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Biallelic pathogenic variants in theANO10gene cause spinocerebellar ataxia recessive type 10. We report two patients, both compound heterozygous forANO10variants, including two novel variants. Both patients had onset of cerebellar ataxia in adulthood with slow progression and presented corticospinal tract signs, eye movement abnormalities and cognitive executive impairment. One of them had temporal lobe epilepsy and she also carried a heterozygous variant inCACNB4, a potential risk gene for epilepsy. Both patients had pronounced cerebellar atrophy on cerebral magnetic resonance imaging (MRI) and reduced metabolic activity in cerebellum as well as in the frontal lobes on 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography ((18F)FDG PET) scans. We provide comprehensive clinical, radiological and genetic data on two patients carrying likely pathogenicANO10gene variants. Furthermore, we provide evidence for a cerebellar as well as a frontal involvement on brain (18F)FDG PET scans which has not previously been reported.

Our study demonstrates that with aging, female C57BL/6N mice exhibit higher in vivo aortic stiffness, reduced modulus of elasticity, aortic wall structural and extracellular matrix remodeling, and elevations in systemic inflammation. These changes are largely reflective of those that occur with aging in women. Thus, female C57BL/6N mice are a viable model of human aortic aging and the utility of these animals should be considered in future biomedical investigations.

OBJECTIVE The degree to which adolescent social media use is associated with depressive symptoms has been the source of considerable debate. Prior studies have been limited by a reliance on cross-sectional data and measures of overall "screen time." This study examines prospective associations between adolescents' emotional responses to social media experiences and depressive symptoms, and examines gender differences in these processes. METHOD A school-based sample of 687 adolescents (48.6% girls; Mage = 14.3; 38.1% White, 29.4% Hispanic, 23.0% Black) completed measures of positive and negative emotional responses to social media experiences and depressive symptoms at two time points, one year apart. RESULTS Higher levels of depressive symptoms were associated with more frequent negative emotional responses to social media experiences one year later, whereas greater positive emotional responses to social media were associated with later depressive symptoms. Girls reported overall greater emotional responses to social media experiences, but gender did not moderate associations between these emotional responses and depressive symptoms. CONCLUSION Findings highlight the importance of examining adolescents' positive and negative emotional experiences in the context of social media use, and the ways in which these experiences intersect with depressive symptoms, so as to identify youth who may be most vulnerable to negative effects of social media use.

The first record is presented of the sejoid genus Uropodella (family Uropodellidae, suborder Sejida) from Baltic amber, based on a well-preserved adult male. Morphologically, the specimen is as modern in structure as adults of the six known extant species of Uropodella. The diagnosis of the fossil in distinction to the extant species justifies naming it as a new species. This record traces the genus back to the Eocene, representing the oldest validated age for a mesostigmatan genus. A key to species of the genus Uropodella is given.

Biobased sprayable mulch (BSM) films are a potential alternative to herbicides, polyethylene plastic mulch film, and hand weeding for specialty crops. We developed a series of BSM films using locally available biomaterials [including corn (Zea mays) starch, glycerol, keratin hydrolysate, corn gluten meal, corn zein, eggshells, and isolated soy (Glycine max) protein] and tested their effects on weeds and crop yield during a total of seven greenhouse or field trials between 2017 and 2019 in Nebraska, USA. Application rates of BSM films applied in pots (greenhouse), planting holes in plastic film (field), or bed tops (field) ranged from 0.9 to 18.2 L⋅m−2; they were applied before and after the emergence of weeds. Weed control efficacy was variable, and results of greenhouse pots were rarely replicated under field conditions. Increasing the viscosity of the final suspension tested [BSM7; a mix of corn starch (72.8 g⋅L−1), glycerol (184.7 mL⋅L−1), keratin hydrolysate (733.3 mL⋅L−1), corn zein (19.8 g⋅L−1), and isolated soy protein (19.8 g⋅L−1)] reduced weed biomass by more than 96% in field-grown kale (Brassica oleracea var. sabellica) when applied to bare soil bed tops before or after weed emergence, but kale yield in treated plots was not different from the weedy control. The results demonstrated the potential for postemergence applications of BSM films, which increase application timing flexibility for growers. Further research is needed to explore the effects of BSM films on soil properties and crop physiology and yield.

