Aim
To describe diabetes nurses' perspectives on the impact of the COVID‐19 pandemic on people with diabetes and diabetes services across Europe.
Methods
An online survey developed using a rapid ...Delphi method. The survey was translated into 17 different languages and disseminated electronically in 27 countries via national diabetes nurse networks.
Results
Survey responses from 1829 diabetes nurses were included in the analysis. The responses indicated that 28% (n = 504) and 48% (n = 873) of diabetes nurses felt the COVID‐19 pandemic had impacted ‘a lot’ on the physical and psychological risks of people with diabetes, respectively. The following clinical problems were identified as having increased ‘a lot’: anxiety 82% (n = 1486); diabetes distress 65% (n = 1189); depression 49% (n = 893); acute hyperglycaemia 39% (n = 710) and foot complications 18% (n = 323). Forty‐seven percent (n = 771) of respondents identified that the level of care provided to people with diabetes had declined either extremely or quite severely. Self‐management support, diabetes education and psychological support were rated by diabetes nurse respondents as having declined extremely or quite severely during the COVID‐19 pandemic by 31% (n = 499), 63% (n = 1,027) and 34% (n = 551), respectively.
Conclusion
The findings show that diabetes nurses across Europe have seen significant increases in both physical and psychological problems in their patient populations during COVID‐19. The data also show that clinical diabetes services have been significantly disrupted. As the COVID‐19 situation continues, we need to adapt care systems with some urgency to minimise the impact of the pandemic on the diabetes population.
In vitro chemical safety testing methods offer the potential for efficient and economical tools to provide relevant assessments of human health risk. To realize this potential, methods are needed to ...relate in vitro effects to in vivo responses, i.e., in vitro to in vivo extrapolation (IVIVE). Currently available IVIVE approaches need to be refined before they can be utilized for regulatory decision-making. To explore the capabilities and limitations of IVIVE within this context, the U.S. Environmental Protection Agency Office of Research and Development and the National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods co-organized a workshop and webinar series. Here, we integrate content from the webinars and workshop to discuss activities and resources that would promote inclusion of IVIVE in regulatory decision-making. We discuss properties of models that successfully generate predictions of in vivo doses from effective in vitro concentration, including the experimental systems that provide input parameters for these models, areas of success, and areas for improvement to reduce model uncertainty. Finally, we provide case studies on the uses of IVIVE in safety assessments, which highlight the respective differences, information requirements, and outcomes across various approaches when applied for decision-making.
•In vitro to in vivo extrapolation uses a model relating active in vitro concentrations to an in vivo response-inducing dose•Models for regulatory use will vary depending on needs: prioritization vs. hazard assessment•Transparency and reporting standards for models are critical during implementation
Molecular mechanics force field parameters for macromolecules, such as proteins, are traditionally fit to reproduce experimental properties of small molecules, and thus, they neglect system-specific ...polarization. In this paper, we introduce a complete protein force field that is designed to be compatible with the quantum mechanical bespoke (QUBE) force field by deriving nonbonded parameters directly from the electron density of the specific protein under study. The main backbone and sidechain protein torsional parameters are rederived in this work by fitting to quantum mechanical dihedral scans for compatibility with QUBE nonbonded parameters. Software is provided for the preparation of QUBE input files. The accuracy of the new force field, and the derived torsional parameters, is tested by comparing the conformational preferences of a range of peptides and proteins with experimental measurements. Accurate backbone and sidechain conformations are obtained in molecular dynamics simulations of dipeptides, with NMR J coupling errors comparable to the widely used OPLS force field. In simulations of five folded proteins, the secondary structure is generally retained, and the NMR J coupling errors are similar to standard transferable force fields, although some loss of the experimental structure is observed in certain regions of the proteins. With several avenues for further development, the use of system-specific nonbonded force field parameters is a promising approach for next-generation simulations of biological molecules.
Impaired neurodevelopment is reported among children conceived by assisted reproductive technologies (ART). However, this might be explained by conditions underlying parental subfecundity, rather ...than the ART procedure.
We examined associations of parental time-to-pregnancy (TTP) and conception by ART with neurodevelopmental traits up to 8 years of age, including motor and language skills, social delays and difficulties, and inattention-hyperactivity, among 92 142 singletons participating in the Norwegian Mother, Father and Child Cohort Study (MoBa). Mothers reported TTP and neurodevelopmental traits through questionnaires. Mean differences in standardized neurodevelopmental traits were estimated using linear regression, adjusting for maternal age, parity, educational level, body mass index and smoking, and paternal age.
A longer TTP was associated with decreased language skills and motor skills at 6, 18 and 36 months (P-values for trend ≤0.01), prosocial skills delay at 36 months (P-values for trend ≤0.001) and increased scores for inattention-hyperactivity traits at all ages up to 8 years (P-values for trend from 0.06 to 0.01). Effect sizes were small, ranging between 0.03 and 0.05 difference in the standardized neurodevelopmental scores. Estimates for ART were imprecise, but there were no differences between children conceived by ART and naturally conceived children of subfecund parents (TTP ≥12 months).
