ABSTRACT
OBJECTIVE: Continuous glucose monitoring (CGM) can detect early dysglycemia in older children and adults with presymptomatic type 1 diabetes (T1D) and predict risk of progression to clinical onset. However, CGM data for very young children at greatest risk of disease progression are lacking. This study aimed to investigate the use of CGM data measured in children being longitudinally observed in the Australian Environmental Determinants of Islet Autoimmunity (ENDIA) study from birth to age 10 years. RESEARCH DESIGN AND METHODS: Between January 2021 and June 2023, 31 ENDIA children with persistent multiple islet autoimmunity (PM Ab+) and 24 age-matched controls underwent CGM assessment alongside standard clinical monitoring. The CGM metrics of glucose SD (SDSGL), coefficient of variation (CEV), mean sensor glucose (SGL), and percentage of time >7.8 mmol/L (140 mg/dL) were determined and examined for between-group differences. RESULTS: The mean (SD) ages of PM Ab+ and Ab- children were 4.4 (1.8) and 4.7 (1.9) years, respectively. Eighty-six percent of eligible PM Ab+ children consented to CGM wear, achieving a median (quartile 1 [Q1], Q3) sensor wear period of 12.5 (9.0, 15.0) days. PM Ab+ children had higher median (Q1, Q3) SDSGL (1.1 [0.9, 1.3] vs. 0.9 [0.8, 1.0] mmol/L; P < 0.001) and CEV (17.3% [16.0, 20.9] vs. 14.7% [12.9, 16.6]; P < 0.001). Percentage of time >7.8 mmol/L was greater in PM Ab+ children (median [Q1, Q3] 8.0% [4.4, 13.0] compared with 3.3% [1.4, 5.3] in Ab- children; P = 0.005). Mean SGL did not differ significantly between groups (P = 0.10). CONCLUSIONS: CGM is feasible and well tolerated in very young children at risk of T1D. Very young PM Ab+ children have increased SDSGL, CEV, and percentage of time >7.8 mmol/L, consistent with prior studies involving older participants.
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This study is the first to investigate the presence and movement of the novel Liberibacter species 'Candidatus Liberibacter brunswickensis' (CLbr) in eggplant, Solanum melongena. The psyllid, Acizzia solanicola can transmit CLbr to eggplant and CLbr can be acquired by CLbr-negative A. solanicola individuals from CLbr-positive eggplants. In planta, CLbr can replicate, move and persist. Investigation into the early development of eggplants showed that CLbr titres had increased at the inoculation site at 14 days post inoculation access period (DPIAP). CLbr had become systemic in the majority of plants tested by 28 DPIAP. The highest bacterial titres were recorded at 35 DPIAP in all samples of the inoculated leaf, the roots, stems and the midrib and petiole samples of the newest leaf (the top leaf). This finding strongly suggests that CLbr movement in planta follows the source to sink relationship as previously described for 'Ca. Liberibacter asiaticus' (CLas) and 'Ca. Liberibacter solanacearum' (CLso). No symptoms consistent with Liberibacter-associated diseases were noted for plants colonised by CLbr during this study, consistent with the hypothesis that CLbr does not cause disease of eggplant during the early stages of host colonisation. In addition, no significant differences in biomass were found between eggplant colonised with CLbr, compared to those that were exposed to CLbr-negative A. solanicola, and to control plants.
