Time for a Reframe: Shifting Focus From Continuous Glucose Monitor Uptake to Sustainable Use to Optimize Outcomes.

Continuous glucose monitors (CGMs) improve glycemic outcomes and quality of life for many people with diabetes. Research and clinical practice efforts have focused on CGM initiation and uptake. There is limited understanding of how to sustain CGM use to realize these benefits and limited consideration for different reasons/goals for CGM use. Therefore, we apply the Information-Motivation-Behavioral Skills (IMB) model as an organizing framework to advance understanding of CGM use as a complex, ongoing self-management behavior. We present a person-centered, dynamic perspective with the central thesis that IMB predictors of optimal CGM use vary based on the CGM use goal of the person with diabetes. This reframe emphasizes the importance of identifying and articulating each person's goal for CGM use to inform education and support.

Cortical activation among young adults during mobility in an indoor real-world environment: A mobile EEG approach.

Human mobility requires neurocognitive inputs to safely navigate the environment. Previous research has examined neural processes that underly walking using mobile neuroimaging technologies, yet few studies have incorporated true real-world methods without a specific task imposed on participants (e.g., dual-task, motor demands). The present study included 40 young adults (M = 22.60, SD = 2.63, 24 female) and utilized mobile electroencephalography (EEG) to examine and compare theta, alpha, and beta frequency band power (µV2) during sitting and walking in laboratory and real-world environments. EEG data was recorded using the Muse S brain sensing headband, a portable system equipped with four electrodes (two frontal, two temporal) and one reference sensor. Qualitative data detailing the thoughts of each participant were collected after each condition. For the quantitative data, a 2 × 2 repeated measures ANOVA with within subject factors of environment and mobility was conducted with full participant datasets (n = 17, M = 22.59, SD = 2.97, 10 female). Thematic analysis was performed on the qualitative data (n = 40). Our findings support that mobility and environment may modulate neural activity, as we observed increased brain activation for walking compared to sitting, and for real-world walking compared to laboratory walking. We identified five qualitative themes across the four conditions 1) physical sensations and bodily awareness, 2) responsibilities and planning, 3) environmental awareness, 4) mobility, and 5) spotlight effect. Our study highlights the importance and potential for real-world methods to supplement standard research practices to increase the ecological validity of studies conducted in the fields of neuroscience and kinesiology.

Stereotactic Ablative Radiation for Oligoprogressive Cancers: Results of the Randomized Phase 2 STOP Trial.

PURPOSE: This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of SABR to standard of care (SOC) systemic therapy. METHODS AND MATERIALS: We enrolled patients with 1 to 5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs noncytotoxic), randomized 1:2 between continued SOC treatment versus SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all nonhematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events, and duration of systemic therapy postrandomization. RESULTS: Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. The median age was 67 years, and 39 (43%) were women. The most common primary sites were lung (44%), genitourinary (23%), and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. The median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs 4.3 months in the SOC arm, but curves cross and 2-year PFS was 9% vs 24%, respectively; P = .91). The median OS was 31.2 months versus 27.4 months, respectively (P = .22). Lesional control was superior with SABR (70% vs 38%, respectively; P = .0015). There were 2 (3.4%) grade 3 and no grade 4/5 adverse events attributable to SABR. CONCLUSIONS: SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

Prevalence and Correlates of Suspected and Diagnosed Traumatic Brain Injuries among US School-Aged Children.

Objective: To (1) estimate the lifetime prevalence of suspected and diagnosed traumatic brain injury (TBI) based on parent report overall and select sociodemographic characteristics; and (2) describe differences in prevalence of health conditions and health-related risk factors by whether a child had a lifetime history of diagnosed TBI. Study design: We analyzed data from the 2020 National Survey of Children's Health, a cross-sectional address-based survey of US households. A categorical variable was created on the basis of parent responses to 3 questions inquiring about their suspicion of their child having a brain injury, if they sought medical care, and if the health care provider provided a diagnosis. Parents also were asked to report on their child's additional health conditions, functional indicators, school and social factors, and health care access and service use. Results: The prevalence of lifetime diagnosed TBI was 4.2% (95% CI 3.8-4.5). Children with a parent-reported lifetime history of diagnosed TBI were more likely to have a variety of health conditions, special health care needs, disabilities, activity limitations, missed days of school, and unmet care coordination needs, compared with those without a history. However, they were more likely to have a usual source of sick care and to receive more health-related services. Conclusions: For school-aged children, a history of TBI is associated with parent-reported health needs and conditions, as well as missed days from school. It is particularly important for parents to seek care when they suspect their child has experienced a TBI to receive a diagnosis and monitor the impacts of the TBI.

