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All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Associations between environmental quality and adult asthma prevalence in medical claims data

Highlights: • Asthma is a complex condition affecting 7.4% of U.S. adults. • Asthma may be driven by multiple exposures operating in tandem. • The Environmental Quality Index measures 5 environmental domains simultaneously. • Worsening overall environmental quality is associated with increasing asthma. • Patterns vary by domain (air, water, land, built, sociodemograhic) and rurality. As of 2014, approximately 7.4% of U.S. adults had current asthma. The etiology of asthma is complex, involving genetics, behavior, and environmental factors. To explore the association between cumulative environmental quality and asthma prevalence in U.S. adults, we linked the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) to the MarketScan{sup ®} Commercial Claims and Encounters Database. The EQI is a summary measure of five environmental domains (air, water, land, built, sociodemographic). We defined asthma as having at least 2 claims during the study period, 2003–2013. We used a Bayesian approach with non-informative priors, implementing mixed-effects regression modeling with a Poisson link function. Fixed effects variables were EQI, sex, race, and age. Random effects were counties. We modeled quintiles of the EQI comparing higher quintiles (worse quality) to lowest quintile (best quality) to estimate prevalence ratios (PR) and credible intervals (CIs). We estimated associations using the cumulative EQI and domain-specific EQIs; we assessed U.S. overall (non-stratified) as well as stratified by rural-urban continuum codes (RUCC) to assess rural/urban heterogeneity. Among the 71,577,118 U.S. adults with medical claims who could be geocoded to county of residence, 1,147,564 (1.6%) met the asthma definition. Worse environmental quality was associated with increased asthma prevalence using the non-RUCC-stratified cumulative EQI, comparing the worst to best EQI quintile (PR:1.27; 95% CI: 1.21, 1.34). Patterns varied among different EQI domains, as well as by rural/urban status. Poor environmental quality may increase asthma prevalence, but domain-specific drivers may operate differently depending on rural/urban status.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2014

Comparison of patient specific dose metrics between chest radiography, tomosynthesis, and CT for adult patients of wide ranging body habitus

Purpose: Given the radiation concerns inherent to the x-ray modalities, accurately estimating the radiation doses that patients receive during different imaging modalities is crucial. This study estimated organ doses, effective doses, and risk indices for the three clinical chest x-ray imaging techniques (chest radiography, tomosynthesis, and CT) using 59 anatomically variable voxelized phantoms and Monte Carlo simulation methods. Methods: A total of 59 computational anthropomorphic male and female extended cardiac-torso (XCAT) adult phantoms were used in this study. Organ doses and effective doses were estimated for a clinical radiography system with the capability of conducting chest radiography and tomosynthesis (Definium 8000, VolumeRAD, GE Healthcare) and a clinical CT system (LightSpeed VCT, GE Healthcare). A Monte Carlo dose simulation program (PENELOPE, version 2006, Universitat de Barcelona, Spain) was used to mimic these two clinical systems. The Duke University (Durham, NC) technique charts were used to determine the clinical techniques for the radiographic modalities. An exponential relationship between CTDI{sub vol} and patient diameter was used to determine the absolute dose values for CT. The simulations of the two clinical systems compute organ and tissue doses, which were then used to calculate effective dose and risk index. The calculation of the two dose metrics used the tissue weighting factors from ICRP Publication 103 and BEIR VII report. Results: The average effective dose of the chest posteroanterior examination was found to be 0.04 mSv, which was 1.3% that of the chest CT examination. The average effective dose of the chest tomosynthesis examination was found to be about ten times that of the chest posteroanterior examination and about 12% that of the chest CT examination. With increasing patient average chest diameter, both the effective dose and risk index for CT increased considerably in an exponential fashion, while these two dose metrics only increased slightly for radiographic modalities and for chest tomosynthesis. Effective and organ doses normalized to mAs all illustrated an exponential decrease with increasing patient size. As a surface organ, breast doses had less correlation with body size than that of lungs or liver. Conclusions: Patient body size has a much greater impact on radiation dose of chest CT examinations than chest radiography and tomosynthesis. The size of a patient should be considered when choosing the best thoracic imaging modality.

