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BackgroundNew wearable devices (for example, AliveCor or Zio patch) offer promise in detecting arrhythmia and monitoring cardiac health status, among other clinically useful parameters in older adults. However, the clinical utility and usability from the perspectives of clinicians is largely unexplored. ObjectiveThis study aimed to explore clinician perspectives on the use of wearable cardiac monitoring technology for older adults. MethodsA descriptive qualitative study was conducted using semistructured focus group interviews. Clinicians were recruited through purposive sampling of physicians, nurses, and allied health staff working in 3 tertiary-level hospitals. Verbatim transcripts were analyzed using thematic content analysis to identify themes. ResultsClinicians representing physicians, nurses, and allied health staff working in 3 tertiary-level hospitals completed 4 focus group interviews between May 2019 and July 2019. There were 50 participants (28 men and 22 women), including cardiologists, geriatricians, nurses, and allied health staff. The focus groups generated the following 3 overarching, interrelated themes: (1) the current state of play, understanding the perceived challenges of patient cardiac monitoring in hospitals, (2) priorities in cardiac monitoring, what parameters new technologies should measure, and (3) cardiac monitoring of the future, “the ideal device.” ConclusionsThere remain pitfalls related to the design of wearable cardiac technology for older adults that present clinical challenges. These pitfalls and challenges likely negatively impact the uptake of wearable cardiac monitoring in routine clinical care. Partnering with clinicians and patients in the co-design of new wearable cardiac monitoring technologies is critical to optimize the use of these devices and their uptake in clinical care.

Focal adhesion kinase (FAK) acts as an adaptor at the focal contacts serving as a junction between the extracellular matrix and actin cytoskeleton. Actin dynamics is known as a determinant step in insulin secretion. Additionally, FAK has been shown to regulate insulin signaling. To investigate the essential physiological role of FAK in pancreatic β-cells in vivo, we generated a transgenic mouse model using rat insulin promoter (RIP)-driven Cre-loxP recombination system to specifically delete FAK in pancreatic β-cells. These RIPcre(+)fak(fl/fl) mice exhibited glucose intolerance without changes in insulin sensitivity. Reduced β-cell viability and proliferation resulting in decreased β-cell mass was observed in these mice, which was associated with attenuated insulin/Akt (also known as protein kinase B) and extracellular signal-related kinase 1/2 signaling and increased caspase 3 activation. FAK-deficient β-cells exhibited impaired insulin secretion with normal glucose sensing and preserved Ca(2+) influx in response to glucose, but a reduced number of docked insulin granules and insulin exocytosis were found, which was associated with a decrease in focal proteins, paxillin and talin, and an impairment in actin depolymerization. This study is the first to show in vivo that FAK is critical for pancreatic β-cell viability and function through regulation in insulin signaling, actin dynamics, and granule trafficking. [ABSTRACT FROM AUTHOR]

Objective: The reversible attachment of small ubiquitin-like modifier (SUMO) proteins controls target localization and function. We examined an acute role for the SUMOylation pathway in downstream events mediating insulin secretion.Research Design and Methods: We studied islets and β-cells from mice and human donors, as well as INS-1 832/13 cells. Insulin secretion, intracellular Ca(2+), and β-cell exocytosis were monitored after manipulation of the SUMOylation machinery. Granule localization was imaged by total internal reflection fluorescence and electron microscopy; immunoprecipitation and Western blotting were used to examine the soluble NSF attachment receptor (SNARE) complex formation and SUMO1 interaction with synaptotagmin VII.Results: SUMO1 impairs glucose-stimulated insulin secretion by blunting the β-cell exocytotic response to Ca(2+). The effect of SUMO1 to impair insulin secretion and β-cell exocytosis is rapid and does not require altered gene expression or insulin content, is downstream of granule docking at the plasma membrane, and is dependent on SUMO-conjugation because the deSUMOylating enzyme, sentrin/SUMO-specific protease (SENP)-1, rescues exocytosis. SUMO1 coimmunoprecipitates with the Ca(2+) sensor synaptotagmin VII, and this is transiently lost upon glucose stimulation. SENP1 overexpression also disrupts the association of SUMO1 with synaptotagmin VII and mimics the effect of glucose to enhance exocytosis. Conversely, SENP1 knockdown impairs exocytosis at stimulatory glucose levels and blunts glucose-dependent insulin secretion from mouse and human islets.Conclusions: SUMOylation acutely regulates insulin secretion by the direct and reversible inhibition of β-cell exocytosis in response to intracellular Ca(2+) elevation. The SUMO protease, SENP1, is required for glucose-dependent insulin secretion. [ABSTRACT FROM AUTHOR]