Magnetic Resonance Imaging to Detect Structural Brain Changes in Huntington's Disease: A Review of Data from Mouse Models.

Structural magnetic resonance imaging (MRI) is a powerful tool to visualize 3D neuroanatomy and assess pathology and disease progression in neurodegenerative disorders such as Huntington's disease (HD). The development of mouse models of HD that reproduce many of the psychiatric, motor and cognitive impairments observed in human HD has improved our understanding of the disease and provided opportunities for testing novel therapies. Similar to the clinical scenario, MRI of mouse models of HD demonstrates onset and progression of brain pathology. Here, we provided an overview of the articles that used structural MRI in mouse models of HD to date, highlighting the differences between studies and models and describing gaps in the current state of knowledge and recommendations for future studies.

Internal tremors and vibrations in long COVID: a cross-sectional study.

BACKGROUND: Internal tremors and vibrations are symptoms previously described as part of neurologic disorders but not fully described as a part of long COVID. This study compared pre-pandemic comorbidities, new-onset conditions, and long COVID symptoms between people with internal tremors and vibrations as part of their long COVID symptoms and people with long COVID but without these symptoms. METHODS: The Yale Listen to Immune, Symptom and Treatment Experiences Now (LISTEN) Study surveyed 423 adults who had long COVID between May 12, 2022 and June 1, 2023. The exposure variable was long COVID symptoms of internal tremors and vibrations. The outcome variables were demographic characteristics, pre-pandemic comorbidities, new-onset conditions, other symptoms, and quality of life. RESULTS: Among study participants with long COVID, median age was 46 years [IQR, 38-56]), 74% were female, 87% were Non-Hispanic White, and 158 (37%) reported "internal tremors, or buzzing/vibration" as a long COVID symptom. The 2 groups reported similar pre-pandemic comorbidities, but people with internal tremors reported worse health as measured by the Euro-QoL visual analogue scale (median: 40 points [IQR, 30-60] vs. 50 points [IQR, 35-62], P = 0.007) and had higher rates of new-onset mast cell disorders (11% [95% CI, 7.1-18] vs. 2.6% [1.2-5.6], P = 0.008) and neurologic conditions (22% [95% CI, 16-29] vs. 8.3% [5.4-12], P = 0.004). CONCLUSIONS: Among people with long COVID, those with internal tremors and vibrations had different conditions and symptoms and worse health status compared with others who had long COVID without these symptoms.

Interim Phase II Results Using Panitumumab-IRDye800CW during Transoral Robotic Surgery in Patients with Oropharyngeal Cancer.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has continually increased during the past several decades. Using transoral robotic surgery (TORS) significantly improves functional outcomes relative to open surgery for OPSCC. However, TORS limits tactile feedback, which is often the most important element of cancer surgery. Fluorescence-guided surgery (FGS) strategies to aid surgeon assessment of malignancy for resection are in various phases of clinical research but exhibit the greatest potential impact for improving patient care when the surgeon receives limited tactile feedback, such as during TORS. Here, we assessed the feasibility of intraoperative fluorescence imaging using panitumumab-IRDye800CW (PAN800) during TORS in patients with OPSCC. PATIENTS AND METHODS: Twelve consecutive patients with OPSCC were enrolled as part of a nonrandomized, prospective, phase II FGS clinical trial using PAN800. TORS was performed with an integrated robot camera for surgeon assessment of fluorescence. Intraoperative and ex vivo fluorescence signals in tumors and normal tissue were quantified and correlated with histopathology. RESULTS: Intraoperative robot fluorescence views delineated OPSCC from normal tissue throughout the TORS procedure (10.7 mean tumor-to-background ratio), including in tumors with low expression of the molecular target. Tumor-specific fluorescence was consistent with surgeon-defined tumor borders requiring resection. Intraoperative robot fluorescence imaging revealed an OPSCC fragment initially overlooked during TORS based on brightfield views, further substantiating the clinical benefit of this FGS approach. CONCLUSIONS: The results from this patient with OPSCC cohort support further clinical assessment of FGS during TORS to aid resection of solid tumors.