One feature of adolescence is a rise in risk-taking behaviors, whereby the consequences of adolescents' risky action often impact their immediate surrounding such as their peers and parents (vicarious risk taking). Yet, little is known about how vicarious risk taking develops, particularly depending on who the risk affects and the type of risky behavior. In a 3-wave longitudinal fMRI study, 173 adolescents completed 1–3 years of a risky decision-making task where they took risks to win money for their best friend and parent (n with behavioral and fMRI data ranges from 139–144 and 100–116 participants, respectively, per wave). Results of this preregistered study suggest that adolescents did not differentially take adaptive (sensitivity to the expected value of reward during risk taking) and general (decision-making when the expected values of risk taking and staying safe are equivalent) risks for their best friend and parent from sixth to ninth grade. At the neural level, preregistered ROI analyses revealed no differences in the ventral striatum and ventromedial pFC during general nor adaptive risk taking for best friend versus parent over time. Furthermore, exploratory longitudinal whole-brain analyses revealed subthreshold differences between best friend and parent trajectories within regulatory regions during general vicarious risk taking and social-cognitive regions during adaptive vicarious risk taking. Our findings demonstrate that brain regions implicated in cognitive control and social-cognitive processes may distinguish behaviors involving peers and parents over time.

A central goal of linguistics is to understand how words evolve over time, and how geographic, demographic, and cognitive variables have influenced this process of evolution. Whereas past research has focused on how macro-level factors like frequency of word usage, population size, and borrowing impact lexical evolution, we draw on insights from cognitive and affective science to test whether the valence (positivity-negativity) of concepts explains variation in rates of lexical evolution. Using estimates of cognate replacement rates for 200 concepts on an Indo-European language tree spanning 6-10 millennia of language evolution, we find that words for negative concepts (e.g., dirty, bad) evolve more quickly than words for positive concepts (e.g., clean, good). In two large online studies, we find that people are more likely to choose to replace words for negative concepts than positive concepts. These effects hold controlling for frequency of use, borrowing, and other semantic properties. Our findings suggest that the valence of concepts affects micro-scale processes of guided variation, which scales up to produce macro-level patterns of lexical evolution. This process informs linguistics research on language change and psychological research on the affective and cognitive properties of lexical semantics.

Barrier islands within sheltered environments are an important natural defense from severe storm impacts for coastal communities worldwide. Despite their importance, these fetch-limited barrier islands remain understudied and their ability to withstand and recover from storms is not well-understood. Here, we present a case study of Sugarloaf Island in North Carolina that demonstrates the operational use of openly accessible LiDAR and aerial imagery data to quantify synoptic habitat, shoreline, and volumetric change between 2014 and 2020, a period that encompasses four hurricanes and a winter storm event. During this time period, our results show: (1) an 11–13% decrease in marsh and shrub habitat, (2) an average landward shoreline migration of 2.9 m yr−1 and up to 5.2 m yr−1 in extreme areas, and (3) a net volume loss of approximately 9800 m3. The results of this study highlight the importance of storms as a driver of morphologic change on Sugarloaf Island and have implications for better understanding the resiliency of fetch-limited barrier islands to storms. This work helps to enhance prerestoration data availability and supports knowledge-based decision-making regarding habitat change, erosional issues, and the efficacy of nature-based solutions to increase the resiliency of a coastal community in North Carolina.

