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Adolescent girls with diabetes are at risk for adverse pregnancy outcomes due to age, risk-taking behavior, poor glycemic control, and lack of knowledge. Our aims were to assess attitudes and behaviors related to reproductive health education (RHE) among diabetes healthcare providers and adolescent girls with diabetes, and to pilot a brief clinic-based RHE intervention. We surveyed 29 providers and 50 adolescent girls with type 1 diabetes about RHE experiences, attitudes, and behaviors. We piloted the RHE intervention with 9 adolescent-parent dyads. 50% of providers were very uncomfortable discussing pregnancy or contraception. Most (72%) did not proactively initiate RHE; common barriers included insufficient time and subject knowledge. Fewer than 10% recommended long-acting reversible contraceptives. A minority (10%) of adolescents had discussed pregnancy or contraception with a provider. RHE sessions lasted a median of 16 (range 13-24) minutes, and there were promising trends for changes in adolescents' self-efficacy and intentions to use contraception and seek preconception counseling and in their knowledge of reproductive health. Adolescent girls with diabetes rarely receive education on pregnancy and contraception due to provider discomfort, limited knowledge, and limited time. RHE using easily-accessible materials with an educator may help address this gap in care.

Concentrations of glycine (Gly) in embryo culture media are often lower (~0.1 mM) than those in oviductal or uterine fluids (≥1.2 mM). The objective of this study was to determine direct and osmolarity-dependent effects of physiological concentrations of Gly on blastocyst formation and hatching, cell allocation to the trophectoderm (TE) and inner cell mass (ICM), and metabolic activity of bovine embryos. In experiment 1, zygotes were cultured with 100 or 120 mM NaCl and 0 or 1 mM Gly for the first 72 h of culture. Blastocyst formation and hatching were improved (P<0.05) when embryos were cultured with 100 compared to 120 mM NaCl. Inclusion of 1 mM Gly improved (P<0.05) blastocyst formation compared to 0 mM Gly, but this effect was only significant (P<0.05) for embryos cultured with 120 mM NaCl, suggesting bovine embryos can utilize Gly as an osmolyte. In experiment 2, embryos were cultured with 0.1, 1.1, 2.1, or 4.1 mM Gly (100 mM NaCl) for the final 96 h of culture. Blastocyst development was not affected (P>0.05) by Gly, but hatching (0.1 mM Gly, 18.2%) was improved (P<0.05) when embryos were cultured with 1.1 (31.4%) or 2.1 (29.4%) mM Gly. Blastocyst, TE, and ICM cell numbers were not affected (P>0.05) by Gly in either experiment. Blastocysts produced alanine, glutamine, pyruvate, and urea and consumed aspartate, but this metabolic profile was not affected (P>0.05) by Gly. In conclusion, Gly (1.0 mM) improves the development of both early and late stage embryos, but beneficial effects are more pronounced for early embryos exposed to elevated osmolarity.

