Spatially distributed atmospheric boundary layer properties in Houston - A value-added observational dataset.

In 2022, Houston, TX became a nexus for field campaigns aiming to further our understanding of the feedbacks between convective clouds, aerosols and atmospheric boundary layer (ABL) properties. Houston's proximity to the Gulf of Mexico and Galveston Bay motivated the collection of spatially distributed observations to disentangle coastal and urban processes. This paper presents a value-added ABL dataset derived from observations collected by eight research teams over 46 days between 2 June - 18 September 2022. The dataset spans 14 sites distributed within a ~80-km radius around Houston. Measurements from three types of instruments are analyzed to objectively provide estimates of nine ABL parameters, both thermodynamic (potential temperature, and relative humidity profiles and thermodynamic ABL depth) and dynamic (horizontal wind speed and direction, mean vertical velocity, updraft and downdraft speed profiles, and dynamical ABL depth). Contextual information about cloud occurrence is also provided. The dataset is prepared on a uniform time-height grid of 1 h and 30 m resolution to facilitate its use as a benchmark for forthcoming numerical simulations and the fundamental study of atmospheric processes.

Midlife cumulative deficit frailty predicts Alzheimer's disease-related plasma biomarkers in older adults.

BACKGROUND: The study explores whether frailty at midlife predicts mortality and levels of biomarkers associated with Alzheimer's disease and related dementias (ADRD) and neurodegeneration by early old age. We also examine the heritability of frailty across this age period. METHODS: Participants were 1,286 community-dwelling men from the Vietnam Era Twin Study of Aging at average ages 56, 62 and 68, all without ADRD at baseline. The cumulative deficit frailty index (FI) comprised 37 items assessing multiple physiological systems. Plasma biomarkers at age 68 included beta-amyloid (Aß40, Aß42), total tau (t-tau) and neurofilament light chain (NfL). RESULTS: Being frail doubled the risk of all-cause mortality by age 68 (OR = 2.44). Age 56 FI significantly predicted age 68 NfL (P = 0.014), Aß40 (P = 0.001) and Aß42 (P = 0.023), but not t-tau. Age 62 FI predicted all biomarkers at age 68: NfL (P = 0.023), Aß40 (P = 0.002), Aß42 (P = 0.001) and t-tau (P = 0.001). Age 68 FI scores were associated with age 68 levels of NfL (P = 0.027), Aß40 (P < 0.001), Aß42 (P = 0.001) and t-tau (P = 0.003). Genetic influences accounted for 45-48% of the variance in frailty and significantly contributed to its stability across 11 years. CONCLUSIONS: Frailty during one's 50s doubled the risk of mortality by age 68. A mechanism linking frailty and ADRD may be through its associations with biomarkers related to neurodegeneration. Cumulative deficit frailty increases with age but remains moderately heritable across the age range studied. With environmental factors accounting for about half of its variance, early interventions aimed at reducing frailty may help to reduce risk for ADRD.

Probable chronic pain, brain structure, and Alzheimer's plasma biomarkers in older men.

Chronic pain leads to tau accumulation and hippocampal atrophy in mice. In this study, we provide one of the first assessments in humans, examining the associations of probable chronic pain with hippocampal volume, integrity of the locus coeruleus (LC)-an upstream site of tau deposition-and Alzheimer's Disease-related plasma biomarkers. Participants were mostly cognitively unimpaired men. Probable chronic pain was defined as moderate-to-severe pain in 2+ study waves at average ages 56, 62, and 68. At age 68, 424 participants underwent structural magnestic resonance imaging (MRI) of hippocampal volume and LC-sensitive MRI providing an index of LC integrity (LC contrast-to-noise ratio). Analyses adjusted for confounders including major health conditions, depressive symptoms, and opioid use. Models showed that men with probable chronic pain had smaller hippocampal volume and lower rostral-middle-but not caudal-LC contrast-to-noise ratio compared to men without probable chronic pain. Men with probable chronic pain also had higher levels of plasma total tau, beta-amyloid-42, and beta-amyloid-40 compared to men without probable chronic pain. These findings suggest that probable chronic pain is associated with tau accumulation and reduced structural brain integrity in regions affected early in the development of Alzheimer's Disease. PERSPECTIVE: Probable chronic pain was associated with plasma biomarkers and brain regions that are affected early in Alzheimer's disease (AD). Reducing pain in midlife and elucidating biological mechanisms may help to reduce the risk of AD in older adults.

