Heparan sulfate (HS) proteoglycans are important components of cells and the extracellular microenvironment. Interaction between growth factors and receptors is often modulated by the amount and degree of HS sulfation. We hypothesize that natural variation in HS composition on adipocytes serves as a rheostat for adipocyte function and impacts susceptibility to develop insulin resistance, type‐2 diabetes and obesity. We use mice with adipose tissue (AT) specific inactivation of the HS biosynthetic enzymes N‐acetylglucosamine‐N‐deacetylase‐N‐sulfotransferase 1 (Ndst1‐AKO) and Exostosin 1 (Ext1‐AKO) mediated by the Adipoq‐Cre driver. These models allow us to study the impact of HS sulfation and chain length, respectively, on adipocyte metabolism and systemic glucose homeostasis in the context of diet‐induced obesity. On a high fat diet both Ndst1‐AKO and Ext1‐AKO mice gain more weight compared to WT littermates and develop significant glucose intolerance and insulin resistance. A pyruvate tolerance test indicates that disturbed adipocyte‐HS significantly affects liver gluconeogenesis. Moreover, hepatic inflammation is elevated in Ndst1‐AKO mice compared to WT controls, indicating that adipocyte‐HS also influences the organ cross‐talk between AT and liver. Previously, it has been shown that fibroblast growth factor 1 (FGF1) is a potent insulin sensitizer with great therapeutic potential. FGF1 signaling depends on the presence of HS on the plasma membrane. We show that the insulin‐sensitizing effect of FGF1 is diminished in Ndst1‐AKO and Ext1‐AKO mice. However, the insulin sensitization response to FGF21, another metabolic active FGF without HS‐dependency, is unaffected by HS alterations in AT. Our data suggest that HS composition in AT regulates FGF1 sequestration and signaling, leading to metabolic complications upon diet‐induced obesity. In this context, our results underline the importance of HS composition in AT for signaling processes that are critical for glucose homeostasis.

As the biopharmaceutical industry evolves to include more diverse protein formats and processes, more robust control of Critical Quality Attributes (CQAs) is needed to maintain processing flexibility without compromising quality. Active control of CQAs has been demonstrated using model predictive control techniques, which allow development of processes which are robust against disturbances associated with raw material variability and other potentially flexible operating conditions. Wide adoption of model predictive control in biopharmaceutical cell culture processes has been hampered, however, in part due to the large amount of data and expertise required to make a predictive model of controlled CQAs, a requirement for model predictive control. Here we developed a highly automated, perfusion apparatus to systematically and efficiently generate predictive models using application of system identification approaches. We successfully created a predictive model of %galactosylation using data obtained by manipulating galactose concentration in the perfusion apparatus in serialized step change experiments. We then demonstrated the use of the model in a model predictive controller in a simulated control scenario to successfully achieve a %galactosylation set point in a simulated fed‐batch culture. The automated model identification approach demonstrated here can potentially be generalized to many CQAs, and could be a more efficient, faster, and highly automated alternative to batch experiments for developing predictive models in cell culture processes, and allow the wider adoption of model predictive control in biopharmaceutical processes. © 2017 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 33:1647–1661, 2017

BackgroundPeople living with chronic obstructive pulmonary disease (COPD) are a group who may be particularly vulnerable to COVID-19. This vulnerability has been associated with increased anxiety or fear about exposure to the virus, which may also impact upon experience in healthcare settings.Aim/objectivesThe aim of this narrative mixed-methods review was to systematically scope, identify and synthesise findings from peer-reviewed qualitative, quantitative and mixed-methods studies published in academic journals describing the healthcare experiences of adults living with COPD independently in the community, following the emergence of COVID-19 in December 2019–June 2022.MethodsDatabases including Ovid MEDLINE, PsychINFO, Ovid Emcare and CINAHL Plus were searched. Studies were uploaded to Covidence to support selection and appraisal of studies. Studies were appraised for quality using the Mixed Methods Appraisal Tool. A narrative synthesis of these themes was provided, and qualitative and quantitative findings are interpreted together in the discussion.FindingsThe quality and experience of care for patients with COPD was impacted through the COVID-19 pandemic. Innovations and adoption of technologies such as telehealth and telerehabilitation were well received and mitigated the potential implications of severe disruption to care access to some extent. Patients feared feeling forgotten and experienced isolation and anxiety; however, telerehabilitation and exercise through modalities such as Zoom classes help support social connection and physical activity.ImplicationsThese innovations are likely to be useful to be offered to patients on an ongoing basis, and education and standardised protocols around their use will benefit healthcare providers and patients alike.PROSPERO registration numberCRD42022341168.

Many individuals with Autism Spectrum Disorder (ASD) experience challenges with social communication, including recognizing and responding to non-verbal cues. The purpose of this study was to assess the efficacy of self-management combined with textual cues to teach adults with ASD to recognize and respond to nonverbal expressions of boredom and confusion during social conversation. A multiple baseline across participants design was used to assess the efficacy of this intervention for three participants. Results showed substantial gains across all participants in their recognition and responsiveness to the targeted nonverbal cues. Moreover, this skill maintained after the completion of intervention and generalized to novel conversation partners and settings with large effect sizes. The findings add to the literature base on interventions for adults with ASD, and further support the use of self-management and textual cues as effective intervention strategies for improving nonverbal communication.