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  • Erickson Malmberg posted an update 2 weeks, 3 days ago

    Animal tuberculosis (TB), which is caused by the Mycobacterium tuberculosis complex (MTC), is a zoonotic disease of global concern, and has a wide variety of wild and domestic reservoirs that can establish complex epidemiological systems. Of all the strategies employed to control TB, reducing the risks of interaction at the wildlife-livestock interface is a cornerstone. However, detailed protocols with which to assess and implement farm-specific preventive actions that can be employed against interactions with wildlife are lacking for extensive production systems. We describe an On-farm Wildlife Risk Mitigation Protocol that is applicable to beef cattle farming in Mediterranean environments in order to control the wildlife-livestock interaction and MTC transmission through the use of Farm-specific Action Plans (FsAP). We assessed the implementation and verification of FsAP in terms of its practical feasibility and acceptability by farmers (n=55 farms). Of the potential risk points, waterers (41.3 %) and water of TB Risk Mitigation Programmes at a nationwide level.All-trans-retinoic acid (ATRA) is effective for preventing cancer and treating skin diseases and acute promyelocytic leukaemia (APL). These pharmacological effects of ATRA are mainly mediated by retinoid X receptors (RXRs) and retinoic acid receptors (RARs). This article provides a comprehensive overview of the clinical progress on and the molecular mechanisms of ATRA in the treatment of APL. ATRA can promote the transcriptional activation of differentiation-related genes and regulate autophagy by inhibiting mTOR, which results in anti-APL effects. In detail, the structures, pharmacological effects, and clinical studies of 68 types of ATRA analogues are described. These compounds have excellent antitumour therapeutic potential and could be used as lead compounds for further development and research.By removing 5-methyl and 6-acetyl groups in our previously reported compound 3, we designed a series of novel 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine derivatives as potential tubulin polymerization inhibitors. Among them, compound 5e displayed low nanomolar antiproliferative efficacy on HeLa cells which was 166-fold higher than the lead analogue 3. Interestingly, 5e displayed significant selectivity in inhibiting cancer cells over HEK-293 (normal human embryonic kidney cells). In addition, 5e dose-dependently arrested HeLa in G2/M phase through the alterations of the expression levels of p-cdc2 and cyclin B1, and caused HeLa cells apoptosis by regulation of expressions of cleaved PARP. Further evidence demonstrated that 5e effectively inhibited tubulin polymerization and was 3-fold more powerful than positive control CA-4. Moreover, molecular docking analysis indicated that 5e overlapped well with CA-4 in the colchicine-binding site. These studies demonstrated that 2,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidine skeleton might be used as the leading unit to develop novel tubulin polymerization inhibitors as potential anticancer agents.The main cause of morbidity and mortality among residents of nursing homes (NHs) is healthcare-associated infections (HAIs). We conducted infection control intervention by applying the WHO multimodal strategy for one year from January to December 2018 in the one NH in South Korea. Healthcare workers (HCWs) in NH were observed by infection control nurse from February to December 2018. Hand hygiene (HH) compliance according WHO 5 moments and type of HH, glove use were measured as main outcomes. During the intervention period, a total of 1,461 cases were observed. HH compliance among HCWs increased from 12.6% to 55.2% after the intervention. According to WHO 5 moments, HH before touching a patient and after touching a patient saw significant improvements. Further, glove misuse decreased significantly from 45.9% to 25.4%. The multifaceted infection control program in the NH group significantly improved the HH compliance of HCWs.

    Reminiscence is a non-pharmacological technique used to manage the behavioral and psychological symptoms of dementia. This integrative review aims to synthesize the research on the health benefits of reminiscence intervention for people with dementia.

    Whittemore and Knafl’s five-step method provided the framework for this review. A comprehensive search of PubMed, CINAHL Plus, SCOPUS, and PsycINFO was conducted. The articles were reviewed for eligibility, critically appraised, and extracted the data.

    Twenty-seven studies met the inclusion criteria. Four themes emerged (a) Recovery from the Darkness of Depressive Symptoms, (B) Enhancement of Cognitive Functions and Filling the Memory Gap, (C) Living a Fulfilling Life in Late Adulthood, and (D) Fulfilling Reminiscence Functions.

    This review provides a better understanding of the potential benefits of using reminiscence intervention for addressing the behavioral and psychological symptoms of dementia. However, improving the methodological rigor of future studies is necessary to attain conclusive evidence.