To report speech outcomes after cochlear implantation (CI) for asymmetric hearing loss (AHL) and assess the influence of contralateral hearing.Retrospective review.Tertiary referral center.One hundred eighty-eight adults (mean age, 70 yr) undergoing CI for AHL from 2015 to 2020. Candidacy included pure-tone average (PTA) at least 70 dB hearing level and AzBio in quiet 60% or less in the implanted ear and AzBio in quiet greater than 40% in the contralateral ear.PTA; Consonant-Nucleus-Consonant (CNC) word, AzBio sentences scores; Speech, Spatial, and Qualities of Hearing Scale (SSQ).Mean preoperative PTA and AzBio in the implanted and contralateral ears were 85.2 and 68.1 dB hearing level and 24.7% and 69.2%, respectively. Mean CNC in the implanted ear increased from 18.3% preoperatively to 44.4% ( p0.0001) at 6 months and 49.3% ( p0.0001) at 12 months. Mean AzBio in the implanted ear improved from 24.7% preoperatively to 60.3% ( p0.0001) at 6 months and 64.3% ( p0.0001) at 12 months. Patients demonstrated significant improvement in all SSQ domains at 6 and 12 months. When comparing patients with preoperative contralateral AzBio greater than 60% versus 41% to 60%, no significant differences existed in postoperative CNC scores (6-mo: 47% versus 41%, p = 0.276; 12-mo: 51% versus 47%, p = 0.543). There were no significant differences in 6-month ( p = 0.936) or 12-month ( p = 0.792) CNC scores between patients with AHL (contralateral ear AzBio40%) and 169 unilateral CI patients meeting the traditional Medicare criteria (contralateral ear AzBio ≤40%).CI recipients with AHL derive significant speech improvements, supporting individual ear consideration for CI candidacy and patient benefit outside of current Medicare criteria.

Precurved cochlear implant (CI) electrode arrays have demonstrated superior audiometric outcomes compared with straight electrodes in a handful of studies. However, previous comparisons have often failed to account for preoperative hearing and age. This study compares hearing outcomes for precurved and straight electrodes by a single manufacturer while controlling for these and other factors in a large cohort.Retrospective cohort study.Tertiary academic medical center.Two hundred thirty-one adult CI recipients between 2015 and 2021 with cochlear (Sydney, Australia) 522/622 (straight) or 532/632 (precurved) electrode arrays.Postactivation speech recognition and audiometric testing.Speech recognition testing (consonant-nucleus-consonant word [CNCw] and AzBio) was collected at 6 and 12 months postactivation. Hearing preservation was characterized by a low-frequency pure-tone average shift, or the change between preoperative and postoperative low-frequency pure-tone average.Two hundred thirty-one patients (253 ears) with 6-month and/or 12-month CNCw or AzBio testing were included. One hundred forty-nine (59%) and 104 (41%) ears were implanted with straight and precurved electrode arrays, respectively. Average age at implantation was 70 years (interquartile range [IQR], 58-77 y). There was no significant difference in mean age between groups. CNCw scores were significantly different ( p = 0.001) between straight (51%; IQR, 36-67%) and precurved arrays (64%; IQR, 48-72%). AzBio scores were not significantly different ( p = 0.081) between straight (72%; IQR, 51-87%) and precurved arrays (81%; IQR, 57-90%). Controlling for age, race, sex, preoperative hearing, and follow-up time, precurved electrode arrays performed significantly better on CNCw (b = 10.0; 95% confidence interval, 4.2-16.0; p0.001) and AzBio (b = 8.9; 95% confidence interval, 1.8-16.0;, p = 0.014) testing. Hearing preservation was not different between electrodes on adjusted models.During the study period, patients undergoing placement of precurved electrode arrays had significantly higher CNC and AzBio scores than patients receiving straight electrodes, even after controlling for age, preoperative hearing, and follow-up time.Understanding the difference in audiometric outcomes between precurved and straight electrode arrays will help to guide electrode selection.To understand differences in speech recognition scores postoperatively by electrode array type (precurved versus straight).To demonstrate a difference in hearing performance postoperatively by electrode type.III.Approved by the Institutional IRB (090155).

This paper studies the health effects of Swedish prison reforms that held sentences constant but increased the share of time inmates had to serve. The increased time served did not harm post-release health and actually reduced mortality risk. We find especially large decreases in mortality for offenders not previously incarcerated, younger offenders, and those more attached to the labor market. Risk of suicide and circulatory death fell for inmates with mental health problems and older inmates, respectively. In-prison health care utilization and program participation increased with time served, suggesting health care treatment and services as the key mechanism for mortality declines. (JEL I12, I18, K42)

