Classifying antibiotics in the WHO Essential Medicines List for optimal use—be AWaRe

International audienc

Regenerative potential of DPSCs and revascularization. direct, paracrine or autocrine effect?

A new source of mesenchymal stem cells has recently been discovered, the so-called dental pulp derived stem cells (DPSCs) which therefore could represent potentially tools for regenerative medicine. DPSC originate from the neural crest and are physiologically involved in dentin homeostasis; moreover, they contribute to bone remodeling and differentiation into several tissues including cartilage, bone, adipose and nervous tissues. DPSCs have also been shown to influence the angiogenesis process, for example through the release of secretory factors or by differentiating into vascular and/or perivascular cells. Angiogenesis, that has a pivotal role in tissue regeneration and repair, is defined as the formation of new vessels from preexisting vessels and is mediated by mutual and reciprocal interactions between endothelial cells and perivascular cells. It is also known that co-cultures of perivascular and endothelial cells (ECs) can form a vascular network in vitro and also in vivo. Since DPSCs seem to have characteristics similar to pericytes, understanding the possible mechanism of interaction between DPSCs and ECs during neo-angiogenesis is dramatically important for the development of advanced clinical application in the field of regeneration. Graphical abstract: [Figure not available: see fulltext.

Skeletal Anomaly Monitoring in Rainbow Trout (Oncorhynchus mykiss, Walbaum 1792) Reared under Different Conditions

The incidence of skeletal anomalies could be used as an indicator of the "quality" of rearing conditions as these anomalies are thought to result from the inability of homeostatic mechanisms to compensate for environmentally-induced stress and/or altered genetic factors. Identification of rearing conditions that lower the rate of anomalies can be an important step toward profitable aquaculture as malformed market-size fish have to be discarded, thus reducing fish farmers' profits. In this study, the occurrence of skeletal anomalies in adult rainbow trout grown under intensive and organic conditions was monitored. As organic aquaculture animal production is in its early stages, organic broodstock is not available in sufficient quantities. Non-organic juveniles could, therefore, be used for on-growing purposes in organic aquaculture production cycle. Thus, the adult fish analysed in this study experienced intensive conditions during juvenile rearing. Significant differences in the pattern of anomalies were detected between organically and intensively-ongrown specimens, although the occurrence of severe, commercially important anomalies, affecting 2-12.5% of individuals, was comparable in the two systems. Thus, organic aquaculture needs to be improved in order to significantly reduce the incidence of severe anomalies in rainbow trout

Rainbow trout (Oncorhynchus mykiss, Walbaum 1792) develop a more robust body shape under organic rearing

Prolonged exposure to captive conditions has led to the development of a rainbow trout ‘farmed’ pheno- type, which is different from that of wild trout. Selec- tion for desirable productive traits in hatcheries has resulted in the development of some morphological traits that are maladaptive in nature. The recent development of organic aquaculture, guided by the well-being of the fish, could potentially produce a new farmed phenotype that would be more adaptive in nature. In this study, rainbow trout reared in intensive and organic farms were compared by means of shape analysis, to detect patterns of shape variation associated with rearing environment. The results of this study highlight a significant effect of the rearing method on rainbow trout shape: organi- cally reared trout showed a higher body profile, in particular in the head and trunk regions, shorter median fins and a deeper caudal peduncle. A combined effect of density and habitat complexity could have contributed to the observed shape differences: in organic rearing systems, lower densi- ties and steady water could increase territoriality and aggressive interactions, promoting body designs more functional in rapid attacks and escapes

Harnessing the wisdom of crowds can improve guideline compliance of antibiotic prescribers and support antimicrobial stewardship

open access articleAntibiotic overprescribing is a global challenge contributing to rising levels of antibiotic resistance and mortality. We test a novel approach to antibiotic stewardship. Capitalising on the concept of “wisdom of crowds”, which states that a group’s collective judgement often outperforms the average individual, we test whether pooling treatment durations recommended by different prescribers can improve antibiotic prescribing. Using international survey data from 787 expert antibiotic prescribers, we run computer simulations to test the performance of the wisdom of crowds by comparing three data aggregation rules across different clinical cases and group sizes. We also identify patterns of prescribing bias in recommendations about antibiotic treatment durations to quantify current levels of overprescribing. Our results suggest that pooling the treatment recommendations (using the median) could improve guideline compliance in groups of three or more prescribers. Implications for antibiotic stewardship and the general improvement of medical decision making are discussed. Clinical applicability is likely to be greatest in the context of hospital ward rounds and larger, multidisciplinary team meetings, where complex patient cases are discussed and existing guidelines provide limited guidance

Hypoxia-Mimetic CoCl2 Agent Enhances Pro-Angiogenic Activities in Ovine Amniotic Epithelial Cells-Derived Conditioned Medium

Amniotic epithelial stem cells (AECs) are largely studied for their pro-regenerative properties. However, it remains undetermined if low oxygen (O2) levels that AECs experience in vivo can be of value in maintaining their biological properties after isolation. To this aim, the present study has been designed to evaluate the effects of a hypoxia-mimetic agent, cobalt chloride (CoCl2), on AECs’ stemness and angiogenic activities. First, a CoCl2 dose-effect was performed to select the concentration able to induce hypoxia, through HIF-1α stabilization, without promoting any cytotoxicity effect assessed through the analysis of cell vitality, proliferation, and apoptotic-related events. Then, the identified CoCl2 dose was evaluated on the expression and angiogenic properties of AECs’ stemness markers (OCT-4, NANOG, SOX-2) by analysing VEGF expression, angiogenic chemokines’ profiles, and AEC-derived conditioned media activity through an in vitro angiogenic xeno-assay. Results demonstrated that AECs are sensitive to the cytotoxicity effects of CoCl2. The unique concentration leading to HIF-1α stabilization and nuclear translocation was 10 µM, preserving cell viability and proliferation up to 48 h. CoCl2 exposure did not modulate stemness markers in AECs while progressively decreasing VEGF expression. On the contrary, CoCl2 treatment promoted a significant short-term release of angiogenic chemokines in culture media (CM). The enrichment in bio-active factors was confirmed by the ability of CoCl2-derived CM to induce HUVEC growth and the cells’ organization in tubule-like structures. These findings demonstrate that an ap-propriate dose of CoCl2 can be adopted as a hypoxia-mimetic agent in AECs. The short-term, chemical-induced hypoxic condition can be targeted to enhance AECs’ pro-angiogenic properties by providing a novel approach for stem cell-free therapy protocols