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Antibodies are critical tools for research into extracellular vesicles (EVs) and other extracellular nanoparticles (ENPs), where they can be used for their identification, characterization, and isolation. However, the lack of a centralized antibody platform where researchers can share validation results thus minimizing wasted personnel time and reagents, has been a significant obstacle. Moreover, because the performance of antibodies varies among assay types and conditions, detailed information on assay variables and protocols is also of value. To facilitate sharing of results on antibodies that are relevant to EV/ENP research, the EV Antibody Database has been developed by the investigators of the Extracellular RNA Communication Consortium (ERCC). Hosted by the ExRNA Portal (https://exrna.org/resources/evabdb/), this interactive database aggregates and shares results from antibodies that have been tested by research groups in the EV/ENP field. Currently, the EV Antibody Database includes modules for antibodies tested for western Blot, EV Flow Cytometry, and EV Sandwich Assays, and holds 110 records contributed by 6 laboratories from the ERCC. Detailed information on antibody sources, assay conditions, and results is provided, including negative results. We encourage ongoing expert input and community feedback to enhance the databases utility, making it a valuable resource for comprehensive validation data on antibodies and protocols in EV biology.

BackgroundYouth experiencing homelessness are more likely than housed youth to experience premature death, suicide, drug overdose, pregnancy, substance use, and mental illness. Yet while youth experiencing homelessness are 6 to 12 times more likely to become infected with HIV than housed youth, with HIV prevalence as high as 16%, many do not access the prevention services they need. Despite adversities, youth experiencing homelessness are interested in health promotion programs, can be recruited and retained in interventions and research studies, and demonstrate improved outcomes when programs are tailored and relevant to them. ObjectiveThe study aims to compare the efficacy of a nurse case management HIV prevention and care intervention, titled Come As You Are, with that of usual care among youth experiencing homelessness aged 16 to 25 years. MethodsThe study is designed as a 2-armed randomized wait-list controlled trial. Participants (n=450) will be recruited and followed up for 9 months after the intervention for a total study period of 12 months. Come As You Are combines nurse case management with a smartphone-based daily ecological momentary assessment to develop participant-driven HIV prevention behavioral goals that can be monitored in real-time. Youth in the city of Houston, Texas will be recruited from drop-in centers, shelters, street outreach programs, youth-serving organizations, and clinics. ResultsInstitutional review board approval (Committee for the Protection of Human Subjects, University of Texas Health Science Center at Houston) was obtained in November 2018. The first participant was enrolled in November 2019. Data collection is ongoing. To date, 123 participants have consented to participate in the study, 89 have been enrolled, and 15 have completed their final follow-up. ConclusionsThere is a paucity of HIV prevention research regarding youth experiencing homelessness. Novel and scalable interventions that address the full continuum of behavioral and biomedical HIV prevention are needed. This study will determine whether a personalized and mobile HIV prevention approach can reduce HIV risk among a hard-to-reach, transient population of youth at high risk. International Registered Report Identifier (IRRID)DERR1-10.2196/26716

BackgroundParents use apps to access information on child health, but there are no standards for providing evidence-based advice, support, and information. Well-developed apps that promote appropriate infant feeding and play can support healthy growth and development. A 2015 systematic assessment of smartphone apps in Australia about infant feeding and play found that most apps had minimal information, with poor readability and app quality. ObjectiveThis study aimed to systematically evaluate the information and quality of smartphone apps providing information on breastfeeding, formula feeding, introducing solids, or infant play for consumers. MethodsThe Google Play store and Apple App Store were searched for free and paid Android and iPhone Operating System (iOS) apps using keywords for infant feeding, breastfeeding, formula feeding, and tummy time. The apps were evaluated between September 2018 and January 2019 for information content based on Australian guidelines, app quality using the 5-point Mobile App Rating Scale, readability, and suitability of health information. ResultsA total of 2196 unique apps were found and screened. Overall, 47 apps were evaluated, totaling 59 evaluations for apps across both the Android and iOS platforms. In all, 11 apps had affiliations to universities and health services as app developers, writers, or editors. Furthermore, 33 apps were commercially developed. The information contained within the apps was poor: 64% (38/59) of the evaluations found no or low coverage of information found in the Australian guidelines on infant feeding and activity, and 53% (31/59) of the evaluations found incomplete or incorrect information with regard to the depth of information provided. Subjective app assessment by health care practitioners on whether they would use, purchase, or recommend the app ranged from poor to acceptable (median 2.50). Objective assessment of the apps’ engagement, functionality, aesthetics, and information was scored as acceptable (median 3.63). The median readability score for the apps was at the American Grade 8 reading level. The suitability of health information was rated superior or adequate for content, reading demand, layout, and interaction with the readers. ConclusionsThe quality of smartphone apps on infant feeding and activity was moderate based on the objective measurements of engagement, functionality, aesthetics, and information from a reliable source. The overall quality of information on infant feeding and activity was poor, indicated by low coverage of topics and incomplete or partially complete information. The key areas for improvement involved providing evidence-based information consistent with the Australian National Health and Medical Research Council’s Infant Feeding Guidelines. Apps supported and developed by health care professionals with adequate health service funding can ensure that parents are provided with credible and reliable resources.