Subject(s)
Plant Diseases , Solanum melongena , Solanum melongena/microbiology , Plant Diseases/microbiology , Plant Leaves/microbiology , Rhizobiaceae/physiology , Liberibacter , Hemiptera/microbiology , Hemiptera/growth & development , Animals , Plant Roots/microbiologyABSTRACT
The effect of population bottlenecks and genome reduction on enzyme function is poorly understood. Candidatus Liberibacter solanacearum is a bacterium with a reduced genome that is transmitted vertically to the egg of an infected psyllid-a population bottleneck that imposes genetic drift and is predicted to affect protein structure and function. Here, we define the function of Ca. L. solanacearum dihydrodipicolinate synthase (CLsoDHDPS), which catalyzes the committed branchpoint reaction in diaminopimelate and lysine biosynthesis. We demonstrate that CLsoDHDPS is expressed in Ca. L. solanacearum and expression is increased ~2-fold in the insect host compared to in planta. CLsoDHDPS has decreased thermal stability and increased aggregation propensity, implying mutations have destabilized the enzyme but are compensated for through elevated chaperone expression and a stabilized oligomeric state. CLsoDHDPS uses a ternary-complex kinetic mechanism, which is to date unique among DHDPS enzymes, has unusually low catalytic ability, but an unusually high substrate affinity. Structural studies demonstrate that the active site is more open, and the structure of CLsoDHDPS with both pyruvate and the substrate analogue succinic-semialdehyde reveals that the product is both structurally and energetically different and therefore evolution has in this case fashioned a new enzyme. Our study suggests the effects of genome reduction and genetic drift on the function of essential enzymes and provides insights on bacteria-host co-evolutionary associations. We propose that bacteria with endosymbiotic lifestyles present a rich vein of interesting enzymes useful for understanding enzyme function and/or informing protein engineering efforts.
Subject(s)
Genetic Drift , Genome, Bacterial , Lysine , Symbiosis , Lysine/biosynthesis , Lysine/metabolism , Lysine/genetics , Hydro-Lyases/genetics , Hydro-Lyases/chemistry , Hydro-Lyases/metabolism , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Proteins/chemistry , AnimalsABSTRACT
Austropuccinia psidii is the causal pathogen of myrtle rust disease of Myrtaceae. To gain understanding of the initial infection process, gene expression in germinating Austropuccinia psidii urediniospores and in Leptospermum scoparium inoculated leaves were investigated via analyses of RNAseq samples taken 24 and 48 hours post inoculation (hpi). Principal component analyses of transformed transcript count data revealed differential gene expression between the uninoculated L. scoparium control plants that correlated with the three plant leaf resistance phenotypes (immunity, hypersensitive response and susceptibility). Gene expression in the immune resistant plants did not significantly change in response to fungal inoculation, while susceptible plants showed differential expression of genes in response to fungal challenge. A putative disease resistance gene, jg24539.t1, was identified in the L. scoparium hypersensitive response phenotype family. Expression of this gene may be associated with the phenotype and could be important for further understanding the plant hypersensitive response to A. psidii challenge. Differential expression of pathogen genes was found between samples taken 24 and 48 hpi, but there were no significant differences in pathogen gene expression that were associated with the three different plant leaf resistance phenotypes. There was a significant decrease in the abundance of fungal transcripts encoding three putative effectors and a putative carbohydrate-active enzyme between 24 and 48 hpi, suggesting that the encoded proteins are important during the initial phase of infection. These transcripts, or their translated proteins, may be potential targets to impede the early phases of fungal infection by this wide-host range obligate biotrophic basidiomycete.
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OBJECTIVE: Technology use in type 1 diabetes (T1D) is impacted by socioeconomic status (SES). This analysis explored relationships between SES, glycemic outcomes, and technology use. RESEARCH DESIGN AND METHODS: A cross-sectional analysis of HbA1c data from 2,822 Australian youth with T1D was undertaken. Residential postcodes were used to assign SES based on the Index of Relative Socio-Economic Disadvantage (IRSD). Linear regression models were used to evaluate associations among IRSD quintile, HbA1c, and management regimen. RESULTS: Insulin pump therapy, continuous glucose monitoring, and their concurrent use were associated with lower mean HbA1c across all IRSD quintiles (P < 0.001). There was no interaction between technology use and IRSD quintile on HbA1c (P = 0.624), reflecting a similar association of lower HbA1c with technology use across all IRSD quintiles. CONCLUSIONS: Technology use was associated with lower HbA1c across all socioeconomic backgrounds. Socioeconomic disadvantage does not preclude glycemic benefits of diabetes technologies, highlighting the need to remove barriers to technology access.