Preventive Service Usage and New Chronic Disease Diagnoses: Using PCORnet Data to Identify Emerging Trends, United States, 2018-2022.

Background: Data modernization efforts to strengthen surveillance capacity could help assess trends in use of preventive services and diagnoses of new chronic disease during the COVID-19 pandemic, which broadly disrupted health care access. Methods: This cross-sectional study examined electronic health record data from US adults aged 21 to 79 years in a large national research network (PCORnet), to describe use of 8 preventive health services (N = 30,783,825 patients) and new diagnoses of 9 chronic diseases (N = 31,588,222 patients) during 2018 through 2022. Joinpoint regression assessed significant trends, and health debt was calculated comparing 2020 through 2022 volume to prepandemic (2018 and 2019) levels. Results: From 2018 to 2022, use of some preventive services increased (hemoglobin A1c and lung computed tomography, both P < .05), others remained consistent (lipid testing, wellness visits, mammograms, Papanicolaou tests or human papillomavirus tests, stool-based screening), and colonoscopies or sigmoidoscopies declined (P < .01). Annual new chronic disease diagnoses were mostly stable (6% hypertension; 4% to 5% cholesterol; 4% diabetes; 1% colonic adenoma; 0.1% colorectal cancer; among women, 0.5% breast cancer), although some declined (lung cancer, cervical intraepithelial neoplasia or carcinoma in situ, cervical cancer, all P < .05). The pandemic resulted in health debt, because use of most preventive services and new diagnoses of chronic disease were less than expected during 2020; these partially rebounded in subsequent years. Colorectal screening and colonic adenoma detection by age group aligned with screening recommendation age changes during this period. Conclusion: Among over 30 million patients receiving care during 2018 through 2022, use of preventive services and new diagnoses of chronic disease declined in 2020 and then rebounded, with some remaining health debt. These data highlight opportunities to augment traditional surveillance with EHR-based data.

Online toolkits for collaborative and inclusive global research in urban evolutionary ecology.

Urban evolutionary ecology is inherently interdisciplinary. Moreover, it is a field with global significance. However, bringing researchers and resources together across fields and countries is challenging. Therefore, an online collaborative research hub, where common methods and best practices are shared among scientists from diverse geographic, ethnic, and career backgrounds would make research focused on urban evolutionary ecology more inclusive. Here, we describe a freely available online research hub for toolkits that facilitate global research in urban evolutionary ecology. We provide rationales and descriptions of toolkits for: (1) decolonizing urban evolutionary ecology; (2) identifying and fostering international collaborative partnerships; (3) common methods and freely-available datasets for trait mapping across cities; (4) common methods and freely-available datasets for cross-city evolutionary ecology experiments; and (5) best practices and freely available resources for public outreach and communication of research findings in urban evolutionary ecology. We outline how the toolkits can be accessed, archived, and modified over time in order to sustain long-term global research that will advance our understanding of urban evolutionary ecology.

Effects of a Patient Portal Intervention to Address Diabetes Care Gaps: Protocol for a Pragmatic Randomized Controlled Trial.