Health care inequities among racial and ethnic groups remain prevalent. For people with type 1 diabetes who require increased medical access and care, disparities are seen in access to care and health outcomes. This article reports on a study by the T1D Exchange Quality Improvement Collaborative evaluating differences in A1C, diabetic ketoacidosis (DKA), severe hypoglycemia, and technology use among racial and ethnic groups. In a diverse cohort of nearly 20,000 children and adults with type 1 diabetes, A1C was found to differ significantly among racial and ethnic groups. Non-Hispanic Blacks had higher rates of DKA and severe hypoglycemia and the lowest rate of technology use. These results underscore the crucial need to study and overcome the barriers that lead to inequities in the care and outcomes of people with type 1 diabetes. Health inequities among racial and ethnic groups persist in both children and adults. Individuals with chronic conditions such as type 1 diabetes require increased medical access and care. Yet, there are disparities in access to care and health outcomes (1). The incidence of type 1 diabetes is increasing in the United States across all populations, and most significantly among Hispanic youths, but despite the higher incidence, health disparities continue to worsen among specific racial and ethnic groups (2,3). Mean A1C levels were found to be higher in Hispanics and non-Hispanic Blacks with type 1 diabetes compared with non-Hispanic Whites in the largest U.S. study to date, which included ∼11,000 youths and young adults in the T1D Exchange clinic network and registry (4). Non-Hispanic Blacks and Hispanics have been reported to perform fewer blood glucose checks per day than Non-Hispanic Whites (5,6). One study evaluating A1C trajectories over time in ∼16,000 youths from Australia, Europe, and the United States found that minority groups were more likely to have increasing A1C levels over time compared with Non-Hispanic Whites, specifically in the T1D Exchange and Diabetes-Patienten-Verlaufsdokumentation registries (7). Disparities also exist in rates of acute complications such as diabetic ketoacidosis (DKA) and severe hypoglycemia, although literature in this area is more limited. One study found that Non-Hispanic Blacks were 2.5 times more likely to have at least one DKA episode in the previous 12 months compared with Non-Hispanic Whites. They were also 2.5 times more likely than Non-Hispanic Whites to have at least one severe hypoglycemic event in the previous 12 months (4). Rates of mortality in diabetes are also twice as high among Non-Hispanic Blacks compared with other racial groups (8). One area of diabetes care that has improved diabetes management is the advancement of technology, including insulin pumps and continuous glucose monitoring (CGM) systems. However, use of these advanced diabetes technologies varies by population. Both the T1D Exchange and the SEARCH for Diabetes in Youth registries reported that Non-Hispanic White youths are more likely to use an insulin pump than their Black and Hispanic counterparts (4,9,10). The T1D Exchange registry found that Non-Hispanic White youths were 1.9 times more likely than Non-Hispanic Black youths and 3.6 times more likely than Hispanic youths to use an insulin pump. This finding is particularly important because it is known that insulin pump therapy can contribute to lower A1C levels (11), and Non-Hispanic Black and Hispanic youths are more likely to have higher A1C levels (4,7). Agarwal et al. (12) recently found that insulin pump use was one variable that helped account for the difference in A1C levels between Black and White young adults with type 1 diabetes. Studies of CGM use among racial and ethnic groups are very limited. One study showed that, among youths <13 years of age, Non-Hispanic Whites were more likely than Hispanics to use CGM, but this difference was not seen in older children or adults (13). Although there have been multiple studies evaluating A1C differences among racial and ethnic groups, there are limited population studies, and none have examined inequities in acute complication rates and technology use. This study uses a dataset with a large cohort of individuals with type 1 diabetes in a real-world setting to examine racial and ethnic differences in glycemic control, acute complications rates, and technology use.

Abstract Objective We examined whether diabetic ketoacidosis (DKA), a serious complication of type 1 diabetes (T1D) was more prevalent among Non-Hispanic (NH) Black and Hispanic patients with T1D and laboratory-confirmed coronavirus disease 2019 (COVID-19) compared with NH Whites. Method This is a cross-sectional study of patients with T1D and laboratory-confirmed COVID-19 from 52 clinical sites in the United States, data were collected from April to August 2020. We examined the distribution of patient factors and DKA events across NH White, NH Black, and Hispanic race/ethnicity groups. Multivariable logistic regression analysis was performed to examine the odds of DKA among NH Black and Hispanic patients with T1D as compared with NH White patients, adjusting for potential confounders, such as age, sex, insurance, and last glycated hemoglobin A1c (HbA1c) level. Results We included 180 patients with T1D and laboratory-confirmed COVID-19 in the analysis. Forty-four percent (n = 79) were NH White, 31% (n = 55) NH Black, 26% (n = 46) Hispanic. NH Blacks and Hispanics had higher median HbA1c than Whites (%-points [IQR]: 11.7 [4.7], P < 0.001, and 9.7 [3.1] vs 8.3 [2.4], P = 0.01, respectively). We found that more NH Black and Hispanic presented with DKA compared to Whites (55% and 33% vs 13%, P < 0.001 and P = 0.008, respectively). After adjusting for potential confounders, NH Black patients continued to have greater odds of presenting with DKA compared with NH Whites (OR [95% CI]: 3.7 [1.4, 10.6]). Conclusion We found that among T1D patients with COVID-19 infection, NH Black patients were more likely to present in DKA compared with NH White patients. Our findings demonstrate additional risk among NH Black patients with T1D and COVID-19.