61 RADIATION PROTECTION AND DOSIMETRY↗
DOE OSTI2015

A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Cortical proteins may provide motor resilience in older adults

Motor resilience proteins may be a high value therapeutic target that offset the negative effects of pathologies on motor function. This study sought to identify cortical proteins associated with motor decline unexplained by brain pathologies that provide motor resilience. We studied 1226 older decedents with annual motor testing, postmortem brain pathologies and quantified 226 proteotypic peptides in prefrontal cortex. Twenty peptides remained associated with motor decline in models controlling for ten brain pathologies (FDR < 0.05). Higher levels of nine peptides and lower levels of eleven peptides were related to slower decline. A higher motor resilience protein score based on averaging the levels of all 20 peptides was related to slower motor decline, less severe parkinsonism and lower odds of mobility disability before death. Cortical proteins may provide motor resilience. Targeting these proteins in further drug discovery may yield novel interventions to maintain motor function in old age.

Buchman, Aron↗
DOE OSTI2020

State Policies on Access to Vaccination Services for Low-Income Adults

Importance State vaccination benefits coverage and access for adult Medicaid beneficiaries vary substantially. Multiple studies have documented lower vaccination uptake in publicly insured adults compared with privately insured adults. Objective To evaluate adult Medicaid beneficiaries’ access to adult immunization services through review of vaccination benefits coverage in Medicaid programs across the 50 states and the District of Columbia. Design, Setting, and Participants A public domain document review with supplemental semistructured telephone survey was conducted between June 1, 2018, and June 14, 2019, to evaluate vaccination services benefits in fee-for-service and managed care organization arrangements for adult Medicaid beneficiaries in the 50 states and the District of Columbia (total, 51 Medicaid programs). Exposures Document review of benefits coverage for adult immunization services and supplemental survey with validation of document review findings. Main Outcomes and Measures Benefits coverage for adult Medicaid beneficiaries and reimbursement amounts for vaccine purchase and administration. Results Public domain document review was completed for all 51 jurisdictions. Among these, 44 Medicaid programs (86%) validated document review findings and completed the survey. Only 22 Medicaid programs (43%) covered all 13 Advisory Committee on Immunization Practices–recommended adult immunizations under both fee-for-service and managed care organization arrangements. Most fee-for-service arrangements (37 of 49) reimbursed health care professionals using any of the 4 approved vaccine administration codes; however, 8 of 49 programs did not separately reimburse for vaccine administration to adult Medicaid beneficiaries. Depending on administration route, median reimbursement for adult vaccine administration ranged from $\$9.81$ to $\$13.98$ per dose. Median per-dose reimbursement for adult vaccine purchase was highest for 9-valent human papillomavirus vaccine ($\$204.87$) and lowest for Haemophilus influenzae type b vaccine ($\$18.09$). Median reimbursement was below the private sector price for 7 of the 13 included vaccines. Conclusions and Relevance Even in programs with complete vaccination benefits coverage, reimbursement amounts to health care professionals for vaccine purchase and administration may not fully cover vaccination provision costs. Reimbursement amounts below costs may reduce incentives for health care professionals to vaccinate low-income adults and thereby limit Medicaid adult beneficiary access to vaccination.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials

Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12-year-old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety. In conclusion, the minimum body weight threshold and selection of an appropriate dose for adolescents in relevant adult oncology clinical trials should ultimately be determined based on available data on pharmacokinetics or pharmacodynamics of the investigational drug with consideration of body size effect on drug exposure, toxicity, and efficacy data (if available), the therapeutic index of the drug, and dose- and exposure-response relationships in adults.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Low functional programming of renal AT{sub 2}R mediates the developmental origin of glomerulosclerosis in adult offspring induced by prenatal caffeine exposure