BACKGROUND: Despite the potential to significantly reduce complications, many patients do not consistently receive diabetes preventive care. Our research team recently applied user-centered design sprint methodology to develop a patient portal intervention empowering patients to address selected diabetes care gaps (eg, no diabetes eye examination in last 12 months). OBJECTIVE: This study aims to evaluate the effect of our novel diabetes care gap intervention on completion of selected evidence-based diabetes preventive care services and secondary outcomes. METHODS: We are conducting a pragmatic randomized controlled trial of the effect of the intervention on diabetes care gaps. Adult patients with diabetes mellitus (DM) are recruited from primary care clinics affiliated with Vanderbilt University Medical Center. Participants are eligible if they have type 1 or 2 DM, can read in English, are aged 18-75 years, have a current patient portal account, and have reliable access to a mobile device with internet access. We exclude patients with medical conditions that prevent them from using a mobile device, severe difficulty seeing, pregnant women or women who plan to become pregnant during the study period, and patients on dialysis. Participants will be randomly assigned to the intervention or usual care. The primary outcome measure will be the number of diabetes care gaps among 4 DM preventive care services (diabetes eye examination, pneumococcal vaccination, hemoglobin A1c, and urine microalbumin) at 12 months after randomization. Secondary outcomes will include diabetes self-efficacy, confidence managing diabetes in general, understanding of diabetes preventive care, diabetes distress, patient portal satisfaction, and patient-initiated orders at baseline, 3 months, 6 months, and 12 months after randomization. An ordinal logistic regression model will be used to quantify the effect of the intervention on the number of diabetes care gaps at the 12-month follow-up. For dichotomous secondary outcomes, a logistic regression model will be used with random effects for the clinic and provider variables as needed. For continuous secondary outcomes, a regression model will be used. RESULTS: This study is ongoing. Recruitment was closed in February 2022; a total of 433 patients were randomized. Of those randomized, most (n=288, 66.5%) were non-Hispanic White, 33.5% (n=145) were racial or ethnic minorities, 33.9% (n=147) were aged 65 years or older, and 30.7% (n=133) indicated limited health literacy. CONCLUSIONS: The study directly tests the hypothesis that a patient portal intervention-alerting patients about selected diabetes care gaps, fostering understanding of their significance, and allowing patients to initiate care-will reduce diabetes care gaps compared with usual care. The insights gained from this study may have broad implications for developing future interventions to address various care gaps, such as gaps in cancer screening, and contribute to the development of effective, scalable, and sustainable approaches to engage patients in chronic disease management and prevention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04894903; https://classic.clinicaltrials.gov/ct2/show/NCT04894903. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56123.

Coarse-grained modeling of annexin A2-induced microdomain formation on a vesicle.

Annexin A2 (A2)-induced microdomain formation is a key step in biological processes such as Ca2+-mediated exocytosis in neuroendocrine cells. In this work, a total of 15 coarse-grained molecular dynamics simulations were performed on vesicle models having a diameter of approximately 250 Å for 15 µs each using the Martini2 force field. Five simulations were performed in the presence of 10 A2, 5 in the presence of A2 but absence of PIP2, and 5 simulations in the absence of A2 but presence of PIP2. Consistent results were generated among the simulations. A2-induced PIP2 microdomain formation was observed and shown to occur in three phases: A2-vesicle association, localized A2-induced PIP2 clustering, and A2 aggregation driving PIP2 microdomain formation. The relationship between A2 aggregation and PIP2 microdomain formation was quantitatively described using a novel method which calculated the variance among protein and lipid positions via the Fréchet mean. A large reduction in PIP2 variance was observed in the presence of A2 but not in its absence. This reduction in PIP2 variance was proportional to the reduction observed in A2 variance and demonstrates that the observed PIP2 microdomain formation is dependent upon A2 aggregation. The three-phase model of A2-induced microdomain formation generated in this work will serve as a valuable guide for further experimental studies and the development of novel A2 inhibitors. No microdomain formation was observed in the absence of A2 and minimal A2-membrane interaction was observed in the absence of PIP2.

McConnell's sign predicts normotensive shock in patients with acute pulmonary embolism.

BACKGROUND: Patients with intermediate-risk pulmonary embolism (PE) and normotensive shock may have worse outcomes. However, diagnosis of normotensive shock requires invasive hemodynamics. Our objective was to assess the predictive value of McConnell's sign in identifying normotensive shock in patients with intermediate-risk PE. METHODS: Patients with intermediate-risk PE who underwent percutaneous mechanical thrombectomy between August 2020 and April 2023 at a large academic public hospital were included in the study. Normotensive shock was defined as systolic blood pressure ≥ 90 mmHg without vasopressor support with pre-procedural invasive measures of cardiac index ≤2.2 L/min/m2 and clinical evidence of hypoperfusion (i.e. elevated lactate, oliguria). The primary outcome was the association between McConnell's sign and normotensive shock. RESULTS: Those with McConnell's sign (29/40, 72.5 %) had higher heart rate (114 vs 99 beats/min, p = 0.008), higher rates of elevated lactate (86 % vs 55 %, p = 0.038), lower cardiac index (1.9 vs 3.1 L/min/m2, p = 0.003), and higher rates of normotensive shock (76 % vs 27 %, p = 0.005). McConnell's sign had a sensitivity of 88 % and specificity of 53 % for identifying intermediate-risk PE patients with normotensive shock. Patients with McConnell's sign had an increased odds (odds ratio 8.38, confidence interval: 1.73-40.53, p = 0.008; area under the curve 0.70, 95 % confidence interval: 0.56-0.85) of normotensive shock. CONCLUSION: This is the first study to suggest that McConnell's sign may identify those in the intermediate-risk group who are at risk for normotensive shock. Larger cohorts are needed to validate our findings.

Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear.

Nonfatal Emergency Department Visits Associated with Fall-Related Fractured Skulls of Infants Aged 0-4 Months.

BACKGROUND: Children aged 0-4 years have the highest rate of emergency department (ED) visits for traumatic brain injury (TBI); falls are the leading cause. Infants younger than 2 years are more likely to sustain a fractured skull after a fall. OBJECTIVE: This study examined caregiver actions and products associated with ED visits for fall-related fractured skulls in infants aged 0-4 months. METHODS: Data were analyzed from the 2001-2017 National Electronic Injury Surveillance System-All Injury Program. Case narratives of infants aged 0-4 months who visited an ED for a fall-related skull fracture were examined to code caregiver actions preceding the fall. Product codes determined fall location and product type involved (e.g., flooring, bed, or stairs). All national estimates were weighted. RESULTS: There were more than 27,000 ED visits (weighted estimate) of infants aged 0-4 months for a nonfatal fall-related fractured skull between 2001 and 2017. Most were younger than 2 months (46.7%) and male (54.4%). Falls occurred primarily in the home (69.9%) and required hospitalization (76.4%). Primary caregiver actions coded involved placing (58.6%), dropping (22.7%), and carrying an infant (16.6%). Floor surfaces were the most common product (mentioned in 24.0% of the cases). CONCLUSIONS: Fall-related fractured skulls are a health and developmental concern for infants, highlighting the importance of a comprehensive assessment at the time of the injury to better understand adult actions. Findings indicated the need to develop prevention messages that include safe carrying and placement of infants.

Repeat Radiosurgery for Sporadic Vestibular Schwannoma After Primary Radiosurgical Failure: An International Multi-institutional Investigation.

OBJECTIVE: To describe outcomes of patients with sporadic vestibular schwannoma (VS) who underwent repeat stereotactic radiosurgery (SRS) after primary SRS failure. STUDY DESIGN: Multi-institutional historical cohort study. SETTING: Five tertiary care referral centers. PATIENTS: Adults ≥18 years old with sporadic VS. INTERVENTION: Primary and repeat treatment with SRS. MAIN OUTCOME MEASURE: Microsurgery-free survival after repeat SRS. RESULTS: Across institutions, 32 patients underwent repeat SRS after primary SRS. Most patients (74%) had tumors with cerebellopontine angle extension at primary SRS (median size, 13.5 mm [interquartile range, 7.5-18.8] mm). After primary SRS, patients underwent repeat SRS at a median of 4.8 years (interquartile range, 3.2-5.7 yr). For treatment modality, 30 (94%) patients received gamma knife for primary treatment and 31 (97%) patients received gamma knife as their repeat treatment. Median tumor volume increased from 0.970 cm3 at primary SRS to 2.200 cm3 at repeat SRS. Facial nerve function worsened in two patients after primary SRS and in two patients after repeat SRS. There were no instances of intracranial complications after repeat SRS. Microsurgery-free survival rates (95% confidence interval; number still at risk) at 1, 3, and 5 years after repeat SRS were 97% (90-100%, 24), 84% (71-100%, 13), and 68% (48-96%, 6), respectively. There was one occurrence of malignancy diagnosed after repeat radiosurgery. CONCLUSION: Overall, repeat SRS for sporadic VS has comparable risk profile, but lower rates of tumor control, compared with primary SRS.

Perinatal exposure to atazanavir-based antiretroviral regimens in a mouse model leads to differential long-term motor and cognitive deficits dependent on the NRTI backbone.