Associations of Subjective Memory with Life Space and Neighborhood Built Environment in Older Adults in the ACTIVE Study.

Objectives: To investigate the longitudinal association of life space and neighborhood and built environment (NBE) with subjective memory among individuals 65 and older, and the mediating role of depressive symptoms, a major correlate of life space mobility, NBE, and subjective memory. Methods: We examined community-dwelling participants in the Advanced Cognitive Training for Independent and Vital Elderly study (N = 2,622, Mean age = 73.7 years, 24.9% Black) across annual assessments of up to 3 years. Results: Baseline life space and NBE were positively associated with subjective memory, and these associations were partly mediated by depressive symptoms. Over time, higher baseline life space predicted a better subjective memory as one aged. Life space was concurrently associated with subjective memory across time, mediated by concurrent depressive symptoms. Discussion: Potentially modifiable environmental factors such as life space and NBE appear to influence level and change in subjective memory as we age. Interventions supporting movement in our environments may help offset subjective memory problems, a potential early sign of dementia.

Social and Neighborhood Context Moderates the Associations Between Processing Speed and Driving Mobility: A 10-year Analysis of the ACTIVE Study.

Objectives: Processing speed is essential to functional independence in later life, such as driving a vehicle. Few studies have examined processing speed and driving mobility in the context of racial differences and social determinants of health (SDoH). This study characterized the longitudinal association between processing speed and driving mobility, and how it varied by race and SDoH. Methods: Using data from the control arm of the Advanced Cognitive Training in Vital Elderly study (n = 581, 24.5% Black), multilevel models examined longitudinal associations between processing speed and driving mobility outcomes (driving space, exposure, and difficulty). Race and SDoH moderations were explored. Results: Decline in processing speed measures was associated with increased self-reported driving difficulty, but only for older adults with below-average to average scores for neighborhood and built environments and social community context SDoH domains. Discussion: Findings emphasize the influence of physical and social environmental characteristics on processing speed and driving mobility.

Harmonisation of read-across methodology for drug substance extractables and leachables (E&Ls).

Health-based exposure limits (HBELs) are derived for leachables from polymeric components that interact with the drug substance which exceed a safety concern threshold (SCT). However, given the nature of leachables, there is not always chemical-specific toxicology data. Read-across methodology specific to extractables and leachables (E&Ls) was developed based on survey data collected from 11 pharmaceutical companies and methodology used in other industries. One additional challenge for E&L read-across is most toxicology data is from the oral route of administration, whereas the parenteral route is very common for the leachable HBEL derivation. A conservative framework was developed to estimate oral bioavailability and the corresponding oral to parenteral extrapolation factor using physical chemical data. When this conservative framework was tested against 73 compounds with oral bioavailability data, it was found that the predicted bioavailability based on physico-chemical properties was conservatively greater than or equal to the experimental bioavailability 79% of the time. In conclusion, an E&L read-across methodology has been developed to provide a consistent, health protective framework for deriving HBELs when toxicology data is limited.

Higher cortical thickness/volume in Alzheimer's-related regions: protective factor or risk factor?

Some evidence suggests a biphasic pattern of changes in cortical thickness wherein higher, rather than lower, thickness is associated with very early Alzheimer's disease (AD) pathology. We examined whether integrating information from AD brain signatures based on mean diffusivity (MD) can aid in the interpretation of cortical thickness/volume as a risk factor for future AD-related changes. Participants were 572 men in the Vietnam Era Twin Study of Aging who were cognitively unimpaired at baseline (mean age = 56 years; range = 51-60). Individuals with both high thickness/volume signatures and high MD signatures at baseline had lower cortical thickness/volume in AD signature regions and lower episodic memory performance 12 years later compared to those with high thickness/volume and low MD signatures at baseline. Groups did not differ in level of young adult cognitive reserve. Our findings are in line with a biphasic model in which increased cortical thickness may precede future decline and establish the value of examining cortical MD alongside cortical thickness to identify subgroups with differential risk for poorer brain and cognitive outcomes.

Chronic Δ9-tetrahydrocannabinol treatment has dose-dependent effects on open field exploratory behavior and [3H] SR141716A receptor binding in the rat brain.