Soil microbiomes are heterogeneous, complex microbial communities. Metagenomic analysis is generating vast amounts of data, creating immense challenges in sequence assembly and analysis. Although advances in technology have resulted in the ability to easily collect large amounts of sequence data, soil samples containing thousands of unique taxa are often poorly characterized. These challenges reduce the usefulness of genome-resolved metagenomic (GRM) analysis seen in other fields of microbiology, such as the creation of high quality metagenomic assembled genomes and the adoption of genome scale modeling approaches. The absence of these resources restricts the scale of future research, limiting hypothesis generation and the predictive modeling of microbial communities. Creating publicly available databases of soil MAGs, similar to databases produced for other microbiomes, has the potential to transform scientific insights about soil microbiomes without requiring the computational resources and domain expertise for assembly and binning.

Higher education outreach and engagement often occurs through student volunteering. Student organizations are one understudied and undertapped mechanism that facilitates such connections. We examined the experience of student leaders of student organizations that promoted volunteerism among their members. The mixed-methods study included a survey (n = 26) and follow-up interviews (n = 5). We found that participants' organizations were highly involved in the community and that participants gained valuable leadership skills in this role. We also found that participants had relatively little insight concerning the community partners' experience of the collaboration. We identified sampling as a unique challenge for this theoretical population and, in the discussion, provide considerations and recommendations for future scholars.

Positive outcomes for students have motivated educators to identify effective strategies for advancing diversity, equity, and inclusion (DEI) in people with intellectual disability (ID), a minoritized population often excluded from DEI efforts. The current study investigated undergraduate student attitudes toward ID and compared changes in attitudes following participation in one of two community-engaged programs alongside adults with ID. Findings indicate both programs were effective in changing all three components of students' attitudes: affect, cognition, and behaviors.

Although the role of RNA binding proteins (RBPs) in extracellular RNA (exRNA) biology is well established, their exRNA cargo and distribution across biofluids are largely unknown. To address this gap, we extend the exRNA Atlas resource by mapping exRNAs carried by extracellular RBPs (exRBPs). This map was developed through an integrative analysis of ENCODE enhanced crosslinking and immunoprecipitation (eCLIP) data (150 RBPs) and human exRNA profiles (6,930 samples). Computational analysis and experimental validation identified exRBPs in plasma, serum, saliva, urine, cerebrospinal fluid, and cell-culture-conditioned medium. exRBPs carry exRNA transcripts from small non-coding RNA biotypes, including microRNA (miRNA), piRNA, tRNA, small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), Y RNA, and lncRNA, as well as protein-coding mRNA fragments. Computational deconvolution of exRBP RNA cargo reveals associations of exRBPs with extracellular vesicles, lipoproteins, and ribonucleoproteins across human biofluids. Overall, we mapped the distribution of exRBPs across human biofluids, presenting a resource for the community.

