RT‐CGM in conjunction with CSII vs MDI in optimizing glycaemic control in T1DM: Systemic review and meta‐analysis

From Wiley via Jisc Publications RouterIntroduction: To determine the impact of real‐time continuous glucose monitoring (RT‐CGM) in conjunction with ‘Open loop’‐ continuous subcutaneous insulin infusion (CSII) as compared to conventional multiple daily injections (MDI) in type 1 diabetes. Methods: We explored the COCHRANE database, MEDLINE, WEB OF SCIENCE, GOOGLE SCHOLARS, PUBMED, EMBASE, and cited literature in articles retrieved (2010–2021) for all randomized controlled trials and real‐world trials of more than 6 months duration in patients with type 1 diabetes that compared RT‐CGM+CSII vs RT‐ CGM+MDI. A total of 1645 publications have been identified; however, only 3 trials fulfilled our inclusion criteria with a total number of 150 patients (72 patients using RT‐CGM+CSII and 78 patients on RT‐CGM+MDI). A Systematic Review and Meta‐analysis were carried out. Results: No statistically significant reduction in HbA1c was found on comparing RT‐CGM+CSII vs RT‐ CGM + MDI, with p‐value = .75. Likewise, impact on TIR, weight and insulin usage was found to be statistically insignificant with p‐value of 0.15, 0.75 and 0.20 respectively. There was an overall homogeneity between the 3 trials in respect to all previous variables with I2 being 0%. Conclusions: Real‐time continuous glucose monitors in conjunction with MDI open‐loop CSII had a similar impact on HbA1c, weight, insulin usage and TIR. In addition, RT‐CGM when combined with CSII was associated with higher costs and reduced quality of life, hence RT‐ CGM+MDI can be considered as a cheaper, safer yet equivalent substitute. Review Registration: This study was registered in PROSPERO (International prospective register of systematic reviews). Registration Name: RT‐CGM in conjunction with CSII vs MDI in optimizing glycaemic control in T1DM: a systematic review. Registration No: CRD42021255333. Accessible at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021255333. Amendments: Few amendments to the above‐mentioned registration were made: (1) Title (Meta‐analysis was added). (2) Prof. Gleeson was added as an author. (3) Real‐world trials were included. (4) Outcomes required in studies as per our inclusion criteria amended to include at least 1 outcome. (5) Bias risk was assessed by the CASP tool.5pubpub

Expansion of Signal Transduction Pathways in Fungi by Extensive Genome Duplication

International audienceno abstrac

Comparative genome structure, secondary metabolite, and effector coding capacity across Cochliobolus pathogens.

The genomes of five Cochliobolus heterostrophus strains, two Cochliobolus sativus strains, three additional Cochliobolus species (Cochliobolus victoriae, Cochliobolus carbonum, Cochliobolus miyabeanus), and closely related Setosphaeria turcica were sequenced at the Joint Genome Institute (JGI). The datasets were used to identify SNPs between strains and species, unique genomic regions, core secondary metabolism genes, and small secreted protein (SSP) candidate effector encoding genes with a view towards pinpointing structural elements and gene content associated with specificity of these closely related fungi to different cereal hosts. Whole-genome alignment shows that three to five percent of each genome differs between strains of the same species, while a quarter of each genome differs between species. On average, SNP counts among field isolates of the same C. heterostrophus species are more than 25× higher than those between inbred lines and 50× lower than SNPs between Cochliobolus species. The suites of nonribosomal peptide synthetase (NRPS), polyketide synthase (PKS), and SSP-encoding genes are astoundingly diverse among species but remarkably conserved among isolates of the same species, whether inbred or field strains, except for defining examples that map to unique genomic regions. Functional analysis of several strain-unique PKSs and NRPSs reveal a strong correlation with a role in virulence

Increasing frailty is associated with higher prevalence and reduced recognition of delirium in older hospitalised inpatients: results of a multi-centre study

Purpose: Delirium is a neuropsychiatric disorder delineated by an acute change in cognition, attention, and consciousness. It is common, particularly in older adults, but poorly recognised. Frailty is the accumulation of deficits conferring an increased risk of adverse outcomes. We set out to determine how severity of frailty, as measured using the CFS, affected delirium rates, and recognition in hospitalised older people in the United Kingdom. Methods: Adults over 65 years were included in an observational multi-centre audit across UK hospitals, two prospective rounds, and one retrospective note review. Clinical Frailty Scale (CFS), delirium status, and 30-day outcomes were recorded. Results: The overall prevalence of delirium was 16.3% (483). Patients with delirium were more frail than patients without delirium (median CFS 6 vs 4). The risk of delirium was greater with increasing frailty [OR 2.9 (1.8–4.6) in CFS 4 vs 1–3; OR 12.4 (6.2–24.5) in CFS 8 vs 1–3]. Higher CFS was associated with reduced recognition of delirium (OR of 0.7 (0.3–1.9) in CFS 4 compared to 0.2 (0.1–0.7) in CFS 8). These risks were both independent of age and dementia. Conclusion: We have demonstrated an incremental increase in risk of delirium with increasing frailty. This has important clinical implications, suggesting that frailty may provide a more nuanced measure of vulnerability to delirium and poor outcomes. However, the most frail patients are least likely to have their delirium diagnosed and there is a significant lack of research into the underlying pathophysiology of both of these common geriatric syndromes

Analysis of the Tissue Movements of Embryonic Wound Healing-DiI Studies in the Limb Bud Stage Mouse Embryo