Objective: The sodium-calcium exchanger isoform 1 (NCX1) regulates cytoplasmic calcium (Ca(2+)(c)) required for insulin secretion in beta-cells. NCX1 is alternatively spliced, resulting in the expression of splice variants in different tissues such as NCX1.3 and -1.7 in beta-cells. As pharmacological inhibitors of NCX1 splice variants are in development, the pharmacological profile of beta-cell NCX1.3 and -1.7 and the cellular effects of NCX1 inhibition were investigated.Research Design and Methods: The patch-clamp technique was used to examine the pharmacological profile of the NCX1 inhibitor KB-R7943 on recombinant NCX1.3 and -1.7 activity. Ca(2+) imaging and membrane capacitance were used to assess the effects of KB-R7943 on Ca(2+)(c) and insulin secretion in mouse and human beta-cells and islets.Results: NCX1.3 and -1.7 calcium extrusion (forward-mode) activity was approximately 16-fold more sensitive to KB-R7943 inhibition compared with cardiac NCX1.1 (IC(50s) = 2.9 and 2.4 vs. 43.0 micromol/l, respectively). In single mouse/human beta-cells, 1 micromol/l KB-R7943 increased insulin granule exocytosis but was without effect on alpha-cell glucagon granule exocytosis. KB-R7943 also augmented sulfonylurea and glucose-stimulated Ca(2+)(c) levels and insulin secretion in mouse and human islets, although KB-R7943 was without effect under nonstimulated conditions.Conclusions: Islet NCX1 splice variants display a markedly greater sensitivity to pharmacological inhibition than the cardiac NCX1.1 splice variant. NCX1 inhibition resulted in glucose-dependent increases in Ca(2+)(c) and insulin secretion in mouse and human islets. Thus, we identify beta-cell NCX1 splice variants as targets for the development of novel glucose-sensitive insulinotropic drugs for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Phosphatidylinositol 3-OH kinase (PI3K) has a long-recognized role in beta-cell mass regulation and gene transcription and is implicated in the modulation of insulin secretion. The role of nontyrosine kinase receptor-activated PI3K isoforms is largely unexplored. We therefore investigated the role of the G-protein-coupled PI3Kgamma and its catalytic subunit p110gamma in the regulation of insulin granule recruitment and exocytosis.Research Design and Methods: The expression of p110gamma was knocked down by small-interfering RNA, and p110gamma activity was selectively inhibited with AS605240 (40 nmol/l). Exocytosis and granule recruitment was monitored by islet perifusion, whole-cell capacitance, total internal reflection fluorescence microscopy, and electron microscopy in INS-1 and human beta-cells. Cortical F-actin was examined in INS-1 cells and human islets and in mouse beta-cells lacking the phosphatase and tensin homolog (PTEN).Results: Knockdown or inhibition of p110gamma markedly blunted depolarization-induced insulin secretion and exocytosis and ablated the exocytotic response to direct Ca(2+) infusion. This resulted from reduced granule localization to the plasma membrane and was associated with increased cortical F-actin. Inhibition of p110gamma had no effect on F-actin in beta-cells lacking PTEN. Finally, the effect of p110gamma inhibition on granule localization and exocytosis could be rapidly reversed by agents that promote actin depolymerization.Conclusions: The G-protein-coupled PI3Kgamma is an important determinant of secretory granule trafficking to the plasma membrane, at least in part through the negative regulation of cortical F-actin. Thus, p110gamma activity plays an important role in maintaining a membrane-docked, readily releasable pool of secretory granules in insulinoma and human beta-cells. [ABSTRACT FROM AUTHOR]

BackgroundSelf-management education for cardiopulmonary diseases is primarily provided through time-limited, face-to-face programs, with access limited to a small percentage of patients. Telecommunication tools will increasingly be an important component of future health care delivery. ObjectiveThe purpose of this study was to describe the patterns of technology use in patients attending a cardiopulmonary clinic in an academic medical center. MethodsA prevalence survey was developed to collect data on participant demographics (age in years, sex, and socioeconomic status); access to computers, Internet, and mobile phones; and use of current online health support sites or programs. Surveys were offered by reception staff to all patients attending the outpatient clinic. ResultsA total of 123 surveys were collected between March and April 2014. Technological devices were a pervasive part of everyday life with respondents engaged in regular computer (102/123, 82.9%), mobile telephone (115/117, 98.3%), and Internet (104/121, 86.0%) use. Emailing (101/121, 83.4%), researching and reading news articles (93/121, 76.9%), social media (71/121, 58.7%), and day-to-day activities (65/121, 53.7%) were the most common telecommunication activities. The majority of respondents reported that access to health support programs and assistance through the Internet (82/111, 73.9%) would be of use, with benefits reported as better understanding of health information (16/111, 22.5%), avoidance of difficult travel requirements and time-consuming face-to-face appointments (13/111, 18.3%), convenient and easily accessible help and information (12/111, 16.9%), and access to peer support and sharing (9/111, 12.7%). The majority of patients did not have concerns over participating in the online environment (87/111, 78.4%); the few concerns noted related to privacy and security (10/15), information accuracy (2/15), and computer literacy and access (2/15). ConclusionsChronic disease burden and long-term self-management tasks provide a compelling argument for accessible and convenient avenues to obtaining ongoing treatment and peer support. Online access to health support programs and assistance was reported as useful and perceived as providing convenient, timely, and easily accessible health support and information. Distance from the health care facility and a lack of information provision through traditional health sources were both barriers and enablers to telehealth. This is particularly important in the context of a cardiopulmonary clinic that attracts patients from a large geographical area, and in patients who are most likely to have high health care utilization needs in the future. Telecommunication interfaces will be an increasingly important adjunct to traditional forms of health care delivery.