Institutional Barriers to the Successful Implementation of Telemedicine for Type 1 Diabetes Care.

The aim of this study was to describe rates of telemedicine use 18 months after the start of the coronavirus disease 2019 pandemic and to assess the institutional barriers to its implementation for type 1 diabetes care across centers of the T1D Exchange Quality Improvement Collaborative. Observational electronic health record data capturing telemedicine rates from 15 U.S. centers between September 2020 and September 2021 and a survey of 33 centers capturing telemedicine rates and key components of telemedicine were analyzed. A capacity score was developed and summed to a total capacity score and compared with overall telemedicine rates across centers. Telemedicine visits decreased by 17.4% from September 2020 to September 2021. Generally, it was observed that the lower the average telemedicine capacity score, the lower the rate of telemedicine visits. Despite a decline in the utilization of telemedicine 18 months after the start of the pandemic, visit rates were still 20% higher than in the pre-pandemic period. However, there is a need to improve structural components to ensure telemedicine capacity and robust telemedicine utilization.

Baseline Quality Improvement Capacity of 33 Endocrinology Centers Participating in the T1D Exchange Quality Improvement Collaborative.

This article describes the evolution of the Type 1 Diabetes Exchange Quality Improvement Collaborative (T1DX-QI) and provides insight into the development and growth of a successful type 1 diabetes quality improvement (QI) program. Since its inception 8 years ago, the collaborative has expanded to include centers across the United States with varying levels of QI experience, while simultaneously achieving many tangible improvements in type 1 diabetes care. These successes underscore the importance of learning health systems, data-sharing, benchmarking, and peer collaboration as drivers for continuous QI. Future efforts will include recruiting additional small- to medium-sized centers focused on adult care and underserved communities to further the goal of improving care and outcomes for all people living with type 1 diabetes.

Optimizing Glycemic Outcomes for Children with Type 1 Diabetes.

Changes in physical growth, neurocognitive development, and pubertal maturation are some of the challenges to achieving blood glucose targets in children with type 1 diabetes mellitus. To optimize glycemic outcomes, a comprehensive approach is crucial to address psychosocial needs, expand the use of diabetes technology, and diminish health inequities.

Physiological changes in rhizobia after growth in peat extract may be related to improved desiccation tolerance.

Improved survival of peat-cultured rhizobia compared to survival of liquid-cultured cells has been attributed to cellular adaptations during solid-state fermentation in moist peat. We have observed improved desiccation tolerance of Rhizobium leguminosarum bv. trifolii TA1 and Bradyrhizobium japonicum CB1809 after aerobic growth in water extracts of peat. Survival of TA1 grown in crude peat extract was 18-fold greater than that of cells grown in a defined liquid medium but was diminished when cells were grown in different-sized colloidal fractions of peat extract. Survival of CB1809 was generally better when grown in crude peat extract than in the control but was not statistically significant (P > 0.05) and was strongly dependent on peat extract concentration. Accumulation of intracellular trehalose by both TA1 and CB1809 was higher after growth in peat extract than in the defined medium control. Cells grown in water extracts of peat exhibit morphological changes similar to those observed after growth in moist peat. Electron microscopy revealed thickened plasma membranes, with an electron-dense material occupying the periplasmic space in both TA1 and CB1809. Growth in peat extract also resulted in changes to polypeptide expression in both strains, and peptide analysis by liquid chromatography-mass spectrometry indicated increased expression of stress response proteins. Our results suggest that increased capacity for desiccation tolerance in rhizobia is multifactorial, involving the accumulation of trehalose together with increased expression of proteins involved in protection of the cell envelope, repair of DNA damage, oxidative stress responses, and maintenance of stability and integrity of proteins.

Techniques for analysis of plant phenolic compounds.

Phenolic compounds are well-known phytochemicals found in all plants. They consist of simple phenols, benzoic and cinnamic acid, coumarins, tannins, lignins, lignans and flavonoids. Substantial developments in research focused on the extraction, identification and quantification of phenolic compounds as medicinal and/or dietary molecules have occurred over the last 25 years. Organic solvent extraction is the main method used to extract phenolics. Chemical procedures are used to detect the presence of total phenolics, while spectrophotometric and chromatographic techniques are utilized to identify and quantify individual phenolic compounds. This review addresses the application of different methodologies utilized in the analysis of phenolic compounds in plant-based products, including recent technical developments in the quantification of phenolics.