BackgroundBy 2034, the number of US individuals with diabetes is predicted to increase from 23.7 to 44.1 million, and annual diabetes-related spending is expected to grow from $113 to $336 billion. Up to 55% of US Hispanics born in the year 2000 are expected to develop diabetes during their lifetime. Poor healthcare access and cultural barriers prevent optimal care, adherence, and clinical benefit, placing Hispanics at disproportionate risk for costly diabetes complications. Mobile technology is increasingly prevalent in all populations and can circumvent such barriers. Our group developed Dulce Digital, an educational text messaging program that improved glycemic control relative to usual care. Dulce Digital-Me (DD-Me) has been tailored to a participant's individual needs with a greater focus on health behavior change.MethodsThis is a three-arm, parallel group, randomized trial with equal allocation ratio enrolling Hispanic adults with low income and poorly managed type 2 diabetes (N = 414) from a San Diego County Federally Qualified Health Center. Participants are randomized to receive Dulce Digital, Dulce Digital-Me-Automated, or Dulce Digital-Me-Telephonic. The DD-Me groups include Dulce Digital components plus personalized goal-setting and feedback delivered via algorithm-driven automated text messaging (DD-Me-Automated) or by the care team health coach (DD-Me-Telephonic) over a 12-month follow-up period. The study will examine the comparative effectiveness of the three groups in improving diabetes clinical control [HbA1c, primary outcome; low-density lipoprotein cholesterol (LDL-C), and systolic blood pressure (SBP)] and patient-provider communication and patient adherence (i.e., medication, self-management tasks) over 12 months and will examine cost-effectiveness of the three interventions.DiscussionOur comparative evaluation of three mHealth approaches will elucidate how technology can be integrated most effectively and efficiently within primary care-based chronic care model approaches to reduce diabetes disparities in Hispanics and will assess two modes of personalized messaging delivery (i.e., automated messaging vs. telephonic by health coach) to inform cost and acceptability.Trial registrationNCT03130699-All items from the WHO Trial Registration data set are available in https://clinicaltrials.gov/ct2/show/study/NCT03130699 .

The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013-2018), Phase 2 of the program (ERCC2, 2019-2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2's current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Islet autoimmunity may contribute to β-cell dysfunction in type 2 diabetes (T2D). Its prevalence and clinical significance have not been rigorously determined. In this ancillary study to the Glycemia Reduction Approaches in Diabetes-A Comparative Effectiveness (GRADE) Study, we investigated the prevalence of cellular and humoral islet autoimmunity in patients with T2D duration 4·0±3·0 y, HbA1c 7·5±0·5% on metformin alone. We measured T cell autoreactivity against islet proteins, islet autoantibodies against GAD65, IA2, ZnT8, and β-cell function. Cellular islet autoimmunity was present in 41·3%, humoral islet autoimmunity in 13·5%, and both in 5·3%. β-cell function calculated as iAUC-CG and ΔC-peptide(0- 30)/Δglucose(0-30) from an oral glucose tolerance test was lower among T cell-positives (T+) than T cell-negatives (T-) using two different adjustments for insulin sensitivity (iAUC-CG: 13·2% [95% CI 0·3, 24·4%] or 11·4% [95% CI 0·4, 21·2%] lower; ΔC-peptide(0-30)/Δglucose(0-30)) 19% [95% CI 3·1, 32·3%] or 17·7% [95% CI 2·6, 30·5%] lower). T+ patients had 17% higher HbA1c (95% CI 0·07, 0·28) and 7·7 mg/dL higher fasting plasma glucose levels (95% CI 0·2,15·3) than T- patients. We conclude that islet autoimmunity is much more prevalent in T2D patients than previously reported. T cell-mediated autoimmunity is associated with diminished β-cell function and worse glycemic control.

The Model Aquatic Health Code (MAHC) provides voluntary guidelines that reduce the risk of disease, injury, and drowning at aquatic facilities. Its use varies across state and local jurisdictions. We sought to develop a swimming pool safety grading system in a metropolitan area by applying the MAHC to city swimming pool inspection data. We conducted a cross-sectional study that involved routine inspections of commercial aquatic venues in Houston, Texas, during 2016. We calculated the overall percentage of items in compliance with the MAHC. Next, we graded swimming pools by assigning points based on the MAHC to corresponding swimming pool violations and assigning a letter grade: A = 95-100%; B = 85-94%; C = 75-84%; and fail (F) = There were 3,100 commercial aquatic venues in Houston that were inspected. Venues were graded for safety as: A = 40.2%; B = 0.5%; C = 0%; and F = 59.3%. Swimming pool enclosure violations were most frequent (18.0%). Most swimming pools, irrespective of the degree of pool safety violations, were located in the Southwest section of Houston. Overall, the MAHC can be applied to grade swimming pool safety in jurisdictions where it has not been adopted. The degree of safety violations can be spatially demonstrated to inform injury-prevention measures., Introduction Drowning is the leading cause of unintentional injury death in U.S. children 1-4 years (National Center for Injury Prevention and Control, 2018). In children, swimming pools account for 33% [...]