Background: Combination antiretroviral therapy (ART) use in pregnancy has been pivotal in improving maternal health and reducing perinatal HIV transmission. However, children born HIV-exposed uninfected fall behind their unexposed peers in several areas including neurodevelopment. The contribution of in utero ART exposure to these deficits is not clear. Here we present our findings of neurocognitive outcomes in adult mice exposed in utero to ART. Methods: Dams were treated with a combination of ritonavir-boosted atazanavir with either abacavir plus lamivudine (ABC/3TC + ATV/r) or tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC + ATV/r), or water as a control, administered daily from day of plug detection to birth. Offspring underwent a battery of behavioral tests that investigated motor performance and cognition starting at 6-weeks of age and ending at 8 months. Changes in brain structure were assessed using magnetic resonance imaging and immunohistochemistry. Expression of genes involved in neural circuitry and synaptic transmission were assessed in the hippocampus, a region strongly associated with memory formation, using qPCR. Findings: Pups exposed to TDF/FTC + ATV/r showed increased motor activity and exploratory drive, and deficits in hippocampal-dependent working memory and social interaction, while pups exposed to ABC/3TC + ATV/r showed increased grooming, and deficits in working memory and social interaction. Significant volumetric reductions in the brain were seen only in the ABC/3TC + ATV/r group and were associated with reduced neuronal counts in the hippocampus. Altered neurotransmitter receptor mRNA expression as well as changes in expression of the neurotrophic factor BDNF and its receptors were observed in both ART-exposed groups in a sex-dependent manner. Interpretation: In our model, in utero ART exposure had long-term effects on brain development and cognitive and motor outcomes in adulthood. Our data show that neurological outcomes can be influenced by the type of nucleoside reverse transcriptase inhibitor backbone of the regimen and not just the base drug, and display sex differences.

Goal change and goal achievement for emerging adults across the pilot FAMS-T1D intervention for type 1 diabetes.

Objective: Interventions for emerging adults (EAs) with type 1 diabetes (T1D) focus on goal setting, but little is known about how goal achievement relates to intervention outcomes. We examined how goals change, how goal achievement relates to diabetes outcomes, and identified barriers and facilitators to goal achievement. Method: EAs with T1D (N=29, M age=21.6 years, 57% female) were coached monthly to set a behavioral goal across a 3-month feasibility trial. Coaching notes were qualitatively coded regarding type, complexity, and changes in goals. Goal achievement was measured via daily responses to texts. HbA1c, self-efficacy, diabetes distress, and self-care were assessed pre- and post-intervention. Results: EAs frequently set food goals (79%) in combination with other goals. EAs overwhelmingly changed their goals (90%), with most increasing goal complexity. Goal achievement was high (79% of days) and not affected by goal change or goal complexity. Goal achievement was associated with increases in self-efficacy and self-care across time. Qualitative themes revealed that aspects of self-regulation and social-regulation were important for goal achievement. Conclusion: Meeting daily diabetes goals may enhance self-efficacy and self-care for diabetes. Practice Implications: Assisting EAs to reduce self-regulation challenges and enhance social support for goals may lead to better diabetes outcomes.

Differential impact of perfluorooctanoic acid and fluorotelomer ethoxylates on placental metabolism in mice.

Poly- and perfluoroalkyl substances (PFAS) are a group of compounds with uses in industry and many consumer products. Concerns about the potential health effects of these compounds resulted in regulation by the Stockholm Convention on the use of three of the most common PFAS, including perfluorooctanoic acid (PFOA). Thousands of PFAS remain in production that are unregulated and for which their toxicity is unknown. Our group recently identified a new class of PFAS, fluorotelomer ethoxylates (FTEOs), in indoor dust and industrial wastewater. In this study, we investigated the effect of PFAS on placental metabolism by exposing healthy, pregnant CD-1 mice to PFOA or FTEOs at one of three concentrations (0 ng/L (controls), 5 ng/L, 100 ng/L) (n = 7-8/group). While PFOA is banned and PFOA concentrations in human blood are decreasing, we hypothesize that FTEOs will cause adverse pregnancy outcomes similar to PFOA, the compounds they were meant to replace. Placental tissue samples were collected at embryonic day 17.5 and 1H solid-state magic angle spinning nuclear magnetic resonance spectroscopy was used to determine the relative concentration of placental metabolites (n = 18-20/group). At the highest concentration, the relative concentrations of glucose and threonine were increased and the relative concentration of creatine was decreased in the PFOA-exposed placentas compared to controls (p < 0.05). In contrast, the relative concentrations of asparagine and lysine were decreased and the relative concentration of creatine was increased in the FTEOs-exposed placentas compared to controls (p < 0.05). Partial least squares - discriminant analysis showed the FTEOs-exposed and control groups were significantly separated (p < 0.005) and pathway analysis found four biochemical pathways were perturbed following PFOA exposure, while one pathway was altered following FTEOs exposure. Maternal exposure to PFOA and FTEOs had a significant impact on the placental metabolome, with the effect depending on the pollutant. This work motivates further studies to determine exposure levels and evaluate associations with adverse outcomes in human pregnancies.

