silane. Each group was divided into subgroups: (1) Adper Scotchbond Multi-Purpose, (2) Adper Scotchbond Multi-Purpose adhesive, (3) Adper Scotchbond Universal, (4) Clearfil SE Bond and (5) One Step Plus...
January 2017: Acta Biomaterialia Odontologica Scandinavica
https://www.readbyqxmd.com/read/28642197/risk-of-hepatocellular-cancer-in-hcv-patients-treated-with-direct-acting-antiviral-agents
#8
Fasiha Kanwal, Jennifer Kramer, Steven M Asch, Maneerat Chayanupatkul, Yumei Cao, Hashem B El-Serag
BACKGROUND AND AIMS: The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct acting antivirals (DAA) is unclear. Our aim was to examine the risk and determinants of HCC in patients cured with DAA. METHODS: We conducted a retrospective cohort study of HCV patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between 1/1/2015 and 12/31/2015. We calculated the annual incidence rates for HCC by SVR...
June 19, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28642181/surgery-outcome-of-growth-hormone-secreting-pituitary-adenoma-with-empty-sella-using-a-new-classification
#9
Qiang Wang, Xiaopeng Guo, Lu Gao, Zihao Wang, Kan Deng, Wei Lian, Renzhi Wang, Huijuan Zhu, Bing Xing
OBJECTIVE: To investigate the outcomes and identified risk factors for a cure and intraoperative cerebrospinal fluid leak following transsphenoidal surgery using a new classification for growth hormone-secreting pituitary adenoma associated with "empty sella". METHODS: This retrospective cohort study included 51 patients enrolled from January 2010 to June 2016. All subjects were categorized into three groups using a new classification scheme: Grade A, whole tumor occupation area beneath a horizontal line drawn along the lowest level of ES; Grade B, tumor occupation area that crossed the horizontal line on one side; and Grade C, tumor occupation area that crossed the horizontal line on two sides...
June 19, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28638709/-cure-for-multiple-sclerosis-ms-evolving-views-of-therapy-goals-in-patients-on-different-stages-of-the-disease-a-pilot-study-in-a-cohort-of-polish-ms-patients
#10
Weronika Chacińska, Marta Brzostowska, Monika Nojszewska, Aleksandra Podlecka-Piętowska, Wiesław W Jędrzejczak, Emilian Snarski
INTRODUCTION: New aggressive treatments promise improvement of results in the treatment of multiple sclerosis (MS), however, with high risk of serious complications. In this study, we analyzed patients' acceptance for risks connected with the MS treatment. METHODS: The study was designed as a prospective nonanonymous online questionnaire. Responders were asked about the definition of the "cure" for MS and crucial goals in the treatment. RESULTS: One hundred and eighty patients filled in the questionnaire (129 women and 51 men), and the mean age was 33 years (SD = 10...
June 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28638377/a-novel-bromodomain-inhibitor-reverses-hiv-1-latency-through-specific-binding-with-brd4-to-promote-tat-and-p-tefb-association
#11
Huachao Huang, Shuai Liu, Maxime Jean, Sydney Simpson, He Huang, Mark Merkley, Tsuyoshi Hayashi, Weili Kong, Irene Rodríguez-Sánchez, Xiaofeng Zhang, Hailemichael O Yosief, Hongyu Miao, Jianwen Que, James J Kobie, James Bradner, Netty G Santoso, Wei Zhang, Jian Zhu
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28638104/anti-proliferative-therapy-for-hiv-cure-a-compound-interest-approach
#12
Daniel B Reeves, Elizabeth R Duke, Sean M Hughes, Martin Prlic, Florian Hladik, Joshua T Schiffer
In the era of antiretroviral therapy (ART), HIV-1 infection is no longer tantamount to early death. Yet the benefits of treatment are available only to those who can access, afford, and tolerate taking daily pills. True cure is challenged by HIV latency, the ability of chromosomally integrated virus to persist within memory CD4(+) T cells in a non-replicative state and activate when ART is discontinued. Using a mathematical model of HIV dynamics, we demonstrate that treatment strategies offering modest but continual enhancement of reservoir clearance rates result in faster cure than abrupt, one-time reductions in reservoir size...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637915/tumour-on-a-chip-microfluidic-models-of-tumour-morphology-growth-and-microenvironment
#13
REVIEW
Hsieh-Fu Tsai, Alen Trubelja, Amy Q Shen, Gang Bao
Cancer remains one of the leading causes of death, albeit enormous efforts to cure the disease. To overcome the major challenges in cancer therapy, we need to have a better understanding of the tumour microenvironment (TME), as well as a more effective means to screen anti-cancer drug leads; both can be achieved using advanced technologies, including the emerging tumour-on-a-chip technology. Here, we review the recent development of the tumour-on-a-chip technology, which integrates microfluidics, microfabrication, tissue engineering and biomaterials research, and offers new opportunities for building and applying functional three-dimensional in vitro human tumour models for oncology research, immunotherapy studies and drug screening...
June 2017: Journal of the Royal Society, Interface
https://www.readbyqxmd.com/read/28637827/islet-encapsulation-physiological-possibilities-and-limitations
#14
Olle Korsgren
A logical cure for type 1 diabetes (T1D) involves replacing the lost insulin-producing cells with new ones, preferably cells from a well-characterized and unlimited source of human insulin-producing cells. This straightforward and simple solution to provide a cure for T1D is immensely attractive but entails at least two inherent and thus far unresolved hurdles: 1) provision of an unlimited source of functional human insulin-producing cells and 2) prevention of rejection without the side effects of systemic immunosuppression...
