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OBJECTIVEWe aimed to compare glucose control in adolescents with type 1 diabetes (T1D) using the MiniMed 780G system who used simplified meal announcement with those who used precise carbohydrate counting.RESEARCH DESIGN AND METHODSThis randomized controlled trial included 34 participants (age 12–18 years) with T1D who were on multiple daily injections or insulin pump and were scheduled to start using the MiniMed 780G system at Sidra Medicine in Qatar. After a 7-day run-in period, participants were randomly assigned to the fix group (simplified meal announcement by preset of three personalized fixed carbohydrate amounts) or the flex group (precise carbohydrate counting) and followed for 12 weeks. Between-group difference in time in range (TIR) was the primary end point. Secondary end points included HbA1c and other glycometrics.RESULTSDuring the 12-week study phase, TIR was 73.5 ± 6.7% in the fix and 80.3 ± 7.4% in the flex group, with a between-group difference of 6.8% in favor of flex (P = 0.043). Time >250 mg/dL was better in the flex group (P = 0.012), whereas HbA1c (P = 0.168), time below range (P = 0.283), and time between 180 and 250 mg/dL (P = 0.114) did not differ.CONCLUSIONSAdolescents using the MiniMed 780G system with a preset of three personalized fixed carbohydrate amounts can reach international targets of glycemic control. Therefore, it may be a valuable alternative to precise carbohydrate counting in users who are challenged by precise carbohydrate counting. Because carbohydrate counting further improves outcomes, these skills remain important for MiniMed 780G users.

Background: The objective of this study was to evaluate glycemic outcomes using a structured initiation protocol for Hybrid Closed Loop (HCL) MiniMed 670G and Advanced Hybrid Closed Loop (AHCL) Minimed 780G system in children and adolescents with Type 1 Diabetes (T1D) previously treated with Multiple Daily Injections. Methods: The data from two separate (HCL and AHCL system) investigations were analyzed in individuals (aged 7-18 years) with T1D on MDI therapy, both followed a structured initiation protocol. Time in Ranges, HbA1c and system characteristics were analyzed between two systems at 3 and 6 months of Automated Insulin Delivery (AID) . Results: 30 children (age 10.24 ± 2.6 years, HbA1c 8.2±1.4% (66±15.3 mmol/mol)) with HCL system and 34 children (12.5 ± 3.7 years, 8.6±1.7% (70±18.6 mmol/mol)) with AHCL system completed the planned 12 weeks of AID. TIR (70-180mg/dl) of 73.4±8.9% with HCL and 78.2±4.3% with AHCL (p=0.01) was achieved at 6 months of AID. No episodes of severe hypoglycemia or DKA were reported using both systems. Conclusion: Individuals using AHCL MiniMed 780G system had more stringent system settings, spent more time in AID with less exits, which possibly lead to further improvements of glycemic control compared to HCL MiniMed 670G system using the same structured protocol. Disclosure G.Petrovski: None. J.Campbell: Advisory Panel; Medtronic. F.Alkhalaf: None. K.Hussain: None.

Introduction: The COVID-19 pandemic forced health authorities to issue restrictive measures on daily activities from March 12th to June 15th, 2020 (‘lockdown’) in Qatar, which may have influenced the glycemic control in patients with type 1 diabetes (T1D). The aims of the study was to evaluate glycemic control between Multiple Daily Injections (MDI) and Hybrid Closed Loop (HCL) system in children and adolescent with T1D during the lockdown. Methods: This single-center analysis included 168 patients with T1D, using MDI or HCL system MiniMed 670G (Medtronic, Northridge, USA) at least 3 months before the study. Glycemic control from face-to-face visits, three months before lockdown were analyzed and compared to face to face or remote visits during the lockdown of 3 months. Data was collected through the electronic medical record system and reports generated by Carelink Therapy Management Software. HbA1c, glucose and insulin data were analyzed before and 3 months after restrictions. Results: Patients were analyzed in two groups: 1) 92 patients (age 12.4±3.1 years, female:51) on MDI and 2) 76 patients (age 11.2±2.6 years, female:36) HCL system. HbA1c in patients on MDI increased from 8.3±1.5% (67±16.4 mmol/mol) before lockdown to 8.9±1.7% (74±18.6 mmol/mol) during the lockdown, compared to patients on HCL system, where HbA1c remained stable (7.0±0.9% (53±9.8 mmol/mol) to 7.1±1.2% (54±13.1mmol/mol) respectively). No significant difference on DKA events were found in MDI group, before and after lockdown, while no DKA was noted in HCL group during the study. No severe hypoglycemia was observed in both groups. Remote visits were 54% in patients on HCL system, compared to 38% in patients on MDI during the lockdown. Conclusion: Children and adolescents using HCL system maintained stabile glycemic control during the lockdown compared to patient on MDI, where the glycemic control deteriorated. Disclosure G. Petrovski: None. J. Campbell: None. K. Hussain: None. Alkhalaf and consultants/educators: n/a.

