Background: Children and adolescents with diabetes may use data from continuous glucose monitoring (CGM) in management decisions and may share it in real time with others involved in their care. CGM ...systems from Dexcom (San Diego, CA) allow real-time sharing with up to 5 remote “Followers.” We explored associations between the presence of Follower(s), device utilization, and glycemic parameters.
Methods: We used estimated glucose values (EGVs) from a convenience sample of 25,000 CGM users of Dexcom's G5 or G6 system ages 2-24 that were uploaded between 5/1/2018 and 9/30/2018 by an app that allows for sharing. The number of Follower(s) was established on 8/10/2018. Each day with ≥1 valid EGV was counted as a day of device usage. Comparisons were made with two-sided Welch’s t-tests.
Results: Overall, 90.0% of the population used the sharing feature and had ≥1 Follower; the mean numbers of Followers for patients ages <8, 8-14, and 15-24 years were 2.73, 2.69, and 1.83, respectively. In all 3 age groups, having a Follower was associated with lower mean EGVs, more EGVs in the 70-180 mg/dL range, fewer EGVs in hypo- or hyperglycemia, and more device utilization (Table).
Conclusions: Real-time sharing and following of CGM data may encourage consistent device usage and facilitate timely interventions by parents of young children with diabetes or improve self-care behaviors among adolescents and young adults with diabetes.
Disclosure
A. Parker: Employee; Self; Dexcom, Inc. M. Derdzinski: Employee; Self; Dexcom, Inc. S. Puhr: None. J. Welsh: Employee; Self; Dexcom, Inc. T.C. Walker: Employee; Self; Dexcom, Inc. A. Jimenez: Employee; Self; Dexcom, Inc.
Background: The Dexcom G6 continuous glucose monitoring (CGM) system differs from Dexcom’s earlier G5 system in that G6 includes a predictive “Urgent Low Soon” (ULS) alert that notifies users when an ...estimated glucose value (EGV) ≤55 mg/dL is predicted in the next 20 minutes. The effect of the ULS alert on the distribution of EGVs was evaluated in the context of traditional threshold alerts.
Methods: We identified individuals who had used G5 and transitioned to G6 between 5/1/2018 and 10/31/2018. Evaluable data were from a subset of 4083 users who had maintained low threshold alerts at either 70 or 80 mg/dL, who used a smartphone to view and upload ≥30 days of data from each system, and who maintained the G6 ULS alert in its default (enabled) state.
Results: Use of the 80 mg/dL low threshold alert was associated with higher mean EGVs, less hypoglycemia, and more hyperglycemia than use of the 70 mg/dL low threshold alert (Table). Over 97% of the G6 systems were used with the ULS feature enabled, and the ULS alert was activated less than once daily. At either low threshold setting, the transition to G6 was associated with reductions in hypoglycemia (<55 and <70 mg/dL) and severe hyperglycemia (>250 mg/dL).
Conclusions: When used in the context of traditional low threshold alerts, the predictive ULS alert may enable timely and appropriate interventions that contribute to further reductions in hypoglycemia among CGM-experienced users.
Disclosure
M. Derdzinski: Employee; Self; Dexcom, Inc. J. Welsh: Employee; Self; Dexcom, Inc. S. Puhr: None. T.C. Walker: Employee; Self; Dexcom, Inc. A. Parker: Employee; Self; Dexcom, Inc. A. Jimenez: Employee; Self; Dexcom, Inc.
Background
Those caring for children and adolescents with diabetes often use glucose concentration and trending information in management decisions. Some continuous glucose monitoring (CGM) systems ...offer real-time sharing and monitoring capabilities through mobile apps carried by the person with diabetes and the caregiver(s), respectively. Few large studies have explored real-world associations between sharing and following, CGM utilization, and glycemic outcomes.
Methods
We performed a retrospective evaluation of device usage and glycemic control in 15,000 youth ranging in age from 2 to 18 years by analyzing anonymized data that had been uploaded with a mobile app that provides optional sharing. The presence or absence of a real-time monitor (a “Follower”) was established on 15 June 2018. Each day with ≥ 1 uploaded glucose values was counted as a day of device usage. Between-group glucose comparisons were made with two-sided Welch’s
t
tests.
Results
Overall, 94.8% of the population used the sharing feature and had at least one Follower. The mean numbers of Followers for patients aged 2–5, 6–12, and 13–18 years were 2.8, 2.8, and 2.4, respectively. In all three age categories, the presence of at least one Follower was associated with lower mean glucose values, more glucose values in the 70- to 180-mg/dL range, correspondingly fewer glucose values representing hypoglycemia and hyperglycemia, and significantly more device utilization.
Conclusion
Real-time sharing and following of CGM data are associated with improved device utilization and glycemic parameters. The observed association suggests either more timely interventions or higher levels of engagement among the caregivers or the youth with diabetes.
Funding
Dexcom, Inc.
Background
T‐cell activation is associated with an adverse outcome in COVID‐19, but whether T‐cell activation and exhaustion relate to persistent respiratory dysfunction and death is unknown.
...Objectives
To investigate whether T‐cell activation and exhaustion persist and are associated with prolonged respiratory dysfunction and death after hospitalization for COVID‐19.
Methods
Plasma and serum from two Norwegian cohorts of hospitalized patients with COVID‐19 (n = 414) were analyzed for soluble (s) markers of T‐cell activation (sCD25) and exhaustion (sTim‐3) during hospitalization and follow‐up.