The transition to autonomous clinical practice for early professionals (EPs) has been found to be a stressful time, but no studies with multiple stakeholder groups have been completed. To examine the perceptions of EPs' integration during role transition from multiple stakeholder groups. Qualitative study. Online interviews. Seventeen EPs in the first 2 years of their first job postcertification (9 women, 8 men, age = 26 ± 5 years, experience = 9.5 ± 5 months), 16 supervisors and mentors of EPs (6 women, 10 men, age = 52 ± 11 years), and 10 faculty members and 8 preceptors (11 women, 7 men, age = 43 ± 10 years). Semistructured interviews using a validated interview guide based on the current literature were conducted. We analyzed data using consensual qualitative research principles. Multiple-analyst triangulation (n = 3), member checking, and peer review served as trustworthiness strategies. We identified 4 themes that defined the integration of EPs during role transition. The integration of EPs was facilitated through role inductance and mentoring. Early professionals struggle finding balance to avoid burnout as they are new to the profession and feel obligated to exceed expectations from a coverage standpoint rather than focusing on the quality of care delivered. Finally, stakeholders suggested a timeline by which EPs become fully integrated into autonomous professional practice and understand all aspects of their role that typically takes anywhere from 1 to 3 years. Early professionals benefited from appropriate graded autonomy during clinical education to develop their clinical reasoning skills, confidence, and mentoring network with past preceptors. Ongoing personal and professional support are needed during the initial few years to ease EPs' role inductance while they gain more experience and establish their clinician identity. Expectations for EPs should be reasonable to allow for the provision of quality care, adequate work-life balance, and integration into the profession without guilt.

The prognosis of cholangiocarcinoma (CC) is dismal. Notch has been identified as a potential driver; forced exogenous overexpression of Notch1 in hepatocytes results in the formation of biliary tumors. In human disease, however, it is unknown which components of the endogenously signaling pathway are required for tumorigenesis, how these orchestrate cancer, and how they can be targeted for therapy. Here we characterize Notch in human-resected CC, a toxin-driven model in rats, and a transgenic mouse model in which p53 deletion is targeted to biliary epithelia and CC induced using the hepatocarcinogen thioacetamide. We find that across species, the atypical receptor NOTCH3 is differentially overexpressed; it is progressively up-regulated with disease development and promotes tumor cell survival via activation of PI3k-Akt. We use genetic KO studies to show that tumor growth significantly attenuates after Notch3 deletion and demonstrate signaling occurs via a noncanonical pathway independent of the mediator of classical Notch, Recombinant Signal Binding Protein for Immunoglobulin Kappa J Region (RBPJ). These data present an opportunity in this aggressive cancer to selectively target Notch, bypassing toxicities known to be RBPJ dependent.

Abstract Fescue toxicosis is a syndrome that impairs growth and reproduction in cattle grazing endophyte-infected tall fescue [Lolium arundinaceum [(Schreb.].) Darbysh)] in the United States, resulting in approximately $1 billion in annual economic loss in species that utilize this forage resource. Approximately 90% of tall fescue contains an endophytic fungus (Epichloë coenophiala) that produces ergot alkaloids. Ergot alkaloids cause vasoconstriction and reduced blood flow to the extremities; however, it remains unknown how blood flow to the reproductive organs is affected in cattle. Therefore, the objective of this study was to determine if ergot alkaloids from endophyte-infected tall fescue reduce blood flow to the reproductive organs, thus hindering reproductive function. Angus heifers (n = 36) naïve to ergot alkaloids were placed in Calan gates and randomly assigned to receive either endophyte-infected fescue seed (E+) or noninfected fescue seed (E−; control) in a total mixed ration for 63 d. Weekly measurements were taken to monitor heifer growth and response to ergot alkaloid exposure. Reproductive measurements, including ovarian structures, uterine and ovarian vessel diameter, and hormone concentrations were determined after heifers were synchronized using the standard CO-Synch + 7 d CIDR protocol to ensure all measurements were collected at the same stages of the estrous cycle (0, 4, 10, and 17 d). Data were analyzed using repeated measures in PROC MIXED of SAS. Average daily gain was decreased for the E+ group (0.8 kg/d) compared to control heifers (1.0 kg/d). Body condition scores tended to be greater in control heifers compared to the E+ group (P = 0.053). Additionally, hair coat and hair shedding scores were greater in E+ heifers compared to controls (P < 0.05). Heart rate, rectal temperature, respiration rate, and blood pressure did not differ between treatments (P > 0.05). Vasoconstriction was observed in the caudal artery, but not the caudal vein, in heifers consuming the E+ fescue seed (P < 0.05). No differences were observed in antral follicle counts, corpus luteum area or circulating progesterone concentrations in E+ heifers compared to controls (P > 0.05). There was a significant decrease in the diameter of arteries and veins servicing the ovary and uterus on day 10 and 17 of the estrous cycle. Reduction in blood flow to the reproductive organs during critical times in the estrous cycle may contribute to the reduced ovarian function and pregnancy rates associated with fescue toxicosis.