Our previous study has indicated that prenatal caffeine exposure (PCE) could induce intrauterine growth retardation (IUGR) of offspring. Recent research suggested that IUGR is a risk factor for glomerulosclerosis. However, whether PCE could induce glomerulosclerosis and its underlying mechanisms remain unknown. This study aimed to demonstrate the induction to glomerulosclerosis in adult offspring by PCE and its intrauterine programming mechanisms. A rat model of IUGR was established by PCE, male fetuses and adult offspring at the age of postnatal week 24 were euthanized. The results revealed that the adult offspring kidneys in the PCE group exhibited glomerulosclerosis as well as interstitial fibrosis, accompanied by elevated levels of serum creatinine and urine protein. Renal angiotensin II receptor type 2 (AT{sub 2}R) gene expression in adult offspring was reduced by PCE, whereas the renal angiotensin II receptor type 1a (AT{sub 1a}R)/AT{sub 2}R expression ratio was increased. The fetal kidneys in the PCE group displayed an enlarged Bowman's space and a shrunken glomerular tuft, accompanied by a reduced cortex width and an increase in the nephrogenic zone/cortical zone ratio. Observation by electronic microscope revealed structural damage of podocytes; the reduced expression level of podocyte marker genes, nephrin and podocin, was also detected by q-PCR. Moreover, AT{sub 2}R gene and protein expressions in fetal kidneys were inhibited by PCE, associated with the repression of the gene expression of glial-cell-line-derived neurotrophic factor (GDNF)/tyrosine kinase receptor (c-Ret) signaling pathway. These results demonstrated that PCE could induce dysplasia of fetal kidneys as well as glomerulosclerosis of adult offspring, and the low functional programming of renal AT{sub 2}R might mediate the developmental origin of adult glomerulosclerosis. - Highlights: • Prenatal caffeine exposure induces glomerulosclerosis in adult offspring. • Prenatal caffeine exposure inhibits fetal kidney development. • Prenatal caffeine exposure causes low functional programming of renal AT{sub 2}R.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Oxygen consumption of sexually mature adult, first-feeding larval, and yearling Pacific Lampreys

Abstract Objective The Pacific Lamprey Entosphenus tridentatus is considered a first food of Native American tribes, such as the Confederated Tribes of the Umatilla Indian Reservation. Populations of this imperiled species have declined such that harvest for traditional use is limited. As a result, propagation and culture of Pacific Lampreys have been initiated to supply animals for restoration and recovery efforts. These efforts require transport and periodic holding of both adults and larvae under static (no-flow) conditions. Hence, guidelines for ensuring an adequate oxygen supply are needed for all life stages of this species. Methods We measured oxygen consumption rates of mature adults, first-feeding larvae, and yearlings under static conditions at 12–15°C. In addition, we recorded indicators of stress during hypoxia for adults and estimated routine respiration rates during and after larval feeding. Result Adults exhibited surprisingly high metabolic rates when at rest in static chambers. At 12°C, a single adult typically reduced dissolved oxygen levels in 10 L to <2 mg/L in just 90 min (oxygen consumption rates of 100–200 mg/kg/h). Adults often started to climb the walls of open chambers when dissolved oxygen levels approached 2 mg/L, allowing them to raise their branchiopores into air. Larvae remained quiescent, even when oxygen levels dropped below 1 mg/L, and costs of feeding increased routine respiration by 22–56%. Conclusion Based on these observations, we recommend that adult Pacific Lampreys always be transported in aerated containers and with access to air at the top of the tank. Although larvae exhibited hypoxia tolerance, care should be taken to ensure adequate oxygen availability, particularly during and immediately after feeding.

