Publications by authors named "D J Brown"

11,553 Publications

Social Needs, Chronic Conditions, and Health Care Utilization among Medicaid Beneficiaries.

Popul Health Manag 2021 May 14. Epub 2021 May 14.

Brown School of Social Work, Washington University in St. Louis, St. Louis, Missouri, USA.

Health care organizations are increasingly assessing patients' social needs (eg, food, utilities, transportation) using various measures and methods. Prior studies have assessed social needs at the point of care and many studies have focused on correlates of 1 specific need (eg, food). This comprehensive study examined multiple social needs and medical and pharmacy claims data. Medicaid beneficiaries in Louisiana (n = 10,275) completed a self-report assessment of 10 social needs during July 2018 to June 2019. Chronic health conditions, unique medications, and health care utilization were coded from claims data. The sample was predominantly female (72%), Black (45%) or White (32%), had a mean age of 42 years, and at least 1 social need (55%). In bivariate analyses, having greater social needs was associated with greater comorbidity across conditions, and each social need was consistently associated with mental health and substance use disorders. In multivariable logistic analyses, having ≥2 social needs was positively associated with emergency department (ED) visits (OR = 1.39, CI = 1.23 - 1.57) and negatively associated with wellness visits (OR = 0.87, CI = 0.77 - 0.98), inpatient visits (OR = 0.87, CI = 0.76 - 0.99), and 30-day rehospitalization (OR = 0.66, CI = 0.50 - 0.87). Findings highlight the greater concomitant risk of social needs, mental health, and substance use. Admission policies may reduce the impact of social needs on hospitalization. Chronic disease management programs offered by health plans may benefit from systematically assessing and addressing social needs outside point-of-care interactions to impact health outcomes and ED utilization. Behavioral health care management programs would benefit from integrating interventions for multiple social needs.
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http://dx.doi.org/10.1089/pop.2021.0065DOI Listing
May 2021

Point absorbers in Advanced LIGO.

Appl Opt 2021 May;60(13):4047-4063

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers). This analysis predicts that the power-dependent reduction in interferometer performance will significantly degrade maximum stored power by up to 50% and, hence, limit GW sensitivity, but it suggests system wide corrections that can be implemented in current and future GW detectors. This is particularly pressing given that future GW detectors call for an order of magnitude more stored power than currently used in Advanced LIGO in Observing Run 3. We briefly review strategies to mitigate the effects of point absorbers in current and future GW wave detectors to maximize the success of these enterprises.
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http://dx.doi.org/10.1364/AO.419689DOI Listing
May 2021

Pathogenic variants in , a chromatin remodeler, cause a range of syndromic neurodevelopmental features.

Sci Adv 2021 May 12;7(20). Epub 2021 May 12.

Division of Genetics and Metabolism, Phoenix Children's Hospital, Phoenix, AZ, USA.

Intellectual disability encompasses a wide spectrum of neurodevelopmental disorders, with many linked genetic loci. However, the underlying molecular mechanism for more than 50% of the patients remains elusive. We describe pathogenic variants in , encoding the ATPase motor of the ISWI chromatin remodeler, as a cause of a previously unidentified neurodevelopmental disorder, identifying 12 individuals with de novo or dominantly segregating rare heterozygous variants. Accompanying phenotypes include mild developmental delay, frequent postnatal short stature and microcephaly, and recurrent dysmorphic features. Loss of function of the SMARCA5 ortholog led to smaller body size, reduced sensory dendrite complexity, and tiling defects in larvae. In adult flies, Iswi neural knockdown caused decreased brain size, aberrant mushroom body morphology, and abnormal locomotor function. loss of function was rescued by wild-type but not mutant SMARCA5. Our results demonstrate that pathogenic variants cause a neurodevelopmental syndrome with mild facial dysmorphia.
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http://dx.doi.org/10.1126/sciadv.abf2066DOI Listing
May 2021

The duration of antibiotic treatment is associated with carriage of toxigenic and non-toxigenic strains of Clostridioides difficile in dogs.

PLoS One 2021 12;16(5):e0245949. Epub 2021 May 12.

Veterinary Pathology, Public Health and Disease Investigation, School of Veterinary Medicine, University of Glasgow, Glasgow, United Kingdom.