In 2019, the first cases of SARS-CoV-2 were detected in Wuhan, China, and by early 2020 the first cases were identified in the United States. SARS-CoV-2 infections increased in the US causing many states to implement stay-at-home orders and additional safety precautions to mitigate potential outbreaks. As policies changed throughout the pandemic and restrictions lifted, there was an increase in demand for COVID-19 testing which was costly, difficult to obtain, or had long turn-around times. Some academic institutions, including Boston University (BU), created an on-campus COVID-19 screening protocol as part of a plan for the safe return of students, faculty, and staff to campus with the option for in-person classes. At BU, we put together an automated high-throughput clinical testing laboratory with the capacity to run 45,000 individual tests weekly by Fall of 2020, with a purpose-built clinical testing laboratory, a multiplexed reverse transcription PCR (RT-qPCR) test, robotic instrumentation, and trained staff. There were many challenges including supply chain issues for personal protective equipment and testing materials in addition to equipment that were in high demand. The BU Clinical Testing Laboratory (CTL) was operational at the start of Fall 2020 and performed over 1 million SARS-CoV-2 PCR tests during the 2020-2021 academic year.

We evaluated the impact of a low intensity web-based and intensive nurse-administered intervention to reduce systolic blood pressure (SBP) among patients with prior MI.Secondary Prevention Risk Interventions via Telemedicine and Tailored Patient Education (SPRITE) was a three-arm trial. Patients were randomized to 1) post-MI education-only; 2) nurse-administered telephone program; or 3) web-based interactive tool. The study was conducted 2009-2013.Participants (n = 415) had a mean age of 61 years (standard deviation [SD], 11). Relative to the education-only group, the 12-month differential improvement in SBP was - 3.97 and - 3.27 mmHg for nurse-administered telephone and web-based groups, respectively. Neither were statistically significant. Post hoc exploratory subgroup analyses found participants who received a higher dose (12 encounters) in the nurse-administered telephone intervention (n = 60; 46%) had an 8.8 mmHg (95% CI, 0.69, 16.89; p = 0.03) differential SBP improvement versus low dose (11 encounters; n = 71; 54%). For the web-based intervention, those who had higher dose (n = 73; 53%;1 web encounter) experienced a 2.3 mmHg (95% CI, -10.74, 6.14; p = 0.59) differential SBP improvement versus low dose (n = 65; 47%).The main effects were not statistically significant.Completing the full dose of the intervention may be essential to experience the intervention effect.The unique identifier is NCT00901277 (http://www.gov/ct2/show/NCT00901277?term=NCT00901277rank=1).

To report Advanced Bionics (AB) Ultra (V1) and Ultra 3D (V1) cochlear implant (CI) electrode failures and revision speech recognition outcomes for patients at a large CI program.Retrospective case series.Tertiary referral center.Patients receiving Ultra (V1) or Ultra 3D (V1) devices as of September 21, 2021.Failure rate, revision surgery, speech recognition scores.To data, 65 (21.1%) of the 308 implanted devices are known failures, with 63 (20.5%) associated with the recent voluntary field corrective action (FCA). Average time to failure was 2.2 ± 1.1 years. Fifty-two patients (82.5%) elected for revision surgery. Among adults, immediate prerevision scores demonstrated a significant decrease from best-achieved scores with the faulty implant, with mean difference of -15.2% (p = 0.0115) for consonant-nucleus-consonant (CNC) and -27.3% (p0.0001) for AzBio in quiet. By 3 months postactivation of the revised device, CNC (p = 0.9766) and AzBio in quiet (p = 0.9501) scores were not significantly different than best prerevision scores. Overall, 15 of 19 patients regained or improved their best prerevision CNC score. The current trajectory for FCA device failures is approximately 6% per year.Compared to manufacturer reporting, a high number of patients experienced hard failures of the Ultra (V1) and Ultra 3D (V1) devices. Early identification of failures is possibly because of the diligent use of electrical field imaging testing. Most patients affected by the FCA regain or exceed their prefailure speech recognition score as soon as 3 months after revision surgery.