AIMS: Acute and chronic Δ9-THC exposure paradigms affect the body differently. More must be known about the impact of chronic Δ9-THC on cannabinoid-1 (CB1R) and mu-opioid (MOR) receptor levels in the brain. The present study examined chronic Δ9-THC's effects on CB1R and MOR levels and locomotor activity. MAIN METHODS: Adolescent Sprague-Dawley rats were given daily intraperitoneal injections of Δ9-THC [0.75mg/kg (low dose or LD) or 2.0 mg/kg (high dose or HD)] or vehicle for 24 days, and locomotion in the open field was tested after the first and fourth weeks of chronic Δ9-THC exposure. Brains were harvested at the end of treatment. [3H] SR141716A and [3H] DAMGO autoradiography assessed CB1R and MOR levels, respectively. KEY FINDINGS: Relative to each other, chronic HD rats showed reduced vertical plane (VP) entries and time, while LD rats had increased VP entries and time for locomotion, as assessed by open-field testing; no effects were found relative to the control. Autoradiography analyses showed that HD Δ9-THC significantly decreased CB1R binding relative to LD Δ9-THC in the cingulate (33%), primary motor (42%), secondary motor (33%) somatosensory (38%), rhinal (38%), and auditory (50%) cortices; LD Δ9-THC rats displayed elevated binding in the primary motor (33% increase) and hypothalamic (33% increase) regions compared with controls. No significant differences were observed in MOR binding for the LD or HD compared to the control. SIGNIFICANCE: These results demonstrate that chronic Δ9-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.

A Traitlike Dimension of Subjective Memory Concern Over 30 Years Among Adult Male Twins.

Importance: Subjective memory concern has long been considered a state-related indicator of impending cognitive decline or dementia. The possibility that subjective memory concern may itself be a heritable trait is largely ignored, yet such an association would substantially confound its use in clinical or research settings. Objective: To assess the heritability and traitlike dimensions of subjective memory concern and its clinical correlates. Design, Setting, and Participants: This longitudinal twin cohort study was conducted from 1967 to 2019 among male adults with a mean (SD) age of 37.75 (2.52) years to follow-up at mean ages of 56.15 (2.72), 61.50 (2.43), and 67.35 (2.57) years (hereafter, 38, 56, 62, and 67 years, respectively) in the Vietnam Era Twin Study of Aging. The study included a national community-dwelling sample with health, education, and lifestyle characteristics comparable to a general sample of US men in this age cohort. Participants were monozygotic and dizygotic twins randomly recruited from the Vietnam Era Twin Registry. Data were analyzed from May 2021 to December 2022. Main Outcomes and Measures: Measures included subjective memory concern at 4 time points; objective memory, depressive symptoms, and anxiety at the last 3 time points; negative emotionality (trait neuroticism) at age 56 years; polygenic risk scores (PRSs) for neuroticism, depression, and Alzheimer disease; APOE genotype; and parental history of dementia. Primary outcomes were heritability and correlations between subjective memory concern and other measures. Results: The sample included 1555 male adults examined at age 38 years, 520 at age 56 years (due to late introduction of subjective memory concern questions), 1199 at age 62 years, and 1192 at age 67 years. Phenotypically, subjective memory concerns were relatively stable over time. At age 56 years, subjective memory concern had larger correlations with depressive symptoms (r, 0.32; 95% CI, 0.21 to 0.42), anxiety (r, 0.36; 95% CI, 0.18 to 0.51), and neuroticism (r, 0.34; 95% CI, 0.26 to 0.41) than with objective memory (r, -0.24; 95% CI, -0.33 to -0.13). Phenotypic results were similar at ages 62 and 67 years. A best-fitting autoregressive twin model indicated that genetic influences on subjective memory concern accumulated and persisted over time (h2 = 0.26-0.34 from age 38-67 years). At age 56 years, genetic influences for subjective memory concern were moderately correlated with genetic influences for anxiety (r, 0.36; 95% CI, 0.18 to 0.51), negative emotionality (r, 0.51; 95% CI, 0.44-0.57), and depressive symptoms (r, 0.20; 95% CI, 0.10 to 0.29) as well as objective memory (r, -0.22; 95% CI, -0.30 to -0.14). Similar genetic correlations were seen at ages 62 and 67 years. The neuroticism PRS was associated with subjective memory concern at age 38 years (r, 0.10; 95% CI, 0.03. to 0.18) and age 67 years (r, 0.09; 95% CI, 0.01 to 0.16). Subjective memory concern was not associated with any Alzheimer disease risk measures. Conclusions and Relevance: This cohort study found stable genetic influences underlying subjective memory concern dating back to age 38 years. Subjective memory concern had larger correlations with affect-related measures than with memory-related measures. Improving the utility of subjective memory concern as an indicator of impending cognitive decline and dementia may depend on isolating its statelike component from its traitlike component.