Acceptability and feasibility of FAMS-T1D mHealth intervention to optimize self- and social regulation for emerging adults with type 1 diabetes.

BACKGROUND: Among emerging adults with type 1 diabetes (T1D), self-regulation and social regulation skills can help avoid high A1c and diabetes distress. FAMS (Family/friend Activation to Motivate Self-care) is mobile phone-delivered intervention that supports development of these skills and is efficacious among adults with type 2 diabetes. However, the acceptability and feasibility of the FAMS intervention among emerging adults with T1D are unknown. METHODS: Therefore, we adapted FAMS for in a new disease context and developmental stage and then conducted a 3-month mixed-methods pre-post pilot study. Participants were emerging adults with T1D and a friend/family member enrolled as a support person (optional). Feasibility/acceptability outcomes and associated progression thresholds were recruitment (≥ 70% eligible emerging adults), retention (≥ 85%), intervention engagement (≥ 70%), and satisfaction (≥ 70%). We also collected qualitative feedback to determine if the intervention addressed relevant needs and explored changes in outcomes of interest (family/friend involvement, self-efficacy, self-management, distress, A1c). RESULTS: Recruitment rates indicate recruitment of emerging adults with T1D (n = 30) and their support persons (n = 20) is feasible - 79% of emerging adults who screened as eligible enrolled and 70% of enrolled emerging adults invited a support person. Emerging adults completed 98% of coaching sessions, and response rates to automated text messages were median 85% IQR [68%, 90%]. Changes in selected measures for outcomes of interest were in expected directions suggesting sensitivity to changes occasioned by the intervention in a future evaluative trial. Emerging adults said FAMS-T1D helped with setting realistic goals, motivated them to prioritize diabetes goals, and increased support, indicating acceptability of the intervention in this new disease and developmental context. CONCLUSIONS: Findings suggest potential for FAMS-T1D to engage emerging adults and their support persons and feasibility for an evaluative trial examining effects on self-regulation (self-efficacy, self-management), social regulation (family/friend involvement), and outcomes (diabetes distress, A1c). TRIAL REGISTRATION: We did not register this study on ClinicalTrials.gov because the purpose of the study was to assess the feasibility and acceptability of the intervention and study procedures and measures in preparation for a future trial. The purpose of that future trial will be to evaluate the effect of the intervention on health-related biomedical and behavioral outcomes, and that trial will be registered accordingly.

Insight into the adaptive role of arachnid genome-wide duplication through chromosome-level genome assembly of the Western black widow spider.

Although spiders are one of the most diverse groups of arthropods, the genetic architecture of their evolutionary adaptations is largely unknown. Specifically, ancient genome-wide duplication occurring during arachnid evolution ~450 mya resulted in a vast assembly of gene families, yet the extent to which selection has shaped this variation is understudied. To aid in comparative genome sequence analyses, we provide a chromosome-level genome of the Western black widow spider (Latrodectus hesperus)-a focus due to its silk properties, venom applications, and as a model for urban adaptation. We used long-read and Hi-C sequencing data, combined with transcriptomes, to assemble 14 chromosomes in a 1.46 Gb genome, with 38,393 genes annotated, and a BUSCO score of 95.3%. Our analyses identified high repetitive gene content and heterozygosity, consistent with other spider genomes, which has led to challenges in genome characterization. Our comparative evolutionary analyses of eight genomes available for species within the Araneoidea group (orb weavers and their descendants) identified 1,827 single-copy orthologs. Of these, 155 exhibit significant positive selection primarily associated with developmental genes, and with traits linked to sensory perception. These results support the hypothesis that several traits unique to spiders emerged from the adaptive evolution of ohnologs-or retained ancestrally duplicated genes-from ancient genome-wide duplication. These comparative spider genome analyses can serve as a model to understand how positive selection continually shapes ancestral duplications in generating novel traits today within and between diverse taxonomic groups.