Subject(s)
Diabetes Mellitus, Type 1 , Humans , Adolescent , Diabetes Mellitus, Type 1/complications , Glycated Hemoglobin , Cross-Sectional Studies , Blood Glucose Self-Monitoring , Blood Glucose , Australia , Social ClassABSTRACT
Advanced hybrid closed-loop (AHCL) therapy with the Medtronic MiniMed™ 780G system improves glycemia; however, the clinical outcomes in younger children remain less established. This pilot study aimed to explore the continuous glucose monitoring (CGM) metrics in very young children on AHCL. Children between 2 and 7 years of age and on insulin pump therapy were recruited. A 2-week phase in manual mode was followed by a 6-week AHCL phase. CGM metrics were analyzed to review glycemic outcomes. Out of 11 participants enrolled [mean (standard deviation [SD]) age 5.3 (0.8) years], 10 completed the study. Time in closed loop was 96.7 (3.9)%. In AHCL, participants had a mean (SD) time in range of 72.6 (7.4)% and spent 3.0 (1.74)% and 0.63 (0.46)% in time <70 and <54 mg/dL, respectively. AHCL is a feasible option for management of young children with type 1 diabetes.
Subject(s)
Blood Glucose Self-Monitoring , Blood Glucose , Diabetes Mellitus, Type 1 , Hypoglycemic Agents , Insulin Infusion Systems , Insulin , Humans , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/blood , Child , Child, Preschool , Male , Female , Blood Glucose/analysis , Pilot Projects , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Insulin/therapeutic use , Treatment Outcome , Glycemic Control/methodsABSTRACT
CONTEXT: Despite the expansion of palliative care (PC) services, the public has little knowledge and holds misperceptions about PC, creating barriers to accessing timely specialty PC. OBJECTIVES: To systematically review the evidence regarding the efficacy of educational interventions to improve knowledge and attitudes about PC among nonhealthcare workers. METHODS: We searched five databases (PubMed/MEDLINE, Embase, CIANHL, Web of Science, and Scopus) for studies investigating educational interventions about specialty PC in adults who identified as patients, caregivers, or members of the public. We included studies that were available in English and had a comparator group. We excluded studies that only sampled health professionals or children. We used the Mixed Methods Appraisal Tool to assess quality and risk of bias. RESULTS: Of 12,420 records identified, we screened 5948 abstracts and assessed 526 full texts for eligibility. Twenty-one articles were extracted for analysis, representing 20 unique educational interventions. Common methodologies included quasi-experimental (9, 45%), randomized controlled trial (4, 20%), and nonrandomized trial (2, 10%). Common components of the educational interventions included video presentations (9, 45%), written materials (8, 40%), and lectures (4, 20%). Content included definition (14, 70%) and philosophy (14, 70%) of PC, distinctions between PC and hospice (11, 55%), and eligibility for PC (11, 55%). Fourteen (70%) interventions showed statistically significant positive differences in either knowledge or attitudes about PC. CONCLUSIONS: While educational interventions can positively impact knowledge and attitudes about PC among nonhealthcare workers, more research is needed to inform the design, delivery, and evaluation of interventions to increase knowledge and attitudes about PC.
Subject(s)
Caregivers , Hospice Care , Palliative Care , Humans , Caregivers/educationABSTRACT
Background: Technology use, including continuous glucose monitoring (CGM) and insulin pump therapy, is associated with improved outcomes in youth with type 1 diabetes (T1D). In 2017 CGM was universally funded for youth with T1D in Australia. In contrast, pump access is primarily accessed through private health insurance, self-funding or philanthropy. The study aim was to investigate the use of diabetes technology across different socioeconomic groups in Australian youth with T1D, in the setting of two contrasting funding models. Methods: A cross-sectional evaluation of 4957 youth with T1D aged <18 years in the national registry was performed to determine technology use. The Index of Relative Socio-Economic Disadvantage (IRSD) derived from Australian census data is an area-based measure of socioeconomic status (SES). Lower quintiles represent greater disadvantage. IRSD based on most recent postcode of residence was used as a marker of SES. A multivariable generalised linear model adjusting for age, diabetes duration, sex, remoteness classification, and location within Australia was used to determine the association between SES and device use. Results: CGM use was lower in IRSD quintile 1 in comparison to quintiles 2 to 5 (p<0.001) where uptake across the quintiles was similar. A higher percentage of pump use was observed in the least disadvantaged IRSD quintiles. Compared to the most disadvantaged quintile 1, pump use progressively increased by 16% (95% CI: 4% to 31%) in quintile 2, 19% (6% to 33%) in quintile 3, 35% (21% to 50%) in quintile 4 and 51% (36% to 67%) in the least disadvantaged quintile 5. Conclusion: In this large national dataset, use of diabetes technologies was found to differ across socioeconomic groups. For nationally subsidised CGM, use was similar across socioeconomic groups with the exception of the most disadvantaged quintile, an important finding requiring further investigation into barriers to CGM use within a nationally subsidised model. User pays funding models for pump therapy result in lower use with socioeconomic disadvantage, highlighting inequities in this funding approach. For the full benefits of diabetes technology to be realised, equitable access to pump therapy needs to be a health policy priority.