Genetic and Environmental Influences on Structural and Diffusion-Based Alzheimer's Disease Neuroimaging Signatures Across Midlife and Early Old Age.

BACKGROUND: Composite scores of magnetic resonance imaging-derived metrics in brain regions associated with Alzheimer's disease (AD), commonly termed AD signatures, have been developed to distinguish early AD-related atrophy from normal age-associated changes. Diffusion-based gray matter signatures may be more sensitive to early AD-related changes compared with thickness/volume-based signatures, demonstrating their potential clinical utility. The timing of early (i.e., midlife) changes in AD signatures from different modalities and whether diffusion- and thickness/volume-based signatures each capture unique AD-related phenotypic or genetic information remains unknown. METHODS: Our validated thickness/volume signature, our novel mean diffusivity (MD) signature, and a magnetic resonance imaging-derived measure of brain age were used in biometrical analyses to examine genetic and environmental influences on the measures as well as phenotypic and genetic relationships between measures over 12 years. Participants were 736 men from 3 waves of the Vietnam Era Twin Study of Aging (VETSA) (baseline/wave 1: mean age [years] = 56.1, SD = 2.6, range = 51.1-60.2). Subsequent waves occurred at approximately 5.7-year intervals. RESULTS: MD and thickness/volume signatures were highly heritable (56%-72%). Baseline MD signatures predicted thickness/volume signatures over a decade later, but baseline thickness/volume signatures showed a significantly weaker relationship with future MD signatures. AD signatures and brain age were correlated, but each measure captured unique phenotypic and genetic variance. CONCLUSIONS: Cortical MD and thickness/volume AD signatures are heritable, and each signature captures unique variance that is also not explained by brain age. Moreover, results are in line with changes in MD emerging before changes in cortical thickness, underscoring the utility of MD as a very early predictor of AD risk.

Severity and correlates of brain fog in people with traumatic brain injury.

Brain fog is one symptom that has been underexplored in traumatic brain injury (TBI). We explored the cognitive and affective correlates of brain fog in people with symptomatic mild TBI (n = 15), moderate-to-severe TBI (n = 15), and a healthy control group (n = 16). Measures across the studies assessed "brain fog" (Mental Clutter Scale), objective cognition (Useful Field of View® and Cogstate Brief Battery®), post-concussive symptoms (Post-Concussion Symptom Scale), and depressive symptoms (Profile of Moods Scale). Brain fog was higher in symptomatic mild TBI and moderate-to-severe TBI compared with healthy controls. Greater brain fog corresponded to greater depressive symptoms in symptomatic mild TBI. Greater brain fog corresponded to poorer episodic memory and working memory in moderate-to-severe TBI. Brain fog appears to reflect challenges in recovery, including depressive symptoms and worse cognitive function. Screening for brain fog might be worthwhile in people with brain injuries.

Rostral-middle locus coeruleus integrity and subjective cognitive decline in early old age.

OBJECTIVES: Abnormal tau, a hallmark Alzheimer's disease (AD) pathology, may appear in the locus coeruleus (LC) decades before AD symptom onset. Reports of subjective cognitive decline are also often present prior to formal diagnosis. Yet, the relationship between LC structural integrity and subjective cognitive decline has remained unexplored. Here, we aimed to explore these potential associations. METHODS: We examined 381 community-dwelling men (mean age = 67.58; SD = 2.62) in the Vietnam Era Twin Study of Aging who underwent LC-sensitive magnetic resonance imaging and completed the Everyday Cognition scale to measure subjective cognitive decline along with their selected informants. Mixed models examined the associations between rostral-middle and caudal LC integrity and subjective cognitive decline after adjusting for depressive symptoms, physical morbidities, and family. Models also adjusted for current objective cognitive performance and objective cognitive decline to explore attenuation. RESULTS: For participant ratings, lower rostral-middle LC contrast to noise ratio (LCCNR) was associated with significantly greater subjective decline in memory, executive function, and visuospatial abilities. For informant ratings, lower rostral-middle LCCNR was associated with significantly greater subjective decline in memory only. Associations remained after adjusting for current objective cognition and objective cognitive decline in respective domains. CONCLUSIONS: Lower rostral-middle LC integrity is associated with greater subjective cognitive decline. Although not explained by objective cognitive performance, such a relationship may explain increased AD risk in people with subjective cognitive decline as the LC is an important neural substrate important for higher order cognitive processing, attention, and arousal and one of the first sites of AD pathology.