    This review provides a better understanding of the potential benefits of using reminiscence intervention for addressing the behavioral and psychological symptoms of dementia. However, improving the methodological rigor of future studies is necessary to attain conclusive evidence.The fate, toxicity and bioaccumulation of copper oxide nanoparticles (nCuO) was investigated in soil, with and without biosolids amendment, through chronic exposures using the earthworm, Eisenia andrei, and the collembolan, Folsomia candida. The effects of copper sulphate (CuSO4) were included so as to compare the behavior of nCuO to a readily soluble counterpart. The fate of nCuO was evaluated through characterization of dissolved and nano-particulate fractions (via single particle ICP-MS) as well as extractable Cu2+ throughout the duration of select tests. Silmitasertib Neither Cu form was particularly toxic to F. candida, but effects on E. andrei reproduction were significant in all treatments (IC50 range 98 – 149 mg Cu kg-1 dry soil). There were no significant differences in toxicity between the Cu forms, nor in extractable Cu2+ activities, indicative that particle dissolution within the soil and, subsequent activity of Cu2+ was likely the primary mode of toxicity in the nCuO exposures. The presence of biosolids did not significantly alter toxicity of nCuO, but did affect Cu2+ activity over time. Bioaccumulation of total Cu in E. andrei when exposed to nCuO (kinetic bioaccumulation factor (BAFk) 0.80 with biosolids and 0.81 without) was lower than exposure to CuSO4 (BAFk 2.31 with biosolids and 1.12 without). Enhanced dark-field hyperspectral imaging showed accumulation of nCuO along the epidermis and gut of E. andrei, with trace amounts observed in muscle and chloragogenous tissue, providing evidence of nCuO translocation within the organism. The present study demonstrates that the current risk assessment approach for trace metals in the environment, based on substance solubility and bioavailability of the dissolved free ion, are applicable for nCuO exposure to soil invertebrates, but that the rate of particle dissolution in different soil environments is an important factor for consideration.Exposure to fine particulate matter (PM2.5) in outdoor air is carcinogenic and associated with the development of lung cancer; however, the underlying mechanism remains unclear. In the present study, the profiles of lncRNA, microRNA and mRNA expression profiles in human bronchial epithelia (HBE) following exposure to PM2.5, diesel exhaust particles (DEPs), or aluminum oxide nanoparticles (Al2O3 NPs) were explored by microarray to reveal the lncRNA-microRNA-mRNA network participating in the malignant transformation of HBE cells following long-term PM2.5 exposure. The results showed that lncRNA SOX2 overlapping transcript (SOX2-OT) was significantly induced in HBE cells exposed to PM2.5, DEPs, or Al2O3 NPs, acting as a sponge to microRNA-345-5p, which subsequently increased the expression levels of epidermal growth factor receptor (EGFR). EGFR is a therapeutic target in non-small cell lung cancer. Here, we found that SOX2-OT is an upstream trigger of EGFR in HBE cells during long-term PM2.5 exposure. Importantly, SOX2-OT knockdown effectively reduced the colony formation and migration capacities of HBE cells, compared to the wild type control. Collectively, SOX2-OT/microRNA-345-5p/EGFR is a ceRNA mechanism underlying the malignant transformation of bronchial epithelia exposed to PM2.5, which improves our understanding of the association between ambient PM2.5 exposure and the development of lung cancer.Despite the important roles of dendritic cells (DCs) in airway allergies, current therapeutic strategies such as drugs, allergen immunotherapy and biologics haven’t been targeted at them. In this study, we established a promising DC-based therapeutic approach for the alleviation of allergic rhinitis (AR)-associated allergic reactions, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated targeted gene disruption. RNA sequencing analysis revealed upregulation of vacuolar protein sorting 37 B (VPS37B) in AR-derived DCs, indicating a novel molecular target. Following antigen presentation, VPS37A and VPS37B enabled endocytosis of the mannose receptor, which recognizes the house dust mite (HDM) allergen Der p 1. DCs with targeted disruption of VPS37A/B alleviated Th2 cytokine production when co-cultured in vitro with allogeneic naïve CD4+ T cell from patients with AR. Furthermore, nasal administration of Vps37a/b-disrupted bone marrow DCs to a mouse model of AR resulted in strongly reduced AR-related symptoms. Thus, this novel modality using genetically engineered DCs can provide an effective therapeutic and preventative strategy for allergic diseases.Endothelialization strategies aim at protecting the surface of cardiovascular devices upon their interaction with blood by the generation and maintenance of a mature monolayer of endothelial cells. Rational engineering of the surface micro-topography at the luminal interface provides a powerful access point to support the survival of a living endothelium under the challenging hemodynamic conditions created by the implant deployment and function. Surface structuring protocols must however be adapted to the complex, non-planar architecture of the target device precluding the use of standard lithographic approaches. Here, a novel patterning method, harnessing the condensation and evaporation of water droplets on a curing liquid elastomer, is developed to introduce arrays of microscale wells on the surface of a biocompatible silicon layer. The resulting topographies support the in vitro generation of mature human endothelia and their maintenance under dynamic changes of flow direction or magnitude, greatly outperforming identical, but flat substrates. The structuring approach is additionally demonstrated on non-planar interfaces yielding comparable topographies. The intrinsically free-form patterning is therefore compatible with a complete and stable endothelialization of complex luminal interfaces in cardiovascular implants.The peri-islet extracellular matrix (ECM) is a key component of the microenvironmental niche surrounding pancreatic islets of Langerhans. The cell anchorage and signaling provided by the peri-islet ECM is critical for optimum beta cell glucose responsiveness, but islets lose this important native ECM when isolated for transplantation or in vitro studies. Here, we established a method to construct a peri-islet ECM on the surfaces of isolated rat and human islets by the co-assembly from solution of laminin, nidogen and collagen IV proteins. Successful deposition of contiguous peri-islet ECM networks was confirmed by immunofluorescence, western blot, and transmission electron microscopy. The ECM coatings were disrupted when assembly occurred in Ca2+/Mg2+-free conditions. As laminin network polymerization is divalent cation dependent, our data are consistent with receptor-driven ordered ECM network formation rather than passive protein adsorption. To further illustrate the utility of ECM coatings, we employed stem cell derived beta-like cell clusters (sBCs) as a renewable source of functional beta cells for cell replacement therapy.