Subject(s)
Diabetes Mellitus, Type 1 , Adolescent , Humans , Blood Glucose Self-Monitoring , Cross-Sectional Studies , Australia , Blood Glucose , TechnologyABSTRACT
Understanding how environmental drivers influence shark and ray spatial and temporal patterns can provide crucial knowledge for their evidence-based protection and long-term monitoring. However, information on which drivers of variation are most important for elasmobranch communities on soft sediments is limited. Using baited remote underwater stereo-video systems (stereo-BRUVs), we investigated how seasonal and environmental variables affected the elasmobranchs of the iSimangaliso Wetland Park marine protected area (MPA) in South Africa (SA). In total, 11 species were identified from 48 sites between 12 m and 33 m water depth in a sandy habitat. While species richness was similar across seasons, the total abundance of elasmobranchs recorded was higher in winter than summer. The species assemblage composition varied significantly between seasons, with the Human's whaler shark Carcharhinus humani prevalent in summer and the Critically Endangered whitespotted wedgefish Rhynchobatus djiddensis more abundant during winter. Most species were sighted throughout the entire depth range, but rays were more common in shallower waters (< 25 m depth), while C. humani and R. djiddensis were more common in the deeper depth zone of this study. This research provides baseline information about this previously unexplored sandy habitat for elasmobranchs in a site of regional and global significance. Records of species of conservation concern in the sampling area highlight the importance of protecting sand environments within an MPA.
Subject(s)
Sharks , Wetlands , Animals , Ecosystem , Sand , Seasons , South AfricaABSTRACT
Triple-negative breast cancer (TNBC) is difficult to treat; therefore, the development of drugs directed against its oncogenic vulnerabilities is a desirable goal. Herein, we report the antitumor effects of CM728, a novel quinone-fused oxazepine, against this malignancy. CM728 potently inhibited TNBC cell viability and decreased the growth of MDA-MB-231-induced orthotopic tumors. Furthermore, CM728 exerted a strong synergistic antiproliferative effect with docetaxel in vitro and this combination was more effective than the individual treatments in vivo. Chemical proteomic approaches revealed that CM728 bound to peroxiredoxin-1 (Prdx1), thereby inducing its oxidation. Molecular docking corroborated these findings. CM728 induced oxidative stress and a multi-signal response, including JNK/p38 MAPK activation and STAT3 inhibition. Interestingly, Prdx1 downregulation mimicked these effects. Finally, CM728 led to DNA damage, cell cycle blockage at the S and G2/M phases, and the activation of caspase-dependent apoptosis. Taken together, our results identify a novel compound with antitumoral properties against TNBC. In addition, we describe the mechanism of action of this drug and provide a rationale for the use of Prdx1 inhibitors, such as CM728, alone or in combination with other drugs, for the treatment of TNBC.
