Kofodchan6000

Background Osteosarcoma (OS) is the most common primary malignant bone tumour in dogs and human beings, characterised by similar genetic and clinical features. With the aim to define similarities and differences in the biological aspects involved in OS progression, a comparative study was performed to create a model to improve patient outcome. Methods First, the expression of microRNAs (miRNAs) belonging to the cluster miR-106b-25 (miR-106b, miR-25 and miR-93-5p) in human and canine OS tissue was compared. Results miR-25 and miR-106b presented a variable expression not significantly different from the corresponding normal bone, while miR-93-5p expression was increased in all OS specimens, with higher levels in the canine subset compared with human. Accordingly, its target p21 presented a weaker and less homogeneous immunostaining distribution in the canine group. Given the high expression of miR-93-5p in all OS specimens, the functional response of human 143B and canine DAN OS cells to miRNA inhibition was evaluated. Although p21 expression increased after miR-93-5p inhibition both at mRNA and protein level, a more significant cell response in terms of proliferation and apoptosis was seen in canine OS cells. Conclusions In conclusion, canine OS tissue and cell line presented higher expression levels of miR-93-5p than human OS. In addition, the introduction of miR-93-5p inhibitor caused a cell response in 143B and DAN that differed for the more intense functional impact in the canine OS cell line. © British Veterinary Association 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.Background Antimicrobial resistance is an increasing problem in human and veterinary medicine and is closely linked to the use of antimicrobials. The objective of this study was to describe antimicrobial prescriptions for selected canine diseases in Switzerland during 2016. Methods Dogs presented to two university hospitals and 14 private practices for acute diarrhoea (AD; n=371), suspected or confirmed urinary tract infections (UTIs; n=245), respiratory tract infections (RTIs; n=274) or wound infections (WIs; n=175) were included. Clinical history, diagnostic work-up and antimicrobial prescription (class, dosage and duration) were retrospectively assessed. A justification score was applied to evaluate appropriateness of antimicrobial therapy based on available national and international consensus guidelines. Results Antimicrobials were prescribed in 65 per cent of dogs with AD, 88 per cent with UTI, 62 per cent with RTI and 90 per cent with WI. Cpd20m The most prescribed antimicrobial classes (monotherapy and combination therapy) were potentiated aminopenicillins (59 per cent), nitroimidazoles (22 per cent), non-potentiated aminopenicillins (16 per cent) and fluoroquinolones (13 per cent). Overall, 38 per cent (95 per cent CI 0.35 to 0.41) of the prescriptions were in accordance with consensus guidelines. In dogs with AD, antimicrobial therapy was associated with the presence of haemorrhagic diarrhoea (P less then 0.05) and complied in 32 per cent with consensus guidelines, which recommend antimicrobial treatment only when sepsis is suspected. A bacterial aetiology was confirmed via culture and/or sediment examination in 36 per cent of dogs with suspected UTI. Conclusions Overall, adherence to consensus guidelines was poor both, at university hospitals and private practices. Antimicrobial stewardship measures are therefore needed to improve prudent use. © British Veterinary Association 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.Human enamel once formed cannot be biologically repaired or replaced. Saliva has a significant role in remineralization of dental enamel. It not only has a buffering capacity to neutralize the oral cavity's low pH generated after acidic encounters, but also acts as a carrier of essential ions, such as fluoride, calcium and phosphate, which have a positive role in enamel's remineralization. This review discusses how salivary contents, like proteins and enzymes, have a natural role in enamel's mineralization. In addition, the presence of ions, such as fluoride, calcium and phosphate, in saliva further enhances its capability to remineralize the demineralized enamel surface. The review further examines modern innovative technologies, based on biomimetic regeneration systems, including dentin phosphoproteins, aspartate-serine-serine, recombinant porcine amelogenin, leucine-rich amelogenin peptide and nano-hydroxyapatite, that promote enamel remineralization. Fluoride boosters like calcium phosphates, polyphosphates, and certain natural products can also play an important role in enamel remineralization. Copyright © 2020 Farooq I and Bugshan A.Developmental and epileptic encephalopathies (DEEs) are a group of severe, early onset epilepsies characterized by refractory seizures, developmental delay or regression associated with ongoing epileptic activity, and generally poor prognosis. DEE is genetically and phenotypically heterogeneous, and there is a plethora of genetic testing options to investigate the rapidly growing list of epilepsy genes. However, more than 50% of patients with DEE remain without a genetic diagnosis despite state-of-the-art genetic testing. In this review, we discuss the major advances in epilepsy genomics that have surfaced in recent years. The goal of this review is to reach a larger audience and build a better understanding of pathogenesis and genetic testing options in DEE. Copyright © 2020 Hebbar M and Mefford HC.Chemotherapy-induced peripheral neuropathy (CIPN) is a common cause of pain and poor quality of life for those undergoing treatment for cancer and those surviving cancer. Many advances have been made in the pre-clinical science; despite this, these findings have not been translated into novel preventative measures and treatments for CIPN. This review aims to give an update on the pre-clinical science, preventative measures, assessment and treatment of CIPN. Copyright © 2020 Gordon-Williams R and Farquhar-Smith P.The management of resistant hypertension presents several challenges in everyday clinical practice. During the past few years, several studies have been performed to identify efficient and safe pharmacological and non-pharmacological options for the management of such patients. The Spironolactone versus placebo, bisoprolol, and doxazosin to determine the optimal treatment for drug-resistant hypertension (PATHWAY-2) trial demonstrated significant benefits with the use of spinorolactone as a fourth-line drug for the treatment of resistant hypertension over doxazosin and bisoprolol. In addition, recent data support that spironolactone may demonstrate superiority over central acting drugs in such patients, as well. Based on the European guidelines, spironolactone is recommended as the fourth-line drug option, followed by amiloride, other diuretics, doxazosin, bisoprolol or clonidine.  Among several device-based approaches, renal sympathetic denervation had fallen into hibernation after the disappointing results of the Renal Denervation in Patients With Uncontrolled Hypertension (SYMPLICITY HTN) 3 trial.