Background: Advanced Hybrid Closed Loop (AHCL) systems provide superior glycemic control in children and adolescents with Type 1 Diabetes (T1D). Current studies included participants with previous pump and Continuous Glucose Monitoring (CGM) experience. We aimed to study transitioning these patients on Multiple Daily Injections (MDI) without prior pump experience to AHCL systems within a short period, utilizing a structured initiation protocol and the glycemic control they achieved with the MiniMed 780G system. Methods: In this prospective open label single-arm, single-center, clinical investigation, we recruited children and adolescents (aged 7-17 years) with T1D on MDI therapy and HbA1c below 12.5% from Sidra Medicine (Doha, Qatar). All participants followed a structured initiation protocol including 4 steps: step 1: AHCL system assessment (1 hour discussion with educator); step 2: AHCL system training (2-hours sessions in 4 consecutive days with groups of 2 to 3 participants and caregivers); step 3: SAP use for 3 days; step 4: AHCL system use for 12 weeks, cumulating in 10 days from MDI to AHCL initiation. The primary outcome of the study was the change in the time spent in the target in range (TIR) of 70-180 mg/dl and HbA1c from baseline (MDI + CGM, 1 week) to study phase (AHCL, 12 weeks). This study is registered with ClinicalTrials.gov, number NCT04308291, and is completed. Findings: Between October 25, 2020, and February 5, 2021, 34 participants were recruited and all of them completed the 12 weeks study. TIR increased from 42.1±18.7% at baseline to 78.8±6.1% in the study phase ( p 70% and a HbA1c of

Due to the coronavirus disease 2019 restrictions in providing diabetes services, we have developed an innovative pump training program, which consisted of technical session, pump training, one in-person practical session, and four consecutive online sessions (Skype Meet Now). A 13-year-old female patient with a 4-year history of type 1 diabetes (T1D) on multiple daily injections (MDI) with glycated hemoglobin 8.9%; 74 mmol/mol) initiated Minimed 670G system using the program. Time in range (70-180 mg/dL) of 39% and sensor glucose (SG) of 214±91 mg/dL (MDI with continuous glucose monitoring) increased to 69% in the first 2 weeks and reached 86% and SG of 140±40 mg/dL in the first month of auto mode initiation, without severe hypoglycemia or hyperglycemia. Virtual pump training program can be an effective tool to initiate a hybrid closed-loop system and to improve glycemic control in people with T1D on MDI.

Objective To evaluate the effect of a 1-year hybrid closed-loop (HCL) system on glycemic control in children and adolescents with type 1 diabetes (T1D) previously treated with multiple daily injections (MDI). Methods This was a 1-year observational study, as a continuation of the previous 3 months prospective study of pediatric patients with T1D conducted at Sidra Medicine in Qatar. The study enrolled individuals aged 7–18 years with T1D > 1 year, on MDI with self-monitoring of blood glucose or continuous glucose monitoring, with no prior pump experience, and with an HbA1c level