July 2017: Diabetes
https://www.readbyqxmd.com/read/28636622/inhibition-of-hepatitis-b-viral-entry-by-nucleic-acid-polymers-in-heparg-cells-and-primary-human-hepatocytes
#15
Clément Guillot, Nora Martel, Françoise Berby, Isabelle Bordes, Olivier Hantz, Matthieu Blanchet, Camille Sureau, Andrew Vaillant, Isabelle Chemin
Hepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs) are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure...
2017: PloS One
https://www.readbyqxmd.com/read/28635633/new-insights-in-thyroid-cancer-and-p53-family-proteins
#16
REVIEW
Livia Manzella, Stefania Stella, Maria Stella Pennisi, Elena Tirrò, Michele Massimino, Chiara Romano, Adriana Puma, Martina Tavarelli, Paolo Vigneri
Thyroid cancers are common endocrine malignancies that comprise tumors with different clinical and histological features. Indeed, papillary and follicular thyroid cancers are slow-growing, well-differentiated tumors, whereas anaplastic thyroid cancers are undifferentiated neoplasias that behave much more aggressively. Well-differentiated thyroid carcinomas are efficiently cured by surgery and radioiodine, unlike undifferentiated tumors that fail to uptake radioactive iodine and are usually resistant to chemotherapy...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635521/assessment-of-an-innovative-voluntary-substance-abuse-treatment-program-designed-to-replace-compulsory-drug-detention-centers-in-malaysia
#17
Farrah Khan, Archana Krishnan, Mansur A Ghani, Jeffrey A Wickersham, Jeannia J Fu, Sin How Lim, Sangeeth Kaur Dhaliwal, Adeeba Kamarulzaman, Frederick L Altice
BACKGROUND: As part of an ongoing initiative by the Malaysian government to implement alternative approaches to involuntary detention of people who use drugs, the National Anti-Drug Agency has created new voluntary drug treatment programs known as Cure and Care (C&C) Centers that provide free access to addiction treatment services, including methadone maintenance therapy, integrated with social and health services. OBJECTIVES:   We evaluated early treatment outcomes and client satisfaction among patients accessing C&C treatment and ancillary services at Malaysia's second C&C Center located in Kota Bharu, Kelantan...
February 22, 2017: Substance Use & Misuse
https://www.readbyqxmd.com/read/28631068/autoinflammatory-diseases-with-periodic-fevers
#18
REVIEW
Erdal Sag, Yelda Bilginer, Seza Ozen
PURPOSE OF REVIEW: One purpose of this review was to raise awareness for the new autoinflammatory syndromes. These diseases are increasingly recognized and are in the differential diagnosis of many disease states. We also aimed to review the latest recommendations for the diagnosis, management, and treatment of these patients. RECENT FINDINGS: Familial Mediterranean fever (FMF), cryopyrin-associated periodic syndrome (CAPS), tumor necrosis factor receptor-associated periodic fever syndrome (TRAPS), and hyperimmunoglobulinemia D and periodic fever syndrome/mevalonate kinase deficiency (HIDS/MVKD) are the more common autoinflammatory diseases that are characterized by periodic fevers and attacks of inflammation...
July 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28631044/-personalized-treatment-of-viral-hepatitis-of-the-present-and-the-future-hepatitis%C3%A2-b-c-delta-and-e
#19
REVIEW
R Bartenschlager, M Cornberg, T Pietschmann
Precision medicine is also possible for infectious diseases as shown for the treatment of chronic viral hepatitis, especially if different options are available. In hepatitis B virus (HBV) infection, treatment indication as well as the choice of treatment and the decisions to stop treatment are based on viral markers and alanine aminotransferase (ALT) level. Future therapies for HBV infection aiming for functional cure or even virus elimination may be even more personalized and have to take into account the immune status of a given patient...
June 19, 2017: Der Internist
https://www.readbyqxmd.com/read/28629727/antigenicity-of-phage-clones-and-their-synthetic-peptides-for-the-serodiagnosis-of-canine-and-human-visceral-leishmaniasis
#20
Lourena E Costa, Beatriz C S Salles, Thaís T O Santos, Fernanda F Ramos, Mariana P Lima, Mayara I S Lima, Áquila S B Portela, Miguel A Chávez-Fumagalli, Mariana C Duarte, Daniel Menezes-Souza, Ricardo A Machado-de-Ávila, Julia A G Silveira, Danielle F Magalhães-Soares, Luiz Ricardo Goulart, Eduardo A F Coelho
In the Americas, Brazil is responsible by 90% of the cases registered of visceral leishmaniasis (VL), and Leishmania infantum is the most common parasite species responsible by disease in Brazilian dogs and humans. A precise diagnosis may allow to a faster and more effective treatment against the disease, which increases the possibility of cure, as well as to induce less toxic effects, due to a lower time exposition for the chemotherapeutics. In a previous study, two L. infantum mimotopes, B10 and C01 clones, were recognized by antibodies in VL dogs sera by a phage display technology, and were well-successfully evaluated as vaccine candidates against visceral and tegumentary leishmaniasis...
June 16, 2017: Microbial Pathogenesis
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