The tissue movements of epithelial spreading and mesenchymal contraction play key roles in many aspects of embryonic morphogenesis. One way of studying these movements in a controlled manner is to make an excisional skin wound to an embryo and watch the wound heal. In this paper we report our studies of healing of a simple excisional lesion made to the limb bud stage mouse embryo. The wounded, living embryo is cultured in a roller bottle; under such conditions the wound heals with a highly reproducible time course and is completely closed by 24 hr. During the healing period the environment bathing the wound can be simply manipulated by adding drugs or factors to the culture medium. We have used DiI to label mesenchymal cells exposed at the margin of the initial wound and, by following their fate and measuring the area of mesenchyme remaining exposed at various time points during the healing process, we have quantified both the extent of mesenchymal contraction and the extent of reepithelialisation by movement of epidermis over mesenchyme. We show that the two types of tissue movement contribute almost equally (50:50) to the total wound closure rate. We have gone on to investigate the cell machinery underlying these processes. In adult wounds the epidermis migrates by means of lamellipodial crawling, but we show that reepithelialisation in the embryo is achieved instead by purse-string contraction of a cable of filamentous actin which assembles in the basal layer of cells at the free edge of the epidermis. Addition of cytochalasin D to the culture medium blocks formation of this actin cable and leads to failure of reepithelialisation. Contraction of adult wound connective tissue appears to be driven by conversion of dermal fibroblasts into a specialist smooth muscle-like fibroblast, the myofibroblast. However, using an antibody recognising the alpha-isoform of smooth muscle actin and specific for smooth muscle cells and myofibroblasts, we show that a similar conversion into myofibroblasts does not occur at any stage during the embryonic wound healing process. These observations indicate that both of the tissue movements of embryonic wound healing utilise cell machinery fundamentally different from that driving the analogous tissue movements of adult healing.sch_die170pub4512pub

Control of cell cycle gene expression in bone development and during c-Fos-induced osteosarcoma formation.

We have used c-Fos transgenic mice which develop osteosarcomas to determine the expression patterns of cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs) in different bone cell populations in order to define the potential mechanisms of c-Fos transformation. Immunohistochemical analysis in embryonic and early postnatal bone demonstrated that cyclin E and its kinase partner CDK2 were expressed specifically in bone-forming osteoblasts. Cyclin D1 expression was absent despite high levels of CDK4 and CDK6, and the CKI p27 was expressed in chondrocytes, osteoclasts, and at lower levels in osteoblasts. Following activation of the c-fos transgene in vivo and before overt tumor formation, cyclin D1 expression increased dramatically and was colocalized with exogenous c-Fos protein specifically in osteoblasts and chondrocytes, but not in osteoclasts. Prolonged activation of c-Fos resulted in osteosarcoma formation wherein the levels of cyclin D1, cyclin E, and CDKs 2, 4, and 6 were high in a wide spectrum of malignant cell types, especially in transformed osteoblasts. The CKI p27 was expressed at very high levels in bone-resorbing osteoclasts, and to a lesser extent in chondrocytes and osteoblasts. These in vivo observations suggest that cyclin D1 may be a target for c-Fos action and that elevation of cyclin D1 in osteoblasts which already express cyclin E/CDK2 and the cyclin D1 partners CDKs-4 and 6, may predispose cells to uncontrolled cell growth leading to osteosarcoma development. This study implicates altered cell cycle control as a potential mechanism through which c-Fos causes osteoblast transformation and bone tumor formation.sch_die22pub4510pub

Growth factors and cutaneous wound repair.

The healing of an adult skin lesion is a well studied but complex affair of some considerable clinical interest. Endogenous growth factors, including the EGF, FGF, PDGF and TGF beta families, are released at the wound site and presumed to be a necessary part of the natural wound healing machinery. Moreover, members of each of these families have been shown to enhance healing if added exogenously to a wound site. In this review we shall briefly discuss what is known about the mechanics and cell biology of adult wound healing, describe the normal cellular source of growth factors during the healing process and, with reference to their known capacities in tissue culture, speculate as to how particular growth factors might be able to enhance healing.sch_die4pub4516pub

Perfect wound healing in the keratin 8 deficient mouse embryo.

It is generally believed that the strength and structural integrity of both adult and embryonic epithelia comes, at least in part, from their internal cytoskeletal network of keratin filaments and associated cell:cell junctions. Indeed, recent keratin depletion experiments in Xenopus suggest that the capacity of embryonic epithelia to undergo natural morphogenetic movements such as gastrulation, or artificially triggered epithelial movements such as wound closure, are severely compromised in the absence of the predominant embryonic keratin, K8 [Torpey et al., 1992: Nature 357:413-415; Klymkowsky et al., 1992: Proc. Natl. Acad. Sci. USA 89:8736-8740]. These experiments contrast with studies of genetically K8 deficient mouse embryos which undergo gastrulation quite normally and, dependent upon background strain, can survive until beyond birth [Baribault et al., 1993: Genes Dev. 7:1191-1202; Baribault et al., 1994: Genes Dev. 8:2964-2973], but to date no wound healing investigations have been carried out on mK8-mice. In this article, we report our studies of healing in embryonic day 11.5 mouse embryos, wounded by amputation of the hindlimb bud and then cultured in roller bottles. In wild-type embryos, wound closure puts severe strain on the embryonic epidermis since it is under tension and gapes immediately upon wounding; subsequently, epithelial cells tug on one another by means of an actin purse-string in order to close the defect. Even given these extremely challenging conditions, we show here that the mK8- epidermis performs no differently from wild-type epidermis, assembling an actin purse-string in the wound marginal cells and closing the wound with identical timecourse to its wild-type counterpart.sch_die35pub4511pub