When wine grapes are exposed to smoke, there is a risk that the resulting wines may possess smoky, ashy, or burnt aromas, a wine flaw known as smoke taint. Smoke taint occurs when the volatile phenols (VPs) largely responsible for the aroma of smoke are transformed in grape into a range of glycosides that are imperceptible by smell. The majority of VP-glycosides described to date are disaccharides possessing a reducing β-d-glucopyranosyl moiety. Here, a two-part experiment was performed to (1) assess the stability of 11 synthesized VP-glycosides towards general acid-catalyzed hydrolysis during aging, and (2) to examine whether yeast strains differed in their capacity to produce free VPs both from these model glycosides as well as from grapes that had been deliberately exposed to smoke. When fortified into both model and real wine matrices at 200 ng/g, all VP-disaccharides were stable over 12 weeks, while (42–50 ng/g) increases in free 4-ethylphenol and p-cresol were detected when these were added to wine as their monoglucosides. Guaiacol and phenol were the most abundantly produced VPs during fermentation, whether originating from natural VP-precursors in smoked-exposed Pinot Noir must, or due to fortification with synthetic VP-glycosides. Significant yeast strain-specific differences in glycolytic activities were observed for phenyl-β-d-glycopyranoside, with two strains (RC212 and BM45) being unable to hydrolyze this model VP, albeit both were active on the guaiacyl analogue. Thus, differences in Saccharomyces cerevisiae β-glucosidase activity appear to be influenced by the VP moiety.

Hypertriglyceridemia (HTG) in the setting of newly diagnosed diabetes is common in both adult and pediatric populations, as insulin deficiency promotes lipolysis and impairs triglyceride (TG) clearance. Severe HTG (defined as TG levels above 1000 mg/dL) in pediatric patients with new‐onset type 1 diabetes mellitus (T1D) is rare; the true incidence and sequela of this phenomenon have not been well characterized. We present a single‐center experience on severe HTG in pediatric patients with new‐onset T1D between 2013 and 2022 and summarize the cases previously reported in the literature. Our cases display variability in their presentation and in their association with high‐risk complications, such as acute pancreatitis. We discuss suggestions of early screening for HTG and pancreatitis in patients with protracted abdominal pain, and close monitoring of those identified to have significant HTG.

Adolescents and young adults have lower uptake of vaccines for preventable diseases than children and older adults. Young adults with type 1 diabetes (T1D) are at risk of complications from many vaccine-preventable illnesses. Given the elevated health risks of SARS-COV-2 infection for people with T1D, it is important to understand COVID-19 vaccination rates and attitudes. We explored vaccine uptake and characterized self-reported reasons for declining vaccination in a cohort of young adults with T1D as they were leaving pediatric care during the COVID-19 pandemic. Participants enrolled in a randomized controlled trial of a transition intervention for young adults with T1D reported COVID-19 vaccination at baseline (2/2021–6/2023). We report rates of COVID-19 vaccination in addition to demographic and medical characteristics. Participants who did not receive vaccination were asked to note the reason(s). From these qualitative responses we identified themes. Of the n = 97 participants reporting vaccination status, 70.1 % reported receiving at least one COVID-19 vaccine. No demographic or medical characteristics were significantly associated with vaccination status (p ≥ 0.05). Themes of reasons for not receiving the COVID-19 vaccination included Doubt, Fear, External Factors, and Indifference. In young adults with T1D, COVID-19 vaccine uptake is below public health targets. Addressing fears about vaccine-related effects on T1D, doubts surrounding vaccine development and efficacy, and other external factors influencing vaccination decisions may be helpful in initiating a dialogue between clinicians and young adults considering vaccination. Further investigation into attitudes about other preventative care measures in this vulnerable population is needed. Clinical trial registry site and number: ClinicalTrials.gov ID Number - NCT04247620. •Despite increased risks in young adults with type 1 diabetes, COVID-19 vaccine uptake was similar to the general population.•Themes of self-reported reasons for not being vaccinated were Doubt, Fear, External Factors, and Indifference.•Addressing these concerns may help young adults with chronic health conditions make preventative healthcare decisions.