Mechanical circulatory support is increasingly used as a long-term treatment option for patients with end-stage heart failure. Patients with implanted ventricular assist devices are at high risk for a range of diverse medical urgencies and emergencies. Given the increasing prevalence of mechanical circulatory support devices, this expert clinical consensus document seeks to help inform emergency medicine and prehospital providers regarding the approach to acute medical and surgical conditions encountered in these complex patients. This article is protected by copyright. All rights reserved.Genome editing via the homology-directed repair (HDR) pathway in somatic plant cells is very inefficient compared to error-prone repair by nonhomologous end joining (NHEJ). Here, we increased HDR-based genome editing efficiency approximately 3-fold compared to a Cas9-based single-replicon system via the use of de novo multi-replicon systems equipped with CRISPR/LbCpf1 in tomato and obtained replicon-free but stable HDR alleles. The efficiency of CRISPR/LbCpf1-based HDR was significantly modulated by physical culture conditions such as temperature and light. Ten days of incubation at 31°C under a light/dark cycle after Agrobacterium-mediated transformation resulted in the best performance among the tested conditions. Furthermore, we developed our single-replicon system into a multi-replicon system that effectively increased HDR efficiency. Although this approach is still challenging, we showed the feasibility of HDR-based genome editing of a salt-tolerant SlHKT1;2 allele without genomic integration of antibiotic markers or any phenotypic selection. Self-pollinated offspring plants carrying the HKT1;2 HDR allele showed stable inheritance and germination tolerance in the presence of 100 mM NaCl. Our work may pave the way for transgene-free editing of alleles of interest in asexually as well as sexually reproducing plants. This article is protected by copyright. All rights reserved.The Fundão tailings dam held back approximately 50 million cubic meters of tailings from an iron ore mine in the state of Minas Gerais, Brazil. The dam failed on November 5, 2015, releasing tailings into the Rio Doce watershed and causing an environmental disaster in a biodiversity hotspot. To guide conservation action following the event, Brazilian authorities demanded an impact assessment focused on terrestrial species threatened by extinction. Post-disaster impact assessment is substantially more challenging than pre-development impact assessment. Pre-disaster baseline data were sparse, and much was unknown about how the Fundão dam failure impacted terrestrial species threatened with extinction. Baseline reconstruction and impact pathway validation/characterization was critical. Ecosystem reconstruction revealed that 1,580 ha of terrestrial ecosystems were destroyed, including ~ 480 ha of Atlantic rainforest. Collaboration with local experts identified 346 species of vertebrates, invertebrates and vascular plants threatened with extinction that were impacted or potentially impacted. Species composition and impacts varied within four distinct segments of the Rio Doce watershed. Nine potential impact pathways were identified using data and literature review combined with information provided by regulators, experts, and media. Not all were valid. Validating and characterizing each pathway within each watershed segment involved data evaluation, an ecological risk screening, and field assessments. Impact pathway evaluation proved critical to dispelling misconception, accurately understanding post-disaster impacts, and directing conservation action; the importance of this step cannot be overemphasized. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Autologous fat grafting (AFG) and synthetic fillers are currently used in esthetic and reconstructive surgery. Challenges in AFG include inconsistent graft retention, donor site morbidities, insufficient harvest, and excessive harvesting times. An allograft adipose matrix (AAM) has been developed as an off-the-shelf alternative to AFG and synthetic fillers. AIMS To evaluate the clinical safety and retention of an AAM over 24 weeks after treatment of bilateral atrophic temples. PATIENTS/METHODS Ten subjects (nine females, one male, aged 47-69 years) with temple atrophy were enrolled in the IRB-approved study. AAM (Renuva® , MTF Biologics, Edison, NJ) was injected ( less then 3 mL) bilaterally into the atrophic temples of each subject. Volume retention, global improvement, and safety were evaluated at 1, 4, 8, 12, 16, 20, and 24 weeks. Biopsy specimens were obtained for adipogenic and angiogenic histological evaluation. RESULTS The mean temple volume improved over the baseline and was retained throughout the study period. Fullness (measure of volume) increased immediately from 0 pretreatment to 2.8 post-treatment (scale 0-4 = none-maximum). Fullness varied from 0.8 to 2.2 from weeks 1 through 12 and was 2.7-3.0 from weeks 16-24, around 75% increase from baseline. Furthermore, skin tone, smoothness, texture, and overall appearance also improved with 71% of subjects being satisfied to very satisfied with the results. Adverse events were minimal and histology revealed native tissue incorporation and remodeling. CONCLUSION AAM is safe and well tolerated, provides at least 6-month volume retention, improves skin quality, and supports adipose tissue remodeling after treatment into temples. © 2020 Wiley Periodicals, Inc.This study evaluated the ability of bisphosphonates (BPAs) of different molecular structures to mitigate the calcification of porcine aortic wall (PAW) and bovine jugular vein wall (BJVW). Tissues cross-linked with glutaraldehyde (GA) or diepoxy compound (DE) were modified with pamidronic (PAM), alendronic (ALE), neridronic (NER) acids (Type 1 BPAs); 2-(2′-carboxyethylamino)ethylidene-1,1-bisphosphonic (CEABA) and 2-(5-carboxypentylamino)ethylidene-1,1-bisphosphonic acids (CPABA) (Type 2); and zoledronic acid (ZOL) (Type 3). After implanting the tissue samples subcutaneously in 100 rats, calcification was examined using atomic absorption spectrophotometry (60-day explants) and light microscopy after von Kossa staining (10- and 30-day explants). The calcium contents in GA-BJVW and GA- and DE-PAW increased up to 100-120 mg/g after 60 days, while being 3 times lower in DE-BJVW. In modified and non-modified PAW samples, calcium phosphates appeared by day 10 and were associated with elastic fibers and devitalized cellular elements. In all groups of BJVW samples, mineralization began in elastic fibers near the subendothelial layer. In addition, calcified collagen was found in the GA-BJVW samples. Minimal calcification was found in GA-PAW treated with Type-1 BPAs and CEABA. For DE-PAW and GA-BJVW, the calcium level significantly decreased with PAM and CEABA. Meanwhile, ALE and NER were effective for DE-BJVW. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.OBJECTIVES Despite the increasingly complex care and demanding health challenges shaping pharmacy, little work has been carried out to understand the global status of advanced and/or specialised pharmacy practice scopes and the models in which they exist. This study aims to describe the current global status of initiatives relating to advancement of pharmacy practice. METHODS A global survey was conducted between January and May 2015 to collect country-level data from member organisations of the International Pharmaceutical Federation (FIP), and national-level contacts from regulatory, professional and government agencies or universities; data requests were sent to 109 countries. The collected data were triangulated (comparing multiple sources from single countries, e.g.), cleaned and analysed by descriptive and comparative statistics. KEY FINDINGS Full data sets from 48 countries and territories were obtained. The findings demonstrate varying systems of advanced pharmacy practice and specialisation often linked to income level. The study found that there are variations within terminology and definitions, frameworks for specialisation and advanced practice, professional recognition mechanisms and benefits across countries. CONCLUSIONS This survey of 48 countries and territories was the first of its kind to describe the range of specialisation and professional recognition systems for advanced pharmacy practice worldwide. Despite the variance, it is clear from this global study that professional advancement and the recognition of advancement in practice are developing around the world and this could be due to the increasingly complex nature of pharmaceutical care delivery and a consequent need to be able to endorse professional capabilities. © 2020 Royal Pharmaceutical Society.OBJECTIVES This study aims to gain a better understanding of the drivers and barriers to the development of advanced practice and specialised systems around the world. Through the synthesis of in-depth country case studies, this paper aims to identify current models of advanced practice and specialisation in pharmacy and illustrate trends, drivers and barriers in policy development. This is the first analysis of its kind to examine pharmacy specialisation and advanced practice in this depth from a global perspective. METHODS A synthesis of country case studies was carried out. The country case study template was reviewed and approved by an expert working group drawn from a cross section of International Pharmaceutical Federations (FIP) experts and special-interest groups. FIP member organisations and country-level contacts from regulatory, professional and government agencies and universities were approached to contribute to the case study database. The data were collected between January and May 2015. Descriptive comparative analysis and qualitative thematic analysis were both used to analyse the data. KEY FINDINGS Case study submissions were received from 17 countries. The findings demonstrate that the pace and depth of change in advanced practice and specialisation are occurring at different rates across countries and regions, although many countries appear to be moving towards recognising advanced and specialised practice of pharmacists and developing frameworks and/or formalised recognition systems. CONCLUSIONS Country-specific examples are useful in identifying factors that may contribute to the rate at which developments in advanced practice and specialisation in pharmacy are taking place and enable progress in around the world. © 2020 Royal Pharmaceutical Society.OBJECTIVE miR-146a is widely induced during the immune response. However, little is known about the biogenesis, function and mechanism of miR-146a in cementoblasts during the pathogenesis of periodontitis. This study aimed to investigate the effects of miR-146a in murine cementoblast derived OCCM-30 cells following IL-1β stimulation. MATERIALS AND METHODS OCCM-30 cells were cultured and exposed to IL-1β. IL-6, IL-1β, TNF-α and miR-146a-5p expression was assessed by qRT-PCR. Mimics/inhibitors were transiently transfected into cells to determine the function of miR-146a-5p. Signalling pathways including p38 MAPK, ERK1/2 and NF-κB were studied by using specific inhibitors. The indicated proteins were measured by western blot analysis and ELISA. RESULTS In IL-1β-stimulated OCCM-30 cells, the expression levels of miR-146a-5p along with IL-6 and IL-1β increased in a time-dependent manner. The ERK1/2, p38 MAPK and NF-κB pathway were activated upon IL-1β stimulation. Blocking the NF-κB pathway decreased IL-6, IL-1β and miR-146a-5p expression.