Demonstrating the Potential of Using Bio-Based Sustainable Polyester Blends for Bone Tissue Engineering Applications

YesHealthcare applications are known to have a considerable environmental impact and the use of bio-based polymers has emerged as a powerful approach to reduce the carbon footprint in the sector. This research aims to explore the suitability of using a new sustainable polyester blend (Floreon™) as a scaffold directed to aid in musculoskeletal applications. Musculoskeletal problems arise from a wide range of diseases and injuries related to bones and joints. Specifically, bone injuries may result from trauma, cancer, or long-term infections and they are currently considered a major global problem in both developed and developing countries. In this work we have manufactured a series of 3D-printed constructs from a novel biopolymer blend using fused deposition modelling (FDM), and we have modified these materials using a bioceramic (wollastonite, 15% w/w). We have evaluated their performance in vitro using human dermal fibroblasts and rat mesenchymal stromal cells. The new sustainable blend is biocompatible, showing no differences in cell metabolic activity when compared to PLA controls for periods 1-18 days. FloreonTM blend has proven to be a promising material to be used in bone tissue regeneration as it shows an impact strength in the same range of that shown by native bone (just under 10 kJ/m2) and supports an improvement in osteogenic activity when modified with wollastonite.We would like to acknowledge the Medical Research Council in the UK (MRC) for funding this research throughout a MRC Proximity to Discovery award (P2D) with grant number MC_PC_16084. We would also like to acknowledge CONACYT for funding DH RamosRodriguez’s work

What has changed in canine pyoderma? A narrative review

Canine pyoderma is a common presentation in small animal practice and frequently leads to prescription of systemic antimicrobial agents. A good foundation of knowledge on pyoderma was established during the 1970s and 1980s, when treatment of infection provided relatively few challenges. However, the ability to treat canine pyoderma effectively is now limited substantially by the emergence of multidrug-resistant, methicillin-resistant staphylococci (MRS) and, in some countries, by restrictions on antimicrobial prescribing for pets. The threat from rising antimicrobial resistance and the zoonotic potential of MRS add a new dimension of public health implications to the management of canine pyoderma and necessitate a revisit and the search for new best management strategies. This narrative review focusses on the impact of MRS on how canine pyoderma is managed and how traditional treatment recommendations need to be updated in the interest of good antimicrobial stewardship. Background information on clinical characteristics, pathogens, and appropriate clinical and microbiological diagnostic techniques, are reviewed in so far as they can support early identification of multidrug-resistant pathogens. The potential of new approaches for the control and treatment of bacterial skin infections is examined and the role of owner education and hygiene is highlighted. Dogs with pyoderma offer opportunities for good antimicrobial stewardship by making use of the unique accessibility of the skin through cytology, bacterial culture and topical therapy. In order to achieve long term success and to limit the spread of multidrug resistance, there is a need to focus on identification and correction of underlying diseases that trigger pyoderma in order to avoid repeated treatment

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E-09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E-23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E-04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

"Tailored" submaximal step test for VO2max prediction in healthy older adults.

We developed and validated a "tailored" version of the Astrand-Rhyming step test (tA-R) and a new equation for VO2max prediction in older adults (OA). 60 subjects (age 68\ub14, 30 M, 30 F) performed our tA-R step test (5-min, 30-cm step, tailored stepping rate) and an incremental cycling test to exhaustion. VO2max was: i) predicted using the standard A-R equation (predictedVO2max); ii) predicted based on our new multiple linear equation (equationVO2max); iii) directly measured by incremental cycling test (directVO2max). Agreement among values of VO2max was evaluated by Bland-Altman analysis. predictedVO2max was not significantly different from directVO2max yet with relatively large imprecision. equationVO2max allowed more precise as well as accurate predictions of VO2max compared to standard A-R prediction. Our "tailored" version of the Astrand-Rhyming step test and our new prediction equation appear suitable for a rapid (5-min), safe (submaximal), accurate and precise VO2max prediction in healthy OA

Non-invasive estimation of microvascular O2 provision during exercise on-transients in healthy young males.

Two methods for estimating changes in microvascular O2 delivery during the on-transient of exercise were evaluated. They were tested to assess the role of the adjustment of the estimated microvascular O2 delivery in the speeding of V\u307o2 kinetics during a Mod1-Hvy-Mod2 protocol (Mod, moderate-intensity exercise; Hvy, heavy-intensity \u201cpriming\u201d exercise), in which Mod2 is preceded by a bout of Hvy. Mod pulmonary V\u307o2 (V\u307o2p) and deoxy-hemoglobin [HHb] data were collected in 12 males (23 \ub1 3 yr); response profiles were fit with a monoexponential. Signals were also 1) scaled to a relative % of the response (0\u2013100%) to calculate the [HHb]/V\u307o2 ratio for each individual and 2) rearranged in the Fick equation for estimation of capillary blood flow (Qcap). A transient [HHb]/V\u307o2 \u201covershoot\u201d observed in Mod1 (1.06 \ub1 0.05; P 0.05); reductions in the [HHb]/V\u307o2 ratio (Mod1 12 Mod2) were related to reductions in phase II \u3c4V\u307o2p (r = 0.82; P < 0.05). For Qcap, a near-exponential response was observed in 8/12 subjects in Mod1 and only in 4/12 subjects in Mod2. The Qcap profile was shown to be highly dependent on the [HHb] baseline-to-amplitude ratio. Thus, accurate and physiologically consistent estimations of Qcap were not possible in most cases. This study confirmed that priming exercise results in an improved O2 delivery as shown by the decreased [HHb]/V\u307o2 ratio that was related to the smaller \u3c4V\u307o2 in Mod2. Additionally, this study suggested that Qcap analysis may not be valid and should be interpreted with caution when assessing microvascular delivery of O2