The purpose of this study was to assess the associations between malignancy, therapeutic regimens, and aorto-iliac aneurysm (i.e., abdominal aortic aneurysm [AAA]) growth rates.A retrospective single centre analysis identified patients with an AAA plus cancer. Patients who had two or more computed tomography angiograms over six months or more and additional malignancy were included. Clinical data and aneurysm diameters were analysed. AAA growth under cancer therapy (chemotherapy or radiation) was compared with a non-cancer AAA control cohort and to meta-analysis data. Statistics included t tests and a linear regression model with correction for initial aortic diameter and type of treatment.From 2003 to 2020, 217 patients (median age 70 years; 92% male) with 246 aneurysms (58.8% AAA) and 238 malignancies were identified. Prostate (26.7%) and lung (15.7%) cancer were most frequently seen. One hundred and fifty-seven patients (72.3%) received chemotherapy, 105 patients (48.4%) radiation, and 79 (36.4%) both. Annual AAA growth (mean ± standard deviation) was not statistically significantly different for cancer and non-cancer patients (2.0 ± 2.3 vs. 2.8 ± 2.1 mm/year; p = .20). However, subgroup analyses revealed that radiation was associated with a statistically significantly reduced mean aneurysm growth rate compared with cancer patients without radiation (1.1 ± 1.3 vs. 1.6 ± 2.1 mm/year; p = .046) and to the non-cancer control cohort (1.7 ± 1.9 vs. 2.8 ± 2.1 mm/year; p = .007). Administration of antimetabolites resulted in statistically significantly increased AAA growth (+ 0.9 mm/year; p = .011), while topoisomerase inhibitors (- 0.8 mm/year; p = .17) and anti-androgens (- 0.5 mm/year; p = .27) showed a possible trend for reduced growth. Similar observations were noted for iliac aneurysms (n = 85). Additionally, the effects persisted for chemotherapy combinations (2.6 ± 1.4 substances/patient).Patients with cancer and concomitant aortic aneurysms may require intensified monitoring when undergoing specific therapies, such as antimetabolite treatment, as they may experience an increased aneurysm growth rate. Radiation may be associated with reduced aneurysm growth.

Generalized epilepsy affects 24 million people globally; at least 25% of cases remain medically refractory. The thalamus, with widespread connections throughout the brain, plays a critical role in generalized epilepsy. The intrinsic properties of thalamic neurons and the synaptic connections between populations of neurons in the nucleus reticularis thalami and thalamocortical relay nuclei help generate different firing patterns that influence brain states. In particular, transitions from tonic firing to highly synchronized burst firing mode in thalamic neurons can cause seizures that rapidly generalize and cause altered awareness and unconsciousness. Here, we review the most recent advances in our understanding of how thalamic activity is regulated and discuss the gaps in our understanding of the mechanisms of generalized epilepsy syndromes. Elucidating the role of the thalamus in generalized epilepsy syndromes may lead to new opportunities to better treat pharmaco-resistant generalized epilepsy by thalamic modulation and dietary therapy.

Interdisciplinary research has seen a substantial growth in the past several decades, and data management plays a crucial role in this trend. New tools and sources of data drive interdisciplinarity and collaborations, and, in turn, interdisciplinary research produces complex, heterogeneous datasets that require different forms of data management and curation. How do interdisciplinary project members negotiate their work around diverse datasets? What role do ethics play in their data practices? How do interdisciplinary teams approach privacy and confidentiality as they collect, store, and organize their heterogeneous datasets? Previous research on interdisciplinary research practices often addresses issues of team dynamics rather than data management and curation. In this presentation we will share results from our study examining several interdisciplinary projects and their complex data practices. Through interviews, observations, and document analysis we have gathered a rich dataset about interdisciplinary data management and curation, and the role of universities in supporting such projects. We will illustrate how interdisciplinary projects, primarily in the social sciences and humanities, collaborate internally and externally and use tools and resources to share, organize, and curate their data. In particular, we will present a use case exhibiting the challenges and nuances of working with vulnerable or historically underrepresented populations. Our findings show that individual disciplinary backgrounds, particularly of the project leaders, affect how projects approach their data and its sensitivity and how they decide to grapple (or not) with issues of representation or privacy. To engage the audience in the further discussion, we will conclude our presentation with insights on data documentation, software interoperability, and collaborative dynamics in interdisciplinary projects.