Papillary Thyroid Carcinoma in a Pediatric Patient With ß-Thalassemia.

ß-Thalassemia is characterized by the abnormal synthesis of ß-hemoglobin chains resulting in hemolytic anemia. Treatment involves frequent blood transfusions, which leads to deposition of iron in many organs, including endocrine glands. To date, several cases of papillary thyroid cancer (PTC) in patients with ß-thalassemia have been reported in the adult literature, but there have been none in pediatrics. Here we report on an female adolescent with ß-thalassemia who initially presented for evaluation of secondary amenorrhea. On examination, her thyroid gland was asymmetric, firm in consistency, with palpable lymph nodes along the right anterior cervical chain. A thyroid ultrasound revealed an enlarged right lobe containing 3 focal hypoechoic masses with calcific foci. Biopsy was consistent with PTC. She underwent total thyroidectomy and histological examination confirmed the diagnosis. Her postoperative course was uncomplicated and she was started on replacement therapy with levothyroxine. This is the first reported case of PTC in a pediatric patient with ß-thalassemia. The incidence of thyroid cancer in patients with ß-thalassemia is currently unknown; however, there may be utility in routine surveillance of this patient population.

The effect of postharvest 1-MCP treatment and storage atmosphere on 'Cripps Pink' apple phenolics and antioxidant activity.

This study investigated the effect of a postharvest 1-methylcyclopropene (1-MCP) treatment, controlled atmosphere and storage time on the total antioxidant activity (TAA) and phenolic compounds in the peel and flesh of 'Cripps Pink' apples (Malus domestica Borkh.). Preclimacteric apples were harvested and treated with 1-MCP then stored in normal atmosphere (NA) or controlled atmosphere (CA) at 0°C for up to 160days. In general, the level of phenolics decreased by 9% in the peel and significantly increased twofold in the flesh during cold storage, regardless of storage atmosphere or 1-MCP treatment. However, treatment with 1-MCP resulted in significantly lower concentrations of chlorogenic acid and procyanidin B2 in apple flesh, and catechin and epicatechin in the peel compared to the control fruits. There was no significant effect of CA on the phenolic compounds during long-term storage, except for quercetin 3-galactoside and quercetin 3-glucoside, which both significantly increased under CA storage. Total antioxidant activity (TAA) is an important nutritional attribute of apples in the human diet. The results showed that TAA in the peel tissue was about eight times higher than that of the flesh, with mean values of 4.75gTE/kgFW and 0.56TE/kgFW, respectively. The TAA in both the peel and flesh tissue increased significantly during storage by 40% and 70%, respectively. The storage atmosphere did not significantly affect TAA in either the peel or flesh, whilst the 1-MCP treatment significantly reduced the TAA in the peel tissue only. These results show the beneficial combined effects of pre-storage 1-MCP treatment and CA on 'Cripps Pink' apple phenolic composition and antioxidant capacity during long term storage.

Clinical findings influencing time to menarche post gonadotropin-releasing hormone agonist therapy in central precocious puberty.

PURPOSE: This study aimed to evaluate the time interval to menarche after gonadotropin-releasing hormone agonist (GnRHa) treatment in females with central precocious puberty (CPP) and to identify factors contributing to timing of menarche. METHODS: We retrospectively reviewed medical records of 39 females with CPP who reached menarche after GnRHa treatment (leuprolide or histrelin). CPP diagnostic criteria were breast development at <8 years old, measurable pubertal luteinizing hormone and/or estradiol concentrations, and bone age advancement. Indications to treat were advanced bone age and psychosocial concerns. Descriptive summaries were reported as frequency and proportion for categorical variables and mean and standard deviation for continuous measures. Linear regression models were developed to evaluate the associations of clinical factors with the time interval to menarche. RESULTS: Mean age was 9.4±1.6 years at treatment onset, and treatment duration was 2.2±1.4 years. Menarche occurred at 12.6±1.1 years, which was 1.04±0.5 years after treatment discontinuation. This was negatively associated with Tanner stage of breast development and bone age at treatment onset and change in bone age during treatment. No association was seen between time interval to menarche and treatment duration, medication, or body mass index. CONCLUSION: We found the average time interval to menarche after GnRHa treatment in our population of female patients with CPP to be 1.04±0.5 years; this is in agreement with other reports. Tanner stage of breast development, bone age at treatment onset, and change in bone age were negatively associated with time interval to menarche. These data provide clinical correlates that assist providers during anticipatory guidance of patients with CPP after GnRHa treatment.