Moser, Mary↗
DOE OSTI2019

Rhabdomyosarcoma in adults: analysis of treatment modalities in a prospective single-center series

Rhabdomyosarcoma (RMS) is rare in adults and it is generally characterized by poor outcome. In a previous retrospective study, we demonstrated a better prognosis in adults treated with multimodality approach resembling pediatric protocols. Thereafter, we developed specific recommendations based on the principles adopted in pediatric oncology. The present analysis reports the results in a subsequent prospective series. The study included 95 consecutive patients (age 18–77 years) treated from 2002 to 2015 for embryonal and alveolar RMS. As in the previous series, patients were stratified by the appropriateness of their treatment according to therapeutic guidelines for childhood RMS. The 5-year event-free survival (EFS) and overall survival (OS) rates were 33.6% and 40.3%, respectively. The 5-year EFS was 40.8% for patients with the highest treatment score, and 15% for those with lower score, while OS was 44.4% and 24.5%, respectively. The developing of specific recommendations enabled an increase in the number of patients treated with intensive multimodal treatment resembling pediatric strategy (69.7% vs. 39.1% in the retrospective series). This study reinforced the idea that adherence to the principles of pediatric protocols, improves adult RMS outcomes. However, treating adults with pediatric-type strategy is not enough to achieve the results obtained in children. Issues in compliance and a more aggressive biology of adult RMS might have a role in the different outcome according to age. Improving the collaboration between pediatric and adult oncologists in promoting specific clinical and biological research is crucial to improve the outcome for this patient population.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2021

The use of teledentistry in facilitating oral health for older adults: A scoping review

Teledentistry is used in many countries to provide oral health care services. However, using teledentistry to provide oral health care services for older adults is not well documented. This knowledge gap needs to be addressed, especially when accessing a dental clinic is not possible and teledentistry might be the only way for many older adults to receive oral health care services. Nine databases were searched and 3,396 studies were screened using established eligibility criteria. Included studies were original research or review articles in which the intervention of interest was delivered to an older adult population (≥ 60 years) via teledentistry. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Review criteria. Nineteen studies were identified that met the criteria for inclusion. Only 1 study was from the United States. Seven studies had results focusing on older adult participants only, with most of those conducted in elder care facilities. The remainder consisted of studies with mixed-age populations reporting distinct results or information for older adults. The included studies used teledentistry, in both synchronous and asynchronous modes, to provide services such as diagnosis, oral hygiene promotion, assessment and referral of oral emergencies, and postintervention follow-up. Teledentistry comprises a variety of promising apps. Lastly, the authors identified and described uses, promising possibilities, and limitations of teledentistry to improve the oral health of older adults.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Modern Senicide in the Face of a Pandemic: An Examination of Public Discourse and Sentiment About Older Adults and COVID-19 Using Machine Learning

Objectives This study examined public discourse and sentiment regarding older adults and COVID-19 on social media and assessed the extent of ageism in public discourse. Methods Twitter data (N = 82,893) related to both older adults and COVID-19 and dated from January 23 to May 20, 2020, were analyzed. We used a combination of data science methods (including supervised machine learning, topic modeling, and sentiment analysis), qualitative thematic analysis, and conventional statistics. Results The most common category in the coded tweets was “personal opinions” (66.2%), followed by “informative” (24.7%), “jokes/ridicule” (4.8%), and “personal experiences” (4.3%). The daily average of ageist content was 18%, with the highest of 52.8% on March 11, 2020. Specifically, more than 1 in 10 (11.5%) tweets implied that the life of older adults is less valuable or downplayed the pandemic because it mostly harms older adults. A small proportion (4.6%) explicitly supported the idea of just isolating older adults. Almost three-quarters (72.9%) within “jokes/ridicule” targeted older adults, half of which were “death jokes.” Also, 14 themes were extracted, such as perceptions of lockdown and risk. A bivariate Granger causality test suggested that informative tweets regarding at-risk populations increased the prevalence of tweets that downplayed the pandemic. Discussion Ageist content in the context of COVID-19 was prevalent on Twitter. Information about COVID-19 on Twitter influenced public perceptions of risk and acceptable ways of controlling the pandemic. Finaly, public education on the risk of severe illness is needed to correct misperceptions.

60 APPLIED LIFE SCIENCES↗