Sea-level rise (SLR) will cause coastal groundwater to rise in many coastal urban environments. Inundation of contaminated soils by groundwater rise (GWR) will alter the physical, biological, and geochemical conditions that influence the fate and transport of existing contaminants. These transformed products can be more toxic and/or more mobile under future conditions driven by SLR and GWR. We reviewed the vulnerability of contaminated sites to GWR in a US national database and in a case comparison with the San Francisco Bay region to estimate the risk of rising groundwater to human and ecosystem health. The results show that 326 sites in the US Superfund program may be vulnerable to changes in groundwater depth or flow direction as a result of SLR, representing 18.1 million hectares of contaminated land. In the San Francisco Bay Area, we found that GWR is predicted to impact twice as much land area as inundation from SLR, and 5,282 additional state-managed sites of contamination may be vulnerable to inundation from GWR in a 1.0 m SLR scenario. Increases of only a few centimeters of elevation can mobilize soil contaminants, alter flow directions in a heterogeneous urban environment with underground pipes and utility trenches, and result in new exposure pathways. Pumping for flood protection will elevate the saltwater interface, changing groundwater salinity and mobilizing metals in soil. Socially vulnerable communities are disproportionately exposed to this risk at both the national scale and in a regional comparison with the San Francisco Bay Area.

Examining kidney fibrosis is crucial for mechanistic understanding and developing targeted strategies against chronic kidney disease (CKD). Persistent fibroblast activation and tubular epithelial cell (TEC) injury are key CKD contributors. However, cellular and transcriptional landscapes of CKD and specific activated kidney fibroblast clusters remain elusive. Here, we analyzed single cell transcriptomic profiles of two clinically relevant kidney fibrosis models which induced robust kidney parenchymal remodeling. We dissected the molecular and cellular landscapes of kidney stroma and newly identified three distinctive fibroblast clusters with “secretory”, “contractile” and “vascular” transcriptional enrichments. Also, both injuries generated failed repair TECs (frTECs) characterized by decline of mature epithelial markers and elevation of stromal and injury markers. Notably, frTECs shared transcriptional identity with distal nephron segments of the embryonic kidney. Moreover, we identified that both models exhibited robust and previously unrecognized distal spatial pattern of TEC injury, outlined by persistent elevation of renal TEC injury markers including Krt8, while the surviving proximal tubules (PTs) showed restored transcriptional signature. Furthermore, we found that long-term kidney injuries activated a prominent nephrogenic signature, including Sox4 and Hox gene elevation, which prevailed in the distal tubular segments. Our findings might advance understanding of and targeted intervention in fibrotic kidney disease.

The introduction of digital identification (e.g., eIDAS) and wallet standards (e.g., EUDI wallet) require compliance with privacy principles and clear communication of the principles through privacy notice and record of consent in the form of a privacy receipt. Regulation needs standards to help set the bar for reducing the privacy infringement risk. Without a standard-based implementation, solutions will be proprietary and siloed with no concern for interoperability, like privacy labels in Google and Apple app stores. Do existing standards address the gap, or do new ones need to be introduced? This article looks at the standards and regulations in three areas to answer this question: privacy protection standards, blockchain and DLT standards, and digital identification and wallet standards.

