Basal insulin requirement of youth with type 1 diabetes differs according to age

We investigated the percentage of total basal insulin dose to total daily insulin dose (%TBD) among Japanese youth of different ages with type 1 diabetes. The study enrolled 69 patients with type 1 diabetes who were treated with multiple daily injections of insulin. The participants were divided into the following age groups: group A, 0 to <10 years (n = 18); group B, 10 to <20 years (n = 31) and group C, 20 to <25 years (n = 20). We found no difference in the sex ratio, body mass index, and glycated hemoglobin and 2‐h postprandial C‐peptide levels among the three groups. Participants assigned to group B had a significantly higher percentage of total daily insulin dose than those in group A and group C (49.7 ± 10.4% vs 38.5 ± 13.7% and 38.3 ± 8.2%, P = 0.0005). In conclusion, the basal insulin requirements of Japanese youth with type 1 diabetes might have an age effect that is associated with puberty.     

Increase of intracellular Ca2+ and relocation of E-cadherin during experimental decompaction of mouse embryos

To determine the role of intracellular Ca²⁺ in compaction, the first morphogenetic event in embryogenesis, we analyzed preimplantation mouse embryos under several decompacting conditions, including depletion of extracellular Ca²⁺, blocking of Ca²⁺ channels, and inhibition of microfilaments, calmodulin, and intracellular Ca²⁺ release. Those treatments induced decompaction of mouse morulae and simultaneously induced changes in cytosolic free Ca²⁺ concentration and deregionalization of E-cadherin and fodrin. When morulae were allowed to recompact, the location of both proteins recovered. In contrast, actin did not change its cortical location with compaction nor with decompaction-recompaction. Calmodulin localized in areas opposite to cell–cell contacts in eight-cell stage embryos before and after compaction. Inhibition of calmodulin with trifluoperazine induced its delocalization while morulae decompacted. A nonspecific rise of intracellular free Ca²⁺ provoked by ionomycin did not affect the compacted shape. Moreover, the same decompacting treatments when applied to uncompacted embryos did not produce any change in intracellular Ca²⁺. Our results demonstrate that in preimplantation mouse embryos experimentally induced stage-specific changes of cell shape are accompanied by changes of intracellular free Ca²⁺ and redistribution of the cytoskeleton-related proteins E-cadherin, fodrin, and calmodulin. We conclude that intracellular Ca²⁺ specifically is involved in compaction and probably regulates the function and localization of cytoskeleton elements.     

Incorporation of molecular characteristics into endometrial cancer management

Histopathological evaluation including subtyping and grading is the current cornerstone for endometrial cancer (EC) classification. This provides clinicians with prognostic information and input for further treatment recommendations. Nonetheless, patients with histologically similar ECs may have very different outcomes, notably in patients with high-grade endometrial carcinomas. For endometrial cancer, four molecular subgroups have undergone extensive studies in recent years: POLE ultramutated (POLEmut), mismatch repair-deficient (MMRd), p53 mutant (p53abn) and those EC lacking any of these alterations, referred to as NSMP (non-specific molecular profile). Several large studies confirm the prognostic relevance of these molecular subgroups. However, this ‘histomolecular’ approach has so far not been implemented in clinical routine. The ongoing PORTEC4a trial is the first clinical setting in which the added value of integrating molecular parameters in adjuvant treatment decisions will be determined. For diagnostics, the incorporation of the molecular parameters in EC classification will add a level of objectivity which will yield biologically more homogeneous subclasses. Here we illustrate how the management of individual EC patients may be impacted when applying the molecular EC classification. We describe our current approach to the integrated diagnoses of EC with a focus on scenarios with conflicting morphological and molecular findings. We also address several pitfalls accompanying the diagnostic implementation of molecular EC classification and give practical suggestions for diagnostic scenarios.     

Clinical validation of a novel web-application for remote assessment of distance visual acuity

Background/ObjectivesOphthalmic disorders cause 8% of hospital clinic attendances, the highest of any specialty. The fundamental need for a distance visual acuity (VA) measurement constrains remote consultation. A web-application, DigiVis, facilitates self-assessment of VA using two internet-connected devices. This prospective validation study aimed to establish its accuracy, reliability, usability and acceptability.Subjects/MethodsIn total, 120 patients aged 5–87 years (median = 27) self-tested their vision twice using DigiVis in addition to their standard clinical assessment. Eyes with VA worse than +0.80 logMAR were excluded. Accuracy and test-retest (TRT) variability were compared using Bland–Altman analysis and intraclass correlation coefficients (ICC). Patient feedback was analysed.ResultsBias between VA tests was insignificant at −0.001 (95% CI −0.017 to 0.015) logMAR. The upper limit of agreement (LOA) was 0.173 (95% CI 0.146 to 0.201) and the lower LOA −0.175 (95% CI −0.202 to −0.147) logMAR. The ICC was 0.818 (95% CI 0.748 to 0.869). DigiVis TRT mean bias was similarly insignificant, at 0.001 (95% CI −0.011 to 0.013) logMAR, the upper LOA was 0.124 (95% CI 0.103 to 0.144) and the lower LOA −0.121 (95% CI −0.142 to −0.101) logMAR. The ICC was 0.922 (95% CI 0.887 to 0.946). 95% of subjects were willing to use DigiVis to monitor vision at home.ConclusionsSelf-tested distance VA using DigiVis is accurate, reliable and well accepted by patients. The app has potential to facilitate home monitoring, triage and remote consultation but widescale implementation will require integration with NHS databases and secure patient data storage.Subject terms: Diagnosis, Health services, Eye manifestations