Subject(s)
Triple Negative Breast Neoplasms , Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Docetaxel/pharmacology , Molecular Docking Simulation , Proteomics , Triple Negative Breast Neoplasms/genetics , Xenograft Model Antitumor AssaysABSTRACT
Continuous glucose monitoring (CGM) systems are used in therapeutic decisions for diabetes management, however, the impact of body composition on CGM accuracy is not known. Body composition variables (body mass index [BMI], midarm circumference, percentage fat, and impedance) were collected in an observational study designed to determine the accuracy of an investigational Medtronic Guardian™ sensor 3. Seven days of sensor glucose data were analyzed from 112 participants >7 years of age with mean BMI Z score 0.48 (<18 years) and BMI 26.7 kg/m2 (≥18 years). The outcome was the absolute relative difference between the sensor and blood glucose readings. Data were analyzed using generalized estimating equations to account for correlation between repeated measures. No statistically significant associations between measures of body composition and device accuracy were found. Body composition does not have a meaningful impact on the accuracy of CGM systems.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 1 , Humans , Adolescent , Diabetes Mellitus, Type 1/drug therapy , Blood Glucose Self-Monitoring , Reproducibility of Results , CalibrationABSTRACT
The Youth Risk Behavior Surveillance System (YRBSS) is the largest public health surveillance system in the United States, monitoring a broad range of health-related behaviors among high school students. The system includes a nationally representative Youth Risk Behavior Survey (YRBS) and separate school-based YRBSs conducted by states, tribes, territories, and local school districts. In 2021, these surveys were conducted during the COVID-19 pandemic. The pandemic underscored the importance of data in understanding changes in youth risk behaviors and addressing the multifaceted public health needs of youths. This overview report describes 2021 YRBSS survey methodology, including sampling, data collection procedures, response rates, data processing, weighting, and analyses. The 2021 YRBS participation map, survey response rates, and a detailed examination of student demographic characteristics are included in this report. During 2021, in addition to the national YRBS, a total of 78 surveys were administered to high school students across the United States, representing the national population, 45 states, two tribal governments, three territories, and 28 local school districts. YRBSS data from 2021 provided the first opportunity since the onset of the COVID-19 pandemic to compare youth health behaviors using long-term public health surveillance. Approximately half of all student respondents represented racial and ethnic minority groups, and approximately one in four identified as lesbian, gay, bisexual, questioning, or other (a sexual identity other than heterosexual) (LGBQ+). These findings reflect shifts in youth demographics, with increased percentages of racial and ethnic minority and LGBQ+ youths compared with previous YRBSS cycles. Educators, parents, local decision makers, and other partners use YRBSS data to monitor health behavior trends, guide school health programs, and develop local and state policy. These and future data can be used in developing health equity strategies to address long-term disparities so that all youths can thrive in safe and supportive environments. This overview and methods report is one of 11 featured in this MMWR supplement. Each report is based on data collected using methods presented in this overview. A full description of YRBSS results and downloadable data are available (https://www.cdc.gov/healthyyouth/data/yrbs/index.htm).
Subject(s)
Adolescent Behavior , COVID-19 , Female , Humans , Adolescent , United States/epidemiology , Ethnicity , Pandemics , Minority Groups , COVID-19/epidemiology , Health Behavior , Risk-Taking , Sexual Behavior , Surveys and Questionnaires , Population SurveillanceABSTRACT
Youths experiencing unstable housing face higher risks for poor physical, mental, and sexual health outcomes and increased risk for suicide compared with their peers experiencing stable housing. In addition, youths of color and sexual minority youths are disproportionately more likely to experience homelessness. For the first time, in 2021, the nationally representative Youth Risk Behavior Survey included an item assessing housing stability, or nighttime residence among students in grades 9-12 in the United States. During 2021, 2.7% of U.S. high school students experienced unstable housing. Among racial and ethnic subgroups, Native Hawaiian or other Pacific Islander youths were most likely to experience unstable housing, followed by American Indian or Alaska Native and Black youths. Sexual minority (lesbian, gay, bisexual, and questioning or other) youths were more likely to experience unstable housing compared with their heterosexual peers. Compared with students who were stably housed, students who were unstably housed were more likely to engage in risky sexual behaviors, substance use, and suicide ideation and attempts, and to experience violence. These findings highlight which adverse health risks and behaviors are elevated among youths experiencing housing insecurity. Focused public health interventions are required to address the disproportionate burden of health risks prevalent among youths who are unstably housed.