Results
Both markers were strongly associated with acute respiratory failure, but only sTim‐3 was independently associated with 60‐day mortality. Levels of sTim‐3 remained elevated 3 and 12 months after hospitalization and were associated with pulmonary radiological pathology after 3 months.
Conclusion
Our findings suggest prolonged T‐cell exhaustion is an important immunological sequela, potentially related to long‐term outcomes after severe COVID‐19.
Silica nanoparticles (SiNPs) released during the burning of sugarcane have been postulated to have a role in chronic kidney disease of unknown etiology. We tested the hypothesis that pristine SiNPs ...of the size present in sugarcane might cause chronic kidney injury when administered through the lung in rats. We administered 200- or 300-nm amorphous SiNPs twice weekly (4 mg/dose), or vehicle by oropharyngeal aspiration for 13 wk to rats followed by euthanasia after an additional 13 wk (26 wk total). Tissues were evaluated for the presence of SiNPs and evidence of histological injury. Both sizes of SiNPs caused kidney damage, with early tubular injury and inflammation (at
) that continued to inflammation and chronic fibrosis at
despite discontinuation of the SiNP administration. Both sizes of SiNPs caused local inflammation in the lung and kidney and were detected in the serum and urine at
, and the 200-nm particles were also localized to the kidney with no evidence of retention of the 300-nm particles. At
, there was some clearance of the 200-nm silica from the kidneys, and urinary levels of SiNPs were reduced but still significant in both 200- and 300 nm-exposed rats. In conclusion, inhaled SiNPs cause chronic kidney injury that progresses despite stopping the SiNP administration. These findings support the hypothesis that human exposure to amorphous silica nanoparticles found in burned sugarcane fields could have a participatory role in chronic kidney disease of unknown etiology.
Inhalation of silica nanoparticles (SiNPs) released during the burning of sugarcane has been postulated to have a role in chronic kidney disease of unknown etiology (CKDu). We administered 200- and 300-nm amorphous SiNPs to rats by aspiration and observed kidney damage with tubular injury and inflammation that persisted even after stopping the SiNP exposure. These findings support the hypothesis that human exposure to SiNPs found in sugarcane ash could have a participatory role CKDu.
Proline is found in a cis conformation in proteins more often than other proteinogenic amino acids, where it influences structure and modulates function, being the focus of several high-resolution ...structural studies. However, until now, technical and methodological limitations have hampered the site-specific investigation of the conformational preferences of prolines present in poly proline (poly-P) homorepeats in their protein context. Here, we apply site-specific isotopic labeling to obtain high-resolution NMR data on the cis/trans equilibrium of prolines within the poly-P repeats of huntingtin exon 1, the causative agent of Huntington’s disease. Screening prolines in different positions in long (poly-P11) and short (poly-P3) poly-P tracts, we found that, while the first proline of poly-P tracts adopts similar levels of cis conformation as isolated prolines, a length-dependent reduced abundance of cis conformers is observed for terminal prolines. Interestingly, the cis isomer could not be detected in inner prolines, in line with percentages derived from a large database of proline-centered tripeptides extracted from crystallographic structures. These results suggest a strong cooperative effect within poly-Ps that enhances their stiffness by diminishing the stability of the cis conformation. This rigidity is key to rationalizing the protection toward aggregation that the poly-P tract confers to huntingtin. Furthermore, the study provides new avenues to probe the structural properties of poly-P tracts in protein design as scaffolds or nanoscale rulers.
We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear.
...In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69).
(i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset.
Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage.
South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).
Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease of unknown etiology (CKDu). However, while the administration of manufactured ...silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here we investigate whether sugarcane ash can induce CKD in rats.
. Sugarcane ash was administered for 13 weeks into the nares of rats (5 mg/day for 5d/week), and blood, urine and kidney tissues were collected at 13 weeks (at the end of ash administration) and in a separate group of rats at 24 weeks (11 weeks after stopping ash administration). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) measured.
. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver and spleen of rats. Mild proteinuria developed although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis, and tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker, LAMP-1, showed decreased staining in ash administered rats consistent with lysosomal activation.
. Sugarcane ash containing silica nanoparticles can cause CKD in rats.
The development of fluorescent proteins (FPs) has revolutionized biological imaging. FusionRed, a monomeric red FP (RFP), is known for its low cytotoxicity and correct localization of target fusion ...proteins in mammalian cells but is limited in application by low fluorescence brightness. We report a brighter variant of FusionRed, “FR-MQV,” which exhibits an extended fluorescence lifetime (2.8 ns), enhanced quantum yield (0.53), higher extinction coefficient (∼140 000 M–1 cm–1), increased radiative rate constant, and reduced nonradiative rate constant with respect to its precursor. The properties of FR-MQV derive from three mutationsM42Q, C159V, and the previously identified L175M. A structure-guided approach was used to identify and mutate candidate residues around the para-hydroxyphenyl and the acylimine sites of the chromophore. The C159V mutation was identified via lifetime-based flow cytometry screening of a library in which multiple residues adjacent to the para-hydroxyphenyl site of the chromophore were mutated. The M42Q mutation is located near the acylimine moiety of the chromophore and was discovered using site-directed mutagenesis guided by X-ray crystal structures. FR-MQV exhibits a 3.4-fold higher molecular brightness and a 5-fold increase in the cellular brightness in HeLa cells based on fluorescence-activated cell sorting (FACS) compared to FusionRed. It also retains the low cytotoxicity and high-fidelity localization of FusionRed, as demonstrated through assays in mammalian cells. These properties make FR-MQV a promising template for further engineering into a new family of RFPs.
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