Clostridioides difficile is a leading cause of human antibiotic-associated diarrhoeal disease globally. Zoonotic reservoirs of infection are increasingly suspected to play a role in the emergence of this disease in the community and dogs are considered as one potential source. Here we use a canine case-control study at a referral veterinary hospital in Scotland to assess: i) the risk factors associated with carriage of C. difficile by dogs, ii) whether carriage of C. difficile is associated with clinical disease in dogs and iii) the similarity of strains isolated from dogs with local human clinical surveillance. The overall prevalence of C. difficile carriage in dogs was 18.7% (95% CI 14.8-23.2%, n = 61/327) of which 34% (n = 21/61) were toxigenic strains. We found risk factors related to prior antibiotic treatment were significantly associated with C. difficile carriage by dogs. However, the presence of toxigenic strains of C. difficile in a canine faecal sample was not associated with diarrhoeal disease in dogs. Active toxin was infrequently detected in canine faecal samples carrying toxigenic strains (2/11 samples). Both dogs in which active toxin was detected had no clinical evidence of gastrointestinal disease. Among the ten toxigenic ribotypes of C. difficile detected in dogs in this study, six of these (012, 014, 020, 026, 078, 106) were ribotypes commonly associated with human clinical disease in Scotland, while nontoxigenic isolates largely belonged to 010 and 039 ribotypes. Whilst C. difficile does not appear commonly associated with diarrhoeal disease in dogs, antibiotic treatment increases carriage of this bacteria including toxigenic strains commonly found in human clinical disease.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245949PLOS
May 2021

4-Ethylguaiacol modulates neuroinflammation and Th1/Th17 differentiation to ameliorate disease severity in experimental autoimmune encephalomyelitis.

J Neuroinflammation 2021 May 11;18(1):110. Epub 2021 May 11.

Department of Microbiology and Immunology, Indiana University School of Medicine, 2101 E. Coliseum Boulevard, Fort Wayne, IN, 46805, USA.

Background: Multiple sclerosis (MS) is a progressive autoimmune disease characterized by the accumulation of pathogenic inflammatory immune cells in the central nervous system (CNS) that subsequently causes focal inflammation, demyelination, axonal injury, and neuronal damage. Experimental autoimmune encephalomyelitis (EAE) is a well-established murine model that mimics the key features of MS. Presently, the dietary consumption of foods rich in phenols has been reported to offer numerous health benefits, including anti-inflammatory activity. One such compound, 4-ethylguaiacol (4-EG), found in various foods, is known to attenuate inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects on modulating the CNS inflammatory immune responses remains unknown. Thus, in this study, we assessed the therapeutic effect of 4-EG in EAE using both chronic and relapsing-remitting animal models and investigated the immunomodulatory effects of 4-EG on neuroinflammation and Th1/Th17 differentiation in EAE.

Methods: Chronic C57BL/6 EAE and relapsing-remitting SJL/J EAE were induced followed by 4-EG treatment. The effects of 4-EG on disease progression, peripheral Th1/Th17 differentiation, CNS Th1/Th17 infiltration, microglia (MG) activation, and blood-brain barrier (BBB) disruption in EAE were evaluated. In addition, the expression of MMP9, MMP3, HO-1, and Nrf2 was assessed in the CNS of C57BL/6 EAE mice.

Results: Our results showed that 4-EG not only ameliorated disease severity in C57BL/6 chronic EAE but also mitigated disease progression in SJL/J relapsing-remitting EAE. Further investigations of the cellular and molecular mechanisms revealed that 4-EG suppressed MG activation, mitigated BBB disruption, repressed MMP3/MMP9 production, and inhibited Th1 and Th17 infiltration in the CNS of EAE. Furthermore, 4-EG suppressed Th1 and Th17 differentiation in the periphery of EAE and in vitro Th1 and Th17 cultures. Finally, we found 4-EG induced HO-1 expression in the CNS of EAE in vivo as well as in MG, BV2 cells, and macrophages in vitro.

Conclusions: Our work demonstrates that 4-EG confers protection against autoimmune disease EAE through modulating neuroinflammation and inhibiting Th1 and Th17 differentiation, suggesting 4-EG, a natural compound, could be potentially developed as a therapeutic agent for the treatment of MS/EAE.
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http://dx.doi.org/10.1186/s12974-021-02143-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111955PMC
May 2021