Subject(s)
Housing , Sexual Behavior , Female , Humans , Adolescent , United States , Risk-Taking , Students , HawaiiABSTRACT
Objective: To explore the impact of missing data on the accuracy of continuous glucose monitoring (CGM) metrics collected for a 2-week period in a clinical trial. Research Design and Methods: Simulations were conducted to examine the effect of various patterns of missingness on the accuracy of CGM metrics as compared with a "complete" data set. The proportion of missing data, the "block size" in which the data were missing, and the missing mechanism were modified for each "scenario." The degree of agreement between simulated and "true" glycemic measures under each scenario was presented as R2. Results: Under all missing patterns, R2 declined as the proportion of missing data increased, however, as the "block size" of missing data increased, the percentage of missing data had a more pronounced effect on the agreement between measures. For a 14-day CGM data set to be considered representative for percentage time in range (%TIR), at least 70% of CGM data should be available over at least 10 days (R2 > 0.9). Skewed outcome measures, such as percentage time below range and coefficient of variation, were more affected by missing data than the less skewed measures (%TIR, percentage time above range, mean glucose). Conclusions: Both the degree and pattern of missing data impact upon the accuracy of recommended CGM-derived glycemic measures. In planning research, an understanding of patterns of missing data in the study population is required to gauge the likely effects of missing data on outcome accuracy. Trial registration number: Australian New Zealand Clinic Trials Registry ACTRN12616000753459.
Subject(s)
Blood Glucose , Diabetes Mellitus, Type 1 , Humans , Glucose , Blood Glucose Self-Monitoring , Benchmarking , AustraliaABSTRACT
BACKGROUND: Identifying children ready for transfer out of the pediatric intensive care unit (PICU) is an area that may benefit from clinical decision support (CDS). We previously implemented a quality improvement (QI) initiative to accelerate the transfer evaluation of non-medically complex PICU patients with viral bronchiolitis receiving floor-appropriate respiratory support. OBJECTIVES: Design a CDS tool adaptation of this QI initiative to further accelerate transfer evaluation of appropriate patients. METHODS: The original initiative focused on identifying for transfer evaluation otherwise healthy children admitted to the PICU with bronchiolitis who had been receiving floor-appropriate levels of respiratory support for at least 6 hours. However, this initiative required that clinicians manually track the respiratory support of qualifying patients. We designed an electronic health record (EHR)-based CDS tool to automate identification of transfer-ready candidates. The tool parses EHR data to identify children meeting prior QI initiative criteria and alerts clinicians to assess transfer readiness once a child has been receiving floor-appropriate respiratory support for 6 hours. We compared time from reaching floor-appropriate support to placement of the transfer order ("time-to-transfer"), PICU length of stay (LOS), and hospital LOS between patients admitted prior to our QI initiative (December 1, 2018-October 19, 2019, "pre-QI phase"), during the initiative but before CDS tool implementation (October 20, 2019-February 7, 2022, "QI phase"), and after CDS implementation (February 8-November 11, 2022, "CDS phase"). RESULTS: CDS-phase patients (n = 131) had a shorter median time-to-transfer of 5.23 (interquartile range [IQR], 3.38-10.0) hours compared with QI-phase patients (n = 304) at 5.93 (IQR, 4.23-12.2) hours (p = 0.04). PICU and hospital LOS values decreased from the pre-QI (n = 150) to QI phase. Though LOS reductions were sustained during the CDS phase, further reductions from QI to CDS phase were not statistically significant. CONCLUSION: An EHR-based CDS adaptation of a prior QI initiative facilitated timely identification of PICU patients with bronchiolitis ready for transfer evaluation. Such tools might allow PICU clinicians to focus on other high-acuity tasks while accelerating transfer evaluation of appropriate patients.
Subject(s)
Bronchiolitis , Decision Support Systems, Clinical , Intensive Care Units, Pediatric , Patient Discharge , Child , Humans , Infant , Bronchiolitis/diagnosis , Bronchiolitis/therapy , Hospitalization , Length of Stay , Retrospective StudiesABSTRACT
AIM: To examine the within-person variability in plasma glucose responses to moderate-intensity morning exercise in young individuals with type 1 diabetes after overnight fasting and under basal insulin conditions. METHODS: In this pilot study, eight participants completed 40 min of moderate-intensity exercise at 60% VÌO2 peak on three separate days. The within-person standard deviation (SDw) in plasma glucose response was analysed both during and 1 h after exercise using the two visits per participant most closely matched by pre-exercise plasma glucose level. RESULTS: When the two closest matched visits per individual were included for analysis, mean (±SD) change in plasma glucose level was -1.8 ± 1.1 mmoL/L during exercise and -0.6 ± 1.0 mmoL/L during recovery, with the SDw of these changes being 0.5 mmol (95% CI 0.2, 0.8) during exercise and 0.8 mmoL/L (95% CI 0.4, 1.3) during recovery. The median intra-individual difference in plasma glucose level change was 0.3 mmoL/L [IQR 0.1, 0.7] during exercise and 0.8 mmoL/L [IQR 0.4, 1.0] during recovery. CONCLUSION: Within-person plasma glucose responses to moderate-intensity exercise may be reproducible under fasting and basal insulin conditions and similar pre-exercise plasma glucose levels. This finding may assist the design of future studies investigating both the reproducibility of glycaemic responses to exercise and blood glucose management for individuals with type 1 diabetes.