ObjectiveType 2 diabetes is a risk factor for cognitive impairment. We examined the relation of glycemia, lipids, blood pressure (BP), hypertension history, and statin use with cognition in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).Research design and methodsCross-sectional analyses from GRADE at baseline examined the association of glycemia (hemoglobin A1c [HbA1c]), LDL, systolic BP (SBP) and diastolic BP (DBP), hypertension history, and statin use with cognition assessed by the Spanish English Verbal Learning Test, letter and animal fluency tests, and Digit Symbol Substitution Test (DSST).ResultsAmong 5,047 GRADE participants, 5,018 (99.4%) completed cognitive assessments. Their mean age was 56.7 ± 10.0 years, and 36.4% were women. Mean diabetes duration was 4.0 ± 2.7 years. HbA1c was not related to cognition. Higher LDL was related to modestly worse DSST scores, whereas statin use was related to modestly better DSST scores. SBP between 120 and 139 mmHg and DBP between 80 and 89 mmHg were related to modestly better DSST scores. Hypertension history was not related to cognition.ConclusionsIn people with type 2 diabetes of a mean duration of

This article provides an overview of how the surveillance systems that are being increasingly deployed against K–12 public school students and their families operate, highlighting the ways in whic they function as a covert form of school policing. In doing so, we ground our analysis in the decades-long work of organizers and activists to reimagine the learning environment, or “school climate,” and heed the warnings of organizers in the broader movement for prison-industrial complex abolition to reject systems of racial and social control and surveillance, including those that purport to promote safety and well-being but “manifest as punishment for those experiencing them.” Next, we discuss the civil rights and civil liberties concerns these surveillance systems illuminate, with a focus on the unique and disproportionate harms they inflict on marginalized students, including students of color and LGBTQ students. We conclude by highlighting the legal conflicts that arise when public schools require the use of these technologies, providing recommendations on how California constitutional and statutory law can be leveraged to challenge the installment of the surveillance infrastructure in the K–12 educational context as the movement to end policing in schools carries on.

Student volunteers provide a valuable source of unpaid labor to nonprofit organizations, particularly organizations in college towns where students make up a significant portion of the population. Indeed, students may be the lifeblood for these organizations. However, students may also be a burden if organizations do not have the volunteer administration capacity to support volunteers, if students are unprepared for volunteer assignments, or if the availability of students does not match the organization's need. The purpose of this exploratory case study is to identify whether students were a burden to or the lifeblood of the voluntary sector in a college town. We surveyed 55 nonprofit leaders to identify their volunteer management capacity, experience of student volunteers (emphasizing the match between supply and demand), and their ideas for improvement. We found student volunteers comprise a significant percentage of their overall volunteer population and brought valuable skills and enthusiasm. However, we also found a mismatch between the demand for student volunteers and the supply of student volunteers, particularly as it relates to availability. We identified a number of recommendations to improve the overall service-learning experience. These findings are of interest to nonprofit organizations and educational institutions in college towns.

In a structure-function study of sulfatides that typically stimulate type II NKT cells, we made an unexpected discovery. We compared analogs with sphingosine or phytosphingosine chains and 24-carbon acyl chains with 0-1-2 double bonds (C or pC24:0, 24:1, or 24:2). C24:1 and C24:2 sulfatide presented by the CD1d monomer on plastic stimulated type II, not type I, NKT cell hybridomas, as expected. Unexpectedly, when presented by bone marrow- derived DCs (BMDCs), C24:2 reversed specificity to stimulate type I, not type II, NKT cell hybridomas, mimicking the corresponding [beta]-galactosylceramide ([beta]GalCer) without sulfate. C24:2 induced IFN-[gamma]-dependent immunoprotection against CT26 colon cancer lung metastases, skewed the cytokine profile, and activated conventional DC subset 1 cells (cDC1s). This was abrogated by blocking lysosomal processing with bafilomycin A1, or by sulfite blocking of arylsulfatase or deletion of this enyzme that cleaves off sulfate. Thus, C24:2 was unexpectedly processed in BMDCs from a type II to a type I NKT cell- stimulating ligand, promoting tumor immunity. We believe this is the first discovery showing that antigen processing of glycosylceramides alters the specificity for the target cell, reversing the glycolipid's function from stimulating type II NKT cells to stimulating type I NKT cells, thereby introducing protective functional activity in cancer. We also believe our study uncovers a new role for antigen processing that does not involve MHC loading but rather alteration of which type of cell is responding., Introduction The recent clinical success of checkpoint inhibitors, which manipulate T cell function and extend patient survival in many cases, provides strong motivation to treat cancer by modulating immunity. However, [...]