Aim: Evaluation of six months experience on MiniMed 670G Hybrid Closed Loop (HCL) system in patients with type 1 diabetes (T1D), previously treated with Multiple Daily Injections (MDI). Methods: This is a 6-months prospective observational study of patients (7 to 18 years) with T1D on MDI, starting the MiniMed 670G system, using a 10-day initiation protocol: 2-days, HCL system assessment; 5-days, HCL system training (2-hours sessions in 5 consecutive days); 3-days, Manual Mode use of HCL system and 6 months, Auto Mode use of the HCL system. Results: MiniMed 670G was initiated in 47 patients (age 12.2±3.2 years). All patients used the system for six months period. Auto Mode usage was 87.2% at the first month and 89.6% at the 6-months of Auto Mode initiation. The mean HbA1c decreased from 8.4±1.5% (68±16.4 mmol/mol) at baseline, 6.7±0.8% (50±8.7 mmol/mol) at 3-months (p=0.021), to 6.9±0.7% (52±7.7 mmol/mol) at 6-months of MiniMed 670G initiation (p=0.024). Time in Range (70-180mg/dL) significantly increased over the time (Figure 1). No severe hypoglycemia nor DKA were found. Conclusion: Children and adolescents with T1D can successfully initiate the HCL system, achieve and maintain better glycemic control than previous MDI regimen. Low attrition rate and the sustainability of the results are likely due to patients’ selection, structured educational program and HCL system by itself. Disclosure G. Petrovski: None. J. Campbell: None. F. AlKhalaf: None. F. Umer: None. K. Hussain: None.

Aim To describe continuous subcutaneous insulin infusion (CSII) characteristics in type 1 diabetes mellitus (T1DM) children and adolescents using a standardized protocol in routine clinical settings in Qatar. Methods A total of 138 T1DM patients (62 males; 76 females; mean age 9.8 ± 3.4 years) with a mean diabetes duration of 2.4 ± 1.9 years initiated CSII (MiniMed® Veo®™ and MiniMed® 640 G insulin pumps; Medtronic, Northridge, CA, USA) in 2016 and 2017. CSII characteristics and glycated hemoglobin (HbA1c) were evaluated 1 year after treatment initiation. Results At 1 year after treatment initiation, the insulin dose had significantly increased (from 0.59 ± 0.23 to 0.74 ± 0.26 U/kg body weight per 24; P

Aim The aim of this study was to evaluate the 10-day initiation protocol for MiniMed 670G hybrid closed-loop (HCL) system in individuals with type 1 diabetes on multiple daily injection (MDI) in achieving desirable glycemic control. Methods An open-label single-arm, single-center, clinical investigation in children aged 7–18 years on MDI following a structured protocol: 2 days, HCL system assessment; 5 days, HCL system training (2-h sessions on 5 consecutive days with groups of 3–5 participants and families); 3 days, Manual Mode use of HCL system; 84 days, Auto Mode use of the HCL system, cumulating in 10 days from MDI to Auto Mode activation. Results A total of 30 children (age 10.24 ± 2.6 years) were enrolled in the study, and all completed the planned 84 days on Auto Mode. The participants used the sensor for a median of 92% of the time and spent a median of 89% in Auto Mode. The mean HbA1c decreased from 8.2 ± 1.4% (66 ± 15.3 mmol/mol) at baseline to 6.7 ± 0.5% (50 ± 5.5 mmol/mol) at the end of the study (p = 0.017). Time in range (70–180 mg/dL) increased from 46.9 ± 18.5% at baseline to 75.6 ± 6.9% in Auto Mode (p

We present the optimization of a hybrid closed-loop (HCL) insulin pump system in a type 1 diabetes (T1D) patient in the first 3 months of using the Minimed 670G. An 11-year-old female with 7 years of T1D history started using the Minimed 670G HCL system at our center. The patient had been using the Medtronic Veo insulin pump without a sensor for almost 4 years with HbA1c levels between 7.8% and 10.2%. We introduced the Minimed 670G to improve overall glucose control, improve quality of life and lessen the diabetes burden. Insulin pump characteristics of the Minimed Veo pump were used as the initial setting in the HCL system. The optimization of the Minimed 670G in the next 3 months led to the following changes: an insulin-to-carbohydrate ratio (ICHR) from 1 to 10 g in the morning period (6 a.m. to 12 a.m.) and 15-12 g for the rest of the day (12 p.m. to 6 a.m.); an active insulin time from 4 to 3 h and insulin sensitivity factor (ISF) from 120 to 90 mg/dl with no change in target range. The HbA1c level decreased by - 1.3%, and the time in range significantly increased to 77% with SG values of 139 ± 60 mg/dl, sensor wear of 82% and an auto mode period of 84% per week. Health providers should consider immediate adjustment of the bolus wizard settings such as the ICHR, ISF and active insulin time. The HCL system can improve overall glucose control with increased time in the range of sensor glucose values and reduction of HbA1c levels.