Longer parental TTP is modestly but robustly associated with offspring neurodevelopmental delays and difficulties, with no added impact of ART. Future studies should investigate the underlying causes of-or aspects related to-parental subfecundity which might explain the association with offspring neurodevelopmental delays and difficulties.
Understanding of the effects of in utero opioid exposure on neurodevelopment is a priority given the recent dramatic increase in opioid use among pregnant individuals. However, opioid abuse does not ...occur in isolation—pregnant individuals abusing opioids often have a significant history of adverse experiences in childhood, among other co-occurring factors. Understanding the specific pathways in which these frequently co-occurring factors may interact and cumulatively influence offspring brain development in utero represents a priority for future research in this area. We highlight maternal history of childhood adversity (CA) as one such co-occurring factor that is more prevalent among individuals using opioids during pregnancy and which is increasingly shown to affect offspring neurodevelopment through mechanisms beginning in utero. Despite the high incidence of CA history in pregnant individuals using opioids, we understand very little about the effects of comorbid prenatal opioid exposure and maternal CA history on fetal brain development. Here, we first provide an overview of current knowledge regarding effects of opioid exposure and maternal CA on offspring neurodevelopment that may occur during gestation. We then outline potential mechanistic pathways through which these factors might have interactive and cumulative influences on offspring neurodevelopment as a foundation for future research in this area.
•Opioid-using pregnant individuals are often affected by many co-occurring risk factors.•Disentangling effects of prenatal opioid use from co-exposures is challenging.•Prenatal opioid use and maternal CA affect fetal brains through similar pathways.
Ecosystems that are coupled by reciprocal flows of energy and nutrient subsidies can be viewed as a single “meta‐ecosystem.” Despite these connections, the reciprocal flow of subsidies is greatly ...asymmetrical and seasonally pulsed. Here, we synthesize existing literature on stream–riparian meta‐ecosystems to quantify global patterns of the amount of subsidy consumption by organisms, known as “allochthony.” These resource flows are important since they can comprise a large portion of consumer diets, but can be disrupted by human modification of streams and riparian zones. Despite asymmetrical subsidy flows, we found stream and riparian consumer allochthony to be equivalent. Although both fish and stream invertebrates rely on seasonally pulsed allochthonous resources, we find allochthony varies seasonally only for fish, being nearly three times greater during the summer and fall than during the winter and spring. We also find that consumer allochthony varies with feeding traits for aquatic invertebrates, fish, and terrestrial arthropods, but not for terrestrial vertebrates. Finally, we find that allochthony varies by climate for aquatic invertebrates, being nearly twice as great in arid climates than in tropical climates, but not for fish. These findings are critical to understanding the consequences of global change, as ecosystem connections are being increasingly disrupted.
Here, we synthesize existing literature on stream–riparian meta‐ecosystems to quantify global patterns of the amount of resource subsidy consumption by organisms, known as “allochthony.” Although both fish and stream invertebrates rely on seasonally pulsed allochthonous resources, we find allochthony varies seasonally only for fish, being nearly greater during the summer and fall than the winter and spring. We also find that consumer allochthony varies with feeding traits for aquatic invertebrates, fish, and terrestrial arthropods, but not for terrestrial vertebrates. Finally, we find that allochthony varies by climate for aquatic invertebrates, being nearly twice as great in arid climates than in tropical climates, but not for fish.
Limited research exists on the time course of long-term retinal and cerebral deficits in diabetic rodents. Previously, we examined short term (4-8 weeks) deficits in the Goto-Kakizaki (GK) rat model ...of Type II diabetes. Here, we investigated the long-term (1-8 months) temporal appearance of functional deficits (retinal, cognitive, and motor), retinal vascular pathology, and retinal dopamine levels in the GK rat.
In GK rats and Wistar controls, retinal neuronal function (electroretinogram), cognitive function (Y-maze), and motor function (rotarod) were measured at 1, 2, 4, 6, and 8 months of age. In addition, we evaluated retinal vascular function (functional hyperemia) and glucose and insulin tolerance. Retinas from rats euthanized at ≥8 months were assessed for vascular pathology. Dopamine and DOPAC levels were measured
HPLC in retinas from rats euthanized at 1, 2, 8, and 12 months.
Goto-Kakizaki rats exhibited significant glucose intolerance beginning at 4 weeks and worsening over time (
< 0.001). GK rats also showed significant delays in flicker and oscillatory potential implicit times (
< 0.05 to
< 0.001) beginning at 1 month. Cognitive deficits were observed beginning at 6 months (
< 0.05), but no motor deficits. GK rats showed no deficits in functional hyperemia and no increase in acellular retinal capillaries. Dopamine levels were twice as high in GK vs. Wistar retinas at 1, 2, 8, and 12 months (
< 0.001).
As shown previously, retinal deficits were detectable prior to cognitive deficits in GK rats. While retinal neuronal function was compromised, retinal vascular pathology was not observed, even at 12+ months. High endogenous levels of dopamine in the GK rat may be acting as an anti-angiogenic and providing protection against vascular pathology.
PDF