The aorta stiffens with aging in both men and women and predicts cardiovascular mortality. Stiffening occurs largely due to aortic wall structural remodeling induced, in part, by chronic low-grade inflammation. Use of animal models in biomedical research is essential for screening interventions for safety/efficacy and providing mechanistic insight that is difficult, or impossible, to obtain in humans. Male C57Bl/6N mice are an established model of aortic aging and have predominantly been used to determine mechanisms of and investigate interventions for mitigating age-related vascular changes. Although some studies have investigated mechanisms of artery stiffening in female mice in midlife, there is still a paucity of information regarding whether female mice are an appropriate model of age-related aortic stiffening/structural remodeling, especially in late life. Purpose: To determine if female C57Bl/6N mice are an appropriate model (i.e., reflective of the human condition) of age-related aortic stiffening, associated structural remodeling and systemic inflammation. Methods and Results: Data are mean ± SE. Aortic stiffness (pulse wave velocity) was higher in old (O; 27-29 mo) vs. young adult (Y; 6-7 mo) male (M) and female (F) C67Bl/6N mice (cm/sec: YM: 347±27, YF: 345±23, OM: 401±32, OF: 413±45; p0.15). Aortic elasticity was inversely related to IL-6 (r2=0.49, p NIH T32 AG000279, F31 FHL160173A, K99 HL159241 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Aging is the main risk factor for cardiovascular diseases (CVD) due in part to stiffening of large elastic arteries (e.g., aorta). High-fiber diets (H-FIB) are associated with reduced risk of CVD, but most people do not meet guidelines for adequate fiber intake. Short-chain fatty acids (SCFA), which are produced by gut microbiome-dependent fermentation of soluble fiber, are thought to mediate many of the benefits of a H-FIB. Acetate, the most prevalent SCFA in circulation, may be an adherable intervention as an oral supplement for improving age-related arterial stiffening and reducing the risk of CVD. PURPOSE: To determine if oral acetate supplementation can reduce age-related aortic stiffness comparably to a H-FIB. METHODS: Young (Y: 3mo; N=11-12/group) and old (O: 24mo; N=24-27/group) C57Bl/6N mice were split into 3 groups per age: 1) controls (YC/OC): standard chow (15% total, 2.5% soluble fiber) and normal drinking water; 2) acetate supplemented (YA/OA): standard chow and 100mM of calcium acetate in drinking water; and 3) H-FIB (YF/OF): chow supplemented with fiber (20% total, 8% soluble fiber) and normal drinking water. Aortic pulse wave velocity (aPWV; standard reference method of in vivo aortic stiffness) and blood pressure (BP; tail cuff) were measured before and after 8 weeks of intervention. Thoracic aortas were harvested to measure: elastic modulus (aEM) of aortic rings (structural measurement of stiffness dependent on engagement of collagen fibers); aortic wall thickness (structural contributor to arterial stiffening); and collagen abundance by immunofluorescence (pro-stiffening structural protein). RESULTS: Data are mean ± SE. aPWV was higher in old vs. young mice at baseline (O: 404±10 vs. Y: 335±4 cm/sec, p FUNDING: K99/R00 HL151818, CU Boulder BSI Scholarship This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Aging is the primary risk factor for cardiovascular diseases (CVD), the leading cause of death worldwide. Vascular endothelial dysfunction, a key antecedent to CVD, is primarily mediated by excess superoxide-related oxidative stress and decreased nitric oxide (NO) bioavailability. High-fiber diets (H-FIB) are associated with lower CVD-related morbidity/mortality, but adherence to guidelines for recommended dietary fiber intake is poor. Benefits of H-FIB are likely mediated by fermentation of soluble fiber into short-chain fatty acids (SCFAs) in the gut, which may improve endothelial function. Thus, supplementing SCFAs may be a more practical/effective intervention to reduce CVD risk with aging. PURPOSE: To determine if oral supplementation with acetate, the most prevalent SCFA in circulation, reverses vascular endothelial dysfunction in old mice as effectively as a H-FIB. METHODS: Old (O: 24mo) and young (Y: 3mo) male C57BL/6 mice (N=10-17/group) were randomized into 3 groups per age: 1) standard chow (15% total & 2.5% soluble fiber) + normal drinking water (YC/OC); 2) standard chow + 100mM calcium acetate supplemented in drinking water (YA/OA); or 3) H-FIB (20% total & 8% soluble fiber [inulin added to the standard chow]) + normal drinking water (YF/OF). Endothelium-dependent dilation (EDD; ex vivo carotid artery dilation to increasing doses of acetylcholine) and associated mechanisms were assessed following 8 weeks of intervention. RESULTS: Data are mean ± SE. Age-related impairments in peak EDD (YC: 92±1%; OC: 81±2%, p0.8 vs. YC), suggesting that the interventions effects are specific to aging. There were no differences in smooth muscle sensitivity to NO (peak dilation to sodium nitroprusside; OC: 98±1%; OA: 99±0%; OF: 99±0%, p=0.1), indicating that differences in EDD were endothelium-dependent. Instead, these changes were likely NO-mediated, as addition of the endothelial NO synthase inhibitor L-NAME abolished differences in peak EDD (OC: 51±4%; OA: 47±8%; OF: 54±6%, p=0.8). Aortic superoxide production (electron paramagnetic resonance spectroscopy) was lower in old acetate-treated mice (OC: 50±7; OA: 29±3 AU, p=0.04), and tended to be lower in H-FIB mice (OC vs. OF: 33 AU, p=0.18). Incubation with the superoxide scavenger TEMPOL improved peak EDD in OC mice (OC: 81±2%; OC+TEMPOL: 93±2%, p K99/R00 HL151818, F31 HL164004 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.