Objectives Brucellosis is one of the most common zoonoses worldwide. Most cases in the United States occur among travelers or immigrants from endemic regions, mostly Central America. In this study, we aimed at describing and comparing the epidemiology and clinical presentation of brucellosis in pediatric and adult patients at two large tertiary care centers in Houston, Texas. Methods We identified patients diagnosed as having brucellosis between January 2000 and December 2009 by searching electronic medical records and reviewing microbiology records for positive cultures. Cases were defined as those with a positive blood culture for Brucella sp, a serum agglutination titer ≥1:80 (or both positive blood culture and serum agglutination titer ≥1:80), along with an epidemiologic risk factor and clinical presentation that is consistent with brucellosis. Results Six adult and 12 pediatric cases were identified; 13 of 18 (72%) cases were immigrants, mostly from Central America. The median ages for adult and pediatric patients were 53 and 3 years old, respectively. Ingestion of unpasteurized milk products was frequently reported. Common clinical features included fever (83%), arthralgias or arthritis (67%), and hepatosplenomegaly (61%). Positive blood cultures were more frequently reported among children than adults (83% vs 33%, P = 0.03). The most common laboratory finding was mildly elevated transaminases. Three adults (50%) but no children developed thrombocytopenia (P = 0.02). Relapsed infection was a frequent occurrence. Conclusions In the southern United States, brucellosis is an important consideration in the differential diagnosis of immigrants presenting with undifferentiated fever and joint complaints. A careful history often reveals an epidemiologic risk factor such as ingestion of unpasteurized dairy products.

Background Higher 25(OH)D3 levels are associated with lower HbA1c, but there are limited UK interventional trials assessing the effect of cholecalciferol on HbA1c. Aims (1) To assess the baseline 25(OH)D3 status in a Manchester cohort of children with type 1 diabetes (T1D). (2) To determine the effect of cholecalciferol administration on HbA1c. Methods Children with T1D attending routine clinic appointments over three months in late winter/early spring had blood samples taken with consent. Participants with a 25(OH)D3 level 10 years) units. HbA1c levels before and after treatment were recorded. Results Vitamin D levels were obtained from 51 children. 35 were Caucasian, 11 South Asian and 5 from other ethnic groups. 42 were vitamin D deficient, but 2 were excluded from the analysis. All South Asian children were vitamin D deficient, with mean 25(OH)D3 of 28 nmol/L. In Caucasians, there was a negative relationship between baseline 25(OH)D3 level and HbA1c (r = −0.484, P t = 1.010, P = 0.328) or at 1 year (t = −1.173, P = 0.248) before and after treatment. One-way ANCOVA, controlling for age, gender, ethnicity, BMI and diabetes duration showed no difference in Δ HbA1c level. Conclusion We report important findings at baseline, but in children treated with a stat dose of cholecalciferol, there was no effect on HbA1c. Further studies with larger sample sizes and using maintenance therapy are required.