Diabetic ketoacidosis drives COVID-19 related hospitalizations in children with type 1 diabetes.

BACKGROUND: Diabetes is a risk factor for poor COVID-19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies. METHODS: T1D Exchange coordinated a US type 1 diabetes COVID-19 registry. Forty-six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID-19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization. RESULTS: Data from 266 patients with previously established type 1 diabetes aged <19 years with COVID-19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID-19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34-1.84) after adjusting for age, gender, insurance, and race/ethnicity. CONCLUSIONS: Higher A1c remained the only predictor for hospitalization with COVID-19. Diabetic ketoacidosis is the primary concern among this group.

Undervirilized male infant with in utero exposure to maternal use of high dose antifungal therapy.

BACKGROUND: Antifungals act on fungal sterols structurally similar to human cholesterol. Ketoconazole reversibly suppresses steroidogenesis by inhibiting cytochrome P450 enzymes and interferes with dihydrotestosterone (DHT) activity by binding to the androgen receptor. Hypospadias was reported in infants exposed to nystatin in utero. CASE PRESENTATION: A male infant exposed to antepartum nystatin presented with severe under-undervirilization and transient adrenal corticosteroid abnormalities. He was born in USA at 31 weeks gestation to a mother treated with vaginal Polygynax capsules (nystatin-100,000 international units, neomycin sulphate-35,000 international units and polymyxin B-35,000 international units) for vaginal discharge in the Ivory Coast. She used approximately 60 capsules between the first trimester until delivery. The infant was born with micropenis, chordee, perineo-scrotal hypospadias and bifid scrotum with bilaterally palpable gonads. The karyotype was 46,XY. No Mullerian structures were seen on ultrasound. Serum 17-hydroxyprogesterone (17 OHP) on newborn screening was high (304 ng/ml, normal < 35). Cortisol response to cosyntropin on the 3rd day of life (DOL) was 10 mcg/ml; the subnormal cortisol response may have resulted from prematurity and the predelivery treatment with betamethasone. The elevation of several adrenal corticosteroids was not consistent with any specific enzymatic defect. Hydrocortisone and fludrocortisone were initiated at another hospital for suspected mild glucocorticoid and mineralocorticoid deficiencies. Genetic screening for adrenal and gonadal developmental defects performed when transferred to our care were normal. All medications were gradually discontinued over 5-8 months. Adrenal and testicular responses to cosyntropin and human chorionic gonadotropin (hCG) were normal at 8 months. CONCLUSIONS: We report severe undervirilization in a 46,XY infant born to a mother treated with prolonged and high dose nystatin during pregnancy. This presentation suggests that prolonged antepartum use of high dose nystatin could lead to severe but transient defects in androgen synthesis and/or action possibly by acting as an endocrine disruptor. Further studies are warranted to confirm this finding. Thus, endocrine disruptors should be considered in male newborns with atypical genitalia not explained by common pathologies.

Primary Cortisol Deficiency and Growth Hormone Deficiency in a Neonate With Hypoglycemia: Coincidence or Consequence?