Increasing Pain Interference Is Associated With Cognitive Decline Over Four Years Among Older Puerto Rican Adults.

BACKGROUND: Pain is associated with cognitive decline among older adults, but few studies have investigated bidirectional associations between pain and cognitive decline, especially in older Hispanic populations. Our objective was to assess the bidirectional association between pain interference and cognitive performance in a sample of older Puerto Rican adults. METHODS: Data came from baseline and 4-year follow-up of the Puerto Rican Elderly: Health Conditions Study, a longitudinal representative study of Puerto Rican older adults aged 60 and older. Pain and cognitive performance were assessed at each wave. A pain interference variable was created using the sum of pain status (yes/no) and pain interference (yes/no; range 0-2). Global cognitive performance was assessed with the Mini-Mental Cabán. We tested bidirectional associations using a path model with concurrent and cross-lagged paths between pain and cognitive performance, adjusting for sociodemographic and health factors (n = 2 349). RESULTS: Baseline pain interference was not associated with baseline cognitive performance (p = .636) or with cognitive performance at follow-up (p = .594). However, increased pain interference at follow-up was associated with greater cognitive decline at follow-up (ß = -0.07, standard error [SE] = 0.02, p = .003). Greater baseline cognitive performance was associated with lower pain interference at follow-up (ß = -0.07, SE = 0.02, p = .007). CONCLUSIONS: These findings highlight the importance of worsening pain interference as a potentially modifiable risk factor for cognitive decline, as pain treatment options exist. Additionally, better baseline cognitive performance may be a protective factor for pain, providing further evidence of the dynamic relationship between pain and cognitive performance.

Erectile Function, Sexual Satisfaction, and Cognitive Decline in Men From Midlife to Older Adulthood.

BACKGROUND AND OBJECTIVES: Vascular theories of cognitive aging have focused on macrovascular changes and cognitive decline. However, according to the artery-size hypothesis, microvascular changes, such as those that underlie changes in erectile function, may also play an important role in contributing to cognitive decline. Thus, we examined associations between erectile function, sexual satisfaction, and cognition starting in middle age because this represents a transition period where declines in these areas emerge. RESEARCH DESIGN AND METHODS: We examined 818 men from the Vietnam Era Twin Study of Aging across three waves at mean ages 56, 61, and 68. Erectile function and sexual satisfaction were measured using the International Index of Erectile Function. Cognitive performance was measured using factor scores for episodic memory, executive function, and processing speed. We tested multilevel models hierarchically, adjusting for demographics, frequency of sexual activity, and physical and mental health confounders to examine how changes in erectile function and sexual satisfaction related to changes in cognitive performance. RESULTS: Lower erectile function at baseline was related to poorer performance in all cognitive domains at baseline and faster declines in processing speed over time. However, baseline sexual satisfaction was unrelated to cognitive performance. Decreases in erectile function and sexual satisfaction were both associated with memory decline. DISCUSSION AND IMPLICATIONS: Decreasing sexual health may signal an increased risk for cognitive decline. We discuss potential mechanisms, including microvascular changes and psychological distress. Discussing and tracking sexual health in middle-aged men may help to identify those likely to face memory decline.

An Automated Virtual Reality Training System for Teacher-Student Interaction: A Randomized Controlled Trial.