Background Extreme variation in provider nutritional practices in the NICU leads to poor growth of premature infants. Standardization of current feeding practices through quality improvement may improve growth trajectory and developmental outcomes. Objectives Increase the mean delta Z score for weight (difference in z-score between birth weight and discharge weight) from −1.8 to −1 within 6 months and sustain for 1 year, for neonates with birth weight (BW) Methods A multidisciplinary team evaluated nutrition practices for VLBW infants and key drivers were determined (figure 1). Re-education around our current feeding protocol and intolerance decision aid, sharing growth information during rounds using an in-house assessment tool (figure 2), increased accessibility to breast pump rentals, standardization of lactation consultation ordering, and development of an infographic to assist mothers in choosing breast milk over formula (figure 3) were interventions tested using the IHI Model for Improvement. Mean delta Z score for weight (primary outcome measure) and number of lactation consultation orders per week (process measure) were recorded and analyzed. Results Mean delta weight Z-score increased from −1.8 to −1.08 (figure 4) following the implementation of all of the noted interventions with centerline shift that has lasted for 8 months (40% improvement). Mean number of lactation consults ordered per week increased from 1 to 4. Conclusions Reducing nutrition practice variation shows marked improvements in infant nutrition status. We continue to test other interventions with the hope of further decreasing growth failure.

This article applies Bateson’s concept of the double bind to the interpretation of emergent problems in custodial grandmothers’ relationships with their other adult offspring and non-custodial grandchildren. The article suggests that women raising grandchildren are placed in a double bind situation in which the two core family values of caring for family members in need and treating all family members equally are in conflict. This conflict of interests is at the heart of many problems within the intergenerational family context and is experienced as both inescapable and distressing by both grandmothers and their adult children. Brief vignettes from two participants in a small-scale qualitative study of New Zealand custodial grandmothers’ lives are presented to illustrate this dynamic.

We aimed to retrospectively evaluate the efficacy of continuous subcutaneous insulin infusion (CSII) therapy in relation to social deprivation in an urban paediatric type 1 diabetic population. Data were compared between 51 children on CSII therapy (mean age 11.2 years and duration of follow-up 1.9 years) and matched controls on multiple daily injection (MDI) therapy. Social deprivation was measured using the UK Office of National Statistics 2007 Index of Multiple Deprivation. Using linear mixed modelling analysis, lower HbA1c levels at 24 months were associated with CSII not MDI therapy (P = 0.02), after adjustment for known variables. Children with the least educated parents showed a rise in HbA1c levels from baseline on MDI therapy (least versus most educated tertile; HbA1c change +0.5% [95% confidence interval −0.1 to 1.1] versus 0% [−0.8 to 0.8]), whereas this was not observed in CSII therapy (least versus most educated tertile; HbA1c change −0.3% [−0.7 to +0.1] versus −0.2% [−0.7 to +0.3], P value for ANCOVA = 0.02, after adjusting for income and employment). Conclusion: Parental educational deprivation was associated with a failure of MDI but not CSII therapy. These outcomes need confirmation by larger studies.

Bacterial lipopolysaccharide (LPS) influences pulmonary vascular endothelial barrier function in vitro. We studied whether LPS regulates endothelial barrier function through actin reorganization. Postconfluent bovine pulmonary artery endothelial cell monolayers were exposed to Escherichia coli 0111:B4 LPS 10 ng/ml or media for up to 6 h and evaluated for: (1) transendothelial 14C-albumin flux, (2) F-actin organization with fluorescence microscopy, (3) F-actin quantitation by spectrofluorometry, and (4) monomeric G-actin levels by the DNAse 1 inhibition assay. LPS induced increments in 14C-albumin flux (P < 0.001) and intercellular gap formation at ≥ 2–6 h. During this same time period the endothelial F-actin pool was not significantly changed compared to simultaneous media controls. Mean (±SE) G-actin (μg/mg total protein) was significantly (P < 0.002) increased compared to simultaneous media controls at 2, 4, and 6 h but not at 0.5 or 1 h. Prior F-actin stabilization with phallicidin protected against the LPS-induced increments in G-actin (P = 0.040) as well as changes in barrier function (P < 0.0001). Prior protein synthesis inhibition unmasked an LPS-induced decrement in F-actin (P = 0.0044), blunted the G-actin increment (P = 0.010), and increased LPS-induced changes in endothelial barrier function (P < 0.0001). Therefore, LPS induces pulmonary vascular endothelial F-actin depolymerization, intercellular gap formation, and barrier dysfunction. Over the same time period, LPS increased total actin (P < 0.0001) and new actin synthesis (P = 0.0063) which may be a compensatory endothelial cell response to LPS-induced F-actin depolymerization. © 1993 Wiley-Liss, Inc.