Subject(s)
Diabetes Mellitus, Type 1 , Insulins , Humans , Diabetes Mellitus, Type 1/therapy , Blood Glucose/analysis , Reproducibility of Results , Pilot Projects , InsulinABSTRACT
Rust fungi (Pucciniales) are a diverse group of plant pathogens in natural and agricultural systems. They pose ongoing threats to the diversity of native flora and cause annual crop yield losses. Agricultural rusts are predominantly managed with fungicides and breeding for resistance, but new control strategies are needed on non-agricultural plants and in fragile ecosystems. RNA interference (RNAi) induced by exogenous double-stranded RNA (dsRNA) has promise as a sustainable approach for managing plant-pathogenic fungi, including rust fungi. We investigated the mechanisms and impact of exogenous dsRNA on rust fungi through in vitro and whole-plant assays using two species as models, Austropuccinia psidii (the cause of myrtle rust) and Coleosporium plumeriae (the cause of frangipani rust). In vitro, dsRNA either associates externally or is internalized by urediniospores during the early stages of germination. The impact of dsRNA on rust infection architecture was examined on artificial leaf surfaces. dsRNA targeting predicted essential genes significantly reduced germination and inhibited development of infection structures, namely appressoria and penetration pegs. Exogenous dsRNA sprayed onto 1-year-old trees significantly reduced myrtle rust symptoms. Furthermore, we used comparative genomics to assess the wide-scale amenability of dsRNA to control rust fungi. We sequenced genomes of six species of rust fungi, including three new families (Araucariomyceaceae, Phragmidiaceae, and Skierkaceae) and identified key genes of the RNAi pathway across 15 species in eight families of Pucciniales. Together, these findings indicate that dsRNA targeting essential genes has potential for broad-use management of rust fungi across natural and agricultural systems.
Subject(s)
Basidiomycota , RNA, Double-Stranded , RNA, Double-Stranded/genetics , Ecosystem , Basidiomycota/genetics , Fungi/genetics , RNA Interference , GenomicsABSTRACT
INTRODUCTION: Access to effective contraception prevents unintended pregnancies among sexually active female youth. Potentially impacted by the Affordable Care Act's Medicaid-related policies, contraception use increased among sexually active high-school students from 2013 to 2019. METHODS: Analyses conducted in 2021 assessed state-level Youth Risk Behavior Survey data among female students in grades 9-12 who reported being sexually active. States that expanded Medicaid were compared with other states in 2013 (baseline) and 2019 (after expansion). Measured outcomes included self-reported use of moderately effective or highly effective, long-acting reversible contraception at last sex. Long-acting reversible contraception included intrauterine devices and implants. Moderately effective contraception included birth control pills, injectables, patches, or rings. Results were weighted and adjusted for age and race/ethnicity. RESULTS: Students in Medicaid expansion states (n=27,564) did not differ significantly from those in nonexpansion states (n=6,048) at baseline or after expansion with respect to age, age at first sex, or the number of sexual partners in the past 3 months; however, race/ethnicity population characteristics changed over time. Postexpansion increased use of intrauterine devices/implants was greater in Medicaid expansion states than in nonexpansion states (238.1% increase vs 120.0% increase, adjusted p=0.047). For those aged 16-17 years, Medicaid expansion states had a 283.3% increase in intrauterine device/implant use compared with an increase of 69.7% in nonexpansion states (adjusted p=0.004). CONCLUSIONS: Medicaid expansion was associated with a greater population-level increase in intrauterine device/implant use among sexually active female high-school students aged 16-17 years. These findings point to the possibility that the Affordable Care Act's Medicaid-related policies played a role in young women's use of intrauterine devices/implants.