BACKGROUND: Shortages in qualified supervision and other resources prevent education personnel from rehearsing effective practices. Interactive simulations, although increasingly used in education, frequently require instructor management. Automated simulations rarely engage trainees in skills related to practice (eg, speech). OBJECTIVE: We evaluated the capability of delivering behavioral skills training through an automated virtual reality (VR) simulation using artificial intelligence to improve the implementation of a nondirective mathematical questioning strategy. METHODS: We recruited and randomly assigned 30 college-aged participants to equivalent treatment (ie, lecture, modeling, and VR; 15/30, 50%) and control groups (ie, lecture and modeling only; 15/30, 50%). The participants were blind to treatment conditions. Sessions and assessments were conducted face to face and involved the use of VR for assessment regardless of the condition. Lessons concerned the use of a nondirective mathematical questioning strategy in instances where a simulated student provided correct or incorrect answers to word problems. The measures included observed and automated assessments of participant performance and subjective assessments of participant confidence. The participants completed the pretest, posttest, and maintenance probes each week over the course of 3 weeks. RESULTS: A mixed ANOVA revealed significant main effects of time (F2,27=124.154; P<.001; ηp2=0.816) and treatment (F1,28=19.281; P<.001; ηp2=0.408) as well as an interaction effect (F2,28=8.429; P<.001; ηp2=0.231) for the average percentage of steps in the questioning procedure. Posttest scores for the intervention group (mean 88%, SD 22.62%) exceeded those of the control group (mean 63.33%, SD 22.64%), with t28=3.653, P<.001, and Cohen d=1.334. Maintenance scores indicated a positive effect of the intervention (mean 83.33%, SD 24.40%) relative to the control (mean 54.67%, SD 15.98%), t28=3.807, P<.001, Cohen d=1.39. A Mann-Whitney U test indicated that the treatment groups' self-ratings of confidence (mean 2.41, SD 0.51) were higher than those of the control group (mean 2.04, SD 0.52), U=64, P=.04, r=0.137. CONCLUSIONS: The results demonstrate the potential of artificial intelligence-augmented VR to deliver effective, evidence-based training with limited instructor management. Additional work is needed to demonstrate the cascading effect of training on authentic practice and to encompass a wider range of skills.

HoloKinect: Holographic 3D Video Conferencing.

Recent world events have caused a dramatic rise in the use of video conferencing solutions such as Zoom and FaceTime. Although 3D capture and display technologies are becoming common in consumer products (e.g., Apple iPhone TrueDepth sensors, Microsoft Kinect devices, and Meta Quest VR headsets), 3D telecommunication has not yet seen any appreciable adoption. Researchers have made great progress in developing advanced 3D telepresence systems, but often with burdensome hardware and network requirements. In this work, we present HoloKinect, an open-source, user-friendly, and GPU-accelerated platform for enabling live, two-way 3D video conferencing on commodity hardware and a standard broadband internet connection. A Microsoft Azure Kinect serves as the capture device and a Looking Glass Portrait multiscopically displays the final reconstructed 3D mesh for a hologram-like effect. HoloKinect packs color and depth information into a single video stream, leveraging multiwavelength depth (MWD) encoding to store depth maps in standard RGB video frames. The video stream is compressed with highly optimized and hardware-accelerated video codecs such as H.264. A search of the depth and video encoding parameter space was performed to analyze the quantitative and qualitative losses resulting from HoloKinect's lossy compression scheme. Visual results were acceptable at all tested bitrates (3-30 Mbps), while the best results were achieved with higher video bitrates and full 4:4:4 chroma sampling. RMSE values of the recovered depth measurements were low across all settings permutations.

Cell-Type-Specific Effects of the Ovarian Cancer G-Protein Coupled Receptor (OGR1) on Inflammation and Fibrosis; Potential Implications for Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a disease characterized by irreversible lung scarring. The pathophysiology is not fully understood, but the working hypothesis postulates that a combination of epithelial injury and myofibroblast differentiation drives progressive pulmonary fibrosis. We previously demonstrated that a reduction in extracellular pH activates latent TGF-ß1, and that TGF-ß1 then drives its own activation, creating a feed-forward mechanism that propagates myofibroblast differentiation. Given the important roles of extracellular pH in the progression of pulmonary fibrosis, we sought to identify whether pH mediates other cellular phenotypes independent of TGF-ß1. Proton-sensing G-protein coupled receptors are activated by acidic environments, but their role in fibrosis has not been studied. Here, we report that the Ovarian Cancer G-Protein Coupled Receptor1 (OGR1 or GPR68) has dual roles in both promoting and mitigating pulmonary fibrosis. We demonstrate that OGR1 protein expression is significantly reduced in lung tissue from patients with IPF and that TGF-ß1 decreases OGR1 expression. In fibroblasts, OGR1 inhibits myofibroblast differentiation and does not contribute to inflammation. However, in epithelial cells, OGR1 promotes epithelial to mesenchymal transition (EMT) and inflammation. We then demonstrate that sub-cellular localization and alternative signaling pathways may be responsible for the differential effect of OGR1 in each cell type. Our results suggest that strategies to selectively target OGR1 expression may represent a novel therapeutic strategy for pulmonary fibrosis.