Lupus vulgaris is a rare form of cutaneous mycobacterial infection that can occur from mycobacterial exposure and even more rarely from exposure to the Bacillus Calmette-Guerin vaccine. We report a child who received this vaccination in China and then developed lupus vulgaris shortly after being adopted in the United States. After histopathologic confirmation, the infection was successfully treated with a combination of antibiotics. This occurrence demonstrates the need for heightened surveillance of Bacillus Calmette-Guerin vaccine-induced lupus vulgaris, given the increasing numbers of overseas adoptions taking place in the United States. To our knowledge, this is the first reported instance of Bacillus Calmette-Guerin immunization-induced lupus vulgaris in the United States.

Previously, we have shown that the Saccharomyces cerevisiae DNA-binding protein ABF1 exists in at least two different electrophoretic forms (K. S. Sweder, P. R. Rhode, and J. L. Campbell, J. Biol. Chem. 263: 17270-17277, 1988). In this report, we show that these forms represent different states of phosphorylation of ABF1 and that at least four different phosphorylation states can be resolved electrophoretically. The ratios of these states to one another differ according to growth conditions and carbon source. Phosphorylation of ABF1 is therefore a regulated process. In nitrogen-starved cells or in cells grown on nonfermentable carbon sources (e.g., lactate), phosphorylated forms predominate, while in cells grown on fermentable carbon sources (e.g., glucose), dephosphorylated forms are enriched. The phosphorylation pattern is affected by mutations in the SNF1-SSN6 pathway, which is involved in glucose repression-depression. Whereas a functional SNF1 gene, which encodes a protein kinase, is not required for the phosphorylation of ABF1, a functional SSN6 gene is required for itsd ephosphorylation. The phosphorylation patterns that we have observed correlate with the regulation of a specific target gene, COX6, which encodes subunit VI of cytochrome c oxidase. Transcription of COX6 is repressed by growth in medium containing a fermentable carbon source and is derepressed by growth in medium containing a nonfermentable carbon source. COX6 repression-derepression is under the control of the SNF1-SSN6 pathway. This carbon source regulation is exerted through domain 1, a region of the upstream activation sequence UAS6 that binds ABF1 (J. D. Trawick, N. Kraut, F. Simon, and R. O. Poyton, Mol. Cell Biol. 12:2302-2314, 1992). We show that the greater the phosphorylation of ABF1, the greater the transcription of COX6. Furthermore, the ABF1-containing protein-DNA complexes formed at domain 1 differ according to the phosphorylation state of ABF1 and the carbon source on which the cells were grown. From these findings, we propose that the phosphorylation of ABF1 is involved in glucose repression-derepression of COX6 transcription.

International audience; Forty-four nucleotides at the 5' terminus of the genomic RNA of Sindbis virus can form a stable stem-loop structure and have been shown previously to be important for viral replication. The structure formed by the complement of this sequence at the 3' end of the minus-strand RNA has been proposed to be a promoter for RNA replication and as such might be bound in a specific fashion by proteins of either cellular or viral origin. Short oligonucleotide probes (either 62 or 132 nucleotides) representing the 3'-terminal sequence of the minus strand were prepared. When added to extracts from infected or uninfected cells, these probes were bound by cellular proteins, as evidenced by a shift in the electrophoretic mobility of the (labeled) oligonucleotide. Competition experiments confirmed the specificity of the interaction. Proteins of apparent molecular sizes 42 and 44 kDa, and to a lesser extent 52 kDa, could be cross-linked to the minus-sense probes by UV irradiation. A mutant minus-strand probe identical to the longer probe except for a single-nucleotide deletion corresponding to nucleotide 5 in the genomic RNA, which is lethal for the virus, was also found to bind the same proteins as the wild-type probe. The half-life of the mutant probe-cellular protein complex was threefold longer than that of the wild-type complex, however, indicating that the mutant probe was bound more tightly than the wild-type probe. We hypothesize that the binding of cellular factors may be transiently required for initiation of transcription of plus-strand RNA from the minus-strand template and that overly tight binding of such factors is deleterious for RNA replication.