Cortisol and growth hormone (GH) deficiencies are causes of neonatal hypoglycemia. When they coexist, a pituitary disorder is suspected. We present an infant with hypoglycemia in whom an ACTH receptor defect was associated with transient GH deficiency. A full-term boy with consanguineous parents presented with hypoglycemia (serum glucose 18 mg/dL) at 4 hours of life with undetectable serum cortisol (<1 µg/dL). Examination showed diffuse hyperpigmentation with normal male genitalia. Patient developed hyperbilirubinemia and elevated transaminase levels. GH levels of 6.8 ng/mL and 7.48 ng/mL during episodes of hypoglycemia, peak of 9.2 ng/mL with glucagon stimulation, and undetectable IGF-1 suggested GH deficiency. Thyroid function, prolactin, and gonadotropins were normal. Baseline ACTH was elevated at 4868 pg/mL, whereas serum cortisol remained undetectable with ACTH stimulation. Hydrocortisone replacement resulted in normalization of blood glucose and cholestasis with decline in ACTH level. GH therapy was not initiated, given improvement in cholestasis and euglycemia. An ACTH receptor defect was confirmed with molecular genetic testing that revealed homozygosity for a known mutation of the melanocortin 2 receptor (MC2R) gene. At 12 weeks, a random GH level was 10 ng/mL. IGF-1 was 75 ng/mL and 101 ng/mL at 7 and 9 months, respectively. This report describes glucocorticoid deficiency from an MC2R mutation associated with GH deficiency. With glucocorticoid replacement, GH secretion normalized. Our findings are consistent with a previously stated hypothesis that physiologic glucocorticoid levels may be required for optimal GH secretion [1].

Phase I/II study of continuous-infusion troxacitabine in refractory acute myeloid leukemia.

PURPOSE: Troxacitabine is a non-natural nucleoside analog with unique structural and metabolic features. Bolus intravenous (IV) troxacitabine regimens have shown significant activity in patients with refractory acute myeloid leukemia (AML) and preclinical data suggest that administration via continuous infusion may result in enhanced antitumor activity. PATIENTS AND METHODS: Patients with refractory AML initially received troxacitabine 10.1 mg/m2 by continuous IV infusion (CIVI) for 48 hours. Infusion duration and daily dose were increased in subsequent patient cohorts. RESULTS: Forty-eight patients, median age 58 years (range, 21 to 81 years), were treated. Dose-limiting toxicities were mucositis and hand-foot syndrome, and 12.0 mg/m2/d for 5 days was established as the maximum-tolerated dose. Seven patients (15%) achieved complete remission (CR) or CR with incomplete platelet recovery (CRp), with a median survival among responders of 12 months. Steady-state concentrations of troxacitabine were found to be linearly and inversely proportionally related to calculated creatinine clearance at doses of 10.1 and 12.0 mg/m2/d. All patients responding to troxacitabine had steady-state serum drug concentration of more than approximately 80 ng/mL. In 27 patients achieving target troxacitabine plasma concentrations (ie, approximately 80 ng/mL) the CR + CRp rate was 26%. CONCLUSION: Troxacitabine administered as a CIVI allows a significant increase in dose-intensity in comparison to IV bolus regimens, has antileukemic activity, and warrants additional investigation in patients with refractory AML. The recommended phase II study dose is 12.0 mg/m2 daily CIVI for 5 days.

The N-terminal SH4 region of the Src family kinase Fyn is modified by methylation and heterogeneous fatty acylation: role in membrane targeting, cell adhesion, and spreading.

The N-terminal SH4 domain of Src family kinases is responsible for promoting membrane binding and plasma membrane targeting. Most Src family kinases contain an N-terminal Met-Gly-Cys consensus sequence that undergoes dual acylation with myristate and palmitate after removal of methionine. Previous studies of Src family kinase fatty acylation have relied on radiolabeling of cells with radioactive fatty acids. Although this method is useful for verifying that a given fatty acid is attached to a protein, it does not reveal whether other fatty acids or other modifying groups are attached to the protein. Here we use matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry to identify fatty acylated species of the Src family kinase Fyn. Our results reveal that Fyn is efficiently myristoylated and that some of the myristoylated proteins are also heterogeneously S-acylated with palmitate, palmitoleate, stearate, or oleate. Furthermore, we show for the first time that Fyn is trimethylated at lysine residues 7 and/or 9 within its N-terminal region. Both myristoylation and palmitoylation were required for methylation of Fyn. However, a general methylation inhibitor had no inhibitory effect on myristoylation and palmitoylation of Fyn, suggesting that methylation occurs after myristoylation and palmitoylation. Lysine mutants of Fyn that could not be methylated failed to promote cell adhesion and spreading, suggesting that methylation is important for Fyn function.