Ogerin mediated inhibition of TGF-ß(1) induced myofibroblast differentiation is potentiated by acidic pH.

Transforming growth factor beta (TGF-ß) induced myofibroblast differentiation is central to the pathological scarring observed in Idiopathic Pulmonary Fibrosis (IPF) and other fibrotic diseases. Our lab has recently identified expression of GPR68 (Ovarian Cancer Gene Receptor 1, OGR1), a pH sensing G-protein coupled receptor, as a negative regulator of TGF-ß induced profibrotic effects in primary human lung fibroblasts (PHLFs). We therefore hypothesized that small molecule activators of GPR68 would inhibit myofibroblast differentiation. Ogerin is a positive allosteric modulator (PAM) of GPR68, inducing a leftward shift of the dose response curve to proton induced signaling. Using PHLFs derived from patients with both non-fibrotic and IPF diagnoses, we show that Ogerin inhibits, and partially reverses TGF-ß induced myofibroblast differentiation in a dose dependent manner. This occurs at the transcriptional level without inhibition of canonical TGF-ß induced SMAD signaling. Ogerin induces PKA dependent CREB phosphorylation, a marker of Gαs pathway activation. The ability of Ogerin to inhibit both basal and TGF-ß induced collagen gene transcription, and induction of Gαs signaling is enhanced at an acidic pH (pH 6.8). Similar findings were also found using fibroblasts derived from dermal, intestinal, and orbital tissue. The biological role of GPR68 in different tissues, cell types, and disease states is an evolving and emerging field. This work adds to the understanding of Gαs coupled GPCRs in fibrotic lung disease, the ability to harness the pH sensing properties of GPR68, and conserved mechanisms of fibrosis across different organ systems.

Longitudinal associations of pain and cognitive decline in community-dwelling older adults.

Pain is inversely associated with cognitive function in older adults, but the effects of pain on cognitive decline are not fully clear. This study examined the associations of baseline pain, pain persistence, and incident pain with changes in cognition across 10 years in a sample of healthy community-dwelling older adults (n = 688; Mage = 74, SD = 6.05) from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial. While ACTIVE was a four-arm single-blind cognitive training randomized controlled trial, the present study includes only participants from the no-contact control group. Pain was examined using the Medical Outcomes Survey SF-36-Item (MOS SF-36) and cognitive tests examined simple processing speed, complex processing speed, divided and selective attention, memory, reasoning, and cognitive status. Multilevel models tested the associations of baseline pain, incident pain, and pain persistence on cognitive function and cognitive decline, adjusted for baseline age, time (years after follow-up), race, gender, education, marital status, and depressive symptoms at baseline and over time. Thirty-one percent reported pain at baseline which was related to worse baseline memory and accelerated decline in processing speed. Forty-two percent of older adults reported incident pain had accelerated decline in complex processing speed, divided attention, memory, reasoning, and cognitive status. On average, older adults reported a mean of two waves of pain persistence related to accelerated decline in memory. In sum, pain is common in community-dwelling older adults and is related to accelerated cognitive decline, especially when the incident. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Downsampled depth encoding for enhanced 3D range geometry compression.

The use of three-dimensional (3D) range geometry is expanding across a variety of disciplines ranging from medicine to the visual arts. A large amount of information is available in 3D range geometry, causing some applications to be limited in their ability to effectively store or transmit captured data. To help alleviate this constraint, a variety of 3D range data compression techniques have been proposed. One method, multiwavelength depth (MWD) encoding, smoothly encodes 3D range geometry into the three color channels of a 2D RGB image. To the best of our knowledge, we present a novel compression enhancement to further reduce file sizes that employs image downsampling, MWD encoding, and lossless (e.g., PNG) or lossy (e.g., JPEG) compression. Image upsampling is used to return downsampled encodings to their original resolution from which the 3D information is then decoded. The proposed method is robust to various scales of downsampling and levels of lossy compression. For example, when this method was applied with 50% downsampling and JPEG 85 to an encoding of a 3D face scan, a compression ratio of 68.85:1 versus the raw data was achieved with a global RMS reconstruction accuracy of 98.77%. Experimental results demonstrate that the proposed method can provide substantial file size savings at minimal reduction in overall reconstruction accuracy.