Publications by authors named "D K Johnson"

12,514 Publications

Sensitive assay design for detection of anti-drug antibodies to biotherapeutics that lack an immunoglobulin Fc domain.

Sci Rep 2021 Jul 29;11(1):15467. Epub 2021 Jul 29.

B2S Life Sciences LLC, 97 East Monroe Street, Franklin, IN, 46131, USA.

Today the evaluation of unwanted immunogenicity is a key component in the clinical safety evaluation of new biotherapeutic drugs and macromolecular delivery strategies. However, the evolving structural complexity in contemporary biotherapeutics creates a need for on-going innovation in assay designs for reliable detection of anti-drug antibodies, especially for biotherapeutics that may not be well-suited for testing by a bridging assay. We, therefore, initiated systematic optimization of the direct binding assay to adapt it for routine use in regulatory-compliant assays of serum anti-drug antibodies. Accordingly, we first prepared a SULFO-TAG labeled conjugate of recombinant Protein-A/G to create a sensitive electrochemiluminescent secondary detection reagent with broad reactivity to antibodies across many species. Secondly, we evaluated candidate blocker-diluents to identify ones producing the highest signal-to-noise response ratios. Lastly, we introduced use of the ratio of signal responses in biotherapeutic-coated and uncoated wells as a data transformation strategy to identify biological outliers. This alternative data normalization approach improved normality, reduced skewness, and facilitated application of a parametric screening cut point. We believe the optimized direct binding assay design employing SULFO-TAG labeled Protein-A/G represents a useful analytical design for detecting serum ADA to biotherapeutics that lack an immunoglobulin Fc domain.
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http://dx.doi.org/10.1038/s41598-021-95055-xDOI Listing
July 2021

Primary Care Shared Medical Appointment for Pain Management: A Pilot Program.

J Pain Palliat Care Pharmacother 2021 Jul 29:1-5. Epub 2021 Jul 29.

Effective strategies that are evidence-based and non-addictive are needed to manage chronic pain and combat the opioid crisis. One potential strategy is to utilize a shared medical appointment (SMA), which is a model of providing clinical care in a group setting with multiple healthcare team members for comprehensive pain management. The purpose of this retrospective chart review is to evaluate the impact of a pain management SMA at the William S. Middleton Veterans Affairs (VA) West Clinic on opioid use and behaviors. Quantitative and qualitative data was obtained from the electronic medical record of 16 Veterans who participated in the pain SMA and analyzed using descriptive statistics. In addition to a reduction in opioid doses six months post SMA, participants gained non-pharmacological referrals, addition of non-opioid pain medications, and a mix of didactic and experiential education on pharmacologic and non-pharmacologic treatment modalities to help manage their chronic pain. This SMA allowed for greater access to healthcare professionals with a sole focus on pain management and provided Veterans with a holistic approach to their pain management.
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http://dx.doi.org/10.1080/15360288.2021.1943597DOI Listing
July 2021

Reducing Cardiovascular Maternal Mortality by Extending Medicaid for Postpartum Women.

J Am Heart Assoc 2021 Jul 29:e022040. Epub 2021 Jul 29.

Cardiovascular Division Washington University School of Medicine St. Louis MO.

Maternal mortality has been increasing in the United States over the past 3 decades, while decreasing in all other high-income countries during the same period. Cardiovascular conditions account for over one fourth of maternal deaths, with two thirds of deaths occurring in the postpartum period. There are also significant healthcare disparities that have been identified in women experiencing maternal morbidity and mortality, with Black women at 3 to 4 times the risk of death as their White counterparts and women in rural areas at heightened risk for cardiovascular morbidity and maternal morbidity. However, many maternal deaths have been shown to be preventable, and improving access to care may be a key solution to addressing maternal cardiovascular mortality. Medicaid currently finances almost half of all births in the United States and is mandated to provide coverage for women with incomes up to 138% of the federal poverty level, for up to 60 days postpartum. In states that have not expanded coverage, new mothers become uninsured after 60 days. Medicaid expansion has been shown to reduce maternal mortality, particularly benefiting racial and ethnic minorities, likely through reduced insurance churn, improved postpartum access to care, and improved interpregnancy care. However, even among states with Medicaid expansion, significant care gaps exist. An additional proposed intervention to improve access to care in these high-risk populations is extension of Medicaid coverage for 1 year after delivery, which would provide the most benefit to women in Medicaid nonexpanded states, but also improve care to women in Medicaid expanded states.
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http://dx.doi.org/10.1161/JAHA.121.022040DOI Listing
July 2021

Prevalence of unmasked and improperly masked behavior in indoor public areas during the COVID-19 pandemic: Analysis of a stratified random sample from Louisville, Kentucky.

PLoS One 2021 28;16(7):e0248324. Epub 2021 Jul 28.

Department of Epidemiology and Population Health, School of Public Health and Information Sciences, University of Louisville, Louisville, Kentucky, United States of America.

Wearing a facial mask can limit COVID-19 transmission. Measurements of communities' mask use behavior have mostly relied on self-report. This study's objective was to devise a method to measure the prevalence of improper mask use and no mask use in indoor public areas without relying on self-report. A stratified random sample of retail trade stores (public areas) in Louisville, Kentucky, USA, was selected and targeted for observation by trained surveyors during December 14-20, 2020. The stratification allowed for investigating mask use behavior by city district, retail trade group, and public area size. The total number of visited public areas was 382 where mask use behavior of 2,080 visitors and 1,510 staff were observed. The average prevalence of mask use among observed visitors was 96%, while the average prevalence of proper use was 86%. In 48% of the public areas, at least one improperly masked visitor was observed and in 17% at least one unmasked visitor was observed. The average prevalence of proper mask use among staff was 87%, similar to the average among visitors. However, the percentage of public areas where at least one improperly masked staff was observed was 33. Significant disparities in mask use and its proper use were observed among both visitors and staff by public area size, retail trade type, and geographical area. Observing unmasked and improperly masked visitors was more common in small (less than 1500 square feet) public areas than larger ones, specifically in food and grocery stores as compared to other retail stores. Also, the majority of the observed unmasked persons were male and middle-aged.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248324PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318281PMC
July 2021

Retinoblastoma from human stem cell-derived retinal organoids.

Nat Commun 2021 07 27;12(1):4535. Epub 2021 Jul 27.

Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN, USA.

Retinoblastoma is a childhood cancer of the developing retina that initiates with biallelic inactivation of the RB1 gene. Children with germline mutations in RB1 have a high likelihood of developing retinoblastoma and other malignancies later in life. Genetically engineered mouse models of retinoblastoma share some similarities with human retinoblastoma but there are differences in their cellular differentiation. To develop a laboratory model of human retinoblastoma formation, we make induced pluripotent stem cells (iPSCs) from 15 participants with germline RB1 mutations. Each of the stem cell lines is validated, characterized and then differentiated into retina using a 3-dimensional organoid culture system. After 45 days in culture, the retinal organoids are dissociated and injected into the vitreous of eyes of immunocompromised mice to support retinoblastoma tumor growth. Retinoblastomas formed from retinal organoids made from patient-derived iPSCs have molecular, cellular and genomic features indistinguishable from human retinoblastomas. This model of human cancer based on patient-derived iPSCs with germline cancer predisposing mutations provides valuable insights into the cellular origins of this debilitating childhood disease as well as the mechanism of tumorigenesis following RB1 gene inactivation.
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http://dx.doi.org/10.1038/s41467-021-24781-7DOI Listing
July 2021
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