Alterations in pancreatic ß cell function and Trypanosoma cruzi infection: evidence from human and animal studies.

The parasite Trypanosoma cruzi causes a persistent infection, Chagas disease, affecting millions of persons in endemic areas of Latin America. As a result of immigration, this disease has now been diagnosed in non-endemic areas worldwide. Although, the heart and gastrointestinal tract are the most studied, the insulin-secreting ß cell of the endocrine pancreas is also a target of infection. In this review, we summarize available clinical and laboratory evidence to determine whether T. cruzi-infection-mediated changes of ß cell function is likely to contribute to the development of hyperglycemia and diabetes. Our literature survey indicates that T. cruzi infection of humans and of experimental animals relates to altered secretory behavior of ß cells. The mechanistic basis of these observations appears to be a change in stimulus-secretion pathway function rather than the loss of insulin-producing ß cells. Whether this attenuated insulin release ultimately contributes to the pathogenesis of diabetes in human Chagas disease, however, remains to be determined. Since the etiologies of diabetes are multifactorial including genetic and lifestyle factors, the use of cell- and animal-based investigations, allowing direct manipulation of these factors, are important tools in testing if reduced insulin secretion has a causal influence on diabetes in the setting of Chagas disease. Long-term clinical investigations will be required to investigate this link in humans.

Dental Support Organizations.

The Association of Dental Support Organizations is a recently formed association of 33 companies representing a range of management and support services for dental practices. These organizations do not engage in the practice of dentistry, although in some cases they operate as holding companies for practices that do, thus separating the legal responsibility of providing treatment from the management and flow of funds. This report summarizes some of the recent trends in oral health care and dentists' practice patterns that are prompting the increased prevalence of this model. The general functioning of the DSO model is described, including some common variations, and the core values of ADSO are featured.

Blood Glucose Alterations and Continuous Glucose Monitoring in Centrifuge-Simulated Spaceflight.

INTRODUCTION: Sympathetic stimulation is known to be associated with transient alterations of blood glucose (BG) concentration; spaceflight acceleration may be similarly associated with alterations of BG, potentially posing a risk to diabetic individuals engaging in future spaceflight activities. Despite prior studies demonstrating diabetic subjects' tolerance to centrifuge-simulated spaceflight, data are lacking regarding blood glucose response to hypergravity. It remains unclear whether hypergravity or associated physiological response may pose a risk to diabetics. Continuous glucose monitors (CGM) offer a means of noninvasive glucose monitoring and may be useful in spaceflight and analog environments. Here, we describe the results of continuous glucose monitoring during centrifuge-simulated spaceflight.METHODS: Subjects participated in 1-5 centrifuge-simulated spaceflight profiles (maximum +4.0 Gz, +6.0 Gx, 6.1 G resultant). Data collection included heart rate, blood pressure, electrocardiogram, continuous glucose via CGM, intermittent fingerstick BG, and postrun questionnaires regarding symptoms related to hypergravity exposure.RESULTS: CGM data were collected from 26 subjects, including 4 diabetics. While diabetic subjects had significantly higher BG compared to nondiabetics, this was not associated with any difference in symptoms or tolerance. Transient hypergravity-associated CGM glucose alterations did not affect tolerance of the centrifuge experience. CGM data were found to be reliable with occasional exceptions, including four instances of false critical low glucose alarms.DISCUSSION: While further study is necessary to better characterize CGM fidelity during hypergravity and other spaceflight-related stressors, CGM may be a feasible option for spaceflight and analog settings. As in prior studies, individuals with well-controlled diabetes appear able to tolerate the accelerations anticipated for commercial spaceflight.Ong KM, Rossitto JJ, Ray K, Dufurrena QA, Blue RS. Blood glucose alterations and continuous glucose monitoring in centrifuge-simulated spaceflight. Aerosp Med Hum Perform. 2022; 93(9):688-695.

AI-Driven Transformation of Dental Benefits.

2021 is shaping up to be the year of artificial intelligence (AI) for the dental industry. Not only are providers adopting AI at a rapid pace, payers are tapping this technology to automate their claims review operations and reduce friction in provider interactions. In part three of this six-part dental AI series, the authors offer their view from the frontlines of dental claims processing and the promising future impact of AI. Representing clinical and business viewpoints, the authors draw on experience working at and with some of the largest dental payers in the country. This article presents a forward-looking perspective on the potential of dental AI to improve payer-provider relations, streamline claims review, and ultimately provide an improved patient experience.

Feasibility and Clinical Implications of Remotely Guided Ultrasound Examinations.

BACKGROUND: Remotely guided ultrasound (US) examinations carried out by nonmedical personnel (novices) have been shown to produce clinically useful examinations, at least in small pilot studies. Comparison of the quality of such exams to those carried out by trained medical professionals is lacking in the literature. This study compared the objective quality and clinical utility of cardiac and pulmonary US examinations carried out by novices and trained physicians.METHODS: Cardiac and pulmonary US examinations were carried out by novices under remote guidance by an US expert and independently by US trained physicians. Exams were blindly evaluated by US experts for both a task-based objective score as well as a subjective assessment of clinical utility.RESULTS: Participating in the study were 16 novices and 9 physicians. Novices took longer to complete the US exams (median 641.5 s vs. 256 s). For the objective component, novices scored higher in exams evaluating for pneumothorax (100% vs. 87.5%). For the subjective component, novices more often obtained clinically useful exams in the assessment of cardiac regional wall motion abnormalities (56.3% vs. 11.1%). No other comparisons yielded statistically significant differences between the two groups. Both groups had generally higher scores for pulmonary examinations compared to cardiac. There was variability in the quality of exams carried out by novices depending on their expert guide.CONCLUSION: Remotely guided novices are able to carry out cardiac and pulmonary US examinations with similar, if not better, technical proficiency and clinical utility as US trained physicians, though they take longer to do so.Dufurrena Q, Ullah KI, Taub E, Leszczuk C, Ahmad S. Feasibility and clinical implications of remotely guided ultrasound examinations. Aerosp Med Hum Perform. 2020; 91(7):592-596.

Kalirin/Trio Rho GDP/GTP exchange factors regulate proinsulin and insulin secretion.

Key features for progression to pancreatic ß-cell failure and disease are loss of glucose responsiveness and an increased ratio of secreted proinsulin to insulin. Proinsulin and insulin are stored in secretory granules (SGs) and the fine-tuning of hormone output requires signal mediated recruitment of select SG populations according to intracellular location and age. The GTPase Rac1 coordinates multiple signaling pathways that specify SG release and Rac1 activity is controlled in part by GDP/GTP exchange factors (GEFs). To explore the function of two large multidomain GEFs, Kalirin and Trio in ß-cells, we manipulated their Rac1-specific GEF1 domain activity by using small molecule inhibitors and by genetically ablating Kalirin. We examined age related secretory granule behavior employing radiolabeling protocols. Loss of Kalirin/Trio function attenuated radioactive proinsulin release by reducing constitutive-like secretion and exocytosis of 2-hour old granules. At later chase times or at steady state, Kalirin/Trio manipulations decreased glucose stimulated insulin output. Finally, use of a Rac1 FRET biosensor with cultured ß-cell lines, demonstrated that Kalirin/Trio GEF1 activity was required for normal rearrangement of Rac1 to the plasma membrane in response to glucose. Rac1 activation can be evoked by both glucose metabolism and signaling through the incretin glucagon-like peptide 1 (GLP-1) receptor. GLP-1 addition restored Rac1 localization/activity and insulin secretion in the absence of Kalirin, thereby assigning Kalirin's participation to stimulatory glucose signaling.