ObjectiveWe investigated sex and racial differences in insulin sensitivity, β-cell function, and glycated hemoglobin (HbA1c) and the associations with selected phenotypic characteristics.Research design and methodsThis is a cross-sectional analysis of baseline data from 3,108 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) participants. All had type 2 diabetes diagnosed

In the US, nearly 11% of adults were living with diagnosed diabetes in 2017, and significant type 2 diabetes (T2D) disparities are experienced by socioeconomically disadvantaged, racial/ethnic minority populations, including Hispanics. The standard 15-min primary care visit does not allow for the ongoing self-management support that is needed to meet the complex needs of individuals with diabetes. "Team-based" chronic care delivery is an alternative approach that supplements physician care with contact from allied health personnel in the primary care setting (e.g., medical assistants; MAs) who are specially trained to provide ongoing self-management support or "health coaching." While rigorous trials have shown MA health coaching to improve diabetes outcomes, less is known about if and how such a model can be integrated within real world, primary care clinic workflows. Medical Assistant Health Coaching for Type 2 Diabetes in Diverse Primary Care Settings - A Pragmatic, Cluster-Randomized Controlled Trial will address this gap. Specifically, this study compares MA health coaching versus usual care in improving diabetes clinical control among N = 600 at-risk adults with T2D, and is being conducted at four primary care clinics that are part of two health systems that serve large, ethnically/racially, and socioeconomically diverse populations in Southern California. Electronic medical records are used to identify eligible patients at both health systems, and to examine change in clinical control over one year in the overall sample. Changes in behavioral and psychosocial outcomes are being evaluated by telephone assessment in a subset (n = 300) of participants, and rigorous process and cost evaluations will assess potential for sustainability and scalability.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has been shown to increase levels of psychological distress among healthcare workers. Little is known, however, about specific positive and negative individual and organizational factors that affect the mental health of emergency physicians (EP) during COVID-19. Our objective was to assess these factors in a broad geographic sample of EPs in the United States.  Methods: We conducted an electronic, prospective, cross-sectional national survey of EPs from October 6–December 29, 2020. Measures assessed negative mental health outcomes (depression, anxiety, post-traumatic stress, and insomnia), positive work-related outcomes, and strategies used to cope with COVID-19. After preliminary analyses and internal reliability testing, we performed four separate three-stage hierarchical multiple regression analyses to examine individual and organizational predictive factors for psychological distress.  Results: Response rate was 50%, with 517 EPs completing the survey from 11 different sites. Overall, 85% of respondents reported negative psychological effects due to COVID-19. Participants reported feeling more stressed (31%), lonelier (26%), more anxious (25%), more irritable (24%) and sadder (17.5%). Prevalence of mental health conditions was 17% for depression, 13% for anxiety, 7.5% for post-traumatic stress disorder (PTSD), and 18% for insomnia. Regular exercise decreased from 69% to 56%, while daily alcohol use increased from 8% to 15%. Coping strategies of behavioral disengagement, self-blame, and venting were significant predictors of psychological distress, while humor and positive reframing were negatively associated with psychological distress.  Conclusion: Emergency physicians have experienced high levels of psychological distress during the COVID-19 pandemic. Those using avoidant coping strategies were most likely to experience depression, anxiety, insomnia, and PTSD, while humor and positive reframing were effective coping strategies.

Community-engaged research (CEnR) builds on the strengths of the Clinical and Translational Science Awards (CTSA) framework to address health in underserved and minority communities. There is a paucity of studies that identify the process from which trust develops in CEnR partnerships. This study responds to the need for empirical investigation of building and maintaining trust from a multistakeholder perspective. We conducted a multi-institutional pilot study using concept mapping with to better understand how trust, a critical outcome of CEnR partnerships, can act as "social capital." Concept mapping was used to collect data from the three stakeholder groups: community, health-care, and academic research partners across three CTSAs. Concept mapping is a mixed-methods approach that allows participants to brainstorm and identify factors that contribute to a concept and describe ways in which those factors relate to each other. This study offers important insights on developing an initial set of trust measures that can be used across CTSAs to understand differences and similarities in conceptualization of trust among key stakeholder groups, track changes in public trust in research, identify both positive and negative aspects of trust, identify characteristics that maintain trust, and inform the direction for future research.

ObjectiveWe evaluated the effect of optimizing metformin dosing on glycemia and body weight in type 2 diabetes.Research design and methodsThis was a prespecified analysis of 6,823 participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) taking metformin as the sole glucose-lowering drug who completed a 4- to 14-week (mean ± SD 7.9 ± 2.4) run-in in which metformin was adjusted to 2,000 mg/day or a maximally tolerated lower dose. Participants had type 2 diabetes for

IntroductionThe 2019 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Prostate Cancer Research: The Next Generation," was held 20 to 23 June, 2019, in Los Angeles, California.MethodsThe CHPCA Meeting is an annual conference held by the Prostate Cancer Foundation, that is uniquely structured to stimulate intense discussion surrounding topics most critical to accelerating prostate cancer research and the discovery of new life-extending treatments for patients. The 7th Annual CHPCA Meeting was attended by 86 investigators and concentrated on many of the most promising new treatment opportunities and next-generation research technologies.ResultsThe topics of focus at the meeting included: new treatment strategies and novel agents for targeted therapies and precision medicine, new treatment strategies that may synergize with checkpoint immunotherapy, next-generation technologies that visualize tumor microenvironment (TME) and molecular pathology in situ, multi-omics and tumor heterogeneity using single cells, 3D and TME models, and the role of extracellular vesicles in cancer and their potential as biomarkers.DiscussionThis meeting report provides a comprehensive summary of the talks and discussions held at the 2019 CHPCA Meeting, for the purpose of globally disseminating this knowledge and ultimately accelerating new treatments and diagnostics for patients with prostate cancer.

Background: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study has enrolled a racially and ethnically diverse population with type 2 diabetes, performed extensive phenotyping, and randomly assigned the participants to one of four second-line diabetes medications. The continuous glucose monitoring (CGM) substudy has been added to determine whether there are racial/ethnic differences in the relationship between average glucose (AG) and hemoglobin A1c (HbA1c). CGM will also be used to compare time in target range, glucose variability, and the frequency and duration of hypoglycemia across study groups. Methods: The observational CGM substudy will enroll up to 1800 of the 5047 GRADE study participants from the four treatment groups, including as many as 450 participants from each of 4 racial/ethnic minority groups to be compared: Hispanic White, non-Hispanic White, non-Hispanic African American, and non-Hispanic Other. CGM will be performed for 2 weeks in proximity to a GRADE annual visit, during which an oral glucose tolerance test will be performed and HbA1c and glycated albumin measured. Indicators of interindividual variation in red blood cell turnover, based on specialized erythrocyte measurements, will also be measured to explore the potential causes of interindividual HbA1c variations. Conclusions: The GRADE CGM substudy will provide new insights into whether differences exist in the relationship between HbA1c and AG among different racial/ethnic groups and whether glycemic profiles differ among frequently used diabetes medications and their potential clinical implications. Understanding such differences is important for clinical care and adjustment of diabetes medications in patients of different races or ethnicities.

Biological nanoparticles, including viruses and extracellular vesicles (EVs), are of interest to many fields of medicine as biomarkers and mediators of or treatments for disease. However, exosomes and small viruses fall below the detection limits of conventional flow cytometers due to the overlap of particle-associated scattered light signals with the detection of background instrument noise from diffusely scattered light. To identify, sort, and study distinct subsets of EVs and other nanoparticles, as individual particles, we developed nanoscale Fluorescence Analysis and Cytometric Sorting (nanoFACS) methods to maximise information and material that can be obtained with high speed, high resolution flow cytometers. This nanoFACS method requires analysis of the instrument background noise (herein defined as the "reference noise"). With these methods, we demonstrate detection of tumour cell-derived EVs with specific tumour antigens using both fluorescence and scattered light parameters. We further validated the performance of nanoFACS by sorting two distinct HIV strains to >95% purity and confirmed the viability (infectivity) and molecular specificity (specific cell tropism) of biological nanomaterials sorted with nanoFACS. This nanoFACS method provides a unique way to analyse and sort functional EV- and viral-subsets with preservation of vesicular structure, surface protein specificity and RNA cargo